FCA Part II Anaesthetic Refresher 2017Course Department of Anaesthesia University of the Witwatersrand

SUPPLEMENT COVER.indd 1 2017/05/09 11:32 AM ContentsContents South Afr J Anaesth Analg • 2017 • Volume 23 • Number 2 • Supplement 1

• Peribulbar (extraconal) eye block and its complications S3 KK Purbhoo ......

• Molar pregnancies with a focus on the thyroid S7 F Bham ......

• Cerebral perfusion during non-neurosurgical procedures: The practicalities of Near Infrared Spectroscopy (NIRS)/ (BIS) S12 M Mphomane ......

FCA Part II • Anaesthesia for related living donor liver transplantation S15 Anaesthetic M Hatchett ...... • The bleeding parturient: anaesthetic perspective S18 Refresher D Nel ...... • Carcinoid syndrome S26 Course 2017 MA Eagar ......

• Analgesia for thoracic S31 NT Hlongwane-Gukuta ......

• Extracorporeal Membrane Oxygenation (ECMO) S36 A Alli ......

• Anaesthetic considerations for inhaled and ingested foreign bodies in children: What? Where? When? S42 AZ Bhettay ......

• Anaesthesia for brainstem response testing in children with autism spectrum disorders S46 MR Correia ......

• Anaesthesia for craniosynotosis surgery S53 D Lines ......

• Anaesthesia for thoracoscopy in paediatric patients S59 S Spijkerman ......

• Mediastinoscopy in paediatric patients S65 S Spijkerman ......

• The obese parturient S70 E Mostert ......

• Laryngospasm in anaesthesia S74 S Spijkerman ......

• Epilepsy and anaesthesia S81 C Hosking ......

• Neonatal S84 KL Borrill......

• Conventional cardiopulmonary bypass and mini-cardiopulmonary bypass S87 MEA Kemp ......

• Posterior of fossa surgery S92 MMA Mashinini ...... FCA Part II Anaesthetic Refresher 2017Course Department of Anaesthesia University of the Witwatersrand

SUPPLEMENT COVER.indd 1 2017/05/09 11:32 AM Contents • The anaesthetist’s role in the endoscopy suite S98 C Quan ......

• Inadvertent burns in the theatre S103 EE Oosthuizen ......

• The postoperative management of a supraventricular tachyarrhythmia S106 HJ Moutlana......

• A study of perioperative deaths in Charlotte Maxeke Johannesburg Academic Hospital, a South African level four central hospital S110 C Lundgren, P Cleaton-Jones......

• Anaesthetic considerations for children with malignancies S114 C Lee......

• Can you sedate a child for a dental procedure? S119 BM Gardner......

• Anaesthesia in pregnancy for non-obstetric surgery S123 FCA Part II NR Madima......

• Anaesthesia for cleft lip and palate surgery Anaesthetic S128 A Oosthuizen...... Refresher • New concepts in anaesthetic emergence S134 AW Moodley......

Course 2017 • Three-stage oesophagectomy S138 ME Sethusa......

• Managing an acute pulmonary embolism on the table S140 E Welch......

• Clinical use of nerve stimulators S143 E Welch......

• Anaesthesia for a patient with Achondroplasia presenting for Caesarean section S147 T Kleyenstuber......

• Anaesthetic management in paediatric burns S149 P N Mogane......

© 2017 SASA. Unless otherwise stated, opinions expressed in the editorial columns of SAJAA should not be taken as reflecting official SASA policy. The appearance of advertising in this publication does not denote a guarantee or an endorsement by SASA of the products or the claims made for the products by the manufactures. Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Peribulbar (extraconal) eye block and its complications

K K Purbhoo

Department of Anaesthesia, Helen Joseph Hospital, University of the Witwatersrand Correspondence to: [email protected]

Local anaesthesia is preferred over by Type of anaesthesia chosen many ophthalmic surgeons with the main reasons being lower This would depend on: perioperative morbidity with quicker patient recovery and fewer 1. The type of surgery complications.1–3 2. The surgeon’s preference Anaesthetists have become increasingly involved in eye blocks 3. Patient’s suitability, and that were previously performed by surgeons. Good anaesthesia 4. Patient cooperation is essential for the performance of safe intraocular surgery and may contribute to the success or failure of the surgery.4,5 Preoperative considerations A routine preoperative assessment has to be done to ensure that Goals of anaesthetic care during elective eye surgery co-morbid conditions are reasonably well controlled. 1. Anaesthesia of the globe, lids and adnexa ensuring pain-free A focused medical history needs to be taken and should include surgery a history determining if the patient is a suitable candidate for 2. Akinesia of the globe and lids facilitating the surgical same day surgery.6 A history of anticoagulant or antithrombotic procedure, and is vital. Patients having cataract surgery that are at a 3. Rapid recovery with adequate postoperative analgesia4,5 high risk of clotting and embolic complications due to cardiac or vascular should continue therapeutic doses of aspirin Anaesthetic techniques available: and warfarin throughout the perioperative period.7,8 There is,

Anaesthesia for eye surgery

Local anaesthesia General anaesthesia

Topical Regional

Peribulbar Retrobulbar Subconjunctival Subtenon block (extraconal) block (intraconal) block block

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however, insufficient data available on dual antiplatelet extraconal compartment and hence considered safer since it for stents and eye surgery. Eye surgery, if possible, should be avoids potential damage to the intraconal structures. postponed until after the minimum period recommended for The motor supply to the eye is from the oculomotor nerve (CN III), daily administration of dual antiplatelet therapy.8,9 the trochlear nerve (CN IV) and the abducens nerve (CN VI). CN A full physical examination needs to be done. It is important to III supplies all the extraocular muscles except superior oblique determine if the patient will be able to lie supine comfortably and lateral rectus muscles. CN III also supplies levator palpebrae under drapes. Conditions that preclude this, e.g. congestive superioris. CN IV supplies the superior oblique muscle and CN VI cardiac failure, claustrophobia or back pain need to be excluded. supplies the lateral rectus muscle. CN IV lies outside the muscle cone and hence is not usually blocked.5 The patient’s communication and cooperation skills also need to be established. During regional anaesthesia you have to be able The sensory supply is from the trigeminal nerve (CN V). CN V is to communicate with the patient and the patient has to be able divided into the ophthalmic branch which is further divided into to follow commands such as avoiding all movement. nasociliary, lacrimal and frontal branches .The nasociliary branch supplies the cornea, perilimbal conjunctiva and the superonasal Monitoring quadrant of the bulbar conjunctiva. The rest of the conjunctiva is Standard ASA monitoring, which includes electrocardiogram, supplied by the lacrimal, infraorbital and frontal nerves.5 pulse oximetry and non-invasive blood pressure monitoring The ciliary ganglion lying within the cone relays sensory fibres together with is essential. Patients need to be from the globe to the ophthalmic division of CN V. It receives a monitored because they can get an occulocardiac reflex or an accidental injection into a blood vessel or the brain.10 parasympathetic branch from CN III and sympathetic fibres from the carotid plexus.14 Supplemental oxygen should be given to decrease the risk of hypoxaemia during sedation and to have a fresh gas flow to Peribulbar (extraconal) block prevent the patient rebreathing clinically significant amounts of The peribulbar block (PBB) was first described in 1986 and was carbon dioxide that may occur as a result of completely covering developed as a safer alternative to the retrobulbar (intraconal) the face. block (RBB) for providing anaesthesia and akinesia of the eye. Vacuum suctioning under the drapes can be used to lower the Similar clinical efficacy of the PBB and the RBB, as evidenced by oxygen concentration and remove expired carbon dioxide.11,12 similar spreading of local anaesthetic injected, but with a higher Before the block is performed one needs to establish good risk of complications associated with introducing the needle into intravenous access. the cone, makes the PBB a better alternative to the RBB.15 Sedation and analgesia With PBB the needle is placed less deeply and at a different angle compared to the RBB. The local anaesthetic (larger volume Short-acting agents can be given immediately before the than with RBB) is injected outside the muscle cone and spreads block to decrease or eliminate pain of needle insertion and by way of diffusion to block the orbital nerves including the injection of local anaesthetic. Minimal sedation is preferable ciliary ganglion, ciliary nerves, CNs II, III, VI and even CN IV. The during the procedure because the surgery requires an awake modifications with needle placement make the PBB less likely and cooperative patient. Excess sedation can lead to a restless, to result in perforation of the globe posteriorly, injury to the confused or unresponsive patient who may have respiratory optic nerve or injection into the brain with resultant brainstem depression with airway obstruction. This can pose a significant anaesthesia.15,16 intraoperative challenge. Even minor movement (highly magnified under a microscope) may result in severe eye injury.4 Technique

If the patient has pain intraoperatively, a supplemental block The classic technique involves two injections. An initial with local anaesthesia should be given. Inadequate analgesia inferolateral injection supplemented with a medial injection. A should not be substituted with heavy sedation.13 single inferolateral injection is often adequate for anaesthesia but may not be predictable for akinesia.5,17 Anatomy of the eye A needle of ≤ 2.5 cm is recommended to decrease the risk of The orbit is pyramidal in shape with its base at the orbital opening injury to structures deep in the orbit. Increasing needle insertion and its apex pointing to the optic foramen. The orbit is occupied depth would be expected to change a PBB to a RBB.18 In addition, by the globe, its muscle cone, loose connective tissue and fat. The a very long needle may reach the apex of the orbit and may globe lies in the anterior part of the orbit and sits high and lateral, result in local anaesthetic being injected through the optic therefore it is nearer the roof than the floor and nearer the lateral foramen.19,20 The Atkinson needle (blunt tip) is normally used as it than medial wall (important for needle insertion points). There may enhance the operator’s ability to identify scleral tissue if it is are four recti muscles and two oblique muscles that control eye encountered before perforation of the globe. Indeed in cadavers movement. The recti muscles form the muscle ‘cone’ around the more pressure is required with short bevel needles to perforate globe. The muscle cone encloses the sensory and motor nerves, the sclera.21 Some clinicians, however, use sharper needles to ciliary ganglion, optic nerve, ophthalmic artery and vein.14 minimise the pain of insertion and to theoretically limit the Retrobulbar anaesthesia is injected in the intraconal amount of damage to the globe if inadvertent perforation does compartment, whereas peribulbar anaesthesia is injected in the occur.4

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After establishing intravenous access, connecting monitors and 1. Globe perforation giving minimal sedation, the patient is asked to lie supine and This can occur as a result of direct trauma. More common look straight ahead. in patients with myopia (axial length > 26 mm), posterior staphyloma, posterior scleral buckling and severe The first injection is inferior and temporal. The junction of the exophthalmos.25 The symptoms of globe perforation are medial two-thirds and lateral one-third of the inferior orbital variable, ranging from intense ocular pain with abrupt rim is palpated, where a groove is felt at the junction of the loss of vision and hypotonus, to no signs or symptoms. maxilla and zygoma. Slightly lateral to this point a 2.5 cm needle Globe perforation and rupture is the most devastating is introduced through the skin and passed slowly backwards complication of eye blocks and has a poor prognosis perpendicular to all planes. If the needle tip contacts bone it especially when the diagnosis is delayed.5 is redirected slightly superomedially to follow the orbital floor once more. The needle is advanced until its tip is about level 2. Intravascular injection with the posterior pole of the globe (until the hub reaches the Inadvertent intra-arterial injection may reverse the blood plane of the iris). The globe should be observed closely for any flow in the ophthalmic artery up to the anterior cerebral or signs of rotation during insertion, indicating scleral contact. After the internal carotid artery. It can result in convulsions, loss of aspiration 6–10 mls of local anaesthetic is injected slowly.5,14 consciousness or, rarely, cardiopulmonary arrest. Treatment A larger volume is needed to spread into the whole corpus is symptomatic.26 adiposum of the orbit including the intraconal space. The larger Inadvertent intravascular injection can lead to systemic volume also allows anterior spread of the local anaesthetic to the toxicity but is unlikely to because of the small amount of lids to provide a block of the orbicularis muscles and to avoid local anaesthetic given. Treatment would be symptomatic the need for an additional lid block.5 PBB produces more reliable and intravenous administration of lipid emulsion.4 akinesia of the orbicularis oculi as compared to a RBB.22,23 3. Retrobulbar haemorrhage If the globe becomes tense or proptosed or if the upper eyelid This occurs as a result of direct trauma to the artery or vein. It falls during injection then you should stop immediately as this may lead to a compressive haematoma (artery injury) which may indicate a RBB which requires a smaller volume of local can threaten retinal perfusion. It is very important that at the anaesthesia.14 time of the haemorrhage an ophthalmologist be present Compression to the eye can be done after injection to lower to monitor intraocular pressure and treat appropriately. intraocular pressure, which increases after injection. Applying a Surgical decompression may be required, but in most cases pressure of 30 mmHg for 5–10 minutes is usually sufficient. surgery has only to be postponed.5 Assess the block after 5–10 minutes and if a greater degree of Venous puncture may occur and leads to a noncompressive akinesia or additional anaesthesia is required a second injection haematoma, the consequence of which is less severe and in should be performed. In the classic technique the second most cases surgery can be continued.5 injection is superior and nasal between the medial one-third and 4. Optic nerve damage the lateral two-thirds of the orbital roof edge.5 It is important to Direct optic nerve trauma by the needle is rare but can cause remember that at the superior nasal site, the distance between blindness. Optic nerve damage may also occur as a result of the orbital roof and the globe is reduced, theoretically increasing vascular occlusion.5 the risk of globe perforation. Additionally the superior oblique muscle can be injured.14 5. Occulocardiac reflex This occurs as a result of stimulation of the trigeminal nerve If both medial and lateral injections are planned, the volume (afferent limb) and leads to a response via the vagus nerve of the solution is 4–5 mls for each. It is important to remember (efferent limb). The patient may develop a bradycardia, an that the first injection may increase the risk of complications arrhythmia or cardiac asystole. It is usually self-limiting but associated with consecutive injections, as it may distort the can be treated with atropine.14 anatomy.24 6. Optic nerve sheath injection Alternate techniques This can result in a subdural or subarachnoid injection. It Numerous alternative techniques and different sites for needle can cause partial or total brainstem anaesthesia. Depending insertion for a PBB have been described.5 The most common on the concentration and volume of the local anaesthetic, alternative is the medial canthus peribulbar block. Here the a bilateral block, cranial nerve palsy with sympathetic needle is introduced at the medial junction of the lids, nasal to activation, confusion, restlessness or total the lacrimal caruncle, in a strictly posterior direction to a depth of with quadriparesis, arterial hypotension, bradycardia 15 mm or less. At this site the space between the orbital wall and and eventually respiratory arrest can occur. Treatment is the globe is similar in size to that of the inferolateral approach symptomatic until the block resolves.27,28 and is free from blood vessels. This site can be used as the second 7. Chemosis (subconjunctival oedema) injection point when the first inferolateral injection needs to be supplemented.5,12 This is usually of minimal concern and disappears with pressure.5 Complications 8. Decreased visual acuity The main reason for complications is needle misplacement. This resolves with resolution of the block.5

S5 6 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1)

9. Myotoxicity nysora.com/mobile/regional-anesthesia/sub-specialties/3029-local-regional- -for-eye-surgery.html. This can occur with a high concentration of local anaesthetic 6. Lawrence D, Fedorowicz Z, van Zuuren EJ. Day care versus in‐patient surgery for or direct injection into the muscle and can result in muscle age‐related cataract. The Cochrane Library. 2015. palsy.29 7. Douketis JD, Berger PB, Dunn AS, et al. The perioperative management of antithrombotic therapy: American College of Chest evidence-based Myotoxicity may progress in three steps; firstly the muscle clinical practice guidelines. CHEST Journal. 2008;133(6_suppl):299S-339S. is paralysed, secondly it seems to recover and thirdly a 8. Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guideline retractile scar develops.5 on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Circulation. 2014:CIR. 0000000000000106. Agents used 9. American Society of Anesthesiologists Committee on Standards and practice parameters. Practice alert for the perioperative management of patients with All available local anaesthetics have been used for eye blocks, coronary artery stents. ; 2009. either alone or as a mixture of two different agents. The choice 10. Committee of Origin: Standards and Practice Parameters. Standards for basic anesthetic monitoring. 2011. Available from: https://www.asahq.org/ and concentration of local anaesthetic used depends on: For-Members/Standards-Guidelines-and-Statements.aspx 1. Speed of onset required (lignocaine for quicker onset of 11. Apfelbaum JL, Caplan RA, Barker SJ, et al. Practice Advisory for the Prevention and Management of Operating Room Fires. An Updated Report by the American action) Society of Anesthesiologists Task Force on Operating Room Fires. The Journal of 2. Duration of block desired or need for postoperative analgesia the American Society of Anesthesiologists. 2013;118(2):271-90. 12. Kung TA, Kong SW, Aliu O, et al. Effects of vacuum suctioning and strategic drape (ropivicaine or bupivacaine for longer duration) tenting on oxygen concentration in a simulated surgical field. Journal of Clinical 3. Availability, and Anesthesia. 2016;28:56-61. 13. American Society of Anesthesiologists. Continuum of depth of sedation: 4. Need for akinesia (higher concentration) Definition of general anesthesia and levels of sedation/analgesia. 2009. Available from: https://www.asahq.org/~/media/For%20Members/Standards%20and%20 Additives Guidelines/2012/CONTINUUM%20OF%20DEPTH%20OF%20SEDATION%20 442012.pdf 1. Hyaluronidase 14. Farmery A. Opthalmic Surgery. In: Allman KG, Wilson IH, editors. Oxford This is an enzyme that helps facilitate spread of anaesthetic Handbook of Anaesthesia. Oxford: Oxford University Press inc.; 2011. p. 558-67. through tissues by increasing permeability of fibrous septa. 15. Ripart J, Lefrant J-Y, de La Coussaye J-E, et al. Peribulbar versus Retrobulbar Anesthesia for Ophthalmic Surgery, An Anatomical Comparison of Extraconal It improves the speed of onset and quality of the nerve and Intraconal Injections 2001 [56-62]. block. It also reduces the increase in intraocular pressure 16. Davis DB, Mandel MR. Posterior peribulbar anesthesia: an alternative and the risk of injury to extraocular muscles.4 Concentrations to retrobulbar anesthesia. Journal of Cataract and Refractive Surgery. 1986;12(2):182-4. between 1 and 7.5 units per ml are commonly used, but 17. Demirok A, Simsek S, Çinal A, Yasar T. Peribulbar anesthesia: one versus two 30 concentrations as low as 0.75 units per ml may be effective. injections. Ophthalmic Surgery, Lasers and Imaging Retina. 1997;28(12):998-9. 2. Clonidine 18. Sarvela J, Nikki P. Comparison of two needle lengths in regional ophthalmic anesthesia with etidocaine and hyaluronidase. Ophthalmic Surgery, Lasers and It enhances intra- and postoperative analgesia when Imaging Retina. 1992;23(11):742-5. added to the local anaesthetic. At a dose of 1 microgram 19. Karampatakis V, Natsis K, Gigis P, Stangos N. The risk of optic nerve injury in per kilogram it does not increase the incidence of systemic retrobulbar anesthesia: a comparative study of 35 and 40 mm retrobulbar needles in 12 cadavers. European Journal of . 1997;8(3):184-7. adverse events such as hypotension or excessive sedation.5 20. Katsev DA, Drews RC, Rose BT. An anatomic study of retrobulbar needle path 3. Epinephrine length. Ophthalmology. 1989;96(8):1221-4. 21. Waller SG, Taboada J, O'Connor P. Retrobulbar anesthesia risk: do sharp needles It is sometimes used to increase the duration of action really perforate the eye more easily than blunt needles? Ophthalmology. of the local anaesthetic. Its use has decreased with the 1993;100(4):506-10. availability of longer acting agents and also because of fear 22. Hessemer V. Peribulbäranästhesie versus Retrobulbäranästhesie mit 5 Fazialisblock-Techniken, Lokalanästhetika und Zusätze, Akinesie und sensible of vasospasm and subsequent retinal ischaemia. Blockade, Komplikationen. Klinische Monatsblätter für Augenheilkunde. 4. Sodium bicarbonate 1994;204(02):75-89. 23. McGoldrick K, Gayer S. Anesthesia for Opthalmologic Surgery. In: Barash P, editor. Alkalinisation of the local anaesthetic solution has been Clinical Anesthesia. Philadelphia: Lippincott Williams and Wilkins; 2013. p. 1373. proposed for decreasing pain during injection and 24. Ball J, Woon W, Smith S. Globe perforation by the second peribulbar injection. accelerating the block onset. The efficacy of this has not Eye. 2002;16(5):663-5. been proven.5 25. Edge R, Navon S. Scleral perforation during retrobulbar and peribulbar anesthesia: risk factors and outcome in 50 000 consecutive injections. Journal of References Cataract and Refractive Surgery. 1999;25(9):1237-44. 26. Aldrete JA, Romo-salas F, Arora S, et al. Reverse arterial blood flow as a 1. Eke T, Thompson JR. The national survey of local anaesthesia for ocular surgery. pathway for central nervous system toxic responses following injection of local II. Safety profiles of local anaesthesia techniques. Eye. 1999;13(2):196-204. anesthetics. Anesthesia and Analgesia. 1978;57(4):428-33. 2. Hamilton RC, Gimbel HV, Strunin L. Regional anaesthesia for 12,000 cataract 27. Nicoll JMV, Acharya PA, Ahlen K, et al. Central nervous system complications extraction and intraocular lens implantation procedures. Canadian Journal of after 6000 retrobulbar blocks. Anesthesia and Analgesia. 1987;66(12):1298-302. Anaesthesia. 1988;35(6):615-23. 28. Singer S, Preston R, Hodge W. Respiratory arrest following peribulbar anesthesia 3. Hodgkins P, Luff A, Morrell A, et al. Current practice of cataract extraction and for cataract surgery: case report and review of the literature. Canadian Journal of anaesthesia. British Journal of Ophthalmology. 1992;76(6):323-6. Ophthalmology Journal Canadien d'Ophtalmologie. 1997;32(7):450-4. 4. Macias AA, Bayes J, McGoldrick KE. Anesthesia for elective eye surgery: 29. Rainin EA, Carlson BM. Postoperative diplopia and ptosis: a clinical hypothesis Up to Date; 2016. Available from: http://www.uptodate.com/contents/ based on the myotoxicity of local anesthetics. Archives of Ophthalmology. anesthesia-for-elective-eye-surgery. 1985;103(9):1337-9. 5. Ripart J, Mehrige K, Robert Della Rocca M, Blocks MCOE. Local and regional 30. DeBroff B, Hamilton R, Loken R, et al. Retrobulbar anesthesia with 705 vs. 0.75 anesthesia for eye surgery: NYSORA; 2009 [00]. Available from: http://www. IU/mL of hyaluronidase. Canadian Journal of Ophthalmology. 1995;30(5):262-4.

S6 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Molar pregnancies with a focus on the thyroid

F Bham

Department of Anaesthesia, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

Gestational trophoblastic disease (GTD) represents a spectrum Clinical presentation of conditions that arise from abnormal cellular proliferation of Molar pregnancies usually present clinically in the second trophoblastic tissue of the developing placenta. It encompasses trimester with: the following main forms: • Vaginal bleeding (most common) 1. Complete and partial hydatiform mole (non-invasive molar • Anaemia pregnancy) • Excessive uterine enlargement 2. Invasive hydatiform mole • Theca lutein ovarian cysts 3. Choriocarcinoma • Hyperemesis gravidarum 4. Placental site trophoblastic tumour1,2 • Passing vesicles (grape-like tissue)

The latter three forms can invade the myometrium and • Features of pre-eclampsia metastasise, and are collectively termed gestational • Abdominal pain trophoblastic neoplasia (GTN). Since the introduction of • Hyperthyroidism chemotherapy into their management, they are amongst the • Respiratory distress1,2,5 most curable of all solid tumours, with cure rates of more than Diagnosis 90% even in the presence of metastatic disease.1 A detailed • Ultrasonography: A vesicular pattern consisting of multiple discussion of GTN is beyond the scope of this review. echoes (holes) within the placental mass (“snowstorm” or There are wide regional variations in the incidence of GTD. The “bunch of grapes” appearance) together with absent foetal incidence of hydatiform mole ranges from 0.57 to 2.00 per 1 000 tissue is suggestive of a complete mole. A partial mole demonstrates a more focal distribution of placental cystic pregnancies.1 One South African study from a single tertiary spaces and the presence of foetal tissue.1,4–6 referral hospital estimates the incidence of molar pregnancy at • β-hCG: The β-subunit of hCG can be measured quantitatively 1.2 per 1 000 deliveries.3 in urine and blood. Hydatiform moles are associated with Pathophysiology markedly elevated levels. A single β-hCG measurement may not differentiate a molar pregnancy from a normal intrauterine The placental trophoblast is composed of a cytotrophoblast, pregnancy, a multiple gestation, a pregnancy complicated by intermediate trophoblast and syncitiotrophoblast, all of which erythroblastocis foetalis or intrauterine infections associated may result in GTD when they proliferate. The syncitiotrophoblast with an enlarged placenta. Stable or rising β-hCG levels produces human chorionic gonadotropin (hCG).1 following evacuation of a molar pregnancy is suggestive of GTN.1,2 Hydatiform mole is characterised by varying degrees of • Pathology: Examination of curettage, biopsy, placenta or trophoblastic hyperplasia and vesicles of swollen hydropic villi, hysterectomy specimens. and is associated with absent (complete mole) or abnormal (partial mole) foetal tissue. GTN can develop after 15–20% of Treatment complete moles and 1–5% of partial moles, as well as after a non- Suction curettage is the preferred method of evacuation of molar gestation.1,4 a hydatiform mole. Hysterectomy should be considered if

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preservation of fertility is not required. Medical induction Table I. Causes of hyperthyroidism in pregnancy7,8 of labour is not recommended as it increases maternal Category Aetiology morbidity, such as blood loss and trophoblastic dissemination. PRIMARY THYROID • Graves’ disease Chemotherapy is the principal therapy for GTN with or without • Acute, subacute or chronic thyroiditis adjuvant surgery or radiation in high risk disease.1 • Toxic adenoma The remainder of this review will focus mainly on hyperthyroidism. • Toxic multinodular goitre Other perioperative considerations in patients presenting for GESTATIONAL • Transient gestational thyrotoxicosis evacuation of a molar pregnancy include the risk of heavy • Multiple gestations bleeding, pre-eclampsia, trophoblastic embolisation, respiratory • Molar pregnancy insufficiency, cardiac failure, disseminated intravascular • TSH-receptor mutation coagulopathy and hyperemesis gravidarum with dehydration, • Hyperplacentosis ketosis and electrolyte abnormalities.1 • Hyperreacto luteinalis FOCUS ON HYPERTHYROIDISM OTHER • Iatrogenic Hyperthyroidism: Thyroid gland overactivity leading to • Struma ovarii excessive thyroid hormone production. • TSH-producing pituitary adenoma

Thyrotoxicosis: Clinical syndrome caused by the circulation of excess thyroid hormones.7 amounts of hCG, proportional to the mass of the tumour. Measured β-hCG level, the amount of desialylation, and the HCG biochemistry and physiology duration of the molar pregnancy correlate with the severity of hyperthyroidism.4,6,12 The prevalence of hyperthyroidism in HCG is a placental glycoprotein hormone that consists of two patients with hydatiform mole has been reported as 25–64%, subunits: a β-subunit, which is unique to hCG, and an α-subunit, with about 5% of patients presenting with thyrotoxicosis.4 which is identical to the α-subunit in thyroid stimulating Various studies have shown a paucity of clinical features of hormone (TSH) and pituitary gonadotropins.1,4 thyrotoxicosis, despite elevated levels of free T4 in many molar HCG has a plasma half-life of about 24 hours.1 Normal secretion pregnancies.6 Hyperthyroidism usually becomes clinically begins in early pregnancy and peaks at 8–12 weeks gestation evident when β-hCG levels exceed 300 U/ml.13 In a developing with levels of 30–100 U/ml.4,6,8 This gradually declines to 5–10 U/ country like South Africa, the lack of ultrasound and quantitative ml during the second trimester.1 HCG stimulates TSH-receptors β-hCG screening may lead to a higher incidence due to delayed on the thyroid follicular cell.9 Peak hCG secretion results in an presentation with higher hCG levels. There have also been case 4,6 increase in total thyroxine (T4) and triiodothyronine (T3) levels, reports of hyperthyroidism in patients with choriocarcinoma. and suppression of TSH, which reflects a mirror image to the hCG Clinical features peak.8 As a result, up to 20% of pregnant women have subnormal TSH levels in the first half of pregnancy, with 1.4% experiencing • Sinus tachycardia • Palpitations transient gestational thyrotoxicosis.8,10 The thyroid gland releases • Hypertension • Atrial fibrillation more T4 than the more potent T3. Most of the circulating T3 is • Cardiac failure • Weight loss 11 formed by peripheral partial deiodination of T4. • Hyperactivity • Tremors • Insomnia • Heat intolerance Biological activity is influenced by variations in the structure • Diaphoresis • Diarrhoea of the hormone. Normal hCG has weak thyrotropic activity, 8,11,14 whereas hCG extracted from molar tissue contains less sialic acid, • Thrombocytopaenia • Muscle weakness 1,4,12 which confers greater thyrotropic potency. Furthermore, The clinical diagnosis of thyrotoxicosis may present difficulties the addition of desalyliated hCG to normal TSH has synergistic as many hypermetabolic signs and symptoms are seen during 12 effects. normal pregnancy, i.e. palpitations, heart rate 90 to 100 beats/min, 7 The main biological function of hCG is the maintenance of corpus mild heat intolerance, warm skin and decreased effort tolerance. luteum function, allowing continued progesterone production. Diagnosis HCG also promotes male sexual differentiation. Hyperemesis • Elevated serum free T and T concentrations gravidarum is associated with increased serum β-hCG levels.1 3 4 • Suppressed serum TSH level Causes of hyperthyroidism in pregnancy • Greatly increased thyroid radioiodine uptake

Graves’ disease is the most common differential diagnosis of • Lower T3:T4 ratio compared to Graves’ disease and multinodular non-transient thyrotoxicosis in pregnancy. Other causes are goitre in which the ratio is > 20.4,13 listed in Table I. Treatment Placental tumours and hyperthyroidism Evacuation of the mole or effective chemotherapy for The association between hyperthyroidism and molar pregnancy choriocarcinoma rapidly achieves clinical and biochemical was first reported in 1955.6 Hydatiform moles secrete large euthyroidism.4,6,9

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Perioperative anaesthetic management Anaesthetic technique: Safe use of general anaesthesia (GA), both volatile- and total intravenous anaesthesia (TIVA) based Patients present to theatre for suction curettage or, less techniques, and spinal anaesthesia have been reported.5 commonly, hysterectomy. A multidisciplinary team approach involving the anaesthesiologist, gynaecologist, endocrinologist Evacuation poses a considerable risk of heavy bleeding. GA and intensivist is essential. provides better haemodynamic stability in these patients and is a definitive indication in unstable patients. History and examination: Includes identification of thyroid dysfunction and its complications, as well as other sequelae of Hyperthyroid patients are more sensitive to sympathetic a molar pregnancy. nervous system (SNS) activation, which may lead to tachycardia, hypertension and ventricular arrhythmias. Laryngoscopy and Investigations: FBC, U&E, thyroid hormone levels, ECG, crossmatch intubation, surgical stimulation and extubation are vulnerable – blood immediately available due to risk of major bleeding. periods. Ensure an adequate depth of anaesthesia and maintain An ABG, INR/PTT, LFT, CXR and/or echocardiogram may be normovolaemia and normothermia. necessary depending on clinical presentation and baseline A short-acting opioid, esmolol, lignocaine, or magnesium investigations. sulphate may be used to suppress the response to intubation. Preoperative optimisation – treatment of hyperthyroidism: Depending on the uterine size, patients will probably require a Evacuation of the molar pregnancy is the only definitive rapid sequence induction. Incompletely treated hyperthyroid amounts of hCG, proportional to the mass of the tumour. management of thyrotoxicosis. Antithyroid drugs usually lead patients can be chronically hypovolaemic, and are prone to Measured β-hCG level, the amount of desialylation, and the to some clinical improvement after one week of therapy, but an exaggerated hypotensive response during induction of duration of the molar pregnancy correlate with the severity may need 4–6 weeks for full effect.15 The combined use of anaesthesia,11 particularly if bleeding as well. of hyperthyroidism.4,6,12 The prevalence of hyperthyroidism in propylthiouracil (PTU), iodide and dexamethasone has been Successful use of spinal anaesthesia for evacuation of molar patients with hydatiform mole has been reported as 25–64%, shown to restore serum T3 concentration to normal within pregnancies with thyrotoxicosis has been reported in both with about 5% of patients presenting with thyrotoxicosis.4 48 hours.13 Delaying surgery increases the risk of bleeding (NOT hypovolaemic) and non-bleeding patients.13,16,17 Various studies have shown a paucity of clinical features of complications such as haemorrhage, pre-eclampsia and Advantages of spinal anaesthesia include the ease of the thyrotoxicosis, despite elevated levels of free T in many molar pulmonary embolisation.10,13 Untreated or poorly controlled 4 technique, providing a sympathetic block, earlier detection pregnancies.6 Hyperthyroidism usually becomes clinically hyperthyroidism on the other hand increases the risk of life- of uterine perforation and thyroid storm in an awake patient, evident when β-hCG levels exceed 300 U/ml.13 In a developing threatening perioperative complications, including a thyroid and avoiding airway manipulation, the tocolytic effects of country like South Africa, the lack of ultrasound and quantitative storm. There is no consensus on the optimum time needed for 13 volatile agents and the effects of ventilation on the pulmonary β-hCG screening may lead to a higher incidence due to delayed medical stabilisation of the hypermetabolic state. Patients system.5,16,17 presentation with higher hCG levels. There have also been case require rapid hormonal improvement and should be clinically reports of hyperthyroidism in patients with choriocarcinoma.4,6 euthyroid before surgery. A normal serum TSH is not the TIVA using propofol and remifentanil with the concurrent primary management target, as it remains suppressed beyond administration of an esmolol infusion has also been used Clinical features normalisation of free T .7 4 successfully. This technique avoids the tocolytic effects of • Sinus tachycardia • Palpitations • Antithyroid drugs (thioamides): PTU; carbimazole; methimazole. volatile agents. It decreases the stress hormone release and • Hypertension • Atrial fibrillation Inhibit thyroxine synthesis.14 PTU also inhibits peripheral haemodynamic response to stimulation. It also allows for a dose- 15 • Cardiac failure • Weight loss conversion of T4 to T3. dependent decrease in blood pressure and heart rate, which is • Hyperactivity • Tremors • Beta-blockers: Propranolol. Thyroid hormones sensitise advantageous in thyrotoxic patients and may decrease blood • Insomnia • Heat intolerance adrenergic receptors to catecholamines. Beta-blockers loss during surgery.18 • Diaphoresis • Diarrhoea control the hyperadrenergic effects of thyrotoxicosis (β ) and 1 An oxytocin infusion should be started after dilatation of the 8,11,14 5,14,15 • Thrombocytopaenia • Muscle weakness decrease the peripheral conversion of T4 to T3 (β2). Target cervix and application of suction.2 Oxytocin decreases the maintaining a heart rate < 100 beats/min.13 The clinical diagnosis of thyrotoxicosis may present difficulties risk of bleeding but early administration increases the risk of • Iodides: Sodium iodide; potassium iodide; Lugol’s solution. as many hypermetabolic signs and symptoms are seen during trophoblastic embolisation and metastases.5 Inhibit thyroid hormone release. Start at least one hour after normal pregnancy, i.e. palpitations, heart rate 90 to 100 beats/min, administration of antithyroid drugs since iodide may cause a Anaesthetic drugs: Hyperthyroidism and its hypermetabolic state mild heat intolerance, warm skin and decreased effort tolerance.7 reflex release of thyroid hormone.7,8,13 can affect the pharmacokinetics of anaesthetic drugs. Propofol Diagnosis or thiopentone may be used for induction of anaesthesia. The The use of plasmapheresis has been reported to decrease latter possesses antithyroid activity.5,18 The volume of distribution • Elevated serum free T3 and T4 concentrations thyroid hormone levels more rapidly in preparation for suction and clearance of propofol is increased in hyperthyroid patients, • Suppressed serum TSH level curettage. This is however an invasive procedure and patients increasing requirements if TIVA/TCI is used.14 Alternatively should be monitored carefully for coagulopathy.9 • Greatly increased thyroid radioiodine uptake etomidate can be used in haemodynamically unstable patients.

• Lower T3:T4 ratio compared to Graves’ disease and multinodular In a bleeding patient it will not be possible to delay emergency Ketamine, indirect acting adrenergic agonists, and other drugs goitre in which the ratio is > 20.4,13 surgery for optimisation of thyroid status. These patients are at that activate the SNS or are unpredictable muscarinic antagonists a particularly increased risk of developing a thyroid storm.14 In are best avoided in patients with current or recently treated Treatment addition to the above-mentioned drugs, they should receive thyrotoxicosis, as they may lead to exaggerated elevations Evacuation of the mole or effective chemotherapy for a glucocorticoid and proceed for surgery with perioperative in heart rate and blood pressure.11 Agents causing histamine choriocarcinoma rapidly achieves clinical and biochemical optimisation. (Beta-blockers are important – however exercise release (atracurium, morphine) and its associated tachycardia euthyroidism.4,6,9 caution in the hypovolaemic hypotensive patient.) should also be avoided.5,18

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Hyperthyroidism does not increase the minimum alveolar PRECIPITANT HISTORY (TRIGGERING FACTOR) concentration of volatile agents11 and excessive concentrations Present 10 should be avoided to minimise the associated uterine tocolytic < 25 unlikely thyroid storm effects, which may increase blood loss. A combination of fentanyl 25–44 suggestive of impending storm ≥ 45 highly suggestive of thyroid storm or sufentanil and paracetamol provide suitable analgesia. Management Monitoring and vascular access: Standard monitoring; large bore IV access; arterial line (+/- CVP) depending on the severity of • Supportive measures: hyperthyroidism; close temperature monitoring. ▫▫ Adequate oxygenation and ventilation

Postoperative care: Hyperthyroid patients should be managed ▫▫ Intravenous fluids in a high care or ICU. There remains a risk of developing a ▫▫ Inotropes/vasopressors 11 thyroid storm postoperatively, despite preoperative medical ▫▫ Correction of glucose and electrolyte abnormalities optimisation.13 Hyperthyroidism resolves rapidly and antithyroid ▫▫ Cooling measures (paracetamol; tepid sponging. NOT medication can be weaned. Aspirin or NSAIDs – may increase free thyroid hormones). Thyroid storm • Management of congestive cardiac failure if present A life-threatening hypermetabolic crisis precipitated by • Appropriate antibiotics if precipitated by infection infection, trauma, surgery, and labour, with mortality rates as • Drugs: Beta-blockade and antithyroid drugs are used as the 7,8,18 high as 15%. It is a clinical diagnosis with accentuated signs first-line treatment.14 and symptoms of thyrotoxicosis, and dysfunction in one or more Beta-blockers: organ systems. Table II lists the main clinical features. Free T4 ▫▫ Esmolol 250–500 µg/kg IV loading dose followed by levels do not correlate with the severity of the symptoms.7 50–200 µg/kg/min infusion OR

Table II. Burch and Wartofsky scoring system for ▫▫ Propranolol 1 mg/min IV OR 60–80 mg PO 4–6 hourly, OR thyroid storm19 ▫▫ Labetalol Criteria Score Glucocorticoids: Inhibit peripheral conversion of T4 to T3. THERMOREGULATORY DYSFUNCTION ▫▫ Hydrocortisone 50–100 mg IV 8 hourly OR Temperature (°C) ▫ Dexamethasone 2–4 mg IV 6 hourly 37.2–37.7 5 ▫ 37.8–38.2 10 Antithyroid drugs: 38.3–38.8 15 ▫▫ Carbimazole 40–60 mg PO/NGT daily, OR 38.9–39.4 20 ▫▫ PTU 1g PO/NGT loading dose then 200–300 mg 6 hourly, 39.4–39.9 25 OR ≥ 40 30 ▫▫ Methimazole 30 mg PO/NGT 6 hourly CENTRAL NERVOUS SYSTEM EFFECTS Iodides: Start at least one hour after antithyroid drugs. Mild (agitation) 10 ▫ Sodium iodide 500 mg IV 8 hourly, OR Moderate (delirium, psychosis, extreme lethargy) 20 ▫ Severe (seizures, coma) 30 ▫▫ Lugol’s Solution 10 drops PO/NGT 8 hourly, OR GASTROINTESTINAL AND HEPATIC DYSFUNCTION ▫▫ Potassium iodide 5 drops PO/NGT 6 hourly7,8,13

Moderate (diarrhoea, nausea/vomiting, abdominal 10 Magnesium sulphate: Decreases adrenergic receptor pain) sensitivity to endogenous catecholamines and associated Severe (jaundice) 30 arrhythmias.14 CARDIOVASCULAR DYSFUNCTION • ICU postoperatively with frequent evaluation of cardiac and Tachycardia (beats/min) respiratory status. 90–109 5 110–119 10 Conclusion 120–129 15 All patients with GTD should be assessed for hyperthyroidism. 130–139 20 Suction curettage is the preferred method of evacuation of ≥ 140 25 molar pregnancies, and leads to normalisation of thyroid Congestive heart failure function. Patients with thyrotoxicosis are at increased risk of life- Mild (pedal oedema) 5 threatening complications such as a thyroid storm, and should Moderate (bibasal crackles) 10 be optimised preoperatively by a multidisciplinary team. The Severe (pulmonary oedema) 15 challenge to the anaesthetist is further increased in the bleeding Atrial fibrillation 10 patient requiring emergency surgery.

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References 10. Chiniwala NU, Woolf PD, Bruno CP, et al. Thyroid storm caused by a partial 1. Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, hydatidiform mole. Thyroid: Official Journal of the American Thyroid Association. clinical presentation and diagnosis of gestational trophoblastic disease, and 2008;18(4):479-81. Epub 2008/03/21. management of hydatidiform mole. American Journal of and 11. Butterworth JF, Mackey DC, Wasnick JD. Morgan and Mikhail's Clinical Gynecology. 2010;203(6):531-9. Epub 2010/08/24. Anesthesiology. 5th ed. New York: McGraw-Hill Education; 2013:733-5. 2. Snyman LC. Gestational trophoblastic disease: An overview. SA Journal of 12. Moskovitz JB, Bond MC. Molar pregnancy-induced thyroid storm. The Journal of Gynaecological . 2009;1(1):32-7. Emergency . 2010;38(5):e71-6. Epub 2009/12/05. 3. Moodley M, Tunkyi K, Moodley J. Gestational trophoblastic syndrome: an 13. Samra T, Kaur R, Sharma N, Chaudhary L. Peri-operative concerns in a audit of 112 patients. A South African experience. International Journal of patient with thyroid storm secondary to molar pregnancy. Indian Journal of Gynecological Cancer: Official Journal of the International Gynecological Cancer Society. 2003;13(2):234-9. Epub 2003/03/27. Anaesthesia. 2015;59(11):739-42. Epub 2016/01/13. 4. Hershman JM. Physiological and pathological aspects of the effect of human 14. Farling PA. Thyroid disease. British Journal of Anaesthesia. 2000;85(1):15-28. chorionic gonadotropin on the thyroid. Best Practice and Research: Clinical Epub 2000/08/06. and Metabolism. 2004;18(2):249-65. Epub 2004/05/26. 15. Marx H, Amin P, Lazarus JH. Hyperthyroidism and pregnancy. British Medical 5. Biyani G, Mohammed S, Bhatia P. Anaesthetic Challenges in Molar Pregnancy. Journal. 2008;336(7645):663-7. Epub 2008/03/22. The Indian Anaesthetists’ Forum. 2013;14(8):1-9. 16. Bhatia N, Mitharwal SM. Hydatidiform mole with uncontrolled hyperthyroidism: 6. Hershman JM. Human chorionic gonadotropin and the thyroid: hyperemesis An anesthetic challenge. Journal of Anaesthesiology Clinical Pharmacology. gravidarum and trophoblastic tumors. Thyroid: Official Journal of the American 2016;32(4):537-8. Epub 2017/01/18. Thyroid Association. 1999;9(7):653-7. Epub 1999/08/14. 17. Solak M, Akturk G. Spinal anesthesia in a patient with hyperthyroidism due 7. Mestman JH. Hyperthyroidism in pregnancy. Best Practice and Research: Clinical to hydatidiform mole. Anesthesia and Analgesia. 1993;77(4):851-2. Epub Endocrinology and Metabolism. 2004;18(2):267-88. Epub 2004/05/26. 1993/10/01. 8. King JR, Lachica R, Lee RH, et al. Diagnosis and Management of Hyperthyroidism 18. Erturk E, Bostan H, Geze S, et al. Total intravenous anesthesia for evacuation in Pregnancy: A Review. Obstetrical and Gynecological Survey. 2016;71(11):675- 85. Epub 2016/12/03. of a hydatidiform mole and termination of pregnancy in a patient with thyrotoxicosis. International Journal of Obstetric Anesthesia. 2007;16(4):363-6. 9. Azezli A, Bayraktaroglu T, Topuz S, Kalayoglu-Besisik S. Hyperthyroidism in molar Epub 2007/04/27. pregnancy: rapid preoperative preparation by plasmapheresis and complete improvement after evacuation. Transfusion and Apheresis Science: Official 19. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Journal of the World Apheresis Association: Official Journal of the European Endocrinology and Metabolism Clinics of North America. 1993;22(2):263-77. Society for Haemapheresis. 2007;36(1):87-9. Epub 2007/03/10. Epub 1993/06/01.

S11 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Cerebral perfusion monitoring during non-neurosurgical procedures: The practicalities of Near Infrared Spectroscopy (NIRS)/Bispectral Index (BIS)

M Mphomane

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of Witwatersrand Correspondence to: [email protected]

Keywords: neuro-monitoring, cerebral perfusion, Near Infrared Spectroscopy (NIRS), Bispectral (BIS), Transcranial Doppler (TCD), monitoring in non-neurosurgical procedures

Introduction Cerebral oxygenation monitoring

Complex non-neurosurgical procedures such as , Near Infrared Spectroscopy (NIRS) monitor major vascular procedures (including carotid endarterectomy), This is a non-invasive, continuous monitor that measures regional liver transplantation, orthopaedic procedures in beach chair cerebral oxygen saturation (rSO2), usually of the frontal area. The position, etc. are commonly associated with devastating values reflect primarily venous saturation as opposed to arterial neurologic complications and poor patient outcome. pulsatile component. Added advantages of NIRS include: that it Neuromonitoring in these procedures assumes a pivotal role in can identify both hypoperfusion and hyperperfusion; and there ensuring timely detection and prevention of permanent brain is no need for blood flow.5 and spinal cord dysfunction. A number of drawbacks are recognised however, and these The most common aetiology of intraoperative neurologic injury include: that it is affected by extracranial blood flow and ambient that can potentially be detected by neuro-physiologic monitoring light; there are no recognised standards or normal values (as is cerebral ischaemia, which may occur as a consequence of variations between individual patients do occur). This means hypoperfusion, embolic stroke, or malperfusion.1 that every patient’s baseline is needed, absolute values are not useful, and trends are more important. Clinically, the major neurologic deficits most commonly observed have been cognitive impairment, seizures, choreoathetosis, Electroencephalogram (EEG) monitor 2 bilateral motor deficits and hemiparesis. This is a measure of spontaneous electrical activity generated by the brain, specifically the cortex; therefore the deeper Multimodal integrated techniques are used to monitor cerebral structures are not assessed. It requires a robust machine with perfusion and thus avoid the above-mentioned complications. multiple electrodes ranging from 8 to 16. Measurements of CBF There is no one modality that has shown to be superior to the are implied from changes in the amplitude, frequency and the other and in practice monitors are used to complement each patterns of the EEG bands (α, β, δ).3 other. The added limitations are that the raw data produced from the Cerebral perfusion monitoring modalities EEG is quite complex, and needs interpretation by experienced personnel and therefore limiting its use. Anaesthetic agents and Cerebral perfusion monitors seek to ensure that adequate also extensively affect it. perfusion to the brain is maintained at all times. In order to perfuse the brain adequately cerebral perfusion pressure (CPP) Bispectral Index (BIS) monitor has to be maintained, and CPP is defined by the following This is a processed EEG, originally designed to assess the equation: hypnotic level of a patient. But it can now be used to detect CPP = MAP – ICP (or CVP)3.4 (MAP – mean arterial pressure, cerebral ischaemia in the intraoperative period. The monitor ICP – intracranial pressure, CVP – cerebral venous pressure) gives a value, called a BIS value ranging from 0 to 100. Reduction in BIS value by more than 10 or by 30–40% may correlate with Adequate perfusion of the brain and prevention of ischaemia ischaemia.4 can be achieved by measuring the following parameters: The limitations of this mode of measurement include delay in Cerebral oxygenation and cerebral blood flow (CBF) reporting of about 30–60 seconds due to processing of data from

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raw EEG data. BIS also does not differentiate between localised NIRS is a measure of cerebral perfusion that relies on the and global ischaemia. difference of absorption spectra between oxyhaemoglobin, deoxyhaemoglobin and the total haemoglobin for calculating Cerebral Blood Flow (CBF) monitoring 2 estimates of regional cerebral oxygen saturation (rSO2). (Beer CBF monitoring offers a rational approach to detect and Lambert law). prevent ischaemic insults to the brain and improve outcome in The technique requires the use of two sensors separated by patients undergoing major non-neurologic procedures. Normal a fixed distance. The proximal sensor records infrared light value of CBF in young adults is 50 ml/100 g brain tissue/min. The ischaemic threshold is 18 ml/100 g/min and below 10 ml/ reflected from superficial tissue while the distal signal represents 100 g/min, irreversible brain damage ensues.3 the brain tissue saturation. The subtraction between these two signals represents a venous weighted estimate of rSO2. The CBF monitors may be classified into two broad categories: direct and indirect measurements. Usefulness of cerebral NIRS Indirect monitoring It is a non-invasive technology that provides continuous monitoring of regional cerebral oxygenation. The machine is Transcranial Doppler (TCD) portable, sensors are easy to apply, and interpretation of results 6 This is a non-invasive, bedside technique that measures local needs no specialised expertise. blood flow velocity. It presents these data graphically as velocity The monitor can identify both hypoperfusion and hyperperfusion. against time. The changes in velocity indicate pathology, e.g. Due to the strategic placement of the electrodes, the watershed hypoperfusion due to stenosis, thrombosis or hyperperfusion. area between the anterior and the middle cerebral artery The limitations of TCD are that it is operator-dependent, there territories are included in the NIRS measurements. is signal interference with numerous electromagnetic apparatus NIRS is relatively resistant to the effects of anaesthetic agents, in the operating room. In 10–15% of patients, there is a lack of but can be affected by the indirect changes in the global blood acoustic transtemporal window, and therefore the test cannot be flow due to physiological changes due to drugs. Therefore, to carried out. allow meaningful interpretation of neuromonitoring results, Stump pressure steady state anaesthetic depth, physiological variables, such as blood pressure, temperature, and patient position should be During carotid endarterectomy, when the proximal common kept stable.4 carotid and external carotid arteries are clamped, the pressure measured in the internal carotid craniad to the clamp site is In non-neurological procedures NIRS has been found very useful the stump pressure. It reflects the back pressure on the internal in determining the risk of significant cerebral ischaemia, and carotid artery, supplied by the collaterals from the circle of therefore implementing appropriate treatment algorithms are Willis. It is considered to be a surrogate marker of perfusion in the following: procedures in beach chair position, repair of aortic the ipsilateral cerebral hemisphere from the contralateral side. coarctation, aortic aneurysm repair, cardiac surgery, carotid A pressure below 40–55 mm Hg is often used as a threshold for endarterectomy, etc. intervention.4 Spinal NIRS monitoring looks to be an attractive alternative Direct monitoring monitoring during procedures such as thoracic and abdominal Positron Emission Tomography (PET) aorta repair.6,7 The same advantages as mentioned above apply here. The problematic issues are also as depicted above. For This mode is an invasive, quantitative measure of CBF, cerebral instance, the interference of the surrounding paraspinal space metabolic rate of oxygen (CMRO ), cerebral blood volume (CBV), 2 tissues. and oxygen extraction fraction. It uses a radioactive compound, and requires patients to be transported to a facility, Limitations of NIRS therefore impractical for intraoperative use. Although it is considered a gold standard, it is expensive, not universally NIRS reading is affected by the scalp tissue composition in available and gives a short single assessment. different individuals, and therefore it is difficult to compare to ‘standards’/‘normals’. Ambient light also affects NIRS reading, Practical use of NIRS and BIS during necessitating proper padding of the electrodes. non-neurosurgical procedures The monitor can only assess regional oxymetry, usually frontal, 6 Near Infrared Spectroscopy (NIRS) so clinically relevant focal cerebral ischaemia outside the monitored area may easily go unnoticed. Patients with previous infarcts may produce erroneous measurements. Bispectral monitor (BIS)

Bispectral analysis represents a processed EEG, originally designed to assess the hypnotic level, and therefore avoid awareness. The BIS monitor gives a single numerical reading between 0–100, that denotes the level of hypnosis.8 It uses

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Table I. Characteristics of various cerebral perfusion monitors9

Characteristics of various cerebral perfusion monitors

Monitor Detection of Cerebral Expense Ease of Comment Ischaemia Use

EEG • High false positive rate ++ ++ • Difficult to interpret • Does not detect subcortical ischaemia • Low sensitivity in previous stroke

Somatosensory evoked • No more specific or ++ ++ potentials (SSEPs) sensitive than EEG

Bispectral index (BIS) • Poor + +++

Stump pressure • High specificity + +++ • No consensus on critical pressure • Low sensitivity ++

Transcranial Doppler (TCD) • Poor ++ + • Useful for detecting emboli • Unusable in 15-20% people • No consensus on critical MCAv value • Operator dependent results • Bulky equipment

Near infrared spectroscopy (NIRS) • High negative predictive ++ +++ • Placement over frontal lobes ot ideal in CEA value • Signal contamination ++ • Low specificity • No 'normal' range • Poor positive predictive value

Jugular venous bulb SpO2 • Low specificity ++ ++ • Invasive technique • Poor positive predictive value

Xenon - 133 • Low specificity +++ + • Very expensive ++ • Experimental • Difficult to interpret results a set of three disposable electrodes attached to the patient’s Studies have shown that no single monitor is capable of frontal and temporal regions. The machine is portable, and in exclusively and conclusively detecting cerebral malperfusion. fact some anaesthetic machines are fitted with cartridges for BIS A multimodal, complementary approach is recommended. monitoring. The accuracy of the BIS to monitor hypnotic state NIRS promises to be quite a valuable technique to use in non- has been questioned due to inconsistencies associated with it neurosurgical procedures to avoid neurologic complications in many studies.4 associated with these high-risk procedures. On the other hand, The recent use of BIS has been to detect cerebral ischaemia BIS has been found to be disappointing in terms of accurately during non-neurosurgical procedures. Reduction in BIS value determining depth of anaesthesia as well as detecting cerebral may correlate with ischaemia.4 ischaemia.

Limitations of BIS monitor for use in detecting cerebral ischaemia References intraoperatively are numerous, and include: 1. Cheung AT. Neuromonitoring in cardiac surgery or deep hypothermic circulatory arrest. Optional or imperative? Scahq.org 2014. • Delay in reporting owing to the time needed for processing 2. Rodriguez RA. Intraoperative brain monitoring: www.anaesthesia.org/ of EEG data. winterlude/w197/l_neuro.html/ • Lack of differentiation between global and focal ischaemia. 3. Mahajan C, Rath GP, Bithal PK. Advances in neuro-monitoring. Anesthesia essays and researches. 2013; 7(3) 31 -318. • Inhalational and intravenous anaesthetic agents decrease 4. So V C, Poon CCM. Intraoperative neuromonitoring in major . Br BIS value in a dose-dependent manner, ultimately resulting J Anaesth (2016) 117 (suppl_2): ii 13-ii 25. in burst suppression and electrical silence similar to severe 5. Mėrat S, Levecque JP, Gulluche Y, et al. Monitoring may allow the detection of hypoperfusion and ischaemia.4,9 Table I gives comparison severe cerebral ischaemia. Can J Anaesth. 2001; 48:1066-1069. amongst different types of cerebral perfusion monitors.9 6. Moerman A. Clinical application of near-infrared spectroscopy in perioperative. biblio.urgent.be/publication/ Conclusions 7. Kawano H, Matsumoto T. Anaesthesia for arthroscopic shoulder surgery in the beach chair position: monitoring cerebral oxygenation using bispectral index Numerous modalities for measurement of cerebral perfusion and near-infrared spectroscopy. Middle East J Anaesthesiol. 2014; 22 (6):613-617. during high-risk non-neurosurgical procedures are available. 8. William M, Lee JK. Intraoperative blood pressure and cerebral perfusion: strategies to clarify haemodynamic goals: Paediatr Anaesth. 2014; 24 (7): The aim of monitoring cerebral perfusion in these procedures 657-667. is to detect cerebral hypoperfusion, malperfusion, and embolic 9. Whiten C, Gunning P. Carotid endarterectomy: intraoperative monitoring of complications early and therefore avoid cerebral ischaemia. cerebral perfusion: current anaesthesia and critical care 20 (2009) 42-45

S14 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Anaesthesia for related living donor liver transplantation

M Hatchett

Wits Donald Gordon Medical Centre Transplant Unit Dunkeld Anaesthetic Practice

Introduction Critical to the concept of LDLT, specifically for adult-to-adult procedures, is the fact that the liver can regenerate its tissue The first liver transplant was performed in 1963 in Colorado, extremely rapidly. Within two to three months of 40% of a liver USA by Dr Thomas Starzl, a man who is acclaimed world-wide having been removed as a donor graft, the liver has regenerated as the father of . His career and list of that volume so that it has regained full function. As regards the accomplishments can, and has been, the individual subject of South African situation with LDLT, most of our cases are those lectures by themselves, but suffice to say that it is difficult to where a parent is donating a portion of their liver to a child. foresee many people surpassing his achievements in medicine. This is usually the left lateral lobe and the volume of liver lost is At one stage in his career it was calculated he was producing small relative to the liver’s original volume. The situation is very a scientific paper for publication every seven days. He died in different where a large proportion of the liver has to be donated March this year at the age of 90. because the recipient is an adult. There can then be a problem having sufficient functioning liver tissue for the donor and/or the As we are all aware, liver transplantation is the only real hope recipient. This phenomenon is known as ‘small for size’ and can for end-stage liver disease. In kidney disease we have dialysis be extremely serious, if not life-threatening. as a method of prolonging life, albeit very restrictive for the patient and certainly not ideal. For progressive liver disease we Advantages of LDLT have liver transplantation or death. The results and outcomes of 1. The LDLT is done as an elective procedure. This means liver transplantation have improved exponentially since 1963, everything is preplanned and controlled. As it is invariably particularly as a result of advances in immunosuppression and scheduled for a morning start, staff are fresh and all support decreased rejection of transplanted organs. The main problem staff should be readily available. This is in stark contrast to that still remains is the perennial shortage of donor organs for cadaver transplants where there is little, if any, control over the huge number of recipients requiring them. when the procedure will go ahead, and often occurs in the middle of the night with on-call staff that may be tired. Deceased vs living donors Ancillary discipline staff may also not be readily available and Traditionally, particularly in South Africa, donor organs have have to be roused from bed and brought in at short notice. come from brain-dead patients with functional cardiac systems 2. Donors are thoroughly investigated with multiple on ventilators. Elsewhere organs have also been procured examinations and investigations over a period of time before from controlled non-heart-beating donors (often for religious being passed fit to donate a liver segment. Any deviations and cultural reasons), or patients on ECMO support after from the norm in the donor’s health usually means they are cardiac death. The huge step forward has been the successful turned down and other potential related donors are sought. introduction of removal of a portion of a healthy donor’s liver This also translates into a good quality donated organ being so that both donor and recipient survive thereafter. There is a recovered. This luxury of extensive preoperative assessment significant difference in transplant patterns between Western of the donor is not always present with cadaver-derived and Eastern countries. The Western countries continue to have organs. higher numbers of liver transplants where the donor organ 3. LDLT procedures allow recipients to ‘jump the queue’. came from deceased donors, whereas in the Eastern countries, Ordinarily patients placed on the liver transplant list at an because of religious, cultural and social differences, living donor institution are prioritised on their MELD score (Model for liver transplants (LDLT) are the commonest means of a patient End Stage Liver Disease). This scoring system is based on receiving a transplant. the patient’s blood levels for bilirubin, creatinine, sodium, as

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well as their INR and their frequency of haemodialysis. The Potential donors must be made acutely aware of all possible more severe their liver disease, the higher their MELD, and adverse outcomes and dangers. Repeated visits and discussions they are then higher on the list and likely to get a transplant with the physicians involved must be held and subjects discussed sooner than those below them. An alternative score is used until the potential donor clearly understands the possible for paediatric patients known as the PELD score and is dangers. An impartial , who is not part of the transplant based on measures of bilirubin, albumin, INR, growth failure team, is appointed as an advocate to any potential donor. This and patient age. As patients are only placed on the list if it person must make sure the donor is completely informed about is felt they will demise in the next twelve months without the procedure and is under no external family pressure to donate. a transplant, and there is a scarcity of donor organs, time On occasion when it is detected that the family is attempting to and placing can be all important in a patient’s survival. With coerce someone into donating, the physician can actually say to a LDLT the specific recipient is done as soon as his related the family that the person is ‘unsuitable’ for some vague health donor is considered suitable and the recipient’s position on reason so that he is not ostracised at home for refusing to donate. the list is immaterial. The guiding principle for LDLTs is that doctors need to maximise 4. With LDLTs there is a decreased ischaemic time. The time benefits to the recipients, while minimising risks to donors. from clamping when the donor segment is removed, to the time when reperfusion occurs in the recipient, is minimal as Donor assessment the two theatres where the donor procedure and recipient 1. A potential donor must be a relative (with special permission procedure occur are usually adjacent theatres and continually a friend is sometimes allowed to donate). liaise with one another. There is thus careful co-ordination 2. Donor must be a healthy adult over 18 years of age and to ensure the recipient team is ready to receive and insert usually less than 60. the donor organ before it is clamped and removed by the donor team. There is a direct correlation between ischaemic 3. Donor and recipient must be of the same blood group. time and graft survival. This contrasts with cadaver organs 4. Physicians consult. that may be harvested in Durban, and make a long journey 5. Surgical consult. before reperfusion occurs in Johannesburg some hours later. 6. Cardiological consult including Echo. If any cause for concern Experienced transplant centres can usually claim a five-year an angiogram may be done. survival rate of above 80% in children receiving a LDLT for biliary atresia. 7. Psychologist consult. 5. The donor pool is significantly increased by investigating all 8. Ultrasound abdomen. listed recipients (particularly paediatric ones) as to whether 9. CAT scan triple phase abdomen. there may be appropriate related living donors. 10. MRCP if adult to adult being considered. Disadvantages of LDLT 11. In females a PAP smear is done, and if over 50 years of age a mammogram is done. The main disadvantage of LDLTs is the significant risk posed to the donor. People that agree to selflessly donate a portion of one 12. If all investigations are acceptable, an assessment of liver of their most vital organs to help save a life of a close or extended size and shape has to be made. The graft to recipient body family member, or occasionally even a friend, must be lauded for weight ratio has to be determined, as well as the graft weight their courage and sense of humanity, and every effort made to relative to the weight of the whole donor liver. minimise any danger to them. Figures differ dramatically from 13. 3D CT angiography will reveal if the vasculature is such that centre to centre but morbidity figures of 25%, and mortality rates the graft can be separated from the donor liver and still of 2%, are relatively commonplace. contain an adequate artery and vein to enable successful anastomosis in the recipient. The horrific occurrence of a healthy donor losing their life because of a medical problem, whilst trying to aid another, 14. 3D MR cholangiography gives the necessary information has far-reaching effects on many people. Besides the patients about the bile duct anatomy of the donor organ. themselves, the effect on the donor’s nuclear and extended 15. An idea of the shape of the donor organ must be obtained. families is devastating. As well, the publicity occurring from a A thin flatter section of tissue is preferable in adult to child death of a donor in a LDLT can be severe enough to close a well- transplants and is more commonly obtained in females. established transplant programme in a respected institution. This has occurred in the United States previously and, as usually Points of interest: occurs in medicine, the one bad event is always remembered 1. Positive testing for HIV, Hep B and Hep C exclude patients long after the hundreds of good ones have been long forgotten. from being donors. An exception is made in Eastern countries There have been cases where the donor has survived and has left where a person is Hep B antibody core positive. Hepatitis B hospital with a new lease on life, but the recipient has demised. infection in Asia is rampant and if past infection/immunity There have also been incidents where the recipient has done is detected in the donor, the recipient is given immunisation well, but post LDLT the donor has had a huge insult to his own and lamivudine is administered and the LDLT can go ahead. hepatic function and has had to receive a liver transplant himself. Naturally this is if a more acceptable donor cannot be found.

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2. ABO incompatible LDLTs have been done in dire emergencies particularly meaningful. The consensus is, however, that fluids where time is running out for the recipient and no alternative must be severely restricted until after the hepatectomy is done, donors are available. Extra immunosuppression is required and thereafter fluids status restored with rapid administration. 3. and a stormy course can ensue. Hypotension intraoperatively should be rectified with 4. Well-controlled hypertension and well-controlled diabetes vasopressors. Low venous pressure is aided by the epidural which mellitus are not necessarily exclusion criteria in most centres. redistributes fluid in dilated vessels. If necessary, venodilators like nitroglycerine can be added but I have never felt a need to 5. Pregnancy is naturally an exclusion criterion for liver employ this method. There are even reports of phlebotomy post- transplantation. There is a case recorded, however, of a second semester parturient in Taiwan donating a liver lobe induction as a method to decrease venous pressures. Note that to her child when no other donor could be found. Both donor there are also reports in the literature of air embolism occurring and recipient did well and mom delivered a healthy term as the liver is divided if the venous pressure is too low. Besides baby. Obviously this would be a very last resort and would the CVP being used as an indicator of venous fluid status, there only be considered with full education on the risks and are also many references advocating Stroke Volume Variance as danger being imparted the potential donor. In the case done a useful indicator. it was recorded that it was done at the mother’s insistence. In good hands the blood loss during the surgery is relatively Donor anaesthesia small. The newer technology available to the surgeons as regards cutting and coagulating simultaneously has changed As regards the actual anaesthesia, this is relatively standard the volume of blood lost over the last 20 years exponentially. We as for all hepatectomies. All the above-mentioned extensive always routinely have a perfusionist in theatre available to do investigations are done prior to the anaesthetist performing his cell-saving if required. preoperative assessment. Unless the patient’s cardiorespiratory and general health is excellent, he will not be presenting for a Serial blood gases done intraoperatively give information donor hepatectomy procedure, but naturally all aspects must be regarding metabolism, blood loss, ventilation and fluid status. rechecked and all investigation results studied. At the end of the procedure the patient is usually extubated, An epidural should always be discussed with the patient as unless there are specific reasons not to do so. Transfer to ICU regards analgesia. The incision is a horizontal “bucket-handle” follows and meticulous attention must be paid to monitoring one and is particularly painful postoperatively. I find the rectus of the patient’s liver function and coagulation profile. Small for sheath catheters for local anaesthetic infusion superb for midline size scenarios can occur if a large graft has been taken. The liver incisions, but less so for the horizontal incisions. The usual hypertrophies quickly and regains full size within three months. epidural contraindications for back pathology apply, but other If there is a marginal deficit in liver tissue and function, ICU contraindications will probably have been eliminated during support for a few weeks may be enough to allow the donor to the extensive investigative phase. Naturally the patient must agree to the epidural insertion. If an epidural is not used, other regenerate enough tissue to survive and regain normal function. standard regimens of analgesia using opiates must be employed. In rare extreme cases donors have ended up requiring transplant Check the coagulation status prior to the removal of an epidural themselves as liver function has been so greatly impaired. catheter as post-hepatectomy derangement can occur. Conclusion A standard technique is used with The introduction and successful mastering of LDLT has been a intubation, ventilation and muscle relaxation. Some articles in huge step forward in the 54 year history of liver transplantation. the literature recommend using atracurium or cisatracurium in It has provided a potential source of organs for patients with case liver metabolism is diminished by the procedure but I think fulminant liver disease that have days to find one. Countless that is highly unlikely. With the advent of sugammadex I feel this infants have been saved that would previously have perished, is unnecessary. via the donation from a parent of a small liver segment. The work A large bore peripheral line should be inserted so fluids can be involved can be very taxing, arduous and stressful, but proficient given rapidly if required. Some articles advocate having a rapid experienced units have very high levels of success and provide fluid administration mechanism in theatre such as a Level One an invaluable service. pump. Bibliography An arterial line must be inserted for beat-to-beat blood pressure 1. Jawan B, et al. Review of anaesthesia in liver transplantation. Acta monitoring and repeat blood gas sampling, and a CVP must Anaesthesiologica Taiwanica 2014;52 185-196. be inserted for venous pressure monitoring and good access. 2. Teo L. Anaesthesia for related liver transplantation. Proceedings of Singapore The patient should be kept ‘dry’ as regards fluid replacement. Healthcare 2012;21 187-193. The literature is virtually unanimous in the conclusion that 3. Balistreri W. What are the risks to donors in living transplantation. 2010. Disclosures September 2010. http//www.medscape.com/viewarticle/728209. decreased venous pressure decreases bleeding from the liver 4. Kowalczyk L. Donor’s death shatters family, stuns surgeons. 2nd February 2014. during surgery. Many articles give a definitive number for the Boston Globe. CVP (usually 4 to 5 mmHg) over which bleeding increases. Other 5. Zuckerman M, Loveland J. Selection and work-up for liver transplantation. SAMJ authors feel an absolute CVP number is inaccurate and not 2012;102(11) 876-878.

S17 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

The bleeding parturient: anaesthetic perspective

D Nel

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of Witwatersrand Correspondence to: [email protected]

Deaths due to obstetric haemorrhage increased by 24.7% between 2002 and 2011.1 The majority of these deaths were deemed preventable.1 Uterine blood flow at term approximates 700 ml/min making bleeding from the uterus a potentially life-threatening complication that requires a rapid response.

Keywords: maternal mortality, massive obstetric haemorrhage, antepartum haemorrhage, postpartum haemorrhage, blood transfusion, cell salvage, antifibrinolytics

You have known me for 9 months a percentage of the total number of severe maternal outcomes. But I have never met you Severe maternal outcomes are deaths plus near-misses. There You had fed me for a lifetime was again a very big difference between low-income countries But I never got as much as a spoonful from your hand and high-income countries with low-income countries having an You had loved me so much iMMR (institutional Maternal Mortality Rate) for PPH of 95/100 Yet I never got a hug from you 000 live births vs 5/100 000 live births in high-income countries.4 For you had given your life so I can live In South Africa there has been a worrying trend where the The same blood that was my breath number of deaths due to bleeding has been steadily increasing Took yours away… since 2002.1,5–8 This trend, however, has also been observed in Mom, I love you so much high-income countries.9 In South Africa, the iMMR for obstetric I wish you were here. haemorrhage was 19.51/100 000 live births in the 2002–2004 ~Dorinka~ triennium compared to 24.32/100 000 in the 2008–2011 Introduction triennium. This is an increase of 24.7%. The majority (89%) of deaths due to bleeding could have been prevented.1,8 One-third For centuries the peripartum period was a dangerous period of deaths due to bleeding were at or after Caesarean delivery.1 in the lives of new mothers. The mortality rates were largely 10 inaccurate till the introduction of national registries. In Britain, Studies on near-misses in South Africa are scanty. Soma-Pillay the Registration of Deaths Act was passed in 1837.2 At this point reported a mortality index for bleeding of 2% in the Pretoria 11 the definition of maternal death was not well defined leading to Academic Complex, while Maswime reported a near-miss further inaccuracies in the data. With time and better definitions, rate of 2.1/1 000 Caesarean deliveries for bleeding at or after however, they were able to get more accurate data. The quest Caesarean section in a cross-sectional prospective study in 13 was then on to improve maternal mortality rates. Mothers were urban public hospitals in South Africa. Significant morbidity dying from puerperial sepsis, bleeding, seizures and illegal associated with obstetric bleeding includes acute kidney injury, abortions. These causes of death remain amongst the most coagulopathy, acute respiratory distress syndrome, shock, loss of 12 common factors involved in maternal morbidity and mortality. fertility and pituitary necrosis.

13 Death due to bleeding remains a big problem, especially in Definitions low-income developing countries where 99% of all maternal • Massive obstetric haemorrhage mortality occurs.3 ▫▫ Blood loss of more than 1 500 ml While death is the worst outcome related to obstetric ▫▫ A decrease in the haemoglobin of more than 4 g/dl haemorrhage, the majority of patients with life-threatening ▫▫ The need for transfusion of more than 4 units of packed obstetric haemorrhage survive the ordeal. It may thus be useful red cells to also look at these “near-misses”. Data on near-misses are less readily available. A recent systematic review of near-misses due • Antepartum haemorrhage to postpartum haemorrhage (PPH) puts the global mortality ▫▫ Bleeding from or into the genital tract that occurs after index for PPH at 6.6%.4 Morbidity index is the number of deaths as the 24th week of gestation but before delivery14

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• Postpartum haemorrhage Neonatal: ▫▫ Primary • Preterm delivery . Obstetric bleeding that occurs from the time of • Small for gestational age infant delivery up to 24 hours postpartum • Neonatal death ▫▫ Secondary . Obstetric bleeding that occurs from 24 hours up to Coagulopathy complicates about 10% of cases with abruption six weeks postpartum placenta. When there is intrauterine foetal demise, the incidence goes up to 30%.30 The biochemical picture is that of low Antepartum haemorrhage fibrinogen, low platelets and increased fibrinogen degradation Placenta abruption products (FDP).

Abruptio placentae complicates about 1% of pregnancies and up The placenta, myometrium, amniotic fluid and the decidua have to 20% of premature deliveries occurs because of abruption.14–16 very high levels of tissue factor (TF) and tissue factor pathway Placenta abruption occurs when placental separation occurs inhibitor (TFPI).20,31 Tissue factor in placenta is up to 7 800 times before the birth of the fetus.17 It can be complete or partial. higher than the plasma concentration. Tissue factor is even more The rupture of the spiral arteries with subsequent formation of abundant in the placentas of patients with pre-eclampsia.32 a retro-placental clot causes the separation.18–20 Surrounding tissue and myometrium is also damaged in the process. Foetal With placental abruption, TF and TFPI are released from the demise can occur especially with a more than 50% abruption.17 damaged placenta and myometrium and concentrate in Clinical signs associated with severe abruption include vaginal the retroplacental clot. From there, they enter the maternal bleeding (usually dark blood), severe abdominal pain and severe circulation where they cause activation of the tissue-factor 15 uterine contractions. Mild cases may be asymptomatic and a pathway. The resultant widespread coagulation leads to a retroplacental clot only detected after delivery of the placenta. consumptive coagulopathy. Fibrinolysis of the intravascular clots Blood loss can also be concealed within the uterus in up to results in the formation of fibrinogen degradation products. High 20–30% of cases.19 levels of FDP have an anti-coagulant effect.33 FDP also interferes There are multiple risk factors for placenta abruption.14,15,21–29 with uterine contractility further aggravating the bleeding.34

Risk factors for abruptio placentae Couvelaire described a complication of utero-placental apoplexy • Abruption in previous pregnancies as early as 1911.35,36 Utero-placental apoplexy was later called • Pre-eclampsia Couvelaire uterus. Couvelaire uterus occurs in approximately 5% • Advanced maternal age of abruption cases.35,37 Blood from the damaged placental vessels • Intrauterine growth retardation extravasates into the decidua and laterally into the myometrium • Presentations other than vertex and can extend to the serosa. It gives the uterus a characteristic • Polyhydramnios blue colour. The uterus becomes thin and weak and there is a • Multiparity risk of uterine rupture especially in the presence of intense • Low BMI uterine contractions.38 The presence of Couvelaire uterus is not • Intrauterine infection necessarily associated with uterine atony and the mere presence • Premature rupture of membranes thereof is not per se an indication for hysterectomy.39 • Abdominal trauma Placenta praevia • Pregnancy after assisted reproductive therapy • Smoking and illicit drug use A placenta covering the internal os, or implanting close to the • Short umbilical cord internal os, is known as a placenta praevia. It is a complete placenta praevia when the internal os is covered, or a marginal Complications associated with abruptio placentae17 placenta praevia when the leading edge of the placenta is within Maternal: 2 cm from the os, but not covering it. The quoted incidence of • Coagulopathy this complication ranges between 0.15%40 to 2.5%.41 • Hypovolaemic shock Although the exact pathophysiology is unknown, it seems that a • Adult respiratory distress syndrome scarred uterus is a major contributing factor.42 • Renal failure • Need for blood transfusion Placenta praevia presents as painless vaginal bleeding in the third • Hysterectomy if uncontrolled bleeding trimester. The lower segment starts to form in the third trimester. As the myometrium thins out, the placental attachment in this Foetal: area is disrupted. The lower segment has an abundance of type 2 • Intrauterine growth retardation PGE2 receptors that cause relaxation. With decreased contractility • Foetal distress in the lower segment, the bleeding vessels cannot be occluded • Foetal death by contraction and bleeding continues.

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Risk factors for placentae praevia24,42–51 ligation and postoperative methotrexate. If placenta percreta is suspected, other surgical disciplines also need to be involved Previous C/S in the surgical delivery. Urological injuries are a concern. The Previous uterine surgery bladder is often involved. The ureters need to be identified Previous placenta praevia and protected and the placement of ureteric stents should be Previous uterine curettage considered.53 Infertility treatment with assisted conception The majority of cases are delivered by Caesarean section.59 Due Endometriosis to the potential risk for torrential blood loss, general anaesthesia Advanced maternal age is the safer choice. Blood bank should be alerted to the possible Multiparity need for massive blood transfusion. Preoperative haemoglobin Multiple gestation levels should be optimised. From a surgical prospective, it is best Previous abortions to avoid manual removal of the placenta.53 Smoking and illicit drug use Uterine rupture Abnormally invasive placenta52 This rare complication can result in significant maternal and An abnormally invasive placenta results when the foetal morbidity and mortality. Uterine rupture occurs when syncytiotrophoblasts invasion extends into the deeper layers there is full thickness rupture of the myometrium and the of the myometrium. The degree of invasion leads to the peritoneum covering the uterus. This is in contrast to scar classification of placenta accreta, increta or percreta. A placenta dehiscence where the peritoneum remains intact and the foetus invading the myometrium only is known as accreta. When this is not expelled into the abdominal cavity. The scar edges in invasion extents to the serosa, it is known as placenta increta. dehiscence typically do not bleed. Uterine rupture can occur in In severe cases, the placenta extends beyond the uterus and both scarred and unscarred uteri. It is, however, more common invades surrounding tissues and organs such as the bladder, in cases with previous uterine surgery especially classical uterine bowel, etc. The reported incidence varies between different incision. Other causes of uterine rupture include induction or studies but is around 10 times higher than the reported incidence augmentation of labour, over-distention of the uterus, abnormal in the 1950s.53 This is likely due to the higher Caesarean section placentation, dystocia, advanced maternal age and post-dates. rate compared to that time period.54 The clinical signs are significant vaginal bleeding, severe Risk factors for abnormally invasive placenta53–55 abdominal pain, foetal distress or foetal demise and palpation Presence of placenta praevia of foetal parts. Previous Caesarean delivery Other causes of antepartum haemorrhage Previous myomectomy • Cervicitis Previous curettage • Trauma to genital tract Advanced maternal age • Vasa praevia Increased parity ▫▫ Foetal blood vessels running close to or across the internal os Submucosal fibroid Asherman syndrome Advanced abdominal (extrauterine) pregnancy

Short period between Caesarean delivery and subsequent This rare complication happens when an ectopic pregnancy conception progresses past 20 weeks gestation within the abdominal cavity.60 The placenta implants into abdominal or pelvic organs, An abnormally invasive placenta poses a major bleeding risk blood vessels or the abdominal wall. About 1% of ectopic to the mother. Blood loss may be between 3 000–5 000 ml.53,56 pregnancies progress to advanced abdominal pregnancies.61–63 Mortality from this condition has been reported to be as high The diagnosis is not always straightforward and the physician as 7%.57 Other complications include the risk for DIC, emergency needs to maintain a high index of suspicion. There are some hysterectomy, ARDS, acute renal failure and injury to surrounding clues that should alert the physician to a possible extrauterine structures.53 pregnancy. These include a history of vaginal bleeding and abdominal pain in the first trimester or persistent abdominal Women with risk factors should be identified antenatally and pain, history of previous pelvic surgery, history of infertility or delivery of confirmed cases should be carefully planned. The fertility treatment, abnormal foetal lie, painful foetal movements, timing of delivery should be individualised and the optimum oligohydramnios, abnormal appearance of the placenta on timing seems to be around 34 weeks gestation and after foetal ultrasound with absence of myometrial tissue between the lung maturation has been achieved.53,58 The management uterus and the bladder,64 features of foetal demise or failed should be multi-disciplinary. Various modalities are employed to induction of labour.65 The pregnancy may also be complicated decrease the blood loss and to try and save the uterus in women by pre-eclampsia as the placentation is abnormal. who desire future fertility. Successful pregnancy afterwards is, however, rare. These strategies include internal iliac balloon Foetal complications are even more common than maternal catheters, uterine artery embolisation, internal iliac artery complications. Foetal demise is the most common outcome

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60,66 with reported incidence of between 40–95%. In cases where Tocolysis placental blood flow is sufficient, the foetus can survive to term. Longer duration of labour 93 Foetal abnormalities can occur due to vascular disruptions or Pre-eclampsia and HELLP syndrome 84 due to the compression from surrounding abdominal structures. Coagulation abnormalities84 Craniofacial abnormalities, joint problems, limb and central nervous system disruptions are the most common associated Predelivery anaemia morbidities.65,66 Causes of postpartum haemorrhage If the diagnosis is made preoperatively, it allows the physicians to plan the delivery and to have blood products readily available.65 One or more of the so-called 4 Ts 69,84,94 may be the cause of PPH

There is controversy around whether the placenta should be • Tone removed or left in situ. Removal of the placenta may be associated ▫▫ Responsible for about 70–90% of cases of PPH69,94 with torrential bleeding that may be difficult to control especially ▫▫ May be episodic and unpredictable if the liver or spleen was the site of placental implantation. ▫▫ Included in this category is uterine inversion and Bleeding is associated with high maternal mortality.67 Leaving abruption placenta the placenta in situ may also lead to complications of sepsis, necrosis or postoperative ascites.61,68 ▫▫ Volatile anaesthetic agents decrease uterine tone • Tissue Choice of anaesthesia should take into consideration that there ▫ Retained placenta or products of conception is the potential for massive blood loss. ▫ ▫▫ Abnormal placentation Postpartum haemorrhage • Trauma Postpartum haemorrhage complicates around 5% of ▫▫ Uterine rupture pregnancies.69 Postpartum haemorrhage is defined as acute ▫▫ Genital tract lacerations/episiotomy blood loss of more than 500 ml in vaginal deliveries and more than 1 000 ml in Caesarean deliveries. The problem with using ▫▫ Broad ligament haematoma/surgical trauma this definition is that blood loss is often under-estimated.70–72 • Thrombin ▫▫ Coagulopathy genetic/acquired Another way of estimating blood loss would be to observe the haematocrit. Unfortunately this is also not particularly useful Prophylaxis and treatment of postpartum as torrential bleeding may become life-threatening before a haemorrhage95 drop in haematocrit is observed, while intravenous clear fluids Oxytocics96 and antenatal haemoconcentration may also make the value unreliable. Oxytocin is the first-line drug in the prevention and treatment of uterine atony. It is also the cornerstone of “active management Risk factors associated with postpartum haemorrhage of the third stage of labour” which in itself is one of the Previous PPH73–75 recommendations to decrease the incidence of postpartum 75,76 Assisted conception haemorrhage.97 Increased BMI75,77,78 Oxytocin has a short half-life and thus needs to be given as an Advanced maternal age79–83 infusion to prevent uterine atony. The infusion dose needs to be Previous C/S84,85 individualised to every patient and situation. A patient with risk Abnormal placentation75 factors for PPH will need a higher dose than a patient with no Placenta praevia especially anterior location Placenta abruption risk factors presenting for an elective delivery. Internationally the Invasive placentae infusion dose range from 5 IU/h to 10 IU/h.95,98 The infusion needs Overdistended uterus to be continued for at least four hours after Caesarean delivery. Multiple gestation75 The South African ESMOE guidelines suggest an infusion of Polyhydramnios 20 IU/1 000 ml crystalloids at 125 ml/hour.99 This can be increased Abnormal lie 7 Post dates to 80 IU/1 000 ml over eight hours. Macrosomia75 Big bolus doses should be avoided as it is associated with Uterine fibroids86 haemodynamic compromise. Dose-finding studies in patients 84 Known uterine abnormality presenting for elective Caesarean section found that doses 75 Chorio-amnionitis between 0.35–3 IU were associated with acceptable uterine tone Instrumental and Caesarean deliveries75,87,88 without the side-effects seen with bigger doses.100–102 Patients Physiological 3rd stage (vs active management)75 with risk factors such as obstructive labour will need the higher Retained placenta75,89 doses in this range.103 Emergency C/S75,90 Patients who are in labour for more than six hours or those who 75,84,86,91,92 Labour induction/augmentation receive exogenous oxytocin for induction or augmentation

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of labour, have down-regulation of oxytocin receptors and mothers expecting a rhesus D positive baby after a previous may need bigger doses of oxytocin or even a different class of pregnancy with a rhesus D positive foetus. With the introduction uterotonics.101,104–109 of anti-D immunoglobulin immunisation of Rh negative mothers, the syndrome is now mostly due to ABO incompatibility and Carbetocin is an oxytocin analogue with a 4–10 times longer half- other alloantibodies.119 Transfusion of blood products in women life. This feature makes it attractive as an alternative to oxytocin of childbearing age, should thus take this into consideration and infusion. At a dose of 100 μg IVI, it is comparable to oxytocin with unnecessary transfusion should be avoided. regards to adequacy of contraction.105,110–112 Transfusion of blood products should ideally be individualised Prostaglandins96 based on point-of-care tests. A patient blood management

Prostaglandin E2 (PGE2) is formed via the arachidonic pathway. strategy (PBM) should be followed rather than a “one-size-fits-all” 98,120 Its receptor has four subtypes (EP1–EP4). Activation of EP1 and dogma. A rough guideline would be to aim for a haemoglobin

EP3 leads to uterine contraction whilst EP2 and EP4 binding is > 8 g/dl, prothrombin time < 1.5 x mean control, aPTT < 1.5 x associated with relaxation of the uterus.110 mean control121 and fibrinogen level of more than 2 g/L.120 In addition, pH should be maintained above 7.2, temperature Prostaglandin F α is no longer available in South Africa. It was 2 above 35 °C and ionised calcium above 1 mmol/L.120 There is used in resistant uterine atony and was given directly into the evidence that fibrinogen plays an important part in coagulation myometrium. Side-effects included nausea, vomiting, diarrhoea in the obstetric patient. Fibrinogen level less than 2 g/L has a 113 and bronchospasm. 100% positive predictive value for severe PPH.122 The best blood Surgical measures product to increase the fibrinogen level is cryoprecipitate. Cryoprecipitate contains 10 times more fibrinogen than fresh Measures that the surgeons can take include B-lynch suture, frozen plasma. To raise the plasma fibrinogen level by 1 g/L uterine tourniquet, intrauterine balloon catheter, selective requires only 3 ml/kg of cryoprecipitate instead of the 30 ml/kg arterial devascularisation and hysterectomy. Interventional FFP that would be needed to achieve the same result.69 radiological strategies include balloon occlusion and arterial embolisation. These may not be readily available in the acute The use of recombinant factor VII remains controversial. It should setting when bleeding is already occurring. only be considered when other measures have failed and in an attempt to prevent hysterectomy.120 It should, however, Anaesthesia for the parturient with obstetric not delay the decision to do a life-saving hysterectomy. It also 13 bleeding should not be given unless the haematocrit is adequate, platelet It is important to note that the pregnant patient can appear count > 50 x 109/L, fibrinogen > 1 g/L, pH > 7.2 and temperature stable despite significant blood loss up to 1 500 ml. This is due > 34 °C.69 The dose is 90 μg/kg over 3–5 minutes. 114,115 to the physiological changes of pregnancy. By the time Cell salvage in Caesarean delivery69,123–125 the arterial blood pressure starts to decrease, the patient may already have lost 25% of her blood volume. In addition, the Cell salvage involves the collection of blood from the surgical pregnant uterus has an average blood flow of about 700 ml/min field, processing and washing those cells and re-infusing them near term,116 thus there is a potential for rapid blood loss. These to the patient. In obstetric patients, the blood from the surgical factors have important implications for the choice of anaesthesia. field will be contaminated with amniotic fluid and foetal debris Regional anaesthesia should only be considered in cases with including foetal blood and foetal squamous cells. The concern mild bleeding where there is no maternal or foetal compromise is thus that amniotic fluid in this cell-saved blood can cause and where the risk for torrential bleeding is low. In most cases, iatrogenic amniotic fluid embolism with resultant DIC and that however, general anaesthesia may be the preferred option. the foetal components can lead to maternal allo-immunisation.123

The anaesthetic considerations are those related to obstetric The amniotic fluid contains tissue factor and it is this factor that anaesthesia such as need for rapid sequence induction, is thought to cause the coagulopathy seen in amniotic fluid prevention of aspiration, prevention of aortocaval compression embolism. Modern cell salvage technology is able to reduce the as well as considerations for potential massive blood loss. total amount of tissue factor in the salvaged blood by 89% and eliminate the active proportion of tissue factor completely.126 Large bore intravenous access should be established and fluid resuscitation started in haemodynamically unstable patients. Foetal squamous cells and foetal haemoglobin are still detectable Invasive monitoring should be considered. Plans should be in the salvaged blood but their levels are comparable with made for postoperative care as a large proportion of patients maternal venous blood at the time of placental separation.123 with massive bleeding will require ongoing intensive care after Multiple studies examined parturients who had received cell- surgery. salvaged blood. There were no serious complications reported Blood transfusion in obstetrics98,117,118 in more than 299 patients and the risk of using cell-saved blood in obstetrics seems to be the same as for the general population. An additional risk associated with blood transfusion in obstetric patients, is the risk of haemolytic disease of the foetus and Precautions to be taken are to discard blood and amniotic fluid newborn (HDFN) in subsequent pregnancies. Historically, this collected before the delivery of the foetus and to use leukocyte complication was mostly associated with rhesus D negative depletion filters.123 Leukocyte depletion filters have been

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associated with a precipitous decrease in arterial blood pressure. 7. Farina Z, Fawcus S. Oxytocin--ensuring appropriate use and balancing efficacy This is thought to be due to cytokine release from the trapped with safety. S Afr Med J. 2015;105(4):271-4. 8. Fawcus S, Moodley J. Deaths NCoCEiM. Haemorrhage associated with caesarean leukocytes. If this complication occurs, it is advised to stop the section in South Africa--be aware. S Afr Med J. 2011;101(5):306, 8-9. 127 transfusion. 9. Knight M, Callaghan WM, Berg C, et al. Trends in postpartum hemorrhage in high resource countries: a review and recommendations from the International Rho(D) immune globulin should be considered in Rh-mothers Postpartum Hemorrhage Collaborative Group. BMC Pregnancy Childbirth. after the use of cell-salvaged blood. 2009;9:55. 10. Soma-Pillay P, Pattinson RC, Langa-Mlambo L, et al. Maternal near miss and The role of antifibrinolytics in obstetric bleeding – maternal death in the Pretoria Academic Complex, South Africa: A population- WOMAN Trial based study. S Afr Med J. 2015;105(7):578-63. 11. Maswime S, Buchmann EJ. Why women bleed and how they are saved: a Antifibrinolytics have shown promising results in reducing cross-sectional study of caesarean section near-miss morbidity. BMC Pregnancy blood loss and mortality due to bleeding in a variety of surgical Childbirth. 2017;17(1):15. situations, trauma and other indications.128–132 The CRASH-2 12. Walfish M, Neuman A, Wlody D. Maternal haemorrhage. Br J Anaesth. 2009;103 Suppl 1:i47-56. 129 trial showed a significant decrease in death due to bleeding 13. Banks A, Norris A. Massive Haemorrhage in Pregnancy. Continuing Education in when tranexamic acid was given (4.9%) vs control (5.7%). The Anaesthesia, Critical Care and Pain. 2005;5(6):195-8. MATTERs studies130,131 have also shown decreased mortality in 14. Antepartum Haemorrhage. Greentop Guideline No 63: Royal College of the military trauma setting. Obstetricians and Gynaecologists; 2011. 15. Oyelese Y, Ananth CV. Placental abruption. Obstet Gynecol. 2006;108(4):1005-16. There have also been studies done in elective Caesarean 16. Tikkanen M. Placental abruption: epidemiology, risk factors and consequences. deliveries where tranexamic acid was given prophylactically Acta Obstet Gynecol Scand. 2011;90(2):140-9. before skin incision and this was associated with a significant 17. Ananth CV, Lavery JA, Vintzileos AM, et al. Severe placental abruption: clinical definition and associations with maternal complications. Am J Obstet Gynecol. reduction in perioperative blood loss as well as a lesser reduction 2016;214(2):272.e1-9. in haematocrit and haemoglobin levels when compared to the 18. Tikkanen M. Etiology, clinical manifestations, and prediction of placental controls. 133,134 abruption. Acta Obstet Gynecol Scand. 2010;89(6):732-40. 19. Hall DR. Abruptio placentae and disseminated intravascular coagulopathy. There is, however, a theoretical concern about the use of Semin Perinatol. 2009;33(3):189-95. antifibrinolytics in pregnant patients due to their physiological 20. Kuczyński J, Uszyński W, Zekanowska E, et al. Tissue factor (TF) and tissue factor hypercoagulable state.34,135,136 pathway inhibitor (TFPI) in the placenta and myometrium. Eur J Obstet Gynecol Reprod Biol. 2002;105(1):15-9. The WOMAN trial137 (Worldwide Maternal Antifibrinolytic trial) is 21. Ananth CV, Smulian JC, Demissie K, et al. Placental abruption among singleton and twin births in the United States: risk factor profiles. Am J Epidemiol. currently underway and results are expected soon. The aim of the 2001;153(8):771-8. study is to evaluate the use of tranexamic acid in the treatment 22. Ananth CV, Oyelese Y, Srinivas N, et al. Preterm premature rupture of of postpartum haemorrhage. 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S25 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Carcinoid syndrome

M A Eagar

ICAN Practice, Johannesburg, South Africa Correspondence to: [email protected]

Keywords: carcinoid syndrome

Introduction gastrointestinal tract pass via the portal system to the liver where they are metabolised. In order to manifest clinically with the Carcinoid tumours are derived from enterochromaffin cells carcinoid syndrome, these vasogenic substances need to spill (also known as Kulchitsky cells) and arise from the different over into the systemic circulation. This situation typically occurs embryonic divisions of the gut. Under electron microscopy, they when carcinoid tumours metastasise to the liver and substances typically contain numerous membrane-bound neurosecretory secreted bypass this metabolism and thereby exert more granules containing hormones and biogenic amines. Carcinoid widespread systemic effects. Carcinoid syndrome is especially tumours are the most common endocrine tumours found in the common in tumours of the ileum and jejunum but also occurs gastrointestinal tract. They account for 13 to 34% of all tumours with bronchial, ovarian, and other carcinoids.4 of the small bowel and 17 to 46% of all malignant tumours of the small bowel.1 Classification

Carcinoid tumours may be increasing in frequency with the One of the more clinically useful classifications of carcinoid highest incidence in some racial groups (4.5 per 100 000 in tumours is according to the division of the primitive gut from African males), suggesting a genetic role associated with which the tumour cells arise and the vascular supply of the their development. The sites of highest incidence are the digestive tract: the foregut, midgut, and hindgut (Table I). gastrointestinal tract (67.5%) and the broncho-pulmonary Foregut carcinoids can occur in the thymus and bronchi and may system (25.3%). Within the gastrointestinal tract, approximately secrete adrenocorticotrophic hormone producing Cushing’s 40% of tumours occur in the small intestine, with a further 27% syndrome. Carcinoid tumours on rare occasions develop in the in the rectum and 10% in the stomach.2 It should be noted that ovary. the carcinoid syndrome occurs in less than 10% of patients with Clinical presentation carcinoid tumours. Carcinoid syndrome is the clinical spectrum produced by release of amine and neuropeptide substances Carcinoid tumours are slow growing and may be asymptomatic into the systemic circulation by carcinoid cells. 71% of patients for years. Initial presentation is typically with vague abdominal with midgut carcinoids have metastatic disease at presentation.3 discomfort that is often misdiagnosed as irritable bowel Vasoactive substances released by carcinoid tumours in the syndrome.5 The average time from onset of symptoms to

Table I Location Clinical Biochemical FOREGUT Atypical carcinoid, ZE, acromegaly, 5HTP, histamine, peptide Lungs, stomach, liver, biliary tract, pancreas, and first portion of the Cushing’s syndrome duodenum MIDGUT Classic carcinoid 5HT, SP, CGRP, kinins and peptides Distal duodenum, the small intestines, the appendix, the right colon, and the proximal transverse colon HINDGUT Silent Non-secretory Distal transverse colon, the left colon, and the rectum 5-HTP = 5-hydroxytryptophan 5-HT = 5-hydroxytryptamine (serotonin) SP = Substance P CGRP = Calcitonin gene related peptide ZE = Zollinger-Elliso

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Table II. Clinical manifestations carcinoid syndrome10 Clinical manifestation Frequency Description Pathophysiology Flushing 85–90% Long-lasting violaceous face and neck (foregut carcinoid) Kallikrein, 5-HTP, Histamine, Transient pink-red flushing (midgut carcinoid) Substance P, PG Gastrointestinal hyper-motility 70 –80% Watery, profuse. Associated nausea, vomiting Gastrin, 5-HTP histamine, PG, VIP Bronchospasm 15% Wheezing Histamine, 5-HT Abdominal pain 35% Progressive Small bowel obstruction, ischaemia Right heart failure 30% Carcinoid heart disease 5-HTP Pellagra 5% Diarrhoea, dermatitis, dementia Niacin deficiency 5-HTP = 5-hydroxytryptophan PG = prostaglandins VIP = Vasoactive intestinal peptides correct diagnosis is nine years.6 Appendiceal carcinoids may Treatment options be found incidentally at appendectomy. Jejunoileal carcinoids Surgery is the treatment of choice for resection of primary are more likely to present with abdominal pain, obstruction, localised tumour or for any obstructive pathology. Even in the or signs of carcinoid syndrome. The classic carcinoid syndrome presence of distant metastases, resection of the primary tumour is characterised by episodic cutaneous flushing, diarrhoea, and mesenteric mass is being advocated.14 The aim of surgical bronchoconstriction, hypo- or hypertension and carcinoid treatment for small intestinal carcinoid tumours should be the 7 heart disease (Hedinger syndrome). Carcinoid heart disease, complete curative en block resection of the primary tumour and which eventually occurs in over 50 percent of patients with its mesenteric lymph node metastases. carcinoid syndrome, may be the initial presentation of carcinoid disease in as many as 20% of patients.8,9 Carcinoid heart disease Somatostatin analogue therapy typically affects the right side of the heart causing fibrous Somatostatin is a 14-amino acid peptide that binds to thickening of the endocardium. This results in retraction and somatostatin receptors expressed on the majority of carcinoid fixation of the tricuspid and pulmonary valve leaflets. Tricuspid tumours. Octreotide and the long-acting analogue lanreotide regurgitation is found in almost all cases, but tricuspid stenosis bind to the somatostatin receptors inhibiting the release of and both pulmonary regurgitation and stenosis may occur. The vasoactive amines. A depot form of octreotide (Sandostatin pathogenesis of the plaque is not completely understood. The LAR) is administered on a monthly basis eliminating the need plaque is composed of smooth muscle cells, myofibroblasts and for self-administered daily subcutaneous octreotide. A depot an overlying endothelial cell layer. The diet drugs, fenfluramine preparation of lanreotide is also available (Somatuline Depot). and dexfenfluramine, which interfere with serotonin metabolism Overall, octreotide and lanreotide have similar efficacy in produce cardiac valve lesions very similar to carcinoid lesions. symptom control and reducing tumour markers and serotonin levels.15 Diagnosis Liver therapies A combination of biomarkers and imaging studies are used to diagnose and locate carcinoid tumours. Ideally tissue specimen Complete hepatic resection of metastases is considered where is required for confirmation of diagnosis. The most common feasible. Cytoreductive hepatic surgery is somewhat more markers for midgut carcinoid are plasma chromogranin A and controversial and may be of benefit in carefully selected patients. urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion. A positive Here liver metastases are debulked by resection in combination result for 5-HIAA has a 73% sensitivity and a 98% specificity for with ablative therapy which may help palliate symptoms and carcinoid tumour.11 Serum chromogranin A is a glycoprotein hormonal overproduction.16 Liver directed ablative therapy secreted with other hormones by neuroendocrine tumours and may include bland embolisation, chemo-embolisation, or is 68% sensitive and 86% specific for carcinoid tumours.12 New radio-embolisation. Experience with radio-embolisation using markers, such as pancreastatin, neurokinin A, and plasma 5-HIAA yttrium-90 (90Y)-labeled resin or glass microspheres is limited may improve the diagnostics and prognostication.13 but growing. Studies suggest that this technique reduces symptoms in a significant number of patients with functioning Various imaging techniques, including endoscopy, endoscopic neuroendocrine tumours.17 ultrasound, and video capsule endoscopy, may be used to locate the tumour. Computed tomography (CT), magnetic resonance Other treatment modalities imaging (MRI), and diagnostic imaging using radiolabeled • Telotristat is a new agent recently approved in the United States somatostatin analogs (Indium-111 pentetreotide [111-In for use in carcinoid tumours in combination with somatostatin pentetreotide, OctreoScan], and positron emission tomography analogues. The mechanism of action is through inhibition of (PET scan) using Gallium Ga-68 DOTATATE [68-Ga DOTATATE]) the enzyme tryptophan hydroxylase (Trp hydroxylase), the are the primary imaging modalities used to identify carcinoid rate limiting enzyme for the conversion of tryptophan to tumours. 5-hydroxy-tryptophan (Figure 1).

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Figure 1

Two pivotal trials, TELESTAR and TELECAST, explored the role of management of carcinoid syndrome dramatically and they form telotristat ethyl in the management of patients with carcinoid the cornerstone of pharmacotherapy. syndrome refractory to somatostatin analogue monotherapy. These studies found that patients with carcinoid syndrome not Preoperative adequately controlled by somatostatin analogues, treatment Careful communication between the surgeon, endocrinologist with telotristat significantly reduced the number of bowel and anaesthesiologist is required for optimal outcome. Fluid 18 movements and urinary 5-hydroxyindoleacetic acid. and electrolyte abnormalities, malnutrition and anaemia may • Interferon therapy has been used in refractory cases of need to be corrected before proceeding with surgery. Careful carcinoid syndrome. In one study, 17 of 36 patients (47%) with preoperative evaluation of the cardiovascular system is essential metastatic carcinoid tumour who were treated with human to delineate cardiac reserve in the face of carcinoid heart disease. leukocyte interferon had objective hormonal responses for Echocardiography is the most readily available technique to 19 a median duration of 34 months. Unfortunately interferon assess the extent of cardiac involvement. Cardiac magnetic usage is often associated with debilitating toxicities, which resonance imaging has been shown to provide clear anatomic can include fatigue, depression, and flu-like symptoms. and functional information on both tricuspid and pulmonary • Everolimus is a derivative of sirolimus and works similarly to valves in situations where adequate windows are unobtainable sirolimus as an inhibitor of mammalian target of rapamycin using echocardiography.22 High right-sided pressures secondary (mTOR). Based on evidence from the RADIANT-4 trial, the to pulmonary stenosis, or severe tricuspid regurgitation may lead US Food and Drug Administration approved everolimus to hepatic congestion and pulsatility predisposing to significant for the treatment of adult patients with progressive, well- intraoperative blood loss during hepatic resection. differentiated non-functional, neuroendocrine tumours of gastrointestinal or lung origin with unresectable, locally Preoperative optimisation includes pharmacotherapy which advanced or metastatic disease. The trial showed treatment either blocks the effect of vasoactive substances, prevents the with everolimus was associated with significant improvement release of these substances, or a combination of both. A lack of in progression-free survival in patients with progressive lung symptoms before surgery does not preclude a potential carcinoid or gastrointestinal neuroendocrine tumours.20 crisis with surgical manipulation of the carcinoid tumour during • Peptide receptor radioligand therapy — Radiolabelled the operative procedure. somatostatin analogues (e.g. 90-Y-DOTA tyr3-octreotide, Octreotide remains the mainstay for prevention and treatment of 90Y-edotreotide, or 177Lu-DOTA0,Tyr3-octreotate) can be the carcinoid crisis. There is some variation between institutions used to deliver targeted radiation to somatostatin receptor- regarding dose and timing of octreotide administration. What expressing tumours. Studies suggest response to radioligand is commonly accepted, however, is that octreotide therapy therapy is associated with improved survival.21 needs to be commenced prior to surgery and continued Perioperative management of patients with carcinoid throughout the procedure with supplemental dosing based on syndrome clinical response. The half-life of octreotide is 60–90 min and 23 Patients with carcinoid syndrome may be presenting for can be administered subcutaneously or intravenously. Some surgery related to the carcinoid tumour (resection of primary or authors have recommended the preoperative subcutaneous secondary mass), or for unrelated surgery. On occasion, patients administration of 100 µg of octreotide and another 100 µg may present for surgery with previously undiagnosed carcinoid administered intravenously just before induction of anaesthesia. disease (e.g. bowel obstruction). The primary goal is to prevent An intravenous octreotide infusion at the rate of 50–100 µg.h-1 release of vasoactive mediators by avoiding factors that trigger can be administered during surgery.24 Another regimen suggests release of these vasoactive amines. The height of catastrophe a continuous infusion of 50 µg.h-1 for 12 hours prior to surgery to is the so-called ‘carcinoid crisis’ with resulting haemodynamic reduce hormonal activity with supplemental doses on an ad hoc instability, hyperthermia, shock, arrhythmia, flushing, or basis.25 It should be noted that octreotide has widespread effects, bronchial obstruction. The introduction of octreotide and important among these are QT prolongation, bradycardia, other somatostatin analogues has changed the perioperative conduction defects, abdominal cramps, nausea, and vomiting.

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Other pharmacological agents that have been used in the Vasoconstrictors perioperative period include corticosteroids, ketanserin, which blocks effects at 5-HT2 receptors, methysergide, and Response to vasoconstrictors can be unpredictable as cyproheptadine, which has antiserotonin and antihistamine administration of catecholamines such as epinephrine and effects. However, strong evidence for use of these agent is norepinephrine may trigger a carcinoid crisis thus paradoxically somewhat lacking.26 Aprotonin, a serine protease inhibitor, has further lowering the blood pressure. Cautious administration of been used in the past to control bradykinin production and the small doses of phenylephrine has, in some reports, been found associated flushing, with limited success.27 Histamine release to be useful.31 Other agents that have been used with variable is most likely to occur with gastric carcinoids and prophylactic success include vasopressin and angiotensin.26 Unfortunately administration of antihistamines may be of benefit in selected these agents are not readily available in all centres. cases. Anxiolytic premedication is recommended as there are Carcinoid crisis case reports of emotional stress triggering serotonin release.24

Intraoperative management Cutaneous flushing may be the harbinger of an impending carcinoid crisis.30 Hypotension tends to occur when large Regional anaesthesia for intra- and postoperative analgesia bulky hepatic metastases are manipulated during the surgical in the form of a thoracic epidural for patients undergoing procedure. Surgery should cease until haemodynamic stability laparotomy is acceptable and effective for decreasing the is attained as further manipulation of the tumour mass can surgical stress response which may precipitate a carcinoid crisis. exacerbate the hypotension. Boluses of octreotide form the This benefit should, however, be weighed against the potential cornerstone of management of a carcinoid crisis. Hypotension exacerbation of intraoperative hypotension associated with from other aetiologies such as blood loss and hypovolaemia release of vasoactive mediators during surgery. need to be excluded and treated appropriately. In the event of Monitors bronchoconstriction, traditional agents such as beta-2 agonists may exacerbate the bronchoconstriction by triggering further Dramatic changes in blood pressure are commonplace during release of vasoactive amines from the carcinoid tumour. surgery for carcinoid syndrome. Thus, in addition to standard Octreotide is especially useful for bronchospasm that is resistant monitoring, invasive monitoring is considered mandatory. In to other treatments. Hyperglycaemia may result from serotonin some institutions, invasive monitoring in the form of central venous access and invasive arterial blood pressure monitoring release and should be managed appropriately. is established prior to anaesthesia with the potential of a Postoperative carcinoid crisis ensuing during the induction process.26 Brisk bleeding may be encountered as abdominal carcinoids have Management in an intensive care environment is appropriate as a rich blood supply. Reliable large bore vascular access is further recrudescence of carcinoid syndrome may occur in cases appropriate. Transoesophageal echocardiography can be of incomplete excision or undetected metastases. The octreotide extremely useful especially in the presence of proven carcinoid infusion should be continued into the postoperative period. heart disease.28 Non-invasive cardiac output monitors may be Delayed emergence, presumably as a result of high circulating 32 useful to guide fluid responsiveness through measurement levels of serotonin, has been described. 5-HT3 antagonists of stroke volume variation as well as the ability to calculate such as ondansetron are first-line agents in the prophylaxis and indices such as systemic vascular resistance. Central venous treatment of perioperative nausea and vomiting.33 Effective pressure monitoring (CVP) is essential in cases of resection postoperative analgesia is essential to ameliorate emotional and of hepatic metastases as maintenance of a low CVP has been physical stress that could potentially trigger release of vasoactive shown to reduce intraoperative blood loss during liver resection. amines from residual carcinoid tumour. A carcinoid crisis may manifest initially with severe bronchospasm during the procedure and thus careful note should be taken of Conclusion any unexpected changes in airway pressures. Patients presenting for surgery with carcinoid syndrome pose Induction unique challenges for the anaesthetist involved. A thorough understanding of the pathophysiology of the disease process The aim is for a stable, smooth induction with minimal is essential for a successful outcome. Introduction of octreotide catecholamine release and adequate depth of anaesthesia and other somatostatin analogues has revolutionised the before intubation. The pharmacological agents used to obtain anaesthesia are debatable with no absolute contraindication to perioperative management of this disease. Careful cardiac any particular drug; however, it would seem intuitive to avoid evaluation is critical to detect the presence and extent of agents that cause histamine release such as atracurium and carcinoid heart disease. Drugs that are traditionally used to large boluses of morphine. Remifentanil has the advantage of treat intraoperative hypotension and bronchoconstriction titratability, ultra-short context sensitive half time and lack of may actually provoke further release of vasoactive substances histamine release and as a result has been used to good effect for from the tumour thus aggravating the situation. Potential for a 29 patients with carcinoid syndrome. These advantages are offset carcinoid crisis should not be underestimated even if symptoms by the potential for hypotension as a common side-effect. appear to be adequately controlled in the preoperative period.

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References 18. Lamarca A, Barriuso J, McNamara MG, et al. Telotristat ethyl: a new option for the 1. Buchanan KD, Johnston CF, O'Hare MM, et al. Neuroendocrine tumors. A management of carcinoid syndrome. Expert Opinion on Pharmacotherapy Vol. European view. Am J Med 81:14-22,1986. 17 , Iss. 18,2016. 2. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. 19. Oberg K, Norheim I, Alm G. Treatment of malignant carcinoid tumors: a Cancer 2003; 97: 934-59. randomized controlled study of streptozocin plus 5-FU and human leukocyte interferon. Eur J Cancer Clin Oncol 25:1475-1479,1989. 3. Yao, C, Hassan M, Phan A, et al. One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 20. Yao JC, et al. Everolimus for the treatment of advanced, non-functional cases in the United States. J Clin Oncol 26:3063-3072,2008. neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): 4. Davis Z, Moertel CG, McIlrath DC. The malignant carcinoid syndrome. Surg a randomised, placebo-controlled, phase 3 study Volume 387, No. 10022, Gynecol Obstet. 137:637-644,1973. p968–977, 5 March 2016. 5. Modlin IM, Kidd M, Latich I, et al. Current status of gastrointestinal carcinoids. 21. Imhof A, Brunner P, Marincek N, et al. Response, survival, and long-term toxicity 2005;128: 1717-51. after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol 2011; 29:2416. 6. Horton KM, Kamel I, Hofmann L, et al. Carcinoid tumors of the small bowel: a multitechnique imaging approach. Am J Roentgenol 2004;182: 559-67. 22. Bastarrika G, Cao MG, Cano D, et al. Magnetic resonance imaging diagnosis of carcinoid heart disease. J Comput Assist Tomogr. 2005;29:756 -759. 7. Sworn MJ, Edlin GP, McGill DA, et al. Tricuspid valve replacement in carcinoid syndrome due to ovarian primary. Br Med J 1980;280(6207):85-6. 23. van der Lely AJ, de Herder WW. Carcinoid syndrome: diagnosis and medical 8. Pellikka PA, Tajik AJ, Khandheria BK, et al. Carcinoid heart disease. Clinical and management. Arq Bras Endocrinol Metabol 2005;49:850-60. echocardiographic spectrum in 74 patients. Circulation. 1993;87(4):1188. 24. Dierdorf SF. Carcinoid tumor and carcinoid syndrome. Current Opinion in 9. Lundin L, Norheim I, Landelius J, et al. Carcinoid heart disease: relationship Anaesthesiology. 2003;16:343-347 of circulating vasoactive substances to ultrasound-detectable cardiac 25. Ramage JK, Davies AH, Ardill J, et al. Guidelines for the management of abnormalities. Circulation. 1988;77(2):264. gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut 10. Mancuso K, Kaye AD, Boudreaux JP, et al. Carcinoid syndrome and perioperative 2005; 54(Suppl 4): iv1-iv16. anesthetic considerations. J Clin Anesth. 2011 Jun;23(4):329-41. 26. Vaughan DJ, Brunner MD. Anesthesia for patients with carcinoid syndrome. Int 11. Feldman JM, O’Dorisio TM. Role of neuropeptides and serotonin in the diagnosis Anesthesiol Clin 1997;35:129-42. of carcinoid tumors. Am J Med 1986;81:41-8. 27. Veall GR, Peacock JE, Bax ND, Reilly CS. Review of the anaesthetic management 12. Zuetenhorst JM, Taal BG. Metastatic carcinoid tumors: a clinical review. of 21 patients undergoing laparotomy for carcinoid syndrome. Br J Anaesth Oncologist. 2005;10:123-131. 1994;72:335-41. 13. Eriksson B, Oberg K, Stridsberg M. Tumor markers in neuroendocrine 28. Neustein SM, Cohen E, Reich D, Kirschner P. Transoesophageal echocardiography tumors. Digestion 62 Suppl 1:33-38,2000. and the intraoperative diagnosis of left atrial invasion by carcinoid tumour. Can J 14. Givi B, Pommier SJ, Thompson AK, et al. Operative resection of primary carcinoid Anaesth 1993;40:664-6. neoplasms in patients with liver metastases yields significantly better survival. 29. Farling PA, Durairaju K. Remifentanil and anaesthesia for carcinoid syndrome. Surgery 140:891-897,2006. British Journal of Anaesthesia 2004;92 (6):893-895. 15. O’Toole D, Ducreux M, Bommelaer G, et al. Treatment of carcinoid syndrome: 30. Grahame-Smith DG. The carcinoid syndrome. Am J Cardiol. 1968;21:376-87. a prospective crossover evaluation of lanreotide versus octreotide in terms of efficacy, patient acceptability, and tolerance. Cancer. 2000; 88:770-776. 31. Powell B, Mukhtar A, Mills G. Carcinoid: the disease and its implications for anaesthesia. BJA Continuing Education in Anaesthesia, Critical Care and Pain. 16. Boudreaux JP, Putty B, Frey DJ, et al. Surgical treatment of advanced-stage 2011;11(1): 913. carcinoid tumors: lessons learned. Ann Surg. 2005; 241:839-845. discussion 845-846. 32. Mason RA, Steane PA. Anaesthesia for a patient with carcinoid syndrome. 17. Jia Z, Paz-Fumagalli R, Frey G2, et al. Single-institution experience of Anaesthesia 1976;31:243-6. radioembolization with yttrium-90 microspheres for unresectable metastatic 33. Graham GW, Unger BP, Coursin DB. Perioperative management of selected neuroendocrine liver tumors. J Gastroenterol Hepatol; 2017 Jan 29. endocrine disorders. Int Anesthesiol Clin 2000;38:31-67.

S30 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Analgesia for thoracic surgery

N T Hlongwane-Gukuta

Department of Anaesthesiology, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

Thoracic surgery has come full circle in terms of incisions Muscle-sparing thoracotomy causes reduced postoperative pain employed, returning to the small incisions with which it began with less analgesia requirements and improved shoulder girdle in its infancy.1 With major advances in surgical and anaesthesia strength although surgical exposure may be compromised.1 techniques, medicine and technology, more complex surgery Video-assisted thoracoscopic surgery (VATS) can be performed 1 can be performed with minimally invasive incisions. on lungs, pleura, oesophagus and posterior and middle 1 Thoracic incisions are indicated for a wide variety of cardiothoracic mediastinum. Advantages of VATS include reduced pain and non-cardiothoracic procedures. All anaesthetists should be postoperatively, better cosmesis and improved shoulder girdle function.1 Long-term benefit in terms of pulmonary function is able to manage anaesthesia and analgesia involving thoracic yet to be proven.1 Generally, three small incisions are required: incisions. one for the camera in the seventh or eighth intercostal space Failure to control pain in the immediate postoperative period, and two for the operating ports in the fifth intercostal space.1 along with pre-existing thoracic pain, are strong predictors Intercostal neuralgia usually results from pressure on the nerve of chronic post-thoracotomy pain.2 Postoperative pulmonary adjacent to a trocar.1 complications can be avoided or reduced considerably by Other incisions used to access the thorax include the anterior administering good analgesia. mediastinoscopy (staging and diagnosing advanced upper- Thoracic incisions lobe lung cancers), transverse thoracosternotomy (resection of large mediastinal masses, double-lung transplantation, bilateral Thoracic incisions can be used both therapeutically (e.g. excision lung metastases, trauma resuscitation) and thoracoabdominal of pulmonary, oesophageal or mediastinal malignancies, chest (thoracoabdominal aneurysms, gastro-oesophageal junction trauma, spinal surgery) and diagnostically (e.g. open lung biopsy malignancies, lower thoracic and upper lumber spine pathology) and mediastinoscopy).1,3 incision.1

The choice of incision among the many that exist depends on The rest of this article will focus on analgesia for what is the most the surgeon, balancing adequate exposure for a successful popular thoracic incision: the thoracotomy. 1 outcome with preserving chest wall function and appearance. Anatomy and pathophysiology of pain in thoracic Median sternotomy and partial sternotomy allow access to surgery midline structures. In general, nomenclature for thoracotomy incisions is determined by their relationship to the latissimus The sensory afferents transmitting nociceptive stimuli after 4,5 dorsi muscle which is itself considered to be lateral.1 ‘A standard thoracotomy include : posterolateral thoracotomy transects the latissimus dorsi muscle. • skin incision and intercostal muscles (intercostal nerves T4–T6) An anterolateral thoracotomy transects the serratus anterior • chest drains (intercostal nerves T7–T8) muscle’.1 The thoracotomy incision gives good exposure to the • mediastinal pleura, lung and mediastinal structures (vagus entire hemithorax including lung, oesophagus, mediastinum nerve, CN X) 1 and cardiac structures and aorta on the left. • central diaphragmatic pleura (phrenic nerve, C3–C5) The anterolateral thoracotomy has regained popularity for use • ipsilateral shoulder (brachial plexus) in minimally invasive cardiac and thoracic surgery, trauma front • parietal pleura is innervated (intercostals and the phrenic room thoracotomy for rapid access to the aorta, pericardium and nerves) and is pain-sensitive while the visceral pleura is other structures.1 sensitive mainly to stretch

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• latissimus dorsi and serratus anterior muscles (thoracodorsal Choice of analgesic technique and long thoracic nerves from the C5 to C7 roots of the Surgical strategies for reducing post-thoracotomy pain include: brachial plexus) non-spreading VATS procedures, muscle-sparing techniques, The intense pain of thoracotomy is due to muscle division, less rib retraction and rib preservation.1 Strict layered closure rib retraction or resection and destruction of the intercostal is essential and approximating each individual layer of muscle nerves.6 The posterolateral thoracotomy incision usually spans correctly.1 In addition, care should be taken to avoid over- approximately six dermatomes commencing at the third approximation of the ribs as this adds to postoperative pain.1 dermatome posteriorly to the seventh or eighth dermatome Factors that determine the choice of analgesia are: the anteriorly.5 Varying degrees of transection of the latissimus dorsi, anaesthetist’s preference (skill and experience), ‘patient factors serratus anterior, pectoralis major and the intercostal muscles (contraindications, preferences), surgical factors (type of occur.5 Pressure on the intercostal nerves is caused by aggressive incision), and system factors (available equipment, monitoring, retraction to improve exposure and may result in acute nursing support)’.4,5 The patient should be counselled adequately intercostal neuritis.5 Up to three chest drains may be required after thoracotomy and are often inserted in the eighth or ninth to allay anxiety and encourage compliance. intercostal space which falls outside of the analgesia provided by ‘The ideal post-thoracotomy analgesic technique will include 5 the epidural or paravertebral block. three classes of drugs: opioids (patient-controlled analgesia Other factors which contribute to pain post-thoracotomy are (PCA)), anti-inflammatory agents, and local anesthetics (epidural, prolonged lateral decubitus position, non-specific shoulder pain intrathecal, paravertebral blocks, intercostal nerve blocks, 4,5 and extreme anxiety associated with this major procedure.5 No cryoprobe neurolysis)’. single analgesic technique can inhibit ALL these pain afferents.4 Systemic agents Analgesia should thus aim to be multimodal. Systemic opioids Why is analgesia post-thoracotomy important? These may effectively control background pain but fail to address An audit by Niraj et al confirmed that 25% of patients experience the acute pain associated with cough or movement.4 The dose persistent moderate to severe pain at six months that severely of opioids required to address acute pain results in sedation 7 affects quality of life in 40% of patients post-thoracotomy. and hypoventilation in the majority of patients with generally Risk factors for chronic post-thoracotomy pain identified in inadequate pain control associated with sleep disruption when this audit included male sex, age > 60 years, preoperative pain opioid levels drop below the therapeutic range.4 and acute pain postoperatively.7 ‘The noxious effects of surgery interact with preexisting and concurrent pain, psychological and Nonsteroidal anti-inflammatory drugs (NSAIDs) emotional factors as well as social environment to determine the These anti-inflammatory agents are analgesic and can ‘reduce nature, severity, frequency, and duration of chronic postsurgical opioid consumption more than 30% after thoracotomy and pain’.7 are particularly useful treating the ipsilateral shoulder pain Poor analgesia post-thoracotomy results in poor ventilatory that is often present postoperatively and is poorly controlled mechanics with shallow breathing and impaired coughing with epidural analgesia’.4 NSAIDs act by reversibly inhibiting which result in atelectasis, retention of secretions both of which cyclooxygenase with decreased platelet function, gastric result in hypoxaemia, hypercapnia and respiratory failure which erosions, increased bronchial reactivity, and decreased renal are accentuated in patients with existing lung disease.5 The function as side-effects.4 rate of these complications has decreased to around 10% with Paracetamol improved postoperative .4 This is ‘an antipyretic/analgesic with weak cyclooxygenase Cardiovascular dysfunction can result from poor pain control inhibition and can be administered orally or rectally in doses as increased sympathetic tone results in increased myocardial up to 4 g/day. It is effective against shoulder pain and has a low oxygen demand, increased afterload, myocardial dysfunction toxicity compared with more potent cyclooxygenase-inhibiting and arrhythmias.5 The incidence of deep venous thrombosis NSAIDs’.4 and pulmonary embolism is higher with poor analgesia as mobilisation is delayed. Longer hospital stay with particular Ketamine increase in ICU admissions has been demonstrated as a result of ‘Low-dose intramuscular ketamine (1 mg/kg) is equivalent to the poor analgesia.5 same dose of meperidine and causes less respiratory depression’.4 Post-thoracotomy chronic pain (PTCP) syndrome is a very Low-dose intravenous infusions may be effective in patients with common (incidence 30%–60%) and debilitating condition refractory pain or those with contraindications to more common and studies suggest that aggressive treatment of acute post- techniques.4 The psychomimetic effects of ketamine are seldom thoracotomy pain may reduce the incidence.8 seen with analgesic doses.4

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Dexmedetomidine likelihood of postoperative pulmonary complications occurring, especially in patients with poor respiratory reserve, is reduced.8 This is a selective adrenergic α -receptor agonist, which has been 2 Better compliance to physiotherapy and reduced ICU and shown to be a good adjunct for post-thoracotomy analgesia hospital are additional benefits.8 because it can significantly reduce opioid requirements when used in combination with epidural local anaesthetics.4 The majority of thoracotomies in the USA receive TEA at ‘Maintenance infusion doses for analgesia in children and adults between T3 and T8 with infusions of bupivacaine and fentanyl or are in the range of 0.3 to 0.4 µg/kg/hr.’4 ‘It is associated with some hydromorphone.4 ‘Combinations of and opioids hypotension, but it seems to preserve renal function’.4 provide better epidural analgesia at lower doses than either drug 4 Local anaesthetics alone’. Synergy exists between opioids and local anaesthetics to produce segmental epidural analgesia: local anaesthetic seems Intercostal nerve blocks to facilitate entry of the opioid from the epidural space into the 4 These can be an ‘effective adjunct to methods of post- cerebrospinal fluid. Bolus techniques are more likely to result thoracotomy analgesia’.4 They can be performed percutaneously in haemodynamic and respiratory instability than infusions or under direct vision during thoracotomy.4 Unfortunately, the which have been used safely in postoperative wards in some 4 duration of analgesia is limited by the type of local anaesthetic institutions. Epidural catheters allow for a wide spread of local used and repetition of the block would be needed to maintain anaesthetic with a single injection point, thus eliminating the analgesia.4 Continuous infusions through indwelling intercostal need for multiple punctures as with PVBs.4 A smaller volume of catheters are difficult to position reliably percutaneously.4 ‘Nerve local anaesthetic is required to produce a good block compared blocks are useful supplements for the pain associated with the with PVBs.8 The placement and use of TEA prior to the start of multiple small port incisions and chest drains following VATS’.4 surgery has the added benefit of allowing pre-emptive analgesia There is a risk of intravascular injection, which one should which is lost by placing the PVB after the surgical incision.8 be meticulous to avoid. The block should be placed near the The doses of bupivacaine used for TEA do not seem to cause posterior axillary line to ensure cover of the lateral cutaneous significant reduction in lung mechanics or increase in airway branch of the intercostal nerve.4 ‘Total bupivacaine dose for a resistance in patients with severe emphysema.4 Increased FRC single session of blocks should not exceed 1 mg/kg (e.g. for a 75-kg patient: 3 mL bupivacaine 0.5% with epinephrine 1:200,000 has been demonstrated in healthy volunteers administered a at each of five levels)’.4 thoracic level epidural, presumably due to an ‘increase in thoracic gas volume caused by a fall in the resting level of the diaphragm Interpleural analgesia without a fall in tidal volume’.4

Local anaesthetics placed in the interpleural space produce ‘The highly lipid-soluble agents (e.g. fentanyl, sufentanil) are 4 a multilevel intercostal block. ‘The analgesia is extremely associated with narrow dermatomal spread, rapid onset, and dependent on patient position, infusion volume, chest drains, low incidence of pruritus/nausea and can be potentiated by and the type of surgery’.4 This technique is unreliable in the epinephrine. However, these lipid-soluble agents have significant analgesia it offers.4 absorption and systemic effects when used as epidural infusions. Cryoprobe neurolysis For incisions that cover many dermatomes (e.g. sternotomy) or for procedures that have combined abdominal and thoracic ‘Application of a −60 °C probe to the exposed intercostal nerves incisions (e.g. oesophagectomy) the hydrophilic opioids intraoperatively produces an intercostal block that can persist for (e.g. morphine, hydromorphone) are preferable.’4 up to six months. This can be moderately efficient to decrease postoperative pain but is associated with an incidence of chronic The use of TEA reduces post-thoracotomy cardiovascular neuralgia that has led many centres to abandon the technique. (supraventricular tachy-arrhythmias) complications by blunting Transcutaneous electrical nerve stimulation (TENS) may be the stress response to surgery, thus reducing sympathetic useful in mild to moderate pain but is ineffective when pain is outflow which results in coronary vasodilation.8 severe’.4 In inexperienced hands, the risk of neurological injury and dural Thoracic epidural analgesia (TEA) puncture when placing TEA is significant because the anatomy is 8 TEA is considered by many to be the gold standard for analgesia different and difficult. The difficulty in placing thoracic epidurals following post-thoracic and upper abdominal surgery.5,9 The has been decreased by the use of the paramedian approach in 4 catheter is usually sited at the midpoint of the dermatomal the midthoracic levels. Indeed, TEA may be easier to teach as distribution of the skin incision.5 Although lumbar epidural the loss of resistance that identifies the space is easier to perceive catheters have been utilised, TEA is superior due to synergy and reproduce as is placement of the catheter compared to achieved by using local anaesthetics and opioids for neuraxial paravertebral blocks.8 analgesia.5 The rate of failure of the block ranges between 1 and 30% Post-thoracotomy, TEA reduces splinting, dynamic pain scores compared to 6.8 to 10% for PVBs and is largely dependent on and results in improved mucociliary clearance which all add the technique used and the experience of the individual placing to improved postoperative respiratory mechanics.4,8 Thus, the the block.8

S33 34 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1)

Paravertebral blocks The serratus anterior plane (SAP) block

Paravertebral blocks (PVB) have increased in popularity in recent This interfascial plane block is a novel technique and may be years.10 The paravertebral space ‘lies deep to the endothoracic considered to be the transversus abdominis plane (TAP) block of 16 fascia that the intercostal nerve traverses as it passes from the chest wall. 4 the intervertebral foramen en route to the intercostal space’. To perform the SAP block, local anaesthetic solution is injected, It is bordered anteriorly and laterally by the parietal pleura, under ultrasound guidance, into either the facial plane posteriorly by the superior costotransverse ligament and superficial or deep to the serratus anterior muscle.17 Thus the medially by the intervertebral foramen as the spinal nerves lateral cutaneous branches of the intercostal nerves are blocked emerge from the spinal column.10 as they course through, prior to dividing into the anterior and posterior branches supplying sensation to most of the chest The thoracic PVB produces sensory and sympathetic block of wall.16 Effective blockade of the lateral branches of intercostal multiple thoracic dermatomes unilaterally or bilaterally (with nerves T2 to T9 has been demonstrated in healthy volunteers.16,17 low likelihood of epidural spread) allowing for more specific analgesia and fewer side-effects.4,10 They can be performed using The posterior primary rami, the anterior cutaneous branches or the intercostal nerves (near the sternum) and the supraclavicular landmark, nerve stimulator, ultrasound-guided techniques or nerves (immediately below the clavicle) may not be covered by under direct vision intraoperatively.10 this block.16 Performed correctly, continuous PVBs can provide good Haemodynamic stability is maintained because no autonomic analgesia for thoracotomy which is as effective as continuous block occurs with the SAPB as compared to TEA and PVB.16 The 11 TEA. Continuous paravertebral block has been found to be SAP block has been used successfully to provide analgesia post- as effective as thoracic epidural infusion for post-thoracotomy thoracotomy, rib fracture, thoracoscopy, shoulder surgery, and pain.12 breast surgery.16 Chu et al described a series of three patients in whom SAP block was used together with multilevel continuous Thoracic PVBs have been purported to have fewer side-effects ultrasound-guided thoracic PVB for analgesia for chest tube pain when compared to TEA.4,10 The unilateral nature may explain not covered by thoracic PVB with great results.15 better pulmonary function with greater peak expiratory flow rates, higher oxygen saturations, reduced infections and less Chest drain-related pain not relieved by thoracic PVB, TEA hypoventilation.12,13 Studies have shown reduced stress response, or selective intercostal nerve blocks is a common problem 15 nausea and vomiting and reduced hypotension with PVB.13 There following thoracic surgery. A possible explanation is ‘unblocked is a risk of pneumothorax which is largely circumvented by the nociceptive signals from the long thoracic nerve (LTN), the phrenic nerve, the thoracodorsal nerve, the vagus nerve, and placement of an ipsilateral chest drain at the end of surgery.10 incompletely blocked intercostal nerves.’15 The SAP block is The risk of serious neurological injury is reduced presumably not equivalent to thoracic PVB, TEA or intercostal nerve blocks because of distance from the epidural space and spinal cord.10 but complements these by blocking only the lateral cutaneous ‘Studies comparing paravertebral versus thoracic epidural branches of the intercostal nerves and offering a solution to 18 analgesia for thoracotomies have suggested the following chest drain related pain. advantages for paravertebral blockade: comparable analgesia, In addition to the absence of autonomic blockade which fewer failed blocks (perhaps due to placement under direct results in haemodynamic stability, the SAP block eliminates vision), decreased risk of neuraxial hematoma, and less the risk of pleural puncture and serious injury to the spinal hypotension, nausea, or urinary retention.’4 cord.16 In addition, the anatomy on ultrasound is simple to identify, with shallow needle placement allowing for easy block A significant disadvantage of PVB is that ‘a single-level PVB may administration.16 have unreliable and limited analgesic coverage that only spans 2 to 4 dermatomes, thereby requiring multiple injections’.8 The analgesia provided by the SAP block has been found to be comparable to TEA for acute post-thoracotomy pain by Khalil ‘The American Society of Regional Anesthesia and Pain Medicine et al.16 advises against the use of deep and plexus blocks including PVB Continuous erector spinae plane (ESP) block in patients on antithrombotic or thrombolytic therapy.’4 Forero et al have used the ultrasound guided ESP block to New frontiers? manage chronic thoracic neuropathic pain, acute surgical pain Although TEA and thoracic PVB are considered the gold standard and as rescue analgesia after failed thoracic epidural post- in managing post-thoracotomy pain, they are not without thoracotomy.6 complications, not least of which is a significant failure rate of When performing the ESP block, local anaesthetic is injected into 15% for TEA and poor coverage of the chest-tube inserting the tissue plane deep to erector spinae muscle but superficial to sites.14,15 The serratus anterior plane block is a possible addition the transverse processes and inter-transverse connective tissues. to traditional regional analgesia, while the continuous erector This local anaesthetic penetrates anteriorly to block the spinal spinae plane block is a possible alternative. nerves.6 Due to the confines of the erector spinae tissue plane,

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extensive craniocaudal spread of local anaesthetic is promoted, 7. Niraj G, Kelkar A, Kaushik V, et al. Audit of postoperative pain management resulting in good analgesia.6 after open thoracotomy and the incidence of chronic postthoracotomy pain in more than 500 patients at a tertiary center. Journal of Clinical Anesthesia. This block is simple to perform using ultrasound, provides 2017;36:174-7. extensive analgesia from a single injection and poses reduced 8. Teeter EG, Kumar PA. Pro: Thoracic epidural block is superior to 6 paravertebral blocks for open thoracic surgery. Journal of Cardiothoracic risk of pleural puncture and epidural spread. Safety is enhanced and Vascular Anesthesia, Vol29, No6 (December), 2015:pp1717-1719. by the absence of neural and vascular structures within the 2015;29(December):1717-9. erector spinae plane.6 9. Rigg J, Jamrozik K, Silbert B, et al. Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial. The Lancet. 2002;359(April Caution should still be exercised in patients with coagulopathy.6 13):1276-82. Further research is being conducted to establish efficacy and 10. Krakowski JC, Arora H. Con: Thoracic epidural block is not superior to optimal dosing for both single-shot and continuous blocks.6 paravertebral blocks for open thoracic surgery. Journal of Cardiothoracic and Vascular Anesthesia. 2015;29(6):1720-2. Conclusion 11. Daly D, Myles P. Update on the role of paravertebral blocks for thoracic surgery: Are they worth it? Current Opinion in Anaesthesiology. 2009;22:38-43. Thoracic incisions are indicated for a wide variety of 12. Joshi G, Bonnet F, Shah R. A systematic review of randomized trials evaluating cardiothoracic and non-cardiothoracic procedures. The strategy regional techniques for postthoracotomy analgesia. Anesthesia and analgesia. for postoperative analgesia requires a multimodal approach with 2008;107:1026-40. regional techniques at the forefront. 13. RG D, PS M, JM G. A comparison of the analgesic efficacy and side-effects of paravertebral vs epidural blockade for thoracotomy – a systematic review References and meta-analysis of randomized trials. British Journal of Anaesthesia. 1. Thoracic Incisions [Internet]. 2015 [cited 12 April 2017]. Available from: http:// 2006;96:418-26. emedicine.medscape.com/article/1972596-overview - a1. 14. Romero A, Garcia J. The state of the art in preventing postthoracotomy pain. 2. Kampe S, Geismann B, Weinreich G, et al. The influence of type of anesthesia, Seminars in thoracic and cardiovascular surgery. 2013;25:116-24. perioperative pain, and preoperative health status on chronic pain six months 15. Chu GM, Jarvis GC. Serratus anterior plane block to address post-thoracotomy after thoracotomy—a prospective cohort study. Pain Medicine. 2016;0:1-6. and chest tube-related pain: A report on 3 cases. International Anesthesia 3. Butterworth JF, Mackey DC, Wasnick JD. Anesthesia for thoracic surgery. clinical Research Society. 2017. anesthesiology. 5th ed: The McGraw-Hill Companies; 2013. p. 545-73. 16. Khalil AE, Abdallah NM, Bashandy G, Kaddah TA-H. Ultrasound-guided serratus 4. Slinger PD, Campos JH. In: Miller RD, editor. Miller’s Anesthesia. Philadelphia: anterior plane block versus thoracic epidural analgesia for thoracotomy pain. Churchill Livingstone Elsevier; 2010. p. 1877-82. Journal of Cardiothoracic and Vascular Anesthesia. 2017;31:152-8. 5. Hughes R, Gao F. Pain control for thoracotomy. Continuing Education in Anaesthesia, Critical Care and Pain. 2005;5(2):56-60. 17. Blanco R, Parras T, McDonnell J, Prats-Galino A. Serratus plane block: a novel ultrasound-guided thoracic wall . Anaesthesia. 2013;68:1107-13. 6. Forero M, Rajarathinam M, Adhikary S, Chin KJ. Continuous erector spinae plane block for rescue analgesia in a thoracotomy after epidural failure: A Case Report. 18. Mayes J, Davison E, Panahi P, et al. An anatomical evaluation of the serratus International Anesthesia Research Society. 2017. anterior plane block. Anaesthesia. 2016;71:1064 -9.

S35 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Extracorporeal Membrane Oxygenation (ECMO)

A Alli

Department of Anaesthesia, Division of Critical Care, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

This is a review of the underlying basic concepts of cardiopulmonary bypass and mini-cardiopulmonary bypass, with a focus on the complications related to cardiopulmonary bypass and whether these complications can be reduced with the use of mini-bypass techniques.

Keywords: conventional cardiopulmonary bypass, mini-cardiopulmonary bypass, comparison, complications

Extracorporeal membrane oxygenation (ECMO) is a form of Indications for the use of ECMO in adults cardiopulmonary bypass. It is an artificial means of supplying The results of the CESAR trial and the use of ECMO during the oxygen, removing CO and/or providing cardiac output. Due to 2 H1N1 epidemic in 2009 have stimulated much progress in the significant advancements in intensive care, perfusion technology, development of ECMO research programmes, excellence centres anticoagulation, circuit, pump and membrane engineering, and registries worldwide.5,6 However, there is controversy modern ECMO is considered to be relatively safe and easy to regarding the indications for ECMO in adult patients. Table I implement. However, ECMO for respiratory disease still carries summarises the current Extracorporeal Life Support Organisation with it a high mortality risk (more than 50%) and therefore in (ELSO) recommended indications for ECMO in the adult patient most circumstances it is indicated only if the current respiratory population. disease process has a more than 80% mortality risk.1 There is sparse literature on the use of ECMO in the non-cardiac theatre, Indications for the use of ECMO in paediatrics but it has also been used with success electively and emergently ECMO use in the paediatric population for various indications in various situations.2,3,4 It is important to appreciate the current has seemingly resulted in greater survival than in adult patients. evidence-based indications and guidelines for the use of ECMO, According to the ELSO registry, 83 % of neonates with a predicted the basic ECMO circuit, and finally the anaesthetic considerations mortality of > 80% survived with the use of ECMO. Infants with regarding procedures related to, or while on, ECMO. meconium aspiration had a 93% survival rate while patients with

Table I. Current ELSO recommended indications and contraindications for ECMO in adult patients1,7 Organ failure Indications Contraindications Respiratory • Hypoxic respiratory failure with: • (All relative)

failure ▫▫ CONSIDER WHEN : PaO2/FiO2 < 150 on FiO2 > 90% • On mechanical ventilation with high settings (FiO2 > 90%,

or Murray score of 2–3 Pplat > 30 cmH20) for 7 days or more

▫▫ INDICATED WHEN: PaO2/FiO2 < 100 on FiO2 > 90% • Severe neutropenia or Murray score of 3–4 • Recent/expanding CNS haemorrhage ▫▫ Despite optimal care > 6 hours • Non-recoverable co-morbidity (major CNS damage/terminal

• CO2 retention with Pplat > 30 cmH20 malignancy) • Severe air leak • Advanced age • Need for intubation in patient on a lung transplant list • Immediate cardiac/respiratory collapse (PE/blocked airway, unresponsive to optimal care) Cardiac failure • Cardiogenic shock • Absolute ▫▫ acute MI, myocarditis, peripartum CMO, decompensated ▫▫ Unrecoverable heart, not a candidate for transplant chronic heart failure, post cardiotomy shock ▫▫ Advanced age • ECMO seen as a bridge to: ▫▫ Chronic organ dysfunction (emphysema, CKD, cirrhosis) ▫▫ Recovery ▫▫ Prolonged CPR without adequate ▫▫ Transplant ▫▫ Poor compliance with management ▫▫ Implantable circulatory support • Relative ▫▫ Contraindication for anticoagulation, advanced age, obesity

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Table II. ELSO-recommended indications for ECMO in paediatric patients (Current August, 2016)9-11 Organ failure Indications Contraindications Respiratory failure Neonates • Absolute • Severe respiratory failure, refractory to medical ▫▫ Lethal chromosomal abnormalities (Trisomy 13 or 18) management with a potentially reversible aetiology ▫▫ Severe neurological compromise (e.g. ICH with mass effect) • Indicated by • Relative ▫▫ Oxygenation index (OI) > 40 for > 4 hours ▫▫ Recent surgery or trauma ▫▫ OI > 20 with lack of improvement (> 24 hours) ▫▫ End-stage liver or renal failure ▫▫ Severe hypoxic respiratory failure with acute ▫▫ Primary pulmonary hypertension

decompensation (PaO2 < 40) ▫▫ Progressive respiratory failure and/or pulmonary hypertension with evidence of RV dysfunction or continued high inotrope requirements Infants (> 30 days) to children (< 18 years) • Potentially reversible respiratory failure within the first 7 days Cardiac Failure Neonates to children (< 18 years) • Futility – the likelihood of recovery is small • Early postoperative cardiac failure (unable to come off • Prolonged, ongoing CPR bypass) • In ICU: refractory shock (to vasopressors/inotropes) • Cardiac arrest from any cause (with response to CPR, with no return of circulation > 5 mins) • Myocardial failure unrelated to surgery: e.g. myocarditis, cardiomyopathy, drug ingestions • Elective support for high risk surgical procedures congenital diaphragmatic hernia had the lowest survival rate at South African recommendations and indications for 62%.8 The reason for the apparent survival benefit over a wide ECMO range of indications and in paediatrics is largely ECMO is a costly modality, and in developing countries such as unknown. However, it may be that ECMO is difficult to study if South Africa, is considered a limited resource. However, published compared against conventional support and that many of the South African recommendations largely mirror international older adult trials were designed with ECMO as a “rescue therapy”, ELSO guidelines. Table III lists the current recommendations hence selecting out patients that would have a poor outcome in and indications for ECMO from a South African perspective as any case. delineated by Richards.12 Nevertheless, there indications for ECMO in the paediatric Extracorporeal cardiopulmonary resuscitation (E-CPR) population are considered to be supported by more substantial evidence than the adult population. Table II lists the current Initiation of ECMO during cardiopulmonary resuscitation (E-CPR) ELSO-recommended indications for ECMO in paediatric patients. has been receiving significant attention in the recent literature.

Table III. South African recommendations for ECMO (Adapted from Richards)12 Exclusion criteria • Non availability of trained multidisciplinary team with access to a specialised intensive care, cardiothoracic and vascular surgical services. • Pulmonary oedema from myocardial dysfunction, unless bridging to transplant or acute myocarditis from which recovery is expected. • Exacerbations of COPD with respiratory failure. • Multiple organ failure from severe sepsis or SIRS. • Pneumocystis jiroveci pneumonia requiring ventilation. • Severe co-morbid illness that will impact significantly on life expectancy (e.g. incurable malignant disease or liver failure). • Inadequate recruitement and/or diuresis/dialysis in the presence of fluid overload. • Any potentially irreversible condition. • Technical difficulty associated with the procedure. • Where systemic anticoagulation is contraindicated. • Immunosuppression not likely to recover rapidly. • Patients mechanically ventilated for > 7 days. • Age > 75 years. Indications – respiratory • Primary ARDS with refractory hypoxaemia: e.g. severe pneumonia (particularly viral, but any pneumonia without failure multiple organ failure), pulmonary contusion, gas inhalation, aspiration, smoke inhalation. • Status asthmaticus or reversible airway obstruction not able to be ventilated conventionally or rapidly ameliorated. • Pulmonary embolism Indications – cardiac • Post cardiac surgery failure to come off cardiopulmonary bypass. failure • Bridge to cardiac transplantation. • Acute myocarditis. • Pulmonary hypertension (after pulmonary endarterectomy or following surgery on congenital heart defects).

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According to the most recent ELSO guidelines on the subject – right atrium/SVC/IVC and aorta respectively. However, central “The American Heart Association guidelines for CPR recommend cannulation is usually reserved for post-cardiac surgery ECMO the consideration of ECMO to aid CPR in patients who have an due to the ease of access. Peripheral cannulae are sited in most easily reversible event and have had excellent CPR.” other instances, with the drainage being from the internal All contraindications to ECMO use in general apply to its use in jugular or femoral vein and the return cannula placed in the the case of E-CPR. In addition, unsuccessful CPR with no return of femoral or carotid arteries (neurologically, infants tolerate spontaneous circulation or poor perfusion (due to poor CPR) for ligation of one carotid artery more than older children). longer than 30 minutes is considered a contraindication. • Veno-venous (VV): This is usually used for sole respiratory support. Examples where VV-ECMO would be used are: It is recommended that patients receiving E-CPR should also be meconium aspiration syndrome, drowning, hyaline membrane cooled for 48–72 hours to augment neurological protection.13 disease, viral pneumonias or chemical pneumonitis. Peripheral Types of ECMO support and ECMO circuits cannulae are sited for VV-ECMO, with the drainage and return ECMO circuits contain the following essential components cannulae being placed in the internal jugular or femoral vein. (demonstrated in Figure 1): A dual-lumen single cannulae is now most commonly placed for VV ECMO. This is a single cannula that is percutaneously • Drainage cannula placed in the right internal jugular vein, with the distal tip in • Return cannula the IVC (the drainage orifice) and the return orifice facing the • Pump (usually centrifugal) tricuspid valve. • Membrane oxygenator (with an oxygen/air blend gas input) Although VA ECMO restores cardiac output as the pump is started, • Heat exchanger (to manage temperature) VV-ECMO will restore RV function in cases of acute cor pulmonale • Conduit tubing – can be heparin bonded secondary to acute hypoxaemic pulmonary hypertension (e.g. in There are two basic types of ECMO support: ARDS). This in turn will improve left ventricular cardiac output. • Veno-arterial (VA): Typically suited for respiratory and When to remove a patient from ECMO circulatory support. Examples where VA-ECMO would be employed are post-cardiac surgery, septic shock, Once there are indications that lung or heart functioning is massive pulmonary embolus, post-CPR or in patients with improving (e.g. improving lung compliance or reduction in

cardiomyopathy. Central drainage and return cannulae can inotrope requirements), ECMO flow or oxygenator FiO2 will be sited in the above situations through a sternotomy, in the be decreased. If the cardiorespiratory function remains stable

Figure 1. The essential ECMO circuit14

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off ECMO support, ECMO will be resumed and a planned in the ICU which would be less of a problem in theatre, such as discontinuation of ECMO will ensue. the availability of various pieces of perfusion equipment and additional gas supply points. The surgeon may prefer theatre in Anaesthetic considerations cases of difficult vessel anatomy where a percutaneous approach The anaesthesiologist is part of a multidisciplinary team is not possible; or in cases where on-table fluoroscopy is required. managing a patient planned for, or on, ECMO. Like all other In these cases ECMO placement may be quicker and easier in members of the team, the anaesthesiologist responsible theatre, with a lower rate of potential complications. Indeed, must be appropriately trained and experienced to deal with the anaesthetist may prefer theatre as it is a more comfortable patients on ECMO. It has been shown that the best outcomes and familiar environment with specialised monitoring such as for patients on ECMO are achieved if every member of the team capnography readily available. Once all relevant members of has the necessary training or experience to manage this highly the multidisciplinary team are consulted, these factors must specialised group of patients. There are local and international be balanced against the risk of moving the patient from ICU to courses and training programmes available to this end. theatre.

The anaesthesiologist may be called upon to: 1) anaesthetise Preoperative assessment and optimisation must be carried out the patient for initiation of ECMO; 2) transport a patient already rapidly, and there are often only a few hours in which to do on ECMO; 3) anaesthetise the patient for a procedure while on this. Standard history, often available from the ICU notes as well ECMO or; 4) anaesthesia for liberation from ECMO and vessel as family members of the patient, and systemic examination repair after decannulation. It is not within the scope of this article must be carried out. Particular attention needs to be given to to discuss all of these scenarios in detail. However, a discussion examining existing venous and arterial access; doses of cardio- on anaesthesia for ECMO initiation follows. active drug infusions; ventilator settings; size and depth of endotracheal tube; depth of sedation and doses of sedative General anaesthetic considerations for placing or analgesic infusions if present. A detailed neurological and patients onto ECMO cardiorespiratory examination needs to be carried out and Patients requiring ECMO have severe cardiac and/or respiratory documented. Large bore intravenous access is recommended, as failure and are already on significant cardiorespiratory support. sudden haemorrhage is a significant possibility. These patients are usually in the intensive care units (ICUs) Special investigations should be focused toward optimising of hospitals and are undergoing multiple mechanical and coagulation parameters and cardiorespiratory support. pharmacological support modalities. Full blood count, international normalised ratio (INR) and The degree of physiological derangement and the risk of thromboelastography (TEG) will assist in directing the transport are the major concerns facing the anaesthetist when appropriate ordering and administration of blood and blood dealing with such patients. products perioperatively. An arterial blood gas allows the calculation of the oxygenation index, and rapid evaluation of Patients with respiratory disease presented for ECMO initiation electrolyte and acid-base derangements. have very little respiratory reserve with most patients being on very high ventilator settings. Non-conventional ventilator A mobile chest x-ray can confirm the position of the endotracheal modes such as adjustable pressure release ventilation (APRV) tube and central venous lines. In addition an x-ray can exclude or high frequency oscillatory ventilation (HFOV) are commonly large pleural effusions or pneumothoraces. used. Similarly, patients with cardiac disease presented for ECMO Echocardiography is especially useful, as both cardiac function initiation are on high-dose inopressor infusions, and some and anatomy can be rapidly assessed. Of particular importance centres still use an intraortic balloon pump as an adjunctive is the exclusion of congenital shunts, abnormal valvular measure in these cases. It must be remembered that severe function and pericardial collections. It is evident that patients respiratory disease can cause acute or chronic right ventricular with cardiogenic shock requiring ECMO will have depressed failure, and these patients also often require high-dose biventricular function. However, patients with respiratory inopressor infusions. Severe organ failure of this nature requiring disease frequently have high pulmonary artery pressures with high levels of support indicates that transient disconnection markedly depressed right ventricular function. from the ventilator or from an inopressor infusion may result in rapid deterioration requiring emergent resuscitation. Therefore The echocardiography probe can also be used to quickly evaluate considerable attention needs to be given to the careful handling for the presence of alveolar collapse, consolidation, pleural of tubing, cabling, power plugs, securing devices and straps to effusions and pneumothorax. A linear ultrasound probe can be ensure that any accidental disconnection does not occur. used to mark the surface anatomy of large vessels, such as the internal jugular vein or carotid artery, to assist the cannulating It is evident that transport of the patient to theatre will carry physician. a high risk of disconnection and subsequent failure of organ support. It is this author’s opinion that these patients are While the ECMO circuit is being prepared and primed by the best initiated on ECMO in the ICU. However, any discussion perfusion team and other preparation measures are being taken, with regards to site of ECMO initiation must be had with the coagulation parameters, cardiorespiratory function, electrolyte perfusionist and cannulating physician (usually a cardiothoracic and acid-base status should be optimised as much as possible surgeon). The perfusionist may have space or equipment issues in the short time available. Unnecessary equipment should

S39 40 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1)

be removed from the patient’s cubicle and emergency drugs, to improved oxygen delivery to the myocardium and reduced airway and vascular access equipment should be prepared pulmonary vascular resistance. In the case of VA-ECMO, and checked. In addition to routine ECG, non-invasive blood myocardial recovery is not expected to be that rapid, and it is pressure and oxygen saturation monitoring, invasive blood most likely due to a direct increase in intra-aortic pressure from pressure measurement is essential. Temperature monitoring the arterial return cannula. Inotropic agents should be stopped and capnography are very helpful if available. Near-infrared during VA-ECMO to reduce myocardial strain. spectroscopy cerebral perfusion monitoring should be employed especially if carotid artery cannulation is being performed. On exposure of the patient’s circulation to the artificial plastic Occasionally the patient would need to be moved to a theatre tubing and membrane, a release of inflammatory mediators bed brought into the ICU. This would usually be to facilitate occurs. The resultant vasodilation and drop in systemic vascular fluoroscopy. Once again, great care needs to be taken to avoid resistance causes a drop in circulating effective blood volume life-threatening disconnections during patient movement. and preload. Mean arterial pressures fall as a consequence. This phenomenon can occur within 15–30 minutes of initiation of Induction of anaesthesia may not be necessary, as these patients are often already receiving infusions of sedative and ECMO. Volume should be replaced with blood to an Hb of 10 g/dl, analgesic agents. Most commonly combinations of ketamine, or isotonic crystalloid. Vasopressor agents should be considered , propofol or fentanyl are employed. Small boluses to reduce the potential for fluid overload. ECMO circuit markers or adjustments of infusion rates of these drugs should be of an increased volume requirement include “shuddering” used to maintain anaesthesia titrated against haemodynamic vibration of the circuit; a fall in pump flow rate despite constant stability. Neuromuscular blockade, with boluses or infusions revolutions per minute; and a fall in pre-oxygenator circuit of intermediate-acting drugs, is often necessary to ensure that pressures. optimal ventilation and surgical conditions are maintained. If in theatre, volatile anaesthesia should be avoided due to its Echocardiography can guide haemodynamic management after depressant effects on cardiovascular function and hypoxic ECMO institution. Important potential complications to exclude pulmonary vasoconstriction. It is essential to note that various after ECMO initiation are pericardial tamponade, left ventricular pharmacokinetic and pharmacodynamic alterations will distention and improper cannulae placement. influence drug dosing, and a slow titration strategy should be Once on ECMO, ventilation should be kept on lung protective employed. settings. The following settings are recommended: PEEP between

After the endotracheal tube is properly secured, the patient 8–10 cmH20; tidal volume of 4–6 ml/kg; driving pressure (plateau is usually placed in a slight anti-Trendelenburg position with minus PEEP) less than 15 cmH20; and FiO2 under 40%. a pillow or bag under the shoulders, for internal jugular vein cannulation. The correct size and depth of the cannulae will be On initiation of ECMO, exposure of blood to ambient temperature decided upon by the surgeon. via the circuit tubing and oxygenator can cause a decrease in body temperature. In neonates and children, this is especially Heparin should be administered as a bolus 2–3 minutes prior to significant, as the proportion of blood volume exposed to cannulation at a dose of between 75 to 100 IU/kg. An activated ambient temperature at any one time is larger than adults. A clotting time (ACT) and activated partial thromboplastin fall in body temperature can cause life-threatening arrhythmias time (aPTT) should be performed prior to and after heparin or coagulation abnormalities. To avoid this problem, it is administration. A heparin infusion should be commenced within recommended that a water heat exchanger is utilised routinely 60–90 minutes at a rate of 25–50 IU/kg/hour. ACT for cannulation on the circuit. Other conventional means of temperature should be in the range of 250–300 seconds, and for maintenance management should also be considered, for example, convective should be in the range of 180–250 seconds. warm air blankets. Once cannulation is performed, the ECMO circuit will be connected and pump blood flow will be commenced. ECMO Further intensive care management of the patient should be led by an intensivist experienced in the management of patients on pump flow should be set at 100–150 ml/kg/minute. FiO2 of 100% should be set on the membrane oxygenator oxygen flowmeter ECMO. and the gas flow or sweep should be set equal to the ECMO Conclusion pump flow rate. The ECMO pump flow rate will be adjusted to perfusion parameters such as serum lactate, and the gas flow ECMO is an organ support modality becoming increasingly rate will be adjusted to PaCO2 during the course of the ECMO run. commonplace in the management of cardiorespiratory failure. The anaesthetist plays an important role as part of the Significant haemodynamic changes can occur during the period immediately after cannulation. Prior to cannulation the patient multidisciplinary team involved in the management of patients may be on high doses of inopressor agents. During cannulation, for ECMO initiation, on ECMO or for liberation from ECMO. These blood pressures may fall due to acute haemorrhage. This can patients have significantly deranged physiological changes be treated with a rapid bolus of isotonic crystalloid or blood. and are heavily dependent on organ support modalities. Immediately on initiation of ECMO, mean arterial pressures Anaesthetists managing such cases need to be appropriately increase significantly requiring a cessation or marked reduction trained and experienced in order deal with the challenges posed of inopressor support. During VV-ECMO, this is most likely due in these scenarios.

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References: 7. ELSO Guidelines for Adult Cardiac Failure v1.3. http://www.elso.org/Portals/0/ IGD/Archive/FileManager/e76ef78eabcusersshyerdocument selsoguidelinesfora 1. ELSO Guidelines for Adult Respiratory Failure v1.3. http://www.elso.org/ dultcardiacfailure1.3.pdf. Accessed Aug 2016. Portals/0/IGD/Archive/FileManager/989d4d4d14cusersshyerdocumentselsoguid 8. ECLS Registry Report: International Summary. Available from https://www.elso. elinesforadultrespiratoryfailure1.3.pdf. Accessed Aug 2016. org/Registry/Statistics/InternationalSummary.aspx. Accessed Aug 2016. 2. Nason KS. Acute intraoperative pulmonary aspiration. Thoracic Surgical Clinics 9. ELSO Guidelines for Neonatal Respiratory Failure v1.3. Available 2015; 25:301-307. from http://www.elso.org/Portals/0/IGD/Archive/FileManager/ 3. Li X, He H, Sun B. Veno-venous extracorporeal membrane oxygenation support 8588d1a580cusersshyerdocumentselsoguidelinesforneonatal respiratoryfailure during lung volume reduction surgery for a severe respiratory failure patient -13.pdf. Accessed Aug 2016. with emphysema. Journal of Thoracic Disease 2016; 8(3):E240-E243. 10. ELSO Guidelines for Pediatric Respiratory Failure v1.3. Available from http:// www.elso.org/Portals/0/IGD/Archive/FileManager/6f129b235acusersshyerdoc 4. Schiff JH, Koninger J, Teschner J, et al. Veno-venous extracorporeal membrance umentselsoguidelinesforpediatricrespiratoryfailure1.3.pdf. Accessed Aug 2016. oxygenation (ECMO) support during anaesthesia for oesophagectomy. Anaesthesia 2013;68: 527-530. 11. ELSO Guidelines for Pediatric Cardiac Failure v1.3. http://www.elso.org/Portals/0/ IGD/Archive/FileManager/518a079853cusersshyerdocumentselsoguidelinesforp 5. Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of ediatriccardiacfailure1.3.pdf. Accessed Aug 2016. conventional ventilatory support versus extracorporeal membrane oxygenation 12. Richards GA. Extracorporeal membrane oxygenation (ECMO). South African for severe adult respiratory failure (CESAR): a multicentre randomised controlled Journal of Critical Care 2013; 29(1):7-9. trial. Lancet 2009; 374:1351-63. 13. ELSO Guidelines for ECPR Cases v1.3. http://www.elso.org/Portals/0/IGD/ 6. The Australia and New Zealand Extracorporeal Membrane Oxygenation Archive/FileManager/6713186745cusersshyerdocumentselsoguidelinesforecprc (ANZ ECMO) Influenza Investigators. Extracorporeal membrane oxygenation ases1.3.pdf. Accessed Aug 2016. for 2009 Influenza A(H1N1) acute respiratory distress syndrome. JAMA 14. Butt W, MacLaren G. Extracorporeal membrane oxygenation. F1000Prime 2009;302(17):1888-1895. Reports. 2013;5:55. doi:10.12703/P5-55.

S41 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Anaesthetic considerations for inhaled and ingested foreign bodies in children: What? Where? When?

A Z Bhettay

Department of Anaesthesia, Nelson Mandela Children’s Hospital, University of the Witwatersrand Correspondence to: [email protected]

Introduction Anaesthetic considerations for removal of inhaled foreign bodies Young children are naturally curious and learn by exploration, often putting objects into their mouths and other orifices. Preoperative Toddlers lack the neuro-motor coordination for proper History and examination swallowing, and the molars necessary to grind food boluses The presentation is largely dependent on the type of FB, where into more innocuous pieces. Additionally, they tend to move it is located, and time elapsed since the incident. Children may around while eating. These factors render them vulnerable to be asymptomatic and completely comfortable, or present in aspiration of food particles.1 Data from local studies report that extremis with imminent respiratory arrest. Up to 45% of patients foreign body (FB) ingestion is the fifth most common cause for may have no findings on clinical examination.5 The suggestion is admission to paediatric trauma units.2 Asphyxiation due to an to adopt a ‘What? Where? When?’ approach. inhaled FB lodged in the tracheobronchial tree remains a leading What? In the younger age group and in the neurodevelopmentally cause of death in children under four years of age.3 delayed, the most commonly aspirated or ingested materials Epidemiological data are food particles. In older children, non-organic matter is more prevalent. In the absence of neurodevelopmental delay, most children are under the age of four, with a peak incidence between 1–2 years. Where? There are multiple potential sites of impaction (see Poverty, overcrowding, number of children in the household, Figure1). young maternal age, low maternal education status and single Incidents per anatomical region parent households, all conditions that abound in certain strata 140 within our society, are associated with greater risk.4 120

Typology of FBs 100 80 Generally, objects may be organic or non-organic (metal or non- 60 metal). Complications arise from objects causing mechanical obstruction with or without pressure necrosis, sharp objects 40 causing internal penetrating trauma, and corrosive objects 20 causing mucosal injury and perforation with leakage of contents 0 and potentially catastrophic infection. Organic materials, nuts Nose Lung Bowel Larynx Mouth Trachea Stomach

especially, cause more chemical inflammation. In Africa, the coin Bronchus Oesophagus Nasopharynx is the most commonly ingested object. Round objects are more Hypopharynx dangerous as they can cause complete obstruction. The most Figure 1. Ingested foreign bodies: anatomical site of object. dangerous ingested objects are lithium button batteries. {Reproduced with permission. Van As, et al6)

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Objects lodged in the larynx or trachea are usually large and non-specific and include hoarseness, dyspnoea, stridor, croupy bulky, and can cause significant airway obstruction. Fortunately, cough, haemoptysis, wheezing or drooling. they are far less common. Occasionally objects are thin and The incidence and severity of complications is directly angular, and can then be missed resulting in diagnostic delay. proportional to the chronicity of the retained FB. Bronchitis, The mortality for aspirated FBs in the upper airways remains high tracheitis, distal atelectasis and pneumonia occur commonly. at around 45%, and even those that survive have a 30% chance Chronic or recurrent infection can lead to bronchiectasis. Chronic 5 of developing hypoxic encephalopathy. A small number of obstruction can lead to localised emphysema. Prolonged organic FBs fragment and lodge in different parts of the airway. inflammation caused by the presence of a FB can cause granulomatous tissue formation, possibly requiring further Location % (rounded off) intervention. Larynx 3 Special investigations Trachea + carina 13 • CXR – posteroanterior (PA) and lateral. Although only Right lung (total) 60 10–15% of aspirated FBs are radio-opaque, the CXR may show Main bronchus 52 secondary pathology. It is normal in 30% of patients.7 Lower lobe bronchus 6 • If a laryngotracheal FB is suspected, PA/lateral neck radiograph Middle lobe bronchus < 1 may reveal subglottic swelling and laryngeal stenosis, Left lung (total) 23 especially if present for > 24 hours. Main bronchus 18 • High resolution spiral computerised tomography (CT) can be Lower lobe bronchus 5 considered in stable patients. Bilateral 2 • Virtual bronchoscopy is a new imaging modality that uses Figure 2. Location of aspirated foreign bodies in children. reconfigured axial images obtained during CT, generating an (Reproduced with permission. Van As, et al6) endoscopic perspective of the trachea and bronchi.3

Most aspirated FBs lodge in the right bronchial tree, causing There is some controversy in the literature as to whether a obstruction (see Figure 2). negative result with CT/virtual bronchoscopy would preclude bronchoscopy. Larger studies are needed to provide more clarity. 5 There are four types of bronchial obstruction that may ensue : Clinicians should be cognisant of the radiation and contrast load. • Bypass-valve effect – partial obstruction occurs during Early diagnosis and management improves outcomes. Removal inspiration and exhalation. The chest radiograph (CXR) is of inhaled FBs is facilitated by rigid bronchoscopy, still the gold usually normal. standard, under general anaesthesia. Where airway patency • Check-valve effect – obstruction occurs on exhalation. The CXR is threatened, rigid bronchoscopy must be embarked upon may show hyperinflation or emphysema of the ipsilateral lung. as an emergency. Where patients are stable, procedures may • Ball-valve effect – partial obstruction by object which be delayed until daylight hours, or until the child is fasted to intermittently prolapses into and obstructs the bronchus. decrease the risk of aspiration as the airway will not be fully protected during the procedure. • Stop-valve effect – complete bronchial obstruction with no movement of air. This leads to segmental collapse of the distal Premedication can be considered, but with care to avoid lung. excessive sedation which may worsen airway obstruction. Consider the use of an anti-sialagogue like glycopyrrolate to Symptoms vary considerably depending on the location of the reduce secretions. FB. Intraoperative

Location Signs and symptoms The surgical and anaesthetic plans should be clearly defined by Larynx + Acute airway distress, hoarseness, stridor, both teams. The goal should be a smooth, coordinated, sharing trachea dyspnoea of the child’s airway with a combination of optimal oxygenation, Bronchi Cough, wheeze, haemoptysis, dyspnoea, ventilation, and surgical exposure, resulting in retrieval of the respiratory distress foreign body. Bronchoscopic removal has a high success rate Lower airway Usually asymptomatic unless secondary infection (> 95%) and low complication rate (around 1%). 7 Thoracotomy is When? Unless acute asphyxiation is caused by a large object rarely indicated. Numerous unsuccessful attempts may result in lodged in the upper airway, which results in urgent presentation, the FB being pushed more distally, making retrieval even more patients can present late. If the delay is significant, morbidity difficult. The experience of the anaesthetist and the endoscopist is critical in ensuring a good outcome and minimising and lung disease may be present. Recurring pneumonia, not complications.7 responding to conventional antibiotic therapies may be elicited on history. Thirty percent of cases are misdiagnosed as infective, Good communication between surgeon and anaesthetist as children present with fever, cough and other signs and is of paramount importance during shared airway surgery. symptoms suggestive of pneumonia.7 Other symptoms may be Although the induction technique of choice is often based on

S43 44 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) the experience of the anaesthetist or institutional practice, Ingested foreign bodies most deem it prudent to maintain spontaneous respiration to In contrast to adults, 98% of all FB ingestion in children is prevent converting partial obstruction to complete obstruction. accidental.1 In the South African context, the number of cases This, however, appears to be a rare phenomenon, and largely of ingested FBs requiring surgical intervention is considerably theoretical. Sevoflurane has emerged as the induction agent of higher when compared to international studies, although the choice. Liberal topicalisation with local anaesthetic under direct need for management guidelines has been highlighted.6 vision, preferably via a laryngo-tracheal atomiser, is a useful adjunct. The commonest ingested FB in Africa is the coin. Food bolus impaction is not uncommon, and can occur in patients who Many different anaesthetic techniques have been employed to are neurodevelopmentally delayed, or may be secondary to facilitate removal while minimising complications and operating oesophageal pathology such as eosinophilic oesophagitis, time. The cumulative evidence doesn’t provide a clear superior strictures, reflux oesophagitis or motility disorders.1 option, although a recent meta-analysis showed that when The most common site of impaction for ingested FBs found controlled ventilation was employed, a lower incidence of on CXR is the proximal oesophagus, followed by the stomach, laryngospasm and shorter operating time resulted.8 A study distal duodenum and distal oesophagus, in descending order.2 evaluating risk factors for hypoxaemia during FB removal found Symptoms include vomiting, drooling and dysphagia, although that manual jet ventilation (MJV) was associated with the lowest few patients are symptomatic at time of presentation. incidence of hypoxaemia, when compared to spontaneous and controlled ventilation.9 A retrospective review found a higher In recent years, there has been a dramatic increase in morbidity incidence of adverse events – laryngospasm, coughing, breath and mortality caused by the ingestion of button batteries (BBs). holding, bronchospasm and patient movement – in patients Newer batteries are composed of lithium, have a higher voltage, who received Propofol and Remifentanyl compared with and are larger in diameter. BBs are ubiquitous, found in hearing Propofol and Sevoflurane.10 When comparing Dexmedetomidine aids, watches, remote controls and games. Newer batteries carry a three-fold greater risk of injury, but even ‘dead’ ones in spontaneously ventilating patients to MJV with Fentanyl carry sufficient charge to cause substantial damage. Lithium BB and Propofol, no difference in adverse events, success rates ingestion is associated with high complication rates and high or haemodynamic changes between groups was found, but mortality, justifying emergency endoscopic removal.1 patients who received Dexmedetomidine required longer stays in the post-anaesthesia care unit.11 The mechanisms of injury include leakage of contents, pressure necrosis or electrical discharge. In the stomach’s acidic Intraoperative complications include hypoxia (most common), environment, batteries can disintegrate, releasing alkaline hypercarbia, laryngospasm, disintegration or dislodgement of solutions – sodium and potassium hydroxide – which cause the FB, haemorrhage, pneumothorax, pneumomediastinum liquefaction necrosis, mucosal disintegration and subsequent (due to tracheal or bronchial laceration), hypoxic brain damage perforation. Heavy metal poisoning is a rare complication and cardiac arrest. Disintegration is more likely with organic FBs. caused by the breakdown of mercury batteries. The most Dislodgement of the FB due to manipulation by the endoscopist common mechanism of injury involves electrical discharge, can cause severe airway compromise, resulting in an inability which is extremely dangerous. Electric current flows through to ventilate with severe hypoxia. The main consideration in the surrounding tissue, generating hydroxide radicals in the this scenario is tracheal obstruction, which requires immediate mucosa. Within 30 minutes, the pH increases from seven to 13 removal of the FB or advancing the FB into the same bronchus at the negative pole of the battery, resulting in caustic injury. initially lodged in.12 If vocal cord movement precludes removal, Within 15 minutes, necrosis occurs within the lamina propria of Suxamethonium should be considered. the oesophagus. After 30 minutes, the necrotic area extends to the outer muscular layer. Continued injury can occur for days to After successful removal of the FB it is prudent to repeat the weeks even after removal of the battery. bronchoscopy, as up to 5% of patients may have additional FBs in-situ, and to assess for airway injury. In patients with a Death caused by the formation of an aorto-enteric fistula has been known to occur weeks later. This is a dreaded complication prolonged history, antibiotics may be required to treat secondary with a very high mortality, and should be the chief concern in any infection. This should be guided by cultures taken at the time of patient presenting with coffee-ground vomitus or haematemesis, the bronchoscopy. Corticosteroids can reduce inflammation even post-endoscopic removal. Classically, patients are under and airway oedema, but no clear guidelines exist advocating for the age of five years, have ingested multiple large BBs, and a single dose vs a course of steroids. present with haematemesis. Impaction at the level of the aortic Postoperative arch, battery size greater than 20 mm, and prolonged time since impaction are other factors that should elicit the greatest Severe laryngeal oedema or bronchospasm may require concern.13 Other complications include tracheoesophageal reintubation or tracheostomy. A CXR is mandatory to exclude fistula (47.9%), oesophageal perforation (23.3%), oesophageal pneumothorax or pneumomediastinum. The postoperative strictures (38.4%), vocal cord paralysis from recurrent laryngeal destination should be individualised and depends on the nerve injury (9.6%), mediastinitis, pneumothorax, cardiac arrest preoperative state and intraoperative course. and death.1

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Management of these cases requires a multi-disciplinary The management of BBs that have passed through the approach, involving physicians, paediatric oesophagus is under debate. Previous guidelines recommended gastroenterologists, interventional radiologists and cardiologists, a period of observation, but more recent guidelines suggest paediatric surgical sub-specialities and anaesthesia.13 Rapid risk endoscopy for evaluation of injury and possible removal in high- assessment and mobilisation of the appropriate resources is risk patients (see above).13 crucial in optimising outcomes. Conclusion CXR helps to distinguish the more innocuous coin from the Ingestion or aspiration of FBs is common in the paediatric dreaded BB. The characteristic ‘halo’ sign diagnostic of a BB age group, causing significant morbidity and mortality. Child should be sought, as well as the ‘step off’ sign, between the accident preventative programmes need to adopt a multi- positive and negative nodes (see Figure 3). pronged strategy aimed at reducing the number of children affected. Anaesthesia for these children can be challenging, with considerable potential for complications. The literature does not provide consensus on anaesthesia techniques, but does advocate for the presence of a skilled and experienced anaesthetist and endoscopist. A multidisciplinary approach is advocated, and good communication is essential. References 1. Kramer RE, Lerner DG, Lin T, et al. Management of ingested foreign bodies in children: a clinical report of the NASPGHAN Endoscopy Committee. Journal of pediatric gastroenterology and nutrition. 2015;60(4):562-74. 2. Delport CD, Hodkinson PW, Cheema B. Investigation and management of foreign body ingestion in children at a major paediatric trauma unit in South Africa. African Journal of Emergency Medicine. 5(4):176-80. 3. Fidkowski CW, Zheng H, Firth PG. The anesthetic considerations of tracheobronchial foreign bodies in children: A Literature Review of 12,979 Cases. Anesthesia and Analgesia. 2010;111(4):1016-25. 4. World Health Organization. World Report on Children Injury Prevention. Switzerland: World Health Organization + UNICEF; 2008. Figure 3. CXR showing the 'halo' of the button battery 5. Zur KB, Litman RS. Pediatric airway foreign body retrieval: surgical and anesthetic perspectives. Pediatric Anesthesia. 2009;19:109-17. CT angiogram can diagnose aortic injury, for which there should 6. Van As A, Du Toit N, Wallis L, et al, editors. The South African experience with ingestion injury in children. International Congress Series; 2003: Elsevier. be a high index of suspicion if the point of impaction is mid- 7. Sultan TA, van As AB. Review of tracheobronchial foreign body aspiration in the oesophageal. Magnetic Resonance Imaging is a useful tool for South African paediatric age group. Journal of Thoracic Disease. 2016;8(12):3787. evaluating the extent of the injury, both at the initial presentation, 8. Liu Y, Chen L, Li S. Controlled ventilation or spontaneous respiration in and for ongoing surveillance.13 Consideration should be given to anesthesia for tracheobronchial foreign body removal: a meta-analysis. Pediatric Anesthesia. 2014;24(10):1023-30. removing ingested button batteries in the cardiac catherisation 9. Chen L-H, Zhang X, Li S-Q, et al. The risk factors for hypoxemia in children laboratory, under fluoroscopic guidance and arteriography, if younger than 5 years old undergoing rigid bronchoscopy for foreign body aortic injury is suspected. removal. Anesthesia and Analgesia. 2009;109(4):1079-84. 10. Chai J, Wu X-Y, Han N, et al. A retrospective study of anesthesia during The most common method employed for removal of ingested rigid bronchoscopy for airway foreign body removal in children: propofol FBs is endoscopy. With the airway secured, anaesthesia for and sevoflurane with spontaneous ventilation. Pediatric Anesthesia. 2014;24(10):1031-6. endoscopy is significantly less challenging than that for aspirated 11. Cai Y, Li W, Chen K. Efficacy and safety of spontaneous ventilation technique FBs. In the absence of life-threatening complications associated using dexmedetomidine for rigid bronchoscopic airway foreign body removal in with certain ingested objects, most complications are mild and children. Pediatric Anesthesia. 2013;23(11):1048-53. can be managed conservatively. These include oesophageal 12. Slabber P. Airway Foreign Bodies. In: KwaZulu-Natal Uo, editor. 2014. 13. Leinwand K, Brumbaugh DE, Kramer RE. Button battery ingestion in children: ulcers, mucosal injury, tears in the oesophageal wall and stricture a paradigm for management of severe pediatric foreign body ingestions. formation.2 Gastrointestinal endoscopy clinics of North America. 2016;26(1):99-118.

S45 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Anaesthesia for audiology brainstem response testing in children with autism spectrum disorder

M R Correia

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

Introduction deficiency, increased oxidative stress and membrane lipid abnormalities may be of concern perioperatively.4 Audiology brainstem response (ABR) testing is used to examine the integrity of the conductive and neuronal auditory pathways Autism is heterogenous in its presentation and no two children in children presenting with developmental delay. Testing needs with ASD will have the same features.1,2,3,4 The condition is to be done with a quiet, co-operative patient preferably under defined based on behavioural symptoms and diagnostic criteria normal sleeping conditions in a sound-proof booth. In infants and includes the following: and children, especially those with associated behavioural • difficulty with social communication and reciprocity problems, this may mean that sedation or even general • restrictive and repetitive behaviours anaesthesia will be necessary to adequately complete testing. A 2015 audit of the ABR service at Chris Hani Baragwanath • symptoms that are present from early in life Academic Hospital found that the rate of co-morbidities in these Significant functional impairment must be present for the children was high with the most common co-morbidities being diagnosis to be made and all other causes must have been autism spectrum disorder (ASD), with or without attention deficit excluded. The Childhood Autism Rating Scale (CARS) may be and hyperactivity disorder (ADHD), epilepsy, cerebral palsy, or a used to identify children who need further testing.5 It consists diagnosed syndrome. of 15 questions asked of the caregiver pertaining to the child’s This review will cover aspects related to the most common co- behaviour. Each question is equally weighted and can be morbid conditions found in ASD children presenting for ABR scored from 1, indicating normal age-appropriate behaviour, testing and the effect that different anaesthetic agents may have to 4, indicating severely abnormal behaviour. A score of 36–60 on the evoked potentials obtained. The author also presents a indicates moderate to severe autism. possible approach to managing these children. The difficulty these children experience with communication Autism spectrum disorder ranges from struggling with the use of everyday language to having no verbal skills at all. They may also find physical and ASD is a neurodevelopment disorder which presents with non-verbal communication challenging. Eye contact may seem deficits in social communication, repetitive behaviours and some sort of sensory hypersensitivity.1,2,3,4 These children have threatening to some and provoke intense anxiety in others. restricted interests and struggle with normal emotional and Ritualistic behaviour patterns with the need for familiar routines physical expression. The term ASD has recently been reviewed and environments are an attempt to control the confusing in the Diagnostic and Statistical Manual of Mental Disorders world around them. A small change in their daily routine can be (DSM-5) to include autistic disorder, high functioning autism, extremely unsettling and aggravate changes in behaviour which Asperger syndrome, pervasive developmental disorder and may be detrimental to both the child and others. atypical autism. The incidence of ASD is estimated at around 1% The inability to process sensory inputs is included under the DSM of the population and is more common in males especially in criteria of repetitive behaviour. These children may be hypo- or children with higher IQ.1 hyperresponsive to stimuli which may involve any of their five The exact aetiology is unknown but is thought to be due to a senses. This can be difficult to manage perioperatively: the use of combination of genetic and neural developmental factors.1,2,4 certain stimuli that evoke pleasure may be used to distract these Emerging evidence suggests that in some children with ASD there children while basic non-painful procedures are carried out but a may be a link with some biochemical and metabolic problems. bright, noisy hospital room with unfamiliar faces and sounds can Mitochondrial dysfunction, increased lactate, B-vitamin complex elicit unmanageable anxiety and fear.

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Management of ASD may be pharmacological or non- well as perioperative opioid use were the same as the control pharmacological. Drugs used may include long-acting group. antipsychotic medications like risperidone. These agents are Treatment for ADHD is multimodal and can be divided into associated with hypotension and arrhythmias under general pharmacological and non-pharmacological strategies. Non- anaesthesia. It is recommended that clozapine be stopped pharmacological therapies involve intensive family and perioperatively and the patient changed to a shorter-acting drug. individual counselling and education, school remediation and Clozapine is associated with agranulocytosis, hyperthermia, behavioural interventions to help patients and their families deal cardiac conduction problems and significant hypotension under with the condition. general anaesthesia (GA). Caution should be exercised when discontinuing these drugs as side-effects include dystonia, Pharmacological strategies are divided into CNS stimulants dyskinesia, delirium and psychosis with sudden withdrawal. and CNS non-stimulants.7 The medications used are effective Consultation with the child’s psychiatrist is mandatory.1 in controlling symptoms and improving overall function. Most of the treatment options increase CNS levels of dopamine and Non-pharmacological strategies used in ASD are usually a noradrenaline leading to increased neurotransmission. combination of psychological, behavioural, developmental, CNS stimulants: therapy-based and sensory-motor. Methylphenidate Other than the essential features noted above, children with Amphetamines ASD often have associated problems that have implications for CNS non-stimulants: the anaesthetist.1,3,4 Additional intellectual disability may make communication even more challenging. Both gross and fine Tricyclic antidepressants motor co-ordination can be impaired with apraxia (difficulty in Monoamine oxidase inhibitors planning their next movement) and hypotonia being common Alpha-2 agonists findings. These children may have an odd gait and appear clumsy. Atomoxetine (noradrenaline re-uptake inhibitor) Patients may also be on pharmacological treatment for anxiety Modafinil (atypical dopamine re-uptake inhibitor) or sleep disorders. Benzodiazepines, antihistamines, alpha-2 Bupropion (noradrenaline re-uptake inhibitor and nicotinic agonists and melatonin may be used by patients and drug receptor antagonist) interactions need to be considered before formulating an Potential drug interactions anaesthetic management plan. Methylphenidate is most commonly prescribed. It is structurally Seventy percent of children with ASD will have at least one similar to the catecholamines and acts as a noradrenaline and associated psychiatric disorder and 40% will have two or dopamine re-uptake inhibitor. It is metabolised to inactive more. ADHD and epilepsy are amongst the most common co- metabolites in the liver which are then excreted via the kidneys. morbidities seen with prevalence rates of around 30% and 20% Concerta is the trade name for the extended release formula respectively.1,3 These conditions have their own anaesthetic which minimises fluctuations between peak and trough drug considerations and are discussed below. levels during the day. Common side-effects include anorexia, Attention deficit and hyperactivity disorder weight loss and sleep disturbances.

ADHD is characterised by inattention, impulsivity and Drug interactions associated with general anaesthesia include hyperactivity.6,7 The incidence is reported as between 2–20% in cardiovascular instability, dose adjustments required for school-aged children. The cause is unknown but there have been minimum alveolar concentrations (MAC) values for the volatile associations shown between ADHD and genetic predisposition, agents, postoperative nausea and vomiting (PONV) and prematurity, low birth weight, maternal smoking, parental decreases in the seizure threshold in at-risk patients. alcoholism and social/family problems. The pathophysiology is Preoperatively, oral midazolam used in regular doses for linked to central nervous system neurotransmitter imbalance or premedication has been shown to be less effective in patients 7 dysfunction. taking methylphenidate. Ketamine use perioperatively is Potential problems associated with the perioperative associated with increased PONV and dehydration. Clonidine, management of patients with ADHD may be due to increased when used as a premed, is associated with less PONV, has an anaesthetic sparing effect, blunts haemodynamic responses to levels of anxiety preoperatively, severe agitation during stimuli and decreases the incidence of shivering. induction and emergence, postoperative behavioural changes and anaesthetic drug interactions with medications prescribed.6,7 Intraoperatively, patients taking CNS stimulants have a blunted Tait et al describe the first prospective trial done that looked at ability to respond to hypotension because of decreased a cohort of ADHD patients presenting for elective ambulatory endogenous catecholamine stores and down regulation of surgery under general anaesthesia.6 They showed that these receptors. They exhibit increased baseline heart rates, are at patients were more likely to be uncooperative at induction and higher risk for the development of arrhythmias and require display exaggerated postoperative maladaptive behaviour. Their increased MAC levels to maintain an adequate depth of premedication regimens, induction and maintenance drugs as anaesthesia. Careful titration of anaesthetic agents is needed

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to avoid large swings in haemodynamic variables and depth of ▫▫ They may present only with transient depressed level anaesthesia monitors such as BIS or entropy should be used. of consciousness, as in absence or petit mal seizures, or generalised muscle contractions which may be tonic, One of the biggest concerns with patients on CNS stimulants clonic or grand mal seizures which involve a combination is the increased risk of seizure activity perioperatively.7 of tonic and clonic movements. Anticonvulsants need to be continued and certain drugs ▫ There is usually always an impaired level of consciousness avoided. Ketamine, tramadol and pethidine may all increase the ▫ associated with generalised seizures. risk of seizures in these patients. The pathophysiology of epilepsy is thought to be related to Epilepsy the loss of gamma-aminobutyric acid (GABA) mediated post- Epilepsy is defined as paroxysmal, abnormal cerebral electrical synaptic inhibition associated with the development of new discharges associated with clinical signs and is one of the most neuronal connections and the increased release of the excitatory common chronic neurological conditions diagnosed. It is twice neurotransmitter glutamate. This, coupled with the presence of as common in children as in adults and may be progressive. The pacemaker cells which contain abnormal calcium currents leads incidence ranges from 0.5–2% and varies with age, sex, race and to abnormal firing of neurones in affected areas of the brain. socio-economic status. There is also an association with mental The harmful consequence of this abnormal activity is termed retardation, cerebral palsy, and behavioural disorders.8 excito-toxicity: the increased depolarisation of neurones and activation of excitatory amino acid receptors leads to an influx Seizures may be primary (idiopathic) or secondary to a host of of calcium. The high intracellular calcium levels eventually lead 9 other conditions. to cell necrosis and apoptosis resulting in loss of neuronal cells 8,9 Secondary causes may be divided into pre-, peri- or postnatal and toxicity. events ranging from inborn errors of metabolism and Treatment for epilepsy is individualised for each patient chromosomal disorders to prematurity and biochemical and is based on seizure type and severity. Management abnormalities such as neonatal hypoglycaemia or hypocalcaemia. strategies include treatment of predisposing factors, dietary, Infectious diseases remain an important cause especially in pharmacological and surgical resection or callosotomy.9 Dietary developing countries. and pharmacological treatments are discussed below. The classification of seizures is divided into partial (focal) or Dietary management generalised.8,9 Dietary strategies are used to help control seizures in patients • Partial seizures with intractable symptoms and unacceptable side-effects on ▫▫ Excessive neuronal discharges originate from one point of anti-epileptic drugs (AEDs.) The use of a ketogenic diet has been a cerebral hemisphere. shown to decrease seizure severity and frequency. A normal diet ▫▫ May be simple or complex depending on whether there is has a fat:carbohydrate (CHO) and protein ratio of 0.3:1 with about an associated depressed level of consciousness. 35% of daily calories coming from fat. A classical ketogenic diet ▫▫ May progress to a generalised seizure. has a fat:CHO and protein ratio of 4:1 with 90% of daily calories coming from fat. Because of the high rates of non-compliance ▫▫ The presentation of partial seizures will depend on the with this diet in children, a revised diet of fat:CHO ratio of 1:1 area of the cortex involved and may present with motor, with 65% of calories from fat has been shown to be as effective sensory, autonomic or psychological signs and symptoms. with better compliance. Important side-effects of a ketogenic • Generalised seizures diet to consider when planning anaesthesia include poor growth ▫▫ Represent bilateral symmetrical brain activity and involve in children < 1 year, renal calculi, long bone fractures, abnormal the thalamic tracts in the generation of diffuse, bilateral liver enzymes, abnormal lipid profile, hypoproteinaemia and discharges. ketoacidosis.

Table I. Commonly used anti-epileptic drugs and their side-effects pertaining to anaesthesia Half-life (hours) Mechanism of action Side-effects Phenytoin 12–24 Sodium channel blocker Enzyme induction, megaloblastic anaemia, highly protein bound Sodium Valproate 6–10 Sodium channel blocker Enzyme induction, thrombocytopaenia, hepatotoxicity, highly protein bound Carbamazepine 4–12 Sodium channel blocker Enzyme induction, pancytopaenia, cholestasis, hyponatraemia, highly protein bound Phenobarbital 12–96 GABA agonist, AMPA blocker Enzyme induction, megaloblastic anaemia, highly protein bound

Clonazepam 18–50 GABAA agonist Sedation, CNS depression Gabapentin 5–7 Calcium channel blocker Sedation, breakdown blocked by sodium valproate Lamotrigine 24 Sodium channel blocker GIT disturbances, sedation, dizziness Topiramate 26 Unknown ?sodium channel Insignificant normal anion gap metabolic acidosis, enzyme inhibition

blocker, GABAA agonist

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Pharmacological management Fluid resuscitation to maintain adequate systemic blood pressure and cerebral perfusion pressure. The aim of treatment with AEDs is control of seizures on monotherapy with minimal to no side-effects.8,9,10 Prognosis is If seizures are not controlled after 30 minutes with second-line usually good with 70% of patients achieving control for five years therapy, consider propofol or low-dose thiopentone infusion or more. Fifty percent of patients that have their anti-epileptic anaesthesia preferably under EEG control. Alternatives include drugs discontinued appropriately will remain symptom free.8 phenobarbital. The most commonly used AEDs and their significant effects with Remember – muscle relaxants stop the seizure movements, but respect to anaesthesia are represented in Table I. not the abnormal cerebral activity, therefore in the paralysed The prevention of seizures perioperatively is paramount. AEDs patient, anti-convulsants are also essential. should be continued up to the time of the planned procedure Auditory brainstem response testing and restarted as soon as possible afterwards. Most drugs have a long half-life so a missed dose is not usually critical. Many of the ABR testing is useful clinically as a measure of hearing sensitivity AEDS do not have parenteral preparations and for those patients and to examine the functional integrity of eighth cranial nerve 13,14 with intractable symptoms or a prolonged nil per mouth period, (CN VIII) and the auditory brainstem neurones. It is reliable, 13 a perioperative treatment plan should be agreed upon with the reproducible and non-invasive. child’s neurologist before the procedure. Premedication in these Auditory brainstem responses are elicited by stimulating the children may prove beneficial as hyperventilation from anxiety auditory pathway with acoustic signals while electrodes on the may decrease the seizure threshold. Caution must be used scalp measure the response. ABRs are separated out from the when administering sedative drugs as some of the AEDs have background electroencephalograph (EEG) using averaging and enzyme induction effects which increase dose requirements and amplification techniques.13,14 It is made up of a series of peaks others have an additive sedative effect. All agents used must in waveforms occurring within 10 milliseconds of the stimulus be individualised per patient depending on their presentation, which is usually a click administered through headphones in one chronic medications and level of anaesthesia required for the or both ears. The waves obtained represent the different areas procedure. of the pathway being examined: Waves I and II originate from CN VIII and waves III–V depend on the neural functioning of the Status Epilepticus is a medical emergency that should cochlear nucleus through the lateral lemniscus. be recognised and treated promptly.8,9,11 It is a rare event perioperatively but must be considered if there are tonic-clonic In order for interference with testing to be minimised, the seizures, loss of consciousness or tongue biting under sedation patient needs to remain still throughout the procedure. Various or delayed emergence, unexplained haemodynamic changes, anaesthetic techniques have been used to facilitate testing. increases in oxygen consumption or increases in end tidal CO2 Spontaneous respiration in a sedated patient is preferred as under general anaesthesia. this minimises interference.15 The administration of general anaesthesia in the operating room (OR) has been shown to 12 Status Epilepticus decrease the number of waveforms obtained with delays in 13,14 Definition: Continuous seizure activity lasting > 30 minutes or latencies and decreases in amplitudes of the ABRs. The causes intermittent seizure activity lasting > 30 minutes during which of diminished test results in the OR are due to both equipment and patient factors. Electromagnetic and background noise consciousness is not regained interference is higher in the OR and changes in patient blood Emergency management oxygenation levels, blood pressure and decreases in body temperature all have a negative effect on the ABR obtained. ABC Interpretation of ABR results in the OR is challenging but • Airway achievable should a GA be required to optimise patient safety.14,16 • Breathing – 100% O2 The ideal setting for ABR testing is in a sound proof booth • Circulation – IV access to minimise interference. This is usually in the audiology • Don't Ever Forget Glucose! – check and correct hypoglycaemia department far away from the familiar theatre environment. The SASA guidelines for the safe use of procedural sedation First-line therapy and analgesia for diagnostic and therapeutic procedures in • IV Benzodiazepines – Lorazepam (0.1mg/kg) or Diazepam children should always be followed when performing sedation (0.1mg/kg) in a remote location. A reliable oxygen source, suction unit, emergency drugs/equipment and devices for advanced airway Second-line therapy if seizures not terminated within 10 min management must be immediately available. Monitoring must • IV Phenytoin (15–17 mg/kg) by slow infusion (rate < 50 mg/ include standard ASA monitors and capnography. min) The sedation technique chosen should ideally use agents that Intubation and ventilation to maintain normal PaO2 and PaCO2 don’t interfere with ABR waveforms, have a rapid and predictable • Rapid sequence induction should be performed (propofol is onset of action and have a short duration of action with an acceptable substitute for thiopentone) minimal respiratory and cardiovascular effects. Emergence and

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awakening should be prompt to minimise recovery times and or at home. Waiting and preprocedure fasting times should be as return the patient to their baseline level of functioning as soon short as possible. Depending on the needs of the child and if the as possible. hospital has the facility, it may be necessary to bring the child in via a separate corridor into a quiet room where no other patients Table II. The effect of commonly used anaesthetic agents for or staff have access. sedation and general anaesthesia on auditory brainstem-evoked potentials14,15,17 Preoperative assessment should be thorough and focus on any Amplitude Latencies co-existing medical conditions that may influence anaesthetic Halogenated volatile agents Decrease Increase management. Birth history, associated syndromes, behavioural (0.5–1.0 MAC without N2O) problems, symptoms of snoring or chronic upper airway Nitrous oxide Decrease No effect obstruction and a history of epilepsy need to be specifically Propofol Minimal decrease No effect elicited from the caregiver and investigated. A detailed history Ketamine Increase Minimal increase of special diets and medications must be asked. As shown in the Opiates Minimal decrease Minimal increase text above, the most important concerns regarding medications Benzodiazepines No effect No effect perioperatively are the potential for drug interactions and side- effects of treatment the patients may be taking. For ABR testing, Dexmedetomidine No effect No effect all chronic medications should be continued on the day of the procedure preferably given more than two hours before the child A recommended approach to children with ASD is sedated and with the minimal amount of volume possible to presenting for ABR testing satisfy fasting guidelines.

Preprocedure It may be difficult to examine these patients and care must be Early identification of these patients is crucial so that the child’s taken not to come across as threatening. Many children with needs can be given due consideration from admission to ASD and normal intelligence will be cooperative as long as they discharge. The child, caregiver and staff need to be prepared know what is expected of them. Visual information cards and 1,5 timeously. Non-threatening but necessary procedures such as videos have shown to be effective in preparing these children. measuring the weight, height and basic vitals of the child should Allowing comfort items to be brought in, especially those that be done before the day of admission, as a part of a familiar hold a special interest, can be very useful distractors. Minimising routine and preferably in an environment that is familiar to them sensory inputs is important to limit sensory hypersensitivity: e.g. their regular paediatrician’s office. examining the child in a quiet, semi-dark room with the minimal number of staff necessary can be helpful in keeping them The caregivers know their children best and should be consulted calm. A focused examination looking for airway abnormalities, before the day of admission as to what stimuli the patient will evidence of upper or lower respiratory infections, hypotonia and respond to. This includes both positive and negative responses. obstructive sleep apnoea should be carried out efficiently to A proposed checklist to be filled out by the caregiver is shown minimise examination time. in Figure 14: Because ABR testing is non-invasive and usually accomplished Admission procedures should be minimised by getting necessary with minimal sedation, blood results are not usually required forms filled out at the hospital before the day of the procedure prior to induction. However, it is recommended that these children have the appropriate Surgeon: Anaethetist: laboratory testing done to check for side-effects Proposed date of surgery: of their chronic medication before undergoing Planned procedure: any surgical procedures. Patient name: Age: Carer name: Contact telephone number Administration of premedication is recommended but can be challenging and Severity of ASD: patients may refuse. Knowing what foods and Developmental level: General health: drinks the child normally likes and using them Mobility needs: to disguise the drug is useful. Evidence is lacking \Medication: as to which premedication is best. Using a drug that you are comfortable with is always best. The Food/drink Activities Objects application of EMLA® cream to potential drip sites Likes/obsessions is useful but should be abandoned if it causes the Dislikes/phobias patient unnecessary distress. The use of physical restraint should be avoided at all times. If there Action taken: Play specialist/anaesthetist informed: is serious risk of injury and the procedure is not urgent, the procedure should be postponed and Figure 1. Proposed pre-operative checklist for caregivers

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an alternative plan discussed. If restraint is unavoidable, consent Ramsay Sedation Assessment Scale must be obtained from the caregiver and preferably trained staff Awake Patient anxious or agitated or both 1 should be involved. Levels: Patient cooperative, oriented and tranquil 2 For premedication, oral midazolam 0.5 mg/kg is effective with Patient responds to commands only 3 minimal side-effects but may not be enough when used as a Asleep A brisk response to a light glabellar tap 4 Levels: single agent especially if the child is on CNS stimulant drugs. A sluggish respnse to a light glabellar tap 5 No response 6 Ketamine 5–7 mg/kg PO may be added or used as an alternative in children with moderate to severe autism who are uncooperative Recovery 1,18 or intellectually impaired. Intramuscular ketamine 3–5 mg/kg Children with ASD often become agitated and distressed on is a reliable choice when the use of oral medication is not possible emergence from anaesthesia or sedation. It can be difficult or ineffective. Side-effects include disorientation, emergence for healthcare workers to differentiate between pain, anxiety, delirium, hyper-salivation and PONV. nausea and . The child should be allowed to recover in a quiet, semi-lit room with caregivers and comfort A retrospective study by Lubisch et al showed that the alpha-2 items standing by. Early removal of the intravenous cannula is agonist dexmedetomidine at 2–5 mcg/kg can be successfully recommended in those patients who seem to be recovering well. used PO to obtain adequate sedation in these patients. Side- Early discharge home and return to a familiar routine is ideal if at effects are minimal and parent satisfaction was greatly improved all possible. with the use of dexmedetomidine/midazolam combination when compared to chloral hydrate and phenobarbital. Clonidine Conclusion 5 mcg/kg PO has also been shown to induce adequate sedation Children with ASD are a challenging group of patients for the for EEG studies in autistic children. Intranasal dosing of the anaesthetist. The perioperative environment is entirely contrary alpha-2 agonists is usually not possible in these children. to their unique needs and can be a source of extreme anxiety and stress for child, caregiver and medical staff alike. They often have Because ketamine has multiple side-effects, it should be viewed significant co-morbidities that necessitate careful anaesthesia as second-line for premedication with midazolam and alpha-2 assessment and planning in the pre-, intra- and postoperative agonists as first-line. Once the patient is calm and cooperative, IV periods. access should be obtained. ABR testing is clinically useful in these patients as it can Maintenance of sedation differentiate causes of delayed development and ultimately allow for progressive treatment options to improve how these Maintenance of sedation during the ABR testing can be achieved children interact with the world around them. with a number of different techniques. Additional dosing may not be required depending on the drug and dose used for Educating healthcare workers and hospital management premedication. The goals of the sedation technique chosen about ASD can go a long way to improving the perioperative should be to provide adequate depth of sedation (Ramsey experience for all concerned. Being imaginative and making score 3–4) with minimal haemodynamic changes, adequate small changes to the environment and how we communicate oxygenation, maintenance of control of airway reflexes and fast with these children can go a long way to improving how we care recovery times. for them. References A combination of propofol and ketamine in a 4:1 dilution is 1. Taghizadeh N. Autism spectrum disorder (ASD) and its peri-operative effective and safe. An initial dose of 0.5–1 mg/kg can be used to management. Pediatric Anesthesia. 2015;25:1076-84. achieve a Ramsey sedation score of 3–4. A maintenance infusion 2. Arnold B. Autistic children and anesthesia: is their peri-operative experience of 50–100 mcg/kg/min titrated appropriately may be used to different? Pediatric Anesthesia. 2015;25:1103-10. achieve adequate levels of sedation. 3. Herbert M. Autism: A brain disorder or a disorder that affects the brain? Clinical Neuropsychiatry. 2005;2(6):354-79. Intravenous dexmedetomidine 1 mcg/kg combined with IV 4. Short JA. Anaesthesia for children with special needs, including autistic spectrum disorder. Continuing Education in Anaesthesia, Critical Care and Pain. ketamine 1 mg/kg causes adequate levels of sedation for ABR 2013;13(4):107-12. testing for at least 40 minutes when combined with midazolam 5. Elgendy H. Variation of anesthetic sedation requirements in children undergoing for premedication. A single IV dose of each drug at the beginning auditory brainstem response (ABR) test: A retrospective cross-sectional study. Journal of Anesthesia and Clinical Research. 2016;7(9). of the procedure is usually sufficient. 6. Tait AR. Anesthesia induction, emergence and postoperative behaviours in children with attention-deficit/hyperactivity disorders. Pediatric Anesthesia. Effective antiemetic medication and adequate IV hydration are 2010;20:323-9. recommended during the procedure as many autistic children 7. Chang C. General anesthesia in a juvenile with attention deficit hyperactivity will refuse oral medication afterwards. This will also facilitate disorder accompanied by long term use of methylphenidate. Acta Anaesthesiology Taiwan. 2009;47(4):208-11. early removal of the intravenous cannula which will probably not 8. Maranhão M. Epilepsy and Anesthesia. Revista Brasileira de Anestesiologia. be tolerated once the child is awake. 2011;61(2):232-54.

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9. Barakat A. Anaesthesia and childhood epilepsy. Continuing Education in 14. Zhou G. clinical experience of auditory brainstem response testing on pediatric Anaesthesia, Critical Care and Pain. 2011;11(3):93-8. patients in the operating room. International Journal of Otolaryngology. 10. Rogawski MA. Chapter 43, Mechanism of action of anti-epileptic drugs. In: Wyllie 2012;2012. E, editor. Wyllie's treatment of epilepsy: principles and practices. Sixth edition ed. 15. Bocskai T. Sedation of children for auditory brainstem response using ketamine- Philadelphia: Wolters Kluwer; 2015. p. 522-9. midazolam-atropine combination – a retrospective analysis. SpringerPlus. 11. Gratrix A. Epilepsy in anaesthesia and intensive care. Continuing Education in 2013;2. Anaesthesia, Critical Care and Pain. 2005;5(4):118-21. 16. Aleshire KM. Examination of the consequences of various anesthetic agents on 12. Epilepsy and Anaesthesia [Internet]. 2006. Available from: www.anaesthesiauk. auditory evoked potential recordings: Ohio State University; 2013. com/documents/EpilepsyandAnaesthesia_final.pdf. 17. Mason K. Effect of dexmedetomidine sedation on the EEG in children. Pediatric 13. Norrix L. The auditory brainstem response: Latencies obtained in children Anesthesia. 2009;19:1175-83. while under general anesthesia. Journal of American Academy of Audiology. 18. Van der Walt JH. An audit of perioperative management of autistic children. 2012;23(1):57-63. Paediatric Anaesthesia. 2001;11:401-8.

S52 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Anaesthesia for craniosynostosis surgery

D Lines

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

Introduction skull growth occurs perpendicular to the fused suture line. This effect is responsible for the common deformities associated with Anaesthesia for craniosynostosis surgery is complex and poses specific suture line involvement.1 numerous challenges to the anaesthesiologist. Evaluation of these patients for surgery needs to be part of a multidisciplinary Craniosynostosis occurs because of premature fusion of team involving anaesthesia, , and skull suture lines. The majority of cases (+/- 80%) occur as an paediatric intensivists. isolated event in an otherwise normal child and the remaining Rudolf Virchow in 1851 first described the relation between facial (+/- 20%) occur as part of a known syndromic condition. Isolated dimorphism and craniosynostosis and the fact that the arrest of craniosynostosis often only involves one suture line (most

Figure 1. Anatomical variations of craniosynostosis. Illustration by Lauren Divito. (Rights reserved).

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commonly the sagittal suture) and is not associated with other Surgical correction of craniosynostosis is necessary for cosmetic congenital abnormalities. Their aetiology as far as is known is as well as medical reasons and these include management of non-genetic and most probably relates to some physical intra- raised intracranial pressure, to allow normal brain growth as well uterine factor which restricts skull growth (multiple pregnancy or as eye protection in severe exorbitism and potential blindness. uterine abnormality).2 Other suspected contributing factors are Numerous sources in the literature have sought to seek a link hyperthyroidism in the mother, warfarin or valproate use during between severe craniosynostosis and mental developmental the pregnancy and if the mother smokes.3 Syndromic craniofacial difficulties including associations with learning difficulties, abnormalities may be associated with craniosynostosis and the hyperactivity and attention deficit disorders. Most of these common ones include, Apert, Crouzon, Muenke, Pfeifer and associations are, however, anecdotal. Saethre-Chotzen.2 These syndromes are associated with specific The timing of surgery needs to be carefully considered. Raised abnormalities in genes coding for fibroblast growth factor intracranial pressure (ICP) by itself may dictate when surgery receptors so that when fibroblast growth factor binds to the will be done but in otherwise normal children it is a balance abnormal receptor for a prolonged time, premature signalling between easier surgery at a young age before six months and occurs for immature bone cells to differentiate early and cause the increased anaesthetic-related risks. Early surgery may also suture lines to fuse. Inheritance is autosomal dominant although increase the risk of re-operation. In older children the bones the majority are new mutations from unaffected parents.2 The are harder and more difficult to remodel as well as bones losing overall incidence of craniosynostosis is approximately 1:2 000 to their ossification properties versus less anaesthetic risks. The 1:3 000 live births.3 optimal time is somewhere between six months and one year Paul Tessier in 1967, a plastic surgeon, pioneered corrective of age which still provides advantages of early surgery with less surgery for these patients, thought previously to be impossible. anaesthesia-related risks. The Johannesburg craniofacial unit He described how bones of the skull in infants could be removed, operates at six to twelve months of age unless raised intracranial remodelled and put back as a free graft and survive.4 This field pressure dictates otherwise. has continued to grow with important advances in surgical as Surgical options well as anaesthetic techniques to make these types of safe for children to undergo. Surgical correction addresses the fused sutures so as to allow normal brain growth and attempts to correct the areas of The three clinical features associated with cranial dysostosis compensatory overgrowth so that the skull can remodel into are craniosynostosis, midface regression and exorbitism. normality. Treatment options include: Common skull deformities are described with craniosynostosis 1. Strip craniectomies depending on which suture lines have closed prematurely. Premature closing of the sagittal suture results in scaphocephaly These procedures are performed mainly for sagittal stenosis or an elongated skull. Bilateral coronal suture fusion results in and are performed at a young age (< 6 months) and rely on brachycephaly with a broad skull. Turricephaly is as a result of rapid brain growth to remodel the calvarium. A high stenosis closure of both sagittal and coronal sutures giving the skull a rate has been found with only 29% returning to normal. triangular shape.4 Fusion of one of coronal or lambdoid sutures This procedure is often combined with helmet moulding results in plagiocephaly with an asymmetrical distorted skull. therapy.2,5 The most common of the syndromic craniofacial abnormalities 2. Spring assisted craniectomies resulting in craniosynostosis are Crouzon’s and Apert syndromes. Springs are inserted across the osteotomy defect created in Crouzon’s syndrome is the most common to be associated with an attempt to open the bi-parietal narrowing and allow rapid craniosynostosis. The suture lines usually affected are the coronal brain growth to remodel the skull. The springs are removed sutures resulting in brachycephaly. It occurs with a frequency of after six months. As with strip craniectomy alone the results 1:25 000 live births with an autosomal dominant inheritance. are less positive than calvarial remodelling. In addition to the skull abnormality these patients also have midface hypoplasia with nasal obstruction and exorbitism. Many Strip craniectomy is a less invasive procedure with less (up to 55%) have hearing loss and up to 33% have fusion of blood loss and shorter hospital stay but at the expense of a cervical spines C2/3 which can make and higher stenosis rate and poorer resolution of the deformity.2 intubation difficult. They are usually mentally normal. Surgery for Endoscopically assisted osteotomies are being performed in the craniosynostosis usually occurs before one year of age and some centres and this is the procedure of choice in a young midface extraction surgery at around four to five years.4 (< 3 months) syndromic patient with raised intracranial pressure. Apert’s is the next most common syndrome associated with 3. Total calvarial remodelling and forehead advancement craniosynostosis. Apert’s syndrome is often associated with mental retardation, midface hypoplasia with or without cleft This is the more definitive procedure performed after six palate, nasal abnormalities, and syndactyly and hearing months of age for multi-sutural synostosis. This procedure abnormalities as a result of chronic middle ear infections. corrects both the fused sutures as well as correcting the Similarly to Crouzon’s the craniosynostosis is corrected before a skull deformity. This procedure is more invasive and involves year of age with midface corrections happening at four to five removal of most of the skull in patients with multi-sutural years of age.4 fusion. The removed skull is then reconstructed with wires,

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screws or absorbable plates and screws and replaced as a available. In children undergoing forehead advancement free graft. The procedure generally takes four to six hours and procedures in the supine position a non-reinforced tube can patients are recovered in the paediatric intensive care. be used bearing in mind that kinking of the tube under the drapes is a real possibility. Many authors advocate the use In patients with metopic, coronal and multiple-suture fusion, of preformed Ring, Adair and Elwyn (RAE) tubes in these forehead advancement together with posterior expansion circumstances. I do not use preformed tubes as the risk of is performed. The orbital bandeau is removed and the bone endobronchial intubation is higher in infants and correcting is cut, bent and reshaped and repositioned to advance the orbital ridge.1 These procedures are performed not only to this once the patient is draped may prove disruptive to the correct calvarial anomalies but also to correct (by advancing surgery and is often difficult to remedy. Children with multi- the supra-orbital rims) and protect the eyes in syndromic sutural fusions undergoing total calvarial remodelling are patients with exorbitism such as in Crouzon’s syndrome. generally done in the prone position on a specially designed foam mattress (Figure 2) or on a horseshoe frame. The foam Anaesthetic management mattress allows for greater exposure of the entire skull and 1. Pre-operative assessment also prevents movement of the head and body during the procedure. The majority of patients presenting for surgery for craniosynostosis are normal children with premature fusion of the skull sutures. The majority of these children do not have raised ICP or other comorbid conditions. The syndromes associated with facial synostosis need a more careful assessment and in particular issues relating to raised intracranial pressure, the airway, the respiratory system and obstructive sleep apnoea (OSA).

Maxillary hypoplasia, nasal obstruction and exorbitism may make mask ventilation difficult. Intubation may also prove a challenge if these children have cervical spine abnormalities. Figure 2. A recent study has shown that children with Apert’s syndrome have a 6.1% respiratory complication rate with these procedures and a recent respiratory infection renders I use reinforced cuffed ETTs in all my cranial vault remodelling them more likely to develop intraoperative respiratory procedures. It is imperative that the tube is securely fixed. This complications.2 may be achieved by secure strapping or suturing the tube to the gums. Once the patient is positioned it is important The midface hypoplasia and choanal atresia predispose these to check that the neck is not overly extended or flexed. The children to OSA with increased risk of airway obstruction patient is usually positioned in slight neck extension to at the time of induction or in the postoperative period. expose the maximum amount of skull (the sphynx position). Examination of the tonsils and adenoids may need to be done A temporary tarrsoraphy is performed to prevent corneal in children with severe OSA and the need for tonsillectomy drying and abrasions. and adenoidectomy assessed before the craniofacial surgery. b) Temperature Preoperative assessment of anaemia and the management with iron supplements or erythropoietin may be indicated. It is important to increase the theatre temperature slightly In addition, a coagulation and biochemical screen should (23–24 degrees Celsius) particularly at the start of the be performed and two units of fresh leuco-depleted blood procedure whilst the patient is being induced and invasive ordered for theatre. lines inserted. Fluid and convection warmers need to be used 2. Intra-operative concerns and management from the beginning to prevent heat loss as these procedures are lengthy and the head and brain are exposed. a) The airway and positioning c) Monitoring The majority of these children have normal airways and pose the same concerns as with any other child. Children The largest bore peripheral intravenous line should be placed with facial synostoses may prove a far greater challenge. after inhalational induction and care taken to ensure that the Midface hypoplasia may cause difficulty with bag mask connections are secure and that the cannula is properly in ventilation and airway adjuncts such as oropharyngeal, the vein. During the procedure access to the drip site will be nasopharyngeal airways need to be close at hand as well as limited so monitoring for leaks and a drip that has dislodged video laryngoscopes and fibre optic intubation devices in becomes difficult. case the need arises. Gaseous inductions are generally the preferred technique with the establishment of intravenous An arterial line is mandatory to monitor blood pressure as access as soon as the child is deep enough. When difficulty is well as providing a port for frequent blood sampling. The anticipated it is often prudent to have a second anaesthetist placement of a central line in many texts is not deemed

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essential,1 however I always insert a 3 lumen central line preoperative haematocrit. This increased requirement may for monitoring and fluid management. My preferred site result in an increased donor exposure and transfusion of is the right internal jugular vein. The femoral vein can also other blood products at a young age.7 A dedicated team with be used if internal jugular cannulation is not possible. a set routine, and an increased volume of cases has been These lines are always placed under ultrasound guidance. shown to reduce blood loss, duration of surgery and length As fluid loss and central blood volume status is difficult to of hospital stay.6 assess in these patients, trends in central venous pressure Reducing blood loss and therefore exposure to donor and arterial pressure together with metabolic changes antibodies has become a major focus in complex craniofacial detected on blood gas analysis are used to guide fluid surgery. The risks associated with homologous blood therapy. Central venous pressure is not always accurate in transfusion are well known such as haemolytic reactions, determining fluid responsiveness but I have found trends transfusion-related acute lung injury, infection and the very useful particularly in these infants that have normal complications of massive transfusion such as coagulopathy, cardiorespiratory function where the surgery does not electrolyte and acid base disturbances. In adult patients involve the thorax or abdomen. Arterial waveform analysis strategies to minimise blood loss and transfusion are well with intermittent positive ventilation (IPPV) has become established, however many of these have serious limitations an acceptable tool to determine fluid responsiveness in in infants undergoing major craniofacial surgery. Good adults, however there is conflicting data as to its accuracy in surgical technique, positioning, temperature regulation, infants and children. Tachycardia is also not a useful indicator a normal metabolic state, the use of anti-fibrinolytics and of hypovolaemia in major craniofacial surgery.1 Blood is a rational transfusion protocol are the mainstay in this administered through the peripheral line and not the central population group to reduce the need for homologous line so that dilution of a potentially high potassium and blood. If time permits, preoperative optimisation of citrate can occur before it returns to the heart.1 I have found haematocrit with good nutrition and the use of recombinant intraoperative urine output measure to be a very poor guide erythropoietin may be feasible. Recent adult data showing of fluid status. a possible increase in thrombotic complications, increased A precordial Doppler has been used to detect venous air risk of stroke, hypertension, renal disease and serious embolism particularly during osteotomy and removal of the cardiac complications have limited its use in the paediatric orbital bandeau. Faberowski et al have shown an incidence population.1 Cell saving techniques are becoming more of venous air embolism (VEA) of 82.6% using precordial feasible with the development of cell savers that require Doppler. Of importance is that they found that the majority small initial volumes for processing. If this type of equipment of episodes detected were clinically not significant.2 I do not is used, changes in draping techniques need to be adopted use precordial Doppler monitoring but take care to minimise for effective collection of blood.1 Studies by Dahmani et al the occurrence by ensuring paralysis and IPPV and ensuring and Carver et al have shown a reduction from two units of that the patient does not become hypovolaemic. packed cells to one unit after the introduction of cell saving.7 Preoperative autologous donation and normovolaemic d) Haemorrhage and strategies to minimise blood loss and dilution are not commonly used as these patients have small transfusion blood volumes and usually are just recovering from the low Complex craniofacial surgery is associated with the potential haematocrits of infancy. Preoperative donation in infancy for massive blood loss. Van Uitert et al looked at 44 patients is also not always feasible as these children need to come undergoing craniosynostotic corrections and found a mean to hospital for numerous donations which often require estimated perioperative blood loss of 55 ml/Kg (blood loss sedation or anaesthesia. estimates were only reported in 27 cases).6 Williams et al The use of an anti-fibrinolytic such as tranexamic acid found that only five of the 27 cases in their study undergoing (TXA) has been shown in numerous studies to be effective major craniofacial surgery had an estimated blood loss in in reducing blood loss with these procedures.7–9 No data excess of 100 ml/Kg.7 Blood loss is generally gradual but in children exists as to the efficacy of aminocaproic acid. significant throughout the procedure and it is important to Tranexamic acid is cheap, easy to administer and seems to appreciate times when blood loss may be rapid. Blood loss have a low incidence of adverse effects. The adverse effects may be rapid when periosteum is lifted off the bone and that have been described in the literature are with large when craniotomies are performed to remove skull bones. doses (> 100 mg/kg) and include seizures and thrombotic Removing bone can be a tedious and lengthy process as the events.9 Dosing schedules quoted in studies vary from an neurosurgeon needs to be meticulous so as not to breech initial bolus of 10–100 mg/kg and a continuous infusion of dural sinuses which can result in a dramatic and rapid blood 1–10 mg/kg/hour.9 Goobie et al studied 23 patients aged loss. Most studies report the use of homologous blood two months to six years, one group receiving TXA as a bolus transfusion in almost all cases of complex craniosynostosis (50 mg/kg) and then an infusion of 5 mg/kg for the duration repair.7 of the surgery. The control group received 0.9% saline. The Independent risk factors for increased requirements for mean total blood loss in the TXA group was 65 ml/kg vs homologous blood transfusion are a young age and 119 ml/kg with postoperative losses being 3 and 12 ml/kg low weight, duration of surgery (> 5 hours) and a low respectively. All their patients did, however, receive blood

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transfusion. These authors suggest that tranexamic acid anti-diuretic hormone (ADH) secretion and cerebral salt effects at the tissue level may outlast its half-life and exhibit wasting syndrome.11 effects well into the postoperative period by possibly an f) Nausea and vomiting unexplained mechanism at the tissue level.8 In a meta- analysis done by Song et al with four studies and 138 An audit done by Hughes et al showed that 60% of children patients included, they concluded that TXA can significantly vomited in the first 24 hours. Vomiting may be deleterious reduce blood loss and transfusion of packed red blood cells as it will increase bleeding, raise intracranial pressure and (PRBCs) in children undergoing major craniofacial surgery, may cause cerebral spinal fluid leaks. Ondansetron and however in a subgroup analysis on randomised controlled dexamethasone have both been shown to be effective in this trials the efficacy of TXA on reducing blood loss compared patient population and should be used routinely.7 to controls was not significant.10 When large blood losses are replaced with crystalloid and PRBCs, dilution coagulopathy Anaesthetic technique seems to be the major cause of bleeding. Williams, in their No anaesthetic technique has been shown to be superior to study, showed that coagulopathy only became a real another in long-term outcomes. The routine at the Johannesburg problem in those infants that bled more than 100 ml/kg or craniofacial unit is as follows: approximately 1.2 times the blood volume.7 If fresh frozen plasma (FFP) is deemed to be necessary as per laboratory The children and parents are admitted on the day before surgery testing or clinical evidence, it is prudent to use the same and seen by the paediatric intensivist and the anaesthesiologist. donor from whom PRBCs are obtained. This would mean Routine blood screens are ordered (haemoglobin and white cell ordering FFP before surgery with the potential of wastage if count, urea and creatinine and electrolytes, C-reactive protein not used or inappropriate use simply because it was available. and coagulation profile) and two units of fresh adult leuco- Haas et al have shown that the use of fibrinogen concentrate depleted PRBCs are ordered for theatre. was effective in decreasing perioperative blood loss without On the morning of surgery the availability of an ICU bed is the need for FFP. High cost may be a disadvantage, however confirmed and the patient brought to theatre. Blood is checked saving the patient a transfusion of other blood products with for correct identification. A gas induction with sevoflurane its attendant allo-immunisation may outweigh the cost.1 is performed, peripheral IV access obtained and the child Vitamin K, activated factor VII, DDAVP have all been used to paralysed with a long-acting non-depolarising muscle relaxant augment coagulation.7 The risks attached to the use of these (Pancuronium 0.1 mg/kg). Intubation is performed with a agents always needs to be taken into account. straight reinforced cuffed ETT and the position is fixed using e) Metabolic and electrolyte disturbances a combination of stretchy pink elastoplast and a ‘tegaderm’ dressing. A pressure-controlled ventilation mode is usually Metabolic and electrolyte disturbances occur for a number of preferred. An oro-gastric tube is passed. reasons. Infants starved for a prolonged period of time may start off with a metabolic acidosis. Significant blood loss with A 3 lumen central venous line is placed in the right internal replacement of crystalloid and PRBCs may lead to metabolic jugular vein under ultrasound guidance and a radial arterial and electrolyte disturbances. Transfusion of 0.9% saline will line is inserted. An arterial blood gas is immediately sent off for result in a hyperchloraemic acidosis and transfusion of PRBCs analysis. If circumstances dictate, a femoral long line is inserted may result in electrolyte disturbances such as hyperkalaemia instead. from packed cells stored for more than two weeks and Antibiotics, 5HT3 receptor blocker and dexamethasone hypocalcaemia from citrated blood. Packed cells stored for are administered. Tranexamic acid is given prior to the more than two weeks may have a potassium concentration commencement of surgery with an initial bolus of 15 mg/kg and greater than 40 mmol/l. an infusion of 5 mg/kg till completion of surgery. The head is Choi et al, looking at metabolic disturbances, found a median shaved; a temporary tarsorrhapy performed to protect the eyes base deficit of -9, with 39% of patients having a base deficit and an indwelling urinary catheter is placed as well as a rectal of less than 10 recorded with the maximum base deficit thermometer. occurring at the end of the procedure in the majority of The patient is then positioned on the foam mattress (Figure 2) cases. Twenty-five percent of cases had a base deficit of lower in the prone position for total calvarial remodelling or placed than -4 at the time of arterial line insertion. The median time supine on a gel head ring if forehead advancement and limited for this to correct was 9.25 hours.7 The degree of metabolic calvarial remodelling is to be done. Fluid warmers and forced disturbance has been found to correlate with the amount air convection warmers are used from the beginning and of PRBCs, colloid or crystalloid given intraoperatively. Cladis temperature kept as near normal as possible throughout the et al described an incidence of hyponatraemia on reviewing procedure. 72 records of 30.6% in children undergoing cranial vault remodelling. Hyponatraemia was associated with increased Ringers lactate and PRBCs are administered according to need. preoperative intracranial pressure, blood loss, females and A combination of blood pressure readings, CVP measurements, in patients receiving hyponatraemic intravenous fluids systolic pressure variation and metabolic parameters on arterial postoperatively. The mechanism is unclear but it has been blood gas are used to determine fluid requirements and fluid suggested to be related to the syndrome of inappropriate responsiveness. On average the crystalloid volume infused

S57 58 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) during the procedure is 40–50 ml/kg and 20–25 ml/kg of PRBCs. Conclusion Volumes larger than this may occasionally be required in difficult Complex craniofacial surgery presents numerous challenges to surgical cases. FFP, platelets and other blood products are not the paediatric anaesthesiologist. These range from managing routinely ordered and in almost all cases are not needed if fresh difficult airways in syndromic children to coping with large blood PRBCs are used. Good communication between surgeons and volume loss in infants and small children. Exposing these children anaesthesiologist is essential particularly when bleeding occurs. to allo-immunisation with blood and blood products may be The unsuspecting anaesthetist can very quickly get behind problematic in later life so all efforts to minimise this exposure on fluids as these children have requirements much higher should be made. Many of the blood conservation techniques than expected. Analgesia is provided with fentanyl boluses used in adults are not always feasible in these children so 5–8 ug/kg as needed and with morphine 0.1 mg/kg once preoperative optimisation of haematocrit, meticulous surgical all the bone is removed and bleeding is under control. A technique, careful positioning, temperature and metabolic dexmetetomidine infusion is started intraoperatively at a rate of control together with the use of anti-fibrinolytic agents and an 0.4 to 0.6 ug/kg/hour which is continued into the postoperative institutional protocol for transfusion triggers forms the mainstay period. Serial blood gases are done to determine metabolic of limiting transfusion of homologous blood and blood products. Advances in cell saving have now made it a viable option in small status, haemoglobin and blood glucose and electrolyte levels. children where it is available. One must also not neglect dealing The total theatre time is usually between 5–6 hours with actual with parenteral anxiety and a detailed preoperative counselling surgical time between 3.5 and 4.5 hours. At the conclusion of of the parents is required. surgery the muscle relaxant is reversed once temperature is References normal and an acceptable metabolic state is achieved. Similar 1. Stricker PA, Fiadjoe JE. Anesthesia for craniofacial surgery in infancy. to what Choi et al found, most patients have a base deficit of Anesthesiology clinics. 2014;32(1):215-35. between -4 and -8 at the end of the procedure and are extubated 2. Thomas K, Hughes C, Johnson D, Das S. Anesthesia for surgery related to craniosynostosis: a review. Part 1. Pediatric Anesthesia. 2012;22(11):1033-41. with these values. The majority of our patients are extubated and 3. Dong TT, Ferschl M. What’s New in Craniosynostosis? Current Anesthesiology placed on nasal oxygen. Dexmetetomidine is continued in the Reports. 2015;5(2):168-76. postoperative period to ensure a calm, non combatative patient. 4. Friedhoff RJ. Anesthesia for Pediatric Craniofacial Surgery. 2000. This is essential so as to avoid bleeding, raised intracranial 5. Pearson A, Matava C. Anaesthetic management for craniosynostosis repair in children. Bja Education. 2016;16(12):410-6. pressure and damage to the skull. It is my experience that these 6. Van Uitert A, Megens JH, Breugem CC, et al. Factors influencing blood loss and children require a larger infusion rate of dexmetetomidine than allogeneic blood transfusion practice in craniosynostosis surgery. Pediatric Anesthesia. 2011;21(12):1192-7. adults and I often have to supplement with another sedative in 7. Hughes C, Thomas K, Johnson D, Das S. Anesthesia for surgery related to the early stages of recovery. craniosynostosis: a review. Part 2. Pediatric Anesthesia. 2013;23(1):22-7. 8. Goobie SM, Meier PM, Pereira LM, et al. Efficacy of tranexamic acid in pediatric Analgesia craniosynostosis surgerya double-blind, placebo-controlled Trial. The Journal of the American Society of Anesthesiologists. 2011;114(4):862-71. As is common with neurosurgical procedures these patients 9. Rakić G, Stanić D, Uram-Benka A, et al. Efficacy of tranexamic acid in experience mild to moderate pain. Intraoperatively analgesia is craniosynostosis repair in an infant. Indian Journal of Neurosurgery. 2015;4(03):190-2. opioid-based with fentanyl or remifentanil and morphine and 10. Song G, Yang P, Zhu S, et al. Tranexamic acid reducing blood transfusion in paracetamol for postoperative pain. Dexmetetomidine is a useful children undergoing craniosynostosis surgery. Journal of Craniofacial Surgery. adjunct both intraoperatively as well as in the postoperative 2013;24(1):299-303. period together with paracetamol and small boluses of morphine 11. Cladis FP, Bykowski M, Schmitt E, et al. Postoperative hyponatremia following calvarial vault remodeling in craniosynostosis. Pediatric Anesthesia. if required. 2011;21(10):1020-5.

S58 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Anaesthesia for thoracoscopy in paediatric patients

S Spijkerman

Department of Anaesthesiology, Steve Biko Academic Hospital, University of Pretoria Correspondence to: [email protected]

Modern equipment and surgical techniques have enabled When the patient is still awake, but positioned in the LDP, endoscopic procedures in smaller patients, making thoracoscopy gravity increases blood flow to the dependent lung with an a possibility for a variety of diagnostic and therapeutic average of 40% blood flow to the non-dependent lung and procedures, even in very young patients.1,2 (Table I) 60% to the dependent lung (disregarding the slight differences between the left and right lungs). Ventilation now also favours To understand the perioperative anaesthetic requirements of the dependent lung. This is due to a vertical gradient in pleural paediatric patients for video-assisted thoracoscopic surgery pressure (Ppl) and because the dome of the lower part of the (VATS), a review of the physiology of one-lung ventilation in the diaphragm is pushed higher into the chest by the abdominal lateral decubitus position and techniques of lung isolation are contents compared to the upper part, resulting in a more curved imperative. A review of the general considerations of paediatric shaped lower diaphragm with enhanced contraction and further anaesthetic practice fall outside the scope of this review, but increase in ventilation to the dependent lung. should be kept in mind during VATS procedures in children. When the patient is anaesthetised and OLV commences, in the Pulmonary physiology of one-lung ventilation in absence of confounders or inhibitors of hypoxic pulmonary children1,3 vasoconstriction (HPV), the absence of ventilation to the non-dependent lung results in HPV with a 50% reduction of Several factors cause ventilation-perfusion mismatch in blood flow to the non-dependent lung (which now receives patients undergoing anaesthesia and one-lung ventilation 20% of blood flow) and subsequent 50% increase in flow to (OLV) in the lateral decubitus position (LDP). Anatomical and the dependent lung (which now receives 80% of blood flow). physiological differences in children compared to adult patients Inhalational anaesthetic agents reduce the effect of HPV so further predispose these patients to hypoxaemia during such that the reduction in blood flow to the non-dependent lung is approximately 40% with 1 MAC isoflurane (compared to 50% in procedures. the absence of vapours). The final blood flow is approximately In the awake, upright adult, the right lung receives 55% and 24% to the non-dependent (non-ventilated) lung and 76% to the the left lung 45% of the total lung blood flow. Perfusion favours dependent (ventilated) lung in the anaesthetised patient during OLV in the LDP. lower (dependent) parts of the lung due to gravitational effects. In terms of ventilation, dependent lung areas are on the steep, During OLV in the LDP, the use of muscle relaxants prevents the high compliant part of the alveolar volume-transpulmonary diaphragm from contracting, and the effect of the curved bottom pressure curve with ventilation favouring these parts of the part of the diaphragm on ventilation is lost. Under anaesthesia lungs, matching ventilation with perfusion. the dependent lung (which is being ventilated) moves to a lower,

Table I. Indications for video-assisted thoracoscopic surgery (VATS) in children1,2 Lungs: Mediastinum: Diaphragm: • Biopsy of pulmonary tissue • Thymectomy • Repair of congenital diaphragmatic hernia • Pulmonary resections (wedge resections to • Posterior mediastinal neurogenic tumour Spine and nerves: lobectomies) resection • Fusions and corrections • Closure of recurrent pneumo thorax • Excision of mediastinal cysts • Thoracic sympathectomy • Diagnosis of broncho-pleural fistula Major vessels: • Drainage of abscess Pleura: • Ligation of patent ductus arteriosus • Decortication of empyema thoracis Heart: • Pleurodesis • Pericardectomy Trachea: Oesophagus: • Trachea-oesophageal fistula repair • Heller’s myotomy • Oesophagus resections

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less compliant part of the alveolar volume-transpulmonary advanced until breath sounds disappear on the operative pressure curve resulting in a reduced functional residual side. Placement may be assisted or confirmed with a fibre capacity (FRC). Muscle relaxants also reduce FRC which is often optic bronchoscope (FOB) passed through or alongside the further reduced by the mediastinum resting on the dependent ETT. Fluoroscopy-guided placement has also been described. lung, weight of the abdominal contents pushing more into the When a cuffed tube is used, the distance from the proximal thoracic cavity of the dependent lung and poor positioning part of the cuff to the tip of the ETT should not exceed the impeding expansion of the dependent lung. Ventilation may length of the bronchus in order to prevent obstruction of the be further decreased due to pre-existing pulmonary disease or contralateral bronchial opening or trachea. An uncuffed tube pooling of secretions in the dependent lung. may result in inadequate seal with failure of lung collapse The above effects lead to ventilation-perfusion (V/Q) mismatch and risk of contaminating the healthy lung. Suctioning of the and susceptibility to hypoxaemia during OLV. The supine position operative lung is not possible and in small children with short (for orthopaedic and other procedures) enhances the mismatch bronchi, the risk of occlusion of the upper lobe bronchus is due to the loss of gravitational effect. Blood distributes to both high. Independent intubation of both main bronchi with lungs, whereas ventilation only occurs in the ventilated lung small ETTs have been described where one ETT is placed, during OLV. The matching of ventilation and perfusion is now after which the second ETT is advanced over a FOB into even more dependent on HPV. the other bronchus. This allows independent ventilation of Paediatric pulmonary physiology4-7 predisposes to further the two lungs but is difficult to place, can potentially cause mismatch and an increased tendency towards hypoxaemia trauma and the thin lumens cause high airflow resistance and during OLV in the LDP. The FRC is reduced in paediatric patients propensity for obstruction. and oxygen consumption is 6–8 ml.kg-1min-1 compared to 3.5 ml.kg-1min-1 in adults, both resulting in a smaller oxygen 2. Balloon-tipped bronchial blockers reserve and susceptibility to desaturation during OLV in children. Bronchial blockers (BB) can be used for a variety of paediatric In adults, placing the sick lung in the non-dependent position (as ages (Tables III and IV). Fogarty embolectomy catheters is the case during surgery on the sick lung) offers considerable advantages to V/Q matching. This is not the case in small children (Edward Lifesciences, Irvine, CA, USA) are placed with FOB due to a variety of factors. The compressible rib cage of the infant guidance and completely seal the bronchus with good cannot fully support the dependent lung, resulting in atelectasis lung isolation. Their closed tips preclude suctioning and during tidal breathing. Due to their smaller size, the hydrostatic continuous positive airway pressure (CPAP) to the operative pressure gradient between the two lungs in the LDP is less in lung. The use of end-hole catheters (Arrow International small children than in adults, resulting in a less pronounced Corp, Redding, PA) could overcome these problems. They increased perfusion to the dependent lung in the LDP. As a result are placed by first inserting a single-lumen ETT into one of the compressible nature of the infant lung, the FRC is closer bronchus, advancing a guidewire through the tube, removing to the residual volume (RV) and airway closure can occur even the tube and railroading the catheter over the guidewire. during tidal breathing. The dependent diaphragm in adults has a An ETT is then placed in the trachea alongside the catheter. mechanical advantage due to the increased abdominal pressure Suctioning is possible (the lumen is too small to suction gradient, resulting in increased ventilation in the dependent secretions but suctioning aids in lung collapse) and CPAP lung. This pressure gradient is absent in infants. is possible to the operative lung. The Arndt Endobronchial Apart from the physiological effects, anatomical considerations Blocker® (Cook Critical Care, Bloomington, IN, USA) can be further result in a higher susceptibility to hypoxaemia. Smaller used for children older than two years (ETT ≥ 4.5). A three- diameter airways necessitate smaller diameter tubes with higher port adapter accompanies the blocker and attaches to the resistance to airflow and an increased tendency to block. Shorter ETT. The blocker is passed through one of the adapter lumens, airways result in easier displacement of airway devices. the FOB through the second and the third is connected to the Techniques of lung isolation in children1–2,4–5,8–9 anaesthetic breathing circuit. The blocker is hooked around the FOB and advanced under vision. Although VATS can be performed during two-lung ventilation with CO2 insufflation and retraction of lung tissue from the Embolectomy catheters Arndt bronchial blocker operating field, OLV is highly desirable. There are several (Photo: NewtechTM medical (Photo: Cook Medical catalogue techniques for OLV in children, each with advantages and devices catalogue) Arndt_Blocker_Balloon_ disadvantages (Table II). The age and size of the child will G44114_P_002) (Permission for use granted by determine the devices available for use (Table III). Cook Medical, Bloomington, Indiana) 1. Single-lumen endotracheal tube

A conventional single lumen endotracheal tube (ETT) may be placed in the ipsilateral mainstem bronchus. Half a size smaller than for tracheal use is selected. When intubating the left mainstem bronchus, the bevel of the ETT is rotated through 180˚ and the patient’s head turned to the right. To place the ETT in the right mainstem bronchus, it is simply advanced deeper than for endotracheal use. The ETT is

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3. Univent tube balloon at the end of each leg. It is placed through a conventional ETT. While inside the ETT, the legs are in close The Univent tube (Fuji Systems corporation, Tokyo, Japan) proximity, but deploy when exiting at the bottom of the ETT comprises a conventional ETT with a second lumen containing a small tube with a balloon tip which is advanced into a to form a Y-shape. Each leg enters one of the main bronchi and bronchus to serve as a blocker. The blocker lumen can be used the two colour-coded balloons are independently inflated. A for suctioning and insufflation of oxygen. Because the blocker multiport is supplied with one port for the blocker, one for is attached to the ETT, displacement is less likely than with the FOB and the third connects to the breathing circuit. Cuff other blockers. The blocker channel does, however, occupy inflation is done under FOB guidance. The blocker is only a sizable portion of the cross-sectional area of the device available in one size with a 7Fr catheter (2.33 mm in diameter) which increases resistance to airflow. The device is placed in and passes through ETT tubes ≥ size 7. the same way as a conventional ETT, after which it is rotated through 90 ˚ so that the blocker sits on the appropriate side. The tube is secured and the blocker is advanced either blindly or under FOB guidance.

EZ-BlockerTM (Photo: Teleflex incorporated catalogue)

5. Double lumen tubes

Double lumen tubes (DLTs) (Mallinckrodt Medical, Inc, St Louis, MO, USA for 28-41 Fr and Rüsch, Duluth, GA, USA for 26 Fr) consist of two cuffed tubes of unequal length moulded together with the shorter tube ending in the trachea and the longer tube in either bronchus. The tube is placed through the Univent tube (Photo: Sharn Anesthesia catalogue) vocal cords and the stylet is removed before it is rotated 90 ˚ towards the appropriate side and advanced until resistance is 4. EZ blockers met. Placement is verified by auscultation ± FOB. The smallest The Rusch® EZ-BlockerTM (Teleflex International Corp, USA) is available size is a 26 Fr which can be used in children from a BB catheter with a bifurcated distal end with an inflatable eight years of age.

Table II. Advantages and disadvantages of various lung isolation techniques

Technique Advantages Disadvantages

Single lumen tube in main • Relatively easy to place • Poor seal if uncuffed (inability to deflate lung and bronchus • Cost-effective possibility of soiling) • No special equipment required • Easily occludes upper lobe bronchus • Can use through tracheostomy tube • Unable to suction operative lung • No CPAP possible to operative lung • Slow conversion from OLV to two-lung ventilation and vice versa

Separate single lumen tube in • Independent ventilation of two lungs • Technically difficult each bronchus • Suction possible • Trauma • Small lumens (resistance to airflow, block easily)

Closed-tip bronchial catheters • Good seal • Inability to suction operative lung (Fogarty) • Relatively easy placement • No CPAP possible to operative lung • Tracheal occlusion if dislodges proximally • Slow lung collapse

End-hole bronchial blocker • Can be used when single lumen ETT already in • Tracheal occlusion if dislodges proximally catheters (BB) place • Slow conversion from two-lung to OLV • Good seal • Independent lung management difficult or • Good lung collapse impossible (suctioning, FOB inspection, split lung • Suctioning possible ventilation in ICU) • CPAP possible • Easily displaces • No need to replace ETT at end of procedure • Selective lobar blockage possible • Can use through tracheostomy

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Univent tube • Easy placement • High airflow resistance • Less displacement • Trauma possible • Suctioning possible through lumen • Balloon has low volume-high pressure • CPAP possible through lumen characteristics predisposing to mucosal injury

• O2 insufflation possible through lumen • Able to switch between OLV and two-lung ventilation

EZ-BlockerTM • Easy placement • Only available for ETT ≥ size 7 • Placed through existing ETT • Selective lobar blockage not possible • CPAP possible to collapsed lung

Double-lumen tubes • Quick placement possible • Trauma possible (DLTs) • Good lung isolation • Only possible in children older than 8 years • FOB not imperative (≥ 30-35 kg) • Displacement less common than BBs • Needs to be replaced by single-lumen ETT at end • Independent lung management possible of procedure (suctioning, FOB inspection, split lung ventilation • Not option in patients who cannot tolerate apnoeic in ICU) period • Quick conversion from OLV to two-lung ventilation • Not possible to place through tracheostomy and vice versa • Hard to place in difficult/abnormal airways • Cannot block selective lobes • Right-sided DLT can occlude the right upper bronchus

Table III. Device selection for lung isolation in children4,8,10 Age (years) ETT (ID)+ Fogarty catheter (Fr)§ BB (Fr) Univent (ID)*** DLT (Fr) 0.5–1 3.5–4.0 3 2* 1–2 4.0–4.5 3 3* **5 3 5.0–4.5 ٲ24 4–6 5.0–5.5 4–5 5** 6–8 5.5–6.0 4–5 5** 3.5 8–10 6.0 cuffed 4–5 5** 3.5 26# 10–12 6.5 cuffed 4–5 5** 4.5 26#–28## 12–14 6.5–7.0 cuffed 5–6 7** 4.5 32## 14–16 7.0 cuffed 5–6 5,7** 6.0 35## 16–18 8.0–8.5 cuffed 5–6 7,9** 7.0 35##,37## ETT = endotracheal tube; ID = internal diameter; BB = bronchial blocker; Fr = French; DLT = double lumen tube; + = Sheridan® tracheal tubes, Kendall Healthcare, Mansfield, MA; § = Edward Lifesciences, Irvine, CA, USA; * = Edwards Lifesciences LLC, Irvine, CA; ** = Cook Critical Care, Inc, Bloomington, IN; *** = Fuji Systems Corporation, Tokyo, Japan; # = Rusch, Duluth, GA; ## = Mallinckrodt Medical, Inc, St. Louis, MO.

Table IV. Arndt blocker sizing for lung isolation in children11,12 Arndt size (Fr) Patient age (years) Smallest ETT (mm) FOB size (mm) 5.0 < 8 4.5 2.8 7.0 8–12 6.5 3.6 9.0 > 12 8 4.2 Fr = French, ETT = endotracheal tube, FOB = fibre optic bronchoscope, mm = millimetres

Perioperative management of paediatric patients for and computerised tomography (CT) scans are done as indicated VATS by the patient’s specific pathology.

Preoperative evaluation Patients should be optimised according to their pathology (mediastinal masses could be shrunk by radiation or Preoperative workup for thoracoscopy should be similar to chemotherapy) and their general condition should be optimised the workup for thoracotomy since these patients will also be with adequate nutrition, chest physiotherapy, bronchodilator anaesthetised, might be in the LDP and will most probably be therapy, antibiotics, steroid supplementation and blood exposed to OLV. The focus of the workup is on pulmonary and transfusion as indicated. As conversion to open thoracotomy is cardiac reserve and function. A full history and examination always a possibility and major vessel injury could occur, blood is followed by special investigations which should routinely should be ordered on standby. include a haematocrit, haemoglobin, serum-electrolytes and a Anxiolytic premedication could be considered in children chest X-ray. Pulmonary function tests (in older children), ECG without respiratory compromise and could include midazolam

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0.3–0.5 mg.kg-1 p.o or a suitable alternative. Antiemetics and considered in addition to the pathology and general condition

H2-antagonists should be administered in patients at risk of of the patient. The decision to extubate the patient in theatre or aspiration. Fasting times resemble guidelines for routine surgery. ventilate postoperatively, will also influence the choice of drugs. Muscle relaxants are commonly used, except in instances where Intraoperative management spontaneous ventilation is mandatory, as is mostly the case Monitoring should include ECG, pulse oximetry, non-invasive with anterior mediastinal masses. A balanced anaesthetic with blood pressure monitoring (NIBP), capnography, temperature opioids and inhalants is probably advisable (see below). Nitrous monitoring and urinary output in longer cases. Neuromuscular oxide should be avoided when gas insufflation is used as it can and depth-of-anaesthesia monitoring are convenient optional enhance gas embolism. This is less of an issue when CO2 is used modalities, the latter being especially useful when a total (solubility of nitrous oxide and carbon dioxide are similar), but intravenous technique is chosen. nitrous oxide is still best avoided.

Large-bore peripheral lines should be placed in the event of OLV is achieved with one of the methods previously described. conversion to thoracotomy or massive bleeding. The literature Especially in smaller children where lung isolation is impossible regards arterial lines mostly as optional or indicated by specific or suboptimal, CO2 insufflation into the operative hemithorax pathological conditions, but the author prefers them in all facilitates lung collapse. At this point displacement of patients undergoing OLV for both blood gas and electrolyte intrathoracic contents and tension pneumothorax can cause analysis and continuous blood pressure monitoring. When end- significant cardiovascular compromise due to increased left ventricular afterload or decreased venous return reducing tidal CO2 (ETCO2) levels drop, a continuous blood pressure trace will differentiate between airway compression and compression cardiac output. Insufflation can also lead to bradycardia due to of the heart or major vessels. When a central venous pressure increased vagal tone caused by activation of pulmonary stretch catheter is indicated (for drug administration or central venous receptors. Therefore, insufflation rate should not exceed 1 litre/ pressure monitoring), the catheter should be placed on the minute and insufflation pressure should be between 4–6 mmHg. side of the thoracoscopy to prevent the eventuality of bilateral Insufflation of CO2 directly into lung parenchyma is possible pneumothoraces. and could lead to sudden increase in ETCO2, subcutaneous emphysema and gas embolism. CO2 is used for insufflation Patient positioning should take meticulous care of pressure because it is more soluble in blood than O2 or air and poses a points as well as optimization of the effect of gravity on perfusion smaller risk for embolisation.14 Methods described to monitor and subsequent matching of ventilation and perfusion. In the for gas embolism include transoesophageal echocardiography LDP, potential pressure points are the dependent eye and ear, (detects 0.1 ml of gas), precordial Doppler (detects 0.5 ml) and acromion process, olecranon, ribs, iliac crest, greater trochanter, capnometric end tidal nitrogen monitoring (for air embolism condyles and malleoli.1 To optimise perfusion to the dependent 15 but not useful in detecting CO2 emboli). ETCO2 monitoring is lung (the ventilated lung) in the LDP, the patient needs to be also useful to detect gas embolism. CO2 insufflation could lead perfectly perpendicular to the bed. Slight ventral or dorsal tilt to hypothermia in small children and meticulous temperature will decrease the gravitational effect and reduce perfusion. When management is mandatory. placing a patient in the LDP, the dependent arm is perpendicular to the body, the dependent knee flexed, padding placed under Hypercarbia during VATS is more common in young children 16,17 the ankles, between the knees, under the hip (for protection than in adults. Possible causes include hypoventilation, CO2 of the greater trochanter and iliac crest), behind the olecranon insufflation and malpositioning of airway devices. and between the arms. The dependent eye and ear should be Hypoxaemia during OLV is not uncommon and several free, the neck supported and in line with the body and a chest management strategies are described (see Table VI). Specific roll (just distal to the axilla) in place. The abdomen should be variables influence oxygenation during OLV and should be 13 allowed unobstructed movement. optimised in the event of hypoxaemia.18 These are pulmonary shunt fraction (Qs/Q ), haemoglobin concentration and the Anaesthetic technique (local anaesthesia, regional anaesthesia T ratio between oxygen consumption and cardiac output (VO / or general anaesthesia) will depend on the age and pathology 2 Q ). Reducing Qs/Q is achieved by optimising HPV in the of the child. Local anaesthesia is rarely an option but could T T non-dependent lung while minimising pulmonary vascular be considered in older children for short procedures without resistance in the dependent lung. This is mainly achieved by intrathoracic surgical manipulation or in moribund patients, good lung isolation and selecting drugs with minimal effect on especially where spontaneous breathing is paramount. Such HPV. Haemoglobin should be optimal for patient age. Cardiac patients are, however, often not able to withstand the required output should be optimal but injudicious use of inotropes will lung collapse for thoracoscopy in which case local anaesthesia be contra-productive as increased Q could increase pulmonary is not a viable option. Regional techniques include epidural, T artery pressure and reduce HPV and inotropes can directly paravertebral block or multi-level intercostal blocks, often reduce HPV. Inhalational agents will decrease VO but will also supplemented with a stellate ganglion block to suppress the 2 reduce Q , negating the positive effect on oxygenation. It is cough reflex. T therefore probably advisable to use a balanced anaesthetic For general anaesthesia, induction and maintenance are technique with opioids and inhalants at concentrations of possible with inhalational or intravenous drugs. The effect < 1 MAC, limiting the reduction in QT. Inhalants are good of each drug on HPV (Table V) and cardiac output should be bronchodilators and their half-life is short, permitting extubation

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in theatre. Further strategies to manage hypoxaemia during OLV exclude pneumothorax or severe atelectasis.8 The perioperative include increasing FiO2, maintaining adequate tidal volume team should focus on early detection and management (too low will cause atelectasis in the dependent lung with of postoperative complications, including bleeding, lung subsequent intrapulmonary shunt and hypoxaemia and too herniation through the chest wall, Horner syndrome, persistent high (> 10 ml.kg-1) will increase pulmonary vascular resistance in air leak, respiratory complications (atelectasis and pneumonia) the dependent lung and will force blood to the nondependent and infection (wound infection, abscess or empyema).1,2 lung which will also increase intrapulmonary shunting), apply Thoracoscopy in children is less invasive than thoracotomy, positive end-expiratory pressure (PEEP) to the dependent lung but due to their smaller size with associated physiological and and apply intermittent two-lung ventilation. Continuous positive airway pressure (CPAP) to the non-dependent lung is probably equipment difficulties, this is often more challenging than not advisable during thoracoscopy as this might compromise anaesthesia for thoracoscopy in adults. Paediatric thoracic visibility. anaesthetists should be well versed in the physiology of OLV and LDP as well as the various types of equipment available for lung Table V. Effects of drugs on hypoxic pulmonary vasoconstriction isolation in children. Minimal effect on HPV Reduces HPV Interests: No interests are declared. • Isoflurane < 1 MAC • Vasodilators (nitroglycerine, • Opioids dobutamine) Acknowledgements: • Propofol • Beta-agonists (salbutamol) • Ketamine • Inhalants if > 1 MAC The author would like to acknowledge the contribution of Dr JM • Benzodiazepines Dippenaar for proofreading and valuable suggestions. • Barbiturates HPV = hypoxic pulmonary vasoconstriction; MAC = minimum alveolar References concentration 1. Kumar K, Basker S, Jeslin L, et al. Anaesthesia for pediatric video assisted thoracoscopic surgery. J Anaesthesiol Clin Pharmacol. 2011;27(1):12-16. Table VI. Strategies to manage hypoxaemia during one-lung 2. Brodsky JB, Cohen E. Video-assisted thoracoscopic surgery. Curr Op ventilation Anaesthesiol. 2000;13(1):41-5. • Check ETT tube positioning 3. Wilson WC, Benumof JL. Anesthesia for thoracic surgery. In: Miller RD, editor. th • Suction airway Miller’s anesthesia. 6 Ed. Philadelphia: Elsevier; 2005. p. 1847-1939. • Check cardiac output 4. Hammer GB. Anesthesia for Thoracic Surgery. In: Cote C, Lerman J, Anderson BJ. th • Check haemoglobin A Practice of Anesthesia for Infants and Children. 5 Ed. Philadelphia, PA: Elsevier • Consider drug effects on HPV – Table V Saunders; 2013. p. 277-290. 5. Fabila TS, Menghraj SJ. One lung ventilation strategies for infants and • Increase FiO2 • Optimise tidal volume children undergoing video assisted thoracoscopic surgery. Indian J Anaesth. 2013;57:339-344. • PEEP to dependent lung (5 cmH2O) • No CPAP during VATS 6. Dave N, Fernandes S. Anaesthetic implications of paediatric thoracoscopy. J Min • Intermittent two-lung ventilation Access Surg. 2005;1:8-14. 7. Fischer GW, Cohen E. An update on anesthesia for thoracoscopic surgery. Curr ETT = endotracheal tube; HPV = hypoxic pulmonary vasoconstriction; FiO2 = inspiratory fraction of oxygen; PEEP = positive end-expiratory pressure; CPAP Op Anaesthesiol. 2010;23(1):7-11. = continuous positive airway pressure; VATS = video-assisted thoracoscopic 8. Golianu B, Hammer GB. Pediatric thoracic anesthesia. Curr Op Anaesthesiol. surgery. 2005;18:5-11. 9. Hammer GB. Single-lung ventilation in infants and children. Pediatr Anesth Analgesic requirements for VATS are less than for thoracotomy 2004;14:98-102. because of smaller incisions without splitting of serratus anterior 10. Tan GM, Tan-Kendrick AP. Bronchial diameters in children – use of the Fogarty and latissimus dorsi muscles and spreading of ribs.1 Chest drains catheter for lung isolation in children. Anaesth Intensive Care. 2002;30:615-618. are, however, painful4 and pleural procedures require more than 11. Bird GT, Hall M, Nel Let al. Case Report: Effectiveness of Arndt endobronchial simple analgesia. Analgesia is often achieved with paracetamol, blockers in pediatric scoliosis surgery: A case series. Pediatr Anesth 2007;17:289-294. nonsteroidal anti-inflammatory drugs, and intravenous opioids 12. Cook Medical [Internet]. Endobronchial blocker sets. [updated 2014; cited 2017 supplemented by local infiltration of the port sites or intercostal Apr 15]. Available from: www.cookmedical.com. nerve blocks. Neuraxial local anaesthetic agents or opioids are 13. Martin JT, Warner MA. Positioning in Anesthesia and Surgery. 3rd ed. reserved for open procedures.2 Philadelphia, PA: W.B. Saunders; 1997. 14. Tobias JD. Anaesthetic implications of thoracoscopic surgery in children. Apart from ventilation and perfusion challenges, intraoperative Paediatr Anaesth. 1999;9:103-110. complications could include dysrhythmias, re-expansion 15. Jones DR, Graeber GM, Tanguilig GG, et al. Effects of insufflation on haemodynamics during thoracoscopy. Ann Thorac Surg 1993;55:1379. pulmonary oedema and massive bleeding. Vigilance on the part 1,2 16. Byon HJ, Lee JW, Kim JK, et al. Anesthetic management of video-assisted of the anaesthetist is paramount. thoracoscopic surgery (VATS) in pediatric patients: the issue of safety in infant and younger children. Korean J Anesthesiol. 2010;59(2):99-103. Postoperative care 17. McHoney M, Mackinlay G, Munro F, et al. Effect of patient weight and anesthetic technique on CO excretion during thoracoscopy in children assessed by Postoperative care for thoracoscopic procedures is not different 2 end-tidal CO2. J Laparoendosc Adv Surg Tech A. 2008;18:147-151. from thoracotomies. Analgesia and chest physiotherapy are 18. Levin AI, Coetzee JF. Arterial oxygenation during one-lung anesthesia. Anesth important and early chest radiographs should be done to Analg 2005;100:12-14.

S64 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Mediastinoscopy in paediatric patients

S Spijkerman

Department of Anaesthesiology, Steve Biko Academic Hospital, University of Pretoria Correspondence to: [email protected]

Mediastinal pathology presents a diagnostic and therapeutic Table I. Clinical presentation of mediastinal tumours1 dilemma that requires management from a multidisciplinary Involved structures Symptoms and signs team, often consisting of members of various specialties, Airways and lungs Cough including an anaesthetist, surgeon, radiologist, oncologist and Dysponea intensivist.1 Discourse and planning are paramount. Orthopnoea (exacerbated in supine position) Anatomy of the mediastinum Stridor Cyanosis The mediastinum is divided into a superior and inferior part, Wheezing the division being an imaginary line extending from the Decreased breath sounds Haemoptysis sternomanubrial junction to the T4 vertebra. The inferior part Hoarseness is further divided into three parts. Of these three parts, the Heart and great Fatigue anterior mediastinum lies posterior to the sternum, anterior arteries Headache to the pericardium, superior to the diaphragm, inferior to the Syncope superior mediastinum and medial to the parietal pleurae. The Orthopnoea Hypotension (tamponade or cardiac middle mediastinum is bordered anteriorly by the anterior compression) margin of the pericardium, posteriorly by the posterior border Pulsus paradoxus of the pericardium, laterally by the mediastinal pleura (parietal Superior vena cava Headache pleura) of the lungs, superiorly by the superior mediastinum and Oedema of the head and neck inferior by the diaphragm, whereas the posterior mediastinum is Distended neck and chest veins situated posterior to the pericardium and great vessels, anterior Plethora Cyanosis of the face, neck and arms to the T4–T12 vertebrae, superior to the diaphragm, inferior to Proptosis the superior mediastinum and lateral to the parietal pleurae.1 Horner syndrome (sympathetic chain involvement) Presentation of mediastinal tumours Other symptoms Pain Dysphagia In children under the age of two years, most tumours are benign and the incidence of malignancies increases above this age.1 Different types of malignant tumours are found in the three and his colleagues in 1959 and the anterior mediastinotomy different parts of the inferior mediastinum. In children, the most approach by Chamberlain4 in 1966. By permitting minimally common anterior mediastinal tumours are lymphoma (Hodgkin invasive access to the mediastinum, mediastinoscopy is utilised and non-Hodgkin), thymoma and teratoma.1 In the middle to obtain biopsies of mediastinal lymph nodes and masses in mediastinum lymphoma is the most common with tumours order to facilitate tissue diagnosis for staging and treatment of neuronal tissue most frequently found in the posterior purposes.5 It is therefore mainly a diagnostic procedure. mediastinum. The clinical presentation depends on where the tumour is situated and which structures are compressed (see Superior (cervical) mediastinoscopy is not commonly used in Table I). children,6 although its safe use has been reported in children older than one year.7,8 The technique utilises a small transvers Techniques of mediastinoscopy incision in the suprasternal notch, with advancement of the Mediastinoscopy was first described by Harken2 in 1954, followed scope through the pretracheal fascia into the mediastinum by the development of the suprasternal approach by Carlens3 and down towards the carina. The scope is therefore inserted

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anterior to the trachea and posterior to the aortic arch and lies pulling the airways open, it moves cephalic at end-expiration in close proximity to several major vessels in the mediastinum.9 during positive pressure ventilation, resulting in further airway Although this technique is advantageous due to its minimally compromise. Gravity pulls the tumour onto the great vessels and invasive nature, it affords the surgeon only limited access to tracheobronchial tree. These effects are exaggerated in small lymph nodes in the superior mediastinum up to the level of the children due to the increased cartilages component of their carina (anterior and lateral para-mainstem bronchial, anterior ribs which results in an increased compliance of the chest wall subcarinal, anterior and lateral paratracheal lymph nodes)9 and and an inability of the chest wall to support the tumour which allows poor access to the aorticopulmonary window.5 Successful then compresses major structures in the mediastinal cavity. biopsy of the thymus has been done through this route.10 The small child already has small diameter airways with high airway resistance. Poiseuille14 teaches that during laminar flow The anterior mediastinotomy (also called anterior in a tube, resistance is inversely proportional to the radius to the mediastinoscopy), of which the Chamberlain’s procedure is power of four. During positive pressure ventilation, laminar flow one example, is a surgical technique where the second or is disrupted and during subsequent turbulent flow, the pressure third intercostal space is incised lateral to the sternum to allow gradient that drives gas flow is proportional to the density of the access to the anterior mediastinum, right paratracheal area and gas. Heliox, a mixture of oxygen and helium (helium has a lower 1 aorticopulmonary window, where biopsies of lymph nodes and density than air) has been used successfully in a child with a anterior mediastinal masses can be obtained. mediastinal mass during anaesthesia with a laryngeal mask and 15 Middle and posterior mediastinal masses are biopsied through spontaneous breathing. Due to the above pathophysiological thoracoscopy or thoracotomy. reasons, spontaneous ventilation is preferred in patients with mediastinal masses. The oxygen demand in children is higher Contraindications to superior mediastinoscopy than in adults and the functional residual capacity (FRC) of the child is reduced, predisposing to faster desaturation. The Absolute contraindications to superior mediastinoscopy are listed addition of CPAP during spontaneous ventilation could maintain as anterior mediastinal masses, inoperable tumours, previous the FRC.16 recurrent laryngeal nerve injury, severely debilitated patients, ascending aortic aneurisms and previous mediastinoscopy (due Two possible disadvantages to spontaneous breathing during to adhesions) while relative contraindications mentioned include superior mediastinoscopy are firstly the possibility that the child severe tracheal deviation, cerebrovascular disease, superior vena might move in the absence of a muscle relaxant, with subsequent cava syndrome and descending thoracic aortic aneurism.9,11 injury to any of the vital structures adjacent to the scope and secondly the possibility of air embolism, as this procedure is Anaesthetic implications of mediastinal masses done in the head-up position to reduce engorgement of blood Patients booked for superior mediastinoscopy usually present vessels and the operative site is therefore above the heart. The with mediastinal lymph nodes but no anterior mediastinal tip of the mediastinoscope is located intrathoracically and masses (as these are contraindications to the procedure).11 therefore directly exposed to pleural pressure, making the Those for Chamberlain’s procedure may present with a range possibility of venous air embolism likely when venous bleeding of symptoms from asymptomatic to severe respiratory or occurs. Spontaneous breathing will enhance this risk due to the cardiovascular compromise. Patients with mediastinal masses generation of negative intrathoracic pressure during inspiration.9 may present with superior vena cava (SVC) syndrome and are Perioperative management of patients for at risk of compression of the heart, the great vessels or the mediastinoscopy tracheobronchial tree (often below the level of an endotracheal tube), especially under anaesthesia (see below). Anaesthetic The preoperative preparation of the child should aim at 1 risk is increased in patients with a narrowing of the trachea optimising respiratory and cardiovascular function. In patients or bronchi on computerised tomography (CT) scan to < 50% with mediastinal masses, the nocturnal sleeping position of of predicted cross-sectional area.12 Symptoms like dyspnoea the child (likely position to cause least compression of major are good predictors of the degree of obstruction, with a good structures) should be determined. A thorough history and clinical 1 correlation between severity of symptoms and cross-sectional examination aim to detect SVC syndrome, tracheobronchial area of the airways.13 compression, compression of the heart or great vessels, involvement of the myocardium, cardiac tamponade and other The compression effects of mediastinal tumours place these complications of mediastinal masses as well as complications patients at severe risk of decompensation under anaesthesia.1 generally associated with malignancies or chronic disease. It During general anaesthesia, especially with the use of muscle should be remembered that wheezing is often the only sign of relaxants and positive pressure ventilation, lung volume is tracheobronchial compression in small children.17 A peripheral reduced due to a loss of inspiratory muscle tone and the loss of lymph node should always be sought. This could be used for the tethering effect of the expanded lung on the airway, which biopsy under local anaesthesia with sedation and will spare is normally present during spontaneous ventilation. There is a the patient a general anaesthetic with the associated risks. reduction in the normal transpleural pressure gradient which The child should also be assessed for contraindications for the distends the airway during spontaneous inspiration, leading procedure.9 Special investigations1 include a full blood count to further reduction in airway caliber. Whereas the diaphragm with platelet count, renal function and electrolytes. Blood gas moves in a caudad direction during spontaneous inspiration, analysis should be done per indication. Imaging should include

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a chest X-ray and a contrast-enhanced CT scan to determine The preferred position then is the one determined preoperatively the size of the mass or lymph node involvement. Magnetic as the patient’s preferred nocturnal sleeping position, failing resonance imaging (MRI) scans may be better able to determine which, the lateral decubitus positions (especially the left lateral nerve plexus and blood vessel involvement and are especially decubitus)21 or prone position should be trialed. indicated in patients with iodine or in thyroid tumours. Standard American Society of Anesthesiologists (ASA) Transthoracic echocardiography can assess the involvement monitoring is applied. Capnography allows early detection of of cardiac structures and supply dynamic information about airway compression or cardiovascular collapse and temperature ventricle compression, SVC compression and compromise monitoring is mandatory, especially in small children. Depth of of the pulmonary outflow tract.16,18 Some authors advocate anaesthesia monitoring permits an adequate anaesthetic plane the usefulness of lung function tests in the supine and sitting during maintenance with intravenous agents or in compromised positions in older children,1 which may reveal distortion of the patients where excessive inhalational agent concentration expiratory flow rate in intrathoracic obstruction, distortion of might further suppress cardiovascular function. Neuromuscular inspiratory flow rate in extrathoracic obstruction and equal transmission monitoring might prevent postoperative residual reduction in inspiratory and expiratory flow rates in fixed lesions. muscle relaxant effects, but is probably more important in adult Others argue against the usefulness of lung function tests in the patients with myasthenic effects of mediastinal malignancies. work-up of patients with mediastinal masses due to their poor Urinary catheterisation is usually not indicated due to the short correlation with the degree of obstruction.16 nature of the procedure. The need for biopsies are often urgent, as some common In patients with mediastinal masses, intravenous access should Hodgkin lymphomas display a doubling time of 12 hours.16 If the be obtained while the patient is awake if at all possible, to tumour is large with significant cardio-respiratory compromise, allow for intravenous administration of emergency drugs if steroids and/or irradiation are suggested in order to shrink the cardiovascular or respiratory collapse ensue. Two large-bore tumour and reduce its compression effects. Although this might lines should be inserted in preparation of possible massive compromise the integrity of the tissue and reduce the likelihood bleeding. In the presence of SVC syndrome, these should be of a proper tissue diagnosis,16 studies have shown that adequate inserted in the lower limbs due to the slow circulation of blood in tissue diagnosis is possible, especially if a section of the tumour the SVC distribution and the possibility of further engorgement is shielded from radiation.19 with fluid administration. Central venous cannulas are not Standard nil per os guidelines are adhered to, prophylactic routinely inserted, but should it be warranted in a patient with antibiotics prescribed or administered in theatre and blood SVC syndrome, the preferred site is the femoral vein. In other products ordered on standby. Sedative premedication is instances, the central venous catheter is placed on the side probably best avoided in patients with cardiovascular or most likely to develop a pneumothorax caused by the surgical respiratory compromise. procedure. If placed in the right radial artery during superior mediastinoscopy, the arterial line tracing may disappear or Theatre preparation includes a variety of reinforced (armoured) display false low readings, when the innominate artery is endotracheal tubes of different sizes, micro-laryngeal tubes occluded. Although this is a way of monitoring the patency of (MLT; Covidien Inc) which are paediatric size tubes but of adult the innominate artery (to prevent cerebrovascular damage), it length, different sizes rigid bronchoscopes, and a competent is preferable to insert the arterial line on the left (in order not surgeon able to use the scopes. These airway devices can be to lose the trace) and to place a second saturation probe (apart used to bypass an obstruction in the tracheobronchial tree. The from the one used to monitor saturation which should be on the presence of perfusion technologists and a cardiopulmonary left) on the right hand for monitoring the innominate artery. bypass (CPB) pump are regarded essential by some, while others feel that CPB should be instituted electively if the risk of complete Local anaesthesia is not indicated in the majority of paediatric cardiovascular or tracheobronchial compression exists, as CPB patients. Older children or moribund younger patients could be cannot be successfully instituted in time in the event of sudden considered for local anaesthesia with sedation. In comparison collapse.1 with general anaesthesia, this has the beneficial effects of being safer in terms of cardiovascular and respiratory function, Patients with mediastinal masses are positioned in the semi-sitting often reduces theatre times and enables early detection of position1 as the supine position often exacerbates symptoms. pneumothorax and recurrent laryngeal nerve injury.22 In adults Patients for superior mediastinoscopy are positioned head-up and much older children, awake fibre optic intubation with (30 °)20 to reduce vascular engorgement,9 thereby reducing the spontaneous ventilation could be attempted.18 risk of vascular injury during surgery. This has the added benefit of displacing the diaphragm in a more caudad direction during Flexible bronchoscopy might precede mediastinoscopy and positive pressure ventilation,16 but increases the risk of venous anaesthesia should be planned accordingly. Induction of air embolism9 (see above). To enable access to the operative site, anaesthesia23 should be done in a semi-fowler or sitting position the trunk of the patient is often elevated and the neck extended, in the presence of symptomatic mediastinal masses and should especially for superior mediastinoscopy. When anaesthetising aim at maintaining spontaneous respiration and cardiovascular patients with mediastinal masses, theatre personnel should be function. The use of inhalational agents or ketamine have been prepared to change the position of the patient at any stage in described.24 It must be kept in mind that ketamine stimulates the case of cardiovascular collapse or tracheobronchial obstruction. formation of secretions25 which might further increase airway

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resistance in small or obstructed airways and necessitates the balanced pharmacological analgesic regimens in conjunction co-administration of an anticholinergic agent. Ketamine may with local infiltration of wound sites. also cause cardiovascular collapse in chronically ill patients with Following both superior mediastinoscopy and anterior depleted catecholamine stores.26 Where muscle relaxants will mediastinotomy, patients are mostly extubated in theatre. be omitted, spraying of the vocal cords with lignocaine might Patients with mediastinal masses should be nursed in the head- aid the blunting of the intubation response and might reduce up position in the postoperative period in order to reduce venous intraoperative coughing,9 but might result in postoperative engorgement, and monitored closely for complications.11,17 They aspiration due to inhibition of sensory innervation of the may experience worsening of obstruction caused by swelling or supraglottic airway.27 Intravenous induction is permitted in increase in turbulent air flow due to pain, coughing, tachypnoea children with intravascular access in the absence of mediastinal 18 masses. Intubation should be done with care in patients with head or anxiety. The incidence of postoperative respiratory and neck engorgement to avoid airway bleeding. A reinforced complications is proportional to the size of the tumour. (armoured) tube should be used in patients with mediastinal Following superior mediastinoscopy, bleeding caused by masses in order to prevent the mass from occluding the airway blood vessel injury might manifest in the postoperative period. and for superior mediastinoscopy to prevent the surgeon from Postoperative hemiparesis may follow intraoperative carotid occluding the tube while working in close proximity with the artery compression, while recurrent laryngeal nerve injury may patient’s head. Endotracheal tubes should be carefully secured cause vocal cord paralysis with stridor or airway compromise to prevent dislodgement by the surgeon, especially during and phrenic nerve injury may result in respiratory compromise. superior mediastinoscopy.18 Any of the two mediastinoscopy sites might be complicated by infection. Maintenance of anaesthesia23 should aim at spontaneous respiration in patients with mediastinal masses and could In summary, the anaesthetic plan for both superior and anterior again be accomplished with inhalational agents or ketamine. mediastinoscopy is determined by the underlying pathology and Inhalational or intravenous techniques are used in patients the selected route of surgical access. Vigilance and adaptability where positive pressure ventilation is permitted. Nitrous oxide are crucial as clinical conditions can change rapidly. Good planning and sound knowledge of the pathology and surgical (N2O) is best avoided due to the possible risk of procedure- related pneumothorax which will expand in the presence of techniques are therefore paramount. N O. The use of muscle relaxants is optional but advisable 2 Interests: No interests are declared. during mediastinoscopy in the absence of compressing lesions, in order to afford the surgeon optimal operating conditions Acknowledgements: and to prevent sudden patient movement with injury to vital The author would like to acknowledge the contribution of Dr JM structures, especially during superior mediastinoscopy. The Dippenaar for proofreading and valuable suggestions. focus of intraoperative care should be on the early identification and management of complications11 caused by the surgical References technique (especially during superior mediastinoscopy) or the 1. Soliman D, Cladis F, Davis PJ. The pediatric patient. In: Fleisher LA, editor. disease process (especially during anterior mediastinoscopy). Anesthesia and uncommon diseases. 6th ed. Philadelphia, PA: Elsevier. 2012. 2. Harken DE, Black H, Clauss R, Farrand RE. A simple cervicomediastinal During anterior mediastinotomy the visibility is better with exploration for tissue diagnosis of intrathoracic disease. N Engl J Med. less likelihood of injury to anatomical structures, but patients 1954;251(26):1041-1044. 3. Carlens E. A method for inspection and tissue biopsy in the superior often present with complications of mediastinal masses. During mediastinum. Dis Chest. 1959;36:343-352. superior mediastinoscopy, the scope is placed adjacent to a 4. Mc Neill TM, Chamberlain JM. Diagnostic anterior mediastinotomy. Ann Thorac number of vital structures and massive bleeding from any of the Surg. 1966;2(4):532-539. major vessels (innominate artery, innominate vein azygos vein, 5. Saund MS, Chang MY, Mentzer SJ. Cervical mediastinoscopy and anterior aorta, bronchial artery, pulmonary artery etc) is possible. Massive mediastinotomy. In: Sugarbaker DJ, Bueno R, Krasna MJ, Mentzer S, Zellos L, editors. Adult chest surgery. 2nd ed. New York: McGraw-Hill; 2009. p. 1101-1107. bleeding requires emergency sternotomy or thoracotomy. In 6. Glick RD. Mediastinal masses. In: Mattei P, editor. New York: Springer; 2011. p. the instance of SVC injury, additional intravenous access should 323-332. be obtained in the lower limbs.18 Other possible intraoperative 7. Gun F, Toker A, Kaya S, et al. Cervical mediastinoscopy for paratracheal masses in complications include pneumothorax, innominate artery pediatric patients. Pediatr Hematol and Oncol. 2008;25;393-397. compression, oesophageal injury, tumour seeding, chilothorax 8. Glick RD, Pearse IA, Trippett T, et al. Diagnosis of mediastinal masses in pediatric patients using mediastinoscopy and Chamberlain procedure. J Pediatr Surg. or air embolism. Intraoperative dysrhythmias are possible due 1999;34(4):559-564. to pressure on the heart or great vessels, pulling on mediastinal 9. Benumof JL. Anesthesia for special elective diagnostic procedures. In: Anesthesia structures, pericardial or pleural effusion, or myocardial for thoracic surgery. Philadelphia: WB Saunder. 1995;491-512. involvement of the malignancy. Negative pressure pulmonary 10. Donnelly RJ, Laquaglia MP, Fabri B, et al. Cervical Thymectomy in the treatment oedema may follow deep inspiratory efforts against obstructed of myasthenia gravis. Ann R Coll Surg Engl. 1984;66:305-308. airways which generate large negative pressures (mainly seen in 11. Ehrenwerth J, Brull SJ. Anesthesia for thoracic diagnostic procedures. In: Kaplan JA, Slinger PD, editors. Thoracic anesthesia. 3rd ed. Philadelphia, PA: Churchill adults). Livingstone;2003. p. 174-195. 12. Shamberger RC, Holzman RS, Griscom NT, et al. CT quantitation of tracheal Due to the minimally invasive nature of mediastinoscopy, cross-sectional area as a guide to the surgical and anesthetic management of intra- and postoperative analgesic requirements are limited to children with anterior mediastinal masses. J Pediatr Surg. 1991;26(2):138-142.

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13. Shamberger RC, Holzman RS, Griscom NT, et al. Prospective evaluation by CT 20. Anesthesia for thoracic surgery. In: Morgan GE, Mikhail MS, Murray MJ, editors. and pulmonary function tests of children with mediastinal masses. Surgery. Clinical anaesthesiology. 4th ed. New York: McGraw-Hill; 2006. p. 585-613. 1995;118(3):468-471. 21. Lerman J. Anterior mediastinal masses in children. Sem Anesth, Periop Med Pain. 14. Sutera SP, Skalak R. The history of Poiseuille’s law. Annu Rev Fluid Mech. 1993; 2007;26:133-140. 25:1-19. 22. Ward PH. Stephenson SE. Exploration of the mediastinum under local 15. Polaner DM. The use of heliox and the in a child with an anesthesia. Ann Otol Rhinol Laryngol. 1966;75:368. anterior mediastinal mass. Anesth Analg. 1996;82:208-210. 23. Ahmed-Nusrath A, Swanevelder J. Anaesthesia for mediastinoscopy. Continuing 16. Hammer GB. Anesthesia for Thoracic Surgery. In: Cote C, Lerman J, Anderson BJ. Education in Anaesthesia, Critical Care and Pain. 2007;7(1):6-9. A Practice of Anesthesia for Infants and Children. 5th Edition. Elsevier Saunders: 24. Datt V, Tempe DK. Airway management in patients with mediastinal masses. Philadelphia, PA. 2013:277-290. Indian J Anaesth. 2005;49(4):344-352. 17. Ferrari LR. Supraclavicular node biopsy and mediastinal masses. In: Stehling L, 25. Heinz P, Geelhoed GC, Wee C, Pascoe EM. Is atropine needed with ketamine editor. Common problems in pediatric anesthesia. 2nd ed. St Louis, MO: Mosby; sedatin? A prospective, randomized, double blind study. Emerg Med J. 1992. p. 457-464. 2006;23(3):206-209. 18. Bussières JS, Rousseau A. Anaesthesia for thoracic surgery. In: Alston RP, Myles 26. Scherer D, Leder M, Tobias JD. Pro-Con Debate: Etomidate or Ketamine for PS, Ranucci M, editors. Oxford textbook of cardiothoracic anaesthesia. Oxford: Rapid Sequence Intubation in Pediatric Patients. Pediatr Pharmacol Ther. Oxford University Press; 2015. p. 365-387. 2012;17(2):142-149. 19. Foley RW, Rodriguez MI. Preoperative irradiation of selected mediastinal masses. 27. Raphael JH, Stanley GD, Langton JA. Effects of topical benzocaine and lignocaine J Cardiovac Surg (Torino). 2001;42:695-697. on upper airway reflex sensitivity. Anesthesia. 1996;51:114-118.

S69 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

The obese parturient

E Mostert

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

Introduction in Table II. This should be determined according to the pre- pregnancy weight.8 The prevalence of obesity worldwide is increasing. In the United States (USA) the prevalence of obesity was found to be Table II. Recommended weight gain during pregnancy 8 35.0% among men and 40.4% among women by the National Pre-pregnancy BMI (kg/m²) Recommended weight gain (kg) 1 Health and Nutritional Examination Survey during 2005–2014. < 18.5 12.5–18 Maternal pre-pregnancy obesity has increased from 17.6% 18.5–24.9 11.5–16 in 2003 to 20.5% in 2009 according to a survey in the USA in 25–29.9 7–11.5 > 30 5-9 20 states.2 Maternal obesity is associated with increased rates of gestational diabetes, pre-eclampsia, operative delivery, long- term risks to the foetus and increased mortality in both mother Anaesthetic considerations in the obese parturient and foetus (Table I).3,4 There is an increased risk in providing anaesthesia for obese Table I. Complications associated with maternal obesity in parturients as compared to normal weight parturients. The pregnancy4–6 combination of physiological changes and obesity may affect Maternal complications: the anaesthetic management of these patients. Obese patients Respiratory: Dyspnoea often pose a diagnostic challenge. The changes in the airway, Obstructive sleep apnoea respiratory and cardiovascular systems are important to note.7 Hypoventilation Cardiovascular: Hypertension/Pre-eclampsia/Eclampsia Placement of monitors, intravenous access and provision of Congestive heart failure labour analgesia, neuraxial anaesthesia or general anaesthesia Thrombo-embolism for Caesarean section have an increased technical difficulty Musculoskeletal: Low-back pain in performing and pose a higher risk in caring for the obese Immobility 5,8 Osteoarthritic knees and hips parturient. Gastrointestinal: Gastroesophageal reflux Fatty liver Airway Endocrine: Gestational diabetes mellitus A failed in the general public occurs in Dyslipidaemia Other: Risk of Caesarean delivery around 1:2 500 patients, however in the obstetric patient the risk Wound infections increases to 1:280 patients. In the obese parturient the risk may Foetal: Prematurity increase to 1:3 for having a difficult or failed intubation.5 Mask Stillbirth 7 Neural tube defects ventilation may also be more difficult. The increased risk of Macrosomia aspiration of gastric content in the pregnant patient should also be taken into consideration. Results from the 4th National Audit Weight gain during pregnancy Project of the Royal College of Anaesthetists and The Difficult Airway Society on major complications of airway management Obesity is usually defined using the Body Mass Index (BMI) where in the United Kingdom (NAP 4) report indicated that airway BMI is equal to weight/height² (kg/m²). Normal weight is defined problems in the obstetric population were reported in four as a BMI of 18.5–24.9 kg/m², overweight as a BMI 25–29.9 kg/m² cases, all were for out-of-hours emergency Caesarean sections, and obesity as a BMI more than 30 kg/m².7 and two had a BMI > 35 kg/m².9

The Institute of Medicine in the USA recommends that women Maltby et al10 found no statistical difference between obese should try and limit weight gain during pregnancy, as shown surgical patients that ingested 300 ml of clear liquid two hours

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before surgery compared to those fasted for six hours. Similar the correct size non-invasive blood pressure cuff. Often in the results were found by Juvin et al11 and Wong et al.12 Obese morbidly obese patient this is not possible and invasive blood patients without other co-morbid conditions should follow the pressure monitoring should be utilised. Peripheral venous and standard starvation guidelines. Labour itself does prolong gastric central venous access may be very difficult to place; ultrasound emptying, and should a general anaesthetic be necessary for a guidance may be useful in this regard.13 Caesarean section, a rapid sequence induction and intubation should be performed.7 Labour analgesia

A comprehensive airway examination focussing on Mallampati There is an increased risk of foetal macrosomia and labour score, mouth opening and range of neck movement should difficulties (shoulder dystocia, prolonged labour, labour be done before embarking on any anaesthetic for an obese induction and augmentation), with increased risk of more painful parturient. Changes in the airway are due to fat deposition in the contractions. Early placement of a functioning labour epidural neck, back and airway in obese patients and pregnancy induced catheter is advised. This can then be used should there be the soft-tissue changes like enlarged breasts.7,13 Factors associated need to convert to Caesarean section.7 with difficult laryngoscopy include: short sternomental and Despite the advantages of labour epidurals, the placement of thyromental distance, increased neck circumference, limited an adequately working epidural catheter can be challenging. neck and jaw movement, receding mandible and prominent Reasons for this include difficulty identifying anatomical teeth.6 landmarks and increase in depth of epidural space. Jordan et Respiratory system al16 found that almost 75% of morbidly obese pregnant patients required multiple attempts in placing an epidural. The midline Changes include displacement of the diaphragm in a cephalad can be difficult to identify, but having the patient seated may position due the enlarging uterus, as well as a reduction in 7 the functional residual capacity (FRC). This can be significant be beneficial. Other risks include catheter dislodgement and enough to cause the closing capacity to exceed the FRC during migration. Leaving a longer length of catheter in the epidural 13 tidal breathing. Furthermore, oxygen consumption and minute space may increase the risk of having a one-sided block. ventilation increases. Hypoxaemia and rapid desaturation The use of ultrasound to identify the midline may be useful but can ensue due to this.14 Obstructive sleep apnoea may be its use in identifying the structures of the vertebral column may present, however there is no validated screening tool specific be limited in the morbidly obese patient. The use of a combined to pregnancy. Postoperative complications are more common, spinal epidural (CSE) may be advantageous in this population, including atelectasis and hypoxaemia. All these contribute to an as it provides fast onset analgesia, but there is the risk of increased risk for in-hospital death.5 developing a post-dural puncture headache (PDPH). PDPH has Cardiovascular changes been postulated to have a decreased incidence in obese patients as compared to normal weight parturients, but a retrospective Normal pregnancy changes in the cardiovascular system include record review by Miu et al17 from 2014 found the incidence of increase in stroke volume, heart rate, cardiac output and pulse PDPH not to differ significantly between obese versus non-obese pressure. All of which may be poorly tolerated in the obese parturients. Should PDPH be present, the performance of an patient. Aortocaval compression may be exacerbated in these epidural blood patch as part of the management may be more patients. Obesity related cardiovascular diseases (hypertension, difficult.13 ischaemic heart disease, diabetes mellitus and congestive heart failure) may be aggravated. Obesity is a risk factor for developing Choice between neuraxial vs general anaesthesia for peripartum cardiomyopathy.5,7 There should be a low threshold Caesarean section for echocardiographic examination. There are risks and complications involved with both neuraxial Anaesthetic management and general anaesthesia techniques. Some recommendations to Pre-labour considerations consider before surgery are shown in Table III.

Ideally all obese pregnant patients should have an anaesthetic Table III. Recommendations pre-, intra- and postoperatively in obese 18 evaluation before labour. This will help identify risk factors parturients and aid in proper planning and preparation to minimise • Cardiac evaluation (baseline ECG, possible cardiology consultation, 6 echocardiogram) complications during labour and possible surgical intervention. • Broad-spectrum antibiotics 20–30 min before skin incision (2 g Multidisciplinary meetings between obstetricians, anaesthetists, Cefazolin) midwives and nursing staff should be held with regard to need • Ensure that the operating table is adequate for weight, may need for additional operating tables, monitoring, and postoperative extra table, or special obese operating table, additional theatre personnel 13 care. It has been demonstrated that despite an antenatal • Consider availability of blood products as necessary due to anaesthetic consultation most obese pregnant women remained increased risk of intra- and postpartum haemorrhage unaware of the risks of obesity in pregnancy.15 • Pneumatic compression stockings should be considered intra- and postoperatively Accurate blood pressure measurements are required during • DVT prophylaxis (BMI > 40 kg/m²) neuraxial analgesia and anaesthesia, it is important to select • Early ambulation

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Regional anaesthesia population.25 The OAA/DAS guidelines for the management of difficult and failed tracheal intubation in obstetric patients Regional anaesthesia is advantageous due to avoidance of suggest the use of nasal oxygenation, but the method is not intubation and decreased risk of aspiration, but it can be clearly described.24 technically challenging owing to the changes in anatomy. For the morbidly obese parturient, single-shot spinal, epidural and • Extubation should occur in a semi-upright position when CSE have all been used successfully. The dose of local anaesthetic the patient is fully awake and alert. The use of supplemental for single-shot spinal should not be reduced, unless the patient oxygen is advocated.14 19 is shorter than 1.5 m tall. Placing a catheter for an epidural or Postoperative care CSE has the benefit of providing prolonged anaesthesia and analgesia should surgery be difficult or longer in duration.13,14 A review of maternal deaths in Michigan from 1985–2003 revealed 855 pregnancy-associated deaths, where eight were In a retrospective study by Vricella et al20 from 2008, 142 morbidly anaesthesia related and seven had contributing factors from obese, 251 obese and 185 normal weight patients coming for anaesthesiology. Five of these deaths were in the postoperative Caesarean section were investigated with regards to outcome period, due to hypoventilation or airway obstruction.26 During of the anaesthetic. Complicated placement (5.6%), failure to 2006–2010, in Wisconsin, among pregnancy-related deaths, 12% establish (2%) and insufficient duration (4%) of block was found were overweight and 65% were obese.27 in morbidly obese patients who had regional anaesthesia. Overall complication rate was 8.4% in the morbidly obese group. Postoperative complications such as hypoxaemia, atelectasis and Continuous spinal anaesthesia and double catheter techniques pneumonia, deep vein thrombosis and pulmonary embolism, have been described for the super morbidly obese patients, but post-partum cardiomyopathy, pulmonary oedema and infective 6 these are technically very difficult to perform, with the added risk complications are more common in the obese parturient. 21,22 of PDPH. Most of these complications can be prevented by good General anaesthesia postoperative care, including good analgesia and thromboprophylaxis and vigilance to prevent hypoxia and There is a greater morbidity and mortality associated with respiratory depression.13 Multimodal analgesia should be 4 general anaesthesia for the morbidly obese parturient. The provided, including nonsteroidal anti-inflammatory agents incidence of inability to visualise the vocal cords is twice as high and local anaesthesia. Sedating agents and opioids should in obese parturients.23 The airway changes, risk of aspiration and be used judiciously.14 Providing adequate analgesia enables difficulty in intubating has been discussed above. early mobilisation and improves respiratory function, which in Strategies to overcome the risks involved with general turn aids prevention of deep vein thrombosis. Despite these anaesthesia includes the following: measures, additional thromboprophylaxis should be provided • Having senior anaesthetic help available.5 for these patients. Patients with obstructive sleep apnoea may require postoperative supplemental oxygen or continuous • Following standard starvation guidelines.7 positive airway pressure.13 • Pulmonary aspiration prophylaxis including sodium citrate, H₂-antagonists and performing a rapid sequence induction.13 Conclusion

• Placing the patient in a ‘ramped’ position by placing folded The prevalence of obesity in increasing. Obese patients have an towels or pillows under the chest and head, in order to ensure increased risk of co-morbidities, complications and mortality. that the external auditory meatus and the sternal notch are A thorough preoperative airway, respiratory and cardiac in a horizontal plane, which aligns the oral, pharyngeal and assessment is essential. Proper preparation before labour tracheal axes.13 analgesia or Caesarean section and good postoperative care • Adequate pre-oxygenation. This is done with a tight fitting may help to reduce complications. mask, breathing 100% oxygen for five minutes or four maximal inspiration breaths.5 References 1. Flegal KM, Kruszon-Moran D, Carroll MD, et al. Trends in obesity among adults in • Availability of rescue airway devices (supraglottic airway the United States, 2005 to 2014. JAMA. 2016;315(21):2284-91. devices, intubating laryngeal mask airways), video 2. Fisher SC, Kim SY, Sharma AJ, et al. Is obesity still increasing among pregnant laryngoscopy devices (CMAC), fibre optic bronchoscopes and women? Prepregnancy obesity trends in 20 states, 2003-2009. Preventive surgical access devices (crycothyrotomy sets).6 medicine. 2013;56(6):372-8. 3. Kim SY, Dietz PM, England L, et al. Trends in pre-pregnancy obesity in nine states, • Following difficult airway algorithms, e.g. The Obstetric 1993–2003. Obesity. 2007;15(4):986-93. Anaesthetist’ Association and The Difficult Airway Society 4. Gaiser R. Anesthetic Considerations in the Obese Parturient. Clinical Obstetrics (OAA/DAS) guidelines for management of difficult and failed and Gynecology. 2016;59(1):193-203. tracheal intubation in obstetrics.24 5. Gupta A, Faber P. Obesity in pregnancy. CEACCP. 2001;11(4). • Possible use of transnasal humidified rapid-insufflation 6. Rao DP, Rao VA. Morbidly obese parturient: Challenges for the anaesthesiologist, including managing the difficult airway in obstetrics. What is new? Indian J ventilatory exchange (THRIVE) to overcome desaturation Anaesth. 2010;54:508-21. and apnoea during induction, however no literature could 7. Roofthooft E. Anesthesia for the morbidly obese parturient. Current Opinion in be identified investigating the use of THRIVE in the pregnant Anesthesiology. 2009;22(3):341-6.

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8. Rasmussen KM, Yaktine AL. Weight gain during pregnancy: Re-examining the 18. Leddy MA, Power ML, Schulkin J. The impact of maternal obesity on maternal guidelines. Council IoMaNR, editor. Washington DC: The National Academic and fetal health. Reviews in Obstetrics and Gynecology. 2008;1(4):170-8. Press; 2009. 19. Carvalho B, Collins J, Drover DR, et al. ED(50) and ED(95) of intrathecal 9. Cook T, Woodall N, Frerk C. 4th National Audit Project of The Royal College bupivacaine in morbidly obese patients undergoing cesarean delivery. of Anaesthetists and The Difficult Airway Society. Major complications of Anesthesiology. 2011;114(3):529-35. airway management in the United Kingdom. London: The Royal College of Anaesthetists; 2011. 20. Vricella LK, Louis JM, Mercer BM, Bolden N. Anesthesia complications during scheduled cesarean delivery for morbidly obese women. American journal of 10. Maltby JR, Pytka S, Watson NC, et al. Drinking 300 mL of clear fluid two hours obstetrics and gynecology. 2010;203(3):276.e1-5. before surgery has no effect on gastric fluid volume and pH in fasting and non-fasting obese patients. Canadian journal of anaesthesia = Journal canadien 21. Coker LL. Continuous spinal anesthesia for cesarean section for a morbidly obese d'anesthesie. 2004;51(2):111-5. parturient patient: a case report. AANA J. 2002;70:189-92. 11. Juvin P, Lavaut E, Dupont H, et al. Difficult tracheal intubation is more common 22. Polin CM, Hale B, Mauritz AA, et al. Anesthetic management of super-morbidly in obese than in lean patients. Anesthesia and analgesia. 2003;97(2):595-600, obese parturients for cesarean delivery with a double neuraxial catheter table of contents. technique: a case series. International journal of obstetric anesthesia. 12. Wong CA, McCarthy RJ, Fitzgerald PC, et al. Gastric emptying of water in obese 2015;24(3):276-80. pregnant women at term. Anesthesia and analgesia. 2007;105(3):751-5. 23. Munnur U, de Boisblanc B, Suresh MS. Airway problems in pregnancy. Critical 13. Tan T, Sia AT. Anesthesia considerations in the obese gravida. Seminars in care medicine. 2005;33(10 Suppl):S259-68. perinatology. 2011;35(6):350-5. 24. Mushambi MC, Kinsella SM, Popat M, et al. Obstetric Anaesthetists' Association 14. Vallejo MC. Anesthetic management of the morbidly obese parturient. Curr Opin and Difficult Airway Society guidelines for the management of difficult and Anaesthesiol. 2007;20:175-80. failed tracheal intubation in obstetrics. Anaesthesia. 2015;70(11):1286-306. 15. Eley VA, Donovan K, Walters E, et al. The effect of antenatal anaesthetic 25. Patel A, Nouraei SAR. Transnasal Humidified Rapid-Insufflation Ventilatory consultation on maternal decision-making, anxiety level and risk perception Exchange (THRIVE): a physiological method of increasing apnoea time in in obese pregnant women. International Journal of Obstetric Anesthesia. 2014;23(2):118-24. patients with difficult airways. Anaesthesia. 2015;70(3):323-9. 16. Perlow JH, Morgan MA. Massive maternal obesity and perioperative cesarean 26. Mhyre JM, Riesner MN, Polley LS, Naughton NN. A series of anesthesia-related morbidity. American journal of obstetrics and gynecology. 1994;170(2):560-5. maternal deaths in Michigan, 1985-2003. Anesthesiology. 2007;106(6):1096-104. 17. Miu M, Paech MJ, Nathan E. The relationship between body mass index and 27. Schellpfeffer MA, Gillespie KH, Rohan AM, Blackwell SP. A Review of Pregnancy- post-dural puncture headache in obstetric patients. International journal of Related Maternal Mortality in Wisconsin, 2006-2010. WMJ : official publication of obstetric anesthesia. 2014;23(4):371-5. the State Medical Society of Wisconsin. 2015;114(5):202-7.

S73 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Laryngospasm in anaesthesia

S Spijkerman

Department of Anaesthesiology, Steve Biko Academic Hospital, University of Pretoria Correspondence to: [email protected]

Laryngospasm is a common and serious respiratory complication nerve supplies all the intrinsic laryngeal muscles other than the in anaesthetic practice which can be fatal if not diagnosed cricothyroid muscle (which is supplied by the external branch of and treated timeously. This review will look at the definition, the superior laryngeal nerve). Laryngospasm is mediated through epidemiology, mechanism, risk factors, clinical presentation, the lateral cricoarytenoid and thyroarytenoid muscles (adductors differential diagnosis, prevention, treatment and complications of the glottis) and the cricothyroid muscle (tensor of the vocal of laryngospasm. cords). Vagal nerve mediated apnoea, bronchoconstriction and bradycardia often accompany laryngospasm.6 Laryngospasm Definition occurs on two anatomical levels (Figure 1). False vocal cord Literature provides multiple definitions for laryngospasm. closure with simultaneous anterior movement and backwards Some clinical definitions regard laryngospasm as any unwanted tilt of the arytenoids and posterior movement of the base of the muscular response of the larynx that produces partial or epiglottis firmly close the larynx. The true vocal cords close at a complete obstruction of the larynx,1 while from an anatomical lower level and posterior to the false vocal cords. Their closure point of view, laryngospasm is seen as prolonged closure of the is not mandatory for laryngospasm to occur, as is evident larynx in association with a ball-valve mechanism involving the from the fact that laryngospasm is possible in bilateral vocal cord paralysis.5 Hypoxia and hypercapnia eventually decrease intrinsic laryngeal muscles.2 brainstem impulses to the superior laryngeal nerve, resulting Epidemiology in decreased intensity of glottic closure and spontaneous cessation of laryngospasm as hypoxia and hypercapnia worsen.7 The reported incidence of laryngospasm differs vastly. The Dangerous complications may however ensue (see below), and overall incidence is said to be 0.87%.1 The paediatric incidence is laryngospasm is best treated timeously. quoted as 1.7% by Olsson1 and 0.1% by Burgoyne3 with a higher incidence in infants of 2.82%. The reported incidence probably Figure 1a: Normal airway anatomy depends on the case mix of the reporting hospital,4 experience Photo credit: Daniel Simpson of the anaesthetist (higher incidence amongst junior personnel or when substantial interruption of clinical work has occurred)5 and the lack of consensus on the definition of laryngospasm. Underreporting probably also skews data, as reporting is not compulsory in all centers5 and cases managed timeously often resolve quickly and remain unreported. It is likely that the incidence has declined with the use of propofol total intravenous anaesthesia and modern, non-irritant inhalational agents.3

Mechanism

Laryngospasm is a protective airway reflex. The afferent leg of the reflex involves mechano-, chemo- and thermoreceptor 1. Epiglottis stimulation of the supraglottic airway which results in activation 2. Base of the epiglottis of the internal branch of the superior laryngeal nerve. The sensory nerve supply to the subglottic airway is via the recurrent 3. False vocal cords laryngeal nerve. Reflex adduction of glottic muscles follows 4. True vocal cords through a vagal efferent pathway. The recurrent laryngeal 5. Arytenoid cartilages

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Figure 1b: Mechanism of laryngospasm5 cause airway hyperactivity, increasing the risk of laryngospasm. This hyperactivity lasts 6 weeks after the infection.18 More laryngospasm occurs in American Society of Anesthesiologists (ASA) class 3 and 4 patients compared to those of class 1 and 2, but emergency surgery does not seem to independently increase the risk of laryngospasm.19 The incidence is increased in children with airway anomalies,20 as well as in adult patients with anatomically long uvulas21 or a history of choking during sleep.22 Chronic smoking also increases airway reflex sensitivity and smokers are advised to abstain from smoking for at least 48 hours prior to surgery.23 Passive smoking also increases airway reactivity. Gastroesophageal reflux is another risk factor for laryngospasm.24 1. Base of the epiglottis moves posteriorly 2. False vocal cords contract c. Surgery-related factors 3. Vocal cords close (deeper level than 1,2 and 4) The type of surgery influences the incidence of laryngospasm. 4. Arytenoids move forward; tilt back Tonsillectomy and adenoidectomy probably have the highest incidence with others like appendectomy, cervical dilation, hypospadia surgery and skin grafts also displaying an increased Causes and risk factors risk.1 Laryngospasm is usually caused by either airway stimulation In thyroid surgery, laryngospasm may occur either secondary (blood, secretions, foreign objects) or a light plane of anaesthesia to superior laryngeal nerve injury or due to hypocalcaemia resulting in inadequate central nervous system depression of following iatrogenic parathyroidectomy.7,25 Oesophageal airway reflexes.8 surgery could cause laryngospasm via stimulation of the distal Risk factors can be divided into three categories (see afferent oesophageal nerves.26 Table I) Presentation of laryngospasm (see Table II) a. Anaesthesia-related factors Two clinical entities are commonly distinguished – partial Insufficient depth of anaesthesia at induction or emergence laryngospasm (chest movement with stridor and limited bag is probably the most common cause of laryngospasm. When movement disproportional to breathing attempts) and complete blood or mucus accumulate in the airway or suction catheters laryngospasm (silent chest movement, no bag movement and no or laryngoscope blades are inserted into the airway at this point, ventilation possible).8,27 The literature is however divided on the laryngospasm is frequently elicited. Sodium thiopentone does not blunt the airway responses and, compared to propofol, the Table I: Risk factors for laryngospasm incidence of laryngospasm is increased.9 Ketamine per se does Anaesthesia- Insufficient depth of anaesthesia not cause laryngospasm, but its tendency to increase secretions related Airway irritation with inhalational agents, blood, may indirectly result in spasm.10 Intravenous maintenance etc. Sodium thiopentone (does not blunt airway of anaesthesia with propofol causes less laryngospasm than responses) sevoflurane, probably due to the ability of propofol to blunt Ketamine induced secretions airway reflexes.11 Of the inhalants, the highest incidence is seen Desflurane, isoflurane, enflurane in awake patients Sugammadex with desflurane, then isoflurane, enflurane and lastly sevoflurane LMA > ETT (on induction) 12,13 and halothane (equal incidence). Sugammadex has been ETT > LMA (on extubation) reported to cause tight glottic closure around two minutes Patient-related Children after administration, which correlates with train-of-four ratios Upper respiratory tract infections in excess of 0.9. This reportedly resolved after 2-3 minutes with ASA class ≥ III the application of positive end-expiratory airway pressure Children with airway anomalies Chronic smoking (including passive smoking) 14,15 (PEEP). The use of laryngeal mask airways (LMA) is listed as Gastroesophageal reflux an independent risk factor for laryngospasm, but studies do not Long uvula; history of choking at night state what proportion of patients were done with LMA, whether Surgery-related Airway surgery (Tonsillectomy and they were breathing spontaneously or assisted or whether the adenoidectomy) LMA was removed deep or awake.4 Other studies found that Appendectomy Genitourinary surgery (hypospadia, cervical laryngospasm occurred more on induction when LMAs were used dilatation) and more on extubation when endotracheal tubes were used.16 Thyroid surgery (SLN injury; hypocalcaemia secondary to b. Patient-related factors iatrogenic parathyroidectomy) Oesophageal surgery The incidence of laryngospasm is higher in children and LMA = laryngeal mask airway; ETT = endotracheal tube; ASA = American especially small babies.17 Upper respiratory tract infections Association of Anesthesiologists; SLN = superior laryngeal nerve.

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existence of “partial laryngospasm”. Some present endoscopic Table III: Differential diagnosis of laryngospasm evidence that, during closure of the true vocal cords, passage of Anaphylaxis some air could occur through the posterior commissure, resulting Angioedema in stridor which should not be seen as partial laryngospasm and Tracheal stenosis Vocal cord polyps or tumours only false cord closure is viewed as laryngospasm. True cord Foreign bodies in the airway closure is possible prior to false cord closure (laryngospasm) or Vocal cord paralysis after laryngospasm has resolved. Laryngospasm is regarded as Laryngomalacia Tracheomalacia 5 silent and stridor as a clinical sign of broken laryngospasm. Other Breath holding or reflex apnoea clinical signs of laryngospasm include a lack of airflow at the Vocal cord dysfunction (VCD) or paradoxical vocal cord motion (PVCM) mouth or nose, intercostal retraction, tracheal tug, paradoxical Loss of upper airway tone breathing and late signs including desaturation, bradycardia and Bronchospasm cyanosis.28 In adults, severe strain against a closed glottis is often evident from engorged neck veins and vigorous movement Prevention (see Table IV) of the body, resembling severe coughing efforts, albeit silent. In babies, desaturation is often the first or only sign (personal The incidence of laryngospasm is lower in the hands of 5 observation). Capnographic evidence of laryngospasm entails a experienced anaesthetists. The use of premedication to decrease laryngospasm is controversial. Anticholinergic drugs lack or severe decrease in end-tidal CO2 (ETCO2). reduce secretions and therefore reduce laryngeal irritation, but they display some undesirable side-effects. Their use should Table II: Presentation of laryngospasm probably be limited to use in conjunction with ketamine or in Chest movement with limited airflow at the mouth or nose and limited bag movement patients known with increased secretions. Benzodiazepines Silence or stridor decrease upper airway reflexes and may reduce laryngospasm. Body movements; engorged neck veins Although it will not prevent laryngospasm, some authors Intercostal retraction feel that N O should be omitted during preoxygenation as to Tracheal tug 2 Paradoxical breathing ensure optimal oxygen reserve in case of laryngospasm or other Desaturation difficulties.31 Inhalational induction should be done with a non- Bradycardia irritating agent like sevoflurane or halothane and the patient Cyanosis should be in a deep anaesthetic plane prior to intravenous Absence of ETCO on capnography 2 cannulation and airway instrumentation.28 Some suggest waiting ETCO = End-tidal carbon dioxide 2 two minutes after loss of the eyelash reflex in children before the intravenous line is placed,32 while others emphasize that a deep Differential diagnosis (see Table III) anaesthetic plane is a clinical diagnosis and not definable by a time interval.31 Similarly, oropharyngeal airways should never be The differential diagnosis probably resembles the differential inserted while a patient is in a light plane of anaesthesia, even if diagnosis of vocal cord dysfunction29 and will include airway obstruction occurs. The airway should rather be opened anaphylaxis, angioedema, tracheal stenosis, vocal cord polyps or by a cautious jaw-thrust manoeuvre. Propofol induction and other tumours, foreign bodies in the airway, vocal cord paralysis, maintenance could cause less laryngospasm than sevoflurane.11 laryngomalacia and tracheomalacia. Breath holding and reflex Extubation should either occur at a deep level of anaesthesia or apnoea (especially in children) due to the Hering-Breuer reflex in a patient who is fully awake; both techniques have advantages 28 occur on over-inflation of the lungs. This will worsen when and disadvantages. Some advocate the “no touch” technique sustained high inflation pressure is administered to the airway, where the patient is left unstimulated with the airway device in situ until fully awake.33 Others extubate while the lungs are fully as is often the case during treatment of laryngospasm.28 Vocal inflated in order to reduce the adductor response of the larynx cord dysfunction (VCD), also known as paradoxical vocal cord and to force the patient to exhale upon extubation, expelling motion (PVCM), is a condition where vocal cords paradoxically secretions and reducing larynx irritation.34 adduct during inspiration leading to stridor, wheezing and dyspnea. This occurs during emotionally stressful times and Some studies have shown intravenous lignocaine (1 mg.kg-1) is a possible cause of postoperative stridor or laryngospasm. to be effective in preventing post-extubation laryngospasm, 35,36 Treatment includes benzodiazepines and reassurance.30 Residual while others were unable to demonstrate a benefit. Glottic topicalization with 2% lignocaine at 4 mg.kg-1 showed some muscle relaxants or opioids cause loss of upper airway tone benefit.37 The potential danger of this practice is postoperative with occlusion of the pharynx by the tongue. This should be aspiration of blood or secretions if the airway is devoid of excluded when stridor occurs in the recovery room. Although -1 sensation. Intravenous MgSO4 (15 mg.kg ) after intubation bronchospasm usually results in expiratory wheezing and not effectively decreased extubation laryngospasm, probably by inspiratory stridor, bronchospasm and laryngospasm often co- increasing the anaesthetic depth and decreasing laryngeal exist, especially when triggered by airway stimulation during 38 muscle tone. In cats, inhaling 5% CO2 for 5 minutes prior to light plains of anaesthesia. Bronchospasm should therefore be extubation reduced laryngospasm, probably because the 39 excluded once laryngospasm has ceased. drive to exhale the CO2 overrides the laryngospasm reflex.

S76 2017 FCA 2 Anaesthetic Refresher Course 77 Figure 2: Personal treatment of the author: algorithm Atropine 20 µg.kg IM = intramuscular; CPR = cardiopulmonary resuscitation. IM = intramuscular; CPR = cardiopulmonary CPAP mask airway; LMA = laryngeal = continuous pressure; positive airway FiO2 of oxygen; fraction IV = intravenous; = inspiratory Suxamethonium Contraindication to suxamethonium? 0.5 mg.kg No IM (children) 4 mg.kg Propofol + -1 -1 IM IV IV access -1

Stimulate laryngospasm notch Stimulate laryngospasm 0.5 mg.kg 1.2 mg.kg Rocuronium Prepare propofol Propofol Complete + Yes -1 -1 IV IM CPR Not improved No Atropine 20 µg.kg Suxamethonium 4 mg.kg Remove stimulus if possible (LMA) Reassess degreeReassess of laryngospasm Open airway (gentle jaw thrust) Open airway Improvement? Degree of laryngospasm? Diagnose laryngospasm Contraindication to suxamethonium? Apply CPAP; F No -1 IM (children) Call help -1 No IV access IM i O 2 = 1 1.2 mg.kg Rocuronium Yes Yes -1 IM Improved Continue anaesthetic/emergence Increase vapour concentration Prepare propofol Partial

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CO2 is of course not routinely available in theatre, and no human insufflation with splinting of the diaphragm might also follow studies exist. The partial success of acupuncture40 is another these high pressures.42,43 Gentle manual assistance of breathing interesting observation, but most anaesthetists are not skilled could be beneficial. Some mention gentle chest compressions acupuncturists. as a treatment option,44 but this study is criticised41 for amongst others methodology and treatment delay while compressions Table IV: Possible strategies to prevent laryngospasm are done. Short-acting opioids like alfentanil can be used, Experienced anaesthetist but will probably cause apnoea and less optimal intubating Anticholinergic premedication conditions than suxamethonium.45 Guidelines concur that in Sedative premedication the less than 25% of cases where propofol is not successful, Propofol induction (rather than thiopentone, ketamine or inhalants) Deep plane of anesthesia prior to IV cannulation, airway suxamethonium should be used. Suggested intravenous dosages instrumentation or surgical stimulation range from 0.1–3 mg.kg-1. Propofol is initially preferred over Propofol maintenance (rather than sevoflurane) suxamethonium because of the latter’s possible interaction with Deep or fully awake extubation non-depolarizing muscle relaxants, range of contra-indications Extubate following maximal inspiration and possibility of suxamethonium apnoea. Suxamethonium Intravenous lignocaine Intravenous magnesium sulphate should however be administered before severe hypoxia ensues, Acupuncture as its administration under these conditions may result in

Inhaled CO2 (cats) bradycardia and cardiac arrest. It is recommended for the same

IV = intravenous; CO2 = carbon dioxide reason, that suxamethonium be preceded by atropine 0.02 mg.kg-1 in children.28 The use of suxamethonium in extubation laryngospasm might follow shortly after the administration Treatment (see Tables V and VI and Figure 2) of neostigmine, in which case it should be remembered that pseudocholine esterase is also inhibited by neostigmine and the Most treatment guidelines concur that the first steps in the breakdown of suxamethonium might be prolonged.46 treatment of laryngospasm should include removing the stimulus, calling for help (to have extra hands to draw up drugs), When laryngospasm occurs in the absence of intravenous access, applying a jaw thrust maneuver and 100% oxygen. Controversy the use of suxamethonium via the peripheral intramuscular surrounds some of the aspects of treatment. As part of removing (deltoid or quadriceps muscles) or intralingual route (4 mg.kg-1 the stimulus, some believe that the airway should be suctioned in both instances), will have an onset of action of 295 seconds and examined for foreign bodies.41 Personal experience has and 265 seconds respectively. It is recommended that both taught that this is firstly very difficult as jaw clenching often submental and peripheral intramuscular injection sites be occurs at this point and inserting a suction device into the throat massaged post-injection as it could reduce the onset of action to during a light plane of anaesthesia might stimulate further spasm 133 seconds.47 The intraosseous route resembles the intravenous of the larynx. Suctioning and inspection of the airway should route in dosage and onset time. The intra-oral intralingual probably only occur after deepening the anaesthetic plane route, could cause bleeding and hematoma formation and or administering a muscle relaxant. A laryngeal mask should may complicate airway management. Mask ventilation is also however be removed if possible if this was the initial trigger. This interrupted while injection occurs. The submental route is is also often only possible after pressure on the “laryngospasm therefore advisable. These non-intravenous routes might have a notch” (see below) or pharmacological treatment of the spasm. slower onset of action than the intravenous route, but muscle Suctioning should only be done under vision and very cautiously relaxation occurs sooner in the larynx than in peripheral muscles, following oropharyngeal surgery. Some authors list, as first line enabling airflow much quicker than the quoted onset times treatment of laryngospasm, the insertion of an oropharyngeal for non-intravenous suxamethonium.48 The duration of action or nasopharyngeal airway.28 This is contested by others because of intramuscular suxamethonium will however be prolonged the patient is probably in a light plane of anaesthesia and to 15–30 minutes, compared to its six- to ten-minute duration inserting an object into the airway might worsen the spasm.5 via the intravenous route.48 Most non-depolarizing muscle Also, an oropharyngeal airway should never be inserted after relaxants are not suitable for intramuscular use in laryngospasm, oropharyngeal surgery, as this might dislodge sutures or cause both due to their unacceptably slow onset of action via this wound trauma. In these cases, laryngospasm should be treated route (mivacurium and atracurium > 10 minutes) and tissue without delay, as coughing and straining will increase venous irritation (atracurium).49 Only rocuronium is deemed to have pressure and cause bleeding. Deepening the anaesthetic is an acceptable onset of action via the intramuscular route,49,50 commonly accepted as a treatment option for laryngospasm, keeping in mind that rocuronium burns intravenously and but some list the use of inhalational agents, even in complete probably intramuscularly and could momentarily trigger further obstruction.28 It might be argued that inhalational agents will not laryngospasm.51 One study describes the use of intramuscular reach the airway during complete laryngospasm5, and deepening vecuronium (0.2–0.3 mg.kg-1) in 12 patients.52 This was not for the plane of anaesthesia during complete laryngospasm is only laryngospasm but rather for routine intubation in conjunction possible with intravenous agents like propofol 0.25–0.8 mg.kg-1,17 with ketamine. Intubation was possible within 3–5 minutes. which is successful in more than 75% of cases. Positive pressure This is similar to the 4 minutes quoted for intramuscular ventilation as a treatment option is also controversial. Some rocuronium (1 mg.kg-1 and 1.8 mg.kg-1 in children < 1 year and regard this as imperative28 while others question its potential > 1 year of age respectively).49 Laryngospasm will probably for breaking a tight laryngospasm and regard the practice as cease even sooner. Intramuscular rocuronium is therefore dangerous due to the potential of stimulating stretch receptors an alternative to suxamethonium in patients with burns or if the patient accidently inhales, causing reflex apnoea.5 Gastric other contraindications to suxamethonium in the absence of

S78 2017 FCA 2 Anaesthetic Refresher Course 79 intravenous access. The duration of action will however exceed Complications 60 minutes.50 The immediate reversal of both rocuronium and vecuronium is possible with sugammadex,53 but intravenous Laryngospasm can be fatal if left untreated. Cardiac arrest, access needs to be established. Although intramuscular bradycardia, pulmonary aspiration and oxygen desaturation have administration was tolerated in rabbits,54 no human studies been reported.20 Post-obstructive negative pressure pulmonary exist and no data is available on the intramuscular route for edema is another concern. This occurs when patients generate a sugammadex (personal communication with the manufacturing large negative pressure when inhaling against a closed glottis.7 company). Sugammadex has also been implicated as a possible Complications following the treatment of laryngospasm is cause of laryngospasm (see above). also possible. This includes the extensive list of side-effects of suxamethonium, hypotension of propofol and trauma caused by Five cases of post-extubation laryngospasm were reportedly treated with doxapram (1.5 mg.kg-1 intravenously)55 and 2 cases high pressure ventilation and intubation attempts with a closed with nitroglycerin (4 µg.kg-1 intravenously)56. The mechanism glottis. of action of doxapram is possibly the stimulation of respiratory Laryngospasm is a treatable condition which can result in serious drive but nitroglycerine is known to act on smooth muscle morbidity and mortality. Vigilance, good decision-making skills and this might not explain laryngeal muscle (skeletal muscle) and thorough education, possibly through simulator training relaxation. and algorithms, are vital for timeous diagnosis and treatment of Two non-pharmacological treatment options have been laryngospasm. described. The first is well known but often applied incorrectly. Larson described a technique where pressure is applied to the Interests: No interests are declared. “laryngospasm notch”. This is often erroneously interpreted as Acknowledgements: pressure on the angle of the jaw or ramus of the mandible. The correct technique is the application of pressure with the middle The author would like to acknowledge the contribution of Dr JM fingers on a point bordered anteriorly by the ascending ramus of Dippenaar for proofreading and valuable suggestions the mandible adjacent to the condyle, posterior by the mastoid process and superior by the base of skull. The operator presses References: firmly inwards and in a cephalad direction (in the direction of the 1. Olsson GL, Hallen B. Laryngospasm during anaesthesia. A computer-aided incidence study in 136929 patients. Acta Anaesthesiol Scand, 1984;28:567-75. styloid process, as cephalad as possible) with the middle fingers 2. Fink BR. The etiology and treatment of laryngeal spasm. Anesthesiology. while performing a jaw thrust manoeuvre with the thumbs and 1956;17:569-77. index fingers to open the airway and maintain a thorough mask 3. Burgoyne L, Anghelescu DL. Intervention steps for treating laryngospasm in seal. The mechanism of glottic relaxation is not well understood, pediatric patients. Paediatr Anaesth. 2008;18:297-302. but probably results from pain-induced autonomic nervous 4. Black AE. Laryngospasm in pediatric practice. Pediatr Anesth. 2008;18:279. systems effects.45 The second technique is superior laryngeal 5. Holzki J. Laryngospasm. Pediatr Anesth. 2008;18:1144-6. nerve block to prevent post-extubation laryngospasm.57,58 6. Orliaguet AG, Gall O, Savoldelli GL, Couloigner V. Case scenario: perianesthetic management of laryngospasm in children. Anesthesiology. 2012;116:458-71. 7. Donlon JV, Doyle DJ, Feldman MA. Anaesthesia for eye, ear, nose and throat Table V: Treatment options for laryngospasm surgery. In: Miller RD, editor. Miller’s Anesthesia. 6th ed. Philadelphia: Elsevier Churchill Livingstone;2005. p. 2527-55. Removal of stimulus Calling for help 8. Hampson-Evans D, Morgan P, Farrar M. Pediatric laryngospasm. Pediatr Anesth. 2008;18:303-7. Jaw thrust maneuver Stimulation of the laryngospasm notch 9. Horita A, Dille JK. Observation on the action of thiopental on the laryngeal 100% Oxygen reflex. Anesthesiology. 1955;16:848-53. Deepen the plane of anaesthesia (propofol, opioids, inhalational 10. Mcglone RG, Howes MC, Joshi M. The Lancaster experience of 2.0 to 2.5 mg/kg agents – partial laryngospasm) intramuscular ketamine for paediatric sedation: 501 cases and analysis. Emerg Positive pressure ventilation Med. 2004;21:290-5. Gentle chest compressions 11. Oberer C, Von Ungern-Sternberg BS, Frei FJ, et al. Respiratory reflex responses Suxamethonium (preceded by atropine in children) or rocuronium of the larynx differ between sevoflurane and propofol in pediatric patients. (see algorithm) Anesthesiology. 2005;103:1142-8. Other (doxapram, nitroglycerine, superior laryngeal nerve block) 12. Fisher D, Robinson S. Comparison of enflurane, halothane and isoflurane for diagnostic and therapeutic procedures in children with malignancies. Anesthesiology. 1985;63:647-50.

Table VI: Dosages and onset of action of different routes of muscle relaxants in laryngospasm Agent Route Suggested dose Onset of action Suxamethonium Intravenous 0.5 mg.kg-1 30–60 s Interosseous 0.5 mg.kg-1 30–60 s Intramuscular 4 mg.kg-1 4 min Intralingual 4 mg.kg-1 4 min Rocuronium Intravenous 1 mg.kg-1 90 seconds Intramuscular 1.2 mg.kg-1 4 min 1.8 mg.kg-1 in infants s = seconds; min = minutes; mg = milligram; kg = kilogram

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13. Coté CJ. Pediatric anesthesia. In: Miller RD, editor. Miller’s Anesthesia. 6th ed. 36. Leicht P, Wisborg T, Chraemmer-Jorgensen B. Does intravenous lidocaine prevent Philadelphia: Elsevier Churchill Livingstone; 2005. p. 2367-407. laryngospasm after extubation in children? Anesth Analg. 1985;64:1193-6. 14. McGuire B, Dalton AJ. Sugammadex, airway obstruction, and drifting across the 37. Koc C, Kocaman F, Aygenc E, et al. The use of perioperative lidocaine to prevent ethical divide: a personal account. Anaesthesia. 2016;71:487-92. stridor and laryngospasm after tonsillectomy and adenoidectomy. Otolaryngol 15. Greenaway S, Shah S, Dancey M. Sugammadex and laryngospasm. Anaesthesia. Head Neck Surg. 1998;118:880-2. 2017;72:405-16. 38. Gulhas N, Durmus N, Demirbileks S, et al. The use of magnesium to prevent 16. Visvanathan T, Kluger MT, Webb RK et al. Crisis management during anaesthesia: laryngospasm after tonsillectomy and adenoidectomy: a preliminary study. laryngospasm. Qual Saf Health Care. 2005;14:e3. Paediatr Anaesth. 2003;13:43-7. 17. Batra YK, Ivanova M, Ali SS, et al. The efficacy of a subhypnotic dose of propofol 39. Nishino T, Yonezawa T, Honda Y. Modification of laryngospasm in response to in preventing laryngospasm following tonsillectomy and adenoidectomy in changes in PaCO2 and PaO2 in the cat. Anesthesiology. 1981;55:286-91. children. Pediatr Anesth. 2005;15:1094-7. 40. Lee CK, Chien TJ, Hsu JC, et al. The effect of acupuncture on the incidence of 18. Nandwani N, Raphael JH, Langton JA. Effects of upper respiratory tract infection postextubation laryngospasm in children. Anaesthesia. 1998;53:910-24. on upper airway reactivity. Br J Anaesth. 1997;78:352-5. 41. Gavel G, Walker RWM. Laryngospasm in anaesthesia. Continuing Education in 19. Murat I, Constant I, Maud’huy H. Perioperative anaesthetic morbidity in children: Anaesthesia, Critical Care and Pain. 2014;14(2):47-51. a database of 24.165 anaesthetics over a 30-month period. Pediatr Anesth. 42. Gal TJ. Airway management. In: Miller RD, editor. Miller’s Anesthesia. 6th ed. 2004;14:158-66. Philadelphia: Elsevier Churchill Livingstone; 2005. p. 1617-52. 20. Flick RP, Wilder RT, Pieper SF, Van Koeverde K, Ellison KM, Marienau MES, et al. 43. Chipas A, Ellis WE. Airway management. In: Nagelhout JJ, Plaus KL. Nurse Risk factors for laryngospasm in children during general anesthesia. Pediatr Anesthesia. 4th ed. St Louis, MO:Saunders;2010. p. 441-64. Anesth. 2008;18:289-96. 44. Al-Metwalli RR, Mowafi HA, Ismail SA. Gentle chest compression relieves 21. Shott SR, Cunningham MJ. Apnea and the elongated uvula. Int J Pediatr extubation laryngospasm in children. J Anesth. 2010;24:854-7. Otorhinolaryngol. 1992;24:183-9. 45. Mevorach DL. The management and treatment of recurrent postoperative 22. Aloe FS, Thorpy MJ. Sleep-related laryngospasm. Arq Neuropsiquiatr. laryngospasm. Anesth Anal. 1996;83:1110-1. 1995;53:46-52. 46. Fleming NW, Macres S, Antognini JF, Vengco J. Neuromuscular blocking 23. Erskine RJ, Murphy PJ, Langton JA. Sensitivity of upper airway reflexes in action of suxamethonium after antagonism of vecuronium by edrophonium, cigarette smokers: effect of abstinence. Br J Anaesth. 1994;73:298-302. pyridostigmine or neostigmine. Br J Anaesth. 1996;77:492-5. 24. Loughlin CJ, Koufman JA, Averill DB, et al. Paroxysmal laryngospasm secondary 47. Redden RJ, Miller M, Campbell RL. Submental administration of succinylcholine to gastroesophageal reflux. Laryngoscope. 1996;106:1502-5. in children. Anesth Prog. 1990;37:296-300. 25. Mortero RF, Orahovac Z, Tsueda K, et al. Severe laryngospasm at tracheal extubation in a patient with superior laryngeal nerve injury. Anesth Analg. 48. Warner DO. Intramuscular succinylcholine and laryngospasm. Anesthesiology. 2001;92:271-2. 2001;95:1039-40. rd 26. Bauman NM, Sandler AD, Schmidt C, et al. Reflex laryngospasm induced by 49. Horowitz BZ. Paralytic agents. In: Dart RC, editor. Medical Toxicology. 3 ed. stimulation of distal afferents. Laryngoscope. 1994;104:209-14. Philadelphia, PA: Lippincott Williams and Wilkens; 2004. p. 579-93. 27. Roy WL, Lerman J. Laryngospasm in paediatric anaesthesia. Can J Anaesth 50. Morgan GE, Mikhail MS, Murray JM, editors. Anesthesia for thoracic surgery. In: th 1988;35:93-8. Clinical Anesthesiology. 4 ed. New York: McGraw-Hill; 2006. p. 585-613. 28. Alalami AA, Ayoub CM, Baraka AS. Laryngospasm: review of different prevention 51. Szmuk P, Radulescu A, Ezri T, Geva D. Intramuscular Rocuronium. Anesthesiology. and treatment modalities. Pediatr Anesth. 2008; 18:281-8. 1997;86:506. 29. Deckert J, Deckert L. Vocal cord dysfunction. Am Fam Physician. 52. Alpert CC, Bailey MK, Brahen NH, Dorman BH. J Cardiothorac Vasc Anesth. 2010;81(2):156-9. 1992;6(2):265. 30. Punj J, Darlong V, Pandey R. Paradoxical vocal cord motion - another cause to 53. Plaud B, Meretoja O, Hofmockel R, Raft J, Stoddart PA, van Kuijk JH, et al: Reversal differentiate from laryngospasm. Pediatr Anesth. 2008;18:979. of rocuronium induced neuromuscular blockade with sugammadex in pediatric and adult surgical patients. Anesthesiology. 2009;110:284-94. 31. Umesh G, Jasvinder K, Ramkumar V. Management of laryngospasm – our concerns and suggestions. Pediatr Anesth. 2008;18:978-9. 54. European Agency. Assessment report for Bridion. London, UK. 2008. 32. Schwartz D, Connelly NR, Gutta S, et al. Early intravenous cannulation in children 55. Owen H. Postextubation laryngospasm abolished by doxapram. Anesthesia. during sevoflurane induction. Pediatr Anesth. 2004;14:820-4. 1982;37:1112-4. 33. Lee KWT, Downes JJ. Pulmonary edema secondary to laryngospasm in children. 56. Sibai AN, Yamout I. Nitroglycerin relieves laryngospasm. Acta Anaesthesiol Anesthesiology. 1983;59:347-9. Scand. 1999;43:1081-3. 34. Landsman IS. Mechanism and treatment of laryngospasm. Int Anesthesiol Clin. 57. Larson CP. Laryngospasm – best treatment. Anesthesiology. 1998;89:1293-4. 1997;3:67-73. 58. Monso A, Riudeubas J, Palanques F, et al. A new application for superior 35. Baraka A. Intravenous lidocaine controls extubation laryngospasm in children. laryngeal nerve block: treatment or prevention of laryngospasm and stridor. Reg Anesth Analg. 1978;57:506-7. Anesth Pain Med. 1999;24:186-93.

S80 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Epilepsy and anaesthesia

C Hosking

Dunkeld Anaesthetic Practice, Johannesburg Correspondence to: [email protected]

Definitions1,2 Generalised seizures

Seizure: an episode of abnormal excessive neuronal discharge • Seizure activity involving both hemispheres of the brain. due to an imbalance between excitatory and inhibitory • These are described in terms of the pattern of the clinical neurotransmission and resulting in clinical manifestations of a particular pattern. manifestations observed as being tonic, clonic, tonic-clonic, myoclonic, atonic or absence in nature. Epilepsy: a brain condition characterised by an enduring predisposition or tendency to developing recurrent, Anaesthetic considerations unprovoked seizures and including the neurobiologic, cognitive, psychological and social consequences of the condition. 1. Preoperative

Status epilepticus: a medical emergency characterised by Patients with epilepsy may present for emergency management continuous seizure activity for ≥ 5 minutes or recurrent seizure of status epilepticus or neurosurgical procedures aimed at activity without full neurological recovery between each seizure. diagnosing or controlling epilepsy such as cortical mapping, (PLEASE REVIEW EMERGENCY MANAGEMENT OF STATUS cortical electrode placement or implantation of anti-seizure EPILEPTICUS WHICH IS NOT COVERED IN THESE NOTES) devices. More commonly, however, patients with epilepsy Aetiology present for elective or emergency surgical procedures unrelated • Genetic, e.g. benign familial neonatal epilepsy, juvenile to epilepsy. As always, a thorough preoperative assessment myoclonic epilepsy • Structural, e.g. tumours, trauma, intracranial haemorrhage includes taking a history, performing a physical examination • Metabolic, e.g. inborn errors of metabolism, porphyria and reviewing special investigations. Of particular importance, • Immune, e.g. autoimmune encephalitis the anaesthesiologist must determine the clinical pattern of • Infectious, e.g. meningitis, brain abscess, HIV, tuberculosis, seizures in order that seizure activity may be readily identified neurocysticercosis, etc. and treated in the perioperative period. • Unknown (previously termed idiopathic) History Type of epilepsy Clinical pattern of seizures Classification1,2 Cause of epilepsy Underlying medical Seizure history conditions Focal seizures Seizure control/last • Previously termed partial seizures. Seizure precipitants seizure Anticonvulsant medication Episodes of status • Seizure activity limited to one hemisphere of the brain. epilepticus

• May occur with or without altered consciousness or awareness. Drugs including doses Partial seizures occurring with altered consciousness or Last dose/next dose awareness are termed dyscognitive seizures. Other medical or surgical Plan to minimise dose therapies interruptions • Focal seizures may evolve to include both hemispheres in Implanted anti-seizure Adverse effects or which case they are termed focal to bilateral (previously devices complications of secondary generalised) seizures. medication

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Examination Clinical features in e.g. neurofibromatosis, circumstances under which they are used. The dose response keeping with underlying tuberous sclerosis, is unpredictable and depends on patient factors, dosages and medical condition or cerebral palsy, post stroke drug interactions5. syndrome Clinical features in e.g. bleeding, bruising, keeping with adverse pallor, jaundice, gum What are the effects of anticonvulsants on anaesthesia? effects or complications of hypertrophy, CNS toxicity medication Almost all anticonvulsants have some CNS sedating effects Investigations Full blood count Exclude adverse effects reducing anaesthetic requirements and placing patients at risk of Urea, electrolytes and or complications delayed emergence and prolonged sedation in the postoperative glucose of medication, e.g. Anticonvulsant drug levels anaemia, electrolyte period. Aconvulsive status epilepticus should be on the list of Electrocardiogram derangements, cardiac differential diagnoses for all patients with delayed emergence arrhythmias and following general anaesthesia. Consideration should be given to sub-therapeutic or toxic regional or local anaesthetic techniques where possible. This is drug levels especially true for patients with poorly controlled epilepsy.

Most anticonvulsants (carbamazepine, phenytoin and Prevention of seizures during the perioperative period depends phenobarbital) are inducers of the hepatic P450 cytochrome largely on maintaining the ‘chain of therapy’ by minimising oxidase enzyme system resulting in several drug interactions: the duration of preoperative starvation and ensuring correct Halothane ↑metabolism ↓efficacy ↑risk halothane doses of anticonvulsant medication are given at the correct hepatitis time.3 Consideration should be given to administration of a Aminosteroid ↑metabolism ↓efficacy benzodiazepine premedication as well as timeous reinstitution muscle relaxants of anticonvulsant medication postoperatively. Nausea and Synthetic opioids ↑metabolism ↓efficacy vomiting may interfere with oral intake causing treatment interruptions and should be aggressively prevented and treated. Through their effect on the hepatic P450 cytochrome Antiemetic agents known to cause extra-pyramidal side effects oxidase system, anticonvulsants may also decrease plasma should be avoided.4 Should a patient be unable to take orally concentrations of many other medications of relevance to the in the days following surgery, intravenous substitutes should anaesthetist including amiodarone, β adrenoceptor blocking be prescribed and therapeutic drug monitoring commenced. agents, calcium channel blocking agents and warfarin.10,11 Not all anticonvulsant medications are available in intravenous These potential drug interactions should be kept in mind when preparations. It is valuable to contact the hospital encountering patients on multiple chronic medications. preoperatively in order to establish the availability of intravenous How does one diagnose seizure activity under anaesthesia? preparations or appropriate substitutes. The typical clinical manifestations of seizure activity are often 2. Intraoperative absent in patients under general anaesthesia. This is especially Do anaesthetic agents cause seizures? true for those patients who have received muscle relaxants. The clinical signs reflect autonomic instability and include Most anaesthetic agents have been shown to be either pro- or hypertension, tachycardia, cardiac arrhythmias, sweating, anti-convulsant, however, several anaesthetic agents have been temperature derangements, poor glycaemic control, electrolyte shown to be both pro- and anti-convulsant depending on the derangements, metabolic acidosis, neurogenic pulmonary

↑seizure threshold ↓seizure threshold Induction agents Thiopentone (infusion>bolus)6 Etomidate Propofol7 Ketamine Benzodiazepines5 Midazolam Lorazepam, etc. Anaesthetic gases and vapors Isoflurane Nitrous oxide Desflurane Enflurane8

Sevoflurane (esp. paediatric patients with ↑Fisevo 9 and ↓PaCO2) Muscle relaxants5 Benzylisoquinolones (atracurium metabolite: laudanosine) Analgesics5 Alfentanyl Remifentanyl Morphine Pethidine (metabolite: nor-pethidine) Local anaesthetics (All agents cross the blood brain barrier and have potential to cause seizures, esp. in toxic doses.)

S82 2017 FCA 2 Anaesthetic Refresher Course 83 oedema, etc.12 Due to their non-specific nature, a high index of References suspicion is required for patients presenting with these signs 1. Commission on Classification and Terminology of the International League against Epilepsy. Proposal for revised classification of epilepsies and epileptic under anaesthesia. syndromes. Epilepsia. 1989;30:389-99. 2. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for 3. Postoperative organization of seizures and epilepsies: report of the ILEA Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010;51:676-85. Following anaesthesia, all patients should be monitored in the 3. Kofke WA. Anaesthetic management for the patient with epilepsy or prior seizures. Current Opinion in Anaesthesiology. 2010;23:391-9. recovery room until they are fully recovered and fulfill criteria 4. Kofke WA. Anaesthetic implications of epilepsy, status epilepticus and epilepsy for recovery room discharge. Patient safety is of paramount surgery. J Neurosurg Anaesthesiol. 1997;9(4):349-72. importance. As such, patients should be recovered on stretchers 5. Perks A, Cheema S, Mohanraj R. Anaesthesia and epilepsy. Br J Anaesth. 2012;108(4):562-71. with secure sides to prevent falls from height. Patients with 6. Lowenstein D, Aminoff M, Simon R. Barbiturate anaesthesia in the treatment epilepsy should be discharged from the recovery room of status epilepticus: clinical experience with 14 patients. . 1988;38:395-400. with reliable vascular access for use should a seizure occur 7. Power KN, Flaatten H, Gilhus NE, Engelsen BA. Propofol treatment in adult postoperatively. In addition, recovery room and ward availability refractory status epilepticus. Mortality risk and outcome. Epilepsy Res. 2011;94:53-60. of benzodiazepines and other anticonvulsants should be 8. Kruczek M, Albin MS, Wolf S, Bertoni JM. Postoperative seizure activity following ensured. enflurane anaesthesia. Anaesthesiology. 1980;53:175-6. 9. Constant I, Seeman R, Murat I. Sevoflurane and epileptiform EEG changes. Patients with well controlled epilepsy may be considered for Paediatric Anaesthesia 2005;15:266-74. 10. Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: day case procedures provided they are adequately supervised interactions between antiepileptic drugs and other drugs. Lancet Neurology. and have easy access to the emergency department should 2003;2:473-81. 11. Anderson J, Moor CC. Antiepileptic drugs: a guide for the non-neurologist. a problem arise. If there is any doubt, overnight postoperative Clinical Medicine. 2010;10:54-8. admission for observation is recommended. 12. Kelso ARC, Cock HR. Status epilepticus. Practical Neurology. 2005;5:322-33.

S83 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Neonatal eye surgery

K L Borrill

Private Practice, Johannesburg Correspondence to: [email protected]

Introduction chromosomal or metabolic disorders, as well as a history of exposure to congenital infection or premature birth. As the primary organ of vision, the eye is an embryological extension of the nervous system. As a result, it shares many Airway management common anatomical and physiological properties with the Although the airway is not strictly shared, draping of the surgical brain.1 The globe itself occupies about one fifth of the orbital field frequently restricts access to the airway. It is therefore volume, the remainder of the space being taken up by extra- ocular muscles, fascia, fat, blood vessels, nerves and the lacrimal recommended that neonates be intubated and ventilation gland.1 Ophthalmic procedures are commonly divided into intra- controlled, except for the shortest of procedures. and extra-ocular surgeries. Intra-ocular procedures encompass Furthermore, a number of syndromes in which there can be those performed on or within the globe, while extra-ocular major difficulties with intubation are associated with cataracts, surgeries are those involving the tissues surrounding the globe, glaucoma or squints. These include the mucopolysaccharidoses, within the orbit. This distinction has important anaesthetic the craniosynostosis disorders (e.g. Crouzon’s, Apert’s and Pfeiffer’s implications. syndromes) and the craniofacial syndromes (e.g. Goldenhar, Types of Surgeries Treacher–Collin and Smith–Lemli–Opitz). The Hallerman–Strieff syndrome, although rare, may present for cataract surgery in the While elective ophthalmic surgery is common in the paediatric neonatal period and invariably is associated with a particularly population, the relative complexity and risk of neonatal difficult airway. Stickler’s syndrome, which is associated with early anaesthesia and potential threat to the developing brain retinal detachment and glaucoma, is a progressive connective preclude surgery in the neonatal period unless a delay in tissue disorder that has some of the features of the Pierre Robin intervention will worsen outcome. sequence; it can also present intubation problems.3 Difficulties in Ophthalmic procedures requiring anaesthesia in the neonatal airway management in these patients should be anticipated and population most commonly include cataract extraction, necessitate a clear plan of action prior to initiating anaesthesia. treatment of congenital glaucoma, examination under Intra-ocular pressure anaesthesia and treatment of retinopathy of prematurity. Normal intra-ocular pressure (IOP) is 10–22 mm Hg. The factors Infants and children frequently present for the following surgeries: strabismus, trauma and lacrimal, vitreo-retinal and that affect IOP are essentially the same as those that affect oculo-plastic surgeries. intracranial pressure. The main factors involved in the regulation of IOP are the choroidal, aqueous and vitreous volumes together Anaesthetic Implications with external pressure.2 Sudden changes in intra-ocular pressure Apart from the anaesthetic concerns and considerations relating may affect measurements, or result in expulsion of ocular to all neonates undergoing anaesthesia, there are some specific contents or haemorrhage. The following strategies should be implications for ophthalmic surgery: employed in an attempt to maintain innate pressures: • Choroidal volume: As venous drainage from the eye is Pre-operative assessment valveless, any cause of raised venous pressure will impede While most children scheduled for ophthalmic surgery are ASA aqueous drainage via the Canal of Schlemm. A 15° head-up tilt class I or II, eye abnormalities in the neonatal population are more should be employed to reduce IOP,2 while coughing, straining frequently manifestations of multisystem disorders.2 Particular and retching should all be avoided. Mean arterial pressure and attention should be paid to the possibility of concomitant PaCO2 should also be maintained constant.

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• Vitreous and aqueous volumes may be affected by the use of Another related reflex, the blepharocardiac reflex (BCR) may be osmotic diuretics and carbonic anhydrase inhibitors, but are elicited by stretching of the eyelid muscle during the placement generally of little significance to anaesthesia. of an eyelid retractor.8 Similar pathways and treatment to the • External pressure: Direct pressure should be avoided. OCR are postulated. Investigation into a similar pathway in Increase in tone of the extra-ocular muscles will increase Sudden Infant Death Syndrome infants indicates that a vagal 9 IOP. Depolarizing muscle relaxants, such as suxamethonium, hypersensitivity may be, in part, hereditary. therefore, cause an increase in IOP. The rise produced by Bacterial endocarditis prophylaxis suxamethonium is maximal at 2 minutes after administration and lasts for 5 minutes. Pretreatment with non-depolarizing The majority of ophthalmic procedures do not produce a muscle relaxants to prevent this effect has been advocated but bacteraemia, the exception being any instrumentation of the nasolacrimal ducts. Those undergoing such surgeries is of unproven value.2 with a susceptible cardiac lesion should receive appropriate Accurate measurement of IOP is essential in the case of suspected prophylaxis. glaucoma. Currently available anaesthetic agents, with the Pharmacological implications exception of ketamine, reduce IOP. The extent of this reduction is unknown and not reproducible, even in the same individual. • Effect of drugs used by surgeons: Topical mydriatic agents This effect can lead to misleading readings of IOP, which has a are frequently administered preoperatively for pupillary detrimental effect on treatment.2 Ketamine has been shown dilatation. Should the effect be insufficient, a repeat dose may to cause only a transient rise in IOP, which can be eliminated be given intraoperatively. While usually well-tolerated, severe side-effects such as hypertension and pulmonary oedema with the use a benzodiazepine as premedication.2 A falsely high may ensue, especially if injected subconjunctivally. reading is preferable to a missed diagnosis. • Anaesthetic drugs that may influence surgical concerns: Cardiorespiratory reflexes ▫▫ Propofol, thiopentone: IOP reduced by 20–30% The oculo-cardiac reflex (OCR) is defined as a 10–30% decrease in ▫▫ Inhalational agents: IOP reduced by 20–30% heart rate from baseline.3 ▫▫ Opioids: Minimal to no effect on IOP Increased IOP (pressure on the globe) or traction on the extra- ▫▫ Ketamine: Minor rise in IOP, marked if dose greater than ocular muscles, particularly the medial rectus, or less commonly 5 mg/kg, can be eliminated by premedication with trauma or pain, invoke a bradycardia via the trigemino-vagal benzodiazepine pathway. Interruption of the stimulus usually results in resolution ▫▫ Non-depolarising muscle relaxants: Minimal to no effect but if left untreated, it may quickly progress to asystole. Other on IOP arrhythmias such as nodal rhythms and ventricular fibrillation ▫▫ Depolarising muscle relaxants: Marked rise in IOP, 2 can also occur. Intravenous atropine 20 μg/kg or glycopyrrolate sustained for 5–7 minutes, can be reduced by pre- 10 μg/kg at induction of anaesthesia or presentation of a treatment with non-depolariser bradycardia will block the OCR. These can be repeated at any ▫▫ Nitrous oxide: no effect on IOP, may diffuse into surgically- time during surgery if the OCR recurs, so it is important to have created gas bubble – avoid in vitreoretinal surgery. the drugs available and ready to use if bradycardia ensues. The reflex can also be counteracted by application of topical local Analgesia anaesthetic eye drops such as tetracaine, or by blocking the While pain is a subjective experience, infants and even premature afferent limb of the reflex with a peribulbar block, which is not neonates possess the basic pathways and nociceptors necessary commonly used in paediatric patients due to the risk of globe for pain perception.10 Most ophthalmic operations performed in perforation.3 neonates, however, are not particularly painful, and only simple OCR has been shown to occur less commonly with sevoflurane analgesia in the form of paracetamol and non-steroidal anti- than with halothane, but is more likely with the use of rocuronium inflammatory drugs, with or without the use of local anaesthetic, 2 than atracurium.4,5 Hypercarbia doubles the incidence of is necessary. significant bradycardia, so controlled ventilation should be Postoperative apnoea employed. In older children, postoperative nausea and vomiting (PONV) has been shown to be more likely to occur in paediatric Immature respiratory control predisposes neonates to apnoea, 11 patients who experience OCR during surgery.6 oxygen desaturation and bradycardia. Risk factors include a postconceptual age of less than 50 weeks in a term infant Extraocular muscles manipulation can also provoke an or 60 weeks in a prematurely-born infant, a history of apnoeic oculorespiratory reflex (ORR) which results in reduction in tidal episodes, concomitant anaemia, hypothermia, sepsis, metabolic volume and respiratory rate.7 Consequent hypercarbia and derangements and the presence of cardiac anomalies, as well hypoxemia may occur, which in turn increase the risk of OCR.3 as exposure to general anaesthesia, muscle relaxation and The ORR shares the same afferent pathways as the OCR which opiates. Apart from modifying those risk factors where possible, relays to the brainstem respiratory control centre, while the pharmacological prophylaxis can be given in the form of efferent pathways are mediated by the phrenic nerves. Caffeine 10 mg/kg or Aminophylline 5 mg/kg per os two hours

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preoperatively. Postoperatively, infants should be transferred The infant is then fed and swaddled and it is hoped that the to a monitored environment, with a minimum of an apnoea infant will sleep through/tolerate the procedure awake. While detection mat until they are at least 24 hours apnoea-free. certainly providing the safest conditions from a postoperative point of view, failure of this technique results in an unstarved Retinopathy of Prematurity child, rendered unsuitable to progress to sedation or general Retinopathy of prematurity (ROP) is a proliferative disorder of anaesthesia. the immature retinal vasculature.12 Classified into five stages, • Sedation: this can be performed in theatre or in a remote the most severe can result in retinal detachment and total and setting. Various combinations of drugs can be used. This irreversible blindness if left undetected and/or untreated. technique carries the same risks as a general anaesthetic with less control and increased propensity to complication. It is not The normal retina begins to vascularise at about sixteen weeks recommended. gestation and is usually complete one month after birth (or • General anaesthesia: This should be performed in a fully- 44 weeks postconceptual age). This process is mediated by high equipped and prepared theatre environment. A mask and levels of Vascular Endothelial Growth Factor (VEGF) in a relatively spontaneous ventilation technique can be employed if the low oxygen (intrauterine) environment. Exposure to increased procedure is anticipated to be particularly short. The shared oxygen concentration, whether under normal circumstances work space can complicate matters should difficulties arise or (term healthy infant birth) or supplemental (premature if the procedure goes on longer than anticipated. As a result, infant with underdeveloped cardiorespiratory system), the safest modality would be to intubate the infant and control VEGF production decreases and retinal development slows. ventilation for the duration of the procedure. It should be Insufficient vascularisation of the developing retina conversely borne in mind that oxygen fluctuations are thought to be the results in a localised hypoxia, which precipitates the release of greatest modifiable contributor to the process and fractional factors stimulating new and abnormal blood vessel growth.13 inspired oxygen content sufficient to maintain oxygen Similarly, Insulin-like Growth Factor (IGF-1) prevents normal saturation of 88–92% should be targeted. General anaesthesia vessel growth when insufficient, but promotes unchecked will marginally increase intervention time relative to the other neovascularisation in excess. options and necessitates the availability of theatre space, but is the preferred modality if resources allow. It is thought that fluctuations in arterial oxygenation place the infant at a higher risk than the amount and duration of oxygen References delivery. 1. Galloway NR, Amouku WM, Galloway PH, Browning AC. Common Eye Diseases and Their Management. Springer; 2006. Apart from premature birth, other risk factors for ROP include 2. Lord J. Anaesthesia for Eye Surgery in Paediatrics. Anaesthesia and . 2007;8(9):393-6. multiple births, maternal preeclampsia, intrauterine growth 3. Ahmed D. Updates in Paediatric Ophthalmic Anaesthesia. Anaesthesia, Pain and restriction, mechanical ventilation, need for blood transfusion, Intensive Care. 2014[18(1):28-78. the presence of a patent ductus arteriosus, intraventricular 4. Gayer S, Tutiven J. Anesthesia for Pediatric Ocular Surgery. Ophthalmol Clin haemorrhage, pulmonary insufficiency, male gender13 and North Am. 2006;19:269-78. infants conceived through assisted reproductive therapy. 5. James I. Anaesthesia for Paediatric Eye Surgery. Continuing Education in Anaesthesia, Critical Care and Pain. 2008;8:5-10. Conduct of Anaesthesia 6. Allen LE, Sudesh S, Sandramouli S, Cooper G, McFarlane D, Willshaw HE, et al. The Association Between the Oculocardiac Reflex and Postoperative Vomiting in Children undergoing Strabismus Surgery. Eye (Lond).1998;12:193-6. These infants frequently present for anaesthesia, for both 7. Allison CE, De Lange JJ, Koole FD, Zuurmond WW, Ros HH, Van Schagen NT, et diagnostic and therapeutic purposes. Screening is mandatory in al. A Comparison of the Incidence of the Oculocardiac and Oculorespiratory all high risk patients. Commonly performed in a clinic setting, the Reflexes during Sevoflurane or Halothane Anesthesia for Strabismus Surgery in Children. Anesth Analg. 2000;90:306-10. use of an eye speculum is the most common source of pain. 8. Johnson RW. Anaesthesia for Ophthlamic Surgery. Current Anaesthesia & Critical Treatment options include cryotherapy or laser photocoagulation Care. 1992;3(1):17-22. (modality of choice) in its less severe stages, and vitreoretinal 9. Khan A, Riazi J, Blum D. Oculocardiac Reflex in Near Miss for Sudden Infant Death Syndrome Infants. . 1983;71(1):49-52. 12 surgery when more severe. Infants frequently require repeat 10. Hertel SA. Do Neonates and Small Infants Feel Pain? Nord Med. interventions every 10–14 days. While surgical intervention 1995;110(11):273-4. will require a general anaesthetic with controlled ventilation, 11. Sale SM. Neonatal Apnoea. Neonatal Anaesthesia, Best Practice & Research Clinical Anaesthesiology. 2010;24(3):323-36. laser- and cryotherapy can be performed under various 12. McCrory C, McCutcheon K. Retinopathy of Prematurity: Causes, Prevention and anaesthetic techniques. Bearing in mind the complexity of Treatment. Br J Midwifery. 2016;24(9):631-4. neonatal anaesthesia and the risk to the infant both intra-and 13. Smith LEH. Pathogenesis of Retinopathy of Prematurity. Seminars in Fetal and postoperatively, the following options are available: Neonatal Medicine. 2003;8(6):469-73. 14. Owen L, Morrison M, Hoffman R, Yoder B, DeAngelis M. Retinopathy of • Local anaesthesia: topical anaesthesia and a mydriatic agent Prematurity: A Comprehensive Risk Analysis for Prevention and Prediction of are applied to the eyes one to two hours prior to intervention. Disease. Public Library of Science One. 2017. p. 1-14.

S86 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Conventional cardiopulmonary bypass and mini-cardiopulmonary bypass

M E A Kemp

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

This is a review of the underlying basic concepts of cardiopulmonary bypass and mini-cardiopulmonary bypass, with a focus on the complications related to cardiopulmonary bypass and whether these complications can be reduced with the use of mini-bypass techniques.

Keywords: conventional cardiopulmonary bypass, mini-cardiopulmonary bypass, comparison, complications

Introduction Fick’s law: Volume of gas diffused α

The concept of a mechanical method of taking over the function Area x Diffusion Constant x Partial Pressure of the heart and lungs dates back to the work of Von Frey in 1885, Membrane Thickness but the technique required the discovery of heparin in order to become feasible. The earliest successful open heart operation Blood Pumps took place in 1953, when John Gibbon repaired an atrial septal Blood flow across pumps follows Hagen-Poiseuille’s law: defect in a young woman. In 2005, according to the American Heart Association,¹ nearly 500 000 coronary artery bypass grafts Blood flow = Pressure gradient x Tube radius x π and nearly 110 000 heart valve replacement surgeries were Fluid viscosity x Tube length x 8 performed using cardiopulmonary bypass in the United States alone. Roller pumps are commonly used – a length of polyvinylchloride (PVC) tubing is compressed against a curved metal backing Principles of conventional Cardiopulmonary Bypass plate by two rollers located on the ends of two rotating arms. (c-CPB)² This allows constant delivery of blood volume, even with minor In essence, blood from the patient, via one or two venous variations in afterload (resistance). Roller pumps are positive catheters (usually in the right atrium or the superior and inferior displacement devices and are occlusive – the tubing is partially vena cavae), drains by means of a gravity siphon into a venous occluded with each cycle of the rotating arms. reservoir. The blood then passes through an oxygenator, a pump Other components of the c-CPB circuit and an arterial filter, and is then returned to the aorta of the patient via an aortic catheter. Heat exchangers allow manipulation of the temperature of the perfusate and of body temperature. Oxygenators A cardioplegia roller pump delivers a potassium rich solution to All oxygenators now used are of a membrane type – the the coronary circulation in order to arrest the heart in diastole. membranes can be flat or spiral and are composed of polypropylene, which has micropores (0.05–0.3 μm), or silicone, Cardiac drainage roller pumps are used for active removal of which is a ‘true’ membrane. Polypropylene membranes allow blood from heart – the “aortic sucker” and the “left ventricular leakage of plasma over time with prolonged bypass. vent”. This blood is often returned into the bypass circuit without washing or filtration. Gas exchange with extra-corporeal oxygenators occurs with Deleterious effects of c-CPB the same physical principles (convection, diffusion, chemical reaction) as natural gas exchange does, but they are always less While c-CPB is necessary for many “open heart” operations, efficient than functional lungs because the diffusion distances the rate of postoperative morbidity and mortality in patients are greater (200 μm vs 10 μm) and the surface area is considerably undergoing c-CPB is relatively high – up to one third of less (1.7–3.5 m² vs 70–100 m²). patients undergoing coronary revascularization have undesired

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effects including cardiovascular instability, arrthymias, renal Activation of complement has been shown to be linked to dysfunction, lung dysfunction and cerebral dysfunction.³ The postoperative morbidity. 30 day mortality after cardiopulmonary bypass is usually quoted The late phase reaction is possibly related to an ischaemia- as 1.5–2 %.⁴ reperfusion type injury, to the presence of endotoxaemia, to Haemodilution coagulation disorders and to heparin-protamine reactions.

The average priming volume (to remove air and wet the Late phase SIRS reactions involve leucocyte dependant and surfaces of the tubing) of a conventional adult c-CPB circuit leucocyte independent pathways, with neutrophil-endothelial is approximately 2 000 ml. The circuit can be primed with a reactions, formation of reactive oxygen species, cytokines and balanced crystalloid solution, colloids, blood, plasma, or with a arachidonic acid metabolites. The sources of endotoxaemia combination of these fluids. are diverse, but there is usually significant splanchnic vessel vasoconstriction during c-CPB, with increases in intestinal In practice, this means that there is always haemodilution of permeability. the patient’s blood, particularly if the circuit is primed with crystalloid. While the associated reduction in fluid viscosity Induction of Nitric Oxide Synthetase (NOS), and the resultant improves flow through the pump, the resultant decrease in elevated nitric oxide levels caused by bypass, has been implicated haemoglobin concentration, together with the potential risk of in the development of the vasoplegic syndrome that can occur large amounts of intra- and postoperative blood loss, causes an post-bypass. increased risk of blood transfusion perioperatively.⁵ Factors that influence the inflammatory response to c-CPB include: The incidence of transfusion intra and post cardiac surgery varies • Preoperative factors, such as renal dysfunction and diabetes – considerably, but up to 50% of patients undergoing cardiac it is postulated that the inflammatory response is different and bypass require blood products. It is also well established that that oxidative stress is increased in diabetics.⁹ morbidity and mortality increases when haematocrit levels fall • Perioperative haemodynamic factors that are postulated to below 19% on bypass and when blood transfusion is required influence the SIRS are low cardiac output states, splanchnic after cardiac surgery.⁶ Blood transfusion itself is associated with hypo-perfusion, anaesthesia drugs and techniques, and lung an increase in in-hospital mortality, increased use of intra-and management strategies during CPB. postoperative intra-aortic balloon pumps, increased risk of • Surgical factors that play a role in the SIRS associated with bleeding and strokes, and an increased risk of repeat CPB runs. cardiac surgery include the type of incision or approach of the surgery; the duration of surgery and the use of the cardiotomy Haemolysis sucker with return of mediastinal blood (potentially containing The action of the occluding roller pumps causes mechanical fat and debris) to the circulating blood.¹⁰ damage to red blood cells, resulting in free haemoglobin and • The factors related to the c-CPB circuit itself that are believed the levels of this rise proportionately with the length of bypass to be responsible for the SIRS include biomaterial dependant time. Free haemoglobin is associated with an increased risk of factors, such as the tubing of the extra-corporeal circuit, the renal dysfunction.⁷ oxygenator and damage to blood components caused by pumps.¹¹ Biomaterial independent factors include the type of Activation of the systemic inflammatory response priming solution, the volume and type of the cardioplegia, the The inflammatory response occurs in the presence of stress and presence of non-pulsatile blood flow, and the return of fat and is necessary for recovery. It is therefore not limited to patients debris containing blood from vents into the circulation. undergoing c-CPB. However, there is strong evidence⁸ that both • Postoperative factors such as the type and length of open heart surgery and c-CPB techniques can provoke a marked mechanical ventilation and organ support strategies probably Systemic Inflammatory Response Syndrome (SIRS) that involves also contribute to the reaction. all components of the inflammatory and coagulation systems. According to Durandy,¹⁰ the aim of interventions regarding the This SIRS is believed to be the cause of much of the post- SIRS should be to modulate the systemic inflammatory response operative morbidity and mortality associated with CPB because so that excessive inflammation is controlled, while preserving a it causes temporary and permanent organ dysfunction (cerebral, level of inflammation necessary for host defences and healing. renal, lung, cardiovascular). Myocardial Damage No consensus has yet been reached on the exact pathophysiology of this SIRS. The cause is almost certainly multi-factorial, with the Myocardial ischaemic and reperfusion injuries are associated reaction divided into “early” and “late” phases. with the use of CPB. In particular, levels of Platelet Activating Factor are increased and this is implicated in compromised The early phase probably results from contact of blood with non- haemodynamic function post-bypass.⁸ physiological surfaces (the polyvinylchloride tubing of the CPB circuit, air in the venous reservoir), causing contact activation of Interventions that can potentially limit the both cellular components, such as endothelial cells, neutrophils, complications of CPB¹¹ lymphocytes and platelets, as well as humoral components, such • The use of off-pump surgery and minimally invasive surgical as the clotting factors, complement and activation of fibrinolysis. techniques.

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• Drugs that limit inflammation have been studied. At present, no Differences between c-CPB and m-CPB single intervention on its own demonstrates strong evidence Mini-cardiopulmonary bypass Conventional cardiopulmonary for limiting adverse outcomes as a result of manipulation of bypass the systemic inflammatory response.¹¹ Venous cannula, usually one. Usually two venous cannulae. Size 29 F, multistage, longer length Size: 34-36 F. A Cochrane database review¹¹ revealed no clinical benefit on Rigid and less prone to collapse Convenient and usually easy to mortality, cardiac or pulmonary outcomes with the use of but requires careful placement as place correctly corticosteroids, although there is also little evidence of harm. it extends down into the inferior vena cava Many other pharmacological attempts to limit SIRS, including Venous line drainage: 3/8 inch. Venous line drainage: ½ inch. Complement C 5 inhibitors, propofol, neutrophil elastase Use of active kinetic drainage Gravity siphon drainage, (suction) to drain blood, which uncontrolled. inhibitors, propionyl-carnitine, intensive insulin therapy, has to be tailored to the individual Excessive negative pressure not nitric oxide donors, preoperative aspirin and fluvostatin patient’s “collapse” pressure. usually a problem so that venous have not conclusively shown to provide any clinical benefit. A venous air filter is required filters not required. because of risk of aspirating air. Venous reservoir must be below the level of the patient’s heart. • CPB (Perfusion) related strategies Venous reservoir not present. Circuit Venous reservoir is present, system Many studies of the perfusion related strategies to reduce is therefore closed and extra volume is open, and fluid can be added to cannot be added. the circuit. complications due to c- CPB are limited by small sample sizes and differing end point selections. Overall, clinical benefits are Blood is exposed to air in reservoir. difficult to prove.¹²,¹³ Blood from the operating field is Vented blood returned directly 1. The use of biocompatible (usually heparin coating) of not returned to the bypass circuit; into the CPB circuit, often without c-CPB circuits has become routine. instead it returns to a cell salvage processing system, where it can be processed 2. Leucocyte depleting filters and ultrafiltration of the and returned to the circulation perfusate have been shown to have some benefit in small intravenously. children undergoing CPB but not in adults. Arterial side: Arterial filter required Gas-micro emboli (GME) detector 3. Pericardial blood processing or discarding of mediastinal and filter required blood does reduce inflammatory markers in some studies Prime volume 700–800 ml (adult). Prime volume 2 000 ml (adult). but, as usual, the clinical benefit is not so easily proven. Significant reduction in circuit blood Circuit blood contact surface area: contact surface area: 1.4–2 m² 4 m² 4. Miniaturized Cardiopulmonary Bypass Circuits (Mini- Biocompatible coating ( usually cardiopulmonary bypass). heparin) Biocompatible coating ( usually heparin) Miniaturized Cardiopulmonary Bypass Circuits Advantages of m-CPB (Mini-cardiopulmonary bypass)¹⁴ Reduction of haemodilution Mini-cardiopulmonary bypass (m-CPB) refers to a variety of novel adjustments to c-CPB circuits that have a common, shared It is generally accepted that blood transfusion requirements philosophy that includes: in adults⁴,¹⁵ are up to 33% less with m-PCB compared to c-CPB, • The use of a centrifugal pump instead of a roller pump. almost certainly as a result of the decrease in priming volume. In low body weight neonates,¹⁶ m-CPB was also associated with Centrifugal pumps use a vane impeller within a plastic casing lower blood transfusion rates and a lower incidence of post- that is magnetically coupled at the base to an electric motor, operative extra-corporeal membrane oxygenation (ECMO) which, when rotated rapidly, generates a centrifugal force support. On bypass, when haematocrit levels were similar, there which is transmitted to the blood within the pump. This is then was no difference in oxygen delivery between the two systems. converted into kinetic energy, producing flow. Centrifugal pumps are therefore not occlusive and cause less damage to Mini-CPB was also associated with less desaturation⁵ as cellular components in the blood. They are, however, afterload measured by cerebral oximetry and with better neurocognitive dependant to a greater degree than roller pumps. function in adults at time of discharge, but a meta-analysis¹⁶ of • Elimination of the venous reservoir in order to reduce circuit nine randomised control trials revealed no difference in overall morbidity and mortality between c-CPB and m-CPB. length, with the aim of limiting haemodilution and decreasing the volume and surface area of the circuit in contact with Haemolysis the blood. This requires that venous blood must be actively CCPB¹⁶,¹7 was associated with an increase in free haemoglobin drained from the body. levels and a decrease in leucocyte count as compared to m-CPB. • Cardioplegia is usually given via a separate roller pump that is Retrospective analyses comparing m-CPB with c-CPB reveal connected to the arterial side of the CPB circuit. that m-CPB was associated with a shorter intensive care stay, a • The mediastinal blood does not return to the circuit but is lower incidence of atrial fibrillation and ventricular arrhythmias, processed via cell salvage techniques and infused separately. a lower postoperative serum creatine and bilirubin level, and less

S89 90 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) postoperative blood loss; but in- hospital mortality did not differ Mini-Cardiopulmonary Bypass vs Conventional between the two groups Cardiac Bypass: Which technique is superior?

Reduction of the Inflammatory Response to Bypass³,¹⁵ In a best evidence review,¹⁵ 144 papers were found on the comparison of c-CPB to m-CPB. A review of the literature reveals that six out of fourteen randomised controlled trials that attempted to assess the effect of Of these, fourteen articles, with a database of 100 patients, m-CPB on markers of inflammation showed clinical significance were believed to show the best evidence to answer the clinical in that inflammatory markers were reduced; however, there question of which technique was superior. was no clear linkage between suppression of inflammation and The results were as follows: clinical outcome. No of Studies ( n = 14) Result Generally speaking, the literature in this regard is poor and 10 Reduced haemodilution meta-analysis is limited by small sample sizes and differing 7 Reduced transfusion requirements 2 Reduced fresh frozen plasma requirements endpoints (traditional endpoints such as death or stroke versus 3 Reduced Intensive Care Stay suppression of inflammation) so that, at present, the evidence 3 Reduced postoperative blood loss base is insufficient to recommend clinical practice with regard to 3 Improved renal function use of m-CPB to reduce inflammation with the aim of improving 4 Better Cardiac Output Index clinical outcomes. 6 Reduced inflammation markers

What is apparent in all the trials comparing m-CPB with c-CPB is Conclusion that m-CPB is as safe as c-CPB. Cardiopulmonary bypass has become an essential adjuvant Myocardial protection⁴ to cardiac surgery but is associated with significant morbidity related to haemodilution of blood volume, damage to blood cell Cardiac specific enzymes suggestive of myocardial damage were components, myocardial damage, and activation of the systemic noted in a study to be lower in patients undergoing m-PCB as inflammatory response with associated organ dysfunction. compared to conventional bypass.¹⁴,¹⁵ Mini-CPB is more expensive and complex to run, although the Limitations of m-CPB literature shows that it is at least as safe as c-CPB. • Mini-CPB requires increased technical prowess, awareness, participation and co-operation from the members of the Mini-CPB shows considerable potential for limiting the degree cardiac team for success. There is a relatively long learning of haemodilution and haemolysis associated with bypass. There curve for surgeons, perfusionists and anaesthetists for using appears to be some evidence that that inflammatory response m-CPB, with many studies estimating that at least fifty bypass associated with bypass is reduced and some of the shorter runs are required to gain competence. term adverse outcomes associated with this do appear to be improved with its use. As yet, the overall morbidity and mortality • There is a risk of micro air bubble formation as a result of venous associated with CPB appears to be similar with both types drainage by suction. Spontaneous formation of microbubbles of bypass techniques. However, the evidence base for these is associated with excessive negative pressure in the venous assumptions is limited. limb of the circuit and this can be transmitted to the left side. In one study,¹⁸ the measured volume of arterial air bubbles in References an m-CPB was 1522 +- 654 μml compared with 4.1 +- 2.5 μml 1. www.health247.com; www.texasheart.org>Topics>Proceed for c-CPB. Mini-CPB requires a special GME filter on the arterial 2. Machin D, Allsager C. Principles of Cardiopulmonary Bypass. Cont. Educ. Anaesth. Crit. Care Pain. 2006;6(5):176-180. doi: https://doi.org/10.1093bjaaccp/ side of the m-CPB circuit. mk/043 • Managing volume status can be challenging because the 3. Baikousisis NG, Papakonstatinou NA, Apostalikis E. The “benefits’ of the perfusionist cannot add to or use the venous reservoir to mini-extra-corporeal circulation in the minial invasive cardiac surgery era. Journal of Cardiology. doi: http://doi.org/10.1016/j.jcc.2013.12.04 compensate for inadequate venous return. Blood lost from the 4. Curtis N, Vohra HA, Ohri SK. Mini extracorporeal circuit cardiopulmonary bypass operating field is salvaged, processed and must be returned system: A review. Perfusion. May 2010;25(3);115-24. intravenously. Some surgeons using m-CPB still prefer to 5. Bennett MJ, Weatherall M, Webb G, et al. The impact of haemodilution and use c-CPB when performing complex procedures with bypass pump flow on cerebral oxygen desaturation during cardiopulmonary bypass – A comparison of two systems of cardiopulmonary bypass. Perfusion. Jul considerable risks of bleeding, and most of the trials using 2015;30(5):384- 94. m-CPB are performed for coronary artery bypass grafting 6. Murphy GJ, Reeves BC, Rogers CA, et al. Increased Mortality, Post-operative procedures. Morbidity and Cost After Red Blood Cell Transfusion in Patients having Cardiac Surgery. Circulation. 27 Nov 2007;116(32). • At Charlotte Maxeke Academic Hospital, the current cost of a 7. Barbosa-Evora PR, Bottura C, Sumarelli A, Albuquerque A. Key Points conventional oxygenator is approximately R5 600 and the cost for curbing Cardiopulmonary Bypass Inflammation. doi: http://dx.doi. of conventional tubing for the CPB circuit is approximately org/10/159050102-86502016001200010 R4 000. The cost of the oxygenator in the m-CPB circuit is 8. Landis RG, Brown JR, Fitzgerald D, Likosky DS, Shore-Lesserson L, Baker RA, et al. Attenuating the Systemic Inflammatory Response in Adult Cardiopulmonary approximately R10 000 and the tubing and filters cost about Bypass: A Critical Review of the Evidence Base. J Extracorpor. Technol. Sep R15 000. (Personal communication) 2014;46(3):197-211.

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9. Modi A, Ohri SK. The Inflammatory Response to Miniaturized Extra-Corporeal Adult Cardiac Surgery. Heart: Official Journal of the British Cardiac Society. Jun Circulation: A Review of the Literature. Mediators Inflamm. 2009;200:707042. 2009;95(12): 964-9. [Epub 2010] 15. Ranucci M, Isgró G. Minimally invasive Cardiopulmonary Bypass: Does it really 10. Durandy Y. Minimizing Systemic Inflammation during Cardiopulmonary Bypass change the outcome?. Crit.Care. 2017;11(2):R45. in the Pediatric Population. Artifi.Organs. Jan 2014;38(1):11-28. PMID 243928460. 16. Alevizou A, Dunning J, Park JD. Can a mini-bypass circuit improve perfusion in 11. Ferraris VH, Brown JR, Despolis GJ, et al. 2001 Update to the Society of cardiac surgery compared to conventional bypass? Interact Cardiovasc Thorac Thoracic Surgeons and the Society of Cardiovascular Anaesthesiologists Blood Surg. doi: https://doi:10.1510/icvts.2008.20083-7 Conservation Clinical Practice Conservation Guidelines. Ann Thorac Surg. March 17. Kim SY, Cho S, Kim WH. Effects of Mini-Volume Priming during Cardiopulmonary 2011;91:944-82. Bypass in Clinical Outcomes in Low Bodyweight Neonates: Less transfusion and Post-operative Extra-corporeal Membrane Oxygenation Support. J Artif Organs. 12. LiuG, Zeng QD, Wang GY, et al. Clinical Application of Modified Minial Jan 2016;40(1):73-9. Cardiopulmonary Bypass compared with Conventional Cardiopulmonary Bypass. Zhonghua Wai ke Za Zhi [Chinese Journal of Surgery]. 1 Aug 18. Anas A, Liebing K, Börgerman J, et al. Excessive Negative Line Pressures and 2016;54(8):613-6. Increased Arterial Air Bubble Counts during Miniaturized Cardiopulmonary Bypass: An experimental study comparing Miniaturized with Conventional 13. Alsatli RA. Mini-cardiopulmonary Bypass: Anaesthetic Considerations. Perfusion Systems. Eur J CardioThorac Surg. Jan 2014;45(1):69 -74. Anaesthes. Essays Res. Jan-June 2012;6(1):10-3. 19. Beghi C, Nicolini F, Agostinelli A, et al. Mini-Cardiopulmonary Bypass 14. Biancari F, Rimpilämen R. Meta-analysis of Randomized Trials comparing the System: Results of a prospective Randomized Study. Ann Thorac Surg. Apr Effectiveness of Miniaturized versus Conventional Cardiopulmonary Bypass in 2006;81(4):1396-1400.

S91 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Posterior fossa surgery

M M A Mashinini

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

This is a review of the underlying basic concepts of cardiopulmonary bypass and mini-cardiopulmonary bypass, with a focus on the complications related to cardiopulmonary bypass and whether these complications can be reduced with the use of mini-bypass techniques.

Keywords: conventional cardiopulmonary bypass, mini-cardiopulmonary bypass, comparison, complications

Introduction the brain with the rest of the body, the aqueduct of Sylvius and the 4th ventricle. Posterior fossa surgery, because of the location of the fossa, its contents and its volume, and the duration of surgery, presents Important foramina in the posterior fossa4 the surgeons and the anaesthesiologists with unique and • Foramen magnum: the fossa communicates with spinal canal significant problems. The most common surgical procedures via this foramen. Structures passing through are: spinal roots done are tumour excisions, correction of congenital and of the Accessory nerve, meningeal branches of the upper acquired craniovertebral junctional anomalies, e. g. Arnold– cervical nerves C1 to C3, meninges, and vertebral arteries Chiari malformation, and surgical procedures to relieve pressure ascending to supply the posterior part of the brain. on the brainstem, e.g. evacuation of cerebellar haematomas, and • Jugular foramina: internal jugular vein, glossophyrageal, vagus decompressive craniotomy to relieve pressure on the brainstem.1 nerve, accessory nerve About 60% of all childhood brain tumours2,3 and about 20% of adult brain tumours originate in the posterior fossa.2 • Hypoglossal canal: hypoglossal nerve • Internal acoustic meatus: facial nerve, vestibular nerve, Anatomical considerations nervous intermedius. The base of the skull is divided into anterior, middle and posterior Surgical pathology fossae. The posterior fossa is the largest and the deepest.4,5 The bony structures comprising the floor of the posterior fossa are: With reference to the 4th ventricle, the posterior fossa can sphenoid, occipital, temporal and the mastoid angle of the be divided into anterior and posterior compartments.6 parietal bone.5 There are two dural reflections in the posterior Histologically, all nervous system tumours can be broadly fossa, the tentorial cerebelli, which form the roof of the fossa divided into three groups: primitive neuroectodermal tumours separating it from the cerebral hemispheres. Between the (which occur in the brain, the sympathetic nervous system and anterior medial part of the right and left is an oval opening, the the eye, e.g. medulloblastomas, etc.), glial tumours (which arise tentorial incisura, which allows the brainstem to pass through from the supportive tissue of the brain or glia, e.g. astrocytomas from the middle to the posterior cranial fossa.4 and gliomas), and metastatic tumours.7

The venous drainage of the whole cranium passes through the Pathophysiology sinuses of the posterior fossa. The important venous sinuses in The location of the tumour in a particular area may give rise to a the posterior fossa are the right and left transverse sinuses which unique syndrome confined in that area, e.g. midline syndrome, join the sagittal sinus and the straight sinus to form confluence cerebellar hemisphere syndrome, ponto-cerebellar angle sinuses which leave the posterior fossa to continue as internal syndrome and brainstem syndrome.8 Depending on the location jugular veins.6 of the tumour, patients may present with a large variety of Contents of the posterior fossa6 clinical symptoms.

The lower part of the midbrain, Pons, Upper Medulla Oblongata, Intracranial Hypertension Syndrome is amongst the first Cerebellum, Reticular Activating System, 3rd to 12th cranial nerves elements of diagnosis. Even a slight increase affects the brain nuclei and many efferent and afferent fiber tracts that connect function in two ways: firstly, decrease in cerebral perfusion

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pressure leading to ischemia; secondly, it may cause herniation • Blindness can result from: pressure on the globe of the eye, of the brain substance, particularly the cerebellar tonsils and or ischemic optic neuropathy or retinal artery thrombosis nervous paths of the brainstem, impairing the brainstem`s vital associated with prolonged procedures in prone position in the functions coordinated at this level.8 absence of direct pressure on the eye and conjunctival edema. Significance of posterior fossa procedures • Venous pooling sufficient to lead to hypotension especially in the elderly debilitated patients. • Vital structures within the posterior fossa. • Incompatibility with cardio pulmonary resuscitation. • Confined space of the posterior fossa: even a relatively small lesion, haemorrhage or oedema in the vital areas may • Danger of necrotic lesions of the face areas and other points of exaggerate the neurologic consequences of the mass effects support due to uneven pressure distribution when head rests of lesion1; hydrocephalus due to obstruction of CSF flow are used. through aqueduct of Sylvius leads to increased ICP. Lateral position • Location and anatomy of the lesions complicating surgical access requiring unusual positions. It is used for unilateral positions, it improves surgical access by gravitational retraction of the cerebellum and drainage of the • Relatively long duration of surgery in extreme positions. CSF and blood from the operating field. • Increased propensity for development of hydrocephalus and or Venous Air Embolism(VAE). Park-bench: modification of the lateral position where the patient is positioned semi-prone with head rotated and neck flexed with Operating positions brow facing the floor. This gives greater access to the midline An ideal operating patient position should facilitate surgical structures when compared to lateral position and in selected access without compromising patient safety.9 Choosing one patients it avoids the need for the prone position. position over the other may be influenced amongst others by Disadvantages: the following8: • Peripheral nerve damage: brachial plexus injury if the arm • location of the tumour is pulled caudally to gain access to the retromastoid area, or • patient age nerve compression on the dependent side from pressure on • preexisting diseases and the patient`s physical status, the axillary or peroneal nerve at the knee. particularly in reference to cardiovascular and pulmonary • Venous engorgement and macroglossia. stability and airway manageability Sitting position • method of surgical approach • technical possibilities of monitoring. It provides optimal surgical access, particularly for the midline structures and the cerebellar pontine angle. Regardless of the position chosen, particular attention should be paid in positioning, as many problems can be avoided with Contraindications: careful positioning and padding of vulnerable parts. Absolute contraindications Supine position • Documented right to left intracardiac shunt, which would facilitate systemic embolization of air. In this position there is maximum rotation (up to 45 degrees can be achieved) # to the contralateral side and head up tilt or • Ventriculo-atrial shunt as air entry from the ventricles during reverse trendelenburg to improve venous drainage. It is used for surgery may migrate into the atrium. access of the lateral structures of the posterior fossa. Relative contraindications Disadvantages: • Include presence of Patent Foramen Ovale, uncontrolled • It is associated with reduced venous return from the brain with hypertension, extremes of age, severe autonomic neuropathy, a possible increase in ICP. severe hypovolemia, severe hydrocephalus, impaired cardiac function, degenerative diseases of cervical spine, significant • Extreme lateral rotation for a prolonged period can cause cardiovascular disease. macroglossia and peripheral nerve damage. Advantages: Prone position • Respiratory system: promotes favorable changes in ventilator Oldest and the most commonly used in posterior fossa surgery. It mechanics8: facilitates easy and optimal surgical access for both midline and ▫▫ Lower airway pressure, ease of diaphragmatic excursion lateral posterior fossa structures.8 ▫▫ Improved ability to hyperventilate. Disadvantages: • Although there is an increase in FRC, redistribution of blood • Amount of blood loss is much higher than in sitting position, due to gravity negates the effects of optimal oxygenation. especially if abdominal compression has not been avoided. There is no evidence of improved pulmonary function after • Difficult access to airway. sitting position.10

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• Cardiovascular system: it promotes drainage of blood and CSF ▫▫ contraction of intravascular blood volume associated with decrease ICP, intraoperative bleeding and transfusion with acute haemorrhage requirements. ▫▫ intraoperative slow continuous gravitational drainage of • Surgery: better surgical exposure, less tissue traction, less CSF in sitting position can result in accumulation of air in cranial nerve damage and a more complete resection of the subdural space.10 tumour possible.8 It can present in the postoperative period as a delayed recovery, • Monitoring: increase access to the ETT and thorax for neurologic deficit, headache, confusion, agitation or convulsions. monitoring, easy access to arms and other extremities for monitoring of fluid and blood administration and sampling. Treatment: high O2 flow reduces pneumocephalus; in severe • Visualization of face for observation of motor responses during cases, neurosurgical treatment. cranial nerve stimulation. • Macroglossia

Disadvantages and complications associated with sitting position: Extreme flexion of head with the chin resting on the chest • Hypotension and cerebral hypo-perfusion during prolonged surgery; prolonged presence of an oral airway leads to obstruction of venous and lymphatic drainage of the The hydrostatic effect of gravity produces a decrease in systemic tongue, airway obstruction, hypoxemia and hypercapnia in the arterial pressure because of venous pooling in the lower postoperative period, particularly in children.5 extremities.10 This may be aggravated by the depressant and • Venous Air Embolism (VAE) the vasodilatory effects of anaesthesia, which may reduce the compensatory response to hypotension, such as an increase VAE is a potentially life threating complication associated with in heart rate and an increase in systemic vascular resistance, all surgery in the steep head up position. The incidence of VAE accentuated by advanced age and associated comorbidities. varies from 25–75% during surgery in sitting position depending Intermittent positive pressure ventilation may contribute to this on the sensitivity of the monitoring used.5 However, it is thought hypotension by reducing the venous return. to be lower in children because the dural venous pressures are higher than in adults.12 It is more likely to occur when the surgical The impact of a decrease in Mean Arterial Pressure due to site is above the level of the heart. The other predisposing factor gravitational effects and anaesthesia may cause a decrease in is the presence of open and noncollapsible venous channels as it cerebral perfusion pressure (CPP) leading to an increased risk of may occur with major dural venous sinuses and diploic veins.11,13 cerebral ischemic damage. For each 2.5 cm increase in vertical height of the head above the level of the heart, there is a 2 mmHg In the sitting position, the site of surgery is above the level of reduction in CPP.10 the heart and this results in a negative venous pressure at • Quadriplegia with cervical spinal ischemia the level of the surgical wound (subatmospheric). A pressure gradient is established which facilitates the open veins to entrain Flexion of head on the neck causes stretching of the spinal atmospheric air into the circulation, resulting in VAE.11 In adults cord at C5 level (mid cervical) or a prolonged focal pressure on the lethal volume is thought to be between 200–300 ml or the spinal cord; regional cord perfusion may be compromised 3–5 ml/kg.14 Dehydration exacerbates the low venous pressure particularly during episodes of significant hypotension resulting and increases the risk of air entrainment.5 in ischemic damage to the spinal cord. Clinical features of VAE depend on the rate and volume of air Blood pressure should be measured at the level of the head entrained. The spectrum of manifestation includes cardiovascular because blood pressure measured at the level of the heart will and respiratory disturbances: grossly under estimate the perfusion pressure for the brain. For each 2.0 cm increase in vertical height of the head above the Cardiac manifestations: 10 level of the heart, leads to a 1.5 mmHg reduction in MAP. Massive air embolism produces abrupt and catastrophic • Pneumocephalus haemodynamic changes due to a large embolus obstructing the outlet of the right ventricle with a sudden onset of right heart It occurs when air enters the brain or spaces around the failure and cardiac arrest.14 This is a rare event. More commonly, brain after dural incision.10 If the volume is large, and this is the slow entrainment of air may produce little or no respiratory accompanied by other factors that cause cerebral oedema, tension pneumocephalus may occur with possible brain or haemodynamic compromise. However, as air is cleared to herniation. the pulmonary circulation, pulmonary vascular resistance, pulmonary artery and right atrial pressures increase, resulting Possible causes: various techniques used to reduce the volume in right sided heart failure, decreased left ventricular filling of the brain may encourage air entry into the intracranial space pressures and decreased cardiac output.5 Tachyarrhythmias and and when the cranial cavity is closed the brain expands, the air myocardial ischemia may ensue. is compressed causing a mass effect with elevated ICP.10,11 The condition is worsened by intraoperative use of N2O. Respiratory manifestations: ▫▫ diminution of brain volume secondary to mannitol The pulmonary vascular obstruction increases dead space administration and or hyperventilation ventilation, resulting in a decrease in end tidal carbon dioxide ▫▫ removal of space occupying lesion with an increase in arterial carbon dioxide tension.

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Hypoxemia may result from partially obstructed pulmonary Preanaesthetic assessment vasculature and the local release of vasoactive substances. Basic principles for assessment of general health for any How to minimize the risk neurosurgical operation. This would include: • Signs and symptoms relating to complications from the Use of trendelenburg tilt and leg elevation to minimize the posterior fossa lesion, cranial nerve palsies, localizing lesion for gradient between the surgical field and the right heart and the brain stem, and cerebellar and craniovertebral junctional optimise hydration. abnormalities which may influence airway management.16 Reduction of risk for development of VAE includes liberal use • Review of imaging of the brain to assess location and size of of bone wax, vigilance, avoidance of N2O and maximisation of the lesion, presence of hydrocephalus or increased ICP. intravascular space. • Sedatives and narcotics should be used cautiously, if needed. Acute treatment of VAE11 The consequences of respiratory depression like hypoxia and hypercarbia in a patient with low intracranial compliance may The surgical team should be notified to identify open sinuses be disastrous. which should be immediately closed surgically or covered with • The induction of anaesthesia and intubation should be gentle saline soaked swabs to prevent further air entrainment and any and smooth; the blunting of laryngoscopy and intubation suspected air entry point sealed with bone wax. response is standard practice. Increase venous pressure: • The significance of the disturbances, such as hyperdynamic response to laryngoscopy and intubation, is much higher If possible the surgical field should be positioned below the in patients with posterior fossa pathology due to decrease level of the heart (trendelenburg). Jugular venous pressure intracranial compliance leading to an increased ICP and compression may be considered as it reduces air entrainment possible ischemia or herniation with brainstem compression. but should be used with caution as it increases ICP and decreases CSF because of the simultaneous compression of the carotid Maintenance of anaesthesia artery. Use of PEEP (CONTROVESIAL). It may greatly increase the The selection of the appropriate anaesthetic agents in risk of hypotension in a patient who is already intravascularly neurosurgery depends on the risk factors inherent to the patient depleted.11 It will raise venous pressure, but also raise right and the procedure. atrial pressure and the possibility of opening a functionally closed foramen ovale, predisposing the patient to paradoxical Drugs used for maintenance should be able to provide the 17 air embolism.11,13 May be considered when all other attempts following : at preventing continuous VAE have failed. Discontinue N2O if in • Brain relaxation use. • Reduction of CMRO2

Support cardiovascular system: • Cerebral protection • Stable systemic and cerebral hemodynamics stability with Volume, Inotropes, vasopressors ease of titration Monitoring modalities for VAE • Preservation of cerebral autoregulation • Pre-cordial Doppler ultrasound: it is sensitive and noninvasive • Minimal effect on ICP (can detect 0.05 ml of air/kg or 0.015 ml/kg/min).15 The • Rapid awakening at the end of the procedure 14 drawback is the interference with the use of cautery. • Minimal effect on electrophysiological monitoring during • Capnography: it is convenient and available on most surgery anaesthetic machines – a change of 2 mmHg of EtCO2 can be • Maintenance of vascular reactivity to CO2 an indicator of VAE.14 Tiva vs inhaled anaesthetics (ia) • Mass spectrometry (End-tidal nitrogen detection): more sensitive than EtCO2 Neuroprotection is the cornerstone of anaesthetic 18 • Pulmonary artery catheter: can detect a rise in right heart management in neurosurgery. Two modalities are commonly pressures – most invasive and less sensitive than the Doppler. used in neurosurgery. Both modalities were found to have neuroprotective properties.18 • Pulse oximetry, clinical vigilance, oesophageal stethoscope, ECG – changes occur later. Total Intravenous Anesthesia (TIVA)

• Transoesophageal echocardiography: more sensitive but For our discussion it refers to a use of hypnotic, e.g. propofol, in 5 invasive and expensive. combination with an opioid, e.g. remifentanil, for anaesthesia Choice of anaesthetic technique induction and maintenance. Propofol favourable features19: Anaesthetic goals are to facilitate surgical access, minimize nervous tissue trauma and maintain respiratory and • potentiates GABAA receptor activity cardiovascular stability.5 • rapid onset of action and offset

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• neuroprotective effect during cerebral ischemia by facilitating early detection of changes in the brain prior to • lowering ICP, CBF, cerebral metabolism and cerebral oedema irreversible damage. It is indicated for monitoring of cranial effect nerve functions for microvascular decompression and tumors • improving cerebral perfusion pressure and MAP of the posterior fossa, thus minimizing the risk of permanent damage to the nerves.18 Evoked potentials monitoring • anticonvulsant properties includes somatosensory evoked potentials and motor evoked • preservation of autoregulation and vascular reactivity. potentials.26 Brainstem auditory evoked potentials are valuable Limitations of TIVA20: intraoperatively for the detection of auditory nerve and brainstem dysfunction, when hearing is at risk and when there is potential • need an experienced anaesthetist danger of damage to the brainstem.27 Electrophysiological • propofol use may lead to accumulation which may delay monitoring (EMG) is also used extensively during operative cases emergence to assist in identifying structures and to minimise facial weakness • prolonged propofol infusion has been associated with when dissecting near cranial nerves V and VII.28 Neuromuscular development of rhabdomyolysis, lactic acidosis and renal blocking agents may need to be avoided during the period of failure monitoring. • it may induce a substantial reduction of cerebral blood volume, leading to complications Effect of anaesthesia on electrophysiological monitoring • relatively expensive. All neuromuscular blocking agents cause depression of evoked potentials and prolongation of latencies.29,30 They are therefore Currently, TIVA is used more frequently in neurosurgery because of the fast onset of action and the ability to monitor neuronal best avoided during electrophysiological monitoring. structures continuously using intraoperative neurophysiological Other intraoperative problems monitoring techniques. Cardiovascular instability A combination of TIVA and a low dose of sevoflurane has been used in some studies with success.21 Surgical stimulation of the floor of 4th ventricle, lower pons, upper medulla and the cranial nerve nuclei may cause Inhaled anaesthetics (IA) (Sevoflurane/Isoforane) hypertension, bradycardia, tachycardia and arrhythmias.5,9 favourable features Cardiovascular disturbances that occur during surgery may be a • Reduced excitotoxicity warning that the surgeon is too close to the vital structures and • Increased physiologic stability a brief interruption of surgery may be enough to address the The effect is mediated by their GABA agonist and NMDA problem, otherwise pharmacological agents can be used. antagonist activity and also to glutamate reduction. At a dose Potential for large blood loss of 1 MAC there is a balance between the drop in CMR and the increase in CBF.18 This may be influenced by the skill of the surgeon, the location of the tumour, the vascularity of the mass and the involvement No significant difference was found between TIVA and sevoflurane of the sinuses in the incidence of postoperative nausea and vomiting (PONV) in a study done on patients who underwent an infratentorial Emergence surgery.22 However, a systematic review done later showed more PONV and greater use of anti-emetics in patients treated with The blunting of extubation response is standard practice. sevoflurane as compared to propofol;23 this was supported by Awakening allows immediate postoperative neurological a meta-analysis done in patients who had undergone elective assessment. When preoperative consciousness is intact, the craniotomy, which showed a lower incidence of PONV in patients surgery relatively uneventful, it is recommended that the patient 24 managed with propofol. be awakened in the operating room.

In patients with adequate intracranial compliance, the use of If, however, the pre-surgery consciousness is impaired, surgery is an IA dose equal or less than 1 MAC has been shown to have prolonged and difficult with frequent traction on the brain stem, minimal interference with autoregulation of cerebral blood flow, there may be a danger of apnea and or decreased sensorium cerebral blood volume and ICP. Generally, in patients with normal with diminished airway reflexes or perioperative problems (e.g. intracranial compliance, the effect of IA on brain haemodynamics is negligible.18 TIVA is preferred in patients with an altered flow/ cerebral oedema, haemodynamic instability), delayed awakening metabolism ratio, unstable ICP, expansive or large lesions.25 is recommended, with the patient remaining intubated and allowed to awaken slowly after a period of monitoring and Electrophysiological monitoring continued ventilation.5,8

The brainstem has a concentration of nerve structures and Postoperative period minor damage to them may result in devastating complications. Intraoperative neurophysiological monitoring plays a major role Ventilated patients may need intracranial pressure monitoring in continuous monitoring of neuronal integrity and function of probe as deteriorating mental status cannot be used for the neuronal structures at risk during the surgical procedure18 postoperative monitoring.

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For extubated patients, close monitoring of vital signs and 15. Gildenberg PL, O`Brien RP, Britt WJ, Frost EA. The efficacy of Doppler monitoring repeated neurological examination is needed. for the detection of venous air embolism. J Neurosurg. 1981;54:75-8. 16. Valiaveedan SS, Rath GP, Bithal PK, Ali Z, Prabhakar H. Posterior fossa demoid: yet Sedation, analgesia and PONV prophylaxis are important another cause of difficult airway. J Anesth. 2008;22(4):124-9. considerations. 17. Schifilliti G, Grasso A, Conti A, Fodale V. Anaesthetic related neuroprotection: intravenous or inhalation agents? CNS Drugs. 2010;24:893-907. References 18. Zuleta-Alarcon A, Castellon-Larios K, Nino-de Mejia MC, Bergese SD. Total intravenous anaesthesia versus inhaled anaesthetics in neurosurgery. 1. Albin MS. Anesthesia for posterior fossa surgery. In: Sperry RJ, ed. Anesthesia and Colombian Journal of Anesthesiology. 2015;43(1):1-14. the Central Nervous System: Kluwer Academic Publishers; 1993. p. 211-35. 19. Deiner S. Highlights of anaesthetic considerations for intraoperative 2. Krane EJ, Phillip BM, Yeh KK, Domino KB. Anaesthesia for paediatric neuromonitoring. Semin Cardiothorac Vasc Anesth. 2010;14:15-53. neurosurgery. In: Smith RM, Montotyama EK, Davis PJ, eds. Smith`s Anaesthesia for infants and children, 7th Edn. Philadelphia: Mosby, 2006. p. 651-84. 3. 20. Cole CD, Gottfried ON, Gupta DK, Couldwell WT. Total intravenous anesthesia: advantages for intracranial surgery. Neurosurgery. 2007;61:369-77. 3. Young J, Miller RW. Incidence of malignant tumors in U.S. children. J Pediatr 1975;86:54-258. 21. Sabbagh AJ, AI-Yamany M, Bunyan RF, Takrouri MSM, Radwan SM. Neuroanaesthesia management of neurosurgery of brain stem tumor 4. Moore KL. Head. Clinically oriented anatomy. Baltimore/London: Williams & requiring neurophysiology monitoring in a i MRI OT setting. Saudi J Anaesth. Wilkins; 1980. p. 901-14. 2009;3(2):91-3. 5. Jagannathan S, Krovvidi H. Anaesthetic considerations for posterior fossa 22. Magni G, Baisi F, La Rosa I, Imperiale C, Fabbrini V, Pennacchiotti ML. No surgery. Continuing Education in Anaesthesia, Critical Care and Pain. difference in emergence time and early cognitive function between sevoflurane- 2014;11(5):202-6. fentanyl and propofol-remifentanil in patients undergoing craniotomy for 6. Chusid JG. Brain. Correlative Neuroanatomy & Functional Neurology. 18 ed. Los supratentorial intracranial surgery. J Neurosurg Anesthesiol. 2005;17:134-8. Altos: Lange; 1982. p. 1-35. 23. Gupta A, Stierer T, Zuckerman R. Comparison of recovery profile after 7. Wilson M, Davies NP, McConville C, Grundy RG, Peet AC. High resolution magic ambulatory anesthesia with propofol, isoflurane, sevoflurane and desflurane: a angle spinning 1H NMR of childhood brain and nervous system tumours. Mol systematic review. Anesth Analg. 2004;98:632-41. Cancer. 2009;8:6. 24. Chui J, Mariappan R, Mehta J, Manninen P, Venkatraghavan L. Comparison 8. Gheorghita E, Ciurea J, Balanescu B. Considerations on anesthesia for posterior of propofol and volatile agents for maintenance of anesthesia during elective fossa-surgery. Romanian Neurosurgery. 2012;3(XIX ):183-92. craniotomy procedures: systematic review and meta-analysis. Can J Anaesth. 9. Chand MB, Thapa P, Shrestha S, Chand P. Peri-operative Anesthetic Events 2014. in Posterior Fossa tumour Surgery. Postgraduate Medical Journal of NAMS. 25. Hans P, Bonhomme V. Why we still use intravenous drugs as the basic regimen 2012;12(2):5-8. for neurosurgical anaesthesia. Curr Opin Anaesthesiol. 2006;19: 498-503. 10. Porter JM, Pidgeon C, Cunningham AJ. Sitting position in neurosurgery: a critical 26. Sala F, Krzan MJ, Deletis V. Intraoperative neurophysiological monitoring in appraisal. Br J Anaesth. 1999;82(1):117-28. pediatric neurosurgery: why, when, how? Childs Nerv Syst. 2002;18:264-87. 11. Osborn IP. Intracranial Mass, Intracranial Pressure, Venous Air Embolism, 27. Fischer C, Bertrand O, Volman D. Neuromonitoring in posterior fossa surgery. Autoregulation. In: Reed AL, Yudkowitz FS, eds. Clinical Cases in Anesthesia. 4th . 1987;66(5):S34. ed. Philadelphia: Elsevier Saunders; 2014. p. 70-6. 28. Sala F, Manganotti P, Bricolo A, Gerosa M. Monitoring of motor pathways during 12. Harrison EA, Mackersie A, McEwan A, Facer E. The sitting position for brainstem surgery: what we have achieved and what we still miss. Neurophysiol neurosurgery for children: a review of 16 years` experience. Br J Anaesth. Clin. 2007;37(6):399-406. 2002;88:12-7. 29. Morgan GE, Mikhail MS, Murray MJ. Neurophysiology and Anesthesia. Clinical 13. Tausk HC, Miller RD. Anesthesia for posterior fossa surgery in the sitting position. Anesthesiology. 4th ed. New York: Lange; 2006. p. 614-30. Bull N Y Acad Med. 1983;59(9):771-83. 30. Wang AC, Than KD, Etame AB, La Marca F, Park P. Impact of anesthesia on 14. Mirski MA, Lele AV, Fitzsimmons L, Toung TJK. Diagnosis and treatment of transcranial electric motor evoked potential monitoring during spine surgery: a vascular air embolism. Anesthesiology. 2007;106:164-77. review of the literature. Neurosurg Focus. 2009;27:E7.

S97 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

The anaesthetist’s role in the endoscopy suite

C Quan

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

Introduction a. Gastroscopy and colonoscopy

The anaesthesiologist’s role in the endoscopy suite is twofold: DIAGNOSTIC 1. Provide safe and comfortable sedation or anaesthesia to the Colonoscopy has been shown to be very effective patients who may present to us on an endoscopy list in detecting precancerous colonic polyps.1 With the 2. Provide acceptable conditions for the endoscopist to implementation of screening programs, the patients perform their work. presenting for screening colonoscopy will increase.

With advances in endoscopy, our role is become increasingly THERAPEUTIC more challenging. New and more invasive procedures (which • There have been many advances in upper previously have been done by surgeons in an operating theatre) gastrointestinal endoscopy, concerning the are being done in the endoscopy suite. Consequently, we are management of bleeding. Techniques employed may being presented with patients with co-morbidities who may, on include the use of clips, injection and glue. the whole be sicker; presenting for more invasive procedures, • Strictures in the upper and lower gastrointestinal tract which take longer than standard endoscopy; and who expect to may be stented. be discharged home on the same day. • Mucosal lesions in the upper and lower gastrointestinal Topic to be discussed further includes: tract may be resected endoscopically. This is known as endomucosal resection. These procedures take longer 1. Advances in endoscopy than the standard endoscopic procedure. 2. Dangers of sedation and how to avoid themHypoxia b. Endoscopic retrograde cholangiopancreatography a. Hypercarbia (ERCP) 3. Pharmacology ERCP requires screening and is therefore often done in a. New sedation drugs a remote location in the radiology suite. It is done in the b. Antispasmodics prone position. Patients often have obstructive jaundice c. Adverse drug reactions and usually require antispasmodics (see later). 4. Disease processes commonly associated with patients c. Endoscopic ultrasound (EUS)2 presenting for endoscopy DIAGNOSTIC a. Visceral hypersensitivity EUS can be employed for use in the upper and lower b. Aortic stenosis gastrointestinal tract. It can be used to define and c. Neuroendocrine tumours examine sub-mucosal lesions as well as periluminal d. Obesity structures such as the pancreatic, posterior mediastinal e. Renal failure and para-aortic lymph nodes. These lesions can then also be sampled, via fine needle aspiration through the f. Liver failure endoscope. 1. Advances in Endoscopy THERAPEUTIC There have been major advances in the field of gastrointestinal • EUS can be used to drain fluid collection or abscesses endoscopy in the last 20 years, both in the diagnostic and in the pancreas or any other area abutting the especially in the therapeutic arena. gastrointestinal tract.

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• Coeliac plexus blocks for cancer palliation can also be Capnography offers an earlier indication of performed via EUS. hypoventilation compared with pulse oximetry and is d. Double balloon endoscopy (DBE) better than visual assessment alone.5 There are pitfalls

DBE can be performed via the upper and lower with pulse oximetry. These arise because at the upper gastrointestinal tract. DBE is employed to access the limit of the oxyhaemoglobin dissociation curve, large small bowel for diagnostic and/or therapeutic purposes. changes in partial pressure of oxygen result in small DBE is a very time-consuming procedure. changes in oxygen saturation. This is especially true in 2. Dangers of sedation and how to avoid them patients receiving supplemental oxygen as this shifts a. Hypoxia the oxyhaemoglobin curve to the left. In addition, pulse oximetry readings can be delayed by up to 50 Most of the sedative drugs depress the respiratory seconds depending on cardiac output and peripheral system. The art of sedation involves giving enough drugs to sedate but not enough to cause hypoxia. There vasoconstriction. is no magic formula for this, but rather an “intelligent” Capnography therefore should be considered in feel one develops with experience. procedures requiring moderate or deep sedation5 and However, if one is worried about hypoxia; remember the in any patient in whom hypoventilation would be a benefits of preoxygenation and supplemental oxygen. problem. Adequate preoxygenation fills the functional residual capacity (residual volume plus expiratory reserve Respiratory volume monitors (RVMs) monitor ventilation volume) with oxygen. In the average adult, this equates in nonintubated patients and may prove to be useful to 2300 ml.3 Oxygen consumption (VO ) in the average 2 in the future. RVMs operate by detecting thoracic adult is 250 ml. Therefore, if the average adult is rendered impedance through electrodes placed over the patient’s apnoeic, it will take approximately 9 minutes 12 seconds before the patient becomes hypoxic. This period of time chest, enabling real-time calculations of respiratory rate, is more than adequate for a standard gastroscope and tidal volume and minute ventilation.5 can provide more margin of error in those patients with 3. Pharmacology less reserve (e.g. obese patients). 6 b. Hypoventilation and hypercarbia a. New Sedation Drugs

Hypoventilation and subsequent hypercarbia is REMIMAZOLAM dangerous in patients with pulmonary hypertension Remimazolam is a short-acting GABA A receptor and especially those with poor right ventricular function. Hypercarbia can set these patients spinning into a agonist that has organ-independent metabolism. downward spiral of worsening pulmonary hypertension, Preclinical animal studies showed that remimazolam exacerbation of hypoxia and hypercarbia and worsening had a more rapid onset and shorter duration of action right ventricular function. than midazolam. Because of its organ-independent Once there is right ventricular dilatation, consequences metabolism and rapid and predictable onset and are4: recovery profile, remimazolam may have advantages • Increase in wall tension, which increases myocardial over other currently available benzodiazepines. oxygen demand as well as decreasing ventricular Its drawback, however, is that, as with the other perfusion. benzodiazepines, it has a respiratory depressant effect. • Functional tricuspid regurgitation, which leads to right ventricular volume overload and further annular FOSPROPOFOL dilatation and right ventricular remodeling. Fospropofol is a water-soluble prodrug of propofol. It is • Ventricular asynchrony, which leads to a decrease in metabolized in vivo by tissue alkaline phosphatases to right ventricular stroke volume and under-filling of liberate propofol, phosphate and formaldehyde. After the left ventricle. intravenous injection it has a lower peak concentration All these factors can lead to a marked decline in and a slower decline in drug concentration than propofol. cardiac output and myocardial ischaemia that can set This prodrug formulation overcomes the disadvantages up a vicious cycle which can be impossible to rectify. These patients can be very tricky to sedate as mere of the lipid-based formulations, the complications of hypoventilation and not apnoea can set up this vicious lipid infusion, and the risk of fluctuations in propofol cycle. levels due to bolus injection.

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METHOXYFLURANE previous unsuccessful sedation, heavy drinking, smoking, upper endoscopy; and a higher dose of is an agent formerly used as a volatile midazolam. The reported incidence in adult patients is anaesthetic but with strong analgesic properties. It is 1.4%. Flumazenil may be used to treat the paradoxical available in South Africa as Penthrox®. It is packaged reaction. as a single-use inhaler. Methoxyflurane is added to a propylene wick within a small chamber, and is PROPOFOL11 vaporized as the patient inhales. There is a dilutor hole The administration of propofol may be associated with on the inhaler that the patient can cover to increase the generalized tonic-clonic seizures, focal motor seizures, inhaled concentration of methoxyflurane. The inhaler increased tone with twitching and rhythmic movements, has a charcoal activated carbon chamber in which opisthotonus and involuntary movements. This is a rare exhaled vapour is adsorbed to minimize environmental adverse event and further investigation is required to contamination.7 elucidate the exact incidence and mechanism. Nguyen has compared methoxyflurane with 4. Disease processes commonly associated with a combination of midazolam and fentanyl for patients presenting for endoscopy colonoscopies.8 They concluded that methoxyflurane is a feasible drug for colonoscopy and as effective as a. Visceral hypersensitivity conventional drugs. It has a shorter recovery time, is not Irritable bowel syndrome (IBS) is one of the associated with respiratory depression and it does not most common gastrointestinal disorders. It is influence success and polyp detection. characterized by abdominal pain and disturbed Problems with methoxyflurane include that it is defaecation that cannot be explained by structural contraindicated in renal failure or impairment.8 or biochemical abnormalities. Increased sensitivity to stimuli arising from the gut wall (visceral b. Antispasmodics hypersensitivity) contributes to the abdominal pain.12 HYOSCINE9 Patients with coeliac disease exhibit increased rates of neuropsychiatric disturbances and visceral Hyoscine is also known as scopolamine and distributed hypersensitivity. These patients may require higher as buscopan®. It has antimuscarinic and anticholinergic amounts of both opioids and midazolam compared effects. Therefore, the side effects include tachycardia, with age- and gender-matched controls.6 dry mouth, paralysis of visual accommodation and b. Aortic stenosis urinary retention. Hyoscine is contraindicated in patients with atrial tachyarrhythmias, congestive cardiac failure, There is an association between chronic gastrointestinal coronary artery disease and mitral stenosis. However, bleeding and calcific aortic stenosis. This is known as the duration of action of hyoscine is short, therefore Heyde syndrome after Edward Heyde, who first described these effects are unlikely to be of concern except in it in 1958. The pathogenesis is due to an acquired type severe disease. IIA von Willebrand syndrome and angiodysplasia.13

Other contra-indications include myasthenia gravis, Aortic stenosis is associated with high shear stress, which glaucoma, megacolon, gastrointestinal stricture and elevates von Willebrand factor-cleaving metalloprotease prostatic hypertrophy. activity. This leads to proteolysis of von Willebrand factor and increases interactions between von Willebrand GLUCAGON9 factor and platelets, leading to degradation of von Glucagon is a naturally occurring hormone produced by Willebrand factor. the α cells of the islets of Langerhans in the pancreas. The management of Heyde Syndrome is Intravenous glucagon causes gastrointestinal smooth multidisciplinary. Unfortunately, the treatment for muscle relaxation by an incompletely elucidated conventional von Willebrands disease (octreotide, mechanism. Glucagon causes hyperglycaemia with a vasopressin, Factor VIII) is ineffective in the acquired form reactive hypoglycaemia occurring about 2 hours after of the disease. Oestrogen-progesterone preparations administration. So it should be used with caution in and thalidomide may be helpful. Blood transfusions and diabetic patients. endoscopic interventions are used as a bridge to valve c. Adverse drug reactions replacement. Bioprosthesis should be considered in MIDAZOLAM10 a patient older than 65 years and it also precludes the need for anticoagulation. Trans catheter aortic valve Paradoxical reactions or disinhibition reactions may implantation is a feasible alternative. occur with midazolam. Paradoxical reactions are c. Neuroendocrine tumours14 characterised by increased talkativeness, emotional release, excitement, excessive movement and even Neuroendocrine tumours (NETs) are malignant growths hostility and rage. Risk factors include: male gender, that arise from neuroendocrine cells. They most

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commonly occur in the gastrointestinal tract (48%), elective and emergent basis. Liver dysfunction can lung (25%) and pancreas (9%). Neuroendocrine cells reduce the clearance of sedative drugs eliminated by can produce hormones such as serotonin, which can hepatic metabolism or biliary excretion and plasma produce symptoms of flushing and diarrhoea. protein binding. Chronic liver disease is also associated with a reduction in drug-metabolizing activities of NETs may be found incidentally or may be suspected enzymes such as CYP450. when they produce clinical symptoms from secreted hormones. These are termed “functioning” tumours. Midazolam has delayed clearance in patients with Most NETs, however, are “nonfunctioning”. cirrhosis, probably due to reduced conjugation ability of the liver and/or decreased portal blood flow. Midazolam Carcinoid syndrome, characterized by flushing, can exacerbate subclinical hepatic encephalopathy in diarrhoea and valvular heart disease, occurs when patients with cirrhosis and Child-Pugh scores A or B. hormones produced by NETs reach systemic circulation. This usually happens when liver metastases are present, Propofol use in patients with chronic liver disease has a allowing for bypass of the hepatic metabolism, which shorter biological half-life and a lower risk of inducing would normally inactivate the hormones. hepatic encephalopathy

Endoscopic ultrasonography is the most sensitive test Conclusion for diagnosis of pancreatic NETs. There has been a rapid advancement in the field of endoscopy d. Obesity15 with better imaging and the ability to do more invasive Patients with a higher body mass index (BMI) have a procedures. In addition, new endoscopes have been introduced higher prevalence of gastrointestinal diseases such as in practice, such as EUS and DBE, enabling endoscopists to gallbladder disease, oesophageal and colon cancer. do procedures never done before. This has made our job as In addition, obesity is associated with hypertension, anaesthesiologists all the more challenging. hyperlipidaemia, diabetes, stroke, osteoarthritis, A study performed in Australia showed that patients presenting sleep apnoea, restrictive lung disease and pulmonary for gastrointestinal endoscopy under anaesthetist-based hypertension. sedation at public hospitals had a high-risk profile. In addition, Obese patients are anecdotally believed to be at higher the incidence of significant unplanned events was 23% and risk for procedural sedation, but this is not extensively the 30 day-mortality was 1.2%.19 This serves to remind us not backed up by the medical literature. to be complacent when we are faced with an endoscopy list. Unfortunately, sedation remains more of an art than a science. Pharmacokinetics (specifically binding, elimination There is no perfect recipe or protocol that will work for all and volume of distribution) is also difficult to predict in patients. Competency usually only comes with experience and obese patients. Higher adipose mass, a reduction in total exposure. body water, higher glomerular filtration rate and normal hepatic clearance, which may lead to higher sedative References dose requirement and thus increased sedation risks. 1. Levin TR, Douglas A. Colorectal-Cancer Screening-Coming of Age. New Engl J Med. 2013;369(12):1164-5. As with obesity, it is thought that obstructive sleep 2. Kwan V. Advances in gastrointestinal endoscopy. Intern Med J. 2012;116-26. apnoea (OSA) may increase the risk of cardiopulmonary 3. Morgan G, Mikhail M, Murray M. Clinical Anaesthesiology. 4th ed. Strauss ML, unplanned events during endoscopy, but this is not Lebowitz H; Boyle PJ, eds. Lange Medical Books / McGraw-Hill Medical Publishing Division; 2006. backed up by medical literature. The ASA guidelines 4. Noordegraaf AVG, Galie N. The role of the right ventricle in pulmonary arterial recommend that capnography should be used for hypertension. Eur Respir Rev. 2011;20(122):243-53. monitoring of ventilation in patients with OSA.5 5. Mahmud NB, Tyler M. Extended Monitoring during Endoscopy. Gastrointest Endosc Clin N Am. 2016;26(3):493-505. e. Renal failure 6. Triantafillidis J, Merikas E, Nikolakis D, Papalois A. Sedation in gastrointestinal Midazolam and fentanyl have been safely used for endoscopy: Current issues. World J Gastroenterol. 2013;19(4):463-81. 16 7. Gaskell AJ, Jephcott CG, Smithells JR, Sleigh JW. Self-administered sedation in renal failure patients on dialysis. methoxyflurane for procedural analgesia: experience in a tertiary Australasian centre. Anaesthesia. 2016;71(4):417-23. Oral sodium phosphate bowel preparations (e.g. 8. Nguyen NQ, Toscano L, Lawrence M, Moore J. Patient-controlled analgesia picolax®, picoprep®, coloprep®) should be avoided in with inhaled methoxyflurane versus conventional endoscopist-provided patients with chronic kidney disease or any patient who sedation for colonoscopy: a randomized multicenter trial. Gastrointest Endosc. 2013;78(6):892-901. is taking drugs, which may affect renal perfusion such as 9. Sanagapalli S, Agnihotri K, Leong R, Corte CJ. Antispasmodic drugs in angiotensin-converting enzyme inhibitors, angiotensin colonoscopy: a review of their pharmacology, safety and efficacy in receptor blockers or non-steroidal anti-inflammatories17 improving polyp detection and related outcomes. Therap Adv Gastroenterol. Polyethylene glycol (moviprep® or cleanprep®). 2017;10(1):101-13. 10. Tae CH, Kang KJ, Min BH, Ahn JH, Kim S, Rhee PLy, et al. Paradoxical reaction to 18 f. Liver failure midazolam in patients undergoing endoscopy under sedation: Incidence, risk factors and the effect of flumazenil. Dig Liver Dis. 2014;46(8):710-5. Diagnostic and/or therapeutic endoscopy is frequently 11. Garg RD, Dehran M. Convulsions with propofol: A rare adverse event. J Postgrad necessary in patients with chronic liver disease on an Med. 2009;55(1):69-71.

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12. Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell G, Santini D, et al. 16. Beathard GU, Urbanes A, Litchfield, T, Weinstein A. The risk of sedation/analgesia Activated Mast Cells in Proximity to Colonic Nerves Correlate With Abdominal in haemodialysis patients undergoing interventional procedures. Semin Dial. 2011;24(1):97-103. Pain in Irritable Bowel Syndrome. Gastroenterology. 2004;126(3):693-702. 17. Hassan CB, Bretthauer M, Kaminski MF, Polkowski M, Rembacken B, Saunders B, 13. Hudzik BW, Krzysztof W Gasior M. Heyde syndrome: gastrointestinal bleeding et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal and aortic stenosis. Can Med Assoc J. 2016;188(2):135-8. (ESGE) Guideline. Endoscopy. 2013;45:142-50. 14. Raphael M, David L, Law C, Singh S. Principles of diagnosis and management of 18. Horiuchi AG, David Y. Special topics in procedural sedation: clinical challenges and psychomotor recovery. Gastrointest Endosc. 2014;80(3):404-9. neuroendocrine tumours. Can Med Assoc J. 2017;189(10):E398-E404. 19. Leslie KA, Allen ML, Hessian EC, Peyton PJ, Kasza J, Courtney A, et al. Safety of 15. Jirapinyo P, Thompson C. Sedation Challenges. Obesity and Sleep Apnea. sedation for gastrointestinal endoscopy in a group of university-affiliated Gastrointest Endosc Clin N Am. 2016;26(3):527-31. hospitals: a prospective cohort study. BJA. 2017;118(1):90-9.

S102 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Inadvertent burns in theatre

E E Oosthuizen

Department of Anaesthesia, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

Other causes for inadvertent skin or mucosa burns include laser devices (mostly airway), pulse Keywords: burns in theatre, accidental burns and surgery,oximeter closed finger claimsprobe andanalysis, electrocardiogram cautery burns lead burns during magnetic resonance imaging, defibrillator paddle burns, and two rare cases of burns due to hot surgical instruments.4,5 Introduction Etiology of inadvertent theatre burns: Etiology of inadvertent theatre burns The incidence of inadvertent patient burns in the operating Other 8% theatre is fairly low with a paucity of reports in the literature. Cautery burn Inadvertent burning of a patient is traumatic and often (non-fire) 12% Bag or bottle catastrophic, not only to the affected patient but equally to 35% the surgical team members. Burns in the operating room environment are caused by electrical current, chemical irritants, induction burns due to magnetic resonance (MRI), contact burns, and inhalation burns.1,2 Physical scars, emotional trauma and prolonged hospital stay are inevitable, depending on the extent of the injury. Doctor-patient relationships often become Cautery fire disrupted with legal consequences to the relevant practitioners. 19% The awareness of the possibility of burns during surgery has to be increased by emphasising the causes, warning signs, and Laser fire 2% Warming recommendations to prevent patient burns.3 devices 23%

Incidence and extent 4 Figure 1. AetiologyFigure of inadvertent 1. Aetiology burns of inadvertent in theatre burns4 in theatre Kressin analysed the American Society of Anaesthesiologists (ASA) Closed Claims Project database, reporting the database Location of inadvertent theatre burns fraction of inadvertent operating theatre burns to beLocation 2%. The of inadvertent burns Location of inadvertent theatre burns Airway commonest cause in this analysis is hot intravenousThe bags trunk or or axilla is the commonest site for inadvertent3% burns, caused commonly by hot intravenous Buttock/thigh/ bottles in contact with skin (35%); 23% of burns werefluid caused bags by used in the positioning of patients for invasive line placement or aiding patient warming. The leg/feet patient warming devices, and electrocautery was responsible Face 21% ASA Closed Claims Registry identified21% the said site in 28% of burns. The buttocks , thighs, and feet were for 19 % intraoperative burns. The latter includes both cautery induced fires and electric ground pad/plate skin burns.involved4,5,6 in 21% of burn claims which were, in 61% of claims, caused by patient warming devices. Burns to the face represents 21% of burns claims, caused by cautery fires in 64% of cases.4 Other causes for inadvertent skin or mucosa burns include Multiple areas/other/ laser devices (mostly airway), pulse oximeter finger probe and unknown electrocardiogram lead burns during magnetic resonance 8% imaging, defibrillator paddle burns, and two rare cases of burns due to hot surgical instruments.4,5 Location of inadvertent burns Arm/hand/finger Trunk/axilla The trunk or axilla is the commonest site for inadvertent burns, 18% 29% caused commonly by hot intravenous fluid bags usedAirway in theFace Trunk/axilla Arm/hand/finger Multiple areas/other/unknown Buttock/thigh/leg/feet 2 Figure 2. Anatomical distribution of inadvertent burns in theatre4 positioning of patients for invasive line placementFigure 2. orAnatomical aiding distribution of inadvertent burns in theatre4 patient warming. The ASA Closed Claims Registry identified the said site in 28% of burns. The buttocks, thighs,Aetiology and feet of inadvertentwere caused burns by patient warming devices. Burns to the face represent 4 involved in 21% of burn claims which were, Skinin 61% heated of claims,to 45°C for 221% hours of producedburns claims, first-degree caused burns,by cautery while fires 3 hours in 64%’ exposure of cases. produced

7 complete epidermalS103 necrosis. Burns inflicted inadvertently in the operating theatre are due to surface contact, convection, electric, chemical, radiant heat, inhalation, and magnetic resonance induced.

1. Conduction (surface contact) Surface contact burns mostly occur in the operating theatre due to hot intravenous fluid bags used for patient positioning when placing of invasive lines, alternatively for optimal surgical positioning. Wrapping of hot fluid bags with substantial layers of surgical drape prior to placement is essential in avoiding contact burns. Using room temperature bags is advised to eliminate the possibility of an inadvertent contact burn.

2. Convection (forced air warming devices)

3 104 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1)

Aetiology of inadvertent burns (electrolyte, cleaning solutions). Commonly found pooling areas for cleaning solutions include the buttocks, scapulae, Skin heated to 45°C for 2 hours produced first-degree burns, and interscapular area including lower posterior neck. while 3 hours’ exposure produced complete epidermal necrosis.7 Burns inflicted inadvertently in the operating theatre are due Fire burns sparked by electrocautery use (cautery fires) is to surface contact, convection, electric, chemical, radiant heat, typically found in conjunction with highly flammable agents inhalation, and magnetic resonance induced. used for skin cleansing. The majority of cautery fires in the 1. Conduction (surface contact) ASA Closed Claims Analysis were encountered during plastic surgery and monitored anaesthesia care. The majority of fire Surface contact burns mostly occur in the operating burns were encountered in the facial area. Highly flammable theatre due to hot intravenous fluid bags used for patient agent usage with the open administration of oxygen (facial positioning when placing of invasive lines, alternatively for mask, nasal prongs) was found to be a common scenario.4 optimal surgical positioning. Wrapping of hot fluid bags with substantial layers of surgical drape prior to placement is Recommendations regarding the safe application of neutral essential in avoiding contact burns. Using room temperature electrodes are:11 bags is advised to eliminate the possibility of an inadvertent Application site contact burn. 2. Convection (forced air warming devices) Avoid application on: ▪▪ bony protuberances Incorrect usage of forced air warming devices is a major cause of burns in theatre. Burns are extremely rare and even ▪▪ obese body regions non-existent with the correct usage of this patient warming ▪▪ metal implants modality. Postoperative burns caused by the incorrect use ▪▪ scar tissue of forced warm air devices are well-described in patients with functional regional or neuraxial blocks.9 Numerous Preparation of application site cases are described in the literature due to “hosing” ▪▪ clean application area, remove traces of grease with forced air warming devices.10 The correct use of the ▪▪ remove hair prescribed dissipating blankets, as prescribed by the relevant ▪ wait for cleaning agents to evaporate before placement manufacturer, prevents burns. ▪ 3. Electrical Positioning ▪ check expiry date of disposable ground plates The incidence of recognisable burns due to aberrant/leakage ▪ currents is an estimated 0.1%.11 Burns are often not identified ▪▪ prevent gel from drying; open just before use immediately after surgery but only days afterwards. Burns ▪▪ do not cut the ground plate to desired size can be misdiagnosed as pressure sores, chemical contact ▪▪ avoid air or bubbles between plate and skin reactions, or an allergic response to a disinfectant solution or ▪ prevent cleaning solution to come in contact with ground even a drug reaction. ▪ plate The technical principles underlying diathermy include a high ▪▪ do not touch the contact surface of the electrode before frequency current (0.4-3 MHz) entering of the body via the or during placement small surface work electrode (diathermy probe/knife) and ▪▪ recheck contact after movement of the patient exiting via the neutral electrode (ground plate). The current density at the work electrode (small contact surface) rises Alarm control to +1000 oC.11 The ground plate contact area has to be large ▪▪ test alarms in order to limit the current density, therefore limiting heat ▪ do not ignore alarm warnings production to a minimum. ▪ ▪▪ limit high frequency output (> 400 W is excessive) Heat generation (Q) increases proportionally with the square of the current intensity (I), duration of the current (t) and the Removal patient resistance (R)11,12: ▪▪ remove slowly to prevent skin damage ▪▪ never pull on the connecting cable Q = t x I2 x R where R = length of the current path ▪▪ never reuse/reapply a disposable ground plate cross-section 4. Chemical Prepping and degreasing agents may be toxic to the skin Factors responsible for inadvertent diathermy-induced burns or react chemically with other substances, producing an include a decreased neutral plate contact area or the existence exothermic reaction with skin destruction. Removal of the of an additional, lower resistance patient ground area. The natural protective lipid layer of the skin with degreasing latter includes patient contact with conductive metal, e.g. agents makes the skin vulnerable to chemical irritants. operating table, via direct contact or via conductive fluid Chemical injury may look similar to thermal injury and makes

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skin more exposed to heat and friction injury. Isopropyl ▪▪ Instruct conscious patients to call out if they experience a alcohol in combination with certain soaps, in combination warming sensation. with pressure or mild heat from a warming blanket is Patient factors known to cause skin injury. Skin exposure to unaerated heat-sensitive items sterilised with ethylene oxide can be Decreased blood flow to skin at risk may predispose to extremely irritating, especially when skin is moist.4 inadvertent burns due to decreased dissipation of heat in the following circumstances: Prepping has to be conducted with great care, at all times. ▪▪ Vasculopathy A collection of fluid beneath the patient or tourniquet must be prevented. Chemically and/or electrocautery burns are ▪▪ Tourniquet usage inevitable when a preventative attitude is not customary. ▪▪ Low cardiac output states 5. Radiant heat ▪▪ Peripheral vasoconstriction ▪▪ Hypothermia Heat radiant devices are known to cause patient burns. Malfunctioning or wrongly applied radiating heaters (e.g. Procedure to follow after inadvertent burn occurrence too close to skin) is a common source of burns. High density Do not assume the cause of a burn but investigate all possible operating lights can cause skin burns in the absence of heat aetiologies and mechanisms. Finding the cause is essential filters. Oximeter probe burns are not unknown due to probe in preventing future incidents. A description of procedures o temperature that can be as high as 44 C. The time threshold to follow investigating all possible causes of inadvertent for skin injury at this temperature is 6 hours. This may be less burns in theatre is available.8,11,12 Contemporaneously in the elderly, neonates, and patients with more sensitive noting investigation procedures followed and the state of 4 skin. Overhead radiant heating devices must be used with the relevant equipment is essential. This includes patient caution, limiting exposure time in conjunction with sensor data, all risk factors, and perioperative occurrences. Colour feedback servo control. photographing of lesions immediately after identifying a 6. Magnetic resonance (MR) induced possible burn is essential for future reference. Burns often have the immediate appearance of an electrical or thermal A thermal injury can occur where skin is in contact with cause but may, after a while, reveal to have a chemical origin.3 monitoring cables or sensor (e.g. ECG skin electrodes or cables, pulse oximeter sensor) or an MR accessory, e.g. Explanation to the patient regarding the possible surface coil. The MR environment induces currents in a mechanism(s) is essential and responsibilities have to conductor. Currents are induced by two magnetic fields, that be taken. A treatment plan is proposed to the patient is the pulsed magnetic-gradient field and the pulsed radio- in conjunction with the most appropriate specialised frequency field. These fields fluctuate and the changing discipline(s). Inadvertent patient burns are not acceptable and awareness has to be fostered amongst all doctors and magnetic flux lines intercept an electrically conductive staff in theatre, including knowledge of risk factors and early loop, inducing an electromotive force. Heating results from patient examination after surgery. the current flowing through the loop. The loop's resistance determines the magnitude of the current. Precautions can be References taken to minimize the likelihood of burns, such as not looping 1. Russel MJ, Gaetz M. Intraoperative electrode burns. J Clin Monit Comput. sensor cables and using high-resistance graphite electrodes 2014;18:25-32. 2. Lee TW, Chen TM, Cheng TY. Skin injury in the operating room. Injury. and cables. An electrical conduction path can be eliminated 1998;29:345-7. by using the specified monitoring equipment, and placing 3. Demir E, O’Dey D, Pallua N. Accidental burns during surgery. J Burn Care Res. the cables and sensors away from the radio frequency coil.8 2006;27:895-900. 4. Kressin KA. Injury in the operating room: A closed claims analysis. SASA Burns in the MR suite can be prevented by adhering to the Newsletter. 2004;86(6):9-11. following basic principles:8 5. Metzner J, Posner KL, Lam MS. Closed Claims’ Analysis. Best Practice & Clinical Research Anaesthesiology. 2001;25:263-276. ▪▪ Use electrically non-conducting paths, e.g. fiber-optic 6. Cheney FW. The American Society of Anaesthesiologists Closed Claims Projects: cables and plastic tubing or high-resistance paths (carbon What we have learned, how it has affected practice, and how will it affect ECG leads), according to the manufacturer’s instructions practice in future? Anesthesiology. 1999;91:552-6 7. Fisher-Hubbard AO, Sung L, Hubbard SA, Hlavaty L. Hyperthermia, thermal ▪▪ Do not loop cables injuries, and death from a forced convection heat source: A case report and experimental model. J Forensic Sci. 2017;62(3):686-90. ▪▪ Place the sensor as far away as possible from the radio- 8. ECRI Institute. Thermal Injuries and Patient Monitoring during MRI Studies frequency coil, and run the cables away from the coil (Internet). 2017 [].http://www.mdsr.ecri.org/summary/detail.aspx?doc_id=8178 whenever possible 9. Chung K, Lee SM, Oh S, Choi J, Cho H. Thermal burn injury associated with a forced-air warming device. Korean J Anesthesiol. 2012;62(4):391-2. ▪▪ Ensure that electrical insulation on sensors and cables 10. Uzun G, Mutluoglu M, Evinc R, Ozdemir Y, Sen H. Severe burn injury associated with is intact and prevent bare metal surfaces touching the misuse of forced-air warming device. J Anesth. 2010;24:980–1. patient 11. Nduka CC, Super IA, Monson JR, Darzi AW. Cause and prevention of electrosurgical injuries in laparascopy. J Am ColI Surg. 1994;179(2):161-70. ▪▪ Keep cables off the patient and run it over blankets 12. Aigner N, Fialka C, Fritz A, Wruhs O, Zoch G. Complications of the use of ▪▪ Remove all unused sensors, cables, and surface coils diathermy. Burns. 1997;23(3):265-74.

S105 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

The postoperative management of a supraventricular tachyarrhythmia

H J Moutlana

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

Keywords: Postoperative arrhythmia, supraventricular tachyarrhythmias, perioperative supraventricular tachyarrhythmias

Introduction or atrioventricular (AV) nodal tissue.2,8 The classification of SVTs may be simplified according to regularity of rhythm into regular Cardiac arrhythmias are a major contributor to morbidity and irregular SVTs. and mortality in the perioperative period.1,2 Postoperative arrhythmias are common1 and the incidence of arrhythmias Regular SVTs following major non-cardiac surgery has been reported between • Sinus tachycardia 4% and 20%, depending on the type of surgery or arrhythmia.3 • Atrioventricular nodal re-entrant tachycardia (AVNRT) Atrial fibrillation is the most common arrhythmia encountered • Atrioventricular re-entrant tachycardia (AVRT) following major non-.3 • Atrial flutter The occurrence of supraventricular tachyarrhythmia (SVT) may • Focal atrial tachycardia affect postoperative hospital and ICU stay, as well as mortality.3-5 • Wolf-Parkinson-White syndrome Several authors reported a mortality of 20–50% in patients with Irregular SVTs new arrhythmias.3,6,7 Although the arrhythmia may rarely be the cause of death, the arrhythmia may have been triggered by the • Atrial fibrillation (AF) underlying condition.3,6,7 • Multifocal atrial tachycardia (MAT) Classification of supraventricular tachyarrhythmias Predisposing factors for postoperative SVTs

Supraventricular tachyarrhythmias (SVTs) are paroxysmal Supraventricular tachyarrhythmias may be a warning sign, which tachyarrhythmias that are initiated and maintained in the atrial may be overshadowing correctable life threatening conditions.10

Narrow QRS complex (<120 ms)

Regular Irregular

P wave visible P wave invisible Atrial fibrillation Atrial flutter with variable AV block Atrial tachycardia with variable AV block Multifocal atrial tachycardia P:QRS>1 P:QRS=1 AVNRT

Atrial flutter Long RP Short RP Atrial tachycardia interval interval (>70 ms) (<70 ms)

AVNRT AVNRT Atypical AVNRT Atrial tachycardia

Figure 1: Classification of SVT9

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The most common reversible conditions, and which should be rapid IV bolus may be given.2,12,16,17 Administration of adenosine is corrected before considering pharmacological antiarrhythmic associated with potential adverse effects including: transient AV therapies, are: block, flushing, chest pain, hypotension and dyspnea. Patients • Hypoxaemia should be warned of these potential adverse effects prior to administration.2,16 • Hypercarbia • Acidosis Ventricular rate control is the next priority in a patient who • Hypotension develops SVT and does not require immediate cardioversion. The advantages of slowing ventricular rate during SVT are: • Electrolyte imbalances prolongation of diastole enhancing left ventricular filling, which • Mechanical irritation: Chest tube enhances stroke volume and improves haemodynamic stability. • Hypothermia The other advantage of rate control is the reduction of myocardial • Adrenergic stimulation oxygen consumption and therefore lowering risk of ischaemia.10 • Proarrhythmic drugs Rate control is achieved with one of a variety of AV nodal • Micro/macro shock blockers. These are agents with class II or IV activity.10 • Cardiac ischaemia.1,10 Beta blockers: esmolol 500 mcg/kg over 1 minute then 50–300 mcg/kg/min titrated to effect, with repeat boluses Management of postoperative SVTs in between each dose increase or metoprolol 2. –5 mg over The management of postoperative SVTs requires a 2 minutes, which can be repeated in 10 minutes up to three comprehensive approach.11 Firstly, the problem is recognized, doses.2,16 Esmolol has ultra-rapid elimination, rendering it easily an arrhythmia is diagnosed and the physiological effect on the titratable.10,18 patient is assessed.3 Assess clinical condition – the heart rate will Both IV verapamil and diltiazem are calcium channel blockers typically be ≥ 150/min if tachyarrhythmia is present.12 A cascade effective for acute treatment of SVT in haemodynamically stable of adverse physiological phenomena may precipitate SVT in the patients.16,19 They are less easily titrated than esmolol but provide postoperative period. Reversible aetiologies should be identified rapid slowing of the ventricular rate in SVT in minutes.10 Diltiazem and treated before antiarrhythmic therapy is instituted, unless 0.25 mg/kg IV bolus over 2 minutes followed by an infusion of the patient is haemodynamically unstable.10,12 Maintain patient 5–10 mg/h or verapamil at a dose of 0.075–0.15 mg/kg IV bolus airway, assist breathing, supplemental oxygen, identify rhythm over 2 minutes.16 If the abovementioned pharmacological with cardiac monitor, monitor blood pressure and oximetry, and treatment is ineffective or not feasible, synchronised obtain IV access.12 cardioversion is recommended. 16 This review will focus on the acute management of SVTs in the Sinus tachycardia postoperative period. The initial acute management goal is to establish haemodynamic stability.1,2,10,13 The haemodynamic Physiological sinus tachycardia may result from causes such instability entails hypotension (systolic blood pressure < 80 mm as fever, dehydration, anaemia, and heart failure. Tachycardia Hg), loss of consciousness, signs of shock, cardiac ischaemia usually resolves with treatment of the underlying causes.16 or acute heart failure.10,12 If the patient is haemodynamically Atrioventricular nodal re-entrant tachycardia unstable, immediate synchronised direct current cardioversion is required to prevent the life threatening complications of AVNRT results from a re-entrant circuit involving anterior and hypoperfusion.2,10,13-15 The initial shock of 50–100 J (biphasic) posterior inputs to the AV node.2 The treatment of AVNRT follows for narrow regular tachyarrhythmia or 120–200 J (biphasic) the general management of regular SVT described earlier. The or 200 J (monophasic) for narrow irregular tachyarrhythmias initial management involves slowing of the AV node conduction is used.2,12,13 Ensure the patient is adequately sedated prior to using vagal manoeuvers, and adenosine if vagal manoeuvers delivering a shock.2 Even though the response to cardioversion fail to slow the heart rate. This is followed by pharmacological may be transient, a brief period of sinus rhythm may provide therapy with IV beta blockers, diltiazem or verapamil in valuable time to correct reversible causes of SVT or instituting haemodynamically stable patients. Synchronised cardioversion pharmacologic therapies.10 is recommended in haemodynamically unstable patients or where pharmacological therapy is ineffective or not feasible. Regular narrow complex SVT IV amiodarone is also recommended where IV beta blockers or In haemodynamically stable patients, acute conversion of regular calcium channel blockers are ineffective or not feasible.16 narrow complex SVTs is attempted with vagal manoeuvers as Atrioventricular re-entrant tachycardia the first line of treatment. These include Valsalva manoeuver or carotid massage.12,16,17 IV adenosine is recommended as a first line AVRT uses an accessory pathway that bypasses the AV node, medication due to a rapid onset and short half-life.2 Adenosine which may have anterograde conduction from the atria to 6 mg rapid IV bolus administered over 1–2 seconds followed by ventricle or retrograde from ventricle to atria. Three types of rapid saline flush. If there is no response within 1–2 min, a 12 mg arrhythmias may be seen as a result: a regular narrow complex

S107 108 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) tachycardia (orthodromic), a regular broad complex tachycardia Multifocal atrial tachycardia (antidromic) or an irregular broad complex tachycardia (AF with Multifocal atrial tachycardia is commonly associated with rapid anterograde conduction via the accessory pathway.2 The underlying medical conditions, for example pulmonary disease, regular narrow complex AVRT follows the same management as pulmonary hypertension, valvular heart disease and coronary regular SVTs.16 artery disease.16 Treatment of the precipitant takes precedent, Atrial flutter as the condition is usually transient and tends to resolve when the underlying medical condition improves.2 Cardioversion is The management of atrial flutter also begins with ascertaining rarely successful in MAT,2,16 and management often involves whether the patient is haemodynamically stable or not. If the conduction slowing at the AV nodal level to control heart rate.16 patient is haemodynamically unstable, the treatment strategy Verapamil has been shown to be effective in patients with MAT begins with synchronised DC cardioversion, followed by rate without ventricular dysfunction, sinus node dysfunction or control with IV amiodarone. In haemodynamically stable AV block. Beta blockers can also be used to treat MAT without patients, the acute management involves rate control with IV respiratory decompensation or AV block.16 beta blockers, IV diltiazem, IV verapamil or IV amiodarone.16 Conclusion

Focal atrial tachycardia This review covered the acute management of SVTs focusing mainly on those presenting as narrow complex. SVT may on Focal atrial tachycardia is regular atrial rhythm originating certain occasions present as a broad complex tachycardia due outside the sinus node, either within the left or right atrium.2 to conduction via an accessory pathway or a bundle branch The management begins with the use of IV adenosine for block. Regular broad complex tachycardia should be treated haemodynamically unstable patients, with synchronised DC as ventricular tachycardia, unless it is an SVT with aberrant cardioversion if adenosine is ineffective or not feasible. In conduction or antidromic AVRT.2 haemodynamically stable patients and the diagnosis of focal atrial tachycardia established, IV beta blocker, IV diltiazem or IV Conflict of interest verapamil may be used, which may be followed by IV amiodarone The author declares that he has no financial or personal or IV ibutilide, if ineffective. If the diagnosis is not established, relationship(s), which may have inappropriately influenced the IV adenosine is administered followed by IV amiodarone or IV writing of this paper. ibutilide if ineffective.16 References Irregular narrow complex SVT 1. Hollenberg SM, Dellinger RP. Noncardiac surgery: Postoperative arrhythmias. Crit Care Med. 2000;28(10 ):145-50. The acute management of irregular narrow complex SVT also 2. Stewart AM, Greaves K, Bromilow J. Supraventricular tachyarrhythmias and their begins with assessment of haemodynamic status and correction management in the perioperative period. CEACCP. 2015;15(2):90-7. 3. Walsch SR, Tang T, Wijewardena C, Yarham SI, Boyle JR, Gaunt ME. Postoperative 2 of reversible causes. The management goal is rate control. arrhythmias in general surgical patients. Ann R Coll Surg Engl. 2007;89:91-5. 4. Mayr A, Ritsch N, Knotzer H, Dunser M, Schobersberger W, Ulmer H, et al. Atrial fibrillation Effectiveness of direct-current cardioversion for treatment of supraventricular tachyarrhythmias, in particular atrial fibrillation, in surgical intensive care The cornerstone of management of AF is rate control and patients. Crit Care Med. 2003;31(2):401-5. anticoagulation.20,21 Atrial fibrillation does not involve the 5. Knotzer H, Mayr A. Tachyarrhythmias in a surgical intensive care unit: A case-controlled epidemiologic study. Intensive Care Med. 2000;26:908-14. AV node in a re-entrant pathway and so AV nodal block by 6. Brathwaite D, Weissman C. The new onset of atrial arrhythmias following adenosine will only produce transient slowing of the ventricular major noncardiothoracic surgery is associated with increased mortality. Chest. 1998;114:462-8. rate; therefore rate control with beta blockers or calcium channel 7. Bender JS. Supraventricular tachyarrhythmias in the surgical intensive care unit: 10 blockers is the first line treatment. an unrecognized event. Am Surg. 1996;62:73-5. 8. Delacrétaz E. Supraventricular tachycardia. N Eng J Med. 2006;354:1039-51. Rate control with beta blockers (esmolol or metoprolol) is 9. Camm J, Savelieva I. Supraventricular Arrhythmias 2015 [Accessed recommended. These agents are negatively inotropic and should on 14/04/2017]. Available from: http://clinicalgate.com/ not be used in patients with severe left ventricular impairment. supraventricular-arrhythmias/. 10. Thompson A, Balser JR. Perioperative cardiac arrhythmias. Br J Anaesth. Diltiazem and amiodarone are recommended for heart rate 2004;93(1):86-94. control in patients with left ventricular impairment.2 11. Perreto G, Durante A, Limite LR, Cianflone D. Postoperative Arrhythmias after Cardiac Surgery: Incidence, Risk Factors, and Therapeutic Management. Cardiol Amiodarone is recommended by the ACC/AHA/HRS for use as a Res Pract. 2014;2014:1-15. rate-controlling agent for patients intolerant of or unresponsive 12. Link MS, Atkin DL, Passman RS, Halperin HR, Samson RA, White RD, et al. Part 6: electrical therapies: automated external defibrillators, defibrillation, 20 to other agents. Postoperative AF predisposes patients to cardioversion, and pacing: 2010 American Heart Association Guidelines for stroke and thromboembolism. Patients with persistent AF Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(suppl 3):S706-S19. should be risk stratified and anticoagulated as soon as it is safe in 13. Hutchins D. Peri-operative cardiac arrhythmias: Part one. Supraventricular the postoperative period.2,22 arrhythmias. ATOTW. 2013;279.

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14. Fernando HC, Jacklitsch MT, Walsh GL, Tisdale JE, Bridges CD, Mitchell JD, et al. 19. Lim SH, Anantharaman V, Teo WS, Chan YH. Slow infusion of calcium channel The society of Thoracic Surgeons Practice Guideline on the Management of blockers compared with intravenous adenosine in the emergency treatment of Atrial Fibrillation Associated With General Thoracic Surgery: Executive Summary. supraventricular tachycardia. Resuscitation. 2009;80(5):523-8. Ann Thorac Surg. 2011;92:1144-52. 20. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, et al. 2014 15. Amar D. Perioperative Atrial Tachyarrhythmias. Anesthesiology. AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: 2002;97(6):1618-23. a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 16. Page RL, Joglar JA, Conti JB, Field ME, Hammil SC, Lindsay BD, et al. 2015 ACC/ 2014;64(21):e1-76. AHA/HRS guideline for the management of adult patients with supraventricular 21. Ferrari R, Bertini M, Blomstrom-Lundqvist C, Dobrev D, Kirchhof P, Pappone C, et tachycardia. JACC. 2016;67(13):e27-115. al. An update on atrial fibrillation in 2014: From pathophysiology to treatment. 17. Luber S, Brady WJ, Joyce T, Perron AD. Am J Emerg Med. 2001;19(1):40-2. Int J Cardiol. 2016;203:22-9. 18. Das G, Ferris J. Esmolol in the treatment of supraventricular tachyarrhythmias. 22. Mann CJ, Kendall S, Lip GYH. Acute management of atrial fibrillation with acute Can J Cardiol. 1988;4:177-80. haemodynamic instability and in the postoperative setting. Heart. 2007;93:45-7.

S109 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

A study of perioperative deaths in Charlotte Maxeke Johannesburg Academic Hospital, a South African level four central hospital

A C Lundgren1, P Cleaton-Jones2

1 Department of Anaesthesiology, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand 2 Steve Biko Centre for Bioethics, University of the Witwatersrand

Background: An adverse outcome during the administration of an anaesthetic may result in morbidity or mortality, the latter providing the most fundamental measure of the safety of anaesthesia. Perioperative deaths due to anaesthesia have not been documented in Gauteng Province, South Africa, since 1955. This study was to document these deaths for comparison with previous South African and overseas studies. Objectives: 1. To investigate the prevalence of perioperative deaths, particularly anaesthesia associated deaths due to both general and regional anaesthesia, in the Charlotte Maxeke Johannesburg Academic Hospital during the period 2000–2004. 2. To examine and comment on current legislation and the causes or possible risk factors involved in the perioperative deaths that were studied. Methods: This was a retrospective longitudinal descriptive clinical audit. Results: The Anaesthetic Contributory Death (ACD) rate at the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) was 0.4 per 10 000, which is an improvement on the 2.1 per 10 000 seen in a pilot study in that hospital in 1999 and is a slight improvement on the 0.7 per 10 000 at Groote Schuur Hospital in the Western Cape by 1987. Conclusions: The ACD rate in this hospital is low; it may not improve any further, as human error cannot be totally eliminated from anaesthetic practice. South African law does not specify a time period from the start of the anaesthetic during which a perioperative death may be classified as an ACD. This is poorly understood by the medical fraternity and general public. An improved reporting system is recommended, with education at all levels, including anaesthetists, surgeons in all specialties, nursing staff, administrators and patients.

Clinical anaesthesia has been described as a state of their own right. Ultimately, these risks may combine into major “physiological trespass”1 and “an indispensable adjunct to the or minor morbidity (complications) or mortality (death). surgical management of disease”.2 “The more injury and disease In South Africa we do not have adequate reporting structures to have encroached on the body’s physiological milieu, the less can quantify anaesthetic associated mortality, let alone anaesthesia- anaesthetic encroachment per se be tolerated, and the more does associated morbidity. This is despite the latter’s importance, the clinical anaesthetist’s margin of error accordingly shrink”.1 particularly from the patient’s perspective. It is also becoming At times, this poses important risk to our patients. increasingly important to include outcomes that affect economic Since the promulgation of the National Health Act of 2003,3 issues, quality of life and patient satisfaction. legislation in South Africa mandates that patients (health care Rates of death due solely to anaesthesia are sometimes difficult users) be informed of the following: the range of diagnostic to ascertain and studies reporting these rates use varying procedures and treatment options available and the benefits, definitions of such deaths. What is clear is that anaesthetic related risks, costs and consequences associated with each option. mortality is rare. In previous studies in South Africa2,4-7 mortality This legislation also states that the information must be is estimated to have ranged from 1 per 2 anaesthetics in the very communicated in a language that the user understands and in a early days, (these were deaths in which anaesthesia played a manner that takes into account the literacy of the user (patient). “role”)7 to 1.1 per 10 000 anaesthetics,8 where anaesthesia was Thus, anaesthetic risk needs to be discussed with each patient considered solely responsible for the patient’s death. prior to receiving an anaesthetic. The first historically reported death due to anaesthesia was In order to determine the risks and consequences of anaesthesia, Hannah Greener who died due to aspiration on induction with multiple factors must be considered. There are those risks due chloroform. The anaesthetic was given to her by the surgeon, Mr. to the anaesthetic itself, the risks of the surgery, and also the Meggison, who was going to “remove the nail from the great toe patient’s co-morbid diseases, which may pose serious risks in of her right foot”.9

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Since then, numerous studies have been published African health facilities. It relies largely on the “voluntary co- internationally on anaesthesia mortality rates. These studies are operation” of anaesthetists and surgeons. often very difficult to compare for the following reasons10: Methods • There are no agreed definitions of what constitutes anaesthesia mortality; Before commencement the study was approved by the • There is no agreement over how much of the perioperative Committee for Research on Human Subjects (Medical) of the period to include (studies vary from 24 hours to 2 years); University of the Witwatersrand; permission to access records was granted by the hospital CEO. • The number of years to be covered by a particular study is frequently not clear. For the purposes of this study, but not in keeping with previous studies2,4,6,8 the following definitions were used: As a result, one cannot compare mortality rates to assess whether mortality from anaesthesia is improving. Each study needs to be An anaesthesia associated death (AAD) is a death occurring looked at individually. after the induction of a general or regional anaesthetic, or after the failure of a patient, conscious before, to regain Derrington and Smith11 reviewed studies of anaesthetic risk, consciousness after anaesthesia, regardless of the time that morbidity and mortality in 1987, and found numerous audits has elapsed since the start of the anaesthetic. and studies on “anaesthetic deaths”. The time perspective in these studies – in other words, the time that the death occurred An anaesthetic contributory death (ACD) is a similar death, in relation to the start of the administration of the anaesthetic but due solely to the anaesthetic. The ACDs therefore form a ranges from 24 hours to 30 days. For example, in 1978 Harrison sub-group of the AADs. looked at deaths within 24 hours of the administration of The 24-hour cut-off period after commencement of the the anaesthetic,6 whilst in 1963 Clifton and Hotten12 looked anaesthetic was also not used. at any death under, or attributable to, or without return of consciousness after anaesthesia. The study period was from the 1st January 2000 to 31st December 2004. All patients who died during or after surgery In South Africa, the Medical, Dental and Supplementary Health during this specified time were studied. They are referred to as Services Professions Act of 197413 states that “the death of a person whilst under the influence of a general anaesthetic or local perioperative deaths. Data were obtained predominantly from anaesthetic, or of which the administration of an anaesthetic has the records in the records store room in the Department of been a contributory cause, shall not be deemed to be a death Anaesthesia, and supplemented by central hospital records. The from natural causes, as contemplated in the Inquest Act, 1959 denominator figures were obtained from the operating theatre (Act 58 of 1959), or the Births, Marriages and Deaths Registration statistics. Data collected included demographics, American Act, 1963 (Act 81 of 1963).” This statement has been amended Society of Anesthesiologists (ASA) grading, surgery category, in the Health Professions Amendment Act of 200714 to read as premedication, pre-operative workup, anaesthetist level, type of follows: “the death of a person undergoing, or as a result of, a anaesthesia, airway management, anaesthetic record keeping, procedure of a therapeutic, diagnostic or palliative nature, or adverse event, and where and when the death occurred. of which any aspect of such procedure has been a contributory Anaesthetist level (of experience and training) was defined cause, shall not be deemed to be a death from natural causes, as follows: registrar, senior registrar (minimum of 3 years of as contemplated in the Inquest Act, 1959 (Act 58 of 1959), or experience and a primary examination for the FCA) and specialist. the Births, Marriages and Deaths Registration Act, 1992 (Act No 51 of 1992).” This means that in these circumstances a medico- Based on all of the information available, deaths were classified legal post-mortem must be performed, and an inquest (paper as caused by the anaesthetic (AAD), and whether it was solely or formal) held. due to the anaesthetic (ACD). If there was any doubt about the latter, the death was classified as an AAD. What was not clear with the original act (of 1974) was the definition of when a patient is no longer “under the influence” of Statistical analysis was with SAS for Windows (version 9.1, SAS an anaesthetic, a matter that still needs to be defined. Likewise, Institute Inc, Cary NC, USA). The statistical methods used were: the phrase “as a result of a procedure of a therapeutic, diagnostic descriptive statistics – frequencies and prevalence ratios; or palliative nature, or of which any aspect of such procedure has analytical statistics – for categorical analysis the Chi-square test been a contributory cause” needs to be clearly and specifically and Fisher’s exact test, depending on the numbers per category defined. What is clear, however, is that South African legislation cell. When a cell number was too low for the Chi-square test to does not state a time limit for recovery after the start of an be appropriate, a combination of categories, based on logic, was anaesthetic or procedure. Thus, a patient who suffers a cardiac used. Statistical significance was accepted at p < 0.05. arrest under anaesthesia with consequent hypoxic brain damage, Results and dies 2 years later, should still be classified as a death to which the anaesthetic contributed. The consequences are that the There were 465 perioperative deaths recorded during the 5-year death is unnatural in such a circumstance, requiring a medico- study period. Overall findings from the study are listed in Table 1. legal post mortem and inquest. This is a fact often ignored by The majority of cases (89%) were emergencies, 85% were in the anaesthetic and surgical colleagues, as well as by many South ASA 4 and 5 categories and 66% were trauma patients.

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A high proportion of patients (75%) were not worked up The prevalence rate for all causes of perioperative deaths preoperatively, probably because so many were emergencies, per 10 000 per year was calculated ((death category/total many of them ASA 5 trauma patients, who were rushed through cases)*10 000). The yearly rates for all deaths are compared to the operating theatre while being resuscitated. with the AAD and ACD rates in Table 4. The prevalence of AAD and ACD is very low in comparison with all of the causes; the Thirty-six percent of the patients (150 trauma and 11 from prevalence of ACDs for the entire 5 years is 0.4 per 10 000. the other categories) did not receive a hypnotic agent as part of the anaesthetic. Many received only a muscle relaxant and Discussion a small dose of opiate; some were apparently too sick to even It is likely that “human error” played a role in some, if not all of tolerate an opiate. What is unclear in this “no anaesthetic” group these ACDs, and at least two of the four had well-known and is whether they received any hypnotic agents “pre-casualty” treatable complications, namely anaphylaxis and a high spinal. or preoperatively, since at the time that these statistics were In both of these cases the anaesthetic was given by a senior being generated, some paramedics administered small to registrar. As Davies and Strunin commented in 198415 “when the moderate doses of hypnotic agents such as midazolam to problem is due to the anesthetic, most mishaps result from the patients. Nevertheless, it is still important to note the high failure of the anesthetist to recognize or cope with a problem.” number of patients who were “analgesed” and paralysed, but not “anaesthetised” with either a volatile or intravenous hypnotic. The data available in published articles and official reports thus far indicate that the risk of death attributable to anaesthesia has Almost all patients (98%) had endotracheal intubation; only probably declined over the years.10,16 The reasons for this are not 24% had a rapid sequence induction. This is unexpected, since entirely clear. They may include new monitoring modalities, new 89% were emergencies, and it would be expected that most of anaesthetic drugs and changes in the anaesthesia workforce. these patients would have received a rapid sequence induction. However, no study has shown improved outcomes with any one However, it is likely that many of the ASA 4 and 5 trauma patients of these, including the advent of pulse oximetry.16 This limitation were intubated either in casualty, or at the trauma scene, thus supports the need for ongoing audits and peer review of all of obviating the need for intubation in the operating theatre the complications relating to anaesthesia, with death being at and explaining the low number of rapid sequence inductions one extreme. recorded. Deaths due to anaesthesia or procedure-related deaths with Statistically significant relationships between ASA categories and anaesthesia as the primary cause are still not clearly defined the following variables were found, all at p < 0.0001: preoperative in South Africa. Harrison’s study included patients who died workup, anaesthetist “level”, whether an anaesthetic (hypnotic within 24 hours of the start of induction of anaesthesia, and he agent) was administered or not, whether a rapid sequence comments that he used this definition for convenience. However, induction was performed, when an adverse event occurred, as is illustrated in this study, three of the ACDs would not have when a patient died in relation to the start of the anaesthetic, been included in the study, if Harrison’s definition had been where a patient died, the surgical category and whether there used. Patients may suffer hypoxic brain damage as a result of an was trauma or not. There was weaker significant effect of airway anaesthetic misdemeanor, remain unconscious, and die months problems (p = 0.013) and no significant effect for the anaesthetic later. They should still be reported as procedure-related deaths. record. Anaesthetic record keeping was suboptimal, with records not appended to the GW7/24 forms. Until deaths due to anaesthesia are notifiable (as with maternal deaths17-20), and all those who administer anaesthesia are suitably The total perioperative deaths, numbers within trauma or other educated and trained, there will not be accurate anaesthetic surgical groups are listed in Table 2. There was an average of 3 mortality statistics in South Africa. Therefore, audits of what we ACD/AADs per year during the 5-year study period. Of these 15 do and how we are doing at it will continue to be inaccurate. cases, 4 may be considered ACDs, where the anaesthetic directly Debriefing and structured peer review needs to occur after caused the patient’s death. Thirteen out of the 15 were adults, all ACDs. A correlation between the clinical and post mortem two were children; seven were males, eight were females; six were causes of death would be very useful.21 ASA 2; five were ASA 3 and there were four ASA 4 patients. One Acknowledgement third of the patients who died from an anaesthetic associated (AAD) cause, died more than 24 hours after the start of the The study was funded by a research grant from the Jan anaesthetic. Four of these deaths were directly attributable to Pretorius Fund, provided by the South African Society of the anaesthetic (ACD), and all four died more than 24 hours after Anaesthesiologists. the start of the anaesthetic. Two of the patients were cardiac surgery patients, both anaesthetised by specialists. The “other” References 1. Moar J. Anaesthetic-associated mortality and anaesthetic contributory death: two patients received spinal anaesthetics. All 4 cases were the South African medicolegal approach. Forensic Sc Int. 1996;78:219-30. either ASA 2 or 3. Two patients had an adverse reaction to an 2. Harrison G. Death due to Anaesthesia at Groote Schuur Hospital, Cape Town - intravenous drug or fluid. Three out of the 4 died > 24 hours after 1956-1987. S Afr Med J. 1990;77:412-15. the start of the anaesthetic; 2 died at 7 and 10 days respectively. 3. South Africa. No 61 of 2003: National Health Act 2004 4. Harrison G. Death due to Anaesthesia at Groote Schuur Hospital, Cape Town - A breakdown of the 4 ACDs is illustrated in Table 3. 1956-1987 Part 2. S Afr Med J. 1990;77:416-21.

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5. Lienhart A, Auroy Y, Pequignot F, Benhamou D, Warszawski J, Bovet M, 14. South Africa. No 29 of 2007: Health Professions Amendment Act 2007. et al. Survey of anesthesia-related mortality in France. Anesthesiology. 15. Davies J, Strunin L. Anaesthesia in 1984: How safe is it? Can Med Assoc J. 2006;105:1087-97. 1984;131:437-41. 6. Harrison G. Death attributable to anaesthesia. A 10-year survey (1967--1976). Br J 16. Miller RD, ed. Risk of Anesthesia. In: Miller's Anesthesia. 6th ed: Churchill Anaesth. 1978;50:1041-6. Livingstone, 2007. 7. Kok O. Deaths associated with Anaesthesia and Surgery; A statistical analysis of 1000 cases. S Afr J Surg. 1964;2:55-70. 17. Moodley J. Saving Mothers: Report on Confidential Enquiries into Maternal Deaths in South Africa 1998. Pretoria, 1999. 8. Coetzee A. Mortality associated with anaesthesia. S Afr Med J. 1996;86:973-6. 18. Moodley J. Saving Mothers: Report on Confidential Enquiries into Maternal 9. Beecher H. The first anesthesia death with some remarks suggested by it on the Deaths in South Africa 1999-2001. Pretoria, 2002. fields of the laboratory and the clinic in the appraisal of new anesthetic agents. Massachusetts General Hospital. 1941:443-9. 19. Moodley J. Saving Mothers: Report on Confidential Enquiries into Maternal 10. Keats A. Anesthesia mortality in perspective. Anesth Analg. 1990;71:113-9. Deaths in South Africa 2002-2004. 11. Derrington MC, Smith G. A review of studies of anaesthetic risk, morbidity and 20. Pretoria, 2006. mortality. Br J Anaesth. 1987;59:815-33. 21. Moodley J. Saving Mothers: Report on Confidential Enquiries into Maternal 12. Clifton BS, Hotten WI. Deaths Associated with Anaesthesia. Br J Anaesth. Deaths in South Africa 2005-2007. Pretoria, 2009. 1963;35:250-9. 22. Carr. The autopsy: lessons from the National Confidential Enquiry into 13. South Africa. No 56 of 1974: Health Professions Act 1999. Perioperative Deaths. J R Soc Med. 2002;95:328-30.

S113 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Anaesthetic considerations for children with malignancies

C Lee

Department of Anaesthesia, Nelson Mandela Children’s Hospital, University of the Witwatersrand Correspondence to: [email protected]

Introduction and accumulation of lymphoid precursors, immature white blood cells (WBC) called lymphoblasts, in the bone marrow. It is estimated that one in 408 children worldwide will be These cells can then spread to other organs. The production of diagnosed with cancer before the age of 15. In Western countries, normal red blood cells (RBC), WBC and platelets is inhibited. ALL cancer is the second most common cause of death in children is commonly seen in children of 2–5 years of age, who present aged 5–14 years, after accidents. with signs and symptoms relating to the underproduction of In South Africa, the five most common childhood cancers are: normal marrow components (fever, infection, fatigue, headache, bruising, bleeding) or the infiltration of other organ systems with 1. leukaemia (25.4%) - most of these are ALL the abnormal cells (lymphadenopathy, hepatosplenomegaly). 2. lymphomas Leukaemias are more common in children with congenital 3. brain tumours abnormalities, including Noonan syndrome, neurofibromatosis 4. nephroblastomas and Fanconi’s anaemia.3 Children with Down syndrome have 5. soft tissue sarcomas1 a 10–20 times higher risk of developing acute leukaemia than non-syndromic children.4 These cancers are treated with chemotherapy, , surgery, bone marrow transplantation, or a combination of these Cure rates for newly diagnosed ALL approach 85%. ALL is typically modalities. The aim of combination therapy is to achieve better treated with high dose prednisone, daunorubicin, vincristine, results while limiting drug toxicity. L’asparaginase, and intrathecal hydrocortisone, methotrexate and cytarabine. Acute myeloid leukaemia (AML) is treated with Children may present for surgical and thus anaesthetic high dose cytarabine, daunorubicin and etoposide, as well as interventions at many points through their disease and intrathecal cytarabine.2 treatment. They may present for diagnostic procedures, like MRI scans, lumbar punctures, bone marrow sampling, and A systems-based approach when looking for the effects of the lymph node or tumour biopsies. They then present during malignancy and treatment should hopefully identify areas of their treatment for port insertions, intrathecal chemotherapy, concern, bearing in mind that certain complications can be and surgery for tumour excision. When assessing and treating subclinical and be unmasked during times of physiological these children, the anaesthetist needs to actively consider the stress, such as surgery and anaesthesia. An excellent in depth following: review of this subject can be found in Latham and Greenberg’s 1. the effects of the malignancy itself (both physical effects, three-part review in Paediatric Anaesthesia in 2010. e.g. masses, and effects on other organ systems, such as 1. The effects of the malignancy myelosuppression) (i) Airway 2. toxicity of therapy (often masked in the ill child) 3. coexisting illnesses, including sepsis While oral tumours are rare, tumours compressing structures lower down the airways are not. 4. psychosocial vulnerability Anterior mediastinal masses are commonly seen in children As leukaemia is seen so often, and is treated with all the drugs with non-Hodgkin’s lymphoma (NHL), T-cell ALL, and Hodgkin’s, that can cause toxicity, it deserves a brief mention. where up to 50% of children may have a mediastinal mass at Almost 80% of childhood leukaemias are acute lymphoblastic presentation.3 Signs and symptoms, where present, relate to leukaemia (ALL). ALL is characterized by the overproduction the compression of major vascular and respiratory structures

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(superior vena cava (SVC) syndrome or superior mediastinal (iii) Respiratory syndrome). A high index of suspicion in children with these While primary lung tumours are rare in children, respiratory malignancies is important as up to 50% of masses are compromise is not. Abdominal tumours can cause splinting and asymptomatic at presentation,3 making a good history and reduced FRC, cancers may be associated with pleural effusions, examination essential. Signs and symptoms include: and pneumonias are common as a result of immunosuppression. 1. cardiovascular: Most respiratory complications are due to treatment.

a. symptoms: chest pain, syncope, nausea, headache (iv) Haematological system b. signs: SVC obstruction, cyanosis, facial swelling, dilated Myelosuppression is a common complication of childhood upper body veins cancer, manifesting with the signs and symptoms of low red cell, 2. respiratory: white cell and platelet counts. Hyperleukocytosis can occur in a. symptoms: wheeze, cough, dyspnea, hoarse voice, AML and can cause clumping of white cells blasts with resultant dysphagia hyperviscosity and intravascular sludging, leading to hypoxia, b. signs: stridor, orthopnoea infarction and haemorrhage. Thrombophilia and thrombosis are also seen, especially in children with sarcomas or haematological Compression and distortion of airway structures like the carina, malignancies.5 trachea and bronchi are of particular concern because they are 2. Toxicities of treatment so compliant in children.5. The severity of symptoms does not correlate well with the degree of compression, with the exception A full review of the pharmacology of chemotherapeutic agents is of stridor, which has been shown to correlate significantly beyond the scope of this lecture, and is comprehensively covered with anaesthetic complications.6 All children with an anterior in Latham and Greenberg’s article7 and others. A systems-based mediastinal mass presenting for surgery should have diagnostic approach is presented here. imaging, which may include CXR, CT/MRI and echocardiography. (i) Airway Children with > 50% compression of the trachea are at high risk of respiratory complications during anaesthesia.3 It should be Oral mucositis has been described as the most painful part of ascertained if their symptoms are positional (may be relieved by a child’s chemotherapy journey. It is associated with high-dose chemotherapy and radiation to the head and neck. Irradiation turning laterally). can also cause soft tissue fibrosis, which may cause limited These tumours can be shrunk with high dose steroids and mouth opening, neck extension, and fibrosis and narrowing of radiation. The problem is in the patient who needs a tissue airway structures.5 diagnosis before treatment can be started, as preoperative Cases of severe mucositis have been associated with difficult irradiation and steroids have traditionally been described as intubation and with airway bleeding and oedema. The airway having the potential to alter the tumour cell histology. This has may be friable and prone to injury. At the same time, airway 6 been shown to not always be the case, and in the symptomatic trauma can cause sepsis in neutropaenic children with mucositis child, preoperative treatment and tumour shrinkage should be and needs to be avoided. In cases where children have received seriously considered. radiation to the head and neck, particularly in the past, smaller endotracheal tubes may be required due to airway stenosis and The second option is to perform the surgery (e.g. lymph node retarded growth. biopsy) under local anaesthetic. This may not be feasible in small or uncooperative children. Beware the “gentle sedation” as it (ii) Cardiac carries significant risks, including loss of the airway. The anthracyclines doxorubicin and daunorubicin, frequently If general anaesthesia is required, the child should be induced used in the treatment of childhood cancer, are the main in a position in which they are comfortable (usually head up or culprits to watch out for. A prospective cohort study from 8 lateral), spontaneous ventilation should ideally be maintained, Pakistan demonstrated that 14% of children developed cardiac dysfunction within a month, and 25% within a year of starting and they should be extubated awake. If IPPV is used, it should treatment with the anthracyclines. In addition, 6.4% died due be demonstrated that the child can be adequately ventilated to severe cardiac dysfunction. It seems that younger patients before a muscle relaxant is given.6. Postoperative ICU facilities are particularly at risk, with studies describing some degree, should be available5,6 and a fibreoptic bronchoscope and rigid often subclinical, of cardiac dysfunction in 18–57%,9 and long- bronchoscope should be available in theatre. There should term follow-up studies demonstrating cardiac toxicity in 70% be good team communication and plans in place in case of of patients previously treated with anthracyclines. Toxicity can cardiorespiratory compromise. present early, with symptoms and signs of a cardiomyopathy, (ii) Cardiac but often presents late, when the damage is progressive. Other effects include myocardial depression and ischaemia, Pericardial effusions may be present in children with lymphomas. hypotension, arrhythmias (including SVT and heart block) and Intracardiac tumours are rare.5 myocarditis.5

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Cardiotoxicity is dose dependent, and it seems that doxorubicin is bleomycin dose (> 400 U/m2), and combination treatment with worse than daunorubicin. Damage is probably caused by oxygen other chemotherapeutic agents and radiation.16 free radical-mediated cytotoxicity and results in impaired left The perioperative use of high FiO has been implicated in ventricular reserve and contractility with long-term myocardial 2 accelerating lung damage in patients being treated with systemic fibrosis.10 Diastolic dysfunction has also been demonstrated.11 bleomycin,17 likely due to increased free radical production. It is Cardiac damage is worse with concomitant chest radiation, recommended that FiO be kept to the lowest sensible limit for which causes damage both to heart muscle and to valves, 2 these children, while avoiding hypoxia. Of note, there have been particularly mitral and aortic, resulting in incompetence.9 no reported cases of pulmonary fibrosis following intralesional There is controversy as to how often patients should be screened. bleomycin sclerotherapy (e.g. a lymphatic malformation), likely Guidelines published in 1992 recommend screening at least because the systemic doses of bleomycin are not high enough. 3 weeks after the last dose and a week before the next dose Several skin changes have been reported in patients receiving of anthracycline therapy,12 but this routine screening has not bleomycin therapy. As with the lung changes, this is probably been shown to change management.13 In our limited-resource because bleomycin is not metabolized in the skin. Reported setting, patients usually have a baseline echo before starting skin reactions include flagellate erythema, Raynaud’s, treatment and then as dictated by their clinical condition.2 This hyperkeratosis, nailbed changes, plantopalmar desquamation lack of regular screening mandates a good history-taking and and hyperpigmentation.18 examination before anaesthesia, with a preoperative echo where clinically indicated. The concern is that our clinical skills may miss There have been a couple of reports of abnormal pigmentation more than 50% of patients with early chemotherapy-induced developing around ECG sticker points following intralesional heart failure,14 meaning we need to maintain a high index of bleomycin injection.19 The changes seem to be inflammatory suspicion and vigilance. It would seem prudent to minimize mediated and increase with heat. It is recommended that if myocardial depressants and negative inotropes. intralesional bleomycin is being used, ECG dots be placed in places where residual hyperpigmentation is less visible, such as Childhood cancer survivors should ideally be followed up with the axillae and soles of the feet. Skin precautions such as those screening echos every 2 to 5 years, as an increased risk of cardiac used for epidermolysis bullosa are not necessary. death has been demonstrated in adults who were exposed to anthracyclines as children.15 Radiation therapy also causes lung damage that can progress from interstitial pneumonitis to pulmonary fibrosis. (iii) Respiratory (iv) Kidney Chemotherapeutics can cause a range of pulmonary toxicity that can manifest as pneumonitis, pulmonary oedema or fibrosis. The Several agents have been implicated in causing nephrotoxicity, signs of pulmonary fibrosis may be insidious and include a dry including cisplatin, carboplatin, ifosfamide, methotrexate, cough, dyspnea, fever and basal crackles.5 The two worst culprits cyclophosphamide and radiation therapy. are bleomycin and methotrexate. Children can clinically present A U&E should be checked prior to surgery. Take care to maintain with either restrictive or obstructive lung disease. renal perfusion and avoid nephrotoxic agents. Exercise caution Bleomycin deserves special mention: when using NSAIDs in children with dehydration or pre-existing renal dysfunction. Bleomycin is an antibiotic used as chemotherapy for the treatment of germ cell tumours and Hodgkin lymphoma, as well The most dramatic cause of acute renal failure is tumour lysis as intralesionally for the sclerotherapy of lymphatic and venous syndrome (TLS): malformations or persistent pleural effusions. It is metabolized TLS occurs when rapidly dividing large volume tumours, e.g. by enzymes that are not present in the skin or lungs, which is the acute leukaemias, lymphoblastic lymphomas and B cell why that is where side effects are seen. lymphomas (including Burkitts lymphoma) are treated with cytotoxic agents.20 The chemotherapy causes rapid cell death The most serious side effect is that of pulmonary toxicity. and tumour breakdown, with an efflux of potassium, phosphate, Bleomycin accumulates in the lung and causes inflammation and and uric acid, causing these children to develop acute renal damage to endothelial cells and alveolar epithelial cells, impairing failure and a hyperkalaemic metabolic acidosis, which may alveolar barrier function. The mechanism is not well understood be fatal. This is considered an oncological emergency and but involves reactive oxygen species. This causes a range of needs to be managed immediately. TLS has been described disease processes, from subclinical lung function abnormalities as being triggered by steroid therapy, intraoperative tumour to life threatening and disabling pulmonary fibrosis. Described manipulation, pyrexia, chemotherapy, radiation, and has been pulmonary disease includes bronchiolitis obliterans organizing described as occurring spontaneously. While originally described pneumonia (BOOP), eosinophilic hypersensitivity, and interstitial in haematological malignancies, cases of TLS have also been pneumonia (most common), which may progress to fibrosis. seen in patients with solid tumours, such as Wilms tumours and Some degree of pulmonary reaction is said to occur in 10% of embryonal tumours. adult patients, with 1% of these dying of pulmonary fibrosis. The onset usually starts a few months after finishing treatment. There are several cases described in the literature of children Risk factors include younger age, higher cumulative systemic developing TLS in the perioperative period. In some cases, the

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TLS seemed to be triggered by surgical handling (especially Leukopaenia and specifically neutropaenia contribute to with large tumours),21 but in most cases the TLS seems to have significant morbidity (up to 30%) and mortality (1%) in children been associated with the administration of a single dose of with cancer,5 due to infections and sepsis. Care should be taken dexamethasone as an anti-emetic. to minimize their contact with children and staff with other infections, such as respiratory infections, chicken pox and Dexamethasone induces apoptosis of B cells, including gastrointestinal infections. These children should be placed on a monoclonal lymphoma and ALL cells.20 It causes rapid theatre list before any known infective cases. cytoreduction, especially in the case of previous chemotherapy. It is thus recommended that dexamethasone be avoided as a Central lines and ports should be accessed using strictly aseptic routine antiemetic in children with malignancies,22 and that a techniques. Hands should be washed before accessing the line high index of suspicion for perioperative TLS be maintained and and gloves worn before cleaning the hub with a chlorhexidine- supportive care started immediately if TLS is suspected. containing wipe. At the end of the procedure, the line should be flushed to ensure that there are no residual drugs in the line or Emergency management23 includes: connectors.3 • aggressive hydration with normal saline and diuresis to avoid obstructive uropathy (vii) Endocrine • reducing the potassium: Steroid therapy may cause features of Cushing’s and impaired ▫▫ insulin 0.1 U/kg with 50% dextrose 2 ml/kg glucose control. There are concerns about these children being able to mount an adequate stress response in the face ▫▫ calcium gluconate 100 mg/kg or calcium chloride of long standing steroid treatment, and a replacement dose of 10–20 mg/kg 1–2 mg/kg of hydrocortisone might be appropriate for major ▫ iv salbutamol ▫ surgery. However, in children at risk for TLS this should be • treating the acidosis (Sodium bicarbonate 1–2 mmol/kg) discussed with their oncologist first, as discussed above.

Dialysis and inotropic support may be required and the child 3. Coexisting illnesses should be transferred to ICU as soon as possible. Coexisting illnesses to look out for include infection, especially (v) GIT pneumonia with respiratory failure, hyperviscosity and thromboembolic phenomena, and complications of bone The side effects of chemotherapy include nausea and vomiting, marrow or stem cell transplantation including GVHD. diarrhoea, mucositis, stomatitis and enterocolitis. Radiation can damage the microvasculature of the gut and cause perforations, 4. Psychosocial vulnerabilities stenoses, enteritis and adhesions. As a result, children may Children with cancer and their families are a particularly present with electrolyte imbalances, dehydration, malabsorption vulnerable patient population. These children are more likely to and malnutrition.5 Antiemetics should always be given with be diagnosed with depression, anxiety, PTSD and behavioural chemotherapy. problems than their healthy peers.14 They may have had numerous (vi) Haematological system procedures and developed their own coping mechanisms to deal with them. They may have particular preferences around Myelosuppression is a common dose limiting effect of induction (iv vs inhalational) or specific rituals they need to many chemotherapeutic agents, particularly methotrexate, follow prior to a procedure. It is worth asking what these are and cyclophosphamide, ifosfamide, vincristine and the what premedication has or has not worked in the past. anthracyclines. It leads to anaemia, thrombocytopaenia and neutropaenia. These children have usually experienced numerous episodes of pain of varying degrees – either from their surgeries or from the Anaemia occurs in over 80% of children with cancer.5. It may cancer itself (both from the tumour and metastases). They may be managed with erythropoietin or transfusion. If transfusion have significant analgesic requirements. is required, it should be with leucodepleted and irradiated products. It is recommended that the child’s haematologist/ Summary oncologist be contacted before electively transfusing patients. Childhood cancer is common. The most common of these are the Platelet transfusion, where required, is not innocuous. The leukaemias, which have a high cure rate but are treated with all data on platelet transfusion thresholds in these children is not the agents that cause multiple organ system toxicities. A child’s clear, but it is suggested that a platelet count above 40 000 is treatment regime should be available and read before embarking adequate for surgery if no other coagulopathy is present. For on anaesthesia and surgery. The child should be examined with bone marrows, a platelet count of 20 000 is said to be sufficient, special focus on the above organ systems, bearing in mind that and a count of 10 000 for an LP appears to be safe. A platelet subclinical cardiac and respiratory dysfunction are common and count above 100 000 is recommended before neurosurgery. A may be unmasked under anaesthesia and the stress of surgery. transfusion of 10 ml/kg of platelets should cause the platelet Preoperative blood and imaging tests should be performed count to rise by 50–100 000.5 where clinically indicated.

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Take home tips: 8. Shaikh AS, et al. Anthracycline-induced cardiotoxicity: prospective cohort study from Pakistan. BMJ Open. 2013;3:e003663. doi: 10.1136/bmjopen-2013-003663 • Avoid dexamethasone as an antiemetic 9. Kucharska W, et al. Cardiotoxicity of oncological treatment in children. Adv Clin • Avoid unnecessary hyperoxia in children treated with Exp Med. 2012;21(3):281-8. bleomycin 10. Kaneko S, et al. Impaired left ventricular reserve in childhood cancer survivors treated with anthracycline therapy. Pediatric Blood Cancer. 2016 63(6):1086-90. • Avoid nephrotoxic agents and NSAIDs in children with any 11. Harasheh A, et al. Diastolic function in anthracycline-treated children. Cardiology renal dysfunction in the Young. 2015;25(6):1130-5. 12. Steinherz LJ, et al. Guidelines for Cardiac Monitoring of Children During and • Ensure organ perfusion – optimize cardiac output and oxygen After Anthracycline Therapy: Report of the Cardiology Committee of the delivery Children’s Cancer Study Group. Pediatrics. 1992;89(5):942-9. 13. Watts RG, et al. Pretreatment and routine echocardiogram monitoring during • Maintain a good relationship with your haem-onc colleagues. chemotherapy for anthracycline-induced toxicity rarely identifies significant cardiac dysfunction or alters treatment decisions. Cancer. 2012;118:1919-24. The child with cancer is physiologically, psychologically and 14. Latham GJ, Greenberg RS. Anesthetic considerations for the pediatric pharmacologically vulnerable, and should be treated as such. oncology patient – part 3: pain, cognitive dysfunction, and preoperative And so should their families. evaluation. Paediatr Anaesth. 2010;20:479-89. 15. Armenian SH, et al. Recommendations for cardiomyopathy surveillance References for survivors of childhood cancer: A report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol. (those marked in bold are recommended reading) 2015;16(3):e123-e126. 1. www.choc.org.za/childhood-cancer/cancer-facts.html 16. Huang T-T, et al. Pulmonary outcomes in survivors of childhood cancer. Chest. 2. Personal communication, Dr J Geel. 2017. 2010;140(4):881901. 3. Oduro-Dominah L, Brennan LJ. Anesthetic management of the child with 17. Allan N, et al. Anaesthetic implications of chemotherapy. Continuing haematological malignancy. Continuing Education in Anaesthesia, Critical Care Education in Anaesthesia, Critical Care and Pain. 2012;12(2):52-6. and Pain. 2013;13(5):158-64. 18. Yamamoto T. Bleomycin and the skin. Br J Dermatol. 2006;155:869-75. 4. Scrace B, McGregor K. Anaesthetic considerations for paediatric oncology. 19. Sainsbury DG, et al. Unexpected hyperpigmentation following intralesional Anaesthesia Tutorial of the Week 280 bleomycin injection. JPRAS. 2009;62:e497-e499. 5. Latham GJ, Greenberg RS. Anesthetic considerations for the pediatric 20. McDonnell C, et al. Fatal peri-operative tumour lysis syndrome precipitated by oncology patient – part 2: systems-based approach to anesthesia. Paediatr dexamethasone. Anaesthesia. 2008;63:652-5. Anaesth. 2010;20:396-420. 21. Dhar M, et al. Intraoperative tumour lysis syndrome in a child with Wilm’s tumor. 6. Hack HA, et al. The anesthetic management of children with anterior Anesth Essays Res. 2016;10(1):145-7. mediastinal masses. Anaesthesia. 2008;63:837-46. 22. Bartlett R, Hartle AJ. Routine use of dexamethasone for post-operative nausea 7. Latham GJ, Greenberg RS. Anesthetic considerations for the pediatric and vomiting: the case against. Anaesthesia. 2013;68:889-98. oncology patient – part 1: a review of antitumor therapy. Paediatr Anaesth. 23. Farley-Hills E, et al. Tumour lysis syndrome during anesthesia. Paediatr Anaesth. 2010;20:295-304. 2001;11:233–6.

S118 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Can you sedate a child for a dental procedure?

B M Gardner

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

Dental procedures may be uncomfortable, painful or simply scary • In 43.2% of cases no emergency drugs were at hand. to any patient. This is a particular problem for young children. • In 19.6% of cases no emergency or resuscitation equipment Because the resource of general anaesthesia in a theatre setting is was at hand. so limited, the option of procedural sedation and analgesia (PSA) in the dental rooms is widely used.1 Apart from the shortage of These results are staggering and terrifying. They show extreme actual theatre space; cost, time and dentist comfort are also major non-compliance with South African Society of Anaesthesiologists drivers. Performing dental work under general anaesthesia in (SASA) sedation guidelines, and in the words of Dr De Wet of the theatre adds significantly to the total financial cost of treatment. Society of Sedation Practitioners of South Africa (SOSPOSA): 2 As specialist anaesthetists are relatively scarce, these dental “This is exactly how sedation should not be done.” room sedations are often performed by non-anaesthetists and in In 2000, Charles Cote et al. did a critical incident analysis of 1 up to 43% of cases, by the dentist themselves. So the question is contributing factors to adverse sedation events in paediatrics.3 not “Can you sedate a child for a dental procedure?” but “Should They obtained data from 3 sources: you?” and if yes, then, “How should it be done?” 1. Food and Drug Administration (FDA) voluntary reports Paediatric dental room sedation is being done globally. Several between 1969 and 1996. tragic case reports have emerged from the USA, mostly where 2. US Pharmacopoeia (USP) drug event reports from a similar dentists have been the sole operator providing both sedation period. and dental care. There is ongoing debate in the USA of where the 3. Survey results from a group of over 1 300 USA practitioners divide lies between anaesthesia and dental scopes of practice. surveyed.

In South Africa, in 2015, Bham F et al. performed an audit of Where possible, the cases were divided into hospital based vs. 1 dental chair sedation practice in Gauteng. Following random non-hospital based locations. They admit that under-reporting sampling, 213 dental practitioners were interviewed. Of these, a may have influenced their results, but did identify a total of 118 total of 94 (44.1%) routinely practice paediatric dental chair PSA. sedation cases across the full spectrum of paediatric sedation This group of 94 practitioners were asked to complete an online where adverse events occurred, from these 3 sources. Of these, survey, to which 52 (55.9%) responded. in 95 cases, the adverse event was purely sedation related. This Bham F et al. found the following: number seems low but the outcome for these 95 cases was that 51 died and 9 suffered permanent neurological damage. While • Overall PSA rate 44.1%. the incidence of respiratory depression was equal in the hospital • Patients mostly 1–5 years old. (76.6% of patients < 6 years of vs. the non-hospital group, other results were all greater in the age). non-hospital setting: • Minimal to moderate sedation targeted most of the time. Non-hospital setting Hospital setting • Midazolam the most frequently used agent. Sometimes Respiratory events ≈ 80% ≈ 80% supplemented with Nitrous Oxide (N O). 2 Cardiovascular events 53.6% 14% • In 28.1% of cases ≥ 3 agents were used. (as 2nd complication) • A pre-sedation assessment was done in 83% of cases. Cardiovascular events 25% 7% (as 3rd complication) • Informed consent was obtained in 75.6% of cases. Inadequate 57.1% 2.3% • In 41.3% of cases no monitoring was used at all. resuscitation • In 41.3% of cases the dentist was the sole operator sedationist Death or permanent 92.8% 37.2% and dentist. neurological injury

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The 35 patients who did not die or suffer permanent neurological In 2013, Helen Lee et al. looked at media reports from injury had all been monitored with pulse oximetry as opposed 2 databases, during the period 1980 to 2011, to find deaths to the other cases, where no documented monitoring could be related to paediatric dental sedation or general anaesthesia.6 ascertained. The media databases used were the Lexis-Nexis Academic search engine and the Raven Maria Blanco foundation website. They Of these 95 patients, 32 (33.7%) had received sedation for dental specifically did not look at any outcome other than death (i.e. procedures, showing that across the full spectrum of possible neurological damage or other adverse outcomes were excluded) reasons to administer paediatric sedation, dental procedures and admit that under-reporting probably affected the accuracy carry the highest risk. of their numbers. Still, some interesting trends did emerge. Cote et al. reached the following conclusions: A total of 44 deaths were found in these media reports. 41 of the patients were completely healthy prior to the event and all the 1. The non-hospital setting carries a higher risk and is associated deaths were believed to have been largely preventable. Three with poorer resuscitation and rescue chances. patients had pre-existing medical conditions which were not 2. Poor monitoring and poor responses to abnormal monitor picked up during a pre-sedation assessment. Lee found that: readings are associated with poorer outcomes. • 21/44 (47.7%) of patients were in the 2 to 5-year age group. 3. Pre-sedation assessments were often inadequate or omitted. • 21/44 (47.7%) of cases occurred in dental rooms. 4. Poorer outcomes correlated more frequently with single • In 25/44 (56.8%) of cases the dentist had been a sole operator. operator sedationists and where an independent observer In most of these cases moderate sedation had been used. was not present. • Most patients initially suffered a respiratory arrest which was 5. Medication errors in paediatric dosing were common. subsequently followed by a cardiac arrest. 6. Inadequate recovery procedures were associated with • Sources of error were found to have been: poorer outcomes. ▫▫ Inadequate or no pre-sedation assessment done. In 2000, Charles Cote et al. also looked at the medications ▫▫ Medication errors. involved when adverse events occurred during paediatric ▫▫ Inadequate or no monitoring used during sedation. sedation in these same 95 cases mentioned above.4 Looking at ▫▫ Inadequate resuscitation equipment availability and poor the 60 patients who suffered death or permanent neurological staff training in resuscitation skills. injury they found the following relationships: In 2016, Nathan Reuter and colleagues from the Department of Incidence of death or Oral Health Practice at the University of Kentucky, USA, published permanent neurological injury a systematic review of death related to dental treatment in Type of drug used No difference general.7 They found itself to be very safe, with the Route of drug administration No difference mortality rate for pure, non-sedated dentistry to be less than Drug overdose ↑ (28/ 60 cases) 1 death per 10 million patients. However, as soon as PSA is added Drug combinations ↑ (Especially if ≥ 3 drugs used) to the picture, this mortality rate jumps to around 1 death per

N O added to other sedative 350 000 patients. In fact, Reuter et al. found 94% of all dentistry 2 ↑ agents related deaths to be anaesthesia, sedation or medication error Giving sedative to parent to linked. They found the following associations: administer at home or en route ↑ • A strong association between death and either the absence to the clinic of an anaesthetist altogether, or when single service providers Non-medical sedationist or single ↑ did the sedation as well as the dentistry; also between the operator sedationist levels of training which the sedationists possessed if they were Discharging patients home too indeed present. early before sedative(s) had ↑ worn off • A strong association between death and deeper levels of sedation being used. A review of the closed malpractice insurance claims for dental • Inadequate monitoring was a causal risk factor in most deaths. related anaesthesia and PSA events, of two liability carriers during the period 1993 to 2007, by Chicka et al. in 2012 uncovered • Poor emergency procedure implementation in these lethal 17 claims.5 Of these, one patient had received a general cases. anaesthetic, three received local anaesthesia alone, and the • Children under 5 years were most at risk. (All were usually remaining 13 all had sedation. 53.6% of patients suffered normal, healthy children pre-procedure). death or permanent neurological damage. The average patient • Causes of respiratory related deaths were predominantly from age was 3.6 years old. In 6 of the 13 sedation cases the dentist airway obstruction due to: had been the sole operator sedationist and dentist. 71% of ▫▫ Foreign body aspiration the sedation mishaps occurred in dental rooms. In 12 of the ▫▫ Angioedema 13 sedation related incidents no monitoring had been used. Again it is monitoring, single operator sedationist/dentists and ▫▫ Hypersensitivity reactions office based sedation that stand out as risk factors. ▫▫ Spasm and asphyxia

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Bellolio et al. did a systematic review and meta-analysis of The patient may not be able to maintain his/her own 13 883 PSA sedations done for children requiring minor procedures airway or breathing, which may require intervention by the in the emergency department in 2016.8 In contrast to studies sedationist. which involve dental procedures, where death or permanent 4. General anaesthesia. neurological damage is the focus, this meta-analysis revealed no deaths at all, and in fact found respiratory complications to be The patient has a depressed level of consciousness from very rare. These were 34 cases of laryngospasm, of which only which he/she cannot be roused, even with painful stimuli. one required intubation. This re-emphasizes the particular risk The patient may not be able to maintain his/her own airway which PSA for dental procedures does carry. or breathing.

PSA for dental anaesthesia is particularly fraught. The greatest While minimal to moderate sedation is generally aimed for challenge is the shared airway. Minimal to moderate sedation is during PSA, it is important that the sedationist is always capable generally planned, but there is always the risk of accidental over- of rescuing a patient who inadvertently progresses to a deeper sedation. The level of stimulation will fluctuate, making it difficult level of sedation. to maintain the sedation level constant without inadvertently slipping too far into the next level of sedation. Applying In the SASA sedation guidelines, a further distinction is made between simple or standard sedation and advanced sedation. topical anaesthesia prior to inserting intravenous lines and SASA endorses single operator sedationist/dentists for the use of dental local anaesthesia injections will help to avoid requiring simple or standard sedation but requires a separate sedationist a deeper sedation plane during these interventions. The use of as soon as the use of advanced sedation is planned. Even N O alone may be sufficient when there is no stimulation, but 2 with single-operator sedation, however, a separate observer generally fails as soon as any painful or deep stimulation is given. must be present to monitor the patient. Simple sedation does The dentist must understand that having the patient in the also require that all safety equipment, monitoring and rescue correct plane of sedation means that the patient should still move. protocols are in place. Non-fasted patients may be offered simple This will probably happen unexpectedly, either spontaneously, or standard sedation. Patients presenting for advanced sedation but especially to painful stimuli. Aspiration of foreign bodies, must all be fasted according to standard anaesthesia fasting blood or irrigation water is also a real danger and apart from guidelines. Fasting guidelines are currently a topic of debate in Mendelsohn’s syndrome, this may provoke laryngospasm and the literature.10 For now, however, the SASA guidelines remain 6 bronchospasm. The dentist must use the minimum amount hours for solids and formula feeds, 4 hours for breast milk and 2 of water to cool their drill and suction pedantically. Even with hours for clear fluids. minimal to moderate PSA, most young children are still not Simple or standard sedation. able to tolerate sitting in the dental chair for very long. Often, only short, limited procedures are possible for these patients A single agent is used. This may be: under PSA. • Administered by an oral or transmucosal route. SASA has published updated guidelines for paediatric PSA • A single titrated intravenous dose of midazolam. 9 in 2016. These guidelines cover the full ambit of PSA for all • Inhaled N2O in 50% oxygen. procedures in children, not only those presenting for dental procedures. SOSPOSA fully endorses these guidelines and is Advanced sedation lobbying for the implementation of training and accreditation • Any drug combination using more than one agent. for sedationists in South Africa. • An intravenous bolus injection or continued transfusions. • Inhaled N O in < 50% oxygen or any other inhaled agents. Sedation end-points are described as follows9: 2 1. Minimal sedation. (Anxiolysis)Cognitive function is impaired The SASA guidelines emphasize the importance of careful but the patient responds normally to verbal commands. patient selection prior to performing PSA9: Ventilatory and cardiovascular function is unaffected. 1. Only ASA I & II patients should be offered PSA. It is important 2. Moderate sedation. to remember that an ASA II patient may deteriorate acutely and be ASA III on the day of the procedure, so a thorough The patient has a depressed level of consciousness but still pre-sedation assessment is warranted. responds purposefully to verbal commands or light touch. The patient maintains his/her own airway and breathing. 2. All patients < 5 years of age must be sedated by practitioners trained specifically in PSA for young children. 3. Deep Sedation. 3. All PSA practitioners must have completed life support This forms part of the spectrum of general anaesthesia and training. may only be practised by practitioners with anaesthesia 4. Children suffering from an acute upper respiratory tract training. infection should be postponed until after this has resolved.

Deep sedation is also known as “monitored anaesthesia care”. 5. Children < 1 year of age and all ASA III or higher patients should be referred to a specialist anaesthetist or highly The patient has a depressed level of consciousness but experienced and trained paediatric sedationist. These responds purposefully to repeated or painful stimuli, i.e. not patients should probably undergo their procedure in a merely a reflex withdrawal to pain. hospital setting and not undergo an office-based procedure.

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The importance of a thorough pre-sedation assessment cannot during moderate sedation in 2005, challenging the guideline to be over-emphasized. Apart from identifying underlying medical monitor with pulse oximetry only.11 They looked at the incidence conditions, a thorough focussed airway assessment must be done of hypopnoea and apnoea diagnosed by observing chest and the ability to communicate with the patient ascertained. It is movement and pulse oximetry vs capnography and their results important to ensure that the child will be able to co-operate and were as follows for patients sedated with identical sedation tolerate minimal to moderate sedation for the procedure. protocols:

Documentation must include: Hypopnoea Apnoea detection • Informed consent. detection rate rate • The pre-sedation assessment. Chest wall 3% detected 0% detected observation and • The sedation chart outlining drugs administered and observed pulse oximetry vital signs. Capnography 56% detected 24% detected • Post-procedure observations. These results beg the question; “Are we simply not seeing the • Home instructions. apnoea or hypopnoea episodes with our current observation Examples of all these documents are included in the SASA methods?” 9 guidelines document. All the conditions required for safe day The addition of supplemental oxygen in particular, may mask the case procedures must also be adhered to. desaturation which would otherwise present when monitoring Short-acting sedative agents are generally recommended and by pulse oximetry alone. where applicable, antidotes must be available in the emergency In conclusion, paediatric PSA for dental procedures is already drug armamentarium. Supplemental analgesia should not being widely done in our country, unfortunately often to poor be forgotten. The SASA guideline document includes a full safety standards, as can be seen from the Bham F et al. study. 9 description of suitable agents for PSA. Paediatric dental PSA is potentially extremely dangerous, but Before office based PSA is commenced, a clear plan for emergency the pitfalls and practice guidelines are quite clear. Education, management and transfer to a hospital setting must be in place. accreditation and implementation of the SOSPOSA and SASA Emergency equipment and drugs required for rescuing a patient guidelines will hopefully go a long way to enhance safety for who proceeds to a deeper level of sedation, or who suffers an a practice which will likely remain popular, given the resource unanticipated complication, must be directly available. A full list constraints we face. 9 of these is available in the SASA guidelines document. References: The SASA guidelines for monitoring of minimal and moderate 1. Bham F, Perrie H, Scribante J, et al. Paediatric dental chair sedation: An audit of current practice in Gauteng, South Africa. SAMJ. 2015;105(6);461-4. sedation include: 2. De Wet; SASA refresher course lecture, March 2017. 1. Level of consciousness (University of Michigan Sedation 3. Cote CJ, Notterman DA, Karl HW, et al. Adverse Sedation Events in Pediatrics: A Scale). Critical Incident Analysis of Contributing Factors. Pediatrics. 2000;105(4):805-14. 4. Cote CJ, Karl HW, Notterman Da, et al. Adverse Sedation Events in Pediatrics: 2. Breathing, ventilation and airway patency. Analysis of Medications Used for Sedation. Pediatrics. 2000;106(4):633-44. 3. Heart rate and rhythm. 5. Chicka MC, Dembo JB, Mathu-Muju KR, et al. Adverse events during pediatric and sedation: a review of closed malpractice insurance claims. 4. Blood pressure. Pediatr Dent. 2012;34(3):231-8. 5. Oxygen saturation. 6. Lee HH, Milgrom P, Starks H, et al. Trends in death associated with pediatric dental sedation and general anesthesia. Paediatr Anaesth. 2013;23(8):741-6. In patients with an underlying cardiovascular disease undergoing 7. Reuter NG, Westgate PM, Ingram M, et al. Death related to dental treatment: a moderate sedation, the additional use of an electrocardiogram systematic review. . 2017;123(2):194-204. (ECG) is advised. 8. Bellolio MF, Puls HA, Anderson JL, et al. Incidence of adverse events in paediatric procedural sedation in the emergency department: a systematic review and meta-analysis. BMJ Open. 2016 [Accessed 12/04/2017];6:e011384:1-16. Available Capnography is not mandatory for moderate sedation but from http://bmjopen.bmj.com/. is recommended for deep sedation according to the SASA 9. South African Society of Anaesthesiologists. Paediatric Sedation Guidelines for guidelines. There is always the risk of moderate sedation Procedural Sedation and Analgesia. SAJAA. 2016;22(1) Suppl 5: S1-33. inadvertently progressing to deep sedation, however. It is also 10. Green SM, Mason KP, Krauss BS. Pulmonary aspiration during procedural sedation: a comprehensive systematic review. BJA. 2017;118(3):344-54. worth remembering that pulse oximetry is a lag monitor. Jenifer 11. Lightdale JR, Goldmann DA, Feldman HA, et al. Microstream Capnography Lightdale et al. of Children’s Hospital in Boston, Massachusetts, Improves Patient Monitoring During Moderate Sedation: A Randomized, did a randomised, controlled trial of microstream capnography Controlled Trial. Pediatrics. 2006;117(6):e1170-e 1178.

S122 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Anaesthesia in pregnancy for non-obstetric surgery

N R Madima

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of Witwatersrand Correspondence to: [email protected]

This is a review of the maternal and foetal concerns with respect to non-obstetric surgery during pregnancy, with a focus on anaesthetic management of such surgery and on teratogenicity.

Introduction neurosurgical conditions (ruptured aneurysm/space occupying lesions). Patients presenting for non-obstetric surgery during the course of their pregnancy present a challenge to attending physicians. Timing of surgery The anaesthetic management is complicated by the need to Emergency procedures should proceed regardless of the balance the anaesthetic requirements of the mother against trimester of pregnancy and a pregnant woman should never be avoiding harmful effects of the anaesthetic on the growing denied indicated surgery regardless of the trimester. However, foetus.1 When a mother needs surgery during pregnancy, a when considering good foetal outcome, we know that the multidisciplinary team approach is necessary to assess the timing of exposure to anaesthesia and drugs is critical. correct timing and approach to surgery.2 To date, no anaesthetic drug has been shown to be harmful to the human foetus The decision to proceed to surgery should be made by a when used appropriately, but it would seem wise to minimise multidisciplinary team involving anaesthetists, surgeons, placental transfer of drugs. The anaesthetic considerations obstetricians and neonatologists. should also include assessment of the surgical disease process, In a study that investigated pregnancy outcome and non- teratogenicity, physiological changes of pregnancy, types of obstetric surgery, the overall miscarriage rate was 5.8%. In anaesthesia, foetal monitoring and tocolysis. surgery in the first trimester of pregnancy, the miscarriage rate The American College of Obstetricians and Gynecologists was 10.8%. 6 (ACOG) Practice Guidelines Committee acknowledges that there The first trimester is associated with the period of foetal are no data to allow for specific recommendations in this group organogenesis (between 3–8 weeks) and thus also associated 3 of patients because of the difficulty of conducting clinical trials. with all the concerns of foetal malformations.

Epidemiology The third trimester or advanced stages of pregnancy pose 0.75% to 2% of pregnant women require non-obstetric surgery problems of operating around the growing uterus and the during pregnancy. In the United States of America, approximately possibility of irritating the uterus, resulting in preterm labour. 75 000 women annually have non-obstetric surgery during their Lower abdominal procedures and the presence of peritonitis pregnancies.4 have been found to be associated with preterm labour.

The incidence of non-obstetric surgery is most common during Semi-elective procedures should be done during the second the first trimester, with 42% of such surgeries occurring then. trimester and purely elective surgery should wait for the patient Thirty-five percent of surgeries occur during the second and to be six weeks postpartum. However, conservative/medical 23% in the third trimester.5 The incidence of surgery is probably management of symptomatic cholelithiasis was associated higher during the first trimester because some women are not with an increased risk of recurrence – 38% of patients treated medically had recurrence of symptoms.7 aware of their pregnancy. Anaesthetic considerations for non-obstetric surgery Appendicitis, cholecystitis, ovarian disorders, trauma and during pregnancy malignancy during pregnancy are the most common conditions requiring non-obstetric surgery during pregnancy.1 Less The aim of anaesthetic and perioperative management is to common causes of surgery during pregnancy may include ensure maternal safety, avoid foetal loss and to deliver a healthy decompensated cardiac lesions such as mitral stenosis and baby.

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Understanding of the physiological changes of pregnancy is the incidence of elective termination following non-obstetric essential for maternal safety during anaesthesia, particularly after surgery was 1.3%. 20 weeks gestation. The hormonal and physiological changes of Appendectomy was associated with a higher rate of surgery- pregnancy are designed to cope with the oxygen and nutritional induced labour (4.6%), with foetal loss in 2.6% of patients. The demands of the developing foetus, but may pose a challenge for airway management, and positioning of the patient for surgery. incidence of foetal loss increased to 10.9% when peritonitis was 6 Precautions must be taken to ensure safety of the mother. present.

Knowledge of the pharmacological profiles of anaesthetic drugs Normal physiological changes that occur in pregnancy that and the placental transfer of drugs is key to avoidance of adverse impact on anaesthesia management are noted in Table I. outcomes in the foetus. Teratogenicity

Foetal considerations and safety Teratogenicity is defined as an observation of any significant Most patients presenting for non-obstetric surgery are concerned change or form of a child secondary to prenatal treatment with about the risk of the anaesthetic and surgery to the developing an external agent, such as a drug. Therefore, any drug that the foetus. To ensure foetal safety, the anaesthetic management patient takes has the potential to disturb the development of the must include maintaining uteroplacental perfusion by avoiding embryo and may result in malformation. maternal hypotension, acidosis and hypoxia. Prior to anaesthesia and surgery, most patients will need A study evaluating pregnancy outcome following non-obstetric information regarding anaesthetic drugs and their possible surgery during pregnancy that included 12 452 patients, found teratogenic effects and it is the duty of the anaesthetist to that maternal mortality is very rare (0.006%); the miscarriage provide them with current information in order for them to be rate was 5.8%; the incidence of preterm labour was 3.5% and able to give informed consent before surgery.

Table I. Normal physiological changes that occur in pregnancy that impact on anaesthesia management Conditions Change during pregnancy Normal pregnancy values Crdiovascular Heart rate Increases 1-20 bpm 75-95 bpm Cardiac output Increases 30-50% 6-8 l/min Mean arterial blood pressure Decreases 10 mmHg in midtrimester 80 mmHg Systematic vascular resistance Decreases 10-15% 1200-1500 dynes/s/cm-5 Respiratory Tidal volume Increased 40% 700 ml Minute ventilation Increased 40% 10.5 l/min Expiratory reserve volme Decreased 15-20% 550 ml Functional residual capacity Decreased 20-25% 1350 ml Blood gas pH Unchanged 7.4-7.45 pCO2 Decreased 27-32 mmHg

pO2 Increased 100-108 mmHg

HCO3 Decreased 18-21 mEq/l Hematologic Blood volume Increased 30-50% 4500 ml Erythrocyte volume Increased 10-15% Hematocrit Decreased 32-34% White blood cell count Increased 5000-15 000/mm3 Factors I, II, V, VII, IX, X and XII Increased Fibrinogen Increased > 400 mg/dl Genitourinary Renal blood flow Increased 50-60% 700 ml/min Glomerular filtration rate Increased 60% 140 ml/min Serum creatinine Decreased < 0.8 mg/dl Serum urea nitrogen Decreased < 13 mg/dl BPM: Beats per min. Source: Women's Health © 2009 Future Medicine Ltd

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Some studies have concluded that virtually every drug used in In summary, most of the commonly used induction agents, anaesthesia can be found to possess teratogenic characteristics opioids, muscle relaxants and volatile agents can be safely used in some species, under some set of circumstances, at some in clinical concentrations. particular point in time, during pregnancy.8 Despite years of Table II. Teratogenic drugs1 animal studies and observational studies, no anaesthetic drug Drug Possible congenital abnormality has been shown to be clearly dangerous to the human foetus Alcohol Foetal alcohol syndrome and there is no optimal anaesthetic technique. The search for NSAIDs Premature closure of ductus arteriosus a clear answer is hampered by lack of human studies and no Cocaine Spontaneous abortions, abruption placenta animal model perfectly mimics human pregnancy.1,2 Sodium valproate Cleft palate, heart and facial defects Methotrexate Abortions Teratogenicity probably depends on some of the following: Isotretinoin Cardiac, CNS, facial and thymus defects (vitamin A) • Anatomy and physiology of the placenta: the human Warfarin CNS defects, spontaneous abortions and placenta is very different from that of animals which makes haemorrhage extrapolation from animal studies not practical. Lithium Cardiac, kidney and thyroid defects Phenytoin Congenital facial abnormalities • Pharmacokinetic profile of the drug: more lipid soluble drugs ACE inhibitors Neonatal renal failure cross the placenta and can result in ‘trapping’ of the drug in Thalidomide Limb abnormalities the placenta. • Time of exposure is crucial: the first 15 days of pregnancy seem Table III. FDA pregnancy categories of drugs to be a period with an ‘all or none phenomenon’ with regard Category Risk A Controlled studies in pregnant women show no risk in to teratogenicity, with the pregnancy either lost or preserved, first trimester while most of the major congenital malformations were most B Animal studies show no risk, unconfirmed risk in humans likely to occur from exposures between days 13 and 60.9 C Animal studies show risks but benefits outweigh risks D Evidence show risk to human foetus, benefits outweigh The two drugs that have been mostly implicated in anaesthesia risks are nitrous oxide and benzodiazepines. X Animal and human studies show harm, risks outweigh benefits Effect of nitrous oxide on DNA synthesis: Anaesthetic management Homocyteine 5-Methyl THF There is no ideal anaesthetic technique and the anaesthetic

N O Methionine choice should be guided by the indication, site and nature of 2 synthase surgery.

Methionine THF Regional and nerve block techniques are preferred over general Folic acid anaesthesia where feasible, in order to minimise the transfer Methylation reactions DNA synthesis of drugs across the placenta. Doses of local anaesthetics for neuraxials need to be reduced during pregnancy and any resultant hypotension must be appropriately managed. There is Nitrous oxide inhibits methionine synthetase and thereby no definite proof or data showing definite superiority of regional inhibits vitamin B and folate metabolism. The inhibition of 12 over general and both have been safely used during pregnancy. folate metabolism interferes with DNA synthesis and may be harmful to the foetus. Exposure to > 50% nitrous oxide for The preoperative assessment should be used to discuss and prolonged periods has been shown to be teratogenic in animal reassure the patient about her concerns (miscarriage, preterm studies. However, no effects have been demonstrated in and teratogenicity). The attending obstetrician and paediatrician women after brief exposure. Rowland et al conducted a study must to be notified and gestational age should be noted. that concluded that women exposed to unscavenged nitrous Important issues in the anaesthestic management include: oxide for prolonged periods had more abortions and decreased • Preoperative evaluation of the airway in view of pregnancy fertility than those who were not exposed.10,11 related airway changes that increase difficulty in airway A subsequent Swedish study of more than 5 000 women failed to management. Adequate preoxygenation prior to induction implicate nitrous oxide in adverse foetal outcome,5 but it would is recommended to avoid hypoxia in the presence of the seem best to avoid using it in modern anaesthetic practice as reduced Functional Residual Capacity and the increased there is a large range of drugs with a better safety profile. oxygen consumption. • Blood investigations required will be determined by the type Benzodiazepine use during pregnancy was associated with of surgery and the disease process. cleft palate and cardiac abnormalities in earlier studies.12 A single • Aspiration prophylaxis from 14 weeks gestation is advisable. dose of benzodiazepine does not appear to be a problem but • Avoid aortocaval compression from 20 weeks gestation by repeated and prolonged use is.13,14 positioning the patient with lateral tilt.

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• Adequate ventilation, aiming for normocarbia to avoid foetal FHR variability can be monitored from 25–27 weeks gestation; acidosis. Hypercarbia and hypocarbia both reduce placental however, because most drugs cross the placenta they can reduce blood flow. FHR variability under general anaesthesia.

• Avoid any reductions in uteroplacental circulation. Prolonged Foetal bradycardia is more concerning during surgery as it may maternal hypoxia causes uteroplacental vasoconstriction be a reflection of foetal distress or compromise (hypoxaemia). and decreased uteroplacental perfusion, which can result in Other factors that may reduce FHR variability include maternal foetal acidosis and death. Maternal blood pressure must be acidosis, hypotension and hypothermia. maintained because a decrease in maternal blood pressure decreases placental perfusion. Tocolysis • Prophylactic glucocorticoid administration 24–48 hours Efficacy of most of the agents used for tocolysis is unproven and preoperatively for lung maturity in case of preterm labour. the significant side-effects of the drugs need to be considered • Anaesthetic drugs: most anaesthetic drugs have been safely before their use. used during pregnancy. Plasma cholinesterase levels are Prophylactic administration of tocolytic agents is controversial reduced up to 35% during pregnancy but recovery from and should be limited to those patients who require uterine succinylcholine is not usually prolonged because of the manipulation intraoperatively and those patients undergoing increased volume of distribution and relative resistance to lower abdominal and pelvic procedures.15 Patients who have succinyl choline associated with pregnancy. MAC values of appendicitis and peritonitis have an increased incidence of inhalational anaesthestics are reduced in pregnancy and foetal loss.6 lower levels of these agents may be required. Atropine may be preferred over glycopyrrolate to counteract the effects of If a patient develops preterm labour, treatment options include use of magnesium sulphate, calcium channel blockers, neostigmine during reversal. Foetal bradycardia may occur B-mimetics, prostaglandin inhibitors (indomethacin) and following administration of neostigmine because neostigmine nitrates.16 Indomethacin is no longer recommended after crosses placenta while glycopyrrolate does not. 28 weeks because it causes premature closure of the PDA. • Prophylactic tocolysis. • Foetal monitoring. Laparoscopy

Foetal heart monitoring Laparoscopy is no longer considered to be contraindicated during pregnancy. The surgical approach should be determined Continuous foetal heart rate should be done, when feasible, by the skills of the surgeon, surgical needs and the availability of from 18–22 weeks of gestation and uterine activity can also be equipment. Concern with laparoscopy in the past has been about monitored, depending on the site of surgery. associated foetal trauma, foetal acidosis with CO2 insufflation and increased intra-abdominal pressure which resulted in decreased The ACOG state that the decision for foetal monitoring should cardiac output and reduced uteroplacental perfusion. be individualised and, if used, should depend on the gestational age, type of surgery and available facilities of the institution.3 Reedy et al conducted a retrospective study comparing laparotomy and laparoscopy for non-obstetric surgery during ACOG guidelines for foetal monitoring3 pregnancy. No difference between the two groups was found In the case of a previable foetus, it is sufficient to ascertain foetal regarding the incidence of preterm labour, the birth weight heart rate (FHR) by Doppler before and after the procedure. of the babies, growth restrictions, malformations and foetal losses.17 In the case of a viable foetus, a minimum of FHR and contraction monitoring before and after the surgical procedure should Rollins et al investigated their own practices during two different be done, in order to assess foetal wellbeing and absence of time periods and concluded laparoscopic cholecystectomy and contractions. appendectomy had increased greatly with no associated adverse foetal outcome.18 Electronic FHR monitoring should be used during a surgical 1 procedure when Important factors for maternal laparoscopy : • Use open technique to enter the abdomen. • A viable foetus is present. • Monitor ETC02 to avoid maternal hypercarbia (30–34 mmHg). • It is physically possible to use the monitor. • Use low pressure pneumoperitoneum (10 cmH20). • A healthcare provider with obstetric knowledge is available and willing to intervene during the procedure for foetal • Limit extent of Trendelenburg or reverse Trendelenburg indications. positions. • The patient has given informed consent for emergency • Try and maintain uterine displacement. Caesarian section delivery. Although the laparoscopic approach can be used during any • The nature of the surgery is such that it can allow interruption trimester of pregnancy, it is technically difficult during the last or alteration for Caesarian section delivery. trimester because of the growing uterus.

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Postoperative management 4. Goodman S. Anaesthesia for non-obstetric surgery in the pregnant patient. Seminars of perinatology. 2002;26:136-45. • Continue monitoring the patient for contractions and foetal 5. Mazze RI, Kallen B. Reproductive outcome after anaesthesia and operation heart rate to ensure safety of the foetus. The obstetrician during pregnancy. A study registry of 5405 cases. American Journal of Obstetrics should review the patient at this stage. If the pregnancy is and 1989;161:1178-1185. maintained for one week after the surgery, the pregnancy is 6. Cohen-Kerem R, Railton C, Koren G. Pregnancy outcome following considered ‘safe’. obstetric surgical intervention. American Journal of Surgery September 2005;190(3):467-473. • Provision of adequate analgesia is important. Peripheral 7. Lu EJ, Caret MJ, El-Sayed Y, Kirkwood KS. Medical versus surgical management nerve blocks and epidural are preferable. Opioids can be of biliary disease in pregnancy. The American Journal of Surgery used to control postoperative pain but the drug of choice is 2004;188(6):755-759. paracetamol. Avoid using nonsteroidal anti-inflammatories 8. Kuczkowski KM. Non-obstetric surgery during pregnancy; what are the risks? Obstetric Gynaecology Survey 2004;59:52-56. because of the risk of side-effects in the foetus, including 9. Tuchmann-Duplessis H. The teratogenic risk. American Journal of Industrial oligohydramnios, premature closure of the ductus arteriosus, Medicine. 1982 Dec; 4(1-2):245-258. necrotising entero-colitis and intraventricular haemorrhage. 10. Rowland AS, Baird DD, Weinberg CR, et al. Reduced fertility among women employed as dental assistants to high levels of nitrous oxide. NEMJ.1982 Conclusion Oct;327:993-7. 11. Rowland AS, Baird DD, Shore DL, et al. Nitrous oxide and spontaneous abortions Non-obstetric surgery during pregnancy is not common, but in female dental assistants. American Journal of Epidemiology. 1995;141:531-8. it appears to be safe if careful attention is paid to maintaining 12. Laegreid L, Olegrd R, Walstrom J, Conradi N. Teratogenic effects of uteroplacental circulation and minimising placental drug benzodiazepine during pregnancy. Journal of Paediatrics. 1989;114:126-131. transfer during anaesthesia and if surgery is performed at the 13. Czeizel AE, Eros E, Rockenbauer M, et al. Clinical drug investigation. 2003;23:451. correct time. Successful maternal and foetal outcome depends 14. McElhatton PR. The effects of benzodiazepine use during pregnancy and upon expert surgical and anaesthetic management of the lactation. Reproductive toxicology. 1994;8(6)461-475. disease process. 15. Hawkins JL. Non-obstetric surgery during pregnancy. CRASH 2013. 16. Nejdlova M, Johnson T. Anaesthesia for non-obstetric procedures during References pregnancy. Continuing Education in Anaesthesia Critical Care and Pain. 1. Reitman E, Flood P. Anaesthetic considerations for non-obstetric surgery during 2012;13(4):203-6. pregnancy. BJA; 2011:107(S1) 172-178. 17. Reedy MB, Kallen B, Kuel TJ. Laparoscopy during pregnancy: A study of five fetal 2. Upadya M. Anaesthesia for non-obstetric surgery during pregnancy. IJA; 2016: outcome parameters with use of Swedish health registry. American Journal of 60(4): 234-241. Obstetrics and Gynaecology. 1997;177:673-9. 3. ACOG committee opinion no 696, 2017 on non-obstetric surgery during 18. Rollins M, Chan KJ, Price RR. Laparoscopy for appendicitis and cholelithiasis pregnancy. during pregnancy. A new standard of care. Surgical Endoscopy. 2004;18:237-241.

S127 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Anaesthesia for cleft lip and palate surgery

A Oosthuizen

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of Witwatersrand Correspondence to: [email protected]

“ Dignity begins with a smile”1 by Nicholas Serra,

Introduction Cleft lip (CL)

Worldwide, cleft lip and palates (CLP) are one of the most Cleft lip occurs in the upper lip and is either unilateral (left side common craniofacial abnormalities requiring surgical treatment more common) or bilateral.7 in the early years of life.2 Cleft lip and palate can impact a child’s The defect may be7: appearance, speech, teeth, eating, hearing and ability to develop socially.3 Cleft lip and palate can be successfully treated using a • Complete (extends across the whole lip and into the nostrils) comprehensive team approach including presurgery support • Incomplete (ranges from small indentations to large defects) 4 and long-term postsurgery care. Cleft palate (CP)

Cleft palate occurs in the soft palate and may extend into the hard palate and is either a unilateral or bilateral fissure.7

The defect may be7: • Complete (both primary and secondary palates are affected) • Incomplete (affects only the secondary palate)

CP may occur with CL but CP without CL is aetiologically and embryologically a distinct entity.6

Embryology

CLP occurs because of palatal growth defects during the first trimester.5 The window of opportunity for fusion to occur is Prevalence relatively short, and suggested theories for failure of fusion include mechanical obstruction by tongue position, structural Internationally the prevalence of cleft lip ranges between 1:300– hypoplasia or primary breakdown.5 Clefts of the lip and alveolus 1 200 live births and for cleft palate 1:2 500 live births but these can be diagnosed reliably at the routine 18–20 week antenatal vary based on ethnicity and country.3 The prevalence in South ultrasound scan, allowing for earlier preparation of support Africa is about 1.4:1 000 live births in Caucasians and 0.4:1 000 services and counselling of parents.5 Clefts of the palate are live births in Africans.4 not easily seen by ultrasound and can only be excluded by CLP is more common in males. Isolated CP is more common in examination of the palate after delivery.5 females.5 Aetiology Classifications (See Picture6) The aetiology is unknown but is multifactorial.7 Both genetic 7 Table I. Types of abnormalities4 and environmental factors play a role. There is also a strong hereditary role.3 Some cases result from mechanical obstruction.7 Unilateral cleft lip 25% There is also an association with teratogen exposure such as Unilateral cleft lip and palate 25% smoking, maternal alcohol use, anticonvulsant drugs (phenytoin Bilateral cleft lip and palate 10% and benzodiazepines) and other drugs such as salicylates and Cleft palate alone 40% cortisone.7 Increased paternal age also plays a role.3

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Table II. Syndromes with orofacial clefts as a feature8,3

Syndrome name(s) Features Anaesthesia implications

Arthrogryposis Multiplex congenita Limb contractures, CHD, stiffness of joints and GU Difficult intubation due to limited mouth defects opening, position, and pad carefully Beare-Stevenson syndrome Craniosynostosis, hydrocephalus, choanal atresia, Difficult airway, beware of tracheal stenosis and midface hypoplasia, proptosis, hypertelorism, cutis caution with neck movements gyratum, tracheal stenosis, and cervical spine defects Beckwith-Wiedemann syndrome Exomphalos, macroglossia and gigantism Hypoglycaemia Tongue reduction required at time of palate repair CATCH 22 (Velocardiofacial syndrome) Most common syndrome associated with CLP Difficult airway Cardiac defect, abnormal face, thymic hypoplasia, Hypocalcaemia cleft palate and hypocalcaemia (Di George syndrome) Cornelia de Lange syndrome Growth failure, micromelia, micrognathia, mental Airway obstruction, difficult intubation retardation, CHD in 15% Down syndrome Short stature, mental retardation (variable), Difficult intubation, airway obstruction and macroglossia, unstable cervical spine, narrow caution with neck movements subglottic space and CHD in 50% Foetal alcohol syndrome Small palpebral fissures, smooth philtrim, thin Behavioural dysfunction upper lip, growth deficiency, CNS abnormalities, Difficult laryngoscopy and tracheal intubation microcephaly Goldenhar syndrome Defect of the 1st and 2nd branchial arches Difficult airway (intubation may become Hemi facial and mandibular hypoplasia more difficult with increasing age), laryngeal Abnormalities of the cervical spine, external ear and anomaly, lung hypoplasia – ventilatory eye problems, cardiac and pulmonary complications Kabuki syndrome Craniofacial and skeletal defects, hypotonia, CHD, Difficult airway visceral and urogenital defects King syndrome Congenital myopathy, MH trait Dysmorphic features (MH) Klippel-Feil syndrome Limited neck movement, renal anomalies Difficult airway Miller syndrome Mandibular defects, limb anomalies and renal Difficult airway defects Multiple Pterygium syndrome Webbing of skin, syngnathia, ankyloglossia, and web Difficult airway (more severe with age) and MH neck association Nager syndrome Malar hypoplasia, micrognathia, CHD, radial Difficult airway, limited mouth opening and hypoplasia, absent thumbs, and vertebral anomalies cervical spine anomalies Oto-palatal-digital syndrome Skull deformity, hearing loss, cervical spine defect, Possible brain-stem compression causing limb defects and thoracic hypoplasia postoperative respiratory depression

Patau’s syndrome (Trisomy 13) Microcephaly, mental retardation, micrognathia, CHD Difficult airway and fatal in infancy Pierre-Robin sequence Micrognathia and cleft palate in 80% of cases Difficult airway, postoperative airway obstruction (Intubation becomes easier with age due to mandibular growth) Seckel syndrome Bird-like face, dwarfism, microcephaly, possible glottis Difficult airway. Monitor ventilation postop narrowing (postoperative apnoea)

Smith-Lemli-Opitz syndrome Growth failure, microcephaly, mental retardation, Possible difficult airway, intraoperative muscle CHD, renal defects, hypotonia, GORD, and thymic rigidity and thermoregulatory problems hypoplasia Stickler syndrome Progressive connective tissue disorder (AD), midface Difficult airway hypoplasia, micrognathia, Pierre Robin sequence, retinal detachment and early cataracts, deafness, hypermobility of joints Spondylo-epiphyseal Dysplasia Dwarfism and C1–C2 instability Caution with neck movements during congenita intubation and positioning Treacher Collins syndrome Hypoplastic zygoma and mandible, macrostomia and Difficult airway (intubation may become more cleft or high arched palate difficult with increasing age) Walker-Warburg syndrome Micrognathia, hypotonia, hydrocephalus, mental Difficult intubation and postoperative retardation and GU anomalies hypoventilation Trisomy 18 Cleft palate, lung hypoplasia, macrognathia and CHD Difficult airway

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Associated syndromes 2. Airway management: is the intubation potentially difficult? ▫ Most non-syndromic infants are not difficult to intubate.9 Most children have an isolated malformation but approximately ▫ 22–37% have an associated malformation.3 Isolated cleft palate ▫▫ Some syndromes are associated with difficult intubation. has the highest incidence of associated malformations (28–47%), ▫▫ Factors associated with difficulty include: bilateral cleft lip, with cleft lip at around 8–13% and CLP from 28–37%. Over 200 retrognathia, micrognathia, infants < 6 months of age and syndromes/sequences (Table II) are associated with CLP and to a lesser extent left-sided cleft lip and alveolus.3 7 some have significant anaesthetic implications. Most syndromes 3. Upper respiratory tract infection (URTI)7 are rare but some of the more common syndromes of interest to ▫▫ Chronic rhinorrhoea is common with CLP due to reflux of anaesthesia are4: food into the nasal passage with resultant overt and often 1. Pierre Robin sequence recurrent URTI. 2. Treacher Collins syndrome ▫▫ Postoperative respiratory complications increase with the 3. Goldenhar syndrome severity of the defect. 4. Velocardiofacial syndrome ▫▫ At risk of reactive airways. 5. Foetal alcohol syndrome 4. Chronic airway obstruction7 6. Stickler syndrome ▫▫ Look for signs of chronic airway obstruction: snoring, 7. Down syndrome apnoea during feeds/ protracted feeding time. 8. Klippel-Feil ▫▫ Older children may have chronic hypoxia, right ventricular hypertrophy and eventually cor-pulmonale requiring a Summary of the associated problems2,7: preoperative Echo. 1. Associated congenital abnormalities (the most prominent ▫▫ Beware of sedative drugs as these patients are more have been highlighted in Table II)3,5 sensitive to their effects. 2. Congenital heart disease (5–10% of patients) 5. Nutrition and hydration 3. Chronic rhinorrhoea ▫▫ Feeding difficulties are common in CLP as it may be difficult 4. Chronic airway obstruction or sleep apnoea to create a sufficient seal during suckling.7 This results in 5. Right ventricular hypertrophy and cor-pulmonale because of the infants being dehydrated and malnourished requiring chronic hypoxia secondary to airway obstruction surgery to be deferred until they can be optimised. 6. Anticipated difficult intubation and extubation ▫▫ Nutritional or physiological anaemia may occur but routine haemoglobin testing is not advocated. Timing of surgical repair 6. Premedication Classically CL is repaired between 3–6 months but there is an ▫▫ Usually not necessary. 2 increasing trend to operate during the neonatal period. ▫▫ Sedatives may aggravate chronic airway obstruction and should be avoided.7 CP is repaired at a later age between 3–9 months sometimes even up to 18 months.2,7 Depending on the surgeon’s preference ▫▫ Establishing a rapport with the infant and caregiver it may be a primary repair or a staged repair to promote normal may prove to be helpful but not always possible with an speech development and reduce nasal regurgitation.7 Surgery anxious patient/caregiver.4 may be delayed to optimise any associated malformations.2 ▫▫ Individualising each patient is essential and premedication may be considered in children > 1 year CLP patients are likely to require further surgery either related (relative) and no airway concerns (syndromes or signs of to the primary problem e.g. plastic improvements to a CL airway obstruction).4 repair, or for associated abnormalities.7 Around 20% will require pharyngoplasty for velopharyngeal dysfunction at around 4–6 ▫▫ Medications that have been used include: oral paracetamol years.7 Primary palatoplasty disrupts normal palate growth and with/without midazolam, oral ketamine mixed with 4 despite orthodontic treatment, some will require significant paracetamol and intra-nasal dexmedetomidine. maxillofacial surgery in their teens to correct midface hypoplasia ▫▫ An anticholinergic (atropine or glycopyrrolate) may be and maxillary retrusion.7 considered to reduce secretions.9 Anaesthesia considerations Intraoperative management Preoperative assessment Generally an inhalational induction is performed but total intravenous anaesthesia (TIVA), using a remifentanil-propofol A thorough preoperative evaluation is essential to reduce any infusion, has compared favourably with a sevoflurane-fentanyl 3 risk of anaesthesia-related morbidity and mortality. anaesthesia in a small group of patients.3 Upon obtaining 1. Is there a syndrome present?9 intravenous access, the airway can be secured using a south- ▫▫ Ensure a thorough examination being sure to evaluate for facing oral Rae endotracheal tube and positive pressure a cardiac defect which may require an Echo; especially if a ventilation initiated.9 Maintain spontaneous ventilation until the murmur is noted. ability to face mask ventilate has been confirmed and a muscle

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relaxant (e.g. suxamethonium 1–2 mg/kg or a non-depolarising • Opiates: agent) can then be administered if no difficulties with intubation ▫▫ Short-acting agents recommended for CL repairs e.g. are anticipated.4 Ten percent of ASA 1 patients for CLP repair fentanyl 1–2 mcg/kg.7 will have difficult laryngoscopy (Cormack and Lehane grade ▫▫ Longer-acting agents may be more appropriate for CP III-IV views) and the incidence in those with associated syndromes repairs as these are more painful e.g. morphine 0,05–0,1 rises.7 mg/kg.7 ▫ Advantage: smoother emergence with less crying which Tricky intubation tips9: ▫ may reduce swelling and bleeding from the surgical site.3,7 • Instead of using a curved laryngoscope blade, consider a ▫▫ The use of long-acting opiates should be titrated to effect straight blade. due to the risk of postoperative airway complications • Large alveolar defects may hamper laryngoscopy – pack the (postoperative sedation and respiratory depression).7 defect with gauze to help prevent the blade from slipping into • Regional anaesthesia: the cleft (especially left-side defects).7 CL repair: • In a patient with bilateral cleft lip, the central lip prominence ▫ Infraorbital nerve blocks can provide effective can hinder midline laryngoscopy – consider using a Miller ▫ postoperative analgesia for up to 19 hours without the blade with a lateral approach.4 risk of respiratory depression when performed with • Always be prepared for a potential difficult intubation with adrenaline-containing bupivacaine. Bilateral blocks can difficult airway equipment readily available especially for any safely be performed.3 syndromic child (e.g. alternative laryngoscopes, a stylet or ▫▫ Studies have shown they provide better analgesia for a gum elastic bougie, and laryngeal masks (LMA)).7 longer duration than peri-incisional infiltration and are superior to fentanyl titrations.9 To prevent soiling of the airway and ingestion of blood; a throat pack should always be inserted. Remember to remove the pack ▫▫ The infraorbital nerve supplies sensation to the skin and mucous membranes of the upper lip, lower eyelid, cheek before emergence. A head ring and roll are placed under the and the alae nasi.3 patient’s shoulders to extend the neck and tip the head down.7 A Boyle-Davis gag is used during palate repair and vigilance ▫▫ The infraorbital nerve can be blocked either intra-orally or extra-orally. Using a small gauge needle in the extra- is needed to prevent inadvertent extubation, intubation of oral approach; is placed superficially to the infraorbital the right main bronchus and endotracheal tube-kinking or foramen bilaterally (0,5–1 ml 0,25%–0,5% bupivacaine occlusion.3,7 with 1:200 000 adrenaline).9 Administer antibiotics, corticosteroids (dexamethasone CP repair: 0,25 mg/kg) to reduce upper airway oedema, and anti- ▫▫ Maxillary nerve blocks via three approaches: intra-orally emetics. Provide appropriate intraoperative fluid therapy and by blocking the palatine nerves, using an infrazygomatic consider 1% dextrose supplementation in patients high risk for approach or a suprazygomatic approach.9 hypoglycaemia (prolonged preoperative fasting, underweight ▫ The maxillary nerve innervates the lower eyelid, the upper children, and children < 4 years/< 15 kg).9 ▫ lip, the skin between them, the roof of the mouth and the Surgery usually lasts 1–2 hours. Blood loss is uncommon but palate.4 CP repairs have the potential for significant blood loss so cross ▫▫ For detailed descriptions on the blocks refer to9: matching facilities should be available.7 In patients who are ▪▪ Bösenberg AT, Kimble FW. Infraorbital nerve block oozing, 10 mg/kg tranexamic acid may be considered but may in neonates for cleft lip repair: anatomical study and 9 be controversial. clinical application. BJA: British Journal of Anaesthesia. Surgery is painful and a multimodal analgesic approach is 1995;74(5):506-8. essential.9 ▪▪ Mesnil M, et al. A new approach for perioperative analgesia of cleft repair in infants: the bilateral • Provide regular dosing of simple analgesics as a baseline suprazygomatic maxillary nerve block. Paediatric ▫ Paracetamol7: ▫ Anaesthesia. 2010; 20:343-349. ▪ As a premedication, orally (20 mg/kg). ▪ ▫▫ Since there is no single effective block for CLP surgeries, ▪▪ After induction, intravenously (15 mg/kg) or rectally pain management should always be supplemented with (40 mg/kg). other modalities keeping in mind that the blocks reduce 2 ▫▫ NSAIDS: the opioid requirements effectively. ▪▪ Effective analgesics. Extubation

▪▪ Generally, only prescribed in infants > 6 months. It is important to remain vigilant and ensure the throat pack is ▪▪ Given in the setting of cleft lip repair but avoided in removed at the end of surgery and this should be included as cleft palate repairs due to the risk of bleeding.9 May part of the swab count according to the WHO Surgical Safety then be considered 12 hours postoperatively.7 Checklist.7,10

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Ensure the oropharynx is inspected for any blood clots and that 4. Laryngospasm. haemostasis has been achieved. Suctioning should be kept to 5. Reduction in pharyngeal tone due to residual a minimum especially with CP repairs to avoid disrupting the volatile agent effects. surgical repair and may cause bleeding.7,10 Non-depolarising 6. Inadequate mouth opening. muscle relaxants should be adequately antagonised if they were used during the procedure. Extubate the child fully awake once 7. Respiratory depression from opioid analgesia. the protective reflexes have returned.7 8. Laryngeal oedema as result of a difficult Postoperative management intubation. 9. Or a combination of factors. It is estimated that 15–20% of CLP repairs are associated with d. Management depends on the degree of the obstruction: postoperative morbidity and a reoperation risk of around 2% related to bleeding and airway obstruction complications.9 i. Simple manoeuvres: Airway complications range from episodes of mild stridor to 1. Place the child in the left lateral or prone, pull 10 complete airway loss requiring re-intubation. the tongue forward to relieve the obstruction. All children should be monitored in the recovery room until they Consider placing a tongue suture to relieve the 10 are fully awake, their pain has been well controlled and there are obstruction. no signs of bleeding.10 2. Consider providing temporary continuous positive airway pressure until the child has fully Factors to consider in the postoperative period: recovered.10 1. Airway obstruction 3. As far as possible avoid placing an oropharyngeal a. Most commonly seen in recovery in the immediate airway as insertion may damage the surgical postoperative period but careful monitoring allows for repair but if in extremis it may be lifesaving.10 early detection as it may occur within the first 12–24 hours but even up to 48 hours post-surgery.7,9 Massive ii. Other airway devices: tongue swelling cases usually present within 90 minutes 1. Place a NPA or LMA. 10 of the end of surgery. iii. Re-intubation: required if simple manoeuvres cannot b. Most likely to occur in children with a preoperative establish a safe airway.10 airway concern.7 Especially in children with congenital 1. Should reintubation be necessary, consider abnormalities, namely Pierre Robin sequence.9 Insert a using a fibre optic scope and as a last resort in nasopharyngeal airway (NPA) at the end of the procedure severe airway obstruction, a surgical airway.9 It in micrognathic patients.9 is imperative to be familiar with the paediatric c. Occurs due to7,9: difficult airway algorithms.4 i. Congenital abnormalities associated with 2. If there are any concerns on emergence of airway micrognathia. compromise, keep the child intubated and ii. Anaesthetic or surgical complications10: ventilated until the swelling subsides.9 1. Swelling of the tongue from gag pressure, usually 3. Anticipate a difficult intubation even if with because of prolonged surgical time related to a the initial procedure it may have been straight wider cleft. The mouth is held open by the gag forward, as postoperative swelling and bleeding which exerts pressure on the alveolar ridge and may distort the view at laryngoscopy.10 tongue. Mucosal oedema results if too much pressure is applied for a prolonged period or iv. Postoperative monitoring: the incorrect size retractor blade is used. This is 1. Ideally all patients should be monitored in a high- due to impaired venous and lymphatic drainage, dependency unit but patients at particular risk as and is worsened by neck overextension and a result of an associated syndrome or any who 9,11 if steep Trendelenburg is used. The Boyles- complicate should be monitored in ICU.7 Davis gag should be released for 5–10 minutes 2. Postoperative analgesia every hour especially during prolonged surgery. Upon removal of the gag inspect the whole a. Multimodal analgesic strategies should be continued oropharynx and base of the tongue.9 Should the into the postoperative period. This should include tongue appear swollen or dusky in colour, decide regular dosing of paracetamol and NSAIDs (infants over whether extubation is appropriate and consider six months) and oral (tilidine 1 mg/kg) or intravenous placing a NPA. The child should be closely opioids in selected cases and older children (morphine observed in a high care environment or placed 0,05–0,1 mg/kg) provided airway obstruction is not a in ICU ventilated until the swelling has resolved.9 problem.3,7 Alternatively, consider rectal analgesics.3 2. A retained throat pack. b. If a nerve block is performed intraoperatively, this 3. Bleeding or blood clots. analgesia will continue into the postoperative period.

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c. Infants may be reluctant to swallow for 24 hours post- 2. Reena, Bandyopadhyay K, Paul A. Postoperative analgesia for cleft lip and repair and intravenous fluids may be required until oral palate repair in children. Journal of Anaesthesiology Clinical Pharmacology. 2016;32(1):5-11. intake has been re-established.3 3. Bösenberg A. Anaesthesia for cleft lip and palate surgery. Southern African Conclusion Journal of Anaesthesia and Analgesia. 2007;13(5):9-14. 4. Govender P. Anaesthesia for cleft lip and palate surgery. Anaesthesia. 2014;6(15). Every three minutes, a child somewhere in the world is born with 5. Somerville N, Fenlon S. Anaesthesia for cleft lip and palate surgery. Continuing a CLP, who, as a result is often unable to eat, speak, socialise or Education in Anaesthesia Critical Care and Pain. 2005;5(3):76-9. smile.1 In Africa, approximately one in every 1 000 babies is born 6. What is cleft palate and cleft lip? [cited © 2012-2015 . Available from: http://www.transformingfaces.org/. with a cleft lip or cleft palate.1 If they do not receive reconstructive 7. Rawlinson E. Anaesthesia for cleft lip and palate surgery. Update in Anaesthesia. surgery, they may have many healthcare issues.1 Despite the 2015;30(30):154-8. anaesthetic challenges we may face, the benefits of surgical 8. Steward DJ. Anesthesia for patients with cleft lip and palate. Seminars in repair are life-changing to these children and very rewarding.4 Anesthesia, Perioperative Medicine and Pain. 2007;26(3):126-32. This is not simple cosmetic surgery nor a simple anaesthetic.3 9. Lee C-A. Anaesthesia for Cleft Lip and Palate Surgery. PACSA supplement 3 November 2012. 2012. References 10. Rawlinson E. Postoperative airway complications after cleft palate repair. 1. Smile O. Operation Smile South Africa: Operation Smile South Africa; Anaesthesia Tutorial of the Week 2011(236):1-11. 2017 [updated 2017; cited 2017 2017]. Available from: www.southafrica. 11. Aziz S. Severe glossal edema after primary palatoplasty. Journal of Oral operationsmile.org. Maxillofacial Surgery. 2009;67:1326-8.

S133 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

New concepts in anaesthetic emergence

A W Moodley

Department of Anaesthesia, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand Correspondence to: [email protected]

The discovery of anaesthesia, over 170 years ago, heralded the discovered a new neuropeptide.2 One group would call this start of an era in which surgery could be performed with greater neuropeptide ‘hypocretin’ and the other group would call it safely and in a more humane manner. Our discovery of a way ‘orexin’. to circumvent pain and temporarily extinguish consciousness Orexinergic neurons center on the lateral hypothalamus and made life-saving surgery possible. The discovery of anaesthesia project widely throughout the brain. This system has been is widely considered to be one of the greatest discoveries in shown to play an important role in appetite, feeding and in the history. maintenance of the awake state (i.e. the orexinergic system is Soon after the first public demonstration of general anaesthesia ‘wake-promoting’).3 at Massachusetts General Hospital in 1846, an unprecedented In 2000, a link between the orexinergic system and narcolepsy, enquiry into the workings of the brain commenced and several a chronic neurological condition, was made.4 Narcolepsy is scientists put forward theories of how they thought anaesthesia characterized by excessive daytime sleepiness, sleep paralysis, worked. In 1847, the German scientist Ernst Von Bibra suggested cataplexy and hypnogogic hallucinations.5 Immune mediated that anaesthetic vapours worked by dissolving the lipid loss of orexinergic neurons has been shown to be key in the components of brain cells.1 development of this condition. This theory persisted for more than 50 years and was developed Case reports have suggested that patients with narcolepsy may further by Meyer and Overton who postulated a unitary be at risk of significantly delayed emergence from anaesthesia.6 hypothesis of anaesthetic action.1 Throughout the subsequent This suggests that the orexinergic system may play an active role decades several theories of anaesthetic action would be in emerging from anaesthesia. formulated but none would completely explain how anaesthetic agents worked. Kelz et al. examined the association between the orexinergic system and anaesthetic emergence.7 Their experiments used Despite all the activity aimed at determining how anaesthetic orexin agonists and orexin receptor antagonists to show the agents worked, surprisingly little attention was given to effects of orexin blockade on general anaesthesia. Their findings explaining how the brain recovered from anaesthesia, that is, support the idea that the orexinergic system does play an how consciousness was reignited once the effects of the drugs essential role in emergence from general anaesthesia since in wore off. In fact, up until very recently the process of emergence those animals subjected to orexin blockade, the emergence was considered to be a passive process, purely related to times were significantly prolonged. Their work also suggests that anaesthetic washout. emergence is a separate active process involving distinct neural However, an examination of dose response curves of anaesthetic substrates and not merely the passive reverse of induction. agents reveals hysteresis in the system, i.e. the reverse process Neural Inertia (emergence) does not exactly mirror the forward process (induction). This results in the emergence curve displaying a left The hysteresis noted in dose response curves implies that within a shift. This observed hysteresis raises some questions about the particular dose range, the sleep-wake state of a subject depends mechanism of emergence from anaesthesia. on whether the subject is undergoing induction or emergence, that is, the current sleep-wake state depends on the previous The Orexinergic System state. At the dose indicated by the arrow in Figure 1, patients may In 1998, two different groups of researchers, working separately be either awake or anaesthetized depending on which pathway and independently from each other, almost simultaneously (i.e. emergence or induction) they are on. This lagging behind of

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observed phenomenon as compared to blood anaesthetic levels could be replicated with propofol anaesthesia.12 These studies was originally attributed to slow receptor kinetics. show that it may be possible to accelerate emergence from anaesthesia.

In an attempt to determine whether this effect was due to a general dopaminergic effect or the action of a specific dopaminergic nucleus, further work was done involving Black line = induction Red line = emergence selective electrical stimulation of dopaminergic nuclei. The two % Awake main dopaminergic nuclei in the brain are the substantia nigra and the ventral tegmentum. It has been found that stimulation of the ventral tegmentum but not the substantia nigra induces emergence from general anaesthesia, similar to the effects seen with methylphenidate.13 These findings narrow the arousal inducing effects to specific circuits, i.e. those emanating from the ventral tegmentum rather than a widespread dopamine- Anaesthetic Dose mediated effect.

Acetylcholine is well known to have stimulatory effects on the Figure 1. Dose Response Curve: Anaesthetic Dose vs. Percentage of brain. The question of whether or not these effects could be Patients Awake put to use in actively inducing emergence was addressed by Kenny et al.14 They used physostigmine, an acetylcholinesterase Recent work however has suggested that this explanation may inhibitor that crosses the blood-brain-barrier, to increase brain be incomplete. Friedman et al suggest that hysteresis may be levels of acetylcholine. Their findings showed that increasing attributed to a property of neural circuits called neural inertia i.e. acetylcholine levels did not induce emergence from anaesthesia the tendency of neural systems to resist a change in their state.8 as was seen by the use of methylphenidate.

This inertia affords the brain some degree of stability. From an Transitional Dynamics evolutionary perspective it appears to be a safety mechanism, Until now, we have had little knowledge of how the brain since if the sleep-wake state lacks stability, one may easily transitions from the anaesthetised state to the awake state; transition between states at any time. This lack of stability is seen however, more and more work is being done these days to in patients who suffer from narcolepsy, in whom uncontrollable answer some fundamental questions about how this happens. episodes of falling asleep occur during the day. The fact that the brain stabilises in either the sleep state or the awake state is It is now known that the brain does not emerge from anaesthesia described as bistability, i.e. the ability to stabilise in one of two in a gradual linear fashion. states. Electroencephalographic (EEG) studies have examined the Animal studies have shown that by manipulating the function transition of the brain through various states as it regains 8 of neural ion channels, neural inertia can be manipulated. An consciousness. Using analogies from protein synthesis and interesting finding of these studies is that emergence can be folding (i.e. Levinthal’s Paradox) it appears that the brain manipulated without affecting induction pathways. This adds does not sample all of the states available to it on the way to weight to the argument that different circuits are involved with consciousness, instead it ‘jumps’ through a distinct set of states induction and emergence. referred to as ‘metastable states’ in that they are stable for a few Facilitating Active Emergence from Anaesthesia minutes at a time.15

After the link between the orexinergic system and anaesthesia Connectomics had been established, the next natural step would be to The relatively new field of connectomics is described as “the determine whether the orexinergic system could be used production and study of connectomes: comprehensive maps of to facilitate a faster emergence from general anaesthesia. connections within an organism's nervous system, typically its Researchers have shown that the use of an orexin agonist could brain…”.16 speed up emergence from ketamine and propofol induced anaesthesia.9,10 The brain has been called a network of networks which is a testament to its astounding complexity. Each neuron may have Dopaminergic and adrenergic pathways in the brain have connections with thousands of other neurons. Connectomics is been thought to be involved in arousal of the brain. Solt et al. therefore an attempt to understand how the brain functions by studied the effects of methylphenidate on emergence from examining its connections. anaesthesia.11 Methylphenidate (Ritalin) inhibits dopamine and noradrenaline reuptake in the brain and is used primarily to Areas of the brain may be connected to each other through treat attention deficit hyperactivity disorder. Their study found axonal tracts, that is, they are spatially connected. These that intravenous methylphenidate rapidly induced emergence connections can be visualised as white matter tracts on images from isoflurane anaesthesia. A follow-up study showed that this produced by tractography which utilises diffusion weighted

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images from MRI scans to display the connections between sleep-like state (theta activity and the presence of spindles). The different areas of the brain. children then woke up gently and without agitation from this stage. Different areas of the brain may also be linked temporally even though they lack a direct anatomical connection, that is, they A small group of children did not transition to the natural sleep- are activated at the same time and are said to be temporally like state, instead they emerged directly from the indeterminate connected. This is also referred to as functional connectivity. state. These children experienced significant delirium upon waking – reiterating the idea that the order of transition to Functional Connectivity wakefulness is important to prevent emergence delirium. Recently there has been increasing interest in using the idea of Current and Future Clinical Applications from the functional connectivity to explain various brain functions. EEG Science of Emergence data, collected over different regions of the brain and over a period a time, is analysed for connections between areas. One of Suvorexant (Belsomra) is a new drug used to treat insomnia. It the proposed mechanisms of anaesthesia is the disconnection belongs to the newly developed class called orexin antagonists. of brain regions from each other thereby disabling the brain’s Since orexins and the orexinergic system stabilise the wake state, ability to generate consciousness. Studies of emergence use the the use of an orexin antagonist allows the wake state to give corollary of this idea, that is, on emergence from anaesthesia way to sleep. It is pharmacologically distinct from traditional different areas of the brain reconnect in order to generate sedatives since it has no action on the benzodiazepine binding consciousness. site on the GABAA receptor.

In their study, Chander et al. describe the brain’s trajectory from Studies that demonstrate the effects of methylphenidate on the anaesthetised state to the awake state using EEG data from general anaesthesia may explain the clinical observation that 100 patients undergoing orthopaedic surgery under general patients who are taking methylphenidate to treat ADHD may anaesthesia.17 According to their nomenclature, Slow Wave require higher doses of anaesthetic agents to achieve sufficient Anaesthesia (SWA) is that state seen just prior to discontinuing depth of anaesthesia. the anaesthetic. This state is characterized by a significantly large Unraveling the mysteries of how the brain regains consciousness delta wave contribution (0.5 – 4 Hz). Non-Slow Wave Anaesthesia is likely to provide answers to important questions in the field of (NSWA) is described as that state having a lower delta wave anaesthesia - like why some patients take longer to emerge than contribution, i.e. it is largely a lower amplitude higher frequency others. The field is lacking in sufficient studies on human subjects signal. in clinical settings but this likely to change as the scientific The majority of patients in this study were shown to transition community gains greater enthusiasm for exploring emergence. from Slow Wave Anaesthesia to Non-Slow Wave Anaesthesia. Even more exciting is the idea that we may be able to control From this state, patients then transitioned to consciousness. emergence in the same way that we control induction. Not only This study also found that the change in EEG patterns from sleep would this be invaluable to the patient with delayed emergence, to awake were not gradual transitions of decreasing delta activity. but it would also allow a greater margin of extubation safety in Instead the findings show rapid transitions from one state to the the patient with a difficult airway or respiratory disease. A rapid, next, where the brain settles for a period of time before rapidly controlled, and clear wake up could ensure that the patient transitioning to the next state. These findings echo the discovery maintains his/her own airway and breathes adequately. by Hudson et al. of the brain jumping from ‘metastable state’ to The economics of healthcare is a consideration the world over, in 15 ‘metastable state’. developing as well as in developed countries. In the perioperative Of particular interest is the fact that the order of state transition environment, operating room time is a hefty contributor to appeared to be important to the quality of the emergence as medical costs. Expediting wake up and extubation would allow experienced by the patients. Those patients who did not cycle for a significant shortening of this time and could therefore drive through the states in a conventional order but woke up directly down expenditure. from the Slow Wave Anaesthesia (SWA) state experienced more Some scientists in the field also point to the fact that increased pain and agitation, described as an undesirable emergence. knowledge about emergence may have beneficial effects in Emergence Delirium and Functional Connectivity non-anaesthetic fields. The hope is that this science will shine a light on how to reanimate the comatose brain. Could there In a study of pediatric patients undergoing minor surgical be a mechanism by which a brain, which has been stabilised in procedures, Martin et al. also examined EEG data collected during the comatose state, could be nudged towards transitioning to emergence from anaesthesia.18 In keeping with the findings of wakefulness? Perhaps the answer to this and other questions Chander et al., this study found a stepwise progression through could be found in the science of emergence. brain states as the patients emerged from general anesthesia. Patients transitioned from a delta dominant state to what they References 1. Perouansky M. The Quest for a Unified Model of Anesthetic Action. described as an indeterminate state characterised by low voltage Anesthesiology. 2012;117(3):465-74. high frequency activity. From this state the majority of patients 2. Ebrahim I, Howard R, Kopelman M, Sharief M, Williams A. The hypocretin/orexin transitioned to a state that had striking similarity to a natural system. JRSM. 2002;95(5):227-30.

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3. Inutsuka A, Yamanaka A. The physiological role of orexin/hypocretin neurons in 11. Solt K, Cotten J, Cimenser A, Wong K, Chemali J, Brown E. Methylphenidate the regulation of sleep/wakefulness and neuroendocrine functions. Frontiers in Actively Induces Emergence from General Anesthesia. Anesthesiology. Endocrinology. 2013;4. 2011;115(4):791-803. 4. Kilduff T. Narcolepsy: a neurodegenerative disease of the hypocretin/orexin 12. Chemali J, Van Dort C, Brown E, Solt K. Active Emergence from Propofol system? Trends in Neurosciences. 2000;23(11):512. General Anesthesia Is Induced by Methylphenidate. Anesthesiology. 2012;116(5):998-1005. 5. Ebrahim IO, Sharief MK, de Lacy S, et al. Hypocretin (orexin) deficiency in narcolepsy and primary hypersomnia. J Neurol Neurosurg 13. Solt K, Van Dort C, Chemali J, Taylor N, Kenny J, Brown E. Electrical Stimulation . 2003;74:127-30. of the Ventral Tegmental Area Induces Reanimation from General Anesthesia. Anesthesiology. 2014;121(2):311-9. 6. Spector M, Bourke DL: Anesthesia, sleep paralysis and physostigmine. Anesthesiology. 1977;46:296-7. 14. Kenny J, Chemali J, Cotten J, Van Dort C, Kim S, Ba D, et al. Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General 7. Kelz M, Sun Y, Chen J, Cheng Meng Q, Moore J, Veasey S, et al. An essential role Anesthesia in Rats. Anesth Analg. 2016;123(5):1210-9. for orexins in emergence from general anesthesia. Proceedings of the National 15. Hudson A, Calderon D, Pfaff D, Proekt A. Recovery of consciousness is mediated Academy of Sciences. 2008;105(4):1309-14. by a network of discrete metastable activity states. Proceedings of the National 8. Friedman E, Sun Y, Moore J, Hung H, Meng Q, Perera P, et al. A Conserved Academy of Sciences. 2014;111(25):9283-8. Behavioral State Barrier Impedes Transitions between Anesthetic-Induced 16. Connectomics [Internet]. En.wikipedia.org. 2017 [cited 9 April 2017]. Available Unconsciousness and Wakefulness: Evidence for Neural Inertia. PLoS ONE. from: https://en.wikipedia.org/wiki/Connectomics 2010;5(7):e11903. 17. Chander D, García P, MacColl J, Illing S, Sleigh J. Electroencephalographic 9. Shirasaka T, Yonaha T, Onizuka S, Tsuneyoshi I. Effects of orexin-A on propofol Variation during End Maintenance and Emergence from Surgical Anesthesia. anesthesia in rats. J Anesth. 2010;25(1):65-71. PLoS ONE. 2014;9(9):e106291. 10. Tose R, Kushikata T, Yoshida H, Kudo M, Furukawa K, Ueno S, et al. Orexin A 18. Martin J, Liley D, Harvey A, Kuhlmann L, Sleigh J, Davidson A. Alterations in Decreases Ketamine-Induced Anesthesia Time in the Rat: The Relevance to Brain the Functional Connectivity of Frontal Lobe Networks Preceding Emergence Noradrenergic Neuronal Activity. Anesth Analg. 2009;108(2):491-5. Delirium in Children. Anesthesiology. 2014;121(4):740-52.

S137 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Three-stage oesophagectomy

M E Sethusa

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of Witwatersrand Correspondence to: [email protected]

Oesophagectomy is performed worldwide for a variety of low socioeconomic status and black race are associated indications ranging from benign conditions like oesophageal with squamous cell carcinoma, whereas in Caucasians, stricture and achalasia to malignant tumours.1 gastroesophageal reflux, Barrett’s oesophagus and obesity are associated with adenocarcinoma.2,4,6 Three-stage oesophagectomy, also known as Mckeown procedure, involves a laparotomy for freeing and mobilisation of Preoperative assessment the stomach, a right thoracotomy for the oesophageal resection and a left-sided neck incision for the anastomosis of either the Because of the increasing early detection of oesophageal gastric tube or oesophageal conduit which could either be the cancers and reflux-associated adenocarcinomas, obesity might jejunum or large colon. be encountered in patients presenting for oesophagectomy. Commonly, patients will be underweight as a consequence of the The stomach mobilisation and oesophageal resection parts dysphagia, poor socioeconomic status and cachexia associated of the three-stage oesophagectomy can be done through a with malignancy. Nutritional support should be considered in laparoscopic and thorascopic route respectively with some the malnourished and a multidisciplinary approach, including authors suggesting that the laparo-thoracoscopic approach dieticians, cannot be overemphasised. Parenteral or enteral could be better than the classical open Mckeown procedure. feeding through a nasogastric or jejunostomy tube should Oesophageal cancer is the eighth commonest cancer in the world be initiated preoperatively where it is deemed necessary. with an increasing incidence;2,3 about 30% of these patients Nevertheless, delaying surgery for the treatment of nutritional are suitable for curative oesophagectomy. There are two main deficiencies by feeding has not been shown to improve outcome.4 histological types of oesophageal cancers these being squamous Haematinics should also be given to treat preoperative anaemia. 4 cell carcinoma and adenocarcinoma. Most oesophageal cancers Dehydration should be corrected with fluid therapy which will are squamous cell carcinoma worldwide, but the incidence of also unmask the haemoconcentration. adenocarcinoma is rising in the western world, accounting for up to nearly 50% of all oesophageal cancers.1 The remainder of this Smoking cessation is advised to minimise respiratory article will focus on oesophagectomy for oesophageal cancer. complications perioperatively and also because of the poor wound healing that is associated with it. Chest imaging is useful Anatomy of the oesophagus in detecting hyperinflation which will suggest obstructive airway In an adult the oesophagus is an 18–26 cm muscular tube disease, and any pulmonary infiltrates from either an infective which serves as a conduit for fluids and food particles from the process or aspiration as a result of the oesophageal cancer. Some oropharynx to the stomach. It originates behind the cricoid centres routinely do a lung function test to risk-stratify patients cartilage at the sixth cervical vertebra and extends up to the preoperatively and for comparisons at the postoperative period tenth thoracic vertebra where it joins the stomach just below the with the preoperative baseline. diaphragm.5 It is in close association with the trachea, recurrent laryngeal nerve, left main bronchus, left atrium and aorta within Neoadjuvant chemotherapy, with or without radiation, is used the thorax. increasingly to improve curative resection rate.1,7 There is a delay of four to six weeks before surgery after the chemoradiation to Risk factors minimise complications like bleeding, poor wound healing and Advanced age, male gender, smoking and thoracic radiation postoperative infection. Commonly used chemotherapeutic are recognised risk factors for both histological types of agents are cisplastin, and 5-fluorouracil at times as a combination oesophageal cancers. Alcohol use, achalasia, poor oral hygiene, therapy which can increase the associated complications.1

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Effort tolerance needs to be established preoperatively. Compression of the heart can also result in arrhythmias. Good Anaerobic threshold of less than 11 mls/kg/min is associated communication between the surgical team and the anaesthetist with poor outcome.4 Cardiopulmonary exercise testing is ideal is important to recognise and deal with the complication where available. Other means of assessing effort tolerance like timeously and appropriately. shuttle walk test, stair test and six minutes’ walk test should be Postoperative used where cardiopulmonary exercise testing cannot be done.8 Patients are cared for in a high dependency unit. With the advent Intraoperative of fast-track surgery, minimally invasive oesophagectomy and As previously mentioned, the Mckeown technique involves adequate pain control with thoracic epidural analgesia, some a laparotomy, right-sided thoracotomy and a left-sided neck authors suggest that patients can be cared for in the ward unless incision.2 Common challenges faced by the anaesthetist include there is a need for ventilation postoperatively which is currently positioning, long duration of surgery, blood loss and one lung uncommon with most patients being extubated in theatre. ventilation (OLV). Conclusion Oesophageal surgery is a relative indication for OLV, but because Success for oncological surgery should not only be limited to of the ease of surgical access, it is almost always done during 30-day morbidity or mortality, but should also include recurrence the oesophageal resection. Any method or device could be of the cancer. Anaesthetists, as the perioperative physicians, can used for lung isolation depending on familiarity. In our setting have an influence on morbidity, mortality and cancer recurrence, a left-sided double lumen tube is used because of availability a concept called “onco-anaesthesia”. and a preference of intubating the bronchus of the ventilated lung. Lung protective ventilation has to be adhered to in order References to minimise respiratory complications postoperatively which 1. Blank RS, Huffmyer JL, Jaeger JM. Anesthesia for esophageal surgery. Principles account for the highest morbidity at quoted rates between and practice of anesthesia for thoracic surgery: Springer; 2011. p. 415-43. 17.7–38%.9 The pulmonary morbidity could either be pneumonia 2. Howells P, Bieker M, Yeung J. Oesophageal cancer and the anaesthetist. BJA Education. 2016:mkw037. or pulmonary insufficiency requiring ventilation including ARDS. 3. Mu J, Gao S, Mao Y, et al. Open three-stage transthoracic oesophagectomy versus minimally invasive thoraco-laparoscopic oesophagectomy for Fluid therapy is important with excess fluids leading to oesophageal cancer: protocol for a multicentre prospective, open and parallel, pulmonary morbidity9 and a high likelihood of anastomotic leak. randomised controlled trial. BMJ open. 2015;5(11):e008328. Inadequate fluids will also compromise haemodynamics with 4. Sherry KM, Smith FG. Anaesthesia for oesophagectomy. Bja Cepd Reviews. 2003;3(3):87-90. hypotension and a need for vasopressors which both can lead to 5. Doherty GM, Way LW. Current surgical diagnosis and treatment: Lange Medical poor capillary perfusion, poor wound healing and anastomotic Books/McGraw-Hill; 2006. 2 leaks. Goal-directed fluid therapy could help in striking a good 6. Park DP, Welch CA, Harrison DA, et al. Outcomes following oesophagectomy in balance. patients with oesophageal cancer: a secondary analysis of the ICNARC Case Mix Programme Database. Critical Care. 2009;13(2):S1. Adequate pain control perioperatively reduces the incidence 7. Huitink JM, Teoh WH. Current cancer therapies–A guide for perioperative of pulmonary complications.10 Thoracic epidural is considered physicians. Best Practice and Research Clinical Anaesthesiology. 2013;27(4):481-92. a gold standard in most centres. Some literature suggests that 8. Murray P, Whiting P, Hutchinson SP, et al. Preoperative shuttle walking testing paravertebral blocks are as efficacious as an epidural with fewer and outcome after oesophagogastrectomy. BJA: British Journal of Anaesthesia. side-effects.2 2007;99(6):809-11. 9. Xing X, Gao Y, Wang H, et al. Correlation of fluid balance and postoperative Hypotension can occur as a consequence of blood loss or pulmonary complications in patients after esophagectomy for cancer. Journal of Thoracic Disease. 2015;7(11):1986-93. compression of major vessels and the heart during thoracic 10. Li W, Li Y, Huang Q, et al. Short and long-term outcomes of epidural or dissection and also as a result of dehydration from the intravenous analgesia after esophagectomy: a propensity-matched cohort preoperative period unmasked by the anaesthetic agents. study. PloS one. 2016;11(4):e0154380.

S139 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Managing an acute pulmonary embolism on the table

E Welch

Dunkeld Anaesthetic Practice, Johannesburg Correspondence to: [email protected]

Pulmonary embolism (PE) occurs in less than 1 in 1 000 in the • Recent surgery, bone fractures, trauma or indwelling catheters general population, but is one of the commonest causes of (especially central venous lines which can be associated with death during hospital admissions. The incidence of pulmonary upper limb DVT). embolism during an anaesthetic, while unknown and • Associated disease states – cerebrovascular accident, cardiac exceedingly uncommon, is a devastating event for all involved, failure, malignancy. having a mortality of over 80%, half of whom will demise within • Pregnancy, hormone therapy and contraceptive pills. the first 15 minutes. • Smoking. The pathophysiology is simple; a piece of clot – usually from • Surgery where non-haematological material may enter the a deep vein thrombosis (DVT) – passes through the heart and venous system – fat embolus, amniotic fluid embolus, tumour lodges in one of the pulmonary arteries or arterioles producing embolus (especially renal cell carcinoma), bone embolus, an ischaemic area of lung with a resultant ventilation:perfusion renal calculi, foreign body embolus, (cement, catheters) and mismatch. The size of this shunt is directly related to the size of air embolus. the clot and the vessel that it occludes. The result is an increase Signs and symptoms in the alveolar–arterial oxygen difference, the arterial–end tidal carbon dioxide difference, hypoxia, acidosis, acute right The classic signs and symptoms of dyspnoea, chest pain, ventricular failure, hypotension and cardiogenic shock and cough, fever, haemoptysis and syncope will not be seen death.1 under anaesthesia, making a reliance on monitors and other investigations the mainstay of diagnosis. Around 30% of PEs are Massive PE is easy to recognise due to catastrophic cardiac asymptomatic, making a history unreliable. The following should collapse, but is very difficult to treat, while smaller non- trigger alarm bells: fatal pulmonary emboli can prove a diagnostic challenge. • Signs of a DVT – unilateral leg swelling is seen in up to 80% of Management after initial diagnosis and resuscitation requires patients with a PE. a delicate balance of anticoagulation and thrombolysis whilst • The classically described S Q T ECG pattern is only seen in avoiding bleeding. 1 3 3 20% of pulmonary emboli. Patients at risk for having a pulmonary embolus 2,3 • Sudden drop in end tidal CO2 (ETCO2). The risk increases exponentially with a greater number of risk • Tachycardia and hypotension. factors. • Hypoxia (especially of sudden onset). • Deep vein thrombosis – having a current DVT or history of Diagnostic tests4 DVTs and/or pulmonary embolus. In the presence of cardiogenic shock (tachycardia, hypotension, • Inherited clotting abnormalities – Factor V Leyden and protein poor perfusion, raised central venous pressure) due to a S and C deficiency. suspected pulmonary embolus, the following investigations can • Advancing age – above the age of 60 the risk doubles every aid the diagnosis: 10 years. • Arterial blood gas (ABG) – classically shows a raised PaCO2, • Gender – there is no male or female predominance. hypoxia and acidosis (predominantly respiratory acidosis but • Immobility – being bed-ridden or immobile for a period of there may be a concomitant metabolic acidosis due to poor time. perfusion following cardiogenic shock).

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▫▫ The PaCO2–ETCO2 difference will be raised due to the Management increased shunt, as part of the lung is no longer being With little time between the onset of symptoms and death perfused. following a pulmonary embolus, diagnosis, resuscitation and ▫▫ Alveolar–arterial O2 gradient will be increased due to management of the condition need to be done simultaneously.7 perfusion:ventilation mismatch. 1. Systemic function support ▫▫ The classic blood gas findings of a PE in an awake, non- ventilated patient can be different to those of the ▫▫ Resuscitating and restoration of cardiovascular function. ventilated patient as hyperventilation accompanying a ▫▫ Early CPR is often needed. pulmonary embolus causes a respiratory alkalosis initially. ▫▫ Ventilation with 100% oxygen in an attempt to reverse • ECHO – TEE or TTE depending on the availability, looking for hypoxia. right ventricular dysfunction. ▪▪ Hyperventilation will not decrease the PaCO2 due to • Spiral CT scan or CT angiogram of the chest is the gold the V:Q mismatch while high levels of PEEP and high standard for diagnosis but is impossible to do on an unstable ventilatory pressures may diminish pulmonary blood patient in an operating theatre. flow from the right ventricle. • D Dimers – these fibrin degradation products show that ▫▫ Inotropic support. formed thrombus is being broken down, but are not available ▫▫ Diagnosis with ABG and ECHO. at the bedside and are also raised following trauma, surgery, as ▫▫ Eliminate other causes of haemodynamic instability well as in DVT and PE. (myocardial infarction, arrhythmias, anaphylaxis, cerebral • Ultrasound of the limbs may produce evidence of a DVT. bleed and aortic rupture). • Troponin assays – elevated troponin T or I indicate myocardial ▫▫ Once stable, CT scan or CT angiogram. damage which is suggestive of an acute coronary syndrome Once the patient is stabilised and a definitive diagnosis is rather than an acute PE. made, a variety of treatment options are available, depending ▫▫ Troponins elevated immediately after a suspected PE is on local expertise and availability of equipment. The optimal suggestive of coronary syndromes as troponin levels take treatment path has not been decided upon yet. Reperfusion 3–6 hours to rise after myocardial damage. should be undertaken as soon as possible and is often ▫▫ Any cardiac condition associated with ischaemia can also needed as a part of resuscitation of a patient who remains raise troponins. haemodynamically unstable.8 • V:Q scans – ventilation:perfusion scans’ role is in awake, stable 2. Reperfusion of area affected by embolus patients, not under anaesthesia. The advantage is they require ▫▫ Thrombolysis – using urokinase, tPA (tissue plasminogen lower doses of radiation and no contrast media offering some activator) is the first-line therapy to attempt to lyse the benefit in pregnancy and renal failure. Positive scans have embolus. It should be administered as soon as a diagnosis great predictive value for initiating treatment while negative has been made in patients who remain haemodynamically scans do not rule out PE. unstable. Differential diagnosis ▪▪ Systemic – easy and quick to deliver and can be given via a peripheral line, but with a high risk of intercranial, While the diagnostic tests may help ascertain a more accurate wound and surgical-site bleeding. diagnosis, the differential diagnosis of any cause of rapid onset ▪▪ Catheter-directed thrombolysis – smaller doses given cardiogenic shock must be considered: into the occluded vessel or area with less risk of • Anaphylaxis bleeding complications.9,10 • Aortic dissection ▪▪ Open sternotomy placement of catheter directly into • Stroke right ventricle or pulmonary artery. • Cardiac arrhythmias (tachyarrhythmias, bradyarrhythmias, 3. Clot removal heart blocks) ▫▫ Standard therapy is an embolectomy from the pulmonary • Sepsis artery and/or right ventricle. • Hypertrophic obstructive cardiomyopathy (HOCM) ▫▫ Percutaneous venous thrombectomy – used if not fit for surgery. Fifty percent success rate. In my personal experience and that of multiple cases reported in the literature, the following conditions represent a pulmonary 4. ECMO embolus under anaesthesia: 1. Sudden-onset hypotension (cardiogenic shock) If instituted rapidly, bypassing the lungs, ECMO allows

2. Sudden decreased ETCO2 for oxygenation while thrombolysis takes place. Veno- 3. Raised PaCO2 arterial cannulation during initial resuscitation pre- or 4. Decreased oxygen saturation postthrombolysis has been described. High risk of bleeding.11 5. Right-sided cardiac dysfunction – if and when an ECHO cardiogram can be done5,6

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5. Prevention of further emboli • Rheumatic disease ▫▫ Initial anticoagulation is started as soon as possible • Cancer at the time of hospital admission to prevent further clot propagation. The practice of combined thrombolysis and anticoagulation in the Conclusion acute period after a PE is well described. Long-term The rare event of sudden hypotension, decreased end tidal anticoagulation must be maintained as the risk of future carbon dioxide and hypoxia under anaesthesia has a potential DVT and PE is increased. The choice of agent is determined fatal outcome and should be managed as a pulmonary embolus, by local practice, the type of surgery, in combination with requiring rapid resuscitation, early diagnosis with thrombolysis the patient’s risk factors. and anticoagulation. Persistent haemodynamic instability ▪▪ Vitamin K antagonists inhibit the synthesis of Factors requires early intervention and clot removal if possible. In the II, VII, IX and X. perioperative period bleeding is an ever-present risk. ▪▪ Heparins inhibit Factor Xa and thrombin indirectly References through antithrombin III. 1. Lang I. Advances in understanding the pathogenesis of chronic thromboembolic ▪▪ Fondaparinux indirectly inhibits Factor Xa only via pulmonary hypertension. Br J Haematol 2010;149:478-483. antithrombin III. 2. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice ▪▪ Rivaroxaban, apixaban and edoxaban directly inhibit guidelines (8th Edition). Chest 2008;133:381S-453S. Factor Xa. 3. Girard P, Musset D, Parent F, et al. High prevalence of detectable deep ▪▪ Dabigatran directly inhibits thrombin. venous thrombosis in patients with acute pulmonary embolism. Chest 1999;116:903-908. ▫▫ Insertion of venocaval filters – though controversial – has 4. Konstantinides SV, Torbicki A, Agnelli G, et al. 2014 ESC Guidelines on the been shown to decrease the incidence of pulmonary diagnosis and management of acute pulmonary embolism. Eur Heart J emboli from proven DVT in high risk patients but may 2014;35:3033-3069. have a risk of venocaval occlusion. New removable filters 5. Khraise WN, Allouh MZ, Hiasat MY, Said RS. Successful management of intraoperative acute bilateral pulmonary embolism in a high grade astrocytoma 7,12 may have a role to play during a high-risk episode. patient. Am J Case Rep. 2016 Aug 31;17:632-6. Bleeding 6. de Lima E, Souza R, Apgaua BT, et al. Severe fat embolism in perioperative abdominal liposuction and fat grafting. Rev Bras Anestesiol. 2016 May-Jun;66(3):324-8. A major complication of thrombolysis and anticoagulation 7. Konstantinides SV, Vicaut E, Danays T, et al. Impact of thrombolytic therapy on is bleeding which is associated with marked morbidity and the long-term outcome of intermediate-risk pulmonary embolism. J Am Coll mortality. Patients who need thrombolysis and anticoagulation Cardiol. 2017 Mar 28;69(12):1536-1544. during or soon after surgery are obviously at high risk for 8. Serhal M, Haddadin IS, et al. Pulmonary embolism response teams. J Thromb developing a bleeding complication and should be managed by Thrombolysis. 2017 Apr 11. maintaining clotting factors and direct pressure where possible. 9. Intracranial hemorrhage in a patient with sub-massive pulmonary embolism treated with EkoSonic endovascular system directed thrombolysis. Catheter Patients who have not had surgery, at increased risk of bleeding Cardiovasc Interv. 2017 Apr 11. 13 after anticoagulant therapy, in descending order, are : 10. Chen G, Shi W, et al. Feasibility of continuous, catheter-directed thrombolysis • Active gastroduodenal ulcer using low-dose urokinase in combination with low molecular-weight heparin for acute iliofemoral venous thrombosis in patients at risk of bleeding. Exp Ther • Bleeding during the three months before admission Med. 2017 Feb;13(2):751-758. • Platelet count < 50/l 11. Corsi F, Lebreton G, et al. Life-threatening massive pulmonary embolism rescued by venoarterial-extracorporeal membrane oxygenation. Crit Care. 2017 Mar • Advanced age ≥ 85 years 28;21(1):76. • Severe renal failure GFR < 30 ml/min/m2 12. Liang N, Genovese EA, et al. Impact of inferior vena cava filter placement on short-term outcomes in patients with acute pulmonary embolism. Ann Vasc • Hepatic failure (INR > 1.5) Surg. 2017 Mar 21. pii: S0890-5096(17)30432-6. • Patients in intensive care unit/coronary care unit 13. Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. • Presence of central venous catheter Chest 2011;139:69-79.

S142 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Clinical use of nerve stimulators

E Welch

Dunkeld Anaesthetic Practice, Johannesburg Correspondence to: [email protected]

Nerve stimulators are used in the following clinical Current output roles: 1. Neuromuscular monitoring of muscle relaxant effects 2. Location of nerves for loco-regional anaesthesia 3. Surface nerve mapping

4. Detection of contractile muscle during surgery. Voltage

The physical properties of each of these monitors differ allowing for different detection techniques and strength of stimulation dependent on the site stimulated. Time The physics behind how a nerve stimulator works 1,2

Maximal stimulus: A pulse duration and current large and long Voltage is the wave height and time: the duration over which enough to stimulate all nerve fibres. the stimulus occurs.

Supra maximal stimulus: A stimulus 10–20% greater than the stimulus required to stimulate all fibres ensuring all muscle fibres Total energy supplied to the nerve = current x duration are stimulated to contract every time, producing the maximal Determinants of neural stimulation force. This is 2.5 –3 times greater than required to produce the initial response – what we use clinically. The following factors will determine if a nerve will respond to a stimulus: The neural response depends on current density not voltage. To achieve a consistent, repeatable maximal response, the current 1. Rheobase of the nerve – the inherent minimum current density must be greater than what is needed to get a maximal needed to stimulate that nerve. response. 2. Chronaxy of the nerve – the inherent length of time the nerve needs to be stimulated to produce a response. Using Ohm’s law where: V=IR [Potential difference (Voltage) 3. Polarity of the electrodes – negative (black) electrodes are = Current x resistance] more efficient at causing a nerve to depolarise. Current = Voltage / Resistance 4. Distance of the nerve from the electrode – the further the nerve is from the electrode the more current is needed to To produce a constant current with changes in skin resistance stimulate it. (normal between 500 –2000Ω) requires a change in voltage. a. Coulombs law: Current required = Minimal current/ Old nerve stimulators required a change in voltage to be dialled distance1 in, to deliver the required current. (The stimulator showed you 5. Area of the electrode – smaller electrodes will produce a what current was given and you had to make the adjustments). greater current density. All current nerve stimulators are constant current stimulators Measurement of response which through feedback detect changes in the current delivered and alter the voltage accordingly, so the desired current is always 1. Visual given. • Inaccurate; unable to see fade.

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2. Tactile Single twitch • Better than visual; may detect fade especially with DBS. 10sec 10sec 3. Clinical • Patients may be able to breathe, lift their head and squeeze a hand while still having 75% of their NMJ receptors blocked. 0.2ms 0.2ms 0.2ms 4. Acceleromyography • The commonest method of monitoring a block. Train-of-four (TOF) • A pizo-electric crystal is usually attached to the thumb and its Four twitches of 0.2msec duration at 2Hz (a twitch every 0.5 sec); acceleration measured after having the ulnar nerve stimulated. 4 twitches allow comparison between each other and are used in • Applying Newton’s second law: assessing recovery from blockade. Force = Mass x acceleration • The thumb provides a constant mass therefore the force of Train-of-four contraction = acceleration. 0.5 sec 0.5 sec 0.5 sec 5. Mechanomyography • A cumbersome time consuming method that involves fixing the limb and applying a preload to the thumb to ensure contraction is detected from zero. 0.2ms 0.2ms 0.2ms 0.2ms • A transducer measures the force of contraction, which is then amplified to produce a value. Blockade with a DMR produces a TOF pattern that has a constant 6. Electromyography diminution in twitch height over time. NDMRs produce a pattern where each twitch is smaller than the preceding, twitch while the • An ECG for muscles that can be used for muscles that are not available for the mechanical stimulation. number of twitches increases with progressive recovery. • 5 Electrodes are attached as follows Two different patterns can be utilised clinically with a TOF. 1. 2 stimulating electrodes over the nerve TOF count: Is the number of twitches present and are referred to 2. 1 receiving electrode over the muscle as T1, T2, T3, T4. 3. 1 reference electrode on the tendon TOF ratio: Once all four twitches in TOF are present the ratio 4. 1 ground electrode to diminish artefact (between the between the first (T1) and fourth twitch (T4) is calculated stimulating and receiving electrodes). which represents the amount of recovery present. This needs • Artefacts are common especially with electrical interference to be objectively measured using an acceleromyograph or a • Electrodes need to be placed at least 15 minutes prior to mechanomyograph. stimulation to diminish early detection. Train-of-four in depolarising and non-depolarising muscle relaxants • Incorrect electrode placement is easy. Depolarising Muscle relaxants Site of measurement

The effect of neuromuscular blocking drugs on different muscle groups is not uniform. The adductor pollicis, which is the easiest Non Depolarising Muscle relaxants muscle to monitor, is much more sensitive to the effects of neuromuscular blocking drugs than the laryngeal muscles and diaphragm, displaying faster onset time, slower recovery and requiring lower doses to produce complete blockade. Recovery of the adductor pollicis therefore ensures recovery of the airway muscles. Other easy-to-use sites are the facial nerve with Train-of-four ratio detection of orbicularis oculi (there is even an acceleromyograph connection made for the upper eyelid), the peroneal and the posterior tibial nerve in the leg. 50% Clinical modes of neuromuscular monitoring3 100% Single Twitch A single twitch of 0.2msec duration is of very little clinical use as it occurs in isolation and demonstrates little other than that the Twitch 1 2 3 4 muscle is stimulated.

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Double burst stimulus (DBS): Phase II block

A burst of 2 or 3 impulses separated by 0.75 seconds. Two patterns Fade occurring on a TOF when using a DMR. The reason is are used, 3:2 or 3:3, representing the number of twitches in each poorly understood, but revolves around continual binding and burst. Each burst occurs at a rate of 50Hz, (3 twitches take 0.06sec activation of the ACh receptor by the DMR, producing an ionic and 2 twitches 0.04 seconds). It is used in place of a TOF when no imbalance in the neuromuscular junction as Na+ is continually objective detector of muscle contraction is available as the larger moving into the cell. AChE inhibitors such as neostigmine will contraction produced is easier to assess manually than a single not reverse this phenomenon. twitch from a TOF. Clinical use of nerve stimulating modalities Double burst stimulus 3:2 0.02 msec 0.02 msec MODE CLINICAL USE Single twitch Little use

0.75 sec Train-of-four Once T2 is present reversal with neostigmine is Train-of-four ratio probable. Recovery of blockade back to normal. Complete reversal. 0.2ms 0.2ms 0.2ms 0.2ms 0.2ms Double burst Recovery from blockade where no objective stimulus monitor is available. Tetanic stimulation: Post tetanic count Depth of block Recovery from intense blockade to a single 50Hz burst of stimulation lasting for 5 seconds. The prolonged twitch on TOF tetanic stimulus mobilises all stores of ACh and stimulates excess Clinical end points of neuromuscular blocking drugs production of ACh to repopulate ACh stores. Clinically, it is combined with a post tetanic count. CLINICAL PARAMETER NERVE STIMULATOR Deep block - no movement possible PTC 0 or 1 Post tetanic count (PTC): Surgical block - movement may occur TOF T1–T2 Uses the mobilised ACh from a tetanic stimulation to evaluate Reversal with neostigmine possible TOF > T2 intense blockade, when no twitch is present on a TOF. 3 seconds Airway reflexes returned TOF ratio > 90% after a tetanic stimulus, a single twitch at 1 second intervals is delivered. The number of twitches present allows an estimation Should all patients receiving NDMR be monitored of how long it will take until T1 appears on a TOF. This varies for with a nerve stimulator? each agent. (As a rough guide 10 twitches on a PTC means that a Viby-Morgensen’s ground breaking study in 1979 alerted one single twitch on a TOF will occur in about 10 minutes.) to the unpredictability of NDMR despite monitoring with nerve stimulators. Studies since have shown that nothing Post tetanic count much has changed in the ensuing years.4,5 Neuromuscular 0.02 msec monitoring has not decreased this unpredictability and the quest for a short acting, predictable agent continues. Residual paralysis has associated morbidity and mortality. 3 sec 1 sec 1 sec 1 sec Why do NDMRs present such a problem with the predictability of termination of effects?

0.2ms 0.2ms 0.2ms 0.2ms 0.2ms 0.2ms 0.2ms 0.2ms 0.2ms 1. No ideal neuromuscular blocking agent exists. 5 sec ▫▫ All agents have an onset time that is inversely related to the agent’s potency (potent agents take longer to work and last longer). Fade ▫▫ All agents require some degree of organ dependent Is a reduction of muscle response from the first to last twitch in a metabolism for their spontaneous elimination. TOF in NDMR. The mechanism of this is twofold: 2. There is vast inter-patient and drug variability.

NDMR block the pre-synaptic cholinergic receptors (along with ▫▫ Renal and hepatic function vary between patients and post-synaptic nicotinic receptors) and this inhibits the reuptake age groups. of choline. This results in less ACh being produced. ▫▫ Adjuvant agents such as magnesium, propofol, sevoflurane and opiates may alter pharmacokinetics and ACh competes with the NDMR for binding sites. Following a dynamics. stimulus, a large excess of ACh is released into the neuromuscular junction. ACh is metabolised faster than the NDMR is removed. 3. Top up doses increase the unpredictability of duration of With each subsequent stimulus, fewer receptors are available as action further. they are bound by the NDMR, producing progressively weaker ▫▫ Doses of 10% of the intubation dose have up to 2-fold muscle contraction. difference in duration of action.

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4. Reversal by competitive antagonism is not completely Inadequate dosing of sugammadex effective. ▫▫ The balance of amount of NDMR to ACh is constantly changing and until the agent is fully metabolised this can revert to paralysis. 5. Reversal agents have significant adverse effects. ▫▫ Neostigmine (bradycardia, peristalsis, abdominal cramps, bronchospasm, nausea and vomiting, muscle paralysis) ▫▫ Glycopyrrolate (tachycardia, dry mouth, cardiac arrhythmia, urinary retention, blurred vision, disorientation) 6. Monitoring provides little improved predictability.

▫▫ Due to constant competition between ACh and the NDMR, This tracing of a TOF ratio shows the danger of inadequate dosing which is compounded by drug and patient variability. of sugammadex. Its recognition and correction was possible due Neuromuscular monitoring in the era of to continuous neuromuscular monitoring. 6 sugammadex • Sugammadex at 0.5 mg/kg was given to an elderly female with The introduction of the novel reversal agent sugammadex has a TOF ratio of 25% provided a solution to the unpredictability of NDMR. Due to its • Initial recovery to a TOF ratio of 80% occurred within 2 minutes. irreversible binding and neutralising of rocuronium, vecuronium • The TOF ratio then reverted to a constant 60–70% and to a lesser degree pancuronium, the effect of even large doses • A second dose of 1 mg/kg of sugammadex was given resulting of amino steroidal muscle relaxants can be rapidly terminated. Logically, one expects that neuromuscular monitoring is no in a sustained TOF of > 95%. longer needed as complete reversal can now occur. Conclusion

Unfortunately, the binding of rocuronium and sugammadex The use of neuromuscular monitoring has provided a snap is a 1 to 1 interaction, so dosing must be adequate to allow shot of an everchanging balance between paralysis (amount encapsulation of all rocuronium molecules. If under-dosing of muscle relaxant present in the body) and reversal (amount occurs, residual curarisation is possible while overdosing of acetycholine present). Due to the unpredicatable nature results in wastage of a rather expensive drug. Neuromuscular of this balance, the use of neuromuscular monitoring has not monitoring has become imperative when using sugammadex as changed the incidence of postoperative residual curarisation it determines the dose of sugammadex needed. even when reversed competitively with neostigmine. The advent Dosing of sugammadex according to nerve stimulation of the neuromuscular blocking agent binding reversal agent sugammadex has produced the need for better understanding Block Nerve stimulator tracing Dose and greater use of neuromuscular monitoring as recovery from Complete: straight after Initial fade may still be 16 mg/kg different depths of blockade can now be predictably controlled intubating dose present and managed. Deep blockade TOF of 0 and a PTC of 0–10 4 mg/kg Moderate PTC > 10 or twitch on TOF 2 mg/kg References and further reading “Neostigmine reversible” TOF of > 2 twitches 2 mg/kg 1. Sykes M, Vickers M, Hull C. Principles of measurement and monitoring in block anaesthesia and intensive care. Blackwell Scientific, 1991. 2. Dorsch J, Dorsch S. Understanding anesthesia equipment, 3rd ed. Construction, care and complications. Williams and Wilkins, 1994. Time course of rocuronium recovery and sugammadex dose 3. Applied pharmacology in anaesthesiology and intensive care. In: Milner A and Welch E, eds. Medpharm publishing, 2012. Onset------> Deep Block Recovery------> 4. Viby-Mogensen J, Jørgensen BC, Ording H. Residual curarization in the recovery room. Anesthesiology. Jun 1979;50(6):539-41. 5. Naguib M, Kopman AF, Ensor JE. Neuromuscular monitoring and postoperative residual curarisation: a meta-analysis. Br J Anaesth. Mar 2007;98(3):302-16. 16 mg/kg 4 mg/kg 2 mg/kg 6. Naguib M. Sugammadex: another milestone in clinical neuromuscular pharmacology. Anesth Analg. Mar 2007;104(3):575-81.

S146 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Anaesthesia for a patient with Achondroplasia presenting for Caesarean section

T Kleyenstuber

Department of Anaesthesia, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand Correspondence to: [email protected]

Introduction Numerous other spinal abnormalities in patients with achondroplasia may result in neuraxial anaesthesia being very Achondroplasia is the commonest form of dwarfism and occurs difficult to perform. Bony landmarks are often difficult to identify in approximately 1.5 per 10 000 live births.1 Achondroplasia is due to the lumbar hyperlordosis and thoracic kyphoscoliosis.9 caused by mutations in the Fibroblast Growth Factor Receptor Abnormally shaped vertebrae and hyperplastic discs result in 3 Gene (FGFR 3) and occurs as a result of sporadic mutations smaller than usual epidural and subarachnoid spaces.1 This in 90% of cases, but may also be inherited as an autosomal may result in difficulties in identifying the epidural space as dominant trait.2 Due to the relatively small maternal pelvis but well as difficulties in feeding epidural catheters. Accidental normal size of the foetal head cephalo-pelvic disproportion is dural puncture is also more common and more difficult to common in pregnant achondroplastic patients3 and the majority identify.9Engorged epidural veins increase the risk of venous of them present for Caesarean delivery. Both general and puncture and contribute to the unpredictable spread of local regional anaesthesia may be complicated in achondroplastic anaesthetic.10 patients especially when performed during the third trimester of pregnancy. The kyphoscoliosis and lumbar hyperlordosis commonly seen in Anatomical and pathophysiological abnormalities patients with achondroplasia may lead to restrictive pulmonary dysfunction characterized by reduced vital capacity and reduced A reduced rate of endochondreal ossification in association with functional residual capacity.1 The restrictive lung disease as normal periosteal bone formation4 results in the characteristic well as the upper airway obstruction and sleep apnoea may appearance of achondroplastic dwarfs: short stature with contribute to the development of pulmonary hypertension proximal limb shortening; large head with frontal bossing, and cor pulmonale.1 In pregnant achondroplastic patients the flattened nasal bridge and maxillary hypoplasia as well as foetal head often cannot engage in the narrow pelvis. As a result spinal deformities in the form of lumbar hyperlordosis and the uterus remains entirely intra-abdominal and splints the thoracolumbar kyphosis.1 diaphragm, further reducing the functional residual capacity.9 The haemodynamic effects of aorto-caval compression by the The brachycephalic large head, facial features, large tongue and narrow upper airway predispose these patients to upper intra-abdominal uterus are also likely to be more pronounced 3,10 airway obstruction and obstructive sleep apnoea.1,4,5 There are especially with neuraxial anaesthesia. also several case reports of difficult laryngoscopy and tracheal Anaesthetic technique intubation6-8 but Mayhew, Katz, Miner et al. encountered no difficulty in the airway management of 26 achondroplastic The anaesthetic management of a patient with achondroplasia patients presenting for 37 general anaesthetics.4 It is however presents unique challenges to the anaesthetist. The addition important to note that none of the 26 patients were pregnant. of the anaesthetic risks associated with the third trimester of pregnancy mandates meticulous planning by a multidisciplinary Proximal spinal cord compression caused by foramen team consisting of anaesthetists, obstetricians, neonatologists magnum stenosis may result in central apnoea in patients with and midwives. A thorough preoperative workup of the patient achondroplasia1 and hyperextension of the neck should always is essential. be avoided.3 This limitation of neck extension may contribute to the difficulties encountered in tracheal intubation.6,7 It has also Historically, despite the potential difficulties associated with been postulated that the increased incidence of hydrocephalus the airway management of achondroplastic patients, general in achondroplastic patients may be due to reduced cerebrospinal anaesthesia has been favoured over regional anaesthesia.7 fluid flow at the level of the foramen magnum stenosis.1 There are however numerous case reports of Caesarean sections

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being performed under regional anaesthesia in patients with for emergency Caesarean section by 30% and produced a block achondroplasia.3,9,11,12 to T3.12 Osorio Rudas, Socha García, Upegui et al. administered 5 mg of hyperbaric bupivacaine together with 64 µg of Due to the proximal limb shortening, non-invasive blood morphine and 16 µg of fentanyl into the subarachnoid space pressure monitoring may be difficult.3 Peripheral intra-arterial as part of a combined spinal epidural technique and produced blood pressure monitoring should be considered in anticipation a sensory block up to T4.14 Crawford and Dutton recommend of the more pronounced haemodynamic effects of aorto-caval the use of microspinal catheters and the administration of compression. The placement of peripheral lines may be more incremental doses of local anaesthetic, if spinal anaesthesia is to difficult due to the presence of excess skin and soft tissue, and be considered.15 the landmarks for the placement of central venous catheters may be more difficult to identify.4The main concern with providing Irrespective of which neuraxial technique is used, the general anaesthesia to pregnant patients with achondroplasia haemodynamic effects of aorto-caval compression may be more is the potential difficulty of the airway management. Aspiration severe than in patients who do not have achondroplasia and prophylaxis should always be administered but sedative should be aggressively managed. premedication is contraindicated in patients with central or obstructive sleep apnoea. A meticulous airway management Summary plan should be in place and excessive extension of the neck The management of a pregnant patient with achondroplasia should always be avoided.3 The endotracheal tube size should requires a multidisciplinary team approach. After a thorough be reduced and should be based on the patient’s weight.4 If preoperative assessment of the patient a meticulous anaesthesia significant thoracolumbar kyphosis is present, cardio-respiratory plan needs to be devised. Both general and regional anaesthesia function may be compromised2 and ventilation may be pose significant risk to patients with achondroplasia, especially problematic. during the third trimester of pregnancy, and management plans All anaesthetic drugs should be dosed according to the patient’s need to be individualized. weight as the use of average adult dosages will possibly result References in overdosing.13The anatomical abnormalities present in the 1. Berkowitz ID, Raja SN, Bender KS, Kopits SE. Dwarfs: Pathophysiology and thoracolumbar spine may make regional anaesthesia technically Anesthetic Implications. Anesthesiology. 1990;73(4):739-59. more difficult in patients with achondroplasia and the risk of 2. Dubiel L, Scott G, Agaram R, McGrady E, Duncan A, Litchfield K. Achondroplasia: complications is increased due to the smaller than usual epidural anaesthetic challenges for caesarean section. Int J Obstet Anesth. and subarachnoid spaces.8,11 Due to the unpredictable spread of 2014;23(3):274-8. local anaesthesia, there are no epidural dosage guidelines. The 3. Brimacombe J, Caunt J. Anaesthesia in a gravid achondroplastic dwarf. Anaesthesia. 1990;45(2):132-4. volume of the test dose should be reduced and local anaesthesia 4. Mayhew JF, Katz J, Miner M, Leiman B, Hall ID. Anaesthesia for the should be titrated against the block height in small incremental achondroplastic dwarf. Can J Anesth. 1986;33(2):216-21. doses.9 Wardall and Frame reported that a dose of only 5 ml of 5. Krishnan B, Eipe N, Korula G. Anaesthetic management of a patient with 0.5% plain bupivacaine produced a block to T4 in a pregnant achondroplasia. Pediatr Anesth. 2003;13(6):547-9. patient with achondroplasia.10 The slow onset of bupivacaine 6. Mather J. Impossible direct laryngoscopy in achondroplasia. Anaesthesia. 1966;21(2):244-8. makes it difficult to titrate precisely and it has been suggested 7. Walts LF, Finerman G, Wyatt GM. Anaesthesia for dwarfs and other patients of that the use of a local anaesthetic with shorter onset time may be pathological small stature. Can J Anesth. 1975;22(6):703-9. 3 more appropriate. Carstoniu, Yee and Halpern gave a test dose 8. Huang J, Babins N. Anesthesia for cesarean delivery in an achondroplastic dwarf: of 1 ml lidocaine 2% with epinephrine 1:200 000 as a test dose. a case report. AANA J. 2008;76(6):435. 5 minutes later they administered 3 2 ml doses of the same 9. Morrow M, Black I. Epidural anaesthesia for caesarean section in an achondroplastic dwarf. Br J Anaesth. 1998;81(4):619-21. solution at 3 minute intervals followed by a 1 ml bolus together 10. Wardall G, Frame W. Extradural anaesthesia for caesarean section in with 50 µg fentanyl prior to skin incision. A T5 level was achondroplasia. Br J Anaesth. 1990;64(3):367-70. 11 established. 11. Carstoniu J, Yee I, Halpern S. Epidural anaesthesia for caesarean section in an achondroplastic dwarf. Can J Anaesth. 1992;39(7):708. As epidural anaesthesia allows for titration of the local 12. Ravenscroft A, Govender T, Rout C. Spinal anaesthesia for emergency caesarean anaesthetic, it is preferred to spinal anaesthesia. However, section in an achondroplastic dwarf. Anaesthesia. 1998;53(12):1236-7. the titration of dose to block height is time consuming and 13. Kalla G, Fening E, Obiaya M. Anaesthetic management of achondroplasia. Br J epidural anaesthesia may not be ideal in patients presenting Anaesth. 1986;58(1):117-9. for emergency Caesarean section. There are only a few case 14. Osorio Rudas W, Socha García NI, Upegui A, Ríos Medina Á, Moran A, Aguirre Ospina O, et al. Anesthesia for cesarean section in a patient with achondroplasia. reports of the successful use of spinal anaesthesia for Caesarean Revista Colombiana de Anestesiología. 2012;40(4):309-12. section in patients with achondroplasia. Ravenscroft, Govender 15. Crawford M, Dutton D. Spinal anaesthesia for caesarean section in an and Rout reduced their standard subarachnoid dosage regime achondroplastic dwarf. Anaesthesia. 1992;47(11):1007-.

S148 Southern African Journal of Anaesthesia and Analgesia 2017; 23(2)(Supplement 1) South Afr J Anaesth Analg ISSN 2220-1181 EISSN 2220-1173 Open Access article distributed under the terms of the © 2017 The Author(s) Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 FCA 2 REFRESHER COURSE

Anaesthetic management in paediatric burns

P N Mogane

Department of Anaesthesia, Chris Hani Baragwanath Academic Hospital, University of Witwatersrand Correspondence to: [email protected]

Introduction Improvement in patient outcomes has been attributed to advances in the understanding of burn injury pathophysiology, Children are typically prone to burns due to the inability to improved burn shock management, early aggressive surgical recognise danger (in younger age groups) and the risk-taking intervention and the development of specialised burn behaviours of the older, mobile child. They also have thinner skin, lose proportionally more fluid, are more prone to hypothermia treatment centres where there is the early protocolised care of a and mount a greater systemic inflammatory response.1 Most multidisciplinary team which appreciates the essential need for burns are caused by thermal injury (scalds, flame or cold) and meticulous attention to detail to ensure good outcomes.5 less frequently by electrical, radiation or chemical injury. The Classification severity of a burn injury is dependent on age, the depth of burn, the total body surface area (TBSA) involved, the location of the Burn wound severity is quantified according to the TBSA 2 burn injury, and the presence of inhalation injury. Surgical burned and the wound depth. The TBSA burned is typically procedures in burns can be broadly divided into four groups: estimated by a head-to-toe visualisation of the wounds and supportive (resuscitation, airway and pain management, subsequently calculated according to the ‘Rule of nines’ in adults, colostomy); decompressive (fasciotomy, laparotomy for and the Lund-Browder age/growth-adjusted chart for children abdominal compartment syndrome); ablative (sloughectomy, (Figure 1). This is essential as it affects many aspects of care, debridement, amputations) and reconstructive (split skin grafts, flaps).3 Nowadays we appreciate that burn anaesthesia has a e.g. fluid resuscitation, drug dosing, surgical intervention, and 5 high complication rate. Contributing to this is sepsis; multiple outcome. Wound depth is based on the anatomical layers of the organ failure; bleeding; difficulties in thermoregulation; the skin (Table 1). Reassessment of burn depth should be repeated hypermetabolic state; nutritional and electrolyte imbalances; 72 hours post injury as this may change as a result of management and the rapid rate at which decompensation can take place.4 and interventions.6

Table I. Classification of burns based on depth 5, 8 New classification Depth Etiology Appearance Sensation Outcome (old classification) Superficial Confined to epidermis Sunburn Dry, red blanches Sharp, uniform pain Heals spontaneously (1st degree) Momentary hot fluid oedematous soft, ± 7 days peeling Partial thickness Scalds Mottled & red Dull or hyperactive (2nd degree) Flash burns blanches pain - Superficial Weak chemicals Red or pink blisters Sensitivity to air or Epidermis & upper Oedema temperature dermis Serous exudate Pressure only Heals spontaneously Thin eschar 14 – 21 days - Deep Epidermis & deep Requires excision & dermis grafting Full thickness Immersion No blanching Painless to touch & Granulates and (3rd degree) Destruction of Flame Pale white or tan pin prick requires grafting; epidermis & dermis Electrical Charred, hard, dry, May hurt at deep limited function Chemical leathery pressure (4th degree) Muscle, fascia, bone Hair absent Requires extensive Thick eschar debridement Skeletonised

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by a hypermetabolic phase which has been known to last up to 18 months after the burn.2, 5, 9

The initial phase occurs due to the release of circulating mediators such as tumour necrosis factor and interleukins that result in a systemic inflammatory response syndrome. Within six to eight hours of injury, increased microvascular permeability, vasodilatation, vascular stasis, decreased cardiac contractility Relative percentage of body surface area (% BSA) affected by growth and cardiac output cause significant Age oedema. The fluid and electrolyte Body Part 0 yr 1 yr 5 yr 10 yr 15 yr a = 1/2 of head 9 1/2 8 1/2 6 1/2 5 1/2 4 1/2 leak from intravascular to interstitial b = 1/2 of 1 thigh 2 3/4 3 1/4 4 4 1/4 2 1/2 space combined with evaporative c = 1/2 of 1 lower leg 2 1/2 2 1/2 2 3/4 3 3 1/4 fluid losses further impairs perfusion Figure 1. Relative percentage of total body surface area (TBSA) affected by growth 7 resulting in burn shock, a combination of distributive, hypovolemic and Pathophysiology cardiogenic shock.5 Fluid requirements in the acute resuscitative phase (first 24 hours) are traditionally Skin protects the host from bacterial invasion, and prevents calculated using the Parklands formula: 2-4 ml x body weight heat, fluid and electrolyte losses. Its elasticity allows movement x TBSA burned. Half of this is given in the first eight hours post and growth; it has excretory (e.g. urea, water, ammonia) injury and the rest over the following 16 hours.3,10 and endocrine (vitamin D) functions; and is the sensory and The hypermetabolic response occurs due to a surge in psychosocial interface.3 Major burns can thus cause massive catecholamines and corticosteroids. The severity of this tissue destruction and the activation of an inflammatory hyperdynamic, hyper catabolic response is related to the TBSA response that are associated with metabolic derangements burned and the duration of exposure. Left untreated this can lead affecting virtually all organ systems. Burn injury pathophysiology to physiologic exhaustion and death. Strategies to ameliorate evolves in two distinctive phases; an acute phase typified by this response include early surgical intervention, maintenance burn shock which usually resolves within 24–48 hours, followed of a warm environment, constant nutritional support to replace

Table 2 Pathophysiological changes during early and late phases of major burn injury2, 3, 5, 9 System Early / resuscitative phase (< 48 hrs) Late / hypermetabolic phase (> 48 hrs) Pulmonary Upper: laryngospasm, obstruction, oedema, hoarseness, stridor Circumferential chest wall restriction, tracheal Lower: inhalation injury, chemical pneumonitis, bronchospasm, stenosis, infection respiratory distress syndrome, pneumonia, pulm oedema, V/Q mismatch Cardiovascular “Fluid creep” oedema after over-resus ↑ CO, ↑ myocardial oxygen consumption, ↓ CO, ↑ SVR, hypovolaemia, ischaemic reperfusion injury tachycardia, ↓SVR, systemic hypertension Renal ↓ GFR, myoglobinuria, early AKI ↑ GFR, tubular dysfunction, late AKI Endocrine & Release of stress hormones, ↓ T₃ and T₄ ↑ metabolic rate, ↑ core body tempt, ↑ muscle Metabolic Hypoparathyroidism → hypoCa, hypoMg, hypoPO₄, hypoNa and catabolism, ↑ lipolysis, ↑ glucolysis, ↑ futile substrate hyperNa cycling, ↑ insulin resistance, ↓ thyroid hormones, ↓ Vit D, ↓ parathyroid hormone, all electrolytes may be affected Hepatic ↓ perfusion, hepatic apoptosis with ↑ AST, ALT, bilirubin ↑ metabolism, ↓ albumin and transferrin, ↑ acute ↑ intrahepatic fat and oedema phase proteins Haematologic Haemoconcentration initially followed by haemodilution with Anaemia, hypercoagulable state, resus, blood loss and erythrocyte damage from heat. Haemolysis, Infection → sepsis, DIC thrombocytopaenia Gastrointestinal ↓ perfusion with mucosal damage (early enteral feed Stress ulcers, adynamic ileus, acalculous cholecystitis encouraged), stasis, ischaemia Bowel ischaemia, endotoxaemia, abdominal Endotoxaemia compartment syndrome Abdominal compartment syndrome Neurologic ↑ cerebral oedema, ↑ ICP, confusion Burn encephalopathy: seizures, hallucinations, personality disorders, delirium, coma; Hypertensive encephalopathy Pain: acute, chronic and neuropathic Pain: acute and nociceptive Psychologic Fear, anxiety, pain Post-traumatic stress disorder, depression Pharmacologic Suxamethonium: hyperK after 12-24 hrs after injury Non-depolarising muscle relaxant resistance, opioid resistance

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the catabolic losses and pharmacological agents such as non- in an enclosed space; clinically patient has burns to the face, specific B-blockers and insulin.3, 9 Systemic manifestations of neck, eyes, nose, upper trunk; or singed facial hair and soot these two phases are listed below (Table 2). in their sputum. One must be cognisant of the fact that symptoms may be delayed for up to 48 hours after the injury. Perioperative consideration Three clinical entities are possible. Upper airway thermal 1. Trauma injury (above larynx) where there is direct damage due to heat energy, this may result in significant swelling of the Despite the temptation to address the burn injury pharynx and epiglottis and typically presents with inspiratory immediately, the child with a burn injury should be managed stridor, hoarseness/change in voice and a swollen uvula. as any paediatric trauma case with a primary and secondary Lower airway thermal injury (below larynx) where there is survey. The standard A,B,C method of assessment can be damage due to the toxic products of combustion. This causes extended in the burns patient: A = airway; B= breathing; sloughing, mucous secretion, inflammation, atelectasis, C = circulation; D = disability or drugs; E = exposure and airway obstruction, subglottic stenosis and a predisposition to environment (consider high risk of hypothermia); F = fluids pneumonia. Typical signs are dyspnoea, coughing, wheezing, and consideration of Foleys catheter (initial fluid resuscitation and production of copious secretions. These solidify to form + maintenance fluid calculated, assessment of adequacy casts which obstruct various sized airways, potentially creating of urinary output, ideal is 0.5 – 1.5 ml/kg/hr especially areas of increased shunt and barotrauma. These patients may if rhabdomyolysis is suspected); and G = glucose and present for direct laryngoscopy or bronchoscopy to confirm gastric tube (gastric decompression, consideration of early the clinical findings.Injury due to noxious gases is the third enteral feeding in major burns provided there is no contra- entity. Carbon monoxide poisoning should be suspected in indication).7, 8 The secondary survey involves an extensive a patient who presents with nausea, vomiting, headache, history and examination which substantiates the events hypotension, convulsions and coma. Pulse oximetry cannot leading to the injury, e.g. time and type of burn, associated differentiate between HbO₂ and HbCO and will overestimate injury, management thus far, the existence of inhalational the true oxygen saturation. Blood gas analysis using co- injury, tetanus immunisation and non-accidental injury, oximetry is required. Cyanide poisoning should be suspected should be excluded. A recent haemoglobin, platelet count, in burn patients with unexplained and persistent lactic coagulation screen, urea and electrolytes, blood gas and chest acidosis despite adequate fluid resuscitation.3, 8, 11, 12 x-ray may be considered depending on which aspects of the 4. Intravenous access and monitoring burn injury the child displays and what surgical intervention is intended.1, 2, 11 Both vascular access and monitoring may be difficult in the burned patient. Considerations for vascular access are: 2. Airway ▫▫ Place vascular access at intact skin where possible. Securing the airway in the burns patient may be challenging. ▫▫ Large bore access is necessary if large fluid shifts and In the acute phase, patients may have thermal injury peri- rapid volume replacement are anticipated orally making bag mask ventilation and securing of the ▫▫ Intraosseous access may be necessary if intravenous endotracheal tube (ETT) difficult. Various techniques have vascular access is impossible. been suggested including the “Gray-Rode technique” whereby an ETT is firmly secured by looping a nasogastric ▫▫ Central venous access may be necessary for rapid tube around the hard palate and securing it to the tube.3 resuscitation, delivering of vasoactive agents and In addition, the airway may be distorted due to oedema or monitoring of blood gases. dressings, narrowed due to healing with stricturing, there may ▫▫ Invasive blood pressure monitoring may be needed for be limited neck mobility and mouth opening due to fibrosis waveform analysis and continuous measurements and contractures and the possibility of a difficult airway ▫▫ Invasive monitors are a potential infection risk.2, 13 should always be considered.2, 3 Depending on the injuries The ASA standard monitors should be used where possible, sustained, patient condition and surgical intervention airway control can be through nasal cannulae with a capnography however monitor placement may be difficult due to the lack port (e.g. when using ketamine infusion), laryngeal mask of available sites because of burn wounds and operative airway or endotracheal tube. Recent evidence suggests that field issues. It may be necessary to change position of low pressure high volume cuffed endotracheal tubes should monitors as the surgery progresses. Pulse oximetry may be be used since patients may have decreased compliance and unreliable due to extremity perfusion and hypothermia may require high ventilatory pressures that may leak around and may need to be placed on the ear lobe, buccal mucosa uncuffed tubes.2 or tongue. Electrocardiogram electrodes can be placed in alternative areas to the chest or skin staples used with 3. Inhalational burns crocodile clips. Useful indicators in assessing the adequacy Inhalational injury is defined as the aspiration of superheated of resuscitation and perfusion include urine output (keep gases, steam, hot liquids, or noxious products of incomplete > 0.5 ml/kg/hr), lactates, base excess, central venous oxygen combustion. It has been found to be an independent saturations, respiratory variations in the arterial waveform predictor of mortality in burn patients and worsens survival. and capillary refill. Where possible, echocardiography can Smoke inhalation is likely to be present if the burn occurred guide haemodynamic monitoring.

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5. Fluid management This is compounded by exposing various degrees of the anaesthetised patient resulting in potential temperature losses Despite advances in haemodynamic monitoring and the of up to 1˚C every 15 minutes when at ambient temperature.14 establishment of “goal-directed fluid therapy” concept, Due to the hypermetabolic state and inflammatory mediators, intravenous fluid management in the burns patient is still severe burn injury causes the hypothalamus to increase the troublesome. In the acute phase the main aim is to preserve threshold set-point by 0.03 ˚ C per % TBSA. It is thus important and restore tissue perfusion, and prevent ischaemia without to maintain euthermia to avoid catecholamine release tissue causing excessive oedema and extravascular displacement catabolism and a further up-regulation of the hypermetabolic of fluids. Balanced crystalloids should be used in the 3 initial resuscitation, although it has been shown that these state. Hypothermia is best prevented by maintaining ambient solutions have smaller volume expansion in comparison temperatures of 28–32 ˚C, warming all fluids (intravenous, to colloids. This is because during the first 24 hours there clysis, and cleaning solutions), minimising body surface area is increased capillary permeability, colloids will pass to the exposed and providing effective convective or conductive extravascular space, exert an oncotic effect and cause a warming devices. Core temperature must be continuously paradoxical increase in what is commonly called the third monitored.2, 3, 5, 8 space. The use of colloids in burn patients still remains 8. Pharmacology controversial. Gelatins have not shown superiority over crystalloids. The small number of studies investigating colloids Pharmacodynamics and pharmacokinetics of drugs may be in burns do not show an increase in mortality or renal injury different in the paediatric burns patient. This is due to: especially when using balanced HES. Hypertonic solutions, ▫▫ Fluid compartment alterations with increased volume of albumin and plasma have been associated with lower volume distribution requirements, lower intra-abdominal pressure, and a lower ▫ Changes in cardiac output incidence of compartment syndrome; hence, they have a role ▫ when appropriately used in burn patients.10 Intraoperatively ▫▫ Variability in organ perfusion a preload of 10–20 ml crystalloid should be considered. This ▫▫ Decreased renal and hepatic function 8 may need to be followed by a blood transfusion. ▫▫ Changes in serum protein levels (e.g. reduction in plasma 6. Blood loss albumin resulting in more free fraction of drugs that bind to albumin; alpha-acid glycoprotein levels may double as For every 1% of burn wound excised, it is estimated it is an acute phase protein) 14 potentially 3.4 % of a child’s blood volume is lost. Most ▫▫ Hypermetabolism severe burns will require blood transfusion at some point, but ▫▫ Alterations in specific drug receptors.3, 13, 14 one must bear in mind the associated risks, e.g. transmission of infectious diseases, immune suppression or transfusion It is important to titrate all medications to effect. Twenty- related lung injury (TRALI) and apply restrictive strategies four hours after the burn the number of extra junctional to blood products where possible. Due to these risks a acetycholine receptors are increased and severe single universal transfusion trigger is being replaced by a hyperkalaemia may occur if depolarising muscle relaxants are physiological trigger. Factors that may guide transfusion are used. This is maximal at days 10–50, with the potassium rising the preoperative haemoglobin measurements, blood volume by 3–5 mmol or more. This persists for years after the injury. In status, acuity of blood loss, development of hypoxemia additional, burn patients (especially those with > 20 % TBSA) and clinical assessment of perfusion.3, 14 Effective blood- will have a marked resistance to non-depolarising muscle conserving techniques include: relaxants. A dose will have a longer onset of action and shorter ▫▫ Subdermal infiltration with tumescent solutions recovery time. There may also be decreased cholinesterase containing vasoconstrictors ± local anaesthetic, e.g. clysis activity with drugs metabolised by these enzymes having a (suggested mix: 100 mg bupivacaine without adrenaline longer duration of action.8, 13 + 2 mg adrenaline into a litre of Ringers lactate or if 9. Nutrition unavailable normal saline; maximum dose of 20 ml/kg).8 ▫▫ Applying adrenaline soaked swabs to excised areas Optimal nutritional support of the burned patient is best accomplished by early initiation of enteral nutrition, as this ▫▫ Using compressive dressings or tourniquets can modulate the hypermetabolic response and lessen ▫▫ Electrocautery catabolism.9 Patients with major burns will undergo multiple ▫▫ Maintaining euthermia surgical interventions with cumulative loss of nutrition which ▫▫ Major excision as early as possible after injury (septic is unacceptably high if feeds are stopped preoperatively for tissue has been noted to bleed more) each procedure. The suggestion is that if a patient is going to have any airway manipulation in the operating theatre, ▫▫ Staged procedures strict fasting guidelines must be adhered to; if there will ▫▫ Fast, competent surgeon. be no airway manipulation (e.g. child is intubated and 7. Temperature regulation ventilated in ICU) cases should be individualised, and feeds can be continued until time of surgery; if there is a confirmed Hypothermia can easily occur in the burns paediatric patient nasojejunal tube in-situ, feeds may be continued until two due to the loss of cutaneous vasoconstriction, evaporative hours preoperatively. Intraoperative post pyloric feeding losses from skin, and high surface area to volume ratio. remains controversial.3, 8

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10. Pain Table 3 Summary of anaesthetic management Burn pain is a combination of: background pain (proportional Preoperative to the thermal injury); procedural pain (brief and intense • relevant history, examination and investigations pain generated by, e.g. debridement, change of dressings, • key considerations are TBSA, depth of burns, at which phase of burn injury, presence of inhalational burns, surgical plan (discussed rehabilitation); breakthrough pain (increase in pain levels prior commencement of intervention, e.g. positioning, extent of at rest, with procedures or due to anxiety); postoperative debridement) pain (predictable and temporary, due to the creation of new • premedication (attention to pain, anxiety, amnesia and sedation); patient may be on β-blockers, insulin and multivitamins and painful wounds); and chronic pain (most frequently preoperatively neuropathic pain which can exist long after the wounds • fasting and nutritional concerns (see above) have healed).2, 6, 15 The challenge in managing burn pain is • informed consent (potential complications communicated, e.g. due to the multiple components that need to be addressed rapid deterioration in major burns or need for transfusion) • planned intra- and postoperative plan and the changing nature of the pain with time. Furthermore, Intraoperative pain assessment is often confounded by physiological manifestation of the burn injury. • early identification of airway or ventilatory compromise that may need support A pre-emptive, multimodal and possibly multidisciplinary • conventional inhalational or intravenous general anaesthetic • ketamine infusion as sole agent for sedation where applicable approach may be necessary especially in patients who present (induction 1–2 mg/kg bolus followed by infusion of 4–12 mg/kg/ for multiple procedures who develop anxiety, post-traumatic hr; ketamine pharmacokinetics requires a decreasing dose every 20 disorders and chronic pain. Beyond simple analgesics, opioids mins from 11, 7, 5 and then 4 mg/kg/hr; tachyphylaxis can occur are the cornerstone of pain control. However, one must be with repeated usage) • considerations of alteration in drug pharmacology with emphasis aware of how the abovementioned changes in pharmacology on muscle relaxants and opioids affect opioid therapy. Furthermore, there is the possibility of • monitoring including theatre and core temperatures, fluid and tolerance (resulting in a higher dose of drug to achieve same blood requirements, glucose • prophylactic antibiotics not used routinely, may be considered in effects) and development of hyperalgesia where pain may bacteraemia with debridement be opioid resistant and require adjuvants such as ketamine, • adequate analgesia prior discharge to ward α₂ antagonists (clonidine or dexmedetomidine), gabapentin, Postoperative benzodiazepines, amitriptyline, lignocaine infusion and • continued monitoring of physiological parameters and pain Entonox. While regional and peripheral nerve blocks may • early resumption of feeds offer benefit, it may be difficult to find appropriates sites. The addition of non-pharmacological methods of pain control 2. Fuzaylov G, Fidkowski C. Anaesthetic considerations for major burn injury in ensures a comprehensive plan.2, 5, 6, 15 pediatric patients. Pediatr Anesth. 2009;19:202-11. 3. Moore R. The Burning Truth(s). S Afr Fam Pract. 2014;56(6):24-6. Anaesthetic management 4. Rode H, Brink C, Bester K, Coleman M, Baisey T, Martinez R. A review of the peri-operative management of paediatric burns: identifying adverse events. S The knowledge of the pathophysiological process involved and Afr Med J. 2016;106(11):1114- 9. the abovementioned perioperative considerations need to be 5. Harbin K, Norris T. Anesthetic management of patients with major burn injury. taken into account when managing the burnt child. Other factors AANA. 2012;80(6):430-9. that must be contemplated are briefly summarised in Table 3. 6. Gandhi M, Thomson C, Lord D, Enoch S. Management of pain in children with burns. Int J Pediatr. 2010;2010:1-9. Conclusion 7. Ross M, McCormack J. Trauma and burns in children. Anaesth Intens Care Med. 2014;15(12):570-6. The management of a paediatric patient is unique in many ways, 8. Thomas J, Bester K. Paediatric burn anaesthesia: the things that make a difference. SAJAA. 2014;20(5):190-6. and much more so when they have sustained significant burns. It 9. Nielson C, Duethman N, Howard J, Moncure M, Wood J. Burns: Pathophysiology is important to understand the multiple physiologic disruptions of the systemic complications and current management. J Burn Care Res. and the alterations in pharmacokinetics and pharmacodynamics 2017;38(1):469-81. of commonly used anaesthetic agents. Thought must be given 10. Guilabert P, Usua G, Martin N, Abarca L, Barret J, Colomina M. Fluid resuscitation management in patients with burns: update. Br J Anaesth. 2016;117(3):284-96. to the surgery intended, fluid resuscitation and potential airway 11. Bishop S, Maguire S. Anaesthesia and intensive care for major burns. Continuing and ventilatory challenges that the patient may present. The Education in Anaesthesia, Critical Care & Pain. 2012;12(3):118-22. central role of adequacy of perfusion and pain management 12. Walker P, Buehner M, Wood L, Boyer N, Driscoll I, Lundy J, et al. Diagnosis should be a constant concern through all the phases.13 Providing and management of inhalational injury: an updated review. Crit Care. 2015;19(351):1-12. anaesthesia for burn surgery is challenging yet rewarding, as 13. Anderson T, Fuzaylov G. Perioperative anesthesia management of the burn it facilitates recovery from some of the most devastating yet patient. Surg Clin North Am. 2014;94(4):851-61. preventable injuries seen in paediatric anaesthesia. 14. Sharar S, Olivar H. Anesthesia for burn patients UpToDate: Wolters Kluwer; 2016 [updated Feb 2017, 13 March 2017]. Available from: https://www.uptodate.com/ References contents/anesthesia-for-burns-patients/print. 1. Fenlon S, Nene S. Burns in children. Continuing Education in Anaesthesia, Critical 15. Richardson P, Mustard L. The management of pain in the burns unit. Burns. Care & Pain. 2007;7(3):76-80. 2009;35:921-36.

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