MIDDLE EAST JOURNAL of ANESTHESIOLOGY Department of Anesthesiology American University of Beirut Medical Center P.O

MIDDLE EAST JOURNAL OF ANESTHESIOLOGY Department of Anesthesiology American University of Beirut Medical Center P.O. Box 11-0236. Beirut 1107-2020, Lebanon

Editorial Executive Board Consultant Editors Editor-In-Chief: Bikhazi George Assem Abdel-Razik (Egypt) Executive Editors Mohamad El-Khatib Bassam Barzangi (Iraq) Editors Chakib Ayoub Marie Aouad Izdiyad Bedran (Jordan) Ghassan Kanazi Dhafir Al-Khudhairi (Saudi Arabia) Sahar Siddik-Sayyid Mohammad Seraj (Saudi Arabia) Managing Editor Mohamad El-Khatib [email protected] Abdul-Hamid Samarkandi (Saudi Arabia) Founding Editor Bernard Brandstater Mohamad Takrouri (Saudi Arabia) Emeritus Editor-In-Chief Anis Baraka Bourhan E. Abed (Syria) Honorary Editors Nicholas Greene Musa Muallem Mohamed Salah Ben Ammar (Tunis) Managing Editor Assistant Iman Jaafar M. Ramez Salem (USA) Webmaster Rabi Moukalled Elizabeth A.M. Frost (USA) Secretary Alice Demirdjian Halim Habr (USA) [email protected] The Middle East Journal of Anesthesiology is a All accepted articles will be subject to a US $ 100.00 publication of the Department of Anesthesiology of (net) fee that should be paid prior to publishing the the American University of Beirut, founded in 1966 by accepted manuscript Dr. Bernard Brandstater who coined its famous motto: “For some must watch, while some must sleep” Please send dues via: (Hamlet-Act. III, Sc. ii). WESTERN UNION and gave it the symbol of the poppy flower (Papaver To Mrs. Alice Artin Demirjian somniferum), it being the first cultivated flower in Secretary, Middle East Journal of Anesthesiology the Middle East which has given unique service to OR TO the suffering humanity for thousands of years. The Credit Libanaise SAL Journal’s cover design depicts The Lebanese Cedar Tree, with’s Lebanon unique geographical location AG: Gefinor.Ras.Beyrouth between East and West. Graphic designer Rabi Swift: CLIBLBBX Moukalled Name of Beneficent The Journal is published three times a year (February, Middle East Journal of Anesthesiology June and October) The volume consists of a two year Acc. No. 017.001.190 0005320 00 2 indexed six issues. The Journal has also an electronic (Please inform Mrs. Demirjian [email protected] issue accessed at www.aub.edu.lb/meja - Name and Code of article The Journal is indexed in the Index Medicus and - Transfer No. and date (WESTERN UNION) MEDLARS SYSTEM. - Receipt of transfer to (Credit Libanaise SAL) E-mail: [email protected] Personal checks, credit cards and cash, are not Fax: +961 - (0)1-754249 acceptable “For some must watch, while some must sleep” (Hamlet-Act. III, Sc. ii) 134

Middle East Journal of Anesthesiology Vol. 23, No. 1, February 2015

CONTENTS

editorial «Routine» Preoxygenation �� Anis Baraka 5

review article The Impact Of Endotracheal Tube Vs Laryngeal Mask Airway On The Incidence Of Postoperative Nausea And Vomiting: A Systemic Review And Meta-Analysis �� Jahan Porhomayon, Sina Davari Farid, Ali A. El-Solh, Ghazaleh Adlparvar, Nader D. Nader 9

scientific articles Renal Protection In The Cardiac Surgery Patient: Peri-Operative Sodium Bicarbonate Infusion (Posbi) Or Not? ��Hassan H. Amhaz, Deepak Gupta, Larry Manders, George McKelvey, Marc S. Orlewicz, Romeo N. Kaddoum 17 Effect Of Ultrasound-Guided Subsartorial Approach For Saphenous Nerve Block In Cases With Saphenous Nerve Entrapment In Adductor Canal For Controlling Chronic Knee Pain �� Arman Taheri, Maryam Hatami, Majid Dashti, Alireza Khajehnasiri, Mahsa Ghajarzadeh 25 Comparison Of The Effects Of Oral Vs. Peritonsillar Infiltration Of Ketamine In Pain Reduction After Tonsillectomy: A Randomized Clinical Trial ��Afsaneh Norouzi, Abolfazl Jafari, Hamid Reza Khoddami Vishteh, Shahin Fateh 29 The Impact Of Anesthetic Techniques On Cognitive Functions After Urological Surgery ��Mahtab Poor Zamany Nejat Kermany, Mohammad Hossein Soltani, Khazar Ahmadi, Hoora Motiee, Shermin Rubenzadeh, Vahid Nejati 35 Comparison Between C-Mac® Video-Laryngoscope And Macintosh Direct Laryngoscope During Cervical Spine Immobilization ��Shahir H.M. Akbar, Joanna SM Ooi 43

Effects Of Memantine On Pain In Patients With Complex Regional Pain Syndrome-A Retrospective Study ��Mohammad-Hazem I. Ahmad-Sabry, Gholamreza Shareghi 51

Effects Of Dexamethasone And Pheniramine Maleate On Hemodynamic And Respiratory Parameters After Cementation In Cemented Partial Hip Prosthesis ��Abdulkadir Yektaş 55

Effect Of Preoperative Oral Pregabalin On Postoperative Pain After Mastectomy �� Mardhiah Sarah, Harnani Mansor, Choy Yin Choy 63

1 M.E.J. ANESTH 23 (1), 2015 Consumption Trends Of Rescue Anti-Psychotics For Delirium In Intensive Care Units (Icu Delirium) Show Influence Of Corresponding Lunar Phase Cycles: A Retrospective Audit Study From Academic University Hospital In The United States �� Deepak Gupta, Vinay Pallekonda, Ronald Thomas, George Mckelvey, Farhad Ghoddoussi 69 Ultrasound-Guided Sciaticoliteal Nerve Block: A Comparison Of Separate Tibial And Common Peroneal Nerve Injections Versus Injecting Proximal To The Bifurcation �� Alberto E. Ardon, Roy A. Greengrass, Upasna Bhuria, Steven B. Porter, Christopher B. Robards, Kurt Blasser 81 Subtenon bupivacaine injection for postoperative pain relief following pediatric strabismus surgery: A randomized controlled double blind trial �� Radwa H Bakr and Hesham M Abdelaziz 91

case reports Straight To Video: Tonsillar Injury During Elective Glidescope-Assisted Pediatric Intubation ��Jason D. Rodney, Zulfiqar Ahmed, Deepak Gupta, Maria Markakis Zestos 101 Percutaneous Balloon Compression Of Gasserian Ganglion For The Treatment Of Trigeminal Neuralgia: An Experience From India �� Anurag Agarwal, Vipin Dhama, Yogesh K. Manik, M. K. Upadhyaya, C. S. Singh, V. Rastogi 105 Bedside Retianed Radial Artery Catheter Removal In A Hemodynamically Unstable Neurocritically-Ill Patient: A Case Report �� Christa O’Hana V. San Luis, Athir H. Morad 111

Esophageal Perforation Following Orogastric Suction Catheter Insertion In An Elderly Patient ��Roland N. Kaddoum, Fadi Farah, Rita W. Saroufim, Salah M. Zeineldine 117

letter to the editor Pediatric Endotracheal Intubation ��Claude Abdallah 123

2 LIFE ON WHEELS

Triumph over the agony of pain and sadness; admission of the ways of the creator and “happy to be alive”; optimism with brilliant accomplishments from a wheelchair and “breathing happiness”, are but few of the accomplishments of faculties endowed on Alon P. Winnie , Professor and Chairman of the Department of Anesthesiology of the University of Illinois.

Fig1. Dr. Winnie among his colleagues ; Dr. Baraka (far left) & Dr. Raj (far right).

In his own words, Dr. Winnie writes « Dear Anis*…

To fulfill my promise to you, the following… Let me preface it by telling you that it was written from the viewpoint of a rocking bed after I had been given my first wheelchair, for which I had waited for an eternity of months while physiotherapy tried to rid me of the rigidity left behind when the pain of the muscle spasms finally subsided… It was the middle of winter and I had a beautiful view of the slum section of the city just behind the hospital…The first half obviously representing the translation of my impression at night and the second during the day…

The sad white eye of this new night Cries myriads of auto tears That criss-cross over its many streeted face; The freckles of which glow dimly

* Dr. Anis Baraka, Department of Anesthesiology, American University of Beirut, Beirut, Lebanon. MEJA 3: 240, 1972.

3 M.E.J. ANESTH 23 (1), 2015 4

And disappear One by one As an angry lock of cloud Slips down And covers sad eye rendered sadder By the loss of legs, Yet soon The bright orange eye of the day Combs back the clouds Revealing life and lives Breathing happiness In little gray-blue puffs From the cigarette chimneys As the city yawns As a sleepy but happy to be alive yawn And readies itself For this new day Of life on wheels…”

Fig 2. Dr. Alon Winnie EDITORIAL

“ROUTINE” PREOXYGENATION

It is a fact of great clinical importance that the body oxygen stores are so small, and if replenishment ceases, they are normally insufficient to sustain life for more than a few minutes. Breathing oxygen causes a substantial increase in the total oxygen stores; most of the additional oxygen is accommodated in the alveolar space (functional residual capacity) from which 80% may be withdrawn without the PaO2 falling below the normal vale. This concept is the basis of the preoxygenation technique1. In 1955, Hamilton and Eastwood demonstrated that denitrogenation of the functional residual capacity of the lung is 95% complete within 2-3 minutes, if a subject is breathing at a normal tidal volume form a circle anesthesia system using an oxygen flow of 5 l/min2. These studies led to the recommendation of preoxygenation as a standard practice before rapid sequence induction of general anesthesia in patients with full stomach. “Routine” preoxygenation has become a new “minimum standard” of care not only during induction of anesthesia and tracheal intubation, but also during emergence from anesthesia and tracheal extubation1. The original American Society of Anesthesiologists (ASA) difficult airway algorithm made no mention of preoxygenation. However, in an updated report of the ASA Task Force on “Management of the Difficult Airway” 2003, the topic of face mask preoxygenation before initiating management of the difficult airway was added3. Preoxygenation before induction of anesthesia was also recommended in patients with low functional residual capacity of the lung, associated with a high oxygen consumption. This category includes the neonates, the pregnant and the morbidly obese patients who rapidly decrease their oxygen saturation during apnea while breathing room air4. Preoxygenation is also recommended in patients with decreased oxygen delivery (Cardiac output x Hb conc x% saturation x 1.34) which include patients with low cardiac output or pulmonary disease, as well as patients with low or abnormal hemoglobin such as methemoglobin. Before induction of general anesthesia, preoxygenation can be achieved either by tidal volume breathing of 100% oxygen for 3-5 minutes using an oxygen flow of 5 l/min as described by Hamilton and Eastwood2, or by the 8 deep breaths technique for 60 seconds using an oxygen flow of 10 L/ min as described by Baraka et al5. The mean time to decrease of hemoglobin oxygen saturation from 100% to 99% is significantly longer during the subsequent apnea following the 8-deep breaths technique of preoxygenation than following the traditional tidal volume preoxygenation technique5. As suggested by Benumof, the 8 deep breaths technique may be considered the best method of preoxygenation for both efficacy and efficiency6. The high efficiency of preoxygenation by the deep breaths technique may be attributed to a relatively larger minute volume, and/or to

5 M.E.J. ANESTH 23 (1), 2015 6 Dr Baraka possible expansion of any collapsed alveoli by the recommended for rapid-sequence induction of deep breathing technique. anesthesia in patients with full stomach, as well as The beneficial effect of preoxygenation by tidal in patients with predicted difficult airway. However, volume or deep breathing, can be further extended the technique is nowadays recommended as a routine during subsequent apnea by the apneic diffusion during induction, as well as during recovery from oxygenation7-9. The technique of ADO has been general anesthesia, since difficult airway may be advantageous not only in patients with a difficult unpredicted. airway or pulmonary disease, but also in children, the Preoxygenation, followed by apneic diffusion pregnant and the morbidly obese patients who have a oxygenation is indicated in patients who desaturate high oxygen consumption associated with a relatively rapidly during apnea such as the neonate, the obese and low FRC4. ADO has been also used to maintain the pregnant patients who have a relatively low FRC oxygenation during bronchoscopy7, and one-lung associated with a high oxygen consumption. ADO is ventilation10. also advantageous in patients with decreased oxygen Apneic diffusion oxygenation (ADO) is achieved delivery such as the elderly, cardiac and pulmonary by preoxygenation by tidal volume2, or deep breathing diseased patients. The technique is also used to technique5, to be followed by insufflations of high maintain oxygenation during certain procedures such flow of 100% oxygen by a catheter into the pharynx as bronchoscopy, and one-lung ventilation. via an open airway. During ADO, the increase in time “Routine” preoxygenation with 100% oxygen to hemoglobin desaturation achieved by increasing is considered a “safety” measure during anesthetic the FIO2 from 0.9 to 1.0 is greater than that caused induction and emergence from anesthesia, and is by increasing the FIO2 from 0.21 to 0.99. During advantageous in critically-ill patients requiring airway ADO, CO2 is not exhaled because of the mass management. However, it must be used as an adjunct movement of oxygen down the trachea. The alveolar rather than an alternative to a sequence of fundamental CO2 concentration (PACO2) shows an initial rise of precautions that minimize adverse sequelae1. 8-16 mmHg during the first minute, followed by a subsequent fairly linear increase of about 3 mmHg/ Anis Baraka, MD, FRCA (Hon) min. Thus, the ADO can maintain oxygenation for a prolonged period. However, the increase of PaCO2 Emeritus Professor of Anesthesiology will limit the period of apnea. American University of Beirut In conclusion, preoxygenation has been initially “ROUTINE” PREOXYGENATION 7

References

1. Baraka AS, Salem MR: Preoxygenation: In Benumof and Hagberg’s volume breathing techniques. Anesthesiology; 1999, 91(3):612-616. Airway management, Third Edition 2013, Chapter 13, pp. 280-297. 6. Benumof JL: Preoxygenation: Best method for both efficacy and 2. Hamilton W, Eastwood D: A study of denitrogenation with some efficiency. Anesthesiology; 1999, 91(3):603-605. inhalation anesthetic systems. Anesthesiology; 1955, 16:861-867. 7. Holmdahl MH: Pulmonary uptake of oxygen, acid-base metabolism, 3. Practice guidelines for management of difficult airway: An updated and circulation. Acta Chir Scand; 1956, 212(supp):1-128. report by the American Society of Anesthesiologists Task force 8. Framery AD, Roe PG: A model to describe the folre of on the management of the difficult Airway. Anesthesiology; 2003, oxyhemoglobin desaturation during apnea. Br J Anaesth; 1996, 98:1269-1277. 76:284-291. 4. Baraka AS, Taha SK, Siddik SM et al: Supplementation of 9. McNamara MJ, Harman JG: Hypoxemia during open airway apnea. oxygenation in morbidly obese patients using nasopharyngeal A computational modeling analysis. Anaesthesia; 2006, 60:741-746. oxygen insufflation. Anaesthesia; 2007, 62:769-773. 10. Baraka A, Aouad M, Taha S, El-Khatib M, et al: Apnea-induced 5. Baraka AS, Taha SK, Aouad MT, El-Khatib MF, Kawkabani hemoglobin desaturation during one-lung vs two-lung ventilation. NI: Preoxygenation: Comparison of maximal breathing and tidal Can J Anaesth; 2000, 47(1):58-61.

M.E.J. ANESTH 23 (1), 2015

REVIEW ARTICLE

The Impact of Endotracheal Tube vs. laryngeal Mask Airway on the Incidence of Postoperative Nausea and Vomiting: A Systemic Review and Meta-analysis

Jahan Porhomayon*, Sina Davari Farid** Ali A. El-Solh***, Ghazaleh Adlparvar**** and Nader D. Nader*****

Abstract

Objective: To investigate the impact of Endotracheal tube (ETT) vs. Laryngeal Mask Airway (LMA) on postoperative nausea and vomiting (PONV) in patients undergoing surgery with general anesthesia. Methods: Key words searching from databases such as Medline, Embase, and Cochrane library provided 14 studies focusing on the use of EET vs. LMA for general anesthesia. Pooled estimate of relative risk with 95% confidence interval using random effect model was conducted. Results: 14 studies were selected for meta-analysis with a total of 1866 patients. 9 studies focused on the outcome of PONV in adult patients. It showed incidence of PONV with of LMA and ETT in adult of about 204/690 (30%) and 145/725 (20%) respectively with [Odds Ratio (OR) = 1.69, 95% CI, 0.76-3.75, P = 0.20]. Heterogeneity was high (I2 = 87%). Five studies focused on the outcome of PONV in pediatric patients with PONV in LMA and ETT group of 85/229 (37%) and 72/222 (32%) respectively with (OR = 1.30, 95% CI, 0.61-2.76, P = 0.50). Heterogeneity was moderate at (I2 = 53%). When all patients were combined heterogeneity was high at 81% with OR = 1.56, 95% CI, 0.87-2.79, P = 0.14. Conclusion: Risk of PONV shows an increase trend toward the use of LMA. Larger randomized trials are needed to assess the impact of airway devices on PONV. Keywords: Postoperative, Nausea and Vomiting, Endotracheal Tube, Laryngeal Mask Airway.

* md, FCCP. Associate Professor of Anesthesiology and Critical Care Medicine VA Western New York Healthcare System, Division of Critical Care Medicine, Department of Anesthesiology, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York. ** md. Anesthesiology Research Fellow VA Western New York Healthcare System, Division of Critical Care Medicine, Department of Anesthesiology, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York. *** md, MPH. Professor of Medicine, Anesthesiology and Preventive Medicine VA Western New York Healthcare System, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York. **** MA, BA. Research Assistant Department of Science University at Buffalo, MCC College, Rochester, New York. ***** M.D., Ph.D., FCCP. Professor of Anesthesiology, Surgery and Pathology VA Western New York Healthcare System, Division of Cardiothoracic Anesthesia and Pain Medicine, Department of Anesthesiology, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York. Corresponding author: Jahan Porhomayon MD, FCCP, VA Medical Center, Rm 203C, 3495 Bailey Ave, Buffalo, NY 14215. Tel: 716 862-8707, Fax 716 862-8707. E-mail: [email protected]

9 M.E.J. ANESTH 23 (1), 2015 10 Porhomay on Jahan et. al

Introduction and only prospective RCTs included7. A total of 6568 articles were identified. 5967 were excluded because PONV remain a common problem occurring in it was not related to risk factors or airway device. in 20-30% of surgical population, and can be as high 601 relevant articles related to PONV risk factors as 70-80% in the high risk population1. It increases and airway device were screened. 584 were excluded cost, and delays discharge, and decreases patient because they were either review, duplicate and non- satisfaction2. In this analysis, nausea is defined as relevant duplications. 17 articles were assessed for uncomfortable feeling of stomach which might lead eligibility with additional 3 articles excluded due to to the eagerness to vomit, while vomiting refers the its retrospective nature and low quality. Finally, 14 actual motion of throwing up. articles included for final analysis [Figure 1]. PONV could lead to pulmonary aspiration of Compared to Yu3, we included newer studies gastric content and may lead to aspiration pneumonia published since, as well as pediatric studies. We also with potentially fatal consequences. Our current included RCTs with the use of non-depolarizers muscle knowledge outlines several well-established risk relaxant and Neostigmine usage in the ETT group. factors for the occurrence of PONV3,4. These risk factors RCTs with regional techniques were also excluded8. include: patient, anesthesia and surgical risk specific risk factors. The patient specific risk factors include, Data Extraction female gender, history of PONV or motion sickness, non-smoking status, age greater than or equal to three, Timing of PONV reporting varied among studies. and family history of PONV in children. Anesthesia Some studies reported PONV in the post-anesthesia related risk factors include volatile anesthetics, use of Nitrous oxide, and opioid use3,5. There is also a dose relation between volatile anesthetics and opioids. Fig. 1 Surgical risk factors include duration of surgery and type of procedure, in particular strabismus correction in children and laparoscopic procedures. In addition to these well-established risk factors, there are other etiologies for development of PONV such as, the lower American society of anesthesiology (ASA) classification, the use of large doses of neostigmine (>2.5mg), restrictive vs. liberal intraoperative fluid strategy, ventilation mode, starvation nausea, heartburn, anxiety, depression, Hepatitis C, P450 inducers/suppressors (medications and food), migraines, and ethnicity6. However, the role of airway devices and its impact on the incidence of PONV remains controversial. Therefore, the following systematic review was conducted to study the influence of airway devices on the incidence of PONV.

Materials and Methods

We conducted databases searches from Embase, Cochrane, Medline with the term “Laryngeal mask AND Endotracheal tube AND Post-operative AND Nausea AND Vomiting”. Abstracts were reviewed Endotracheal tube vs LMA for PONV 11 recovery unit (PACU) while others reported PONV type, usage of anesthetics and prophylactic anti- on the first postoperative day. When confronted with emetics. The following outcomes were also extracted multiple data points, data extracted for analysis with including the incidence of PONV for both ETT and earliest time for PONV was reported. This was an LMA group. After data searching and study selection, effort to reduce confounding factors such as, rescue 14 studies were included in our meta-analysis. Study anti-emetics given after surgery. Furthermore, PACU characteristics and demographics were shown in Table treatment for PONV was not always standardized and 1. 12 studies reported postoperative vomiting as the was often based on individual patient variables and primary outcome and 10 reported postoperative nausea anesthesiologist preference. Characteristics of each as the primary outcome. One study did not differentiate study was extracted, which included last name of first between nausea and vomiting. Results were shown in author, publication year, patient age range, procedure Table 2.

Table 1 Studies Included

Joshi 199717 Adult ASA 1or 2; Succinylcholine or non-depolizer + Neostigmine sometimes used in ET group; Higher overall fentanyl dose in intra-op ETT group; post-op pain management unstated

Patel 201013 Age 3-10; ProSeal LMA vs ETT; lower abdominal procedures; no opioids given intraop; caudal injection with GA with Sevo + N2O; universal OG tube use

Klockgether 199614 Age 4-14, strabismus surgery, identical induction (Propofol, Vecuronium, Alfentanil), identical maintenance (67% N2O, Propofol, Alfentanil). PONV incidence by 24 hours reported

Doksrod 201015 Age 3-16 tonsillectomy & adenoidectomy; prophylactic Dexamethasone used; nausea and vomiting not reported separately

Gulati 200416 Age 1-12 ophthalmologic procedures; greater duration of surgery and more strabismus procedures in LMA group

Hohlrieder 2007a7 Adult 18-75, standardized induction and maintenance with oral midazolam, propofol, fentanyl, and Neostigmine in both groups. ProSeal LMA used along with ETT; Universal use OG tube placement and decompression; No prophylactic anti-emetics Cork199420 Adult outpatient peripheral orthopedic procedures; Non-depolarizers and Neostigmine used in both groups; no sig differences in patient population or duration or opioids intra-op; greater morphine post-op in ET group

Hohlrieder 2007b8 Adult female 18-75 for laparoscopic gynecological surgery; iv induction after oral midazolam, ProSeal LMA used along with ETT; Universal OG placement + Dexamethasone 4mg + Tropisetron 2mg prophylactic dose administered Quinn 199618 Adult 18-64; Nasal ET with Mivacurium vs. none for LMA group; no prophylactic anti-emetics Swann 199321 Adult laparoscopic gynecological surgeries; ASA 1-2 single blinded RCT LMA vs ET. Atracurium and Neostigmine 2.5mg given in ET group only; controlled ventilation with ETT vs intermittent manual assistance to maintain ETCO2 in LMA group Griffiths 201310 Adult ASA 1-2 Laparoscopic gynecological procedures. Single blinded RCT ProSeal LMA vs ET: same induction; Dexamethasone prophylaxis; universal reversal with Neostigmine 2.5mg

Idrees 200019 Adult ASA 1-2 Limb surgery. Single blinded RCT ProSeal LMA vs ETT; Standardized induction + maintenance; Dexamethasone prophylaxis;

Gul 201211 Age 1-12 strabismus surgery; ProSeal LMA vs. ETT; inhaled induction, 50% N2O, Atracurium in both groups. Universal OG tube and gastric decompression

Porhomayon12 Adult, mostly male, undergoing general anesthesia with N2O in knee surgery

M.E.J. ANESTH 23 (1), 2015 12 Porhomay on Jahan et. al

Table 2 Outcomes on Postoperative Vomiting and Nausea Author Postoperative Vomiting Postoperative Nausea

ETT LMA ETT LMA

Joshi 199717 8/174 (4.6%) 15/207 (7.2%) 23/174 (13.2%) 28/207 (13.5%)

Patel 201013 1/30 (3.3%) 0/30 (0) NR NR

Klockgether 199614 24/50 (48%) 16/50 (32%) 14/50 (28%) 8/50 (16%)

Doksrod 201015 NR NR 36/69 (52.2%) 37/62 (59.7%)

Gul 201211 NR NR 4/40 (10%) 2/40 (5%)

Gulati 200416 2/30 (6.7%) 5/30 (16.7%) NR NR

Hohlrieder 2007a7 18/100 (18%) 4/100 (4%) 45/100 (45%) 13/100 (13%)

Cork199420 1/22 (4.5%) 1/22 (4.5%) 3/22 (13.6%) 5/22 (22.7%)

Hohlrieder 2007b8 6/50 (12%) 1/50 (2%) 10/50 (20%) 2/50 (4%)

Quinn 199618 3/50 (6%) 2/50 (4%) 13/50 (26%) 9/50 (18%)

Swann 199321 4/30 (13.3%) 8/30 (26.7%) 6/30 (20%) 15/30 (50%)

Griffiths 201310 27/57 (47.4%) 28/59 (47.5%) NR NR

Porhomayon12 25/157 (15%) 12/157(7%) 25/157 12/157

Idrees19 50/3(1.6%) 50/12(4%) NR NR

Statistical Analysis Meta-analysis of subgroups

RevMan 5.2 was used to calculate the odds In terms of PONV in subgroups of adults and ratio for the incidence of PONV. Subgroup analysis pediatric patients, the incidence of PONV was higher in adults’ patients. PONV in adult with the use of LMA including only adult or pediatric patients was also and ETT was about 204/690(30%) and 145/725(20%) performed. I2 was used to assess heterogeneity with respectively with (OR = 1.69, 95% CI, 0.76-3.75, P a value below 30% standing for low heterogeneity, a = 0.20). In pediatric population PONV in the LMA value between 30% and 50% standing for moderate and the ETT group was 85/229(37%) and 72/222 heterogeneity and a value above 50% standing for high (32%) respectively with (OR = 1.30, 95% CI, 0.61- heterogeneity. Random effect model was used in all 2.76, P = 0.50). Overall, LMA was associated with analyses. A p value of <0.1 was significant. higher incidence of PONV. Statistical heterogeneity for adult and pediatric patients was 87% and % 53 % respectively. Test for subgroup difference was not Results statistically significant with p value of 0.64 and 2I = 0.

A total of 1899 patients were included. The Discussion incidence of PONV with of LMA and ETT was 289/919 (31%) and 217/947 (22%) respectively. In all patients The impact of the airway device on PONV heterogeneity was high at 81% with OR = 1.56, 95% remains unresolved. Previous models included the CI, 0.87-2.79, P = 0.14 [Figure 2, 3]. influence of airway devices on development of PONV, Endotracheal tube vs LMA for PONV 13

Fig. 2

LMA ETT Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.1 Adult cork 4 22 6 22 6.1% 0.59 [0.14, 2.48] Griffiths 27 57 28 59 8.4% 1.00 [0.48, 2.07] Hohlrieder 63 100 17 100 8.6% 8.31 [4.29, 16.10] Hohlrieder1 16 50 2 50 5.8% 11.29 [2.44, 52.38] Idrees 12 50 3 50 6.4% 4.95 [1.30, 18.81] Joshi 31 174 43 207 9.0% 0.83 [0.49, 1.38] porhomayon 25 157 12 157 8.4% 2.29 [1.11, 4.74] quinn 16 50 11 50 7.9% 1.67 [0.68, 4.08] swann 10 30 23 30 7.1% 0.15 [0.05, 0.47] Subtotal (95% CI) 690 725 68.0% 1.69 [0.76, 3.75] Total events 204 145 Heterogeneity: Tau² = 1.22; Chi² = 60.13, df = 8 (P < 0.00001); I² = 87% Test for overall effect: Z = 1.29 (P = 0.20)

1.1.2 Pediatric Doksrod 36 69 37 62 8.5% 0.74 [0.37, 1.47] Gul 4 40 4 40 6.0% 1.00 [0.23, 4.31] Gulati 6 40 7 40 6.9% 0.83 [0.25, 2.74] Klockgether 38 50 24 50 8.0% 3.43 [1.46, 8.06] Patel 1 30 0 30 2.4% 3.10 [0.12, 79.23] Subtotal (95% CI) 229 222 32.0% 1.30 [0.61, 2.76] Total events 85 72 Heterogeneity: Tau² = 0.36; Chi² = 8.45, df = 4 (P = 0.08); I² = 53% Test for overall effect: Z = 0.67 (P = 0.50)

Total (95% CI) 919 947 100.0% 1.56 [0.87, 2.79] Total events 289 217 Heterogeneity: Tau² = 0.92; Chi² = 69.58, df = 13 (P < 0.00001); I² = 81% 0.01 0.1 1 10 100 Test for overall effect: Z = 1.48 (P = 0.14) LMA ETT Test for subgroup differences: Chi² = 0.22, df = 1 (P = 0.64), I² = 0% The graph favors ETT with less PONV. but failed to show sufficient independent significance and children. This systematic review and meta-analysis to be included in the final models. But we continue includes 14 total studies focusing on the incidence to see investigators including PONV as a variable of PONV comparing the different airway devices outcome difference between LMA and ETT. Two including ETT and LMA. Overall, no statistically prospective randomized control trials (RCT) by significant difference was noted between airway Holhreidner reported statistically significant reduction devices, although a trend towards higher incidence was of PONV with the use of Pro-Seal LMA7,8. A recent noted with the use of LMA group. Subgroup analysis meta-analysis of RCTs in 2010 by Yu9 looked at the included only children and adult, showed similar trend risk of airway complications between the LMA and with stronger association in adult patients. ETT. Since the primary goal of Yu study was to look at Compared with previously meta-analysis by Yu9, the airway complications, he failed to show statistical we included 3 newer studies10-12 and 5 pediatric RCTs13- significance in the incidence of PONV between the two 17. Therefore, our final analysis was more reliable. Of devices. Additionally, pediatric studies were excluded the studies included, only the four by Holhreider7,8, due to differences in airway anatomy between adult Quinn, Idrees and Klockgether-Radke14,18,19 showed a

M.E.J. ANESTH 23 (1), 2015 14 Porhomay on Jahan et. al

Fig. 3

SE(log[OR]) 0

0.5

1.5

OR 2 0.01 0.1 1 10 100 Subgroups Adult Pediatric statistically significant reduction in PONV with LMA. showed a higher trend of PONV in the LMA group. Of note, the studies by Holhreider7 were conducted This study was underpowered and additional trials are with Pro-Seal LMA and universal oro-pharyngeal necessary to address this hypothesis. tube placement with gastric decompression. Therefore gastric decompression may have a role in preventing Limitations PONV. The study by Joshi, Swann, Doksrod and Due to nature of meta-analysis, results were Cork15,20,21 indicated higher PONV with the use of analyzed from wide variety of RCTs with differing ETT. One hypothesis leading to the difference in the anesthetic techniques, types of surgery, anesthesiologist incidence of PONV between the airway devices may experience, various types of LMA, and time when be related to greater stimulation with the use of ETT outcome was measurement. Heterogeneity was high requiring higher doses of anesthetics and opioids3 when due to different anesthetic techniques23, type of surgeries compared to the LMA group6. Opioids and volatile and heterogeneous population. However, with RCT anesthetics have also a role in the development of there was standardization of anesthetic techniques PONV with a dose dependent effect on the development between two groups to minimize confounding factors. of PONV. Alteration in barometric pressure was Those without standardization between two groups demonstrated by Nader et al22 when LMA was used were excluded from the trial. Despite standardization in comparison to ETT. Although the authors of that of anesthetic techniques, there were differences in article did not demonstrate a statistically significant duration of anesthesia and intra-operative opioid difference in PONV between the ETT and LMA, they usage. There were statistically significant differences Endotracheal tube vs LMA for PONV 15 in patient selection as well as type of procedure within Conclusion some of the RCTs. Additionally; patient Characteristics relevant to the risk of PONV was not always reported. Further research and additional randomized Consistent with previously performed meta- controlled trials are needed to precisely identify the analysis9 studying the same outcome, we were able to influence of airway device on PONV. These trials identify only a limited number of studies addressing should provide essential information for the design, the influence of airway device on PONV. Furthermore, conduct, and presentation of these studies. When many of the RCTs had small sample sizes limiting comparing group, comparability should be based on reliability in concluding the incidence PONV between well-proven risk factors. And lastly, interpretation of the two groups. Furthermore, two large retrospective results should take into account the study hypothesis, studies24,25 were identified, but were not included in sources of potential bias or imprecision, and the the final analysis due to high degree of variability in difficulties associated with multiplicity of analysis and anesthetic techniques. outcome.

M.E.J. ANESTH 23 (1), 2015 16 Porhomay on Jahan et. al

References

1. Apfel CC, Philip BK, Cakmakkaya OS, Shilling A, Shi YY, Leslie 13. Patel MG, Swadia V, B ansal G: Prospective randomized JB, et al: Who is at risk for postdischarge nausea and vomiting after comparative study of use of PLMA and ET tube for airway ambulatory surgery? Anesthesiology; 2012, 117:475-486. management in children under general anaesthesia. Indian J 2. Habib AS, Chen YT, Taguchi A, Hu XH, Gan TJ: Postoperative Anaesth; 2010, 54:109-115. nausea and vomiting following inpatient surgeries in a teaching 14. Klockgether-Radke A, Gerhardt D, Muhlendyck H, Braun hospital: a retrospective database analysis. Curr Med Res Opin; U: [The effect of the laryngeal mask airway on the postoperative 2006, 22:1093-1099. incidence of vomiting and sore throat in children]. Anaesthesist; 3. Gan TJ: Risk factors for postoperative nausea and vomiting. 1996, 45:1085-1088. Anesthesia and analgesia; 2006, 102:1884-1898. 15. Doksrod S, Lofgren B, Nordhammer A, Svendsen MV, Gisselsson 4. Gan TJ, Meyer TA, Apfel CC, Chung F, Davis PJ, Habib AS, et al: L, Raeder J: Reinforced laryngeal mask airway compared with Society for Ambulatory Anesthesia guidelines for the management endotracheal tube for adenotonsillectomies. Eur J Anaesthesiol; of postoperative nausea and vomiting. Anesthesia and analgesia; 2010, 27:941-946. 2007, 105:1615-1628, table of contents. 16. Gulati M, Mohta M, Ahuja S, Gupta VP: Comparison of laryngeal 5. Wilkins CJ, Cramp PG, Staples J, Stevens WC: Comparison of the mask airway with tracheal tube for ophthalmic surgery in paediatric anesthetic requirement for tolerance of laryngeal mask airway and patients. Anaesth Intensive Care; 2004, 32:383-389. endotracheal tube. Anesth Analg; 1992, 75:794-797. 17. Joshi GP, Inagaki Y, W hite PF, Taylor-Kennedy L, Wat LI, Gevirtz pfel eidrich ukar ao alota ornuss 6. A CC, H FM, J -R S, J L, H C, C, et al: Use of the laryngeal mask airway as an alternative to the Whelan RP, et al: Evidence-based analysis of risk factors for tracheal tube during ambulatory anesthesia. Anesth Analg; 1997, postoperative nausea and vomiting. British journal of anaesthesia; 85:573-577. 2012, 109:742-753. 18. Quinn AC, Samaan A, McAteer EM, Moss E, Vucevic M: The 7. Hohlrieder M, Brimacombe J, Eschertzhuber S, Ulmer H, Keller reinforced laryngeal mask airway for dento-alveolar surgery. Br J C: A study of airway management using the ProSeal LMA laryngeal Anaesth; 1996, 77:185-188. mask airway compared with the tracheal tube on postoperative 19. Idrees A, Khan FA: A comparative study of positive pressure analgesia requirements following gynaecological laparoscopic ventilation via laryngeal mask airway and endotracheal tube. J Pak surgery. Anaesthesia; 2007, 62:913-918. Med Assoc; 2000, 50:333-338. 8. Hohlrieder M, Brimacombe J, Von Goedecke A, Keller C: 20. Cork RC, Depa RM, Standen JR: Prospective comparison of use of Postoperative nausea, vomiting, airway morbidity, and analgesic the laryngeal mask and endotracheal tube for ambulatory surgery. requirements are lower for the ProSeal laryngeal mask airway than Anesth Analg; 1994, 79:719-727. the tracheal tube in females undergoing breast and gynaecological 21. Swann DG, Spens H, Edwards SA, Chestnut RJ: Anaesthesia for surgery. British journal of anaesthesia; 2007, 99:576-580. gynaecological laparoscopy--a comparison between the laryngeal 9. Yu SH, Beirne OR: Laryngeal mask airways have a lower risk of mask airway and tracheal intubation. Anaesthesia; 1993, 48:431- airway complications compared with endotracheal intubation: a 434. systematic review. J Oral Maxillofac Surg; 2010, 68:2359-2376. 22. Nader ND, Simpson G, Reedy RL: Middle ear pressure changes after 10. Griffiths JD, Nguyen M, Lau H, Grant S, Williams DI: A nitrous oxide anesthesia and its effect on postoperative nausea and prospective randomised comparison of the LMA ProSeal versus vomiting. Laryngoscope; 2004, 114:883-886. endotracheal tube on the severity of postoperative pain following 23. Klockgether-Radke A, Piorek V, C rozier T, Kettler D: Nausea gynaecological laparoscopy. Anaesth Intensive Care; 2013, 41:46- and vomiting after laparoscopic surgery: a comparison of propofol 50. and thiopentone/halothane anaesthesia. Eur J Anaesthesiol; 1996, 11. Gul R, Goksu S, Ugur BK, Sahin L, Koruk S, Okumus S, et al: 13:3-9. Comparison of proseal laryngeal mask and endotracheal tube for 24. Ayala MA, Sanderson A, Marks R, Hoffer M, Balough B: airway safety in pediatric strabismus surgery. Saudi Med J; 2012, Laryngeal mask airway use in otologic surgery. Otol Neurotol; 33:388-394. 2009, 30:599-601. 12. Porhomayon J, Wendel PK, Defranks-Anain L, Leissner KB, 25. Anderson BJ, Pearce S, McGann JE, Newson AJ, Holford NH: Nader ND: Do the choices of airway affect the post-anesthetic occurrence of nausea after knee arthroplasty? A comparison between Investigations using logistic regression models on the effect of the endotracheal tubes and laryngeal mask airways. Middle East J LMA on morphine induced vomiting after tonsillectomy. Paediatr Anesthesiol; 2013, 22:263-271. Anaesth; 2000, 10:633-638. SCIENTIFIC ARTICLES

Renal Protection in the Cardiac Surgery Patient: Peri-Operative Sodium Bicarbonate Infusion (POSBI) or Not?

Hassan H. Amhaz*, Deepak Gupta**, Larry Manders**, George McKelvey***, Marc S. Orlewicz** and Romeo N. Kaddoum**

Abstract

Background: Acute renal failure following cardiac surgery is not uncommon and carries a high level of morbidity and mortality. The aim of our study was to determine whether perioperative sodium bicarbonate infusion (POSBI) would decrease acute kidney injury in cardiac surgery patients and improve post-operative outcomes. Methods: A retrospective analysis of 318 cardiac surgery patients from 2008-2011 was performed. Clinical parameters were compared in patients receiving POSBI versus sodium chloride. Serum creatinine levels were measured in the first five post-operative days. The primary outcome measured was the number of patients developing post-operative renal injury. Secondary outcomes included three-month mortality, intensive care unit and hospital length of stay. Results: Patients given POSBI showed no significant differences compared to the normal saline cohort in regards to increases in serum creatinine [<25% rise in Cr: 93% vs 94%; >25% rise in Cr: 6% vs 6%; >50% rise in Cr: 1% vs 1%; >100% rise in Cr: 1% vs 0%, all with p-value >0.99]. There were fewer patients with AKIN stage 1 renal failure receiving POSBI [8% vs 28%, p = 0.02] however there was no difference between POSBI and sodium chloride cohorts in AKIN stages 2 and 3 renal failure. Mortality, duration of hospitalization and ICU stay were not statistically significant. Conclusions: POSBI resulted in fewer patients developing AKIN stage 1 renal failure. Despite this, there appears to be little benefit in the prevention of acute kidney injury after 48 hours or mortality reduction in cardiac surgery patients.

* md, MS. ** MD. *** PhD. Affiliation: Department of Anesthesiology, Wayne State University, Detroit Medical Center; Detroit, Michigan, United States. Corresponding author: Romeo N. Kaddoum, MD. Assistant Professor; Wayne State University, Detroit Medical Center; 3990 John R, Rm 2901; 2-Hudson, Detroit, MI 48201, United States. Office: 1-313-745-7233, Fax: 1-313-993-3889. E-mail: [email protected]

17 M.E.J. ANESTH 23 (1), 2015 18 Romeo Kaddoum et. al

Introduction liter of D5W. The protocol was to infuse the sodium bicarbonate at a rate of 1-1.5cc/kg/hr starting from the Acute kidney injury (AKI) in patients undergoing beginning of surgery for a total of 24 hours as normal cardiac surgery is a common and serious occurrence saline was previously done. with an incidence ranging between 3% and 50% of Table 1 patients and is associated with significant morbidity Study Inclusion and Exclusion Criteria* 1,2,3 and mortality rates as high as 38% . Of these patients, Inclusion criteria Exclusion criteria 1% will require dialysis, with associated mortality Age 18-80 End Stage Renal Disease 4,5,6 rates in this group as high as 60%-70% . There (ESRD) are numerous factors that contribute to postoperative CABG +/- valve surgery, Emergency cardiac surgery renal failure, including ischemia, drugs, generation of intracardiac surgery reactive oxygen free radicals, hemolysis and activation Redo cardiac surgery Use of intra-aortic balloon pump 1,4,6 of inflammatory and complement pathways . (IABP) Additionally, numerous independent risk factors have Pre-operative plasma Currently enrolled in another been found to be predictive of post-operative AKI creatinine concentration study following cardiac surgery4,6-10. Although some studies >1.3 mg/dL have shown sodium bicarbonate to ameliorate post- NYHA class III/IV Known blood-borne Infectious operative kidney injury, its use in cardiac surgery disease remains controversial. We present a retrospective Left Ventricle EF <35% Chronic corticosteroid therapy multi-centered study of 318 patients undergoing * Cardiac surgery patients having one or more of the listed cardiac surgery to evaluate whether peri-operative criteria sodium bicarbonate infusion (POSBI) would reduce post-operative AKI. To determine a sample size for the study a Chi-squared power analysis was chosen to obtain an alpha error probability of 0.05 and a power of 0.95. Material and Methods A sample size of 300 patients (at least 150 in each group; effect size d=0.2 small -medium) was deemed After institutional review board approval (Wayne to give the study sufficient power. Repeated Measures State University IRB committee, IRB#065611M1E), Analysis of Variance (ANOVA) and T-tests (Unpaired; a retrospective analysis of 318 post-cardiac surgery two sided) were used where appropriate to measure patients, from two institutions within our medical continuous variables between the 2 patient groups center over a four-year period (2008-2011) was with post hoc differences measured using the Student- performed. Biochemical and clinical parameters Neuman-Keuls test. Comparisons between study were compared in patients receiving POSBI versus groups on proportional differences were examined sodium chloride. Inclusion and exclusion criteria of using a non-parametric Fisher’s Exact Chi-square test, the study are listed in Table 1. Serum creatinine levels when applied to 2X2 tables. A p-value of <0.05 was were measured in the first five post-operative days in considered significant. patients who received sodium bicarbonate and those Of note, the 318 patients that were included in receiving sodium chloride. our study were patients of only two cardiothoracic Starting in 2009, our medical center instituted surgeons who used sodium bicarbonate consistently a sodium bicarbonate infusion protocol for patients following the protocol implementation in 2009. Hence, undergoing cardiac surgery due to new literature when data before 2009 was obtained for patients not showing possible benefit from POSBI. Previously, receiving POSBI we used the patients from only these patients received normal saline at a rate of 1-1.5cc/ two surgeons. For this reason, the 318 cardiac surgery kg/hr from the start of surgery for a total of 24 hours. patients only represent a smaller fraction of total The sodium bicarbonate infusion protocol simply cardiac surgery patients at our institution. This was added 3 Amps (150mEq) of sodium bicarbonate in 1 done to minimize surgeon bias and to exclude surgeons Renal Protection in the Cardiac Surgery Patient 19 who did not consistently use POSBI. secondary outcomes that were measured included The primary outcome measured was the number intensive care unit (ICU) and hospital length of stay, and three-month mortality rates. of patients who developed post-operative renal injury following cardiac surgery. Kidney injury was Table 2 defined into four categories which were based on Acute Kidney Injury Network (AKIN) Classification Criteria baseline serum creatinine levels to those on the fifth Classes Serum Cr (sCr) Criteria postoperative day: serum creatinine increases <25%, 1 sCr increase x 1.5 - 2 (50%-100%) or sCr an increase greater than 25%, greater than 50%, and increase >0.3 mg/dL from baseline 2 sCr increase x 2 - 3 (101%-200%) from baseline greater than 100% from baseline. The proportion of 3 sCr increase x 3 (>201%) or sCr >4 mg/dL with kidney injury between these groups as defined by increase >0.5 mg/dL the AKIN criteria was also compared, Table 2. Other

Table 3 Patient pre-operative characteristics Sodium Characteristics Sodium Chloride p-value Bicarbonate Demographic data Age, yr, mean (SD) 62 (11) 63 (12) 0.56 Gender 0.01 Males, n (%) 119 (68) 77 (54) Females, n (%) 56 (32) 66 (46) Race 0.39 African Americans, n (%) 118 (67) 103 (72) Non - African Americans, n (%) 57 (33) 40 (28) Comorbidities Hypertension, n (%) 158 (90) 133 (93) 0.42 Chronic kidney disease, n (%) 47 (27) 38 (27) >0.99 Peripheral vascular disease, n (%) 28 (16) 40 (28) 0.01 Hypercholesterolemia, n (%) 146 (83) 114 (80) 0.47 Chronic obstructive pulmonary disease, n (%) 57 (33) 39 (27) 0.33 Diabetes Mellitus, n (%) 77 (44) 65 (45) 0.82 Left ventricular ejection fraction, percent (SD) 49 (15) 49 (15) 0.83 Hemodialysis, n (%) 13 (7) 17 (12) 0.18 Medications Beta-blockers, n (%) 137 (78) 86 (60) 0.0005 ACE inhibitors or angiotensin blockers, n (%) 86 (49) 83 (58) 0.12 HMG-CoA reductase inhibitor, n (%) 144 (82) 96 (67) 0.003 Pre-operative creatinine levels 0.17 Cr <1.0, n (%) 60 (34) 56 (38) 1.0 2, n (%) 21 (12) 23 (16) Pre-operative Ejection Fraction (EF) 0.47 EF <15%, n (%) 0 (0) 3 (2) 15% 55%, n (%) 90 (49) 73 (48)

M.E.J. ANESTH 23 (1), 2015 20 Romeo Kaddoum et. al

Results more patients who underwent mitral valve repair received POSBI. However, when considering all valve Three hundred and eighteen patients underwent surgeries combined, there was no significant difference cardiac surgery at our institutions from 2008 thru 2011. seen between the POSBI and normal saline groups. There were 175 patients who received POSBI and 143 Although aortic clamp times did not differ between patients received only sodium chloride. Preoperative the groups, cardiopulmonary bypass (CPB) time patient characteristics of the study are listed in Table was slightly lower in the sodium bicarbonate group, 3. Patient characteristics were fairly matched between Table 4. POSBI and normal saline groups with the exception Serum creatinine levels measured on the fifth that recipients of POSBI were more likely to be male post-operative compared to baseline were divided into and be on β-blockers and statins. However, more four categories: <25%, >25%, >50%, and >100%. peripheral vascular disease was seen in patients There were no significant differences between patients receiving normal saline. New institutional mandates receiving POSBI versus normal saline, Table 5. When regarding patients receiving preoperative β-blockers, renal dysfunction was defined using the AKIN criteria, around the same time the sodium bicarbonate infusion creatinine levels 48 hours post-operatively compared protocol was instituted, is a likely reason for why the to baseline, patients receiving POSBI had fewer sodium bicarbonate group received more β-blockers. patients with AKIN stage 1 renal failure. However, no Regarding the surgery type, no significant differences significant differences were observed between the two were seen between groups with the exception that groups in regards to AKIN stage 2 and 3, Table 6. The

Table 4 Type of surgery and patient intra-operative characteristics Characteristics Sodium Bicarbonate Sodium Chloride p-value Cardiac surgery 0.08 Valve surgery only, n (%) 58 (33) 41 (27) 0.29 Aortic valve replacement, n (%) 25 (14) 18 (12) 0.57 Mitral valve replacement, n (%) 14 (8) 16 (10) 0.39 Mitral valve repair, n (%) 12 (7) 3 (2) 0.04 Double valve surgery, n (%) 7 (4) 4 (3) 0.52 CABG only, n (%) 100 (57) 80 (54) 0.56 Valve and CABG surgery, n (%) 17 (9) 22 (14) 0.16 Cardiopulmonary bypass time, mins (SD) 106 (38) 119 (57) 0.02 Aortic clamp time, mins (SD) 86 (32) 93 (52) 0.16

Table 5 Post-operative sCr changes in patients receiving POSBI vs Normal Saline Post-operative sCr change Sodium Bicarbonate Normal Saline p-value <25% sCr Rise 163 (93%) 134 (94%) >0.99 >25% sCr Rise 10 (6%) 8 (6%) >0.99 >50% sCr Rise 1 (1%) 1 (1%) >0.99 >100% sCr Rise 1 (1%) 0 (0%) >0.99 Total 175 143 Renal Protection in the Cardiac Surgery Patient 21

Table 6 Post-operative AKIN stage in patients receiving POSBI vs Normal Saline Post-operative AKIN stage Sodium Bicarbonate Normal Saline p-value Normal 148 (85%) 110 (62%) 0.09 AKIN Stage 1 14 (8%) 24 (28%) 0.02 AKIN Stage 2 7 (4%) 5 (3%) >0.99 AKIN Stage 3 6 (3%) 4 (3%) >0.99 Total 175 143

Table 7 Secondary outcomes measured Secondary outcomes Sodium Bicarbonate Normal Saline p-value Mortality, n (%) 27 (15) 25 (16) 0.76 Intensive Care Unit stay, days (SD) 9.2 (8.6) 10 (9.2) 0.39 Duration of hospitalization, days (SD) 10.7 (9.9) 12 (8.7) 0.22 secondary outcomes that were measured in the study or other adjuvant therapies (N-acetylcysteine and included 30-day mortality, length of hospitalization fenoldopam) in the prevention of acute kidney injury and ICU stay, Table 7. Our average ICU length of stay following cardiac surgery. Haase et al1, conducted was higher than other studies secondary to several a pilot double-blinded, randomized control trial of patients in each cohort with ICU stays longer than 100 cardiac surgery patients. The patients underwent one month. However, total hospital length of stay was treatment to see if POSBI can attenuate postoperative consistent with other published studies1. No significant increases in serum creatinine. Their primary outcome differences were seen between groups in regards to 30- was reaching a serum creatinine of >25% above day mortality, length of hospitalization or ICU stay. baseline within the first five postoperative days. They found a statistical significance using bicarbonate in Discussion patients with creatinine increases >25% however there was no difference in patients with creatinine increases Acute kidney injury (AKI) is a common and of either >50% and >100%. There was no statistical serious complication following cardiac surgery significance found when acute kidney injury was with an incidence ranging from 3% to 50%1,7. AKI defined by the AKIN criteria. No mortality benefit following cardiac surgery carries a significant cost was seen in patients receiving POSBI. Furthermore, burden and is an independent predictor of mortality. other large RCT studies looking at N-acetylcysteine, Pre-operative serum creatinine levels are the most fenoldopam and statins failed to show a clear benefit important predictive factor for post-operative AKI7,10. in postoperative renal protection. Approximately 10% to 20% of patients with baseline Post-operative renal failure is multifactorial: creatinine levels between 2mg/dL and 4mg/dL will ischemia-reperfusion injury seen from hemodynamic require dialysis and those with creatinine levels instability and aortic cross clamping, low cardiac greater than 4mg/dL will require dialysis 30% of the output states, loss of pulsatile flow while on bypass, 7 time . Patients requiring post-operative dialysis have nephrotoxic drugs, generation of reactive oxygen a mortality rate of 60-70%. To date, no treatment free radicals, and the activation of neutrophils, including peri-operative sodium bicarbonate infusion inflammatory and complement pathways7,10,11. has been shown to be effective in preventing renal Furthermore, mechanical and shear forces on red blood 1,7,9 failure after cardiac surgery . cells seen in cardiopulmonary bypass is associated Only a few prospective randomized control trials with levels of free hemoglobin which exceeds the have been done to evaluate the role of sodium bicarbonate capacity of haptoglobin. Thus, longer bypass times are

M.E.J. ANESTH 23 (1), 2015 22 Romeo Kaddoum et. al

Table 8 Major Risk Factors for Developing Acute Kidney Injury Patient Risk Factors Surgical Risk Factors Age Pre-operative use of an IABP Female CABG, Valve or combined procedures Pre-operative serum creatinine CPB duration EF <35% Hemodilution during CPB Insulin Dependent Diabetes Mellitus Emergency surgery Chronic obstructive pulmonary disease

associated with increased free hemoglobin exposure study showed that 1.1% of these patients had AKI after and can theoretically worsen kidney injury. Under surgery, and the mortality in this group was 63.7%. The acidic conditions increased free iron release from end result of the study was that cardiac surgery was an hemoglobin occurs which catalyzes the Haber-Weiss independent risk factor for developing AKI, and was reaction promoting hydroxyl radical formation. The associated with a high mortality rate. The rate of AKI alkalinizing effects of sodium bicarbonate on the urine and AKI-related mortality could not be explained by are thought to provide some degree of renal protection comorbidities alone12. In addition to cardiac surgery, due to the reduction in hydroxyl radical formation cardiopulmonary bypass itself was found to be an from free iron and tubular cast formation1,7,10,11. independent risk factor for the development of AKI6. Classification of renal injury, as with AKIN, Although there appears to be a beneficial effect does not provide insight into the nature of the injury. of POSBI within the literature there are several Typically, the window for therapeutic intervention has important factors that must be considered. First, the passed once serum creatinine levels begin to rise4. As definition of “AKI”, an increase in serum creatinine a result, biomarkers for the early detection of renal >25%, is quite liberal. This equates to less than a injury have been sought after. Neutrophil gelatinase- 0.1mg/dL/day increase in serum creatinine over the associated lipocalin (NGAL), cystatin C, IL-18, first five post-operative days5. Mehta and colleagues13 kidney injury molecule-1 (KIM-1) and many more convened in an international meeting to develop a have all been studied1,4,7,10. Urinary NGAL levels are uniform system for the diagnosis and classification of virtually undetectable in patients with normal kidney acute kidney injury, which is formally known as the function and serve as a marker of oxidative stress. AKIN criteria, Table 2. When AKI is defined as an Urinary NGAL levels greater than 100ng/mL two increase in serum creatinine >50%, no difference is hours following cardiopulmonary bypass predict acute found between POSBI and normal saline groups seen kidney injury (sensitivity, 82%; specificity, 90%); much in the prospective pilot study1,5. Regardless of stage, no higher than other studied biomarkers1,10. In a study significance was found when the AKIN criteria were by Haase et al1, the use of sodium bicarbonate does used5. Although we found a lower incidence of AKIN not appear enough to thwart the acute kidney injury stage 1 renal failure in patients receiving POSBI, seen following cardiac surgery despite a significant it appears that by the fifth post-operative day these attenuation in urinary NGAL. benefits are no longer seen. Several risk factors have been identified that The use of sodium bicarbonate and its resulting are associated with AKI in cardiac surgery patients, alkalemia is not benign. Mortality, CO2 retention and Table 84,6-10. Chertow et al12, conducted a large cohort associated hypoxia from impaired oxygen delivery are study of 42,273 patients undergoing coronary artery all potential complications of POSBI5. Haase et al1, bypass graft (CABG) or valvular heart surgery. This showed considerable group differences from baseline Renal Protection in the Cardiac Surgery Patient 23 to 24 hours post-operatively in plasma bicarbonate Conclusion concentration, base excess, and pH levels. Therefore, careful monitoring of plasma pH and bicarbonate levels We present a retrospective multicenter study would be warranted in instances where large amounts comparing the use of POSBI to that of sodium chloride of sodium bicarbonate are being administered. in patients undergoing cardiac surgery to prevent postoperative renal failure. Despite a lower incidence of Our study has several limitations that should be patients developing AKIN stage 1 renal failure in the noted. Although retrospective, pre-operative patient POSBI cohort, the benefit does not persist through the characteristics between cohorts were fairly matched fifth post-operative day. With no reduction in mortality, however if we were to match for every characteristic hospital or ICU length of stay, there currently appears the overall numbers would be low and the study to be no benefit with the use of POSBI in cardiac underpowered. Additionally, we did not include surgery patients. patients with new-onset hemodialysis requirements following cardiac surgery. Numerous patients have Acknowledgments multiple uncontrolled comorbidities with baseline renal dysfunction that may have contributed to the Dimitrios Apostolou, MD - cardiothoracic extended ICU length of stay compared to other studies surgeon of patients in study however overall length of hospitalization remained Ali Kafi, MD - cardiothoracic surgeon of patients 1 consistent . in study

M.E.J. ANESTH 23 (1), 2015 24 Romeo Kaddoum et. al

References

1. Haase M, Haase-Fielitz A, Bellomo R, et al: Sodium bicarbonate Ann Thorac Surg; 2011, Oct; 92(4):1539-47. Epub 2011, Aug 27. to prevent increases in serum creatinine after cardiac surgery: a pilot Review. double-blind, randomized controlled trial. Crit Care Med; 2009, Jan; 8. McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill 37(1):39-47. WW: Acute renal failure after coronary intervention: incidence, 2. Adabag AS, Ishani A, Bloomfield HE, Ngo AK, Wilt TJ: Efficacy risk factors, and relationship to mortality. Am J Med; 1997, Nov; of N-acetylcysteine in preventing renal injury after heart surgery: 103(5):368-75. a systematic review of randomized trials. Eur Heart J; 2009, Aug; 9. Ranucci M, Soro G, Barzaghi N, et al: Fenoldopam prophylaxis 30(15):1910-7. of postoperative acute renal failure in high-risk cardiac surgery 3. Liakopoulos OJ, Choi YH, Haldenwang PL, et al: Impact of patients. Ann Thorac Surg; 2004, Oct; 78(4):1332-7; discussion preoperative statin therapy on adverse postoperative outcomes in 1337-8. patients undergoing cardiac surgery: a meta-analysis of over 30,000 10. Kumar A, Suneja M. Cardiopulmonary bypass-assicated acute patients. Eur Heart J; 2008, Jun; 29(12):1548-59. kidney injury. Anesthesiology; 2011, Apr; 114(4):964-70. 4. Coleman MD, Shaefi S, Sladen RN: Preventing acute kidney injury 11. Haase M, Haase-Fielitz A, Bagshaw SM, Ronco C, Bellomo R: after cardiac surgery. Curr Opin Anaesthesiol; 2011, Feb; 24(1):70- Cardiopulmonary bypass-associated acute kidney injury: a pigment 6. nephropathy? Contrib Nephrol; 2007, 156:340-53. 5. Weisberg L: Sodium bicarbonate for renal protection after heart 12. Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J: surgery: let’s wait and see. Crit Care Med; 2009, Jan; 37(1):333-4. Independent association between acute renal failure and mortality 6. Stallwood M, Grayson A, Mills K, Scawn N: Acute renal following cardiac surgery. Am J Med; 1998, Apr; 104(4):343-8. failure in coronary artery bypass surgery: independent effect of 13. Mehta RL, Kellum JA, Shah SV, et al: Acute Kidney Injury cardiopulmonary bypass. Ann Thorac Surg; 2004, Mar; 77(3):968- Network. Acute Kidney Injury Network: report of an initiative 72. to improve outcomes in acute kidney injury. Crit Care; 2007, 7. Mariscalco G, Lorusso R, Dominici C, Renzulli A, Sala A: 11(2):R31. Acute kidney injury: a relevant complication after cardiac surgery. Effect of ultrasound-guided subsartorial approach for saphenous nerve block in cases with saphenous nerve entrapment in adductor canal for controlling chronic knee pain.

Arman Taheri*, Maryam Hatami**, Majid Dashti***, Alireza Khajehnasiri**** and Mahsa Ghajarzadeh*****

Abstract

Background: Saphenous nerve neuropathy is one of the causes of chronic pain of the knee. Blockade of saphenous nerve under sonographich guide has been used for controlling pain in recent years. The goal of this study was to evaluate the effect of saphenous nerve block for controlling pain in patients with chronic knee pain. Method: Thirty five patients with chronic knee pain referred to Amir Alam hospital during June 2012-June 2013 were enrolled in this study. Under sonographic approach, subsartorial blockade of saphenous nerve conducted and patients were followed up for 3 months after treatment. Demographic data, ASA (American Society of Anesthesiologists) category, weight, height, complications of intervention and pain scores were recorded. Results: In 54%, the NRS was zero 30 minutes after intervention. In one patient (2.8%) all NRSs were 0 after intervention. We observed no sensory dysfunction in enrolled cases. Conclusion: the result of current study showed that ultrasound guided subsartorial approach is moderately effective in blockade of saphenous nerve in cases with saphenous nerve entrapment in adductor canal for controlling chronic knee pain. Keywords: ultrasound-guided block, knee pain, pain management.

Introduction

Saphenous nerve is a terminal branch of the femoral nerve which innervates medial, anteromedial, and posteromedial aspects of the lower extremity1. Saphenous nerve entrapment is one of the causes of chronic knee pain (especially at medial site) which could mimic orthopedic disorders of the knee or L4 radiculopathy2.

* FIPP, Assistant professor of Anesthesiology, Iran section of World Institute of Pain Director, Chairman of Tehran University of Medical Science Fellowship Program, Department of Anesthesia & Pain Management Amiralam Hospital, Tehran University of Medical sciences, Tehran, Iran. ** Pain fellowship, Department of Anesthesia & Pain Management, Tehran University of Medical Sciences, Tehran, Iran. *** Cardiac anesthesia fellowship, department of anesthesia, Shahid rajaee hospital, Tehran University of Medical Sciences, Tehran, Iran. **** assistant Professor of Anesthesiology and Pain, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. ***** Brain and Spinal Injury Repair Research Center, Tehran University of Medical Sciences, Tehran, Iran. Corresponding author: Maryam Hatami MD. E-mail: [email protected]

25 M.E.J. ANESTH 23 (1), 2015 26 Maryam Hatami et. al

Blockage of saphenous nerve could be applied located. After negative aspiration, 10 cc Bupivacaine for procedures on the medial aspect of the distal leg3. 25% and 40 mg methyl prednisolone sulphate under Different approaches could be applied for blockage of the sonography guidance were injected. Maximal NRS saphenous nerve such as perifemoral, trans-sartorial, was recorded after 30 minutes, one week, one month block at the medial femoral condoyle, below-the-knee and three months after intervention. The Numeric field block, and blockade at the level of the medial Rating Scale (NRS) is a 10-point scale for patient self- malleolus. Benzon et al found that trans-sartorial reporting of pain. Zero means ‘No pain’ and 10 means approach was the best approach for complete sensory ‘Worst possible pain’. blockade4. Official approval from ethics committee of In recent years, blockade of the saphenous nerve TUMS was obtained for the study and all the patients under the guidance of ultrasound has been considered gave informed consent. as an acceptable approach. Tsai et al reviewed the medical records of 39 cases who underwent subsartorial Demographic data, ASA, weight, height, and saphenous nerve block for lower extremity surgery complication of intervention were recorded. and found that this technique was successful in 77% Statistical analyses were performed with SPSS 5 of cases . software version 18.0 (Statistical Product and Service The aim of the study is to evaluate effect of Solutions, SSPS Inc., Chicago). Results are presented saphenous nerve block in cases with saphenous nerve as mean ± SDs, and frequencies. The Student’s t test entrapment in adductor canal for controlling chronic was used for continuous variables, and the Pearson x2 knee pain. test with Fisher’s exact test was applied for categorical variables. Repeated measure ANOVA was used to Method and material compare mean NRS during study period. P value <0.05 was considered statistically significant. In this cross sectional study which conducted between June 2012-June 2013 in Amir Alam hospital Results (affiliated hospital of Tehran university of medical sciences), patients with chronic knee pain (pain Thirty five cases enrolled in this study. Mean more than 3 months), Numeric rating scale ≥7 and age of all cases was 54.6 ± 12.8 years. Twenty four tenderness in adductor canal were enrolled. Patients cases (68.6%) were female and 11 (31.4%) were male. with previous surgery of lower extremities, recent Twenty there (65.7%), 9 (25.7%), and 3 (8.6%) patients trauma to the knee, consumption of anti-coagulant were ASA class I,II, and III respectively. Only the left agents, drug abuse, severe osteoarthritis (according to knew was affected in 9 patients (25.7%), only the right radiologic findings), allergy to local anesthetic agents, psychologic disorders, and active infection were knee was affected in 11 patients (31.4%) while both excluded. knees were affected in 15 patients (42.9%). For blockade, patients were placed in supine Mean BMI, and pre-intervention NRS were 25.1 2 position, with the lower extremity rotated externally ± 2.3 (kg/m ) and 8 ± 0.8 (7-10) respectively. at the hip, and the knee slightly flexed. The mid- Repeated measure ANOVA showed that mean thigh area was prepped and 8-12 MHz linear probe NRS significantly decreased throughout the evaluation was placed at the proximal aspect of the leg (10 cm time (p <0.001) (Table 1). proximal to medial condyle) to obtain a cross-sectional In nineteen patients (54%), the NRS was zero at view of the femoral artery in short-axis. The saphenous 30 minutes after intervention (Table 2). nerve was defined as a highly hyperechoic structure medial to femoral artery. The needle was inserted Only one patient (2.8%) had a NRS of 0 lateral to femoral artery then proceeded to the medial throughout the study period. We observed no sensory aspect of the artery where the saphenous nerve was dysfunction in in all enrolled cases. saphenous nerve block in knee pain 27

Table 1 (mean ± SD) NRS during evaluation time

NRS before intervention NRS after 30 NRS after one NRS after one NRS after 3 P value minutes week month months 8 ± 0.8 0.7 ± 0.8 1.5 ± 1.3 2.2 ± 1.8 5.2 ± 2.6 <0.001

Table 2 Success rates during follow up

Success rate Reduction of NRS scores to 0 after 30 minutes 19 (54.3%) Reduction of NRS scores to 0 after one week 7(20%) Reduction of NRS scores to 0 after one month 4(11.4%) Reduction of NRS scores to 0 after 3 months 3 (8.6%)

Discussion In another studyby Manickam, et al, blockade of the saphenous nerve at the distal part of adductor The result of this study showed that ultrasound- canal for patients who underwent ankle or foot surgery guided sub-sartorial blockade of saphenous nerve in resulted in 100% success rate7. cases with saphenous nerve entrapment in adductor The lower success rate in the current study could canal is a successful method for controlling pain during be attributed due to our first experiment in doing sub- post intervention period in patients with chronic knee sartorial blockade of saphenous nerve. pain. During follow up we found that NRS decreased We observed that pain NRS became zero 30 significantly and then increased but the mean score at minutes after intervention in 54% of cases and pain the end of follow up was lower than pre intervention eradicated in 2.8% of patients who suffer from chronic score. It could show that this approach is useful for knee pain. However, this success rate is lower that the reducing pain for a short time and it is not applicable rates in previous studies. for eradicating pain. May be continuous blockades or other methods such as radio frequency (RF) is Romanoff et al evaluated 30 patients with necessary for eradicating pain in cases with chronic saphenous nerve entrapment in adductor canal who knee pain. underwent series of nerve blockade (mean 1.9 of Chronic knee pain is a disabling condition blockade). They reported VAS score of 6.4 at baseline which affects quality of life of the patients and and 2.8 at the end of the study. Eighty seven of cases limits daily activity8. Different underlying diseases had improved at the final stage of the study6. such as osteoarthritis, rheumatoid arthritis, bursitis, Their findings along with our results show that chondromalacia patella, baker’s cyst and jumper’s saphenous nerve blockade in cases with saphenous knee are among common causes of chronic knee pain. nerve entrapment in adductor canal is effective for This study has some limitations. First, the sample controlling pain. size was low and the follow up period was short. Larger In Tsai et al study the success rate of saphenous studies with long follow up periods are recommended. nerve blockade in cases who underwent lower Conclusion: The results of the current study extremity surgery was 77% and in Benzon et al study showed that ultrasound guided subsartorial approach the success rate was 70%4-5. In their study saphenous is moderately effective in blockade of saphenous nerve nerve block was performed in conducted for patients in cases with saphenous nerve entrapment in adductor who were candidate for menisectomy. canal for controlling chronic knee pain.

M.E.J. ANESTH 23 (1), 2015 28 Maryam Hatami et. al

References

1. Horn J-L, Pitsch T, Salinas F, Benninger B: Anatomic basis to the 7. Manickam B, Perlas A, Duggan E, Brull R, Chan VW, Ramlogan ultrasound-guided approach for saphenous nerve blockade. Reg R: Feasibility and efficacy of ultrasound-guided block of the anesth pain med; 2009, 34(5):486-9. saphenous nerve in the adductor canal. Reg anesth pain med; 2009, 2. Brad McKechnie D: Saphenous Nerve Entrapment Neuropathy. 34(6):578-80. Dynamic Chiropractic; May 22, 1995, 13(11):1-3. 8. Ikeuchi M, Ushida T, Izumi M, Tani T: Percutaneous Radiofrequency 3. Akkaya T, Ersan O, Ozkan D, Sahiner Y, A kin M, Gümüş H, et Treatment for Refractory Anteromedial Pain of Osteoarthritic al: Saphenous nerve block is an effective regional technique for Knees. Pain Med; 2011, 12(4):546-51. post-menisectomy pain. Knee Surgery, Sports Traumatology. 9. Tsui BC, Özelsel T: Ultrasound-guided transsartorial perifemoral Arthroscopy; 2008, 16(9):855-8. artery approach for saphenous nerve block. Reg anesth pain med; 4. Benzon HT, Sharma S, Calimaran A: Comparison of the different 2009, 34(2):177-8. approaches to saphenous nerve block. Anesthesiology; 2005, 10. Krombach J, Gray AT: Sonography for saphenous nerve block near 102(3):633-8. the adductor canal. Reg anesth pain med; 2007, 32(4):369-70. 5. Tsai PB, Karnwal A, Kakazu C, Tokhner V, J ulka IS: Efficacy 11. Mansour N: Sub-sartorial saphenous nerve block with the aid of of an ultrasound-guided subsartorial approach to saphenous nerve nerve stimulator. Reg anesth; 1992, 18(4):266-8. block: a case series. Can J Anesth; 2010, 57(7):683-8. 12. Bouaziz H, Benhamou D, Narchi P: A new approach for saphenous 6. Romanoff ME, Cory PC, Kalenak A, Keyser GC, Marshall WK: nerve block. Reg anesth; 1996, 21(5):490. Saphenous nerve entrapment at the adductor canal. Am J Sports 13. Gray AT, C ollins AB: Ultrasound‐Guided Saphenous Nerve Block. Med; 1989, 17(4):478-81. Reg anesth pain med; 2003, 28(2):148. Comparison of the effects of oral vs. peritonsillar infiltration of ketamine in pain reduction after tonsillectomy: a Randomized Clinical Trial

Afsaneh Norouzi*, Abolfazl Jafari**, Hamid Reza Khoddami Vishteh*** and Shahin Fateh****

Abstract

Background: Although oral ketamine has been used in some cases to reduce pain in children, the use of this drug to reduce pain after tonsillectomy has not been studied yet. Methods: This double-blind clinical trial was conducted in 2009 in 92 children who were aged three to nine years old, met ASA I or II criteria, and were candidate for tonsillectomy. Patients were divided randomly into two groups. Half an hour before general anesthesia, 5 mg/kg ketamine mixed in 2 cc/kg apple juice was given to the children in oral ketamine group and 2 cc/kg of apple juice alone was given to the children in the peritonsillar group. After general anesthesia and three minutes before surgery 1 cc of 0.9% normal saline in the oral group and 1cc of ketamine (0.5 mg/ kg) in the peritonsillar group was injected to the tonsil bed of patients. Results: There was no difference between the two groups in terms of sex, age, and weight. Duration of surgery was significantly shorter in the peritonsillar group (P <0.001) and the severity of postoperative bleeding was significantly higher in peritonsillar group (P = 0.022). However, postoperative bleeding recurred in 25 patients (27%) and there was no statistically significant difference between the two groups. The level of pain in children six hours after surgery according to CHEOPS criteria was significantly lower in the peritonsillar group (0.9 ± 0.8) than in the oral group (2.6 ± 1) (P <0.001). Conclusions: The finding of this study showed that, compared with the peritonsillar infiltration of ketamine, the use of oral ketamine before general anesthesia was less effective in reducing postoperative pain of tonsillectomy in children. Keywords: tonsillectomy, adenotonsillectomy, postoperative pain, ketamine.

* assistant Professor (MD), Department of Anesthesiology and Intensive Care Medicine, Arak University of Medical Sciences, Arak, Iran. ** assistant Professor (MD), Department of Otolaryngology, Arak University of Medical Sciences, Arak, Iran. *** General Practitioner, Arak University of Medical Sciences, Arak, Iran. **** Assistant Professor (MD), Thoracic surgeon, Department of Surgery, Arak University of Medical Sciences, Arak, Iran. Corresponding author: Afsaneh Norouzi, Assistant Professor (MD), Department of Anesthesiology and Intensive Care Medicine, Arak University of Medical Sciences, Arak, Iran. Address: Valiasr hospital, Arak, Markazi province, Iran. Tel: +989181611365, Fax: +988613137474. E-mail: [email protected], [email protected]

29 M.E.J. ANESTH 23 (1), 2015 30 Afsaneh Norouzi et. al

Introduction Materials and Methods

Adenotonsillectomy is one of the most This double-blind clinical trial was conducted common ear, nose, and throat surgeries in children in 2009 on 92 children aged three to nine years old and postoperative pain is one of its important who were referred to Amir Kabir hospital in Arak complications. Inadequate control of postoperative City. Inclusion criteria were: being aged three to nine pain leads to different complications such as poor years old, meeting ASA I or II criteria, and candidate nutrition, dehydration, sleep disorders, behavioral for tonsillectomy surgery. Exclusion criteria were: the changes, nausea, and vomiting1; moreover, it can presence of an underlying disease, and the presence increase the length of hospitalization and consequently of contraindications to the use of ketamine including increase healthcare costs2. Despite the high prevalence upper airway active infection, increased intracranial of pain after tonsillectomy and adenotonsillectomy3, 4 pressure, open eyes surgery, and seizures. The study and the presence of different analgesics and assessment was approved by the Ethics Committee of the Arak tools for measuring age-related pain5, the choice of University of Medical Sciences. appropriate analgesic to be used after tonsillectomy After explaining the procedures of the study to 6 operation is still controversial . parents and obtaining their informed consent, patients To reduce pain after tonsillectomy in children, who met inclusion criteria were divided randomly into different groups of drugs (oral paracetamol, opioids, two groups. In order to double-blind study, injectable NSAIDs, and local anesthetics) have been studied. medications were tagged using similar labels and oral Although paracetamol is a safe and effective analgesic, ketamine was also given to patients mixed in apple when it is used alone it cannot achieve an appropriate juice by a medical student. Anesthesiologist and ENT analgesic effect after tonsillectomy7. Opiates may specialists were unaware of the patient group and used reduce upper airway tone, suppress the cough reflex, apple juices and injectable medications for patients, cause sedation and respiratory depression (especially respectively. Anesthesia was started using fentanyl in unintended outpatient surgery), and also lead to and atropine as premedication and then anesthesia postoperative nausea and vomiting4. Although NSAIDs was induced using sodium thiopental 6 mg/kg and are an alternative to opioids, they may increase the risk atracurium 0.5-1 mg/kg and it was sustained with of postoperative bleeding and reoperation8. In addition, isoflurane 1%, NO2 and O2 with a ratio of 50%. All local anesthetics are associated with vasoconstriction9. patients were intubated and to prevent entering blood N-methyl-D-aspartate (NMDA) receptors in the to the throat, which is of the factors causing nausea, dorsal horn of the spinal cord are involved in central gauze was placed in the throat. sensitization to painful stimuli10. Ketamine is a non- Half an hour before general anesthesia, 5 mg/kg competitive antagonist of NMDA receptors which has ketamine mixed in 2 cc/kg apple juice was given to the analgesic effects at sub-anesthetic doses10. Safari et al children in oral ketamine group and 2 cc/kg of apple showed that the use of ketamine reduced the need for juice alone was given to the children in the peritonsillar postoperative opioids and other analgesics in children group. After the induction of general anesthesia and undergoing tonsillectomy11. Intravenous injection12, three minutes before surgery 1 cc of normal saline peritonsillar infiltration13, rectal14, spray at the site of 0.9% in the oral group and 1cc of ketamine (0.5 mg/ surgery15, continuous infusion16 and subcutaneous kg) in the peritonsillar group was injected to the each injection11 of ketamine have been investigated for pain tonsil bed of patients (a total of 2 cc injections for each reduction after tonsillectomy, too. To our knowledge, child). Injection was performed by an ENT specialist. no previous studies have evaluated the role of oral Age, sex, weight, duration of surgery, ketamine for pain reduction after tonsillectomy. intraoperative blood loss, postoperative bleeding (in the The aim of the current study is to compare oral recovery room), nausea, vomiting, and postoperative ketamine to peritonsillar ketamine infiltration for pain bleeding recurrence six hours after surgery were relief after tonsillectomy. recorded by the medical student who was unaware of Oral ketamine vs. peritonsillar infiltration in tonsillectomy 31 patient group. In order to measure the pain six hours order to compare the two groups, chi-square test and after surgery, Modified Scoring CHEOPS criterion Mann-Whitney U test were used. P-value less than was used (Table 1). The range for this criterion is from 0.05 was considered as a significant level. 0 to 10 where a higher score indicates greater pain17. Power calculations had indicated that 46 children Results would be required per group to detect a difference of 30% in facial CHEOPS pain scoring with a power of There were no differences between the two 85% and α =0.05 . SPSS 13 software was used for data groups in terms of sex, age, and weight (Table 2). analysis. Qualitative variables were described using Table 3 shows the comparison of the characteristics of frequencies and percentages and quantitative variables surgeries and postoperative complications between the were described using mean and standard deviation. In two groups. Duration of surgery was ≤20 minutes in

Table 1 Modiﬁed CHEOPS scoring Score 0 1 2 Cry No cry Crying, moaning Scream Facial Smiling Neutral Grimace Verbal Positive statement Negative statement Suffering from pain, another complaint Torso Neutral Variable, taut, upright Stretched Legs Neutral Kicking Stretched, continuous move

Table 2 Comparison of demographic characteristics between groups Oral group Peritonsillar group P value (N = 46) (N = 46) Sex Male 37 (80%) 9 (20%) 0.101 Female 30 (65%) 16 (35%) Age group ≤5 yr 9 (20%) 12 (26%) 6-7 yr 18 (39%) 11 (24%) 0.278 ≥8 yr 19 (41%) 23 (50%) Weight ≤20 Kg 18 (39%) 18 (39%) 21-24 Kg 18 (39%) 12 (26%) 0.275 ≥25 Kg 10 (22%) 16 (35%)

Table 3 Comparison of surgery time and side effects between groups Oral group Peritonsillar group P-value (N = 46) (N = 46) Surgery time ≤20 min 0 (0%) 19 (41%) 21-29 min 18 (39%) 7 (15%) <0.001 ≥30 min 28 (61%) 20 (44%) Post-op bleeding Mild 9 (20%) 14 (30%) Moderate 37 (80%) 27 (59%) 0.022 Severe 0 (0%) 5 (11%) Post-op bleeding recurrence 9 (20%) 16 (35%) 0.101 Nausea & Vomiting 0 (0%) 2 (4%) 0.153

M.E.J. ANESTH 23 (1), 2015 32 Afsaneh Norouzi et. al

19 patients (21%), 21-29 minutes in 25 patients (27%), while only 30% of children in the oral group had and ≥30 minutes in 48 patients (52%). The durations of neutral condition (P <0.001). There was no significant surgeries were significantly shorter in the peritonsillar difference between the two groups in terms of children group than in the oral group (P <0.001). The severity of cry and their body shape (Torso). postoperative bleeding was mild in 23 patients (25%), moderate in 64 patients (70%), and severe in five Discussion patients (5%); overall, the incidence of postoperative bleeding was significantly higher in peritonsillar The findings of this study showed that, compared group than in the oral group (P = 0.022). Postoperative with oral ketamine, the peritonsillar infiltration of bleeding recurred in 25 patients (27%) and there was ketamine after general anesthesia and immediately no statistically significant difference between the two groups. Only two patients had postoperative nausea before tonsillectomy shortened the duration of and vomiting, and there was no significant difference operation and reduced the severity of postoperative between the two groups. pain. Although postoperative bleeding was more in the ketamine peritonsillar group, the recurrent bleeding, The level of pain in children six hours nausea, and vomiting after surgery was not significantly after surgery according to CHEOPS criteria was different between the two groups. Thus, it seems that, significantly lower in the peritonsillar group (0.9 ± compared to peritonsillar infiltration, the use of oral 0.8) than in the oral group (2.6 ± 1) (P <0.001). Table ketamine 5 mg/kg is less effective in reducing pain in 4 shows the characteristics of pain in each item. All children after tonsillectomy. the children in the peritonsillar group had neutral facial expression; however in the oral group only half the Ketamine is a noncompetitive antagonist of the children had neutral facial expression (P <0.001). In NMDA receptor. These receptors are located in the the peritonsillar group, 39% of children were suffering dorsal horn of the spinal cord and play an important role from pain, whereas 76% of patients in the oral group in the development of central sensitization to painful were suffering from pain (P <0.001). The leg condition peripheral stimuli. Seemingly, hyperexcitability of the was neutral in all children in the peritonsillar group, central nervous system appears to be the cause of the

Table 4 Comparison of pain based on CHEPOS between groups Oral group Peritonsillar group P-value (N = 46) (N = 46) Cry No cry 28 (61%) 36 (78%) Crying, moaning 18 (39%) 10 (22%) 0.070 Scream 0 (0%) 0 (0%) Facial Smiling 0 (0%) 0 (0%) Neutral 23 (50%) 46 (100%) <0.001 Grimace 23 (50%) 0 (0%) Verbal Positive statement 0 (0%) 16 (35%) Negative statement 11 (24%) 12 (26%) <0.001 Suffering from pain, another complaint 35 (76%) 18 (39%) Torso Neutral 46 (100%) 46 (100%) Variable, taut, upright 0 (0%) 0 (0%) 1.000 Stretched 0 (0%) 0 (0%) Legs Neutral 14 (30%) 46 (100%) Kicking 0 (0%) 0 (0%) <0.001 Stretched, continuous move 32 (70%) 0 (0%) Oral ketamine vs. peritonsillar infiltration in tonsillectomy 33 wind-up phenomenon and subsequent hyperalgesia in ketamine with doses of 0.5 or 1 mg/kg reduced pain the place of injury18. The goal of preemptive analgesia after tonsillectomy, compared to control13. Our study is to prevent the afferent impulses to the spinal cord also showed that peritonsillar infiltration of ketamine that is causing such a phenomenon. Hence, preemptive could be a useful method for reducing pain following analgesia may prevent pain memory in the central tonsillectomy in children. nervous system and reduce the need for analgesics Although ketamine has been used via different 19 in the postoperative period . It has been shown that methods to reduce pain after tonsillectomy, oral ketamine’s effects on these receptors can reduce pain method, however, has not been used yet for this 20 in humans . purpose. Filatov et al. have compared oral ketamine Ketamine has been used in different ways, at as premedication with rectal diazepam/diclofenac different doses and different times as an analgesic after in adenoidectomy surgery and reported that oral tonsillectomy surgery, but the reported results were ketamine group had slightly higher pain scores than not consistent have been various. Some studies failed other group27. However, they conclude that oral to show the effect of ketamine on reducing pain after ketamine is not suitable for premedication in upper tonsillectomy. O’Flaherty et al’s study which compared airway surgeries27. Oral ketamine has been effective in the effects of the administration of intravenous children for controlling pain in different cases such as ketamine with that of placebo4 and Van Elstraet et al’s abdominal malignancy surgery, sickle cell crisis, and 28-30 study which examined the effect of ketamine on pain chronic pains . It has also been used for anesthetic after tonsillectomy in adults21 did not show a positive premedication in children in surgeries such as dental, 31-33 effect in reducing pain after tonsillectomy. However, ophthalmic and minor surgeries . In addition, oral other studies reported that using ketamine was ketamine is effective in postoperative agitation in 34 effective in reducing pain following tonsillectomy. children . In the present study we examined the effects Murray et al showed that a low-dose of intravenous of oral ketamine in reducing pain after tonsillectomy ketamine may be effective in reducing pain after and compared it with peritonsillar ketamine. Although tonsillectomy22. Marcus et al23 and Elhakim et al24 Ketamine reduced postoperative bleeding, overall stated that the intramuscular ketamine can be used it was associated with more pain in children than as an alternative analgesic for tonsillectomy. Erhan peritonsillar infiltration. Thus, it seems that oral et al. reported that ketamine injection in the tonsillar ketamine with a dose of 5 mg/kg is less effective in area was more effective than placebo in reducing reducing pain in children after tonsillectomy compared pain without inducing sedation or nausea25. Dal et al. to peritonsillar infiltration. reported that intravenous or peritonsillar infiltration of ketamine before adenotonsillectomy surgery Conclusions could reduce postoperative pain and reduce the need for analgesics without causing any adverse effects26. The finding of this study indicated that, compared More recent studies have also suggested the effect of with the use of oral ketamine before tonsillectomy, ketamine on reducing pain after tonsillectomy. Sizer the peritonsillar infiltration of ketamine after general et al12 showed that intravenous ketamine was effective anesthesia and immediately before tonsillectomy in reducing pain following tonsillectomy. According to was more effective in reducing postoperative pain in a study by Siddiqui et al. peritonsillar infiltration of children.

M.E.J. ANESTH 23 (1), 2015 34 Afsaneh Norouzi et. al

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Jennings CA, Bobb BT, Noreika DM and Coyne PJ: Oral ketamine vomiting and postoperative pain relief in children following for sickle cell crisis pain refractory to opioids. J Pain Palliat Care tonsillectomy. Med Arh; 2012, 66(2):111-5. Pharmacother; 2013, 27(2):150-4. 12. Sizer C, Kara I, Topal A and Celik JB: A comparison of the effects 30. Ugur F, Gulcu N and Boyaci A: Oral ketamine for pain relief in a of intraoperative tramadol and ketamine usage for postoperative pain child with abdominal malignancy. Pain Med; 2009, 10(1):120-1. relief in patients undergoing tonsillectomy. Agri; 2013, 25(2):47-54. 31. Khattab AM, El-Seify ZA, Shaaban A, Radojevic D and Jankovic 13. Siddiqui AS, Raees US, Siddiqui SZ and Raza SA: Efficacy of pre- I: Sevoflurane-emergence agitation: effect of supplementary low- incisional peritonsillar infiltration of ketamine for post-tonsillectomy dose oral ketamine premedication in preschool children undergoing analgesia in children. J Coll Physicians Surg Pak; 2013, 23(8):533-7. dental surgery. Eur J Anaesthesiol; 2010, 27(4):353-8. 14. Heidari SM, Mirlohi SZ and Hashemi SJ: Comparison of 32. Darlong V, Shende D, Subramanyam MS, Sunder R and Naik A: Oral the preventive analgesic effect of rectal ketamine and rectal ketamine or midazolam or low dose combination for premedication acetaminophen after pediatric tonsillectomy. Int J Prev Med; 2012, in children. Anaesth Intensive Care; 2004, 32(2):246-9. 3(Suppl 1):S150-5. 33. Astuto M, Disma N and Crimi: Two doses of oral ketamine, given 15. Hosseini Jahromi SA, Hosseini Valami SM and Hatamian S: with midazolam, for premedication in children. Minerva Anestesiol; Comparison between effect of lidocaine, morphine and ketamine 2002, 68(7-8):593-8. spray on post-tonsillectomy pain in children. Anesth Pain Med; 34. Kararmaz A, Kaya S, Turhanoglu S and Ozyilmaz MA: Oral 2012, 2(1):17-21. ketamine premedication can prevent emergence agitation in children 16. Quibell R, Prommer EE, Mihalyo M, Twycross R and Wilcock A: after desflurane anaesthesia.Paediatr Anaesth; 2004, 14(6):477-82. Ketamine. J Pain Symptom Manage; 2011, 41(3):640-649. The Impact of Anesthetic Techniques on Cognitive Functions after Urological Surgery

Mahtab Poor zamany Nejat kermany*, Mohammad Hossein Soltani**, Khazar Ahmadi***, Hoora Motiee***, Shermin Rubenzadeh*** and Vahid Nejati***

Abstract

Background: Postoperative cognitive dysfunction (POCD) is a well-recognized complication of cardiac and noncardiac surgery. However, contradictory results concerning postoperative mental function have been reported. The aim is to determine the effect of anesthetic techniques (general or spinal) on cognitive functions using more sensitive neuropsychological tests in patients undergoing urological surgery. Material and Methods: A total of thirty patients were enrolled in the study and assigned to receive either general (n=15) or spinal (n=15) anesthesia. A battery of neuropsychological tests including Wisconsin Card Sorting Test, Iowa Gambling Task, Stroop Color-Word Test, N-back Task and Continuous Performance Test was performed preoperatively and three days later. Results: The two experimental groups were similar at baseline assessment of cognitive function. Although there were no statistically significant differences between general and spinal anesthetic groups with respect to Wisconsin Card Sorting Test and Iowa Gambling Task, a significant intergroup difference between pre-and postoperative N-back scores was detected in the general anesthesia group (p=0.001&p=0.004). In addition, patients within this group had significantly higher error rates on the Stroop Color-Word (p=0.019) and Continuous Performance Tests (p=0.045). In contrast, patients receiving spinal anesthesia exhibited little change or marginal improvement on all subscales of the battery. Conclusions: Our findings indicate significant decline in specific aspects of mental function among patients who were administered general anesthesia compared with the other technique. It seems that spinal anesthesia contributes to lower disturbance after surgery. Key word: Anesthesia - Cognitive function - Urology.

* Anesthesiology Department of Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, I.R. Iran. ** Urology Department of Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, I.R. Iran. *** Neuroscience department of Shahid Beheshti University of Medical Sciences (SBMU), Tehran, I.R. Iran. Address: No#99, 9th Boston St., Pasdaran Ave, Tehran, Iran.Tel & Fax: 0098-21-22588016 . Corresponding author: Vahid Nejati , Urology Department of Shahid Labbafinejad Medical Center, Email :v_nejati@sbu. ac.ir

35 M.E.J. ANESTH 23 (1), 2015 36 Mahtab poor zamany Nejat kermany et. al

Introduction It has been speculated that POCD risk could be reduced by performing certain surgical procedures Postoperative cognitive dysfunction (POCD) is under regional anesthesia. Results of a study indicated a common complication in adult patients undergoing that the maintenance of mental function in an elderly surgical procedures which refers to decline in variety population was better following spinal anesthesia when of neuropsychological domains such as verbal or compared with general anesthetic technique17. Similarly, visual memory, executive functioning, language another report showed that the incidence of cognitive comprehension, attention and concentration1. Although deterioration was lower after epidural anesthesia18. primarily observed after cardiac surgery, it has also A recent study found that general anesthesia posed been detected following major noncardiac surgeries2,3. a significant risk for the occurrence of early POCD While POCD is presumed to be transient and the long- in elderly patients that could persist for 3 days after term effects are considered uncertain4,5, recent studies surgery19. However, review of the existing literature suggest that the symptoms of neurocognitive change has not revealed a significant difference between the may persist long after the operation6,7 and diminish two intraoperative anesthetic techniques20,21. The quality of life. Patients with POCD are more likely to heterogeneity of procedures used to measure cognitive withdraw from employment and social activities that deficits and methodological inconsistencies make the will lead to premature dependency8,9. The ISPOCD 1 limited literature on POCD difficult to interpret22,23. study (International Study of Post-Operative Cognitive Most of these tests are subsets of test banks used to Dysfunction) of 1,218 elderly patients (60 yr or older) assess the memory and intelligence of adults. The use of scheduled for major noncardiac surgery showed that more sensitive neuropsychological tests may elucidate cognitive impairment was present in 25.8% patients more prolonged damage to cognitive performance. In one week after the operation and in 9.9% of them after 3 addition, the majority of previous investigations have months10. Furthermore, postoperative cognitive decline primarily focused on elderly patients, a population with has been associated with significantly higher risks of an increased vulnerability to neurological deterioration postoperative morbidity and mortality, particularly in after exposure to anaesthesia24,25. As a result, the elderly11. A similar study revealed that patients with cognitive effects of anesthesia and surgery in young POCD at hospital discharge were more likely to die and middle-aged adults are poorly understood. The whitin 3 months of the discharge12. In general, the rate objective of this study was to evaluate post-operative of cognitive dysfunction has been positively correlated mental function of patients who had undergone general with mortality risk. Several studies show an increased or spinal anesthesia for a urologic surgery, and to risk of early mortality in elderly individuals with compare the effect of these two anesthetic techniques cognitive deterioration13,14. on mental function. The etiology of POCD is likely multifactorial with type of surgical procedure (due to differences Material and Methods in duration) metabolic/endocrine stress response, imbalance of neurotransmitter system (particularly From July to September 2011, 30 patients acetylcholine and serotonin), hypoxia and undergoing urological surgery following either general hospitalization, all potentially playing a role15. or spinal anesthesia were participated in the study at Advanced age, history of cerebral vascular accident Shahid Labbafinezhad Hospital. Written informed with no residual impairment, lower educational consent was taken from all patients and university level, evidence of cognitive dysfunction at hospital ethics committee approved the study structure. Entry discharge and alcohol abuse also contribute to the criteria included age (24+ yr), normal mental status, pathogenesis of POCD12,16. With further identification speaking and reading fluency in the Persian language of preoperative risk factors for POCD, patients and and the absence of any serious vision or hearing healthcare providers can be better informed before impairment that would preclude neuropsychological making a decision to proceed with major surgery. testing. Participants were excluded if they had any Impact of anesthesia on cognitive function 37 prior history of dementia, central nervous system to maintain vigilance and react to the presence or disease, psychiatric disorders, alcoholism and drug absence of specific stimuli within a continuously abuse. In addition, any patients with history of allergy presented set of distracters30,31. N-Back Task is one of to anesthetic drugs were also excluded. Information the most popular experimental paradigms for studies about the demographic status, medical history, of working memory, in which subjects are asked to education and occupational history of the subjects monitor the identity or location of a set of verbal or were documented. nonverbal stimuli and to indicate when the currently presented stimulus is the same as the one presented in 32,33 Anesthetic techniques and agents trials previously . Iowa Gambling Task evaluates decision-making under initially ambiguous conditions. It simulates real-life decision making by testing the All patients received 5cc/kg normal saline ability of subjects to learn to sacrifice immediate serum before anesthesia. In the group of patients who rewards in favor of long-term gains34,35. underwent general anesthesia, the following agents were used for the induction of anesthesia: Fentanyl (2µ/kg), Midazolam (1mg), Lidocain (1.5mg/kg), Statistical Analysis Propofol (2mg/kg) and Atracurium (0.5mg/kg). For maintenance phase of general anesthesia, Propofol Given the large number of dependant variables, (100-200µ/kg) and Remifentanil (0.1 µ/kg/min) comparison of the cognitive function between the two were used. Spinal Anesthesia was done by injection anesthesia groups was performed with multivariate of 2.5 to 3 cc bupivacaine 0.5% (Marcaine®) in the analysis of covariance (MANCOVA) using SPSS subarachnoid space. For post-operative pain control, (version 18). Follow-up tests were conducted when intravenous pethidine (25-50 mg) was administrated in warranted by multivariate results with ANOVA and the recovery room and Diclofenac 100mg suppository paired t-tests. Pre-test scores were considered to be was given in the ward as needed. covariate variables in order to control for the practice effect. The customary two-tailed α level of significance Neuropsychological Assessment was set at 0.05.

The cognitive function evaluation was performed Results in an undisturbed room with only the patient and the psychometrician present. Patients completed the tests Thirty patients (13 women and 17 men) were one day prior to surgery and at hospital discharge (three recruited. The subjects had a mean age of 44.6 days after the operation). The psychological measures (±12.66). 36.6% subjects were classified as young included Wisconsin Card Sorting Test, Stroop Color- (24-39yr), 53.33% were middle-aged (40-59) and 10% Word Task, Continuous Performance Test, N-Back were elderly (60-65). General anesthesia was used in Task and Iowa Gambling Test that were administered 15 patients (50%), and the remaining subjects received in about 30 minutes. These measures primarily focus spinal anesthesia. on executive functions and memory, elaborated as The baseline characteristics of the patients included follows: in the study are listed in table 1. Data analysis revealed Wisconsin Card Sorting Test is commonly that the two groups did not differ in preoperative scores. regarded as “the gold standard executive function However, statistically significant differences were task”26,27. Patients were asked to match response cards observed when postoperative scores were compared to reference cards according to three dimensions of with the baseline levels. Results indicated significant sorting principle (color, form and number)28. Stroop association between general anesthetic technique and Color-Word Test estimates the patient’s ability damage to particular domains of cognitive functions. to concentrate and ignore distracting stimuli29. Although subtests of the Wisconsin Card Sorting Test Continuous Performance Test (CPT) requires subjects and Iowa Gambling Task did not change significantly

M.E.J. ANESTH 23 (1), 2015 38 Mahtab poor zamany Nejat kermany et. al between the two groups, separate univariate analysis the study was based on MANCOVA which provided and paired t-test showed that patients were more more statistical power. Our data revealed that general likely to have worse 1-and 2-back test performance anesthesia was associated with weaker performance in after general anesthesia (p=0.001& p=0.004). These the memory and concentration domains. These results patients also had significantly higher omission error are in accordance with the findings of Chung et al, score on the Continuous Performance Task (p=0.045) who found that patients receiving general anesthesia and considerable error rates on the 3rd part of the performed worse on digit-symbol substitution for 2-3 Stroop Color-Word Test (p=0.019). It is worth noting days after surgery36. Herbert and colleagues also noted that patients receiving spinal anesthesia showed that choice reaction time was impaired for 36hours little change or slight improvement on all subscales after administration of general anesthesia37. Findings of the battery. The mean pre-and postoperative of another study indicated that general anesthesia neuropsychological test scores are exhibited in patients perceived residual impairment of their Table 2. cognitive faculties after 3 days38. Previous research addressing the role of anesthesia Discussion on cognitive deterioration has yielded conflicting results. The absence of a consistency regarding the This study is one of the few investigations of operational definition of POCD may contribute to postoperative cognitive function that includes younger this issue. Our findings are inconsistent with the population. In the current study, we used some of vast majority of existing evidence demonstrating no the most popular neuropsychological tasks to assess significant difference between intraoperative regional executive functions. Comparison of the two arms of and general anesthesia in preserving postoperative

Table 1 General characteristics of the patients, compared in two groups (general vs. spinal anesthesia.) General Spinal Anesthesia Total P value Anesthesia Mean Age 46.9 42.26 44.6 0.614 Age Groups 24-39 (Young) 6 5 11 0.120 40-59 (Middle-aged) 8 8 16 60 and above (Elderly) 1 2 3 Sex Male 7 10 17 0.211 Female 8 5 13 Education Less than High school 4 7 11 0.340 High School 6 4 10 More than High school 5 4 9 Type of Lithotripsy 4 1 5 0.151 surgery Intravesical injection 1 2 3 Radical Nephrectomy 2 0 2 Varicocelectomy 2 3 5 Bladder Stone Removal 2 2 4 TUL 1 5 6 TURT 1 2 3 Impact of anesthesia on cognitive function 39

Table 2 Pre-and postoperative (at hospital discharge) test results Preoperative Postoperative General Spinal General Spinal (n-15) (n-15) (n-15) (n-15)

Wisconsin Card Sorting Test

Achieved Clusters 1.66±0.61 1.60±0.63 1.66±0.72 2.00±0.84 Number of Total Errors 37.93±6.39 38.2±5.79 37.53±6.01 36.26±7.53 Perseverative Errors 15.46±3.62 14.86±2.13 14.8±3.66 12.00± Iowa Gambling Task 25.20±2.48 23.53±3.29 26.20±1.97 23.46±3.99 N-Back Task

1-back 19.93±6.71 16.26±6.30 16.20±5.99* 17.73±6.41 2-back 8.13±3.29 8.73±3.97 5.60±2.55* 10.33±3.90 Continuous Performance Test Omission Error 16.06±8.67 16.33±8.10 19.20±7.93* 13.60±6.56 Commission Error 1.064±0.51 1.157±0.94 1.11±0.35 1.151±0.56 Hit Reaction Time 0.548±0.06 0.562±0.04 0.606±0.1 0.541±0.05 Stroop Color-Word Task Error Rates 1 1.33±0.97 1.40±0.82 1.60±1.88 0.66±0.61 Reaction Time 1 0.46±0.45 0.33 ±0.37 0.42±0.54 0.25±0.32 Error Rates 2 0.53±0.74 0.53±0.63 2.13±1.95 0.26±0.59 Reaction Time 2 0.34±0.55 0.27±0.34 0.79±0.81 0.22±0.46 Error Rates 3 17.40±7.91 19.33±7.006 22.06±6.94* 16.60±6.99 Reaction Time 3 1.85±0.93 1.34±0.55 2.11±0.91 1.53±0.61

Values are given as mean±SE. “*” mark indicates significant difference in the assigned group before and after the operation. cognitive function. For instance, in a prospective, Detection of POCD requires two crucial randomized study, Williams-Russo et al, compared elements: a sensitive battery of tests and controlling for the effect of epidural versus general anesthesia the practice effect. We used some of the well-known on the incidence of POCD in patients undergoing psychological measurements to determine more subtle elective unilateral total knee replacement and found defects. The enhancement observed in this trial cannot 20 no significant difference postoperatively . In another be attributed to practice effect. In as much as, pretest randomized trial, no significant differences were found scores were considered as covariate variables. in the postoperative mental abilities between patients who received general, regional or combined anesthetic There may be several factors that might have a techniques39. O’Hara et al, observed no clinically negative impact on cognitive function after general important impacts on major outcomes in patients anesthesia. Some agents that are used to induce and who were administered general or spinal anesthetic maintain anesthesia may deteriorate cognition and techniques after the hip surgery40. In a systematic memory10. In addition, there may be a possibility of review, Wu et al, found that intraoperative neuraxial hemodynamic instability, hypoxia and stress induced anesthesia does not decrease the incidence of POCD response due to prolonged intubation; the factors that when compared with general anaesthesia41. are not commonly related to regional anesthesia15.

M.E.J. ANESTH 23 (1), 2015 40 Mahtab poor zamany Nejat kermany et. al

This study was limited by two major factors. mental function. Local anesthesia might have an Firstly, patients were not allocated randomly to the advantage over general anesthesia in terms of general or spinal anesthesia groups. Secondly, we neuropsychological functioning. were unable to include a control group of healthy volunteers matched with the experimental groups in Acknowledgments the present study. Hospitalized patients not undergoing surgery or any other intervention were also considered The authors thank the hospital staff and patients as a better control group, but a sufficient sample size for taking part in this study. Their assistance was for comparison could not be attained due to lack essential for data collection and the coordination of the of participation. Our findings should therefore be research protocol. interpreted with caution. A more extensive study with follow-up testing is required to determine the precise profile of the postoperative cognitive impairment. Conflict of interest: In conclusion, our results suggest a linkage The authors have no conflict of interest. between general anesthesia and weaker postoperative Impact of anesthesia on cognitive function 41

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gambling. Addiction Research Report; 2010, 106:383-390. 39. Riss J, Lomholt B, Haxholdt O, et al: Immediate and long term 36. Chung F, Seyone C, Dyk B, Chung A, Ong D, Taylor A, Stone R: recovery from general versus epidural anaesthesia in elderly Age related cognitive recovery after general anaesthesia. Anesthesia patients. Acta Anaesthesiol Scand; 1983, 27:44-9. and Analgesia; 1990, 71:217-224. 40. O’Hara DA, Duff A, Berlin JA, et al: The effect of anaesthetic 37. Herbert M, Healy TEJ, Bourke JB, Fletcher IR, Rose JM: Profile technique on postoperative outcomes in hip fracture repaire. of recovery aftergeneral anaesthesia. British Medical Journal; 1983, Anesthesiology; 2000, 92:947-57. 286:1539-1542. 41. Wu ChL, Hsu W, Richman JM, Raja SN: Postoperative Cognitive 38. Tzabar Y, Asbury AJ, Millar K: Cognitive failure after general Function as an Outcome of Regional Anaesthesia and Analgesia. anaesthesia for day-case surgery. Br J Anaesth; 1991, 67:262-8. Regional Anesthesia and Pain Medicine; 2004, (29)3:257-268. Comparison between C-MAC® video-laryngoscope and Macintosh direct laryngoscope during cervical spine immobilization

Shahir HM Akbar* and Joanna SM Ooi**

Abstract

Background: Video-laryngoscopes have gained popularity in the recent years and have shown definite advantages over the conventional Macintosh direct laryngoscopes. However, there is still insufficient evidence comparing the C-MAC® with the Macintosh for patients during manual inline stabilization (MILS). Methods: This prospective, randomized, single blind study was carried out to compare tracheal intubation using the C-MAC® video-laryngoscope and Macintosh laryngoscope in patients during MILS. Ninety consented patients, without features of difficult airway, who required general anesthesia and tracheal intubation were recruited. Intubation was performed with either the C-MAC® video-laryngoscope or the Macintosh laryngoscope by one single investigator experienced with both devices. Various parameters which included Cormack and Lehane score, time to intubate, intubation attempts, optimization maneuvers, complications and hemodynamic changes were recorded over the initial period of 5 minutes. Results: C-MAC® video-laryngoscope performed significantly better with lower Cormack and Lehane grades, shorter time to intubate of 32.7 ± 6.8 vs. 38.8 ± 8.9 seconds (p=0.001) and needed less optimization maneuvers. There were no significant differences seen in the intubation attempts, complications or hemodynamic status of the patients with either device. Conclusion: The C-MAC® video-laryngoscope was superior to the Macintosh laryngoscope for patients requiring intubation when manual inline neck stabilization was applied. Keywords: C-MAC® laryngoscope, Macintosh laryngoscope, intubation, neck immobilization, manual inline stabilization.

Introduction

Securing the airway with tracheal intubation in a patient suspected or known to have a cervical spine injury has always been a challenge regardless of whether it is conducted in a controlled operating room environment, in a busy critical zone of the emergency department or in an out-of-hospital setting. This has been recognized since the early 1950’s and by the early 1980’s the standard of care to overcome this scenario was to use the time tested formulae of direct laryngoscopy with tracheal intubation using manual inline stabilization (MILS)1 with a Macintosh laryngoscope. MILS is a maneuver that ensures a neutral alignment and motionless cervical spine

* MBBS, Master in Medicine (Anesthesiology). ** MD, Master in Medicine (Anesthesiology). Corresponding author: Professor Dr. Joanna Su Min Ooi. Address: Department of Anesthesiology and Intensive Care, University Kebangsaan Malaysia Medical Center, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. Tel: +0193207265, Fax: +60391456585. E-mail: [email protected]

43 M.E.J. ANESTH 23 (1), 2015 44 J.Su Min Ooi et. al during the intubation process and is carried out by a the C-MAC® video-laryngoscope or the Macintosh healthcare personnel who places a hand on each side laryngoscope during MILS. The time taken to intubate of the patients neck with fingers pressed on each (seconds), number of intubation attempts, optimization mastoid process and the hands then pressed firmly maneuvers required, complications encountered and into the operating table2. While the practice of MILS the changes in hemodynamic parameters of the patients was considered to be the standard care with regards to being intubated were also compared. prevention or worsening of any neurological morbidity, it has been found that MILS produced significantly Methods worse laryngoscopy view upon direct laryngoscopy for 3-5 tracheal intubation . The delay in or a failed tracheal This study design was based on a prospective, intubation could potentially result in hypoxia leading randomised, single-blinded clinical trial that was done to worse outcomes and is a leading cause of morbidity following approval of the Dissertation Committee and mortality for patients in both the operative setting of the Department of Anesthesiology and Intensive 5,6 and in an emergency situation . Care, Universiti Kebangsaan Malaysia Medical Center With due consideration to the above, advances (UKMMC) and the Research Ethics Committee of in technology have provided alternatives to the UKMMC (Research No. FF-024-2011). conventional Macintosh laryngoscope to perform After obtaining written informed consent, ninety direct laryngoscopy during a MILS scenario. patients between 18 and 60 years of age with American Considerable development has occurred especially Society of Anesthesiology (ASA) physical status I or II, in the field of indirect laryngoscopy using video- scheduled for elective surgery under general anesthesia assisted techniques producing devices such as that required tracheal intubation were enrolled in the ® the Glidescope (Saturn Biomedical System study. Those patients who had features of difficult ® Inc., Burnbaby, Canada) and the Airwayscope airway (e.g. Mallampati grade >III, thyromental laryngoscope (Pentax Corporation, Tokyo, Japan). distance <6cm or a Body Mass Index >35kg/m2), These new devices have been shown to have pregnant or had other conditions associated with an definite advantages over the conventional Macintosh increased risk of pulmonary aspiration were excluded direct laryngoscopy in scenarios where MILS was from the study. Likewise patients who had pre-existing applied. These included better glottic visualization, cervical neck pathologies, hypertensive individuals less optimizing maneuvers needed for a successful and those with allergies or contraindications to intubation and more favorable hemodynamic profiles medications used for general anesthesia were excluded during the intubation itself7-10. as well. The C-MAC® (Karl Storz, Tuttlingen, Germany), The selected patients were then randomised a portable video-laryngoscope is unique as it offers an into two arms. Group 1 patients were intubated with original Macintosh blade shape with an approximately the C-MAC® video-laryngoscope whereas patients in 80° angle of view and practically eliminated fogging Group 2 were intubated with the Macintosh (MAC) of the camera11. Owing to its similar design to the laryngoscope. This randomisation process was done Macintosh blade, there would not be very much of a using ‘Random Numbers Tables’ that were computer learning curve to using it by most anesthetic doctors. generated. An initial study showed great promises in it being able In the operating room, all patients received to obtain good view of the glottis on the first attempt a standardized general anesthetic. Both groups 12 in all patients . At this point of time the question of of patients were started on IV fluid of Lactated whether any video-laryngoscope is definitely better in Ringer’s solution. Induction of anesthesia with the 3 MILS is yet to be answered convincingly . administration of 100% oxygen at 6 liters/min, IV The aim of this study was to compare fentanyl (2 mcg/kg) and IV propofol (up to 2 mg/kg) laryngoscopic views (based on Cormack and Lehane was carried out to induce unconsciousness defined grading) during tracheal intubation when using either as loss of eyelash reflex. Subsequently manual C-MAC® video-laryngoscope during manual inline stabilization 45 ventilation was initiated with sevoflurane (2.0%) in bougie (GEB), external laryngeal manipulation (ELM) oxygen as test ventilation, before administration of IV or presence of a second assistant were also recorded. rocuronium (0.6 mg/kg) as a muscle relaxant. Standard Complications including fogging of lens, local trauma anesthetic monitoring which included ECG, non- (mucosal/lip/dental), hypoxia (SpO2 <92%) and failed invasive blood pressure (NIBP), oxygen saturation intubation were recorded. Recording of the patient’s

(SpO2), end tidal carbon dioxide (EtCO2) and a multi- baseline mean arterial pressure (MAP) and heart gas analyzer were provided to both groups of patients. rate (HR) along with repeat recordings at fixed one After full muscle relaxation was confirmed with a minute time intervals for 5 minutes were done. No nerve stimulator, the patient’s neck was immobilized other medications were administered, or procedures utilizing MILS technique. The MILS was performed performed during the 5-minute data collection period by another medical officer who stood at the right side after tracheal intubation. Subsequent management was of the patient caudal to the intubator and the patient’s left to the discretion of the anesthetist providing care airway. The assistant placed a hand on each side of the for the patient. patient’s neck with fingers pressed on each mastoid The sample size was obtained using the computer process and the hands were then pressed firmly into software: “Power and Sample Size Calculations the operating table ensuring neutral alignment and a Version 3.0.14, January 2009” otherwise known as PS2. motionless cervical spine as described in Advanced (http://bisotat.mc.vanderbilt.edu/powersamplesize ). 2 Trauma Life Support . The alpha error was set at 5% (p<0.05) and a beta error Intubation was then performed with one of the two of 20% (power = 0.8). The p0 was set at 0.2 from a devices (both with blade #3) as per the group that the previous study with the Macintosh laryngoscope using patient was in . A tracheal tube size #7.5 - 8 for males MILS where 20% of patients obtained CL grade 1 and #7 - 7.5 for females was used. Once the vocal cords views9. Since the C-MAC® video-laryngoscope has not were visualized they were graded using the Cormack been studied previously in this manner, the probability and Lehane (CL) grading. After successful tracheal of obtaining a CL grade 1 view was estimated as intubation in all patients, mechanical ventilation was 50% from a preliminary study12. Thus the p1 was commenced for the duration of the procedure with set at 0.5 and the results calculated using the sample anesthesia being maintained with sevoflurane (1.0 size software as discussed previously. The sample size required was found to be 38 patients, which was MAC) and air-oxygen mixture (FiO2 0.5). rounded up to 40 patients on each arm. A dropout rate In each group, tracheal intubation was considered of 10% was factored in to give a sample size of 45 a failure if it could not be established with three attempts, patients in each arm and thus a total sample size of 90 within three minutes or desaturation of SpO <92%. In 2 patients. the event of such an incident, MILS was abandoned and intubation was performed using the Macintosh Data analysis was done using Chi-square test for blade with optimal patient head and neck positioning. non-parametric data and Student’s t-test for parametric Any additional instruments to aid intubation were used data. A p value of less than 0.05 was considered as if deemed necessary. All intubations were performed statistically significant. All analysis was performed by the investigator SH, an anesthetic trainee whose using SPSS for Windows (version 12.0, Chicago, IL). previous experience includes >30 intubations with the C-MAC® and more than 5 years frequent use of the Results Macintosh laryngoscope. Data collected included CL score, time to intubate A total of 90 patients were enrolled into the in seconds (defined as when either of the blades was study with 45 patients in each group. There were no inserted beyond the lip until first appearance of the significant differences in the patient characteristics capnograph waveform) and number of intubation such as age, gender, ASA physical status, BMI and attempts. In addition, the nature of optimisation Mallampati grades between the two groups as shown maneuvers done such as the use of a gum elastic in Table 1.

M.E.J. ANESTH 23 (1), 2015 46 J.Su Min Ooi et. al

Table 1 Table 2 Demographic and patient characteristics. Values expressed as Intubation characteristics. Values are expressed as Mean ± SD Mean ± SD or number (%) or numbers (%) C-MAC® MAC C-MAC® MAC (n = 45) (n = 45) (n=45) (n=45)

Age (years) 40.8 ± 15.1 41.6 ± 14.8 TTI ( seconds) 32.7 ± 6.8* 38.8 ± 8.9 Female 22 (48.9) 24 (53.3) 1 44 (97.8) 39 (86.7) Gender Male 23 (51.1) 21 (46.7) Intubation 2 1 (2.2) 4 (8.9) BMI (kg/m2) 26.2 ± 4.7 26.9 ± 3.7 attempts 3 0 2 (4.4) I 30 (66.7) 32 (71.1) ASA II 15 (33.3) 13 (28.9) None 38 (84.4)** 27 (60.0) I 25 (55.6) 22 (48.9) GEB 3 (6.7) 1 (2.2) Mallampati II 20 (44.4) 23 (51.1) ELM 3 (6.7) 14 (31.1)

Optimization ELM + GEB 1 (2.2) 3 (6.7) maneuvers The CL grade was significantly better in Group Second 0 0 ® 1 using the C-MAC producing a CL Grade I for assistant 67% of the study population compared to Group 2 Blade size 0 0 with only 38% of the sample having CL Grade I as change shown in FIGURE 1 (p <0.05). None of the patients in Group 1 had CL Grade IV whereas there was one Failed 0 2 (4.4) patient in Group 2 with CL grading of IV. The majority intubation of patients intubated with the MAC (56%) were found Lip trauma 0 1 (2.2) to have a CL Grade of II. The CL grading correlated well with the time to intubate (TTI) which was found Esophageal 0 0 Complications intubation to be significantly shorter in Group 1 with a mean time of 32.7 ± 6.8 vs. 38.8 ± 8.9 seconds for Group 2 (p = Dental 0 0 0.001) as shown in Table 2. trauma

The number of intubation attempts required SpO2<92% 0 0 in the two groups however was found to be not * p = 0.01, ** p <0.05. significantly different. The majority of patients in both

Fig. 1 Cormack and Lehane grades obtained in the two groups

* p <0.05 C-MAC® video-laryngoscope during manual inline stabilization 47 groups were able to be intubated in the first attempt. due to the presence of a built in software system that Optimisation maneuvers were found to be commonly initiates pre-warming of the optical system by the required for patients in Group 2 with 31% of them camera light12. requiring ELM and 7% required both ELM and GEB. Both groups had similar trends of MAP and HR In contrast 84% of Group 1 patients required no such over the 5-minute data collection period as shown in measures for successful tracheal intubation and only Figures 2 and 3. There were no recorded increases of 7% of patients needed the help of either a GEB or more than 20% of their respective baseline values of ELM (p =0.01). these two parameters. However at one point of time There were no reported complications in patients (T +1: one minute post intubation) Group 2 had a from Group 1. In Group 2, there were two cases of higher MAP of 93.5 ± 16.0 vs. 86.9 ± 10.4 mmHg for failed intubation and one case of minor lip trauma. Group 1(p<0.05). The rest of the data points were not However on statistical analysis these results were statistically different between the groups. not significant. Additionally, there was no occurrence of oxygen desaturation or esophageal intubation encountered on both the study arms. On a side note, Discussion we experienced fogging occurring in 11% of the cases on the C-MAC® arm but this was not severe enough to From this study, we found that using the C-MAC® impair the performance of the device. This was likely video-laryngoscope would be of benefit in patients with

Fig. 2 Changes in MAP during tracheal intubation. Values are expressed as Mean ± SD

* p <0.05

Fig. 3 Changes in mean heart rate following tracheal intubation. Values are expressed as Mean ± SD

M.E.J. ANESTH 23 (1), 2015 48 J.Su Min Ooi et. al

MILS due to its superiority in various aspects compared Using the C-MAC® also resulted in less need to the Macintosh laryngoscope. The C-MAC® was for additional optimization maneuvers compared to able to obtain better CL scores with a majority of the Macintosh Group. In our study we found that the them being CL Grade I without requiring additional Macintosh group required the use of ELM in 61% of optimization maneuvers. The Macintosh laryngoscope patients which was similarly seen in other studies as on the other hand had majority of CL II grades. Poor well9,10. The main reason behind this was because of laryngoscope views in the setting of MILS is a known the need for the intubator to obtain a best line of sight factor that will complicate intubation in this group of by aligning the intubation axis as has been discussed patients1. The limited neck movement from the MILS earlier. This however is not needed when using the ® made direct laryngoscopy become more challenging C-MAC as the vocal cords are readily visualized due 12 mainly due to difficulties in aligning the oral, to the blade mounted camera and 80° angle of view . During the course of our intubations, we did not require pharyngeal and laryngeal axis which was required for a change in blade size or use of second assistant for a successful tracheal intubation10. In order to overcome either of the groups and blade size #3 was used for this situation, having an indirect laryngoscope such both devices. as the C-MAC® with a camera mounted on the blade capturing live images and projecting them onto a video Patients from both groups had no significant screen dramatically reduces the line of sight required complications. Oxygenation was well maintained which in turn resulted in the much improved CL scores despite the variation in intubation times due to the as seen occurring in our study. This advantage was also process of preoxygenation that was conducted in our study. There may possibly have been hypoxemia noted by McElwain and Laffey where 35 % of patients if this crucial step was omitted highlighting once intubated with the C-MAC® had a CL Grade 1 vs. the again its importance especially in emergency airway Macintosh which produced CL Grade 1 in 19% of their management. The lack of significant airway trauma study sample10. in both groups as observed in our study arise possibly The mean difference of 18 seconds reduction because of the similar shape and structure of the two in TTI for the C-MAC® obtained in our study may laryngoscope blades that results in similar mechanical initially seem unremarkable at its face value especially forces and movements during intubation when using since the lengthened period of apnea for the Macintosh either of the devices. These similarities in the low group was not associated with desaturation or other occurrence of airway trauma was also observed in hemodynamic changes. However, in an emergency other studies as well10,13. airway management situation where the patient is There are a few limitations that can be identified at risk of hypoxia, any reduction in the TTI could in our study. Firstly, it is not possible to blind be a very crucial factor. In a similar study the TTI the investigator about the device being used. The recorded however was longer although insignificantly performance of the device is highly dependent on the for the C-MAC® [TTI of 27secs IQR 18, 47] vs. capabilities of the operator. However due to the overall Macintosh [TTI of 23 sec IQR 14, 47]10. A point to similar design of the two blades this would be quite note in that study was that the measurement of TTI unlikely to affect performance markedly. Nevertheless was not standardized. The investigators measured the all the intubations were carried out by a single TTI from the time the laryngoscope blade passed the investigator (SH) so that the variability in technique lips up till they visualized the ETT passing the vocal and operator bias could be minimized. The other issue cords and in cases where the ETT was not visualized, lies with the subjectivity of the CL scoring. Once again the appearance of capnograph tracing was taken as by utilizing a single operator we hope that this can be the end point. In our study the TTI was standardized overcome as well. and recorded for all intubations from the time the One important factor to keep in mind is that laryngoscope blade passed the lips till the appearance this study was conducted on adequately fasted, of the capnograph. pre-oxygenated patients with no difficult airway C-MAC® video-laryngoscope during manual inline stabilization 49 management anticipated. These patients underwent Conclusion elective surgery exclusively. Thus the situation would be expected to be very different in the post-trauma In conclusion, our study demonstrated that patients presenting to the emergency department or the C-MAC® video-laryngoscope was superior for operating room for emergency airway management. patients being intubated during manual inline neck Further well planned studies will be required to assess stabilization when compared to the standard Macintosh how the C-MAC® performs in these situations. laryngoscope.

M.E.J. ANESTH 23 (1), 2015 50 J.Su Min Ooi et. al

References

1. Manoach S, Paladino L: Manual In-Line Stabilisation For Acute laryngoscope, is more effective than the Macintosh laryngoscope Airway Management Of Suspected Cervical Spine Injury: Historical for tracheal intubation in patients with restricted neck movements: a Review And Current Questions. Ann Emerg Med; 50:236-45 2007. randomised comparitive study. Br J Anaesth; 2008, 100:544-8. 2. Committee on Trauma, American College of Surgeons. ATLS: 9. Malik MA, Maharaj CH, Harte BH, et al: Comparison of Advanced Trauma Life Support Program for Doctors (8th ed.). Macintosh, Trueview EVO2®, Glidescope®, and Airwayscope® Chicago: American College of Surgeons, 2008. laryngoscope use in patients with cervical spine immobilisation. Br 3. Calder I and Pearce A: Core Topics in Airway Management. J Anaesth; 2008, 101:723-30. 9780521111881. 2nd Edition. 248. Cambridge; Cambridge 10. Mcelwain J and Laffey JG: Comparison of the C-MAC®, Airtraq®, University Press, 2010. and Macintosh laryngoscopes in patients undergoing tracheal 4. Nolan JP, Wilson ME: Orotracheal intubation in patients with intubation with cervical spine immobilisation. Br J Anaesth; 2011, potential cervical spine injuries. An indication for the gum elastic 107(2):258-264. bougie. Anesthesia; 1993, 48:630-3. 11. Thierbach A, Piepho T: Emergency Airway Management. Tuttlingen, TM 5. Heath KJ: The effect of laryngoscopy of different cervical spine Germany: Endo Press 2009. immobilisation techniques. Anesthesia; 1994, 49:843-5. 12. Cavus MD, Kieckhaefer J, Doerges V, et al: The C-MAC® video- 6. Mort TC: Emergency tracheal intubation: complications associated laryngoscope: first experiences with a new device for video- with repeated laryngoscopy attempts. Anaesth Analg; 2004, 99:607- laryngoscopy guided intubation. Anaesth Analg; 2010, 110:473-7. 13. 13. Maharaj CH, Buckley E, Harte BH, et al: Endotracheal 7. SUN DA, WARRINER CB, PARSONS DG, et al: The Glidescope® intubation in patients with cervical spine immobilisation. A video-laryngoscope: randomised clinical trial in 200 patients. Br J comparison of Macintosh and Airtraq laryngoscope®. Br J Anaesth; 2005, 95:381-4. Anaesth; 2007, 107:53-9. 8. Enomoto Y, Asai T, Arai T, et al: Pentax-AWS®, a new video- Effects of Memantine on Pain in Patients with Complex Regional Pain Syndrome-A Retrospective Study

Mohammad-Hazem Ahmad-Sabry* and Gholamreza Shareghi**

Abstract

Introduction: Memantine was discovered in 1968 and is used as a treatment for Alzheimer’s disease. We evaluated the use of memantine to treat complex regional pain syndrome in this retrospective study. Patients and methods: 56 patients with CRPS, who were treated with trial of memantine for at least two months with 40mg QHS from 2007 until 2009. Results: 34 females and 22 male patients. Age-46.0+/-9.7 years. Number of years with CRPS-9.24 ± 5.7 years. Mean age-46.0+/-9.7 years. Memantine was started at 5 or 10mg QHS, before being increased by 5 or 10mg every 4-7 days, as tolerated, to a maximumdose of 40mg- 60mg, as tolerated. In all, 13 patients showed complete remission from CRPS with VAS 0 and the disappearance of allodynea for at least nine months after the use of memantine. In addition, 18 patients showed partial improvement of VAS and allodynea. Eight patients showed no improvement even after continuous use of memantine at a dose of 40mg QHS for two months. Seven patients could not take more than 5mg of memantine per day and had to stop it due to side effects. In terms of subjective improvement in short-term memory, nine patients showed much improvement, 14 patients showed some improvement, three patients showed no changes and one patient didnot answer the questionnaire. Regarding subjective feelings of a having better quality of life, 17 patient answered yes, three did not feel any changes, six could not give an answer and two did not fill out the questionnaire. Conclusions: Memantine is a promising option for the treatment of CRPS. A randomised controlled study is needed to evaluate its efficacy*.

Introduction

Bowsher (1991) found that neuropathic pain affected 25-50% of chronic pain patients in most pain clinics1. Richards (1967) reported the history of CRPS and its terminology2. Although previous descriptions were of single cases, Weir Mitchell, Morehouse and Keen (1864) first described the condition in full in the book “Gunshot Wounds and other Injuries of Nerves”. The

* MB, ChB MSc FRCPC MD ABPM. ** MD, PhD, DABIPP. department of Anesthesia and Surgical Intensive Care, Alexandria Faculty of Medicine, Alexandria University, Alexandria, Egypt, Advanced Pain Therapeutics of Knoxville, Knoxville, TN, USA. Correspondence author: Mohammad-Hazem I. Ahmad-Sabry MB, ChB MSc FRCPC MD ABPM, Alexandria Faculty of Medicine, Khartoum Square, Shalalat, Alexandria, EGYPT, 21111. Tel: +2016-271-8827 or +203-487-0509, Fax: +203-484- 2236. Email:[email protected]

51 M.E.J. ANESTH 23 (1), 2015 52 Ahmad-Sabry et. al authors described the condition as a burning pain, hallucinations, wild dreams, and psychotic ideations which Weir Mitchell later described as causalgiain were the frequent complaints while on memantine. 3 1872 in the Merck Manual for Health Professionals . The mean age of the participants was 46.0 ± Thomas and Grossberg explained the multimodal 9.7 years. The average number of years since the therapies and treatments used for Alzheimer’s disease, participants’ diagnoses of CRPSwas9.24 ± 5.7 years. 4 including memantine which was discovered 1968 . Memantine was started at 5 or 10mg QHS, before Siniset al. (2007) published his preliminary being increased by 5 or 10mg every 4-7 days, as report on the use of memantine in complex regional tolerated, up to a maximum level of 40mg, or 60mg pain syndrome with promising results5. Scheleyet al.’s if a better response was achieved with no side effects. (2007) experiment with memantine in patients with No changes were made in any of the patients’ current phantom limb pain, in combination with continuous poly-pharmacy treatment plans for CRPS during the brachial plexus blocks, showed a decrease in phantom experiment until the patients asked for to stop or pain up for to six months6. However, treating CRPS decrease their non-experimentalmedications. remains an off-label use for memantine. In this study, Before the starting memantine, all of our patients we evaluated the use of memantine in patients with had been taking a large variety of CRPS treatments complex regional pain syndrome. including: Several diagnostic/therapeutic sympathetic Patients and methods blocks (all patients), and/or continuous sympathetic blocks (if possible, some patients). We reviewed the charts of patients with diagnosed with CRPS that were treated in our clinic from 2007 Table 2 until 2009. In all, 56 CRPS patients (52 CRPS I, four Paired Samples Statistics CRPS II) were treated with memantine, including 34 Std. Error Std. N Mean females and 22 males. Retrospective, open label data Mean Deviation and results were gathered from treating our patients .20065 1.40456 49 8.1633 VASB during at least two years of follow-up after beginning 0.44134 3.08937 49 3.5510 VASA memantine. All patients consented to the off label use .29776 2.08432 49 7.7755 Burn B of memantine for the treatment of CRPS. .41853 2.92973 49 3.7143 Burn A

Table 1 Patient Demographics A number of months of proper physical therapy. Percentage Frequency Psychological therapy, if needed. 42.9 21 Male Extensive poly-pharmacy therapy: membrane 57.1 28 Female stabilisers, NSAIDS, anti-depressants, muscle 100.0 49 Total relaxants, alpha-2 agonists, alpha-1 antagonists, steroids, opioids and/or biphosphonats. Patients received a minimum dose of 40mg/day- A few had intrathecal delivery systems ([opioids/ 60mg/day, as long as a better response was achieved baclofen/clonidine/local anaesthetic] combinations). with no side effects. Seven patients were excluded from A few had epidural Dorsal Column Stimulation the study because they did not tolerate a memantine for pain modulation. dose of even 5 mg a day. Five of the seven patients had already been diagnosed with bipolar affective disorder A few had a combination of treatments five and at least two years prior to their CRPS diagnosis six. and were on antipsychotic medications and mood Each patient was encouraged to maximise stabilisers prior to receiving the memantine. Severe participation in daily living activities. Effects of Memantine on Pain in Patients with Complex Regional Pain Syndrome-A 53 Retrospective Study

All patients received a monthly evaluation for The mean VAS was 8.1633 (SD: 1.40456) before signs of changes in: the use of memantine and 3.5510 (SD: 3.08937) • Allodynia after the use of memantine, which was statistically • Burning pain significant atp <0.001. Those that responded positively • Short-term memory loss to the memantine did not ask for any increase in other • Anger level pain medications, and instead, asked for the dosages • Normalcy in everyday life of the other medications to be decreased. The mean To assess for burning pain, the following burning pain was 7.7755 (SD: 2.08432) before the assessments were used: use of memantine and 3.7143 (SD: 2.92973) after the use of memantine, which was statistically significant 1) Quantitative Visual Analog Scale (VAS) before and at p <0.000. Out of 49 patients, 13 (26.5%) showed after six months on the full dose of memantine. a complete disappearance of the pain, burning and 2) Quantifying the number of exaggerated burning allodynea. attacks per month on the primary CRPS extremity (patients voted to call these “a 10/10 Fire Storm”). Allodynia was assessed according to the Discussion following: 1) Percentage of decrease of the disgusting unpleasing Memantine is a drug with the ability to block feelingsrelated tosoft touch of the skin of the area NMDA receptors in the brain. Juliato Piovesan et al. affected by CRPS. (2008) suggested that memantine was much more 2) for the patients that enjoyed taking a shower prior potent inhibitor of central and peripheral sensitisation 7 to the development of CRPS,the time spent in the than were non-NMDA antagonists . Park et al. (2012) 8 shower from before and after six months on me- tested the drug on trigeminal pain in rats . Belozertseva mantine. and Bespalov (1998), as well as Popik and Kozela (1999), showed that memantine could attenuate the To assess for CRPS-related migraine headaches, a 9,10 quantitative decrease in the numberof migraine attacks/ tolerance to morphine in animal models . Davidson monthbefore and after six months on memantine was and Carlton’s (1998) experiment demonstrated that the examined. local use of memantine in attenuating pain in animal modelswas comparable to the use of dexmethorphan We followed the patients for at least two years and ketamine11. Eisenberg et al. (1998) failed to find after the start of the memantine. clinical benefits of using memantine for post-herpetic neuralgia when using doses of 10-20mg/day12. Results Nikolajsen et al. (2000), in a randomised cross-over study,could not find any difference when using 20mg/ In all, 56 patients were enrolled in the study, day of memantine after amputation or nerve injury and ultimately, seven were excluded, as they did not surgery13. Siniset al. (2007) published preliminary tolerate the memantine. Of the patients that were results in human patients with CRPSthat had good excluded, six were females and one was male. Five responsesto the medication when using 20 mg/day5. of the seven patients had been already diagnosed Scheleyet al. (2007) found a decrease in the medication with bipolar affective disorder at least two years prior requirements, as well as in the phantom limb pain, when to the CRPS diagnosis, and were on antipsychotic using memantine at doses of 20-30mg/day compared medications and mood stabilisers prior to beginning to those people that did not use the drug6. Grande et memantine. Severe hallucinations, wild dreams, and al. reported the use of memantine with small doses psychotic ideations were the frequent complaints of ketamine for opioid tolerant oncology patients, related to side effects while on memantine. Out of the demonstrating less opioid consumption at memantine 49 patients that continued to use memantine, 21 were doses of 20mg a day, and recommended more studies male (42.9%) and 27 were female (57.1%). be done in this area14. Thomas and Grossberg (2009)

M.E.J. ANESTH 23 (1), 2015 54 Ahmad-Sabry et. al recommended the use of memantine for Alzheimer’s the other studies, which might also contribute to the disease and other neuropsychiatric diseases due toits conflicting results. Our study was limited in the lack level of safety4. Olivan-Blázquezet al. (2014) found of randomisation with a controlled group that used promising results for memantine use at doses of 20g/ aplacebo. However, in our study, we compared the day when used for fibromyalgia15. same patient before and after the use of memantine, We used the memantine in our practice for using the patients’ data before the treatment as the resistant cases of CRPS and used largerdoses than control. We concluded that memantine is effective and what was recommended for use in patients with is a promising option for the treatment of CRPS. More Alzheimer’s disease (40mg/day), which could be why studies are needed using blinding, randomisation and other studies results did not show the same benefits. possibly placebo procedures. Also, in our study, the pathology was different than in

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Abdulkadir Yektaş*, Funda Gümüş*, Tolga Totoz*, Nurten Gül*, Kerem Erkalp* and Ayşin Alagöl*

Summary

Purpose: To prevent hemodynamic and respiratory changes that are likely to occur during cementation in partial hip prosthesis by prophylactic use of pheniramine maleate and dexamethasone. Methods and Materials: The study included 40 patients aged between 60 and 85 years with an American Society of Anesthesiologists (ASA) grade of II-III who underwent partial hip prosthesis. Just after spinal anesthesia, 4 mL normal saline was pushed in patients in Group S, whereas 45.5 mg pheniramine maleate and 8 mg dexamethasone mixture was pushed intravenously in a total volume of 4mL in patients in Group PD. Results: Amounts of atropine and adrenaline administered after cementation were significantly higher in Group S than in Group PD (P <0.05). There was a significant difference between SpO2 values before and after cementation in Group S; SpO2 value was lower after cementation (P <0.05) except for 1. min after cementation. SpO2 value increased 1 min after cementation (P = 0.031) Conclusion: Prophylactic use of pheniramine maleate and dexamethasone in partial hip prosthesis led to an increase in SpO2 value and a decrease in the utilization of adrenaline and atropine after cementation. Keywords: Methylmethacrylate, partial hip prosthesis, bone cement implantation syndrome, pheniramine maleate, dexamethasone.

Introduction

Partial hip arthroplasty is usually performed in elderly population in whom concomitant diseases may enhance the likelihood of a more progressive BCIS (Bone Cement Implantation Syndrome). BCIS is the most important cause of intraoperative morbidity and mortality in patients undergoing cemented hip arthroplasty, and rarely, hypoxia and confusion may be encountered in the postoperative period. Intraoperative mortality rate is 0.43 % for cemented partial hip prosthesis in patients with or without femur fracture1. Although the etiology and pathophysiology of BCIS have not been understood clearly, few mechanisms including monomer-mediated model, embolic model, histamine release and hypersensitivity, complement activation, and multimodal model

* anesthesiology and Reanimation Clinic, Bagcilar Training and Research Hospital, Istanbul, TURKEY. Corresponding author: Abdulkadir Yektas. Address: Bagcilar Egitim ve Arastirma Hastanesi Anesteziyoloji ve Reanimasyon Klinigi 34200 Bagcilar, Istanbul, TURKEY, Tel: + 90 505 388 18 84, Fax: + 90 212 488 69 63. E-mail: [email protected]

55 M.E.J. ANESTH 23 (1), 2015 56 A.Yektas et. al have been suggested. In a study, blockade of histamine operated being on top, and an 18 G intravenous canula receptors by clemastine and cimetidine (H1 and H2 was placed into a pheripherial vein in the dorsal aspect antagonists) was reported to have protective effects3. of the hand opposite to the surgery side and 0.9% NaCl was administreted at a rate of 10 mL kg-1 h-1 for first Pheniramine maleate is an H1 receptor antagonist. hour and than 5 mL kg-1 h-1. In order to obtain blood H1 receptor antagonists have been successfully used before drug infusion to prevent and for acute treatment sample for blood gas analysis, an intra-arterial catheter of type I hypersensitivity9. Dexamethasone is a was inserted into the radial artery of the arm on the synthetic glucocorticosteroid. In animal studies, this surgery side via a 20-gauge intravenous catheter, and it glucocorticosteroid has been demonstrated to inhibit was washed with heparinized fluid and closed using a airway eosinophilia in the presence of antigen by three-way tap. The patients were administrated oxygen inhibiting interleukin-5 synthesis and to be successfully at a rate of 2 L/min through a free oxygen mask which used for the prophylaxis of type I hypersensitivity was fixed hole in any side of the free oxygen mask in 10,11 reaction . which the free end of end-tidal CO2 (ET-CO2) line. All patients underwent electrocardiography, non-invasive The aim of the present study is to assess the arterial blood pressure measurement, peripheral pulse effect of pheniramine maleate and dexamethasone on oximetry and end-tidal CO monitoring. All patients incidence of hypotension, bradycardia and hypercarbia 2 underwent spinal anesthesia. Patients in both groups associated with BCIS. were positioned laterally with the leg that would be operated being on top, and spinal anesthesia was Methods and Materials performed via a 27-gauge Quincke-type needle after performing cutaneous-subcutaneous infiltration After obtaining approval from the Ethical anesthesia using 2 mL of 2% lidocaine through L4- Committee of Bağcılar Training and Research L5 space. After observing cerebrospinal fluid (CSF) Hospital and written informed consents of the patients, outflow, 1 mL (5 mg) isobaric bupivacaine and 25 µg 40 patients aged between 60 and 85 years with an (0.5 mL) fentanyl were administered in a total volume American Society of Anesthesiologists (ASA) grade of 1.5 mL. Spinal anesthesia was performed by a of II-III who underwent partial hip prosthesis with specialist in both groups. The patients in whom spinal cement due to femur neck fracture under spinal anesthesia was unsuccessful three times were excluded anesthesia were included in the study. The present from the study. Then the patient were randomly divided study was designed as a prospective, randomized and into the following two groups using sealed envelopes: double-blinded study. 1) Group S (n = 20) patients were administrated 4 mL Data of the patients regarding age, height, weight, of normal saline, 2) Group PD (n = 20) patients were gender, concomitant diseases, medications, smoking administrated 45.5 mg pheniramine maleate and 8 mg status, ASA classification and surgery duration of dexamethasone. Prior to spinal anesthesia, basal values surgery were recorded. of arterial blood pressure, heart rate, oxygen saturation by pulse oximeter (SpO ), end-tidal CO (ETCO ), and Patients with allergic diseases, those using anti- 2 2 2 allergic medications or corticosteroids, who have blood gases were recorded. Pre-prepared syringes were deep venous thrombosis and lower extremity venous used; thus, both the anesthesiologist and the patient insufficiency, those with cardiac disease likely to cause were blinded to the content. atrial fibrillation or thromboembolism, or paraplegia- Cephazoline sodium 1 g was administered hemiplegia, who were immobile before fracture (i.e., iv approximately 30 to 60 min prior to surgery for bedridden patients), those with previous cardiac prophylaxis. surgery, and those having a contraindication for Values of arterial blood pressure, heart rate, regional anesthesia were excluded from the study. SpO2, end-tidal CO2, and blood gases were recorded The patients did not receive any premedication. for all patients prior to surgical procedure and at 10- The patients were positioned with the hip that would be min intervals until the first minute before cementation. Dexamethasone & pheniramine in hip prosthesis 57

Amount of bleeding, amount of crystalloid of bleeding throughout surgery before and after administered by IV route, and, if used, doses of cementation, amount of crystalloid, amount of atropine atropine and adrenaline were also recorded until the and adrenaline were compared between the groups by first minute before cementation. Those parameters an independent-t test.. Data analyses were performed were recorded at 1-min intervals in the first 5 min after using the Statistical Package for the Social Sciences cementation and then every 5 minutes. Measurements (SPSS, Inc. Chicago, IL, USA) version 11.5. A P value were discontinued at the 25th min after cementation. <0.05 was considered statistically significant. Amount of administered crystalloid throughout the surgical procedure and amount of bleeding were Results recorded. Arterial blood gases were analyzed before spinal anesthesia, just before cementation, and at the Distributions of age, weight, height, type of 10th and 25th min after cementation. surgery, duration of surgery, duration of cementation, A 5 µg adrenalin was pushed via venous route ASA grades and gender in the study groups are in the following conditions: 1) a decrease in mean presented in Table 1. There were no statistically blood pressure more than 30% of the initial value until significant differences between the groups in terms of cementation, 2) after cementation, a more than 30% age, weight, height, type of surgery, duration of surgery, decrease in the blood pressure value measured before duration of cementation, ASA grade and gender. cementation. In case of a decrease in heart rate below 50 beats/min, 0.5 mg atropine was injected. Patients Table 1 in whom amount of bleeding before cementation Distribution of age, weight, height, type of surgery, duration exceeded 400 mL were excluded from the study of surgery, duration of cementation, the American Society of (bleeding before cementation exceeded 400 mL in any Anesthesiologists grades and gender in the study groups. Data of the patients), and blood loss was replaced by normal are presented as mean ± SD saline. Group S Group PD P When the surgical procedure was completed and (n = 20) (n = 20) following postoperative observation, patients with a modified Aldrete score of ≥9 were transferred to the Age (years) 80.50 ± 7.05 76.85 ± 9.31 0.198 clinic. Weight (kg) 70.75 ± 11.14 70.60 ± 10.45 0.989

Statistical Analysis Height (cm) 168.45 ± 8.40 166.35 ± 5.65 0.462

Duration of Based on a preliminary study performed in 10 79.30 ± 27.29 84.55 ± 18.01 0.579 patients, we estimated that a sample size of 20 patients surgery (min) in each group would be sufficient with a 5% error and Duration of a statistical power of 80% assuming that the mean cementation 61.60 ± 22.87 64.35 ± 10.55 0.968 (min) arterial pressure on the 25th min would be 92 ± 15 mmHg in Group PD and 85 ± 15 mmHg in Group S. ASA (II/III) 14/6 13/7 0.708 Descriptive statistics of data were expressed as Gender 11/9 12/8 0.061 mean ± standard deviation. Normal distribution of (F/M) variables was tested by Kolmogorov Smirnov test. Comparison of data regarding age, height, weight, SD: standard deviation; ASA: the American Society of Anesthesiologists; F: female; M: male gender, type of surgery, duration of surgery, time elapsed from spinal anesthesia to cementation, and ASA grades were performed using the Chi square Doses of atropine and adrenaline and the amounts test. Heart rate, arterial blood pressure values, SpO2, of intravenous fluid and bleeding in the study groups end-tidal CO2 and blood gas measurements, amount are presented in Table 2. The dose of adrenaline used

M.E.J. ANESTH 23 (1), 2015 58 A.Yektas et. al

Table 2 Distribution of amounts of atropine, adrenaline, and intravenous fluid, and the amount of bleeding in the study groups. Numbers are presented as mean ± SD. Group S Group PD P (n = 20) (n = 20) Adrenaline after cementation (µg) 4.50 ± 11.34 0.75 ± 1.83 0.022 Atropine after cementation (mg) 0.25 ± 0.91 0.00 ± 0.00 0.014 Intravenous crystalloid before cementation (mL) 560.50 ± 206.33 480.00 ± 176.51 0.345 Intravenous crystalloid administered throughout 890.00 ± 282.65 827.50 ± 181.71 0.274 surgical procedure (mL) Amount of bleeding before cementation (mL) 184.25 ± 96.99 158.75 ± 77.01 0.243 Total amount of bleeding (mL) 228.75 ± 118.73 211.00 ± 77.50 0.059 SD: standard deviation

after cementation was significantly higher in Group S pH (P = 0.102), PaCO2 (P = 0.063), PaO2 (P = 0.175) and th than in Group PD (P = 0.022). The dose of atropine end-tidal CO2 values (P = 0.448) and 25 min pH (P = used after cementation was significantly higher in 0.193), PaCO2 (P = 0.186), PaO2 (P = 0.084) and end-

Group S than in Group PD (P = 0.014). tidal CO2 values (P = 0.054) min after cementation. Comparison of the study groups in terms of One patient in Group S developed cardiopulmonary systolic diastolic and mean arterial pressures, heart rate arrest at the 1st min after cementation and accepted as dead after performing cardiopulmonary resuscitation and SpO2 before and after cementation are presented in Table 3. There were no statistically significant (CPR) for 45 min. Blood gas values and end-tidal CO2 differences between the groups in terms of systolic/ values of this case was not consistent with pulmonary diastolic and mean arterial pressure, heart rate and embolus.

SpO2. Heart rate increased significantly 2 min after All patients were transferred to the clinic after cementation in Group PD when compared to before (p observing postoperatively in recovery room for 2 = 0.008) (Table 3). hours and then all patients were discharged. None of the patients developed postoperative hypoxia or confusion. In Group S, SpO2 increased 1 min after cementation (P = 0.031), and were significantly lower Discussion at the rest of all times when compared to the value before cementation (P = 0.003, P = 0.003, P <0.001, Respiratory and cardiovascular changes during P = 0.003, P = 0.001, P = 0.001, P = 0.001, P = 0.004, partial hip replacement seriously affect the prognosis respectively) (Table 3). of patients. These changes exist in a wide spectrum of There were no significant differences between disorders ranging from temporary hypoxia to cardiac 12,13 Group S and Group PD in terms of PH (P = 0.168), rhythm disorders and even cardiac arrest . partial arterial carbon dioxide pressure (P CO ) (P = A 2 Several mechanisms have been suggested in 0.067), partial arterial oxygen pressure (P O ) (P = A 2 the etiology and pathophysiology of BCIS including 0.056) and end-tidal CO values before cementation 2 monomer-mediated model, embolic model, histamine and at the 10th (P = 0.067) and 25th (P = 0.152) min release and hypersensitivity, complement activation, after cementation. and multimodal model2. A study has shown that In addition, there were no significant differences implantation of methacrylic bone cement into the femur in both groups in terms of pH, PaCO2, PaO2 and end- may increase plasma histamine level by more than 1 th tidal CO2 values before cementation, and at the 10 min ng/mL. Temperate histamine release may cause severe, Dexamethasone & pheniramine in hip prosthesis 59 25.min 96.0 ± 2.6 70.6 ± 20.8 68.4 ± 12.1 92.4 ± 25.3 85.2 ± 19.9 81.5 ± 27.5 87.1 ± 17.5 133.6 ± 26.1 131.6 ± 22.2 92.7 ± 22.0* 20.min 95.5 ± 3.3 69.1 ± 11.6 89.9 ± 18.5 84.4 ± 13.9 81.2 ± 27.2 87.41 ± 7.9 135.1 ± 24.1 131.6 ± 23.9 72.2 ± 19.01 92.5 ± 21.9* 15.min aline; Group; PD : Group; S : aline; O xygen S aturation; 93.4 ± 9.8 70.7 ± 11.8 93.2 ± 26.1 90.8 ± 14.9 72.9 ± 21.4 79.7 ± 25.1 88.4 ± 20.3 130.2 ± 28.4 134.6 ± 23.5 92.2 ± 21.9* 10.min 95.6 ± 2.9 91.8 ± 26.3 87.7 ± 15.8 74.2 ± 21.4 70.9 ± 12.4 75.1 ± 25.7 87.3 ± 17.9 135.3 ± 24.3 132.8 ± 20.3 92.7 ± 21.9* S p O 2: P eripheral 5.min 95.9 ± 2.8 89.5 ± 20.6 81.9 ± 15.8 74.0 ± 20.1 68.0 ± 13.6 74.4 ± 23.1 87.6 ± 19.3 119.9 ± 34.1 119.9 131.5 ± 25.5 92.7 ± 21.9* 4.min 95.8 ± 2.8 91.6 ± 27.2 79.5 ± 16.2 74.3 ± 23.1 67.9 ± 15.4 74.7 ± 24.6 88.3 ± 18.7 P ressure; HR : H eart R ate; 130.3 ± 28.3 122.1 ± 22.7 92.2 ± 21.9* Table 3 Table A rterial 3.min 96.0 ± 3.0 87.9 ± 25.3 78.9 ± 17.4 74.3 ± 21.8 67.8 ± 13.6 75.7 ± 24.0 86.9 ± 22.2 127.2 ± 25.9 121.1 ± 22.9 92.1 ± 21.9* 2.min 95.9 ± 3.2 88.3 ± 20.7 81.7 ± 16.9 73.6 ± 17.4 67.0 ± 14.3 76.1 ± 23.9 P ressure; MAP : M ean 118.8 ± 27.6 118.8 92.6 ± 21.9* 128.2 ± 24.4 95.1 ± 24.5* >0.05) A rterial 1.min 97.8 ± 2.8 96.3 ± 2.9 83.1 ± 22.1 81.7 ± 16.9 69.9 ± 17.7 69.8 ± 15.6 79.4 ± 18.9 87.1 ± 21.8 127.2 ± 28.3 124.0 ± 26.0 Systolic, Diastolic and Mean Arterial Pressure, Heart Rate and Peripheral Oxygen Saturation (Mean ± SD) Arterial Pressure, Systolic, Diastolic and Mean Before C Before 97.5 ± 2.8 97.2 ± 2.4 93.8 ± 20.7 85.4 ± 21.8 76.4 ± 21.0 71.8 ± 16.5 76.4 ± 13.0 84.4 ± 18.7 137.4 ± 27.0 125.6 ± 22.1 P ressure; DAP : D iastolic S S S S S PD PD PD PD PD Group A rterial 2 HR SAP DAP SpO MAP <0.05 when compared with Before C ementation. SAP : S ystolic pheniramine maleate-dexamethasone; Before C : cementation. between groups ( P T here is no statistical difference * P

M.E.J. ANESTH 23 (1), 2015 60 A.Yektas et. al sometimes fatal, cardiovascular complications in very study, there were no significant differences between old patients in case they have signs of hypovolemia or the groups in terms of the amounts of crystalloid cardiac diseases3. and bleeding before cementation and throughout the Cardiac problems defined to date have been surgical procedure. mostly about wall motion and rhythm disorders, with The amount of adrenaline administered in Group no remarkable changes in heart rate14,15. We also found S was significantly higher than that administered in no significant difference between heart rates before Group PD; however, as blood pressure was measured and after cementation; heart rate at the 2nd min after at specific time intervals, such variations in blood cementation was higher than before cementation only pressure had no impact on the statistical outcomes. in Group PD. In Group S, as compared with before A patient in Group S developed hypotensive nd cementation, heart rate decreased by 0.40% at the 2 bradycardic arrest at the 1st min after cementation, rd th min, 1% at the 3 min, 2.5% at the 4 min and 3.1% at which was not responsive to CPR. There were no the 5th min, but thereafter returned to the normal values. significant differences in PaO2, pH, PaCO2 and end- The dose of atropine administered was significantly tidal CO2 values of this patient before cementation and higher in Group S than in Group PD. However, as during CPR performed after cementation; this ruled heart rate was recorded with 5-min intervals, such out the possibility of massive embolism. decrements in HR were not reflected in the statistical In the present study, despite oxygen provided analysis. In Group PD, an increase in the heart rate was through a free oxygen mask at a rate of 2 L/min in observed by 12.73% at the 2nd min (P <0.05), 3% at the both groups, there was a significant difference between 3rd min, 4.62% at the 4th min and 3.79% at the 5th min. SpO2 values before and after cementation in Group S. Potential causes of hypotension, one of the An increase by 0.25% at the 1st min after cementation parameters of BCIS, include histamine release and and a decrease by 7.1% at the 2nd min after cementation type I hypersensitivity reaction, or hemodynamic were observed, and this decrease continued until the impairment caused by pulmonary air or by fat end of surgery in the same manner. Various studies embolism and reflex mechanisms responsive to have demonstrated hypoxia development during this16,17. An experimental study has demonstrated that hip and knee arthroplasty24,25. This has been thought methylmethacrylate monomers influence intracellular to result from pulmonary embolism or pulmonary and extracellular calcium mobilization, resulting vasoconstriction due to cement toxicity21,26. In the in direct relaxation in venous and arterial smooth present study, there was no significant difference muscles18,19. Nevertheless, this hypothesis has not between SpO2 values before and after cementation been verified by in vivo animal experiments and it in Group PD; this suggests that dexamethasone and has been determined that plasma methylmethacrylate pheniramine maleate prevented bronchospasm resulted concentration after cemented hip arthroplasty is lower from pulmonary vasoconstriction caused by cement than the concentration that is likely to cause pulmonary toxicity and pulmonary embolism. Studies performed or cardiovascular effects20,21. A clinical study evaluating after observation of intraoperative deaths occurred plasma concentrations revealed that maximum levels during cemented arthroplasty have demonstrated the of serum methylmethacrylate was measured 30 s after presence of bone marrow embolism, fat embolism and cementation and this was thought to cause a decrease bone embolism and methylmethacrylate particles in the in arterial blood pressure20. Another study compared lungs27,28,29. Medulla residue may cause embolism in the non-cemented hip arthroplasty with cemented hip lungs, heart or paradoxically in the brain and coronary arthroplasty using transesophageal echocardiography arteries30,31. This suggests that hypotension occurs and demonstrated a higher embolic load in the cemented due to characteristic hypoxia and right ventricular hip arthroplasty group22. The authors concluded dysfunction as the consequence of pulmonary that, embolism might also cause hypotension due to embolism21. However, a definite correlation could not increase in pulmonary arterial pressure together with be established in the literature between the degree of decrease in right ventricular function23. In the present embolism detected by performing transesophageal Dexamethasone & pheniramine in hip prosthesis 61 echocardiography and the severity of hypoxia22. levels were not studied in the present study. We It has been reported that blood cement monomer thought that complement activation might have been levels do not reach high concentrations that likely can prevented by dexamethasone, due to the less decrease cause toxicity in human32, in which both mechanisms in hemodynamic values-although no statistically are considered to play a role. Among anaphylatoxins, difference was found, but clinically important-1 min C3a and C5a are potent mediators that lead to after cementation and lack of desaturation in Group PD vasoconstriction and bronchoconstriction33. The In conclusion, the dose of adrenaline and atropine levels of C3a and C5a have been observed to increase used after cementation was significantly lower and, in cemented hemiarthoplasties by complement SpO2 values were stable after cementation in Group PD; 33 activation . In human studies, high dose (2g) on the other hand, in Group S, SpO2 values decreased methylprednisolone have been demonstrated to reduce after cementation, except for 1. min after cementation. hypoxia and complement activation. The decreases SpO2 value increased 1 min after cementation. in anaphylatoxin release and oxygen saturation are This suggests that prophylactic administration reduced by methylprednisolone33. However, whether of pheniramine maleate and dexamethasone may methylmethacrylate particles or embolus material minimize the clinical symptoms of BCIS. causes complement activation is not clear. Complement

M.E.J. ANESTH 23 (1), 2015 62 A.Yektas et. al

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Sevitt S: Fat embolism in patients with fractured hips. Br Med J; of airways inflammation by dexamethasone is followed by reduced 1972, 2:257-262. bronchial hyperreactivity in BP2 mice. Clin Exp Allergy; 1996, 28. Byrick RJ, Mullen JB, Mazer CD, Guest CB: Transpulmonary 26:971-979. systemic fat embolism. Studies in mongrel dogs after cemented 11. Fürll M, Wujanz G, Strauch A, Drechsel J: Anaphylactic shock in arthroplasty. Am J Respir Crit Care Med; 1994, 150:1416-1422. swine. 5. Studies on the prophylactic effect of dexamethasone and 29. Wheelwright EF, Byrick RJ, Wigglesworth DF, Kay JC, Wong PY, dexamethasone-metapyrine combination (in German with English Mullen JB, Waddell JP: Hypotension during cemented arthroplasty. abstract). Arch Exp Veterinarmed; 1986, 40:445-452. Relationship to cardiac output and fat embolism. J Bone Joint Surg 12. Fallon KM, Fuller JG, Morley-Forster P: Fat embolization and Br; 1993, 75:715-723. fatal cardiac arrest during hip arthroplasty with methylmethacrylate. 30. Lafont ND, Kalonji MK, Barre J, Guillaume C, Boogaerts Can J Anaesth; 2001, 48:626-629. JG: Clinical features and echocardiography of embolism during 13. Duncan JA: Intra-operative collapse or death related to the use of cemented hip arthroplasty. Can J Anaesth; 1997, 44:112-117. acrylic cement in hip surgery. Anaesthesia; 1989, 44:149-153. 31. Ries MD, Lynch F, Rauscher LA, Richman J, Mick C, Gomez M: 14. Propst JW, Siegel LC, Schnittger I, Foppiano L, Goodman SB, Pulmonary function during and after total hip replacement. Findings Brock-Utne JG: Segmental wall motion abnormalities in patients in patients who have insertion of a femoral component with and undergoing total hip replacement: correlations with intraoperative without cement. J Bone Joint Surg Am; 1993, 75:581-587. events. Anesth Analg; 1993, 77:743-749. 32. Bengtson A, Larsson M, Gammer W, Heideman M: Anaphylatoxin 15. Vazeery AK, Skeie S, Anda O: Changes in cardiac output and release in association with methylmethacrylate fixation of hip systemic arterial pressure after insertion of acrylic cement during prostheses. J Bone Joint Surg Am; 1987, 69:46-49. trimetaphan, sodium nitroprusside and glycerol trinitrate-induced 33. Gammer W, Bengtson A, Heideman M: Inhibition of complement hypotension. A comparison with changes during normotension. Br activation by high-dose corticosteroids in total hip arthroplasty. Clin J Anaesth; 1983, 55:783-790. Orthop Relat Res; 1998, 236:205-209. 16. Rinecker H: New clinico-pathophysiological studies on the bone Effect of preoperative oral pregabalin on postoperative pain after mastectomy

Mardhiah Sarah Harnani Mansor and Choy Yin Choy**

Abstract

Background: This was a randomized, double-blinded clinical trial to study the effects of a single oral dose of pregabalin 150 mg in postoperative pain management after mastectomy. Methods: Design: forty nine patients ASA I or II, aged between 20-60 years, scheduled for mastectomy with or without axillary lymph nodes dissection (ALND) were recruited into this study. They were randomized into two groups, placebo (n = 24) or pregabalin (n = 25) receiving either oral pregabalin 150 mg or placebo when called to operation theatre (OT). The assessment of pain score were performed at recovery, 2, 4, 6 and 24 hours postoperatively at rest and on movement, using the verbal numeral rating score (VNRS). Results: VNRS scores for pain at rest were lower in the pregabalin group at 2 (p = 0.024), 4 (p = 0.006) and 6 (p = 0.003) hours postoperatively, and also at 4 (p = 0.005) and 6 (p = 0.016) hours postoperatively on movement compared to the placebo group. Incidences of dizziness were common, however, side effects such as nausea and vomiting, headache, somnolence and visual disturbance were low and comparable in both groups. Conclusion: a single dose of 150 mg pregabalin given preoperatively compared to placebo significantly reduced postoperative pain scores after mastectomy. Keywords: pregabalin, postoperative pain, mastectomy, opioid.

Introduction

Preventive analgesia is a treatment approach that aims to reduce the development of central sensitization in the postoperative period by reducing peripheral nociceptive input into the central nervous system, thus reducing postoperative pain and analgesics consumption. The concept of preventive analgesia includes multimodal antinociceptive techniques with analgesics that exceed the expected duration of action and also attenuate peripheral or central hypersensitivity2,3,4. Effective methods include systemic NSAIDs, single dose epidural analgesia, systemic NMDA receptor antagonists, systemic opioids and local anaesthetic infiltration. Gabapentin and pregabalin have been proven to be effective medications in serving these purposes. Pregabalin was originally developed as an antiepileptic drug with an improved pharmacological profile when compared to that of its predecessor gabapentin5. Although gabapentin and pregabalin were first identified as useful in the treatment for neuropathic pain, recent reviews showed that they reduced postoperative acute pain and analgesic consumption as well. Gabapentin has been shown to be an effective analgesic for tonsillectomy, mastectomy and knee arthroplasty6,7,8,

* Department of Anaesthesiology and Intensive Care, Universiti Kebangsaan Malaysia Medical Centre. Corresponding author: Choy Yin Choy, e-mail: [email protected]

63 M.E.J. ANESTH 23 (1), 2015 64 Mardhiah Sarah Harnani Mansor and Choy Yin Choy however pregabalin appears to be a better option when medication use in the study, patients with chronic pain compared with gabapentin as it has better analgesic or on daily intake of analgesic and impaired kidney efficacy and an improved pharmacokinetic 9profile . function (creatinine level >80 µmol/L). Patients were

Pregabalin and gabapentin bind to the α2δ sub-unit randomized using computer-generated randomized of pre-synaptic voltage-gated calcium channels in numbers to receive either pregabalin (Lyrica®) or the spinal cord and brain1,2,3,4,5. By altering calcium placebo (vitamin B complex). Information regarding currents, it reduces or modulates the release of several the study and the verbal numerical rating scale (VNRS) excitatory neurotransmitters including glutamate, range from 0 – 10 was explained to the patients. On the norepinephrine, substance P and calcitonin gene- day of surgery, all patients were given premedication related peptide, producing inhibitory modulation of of oral midazolam 7.5 mg with either oral pregabalin ‘over-excited’ neurons and returning them to a normal 150 mg (in 2 tablets) or oral vitamin B complex (in 2 state. tablets) one hour before being sent to operating room. One advantage of pregabalin in clinical use is Patients were instructed to close their eyes before that it has higher bioavailability when giving orally given the test drug to swallow. with linear pharmacokinetics property compared to In the operation theatre, basic monitoring gabapentin. It is rapidly and extensively absorbed after included electrocardiogram (ECG), oxygen saturation oral dosing in the fasting state with maximal plasma (SpO2) and non invasive blood pressure (NIBP). concentration occurring within 1 hour after single or General anesthesia was induced with IV propofol multiple doses9. Absorption of gabapentin is limited 1.5 – 2.5 mg/kg and IV fentanyl. After the patient by saturable, active and dose dependent transport in was adequately anaesthetized, a supraglottic airway gastrointestinal tract but absorption of pregabalin is not device was inserted. Anaesthesia was maintained with saturable, resulting in a linear pharmacokinetic profile sevoflurane in 50% O2 / 50% air mixture maintaining with bioavalability exceeding 90% and independent minimum alveolar concentration (MAC) of 0.8–1.0. 3,5 of dose . In recent years, pregabalin has been Intraoperatively, patients were given IV morphine 0.1– introduced as an adjunct in multimodal management 0.2 mg/kg as an analgesic. Additional IV parecoxib 40 of postoperative analgesia in many studies because of mg was given at the time of skin suturing. Adequate 10-15 its favourable pharmacokinetics . local anesthetic infiltration of levobupivacaine up to 2 The aim of this study was to compare the effect mg/kg was given by the surgeon at the incision site. of single-dose 150 mg oral pregabalin to placebo on Pain was assessed by independent observer in postoperative pain after mastectomy for breast cancer. the recovery area, 2, 4, 6 and 24 hours postoperatively using the VNRS at rest and on movement. In the Methods ward, all patients received oral etoricoxib 120 mg daily with oral paracetamol 1g every 6 hours as a This randomized, double-blinded clinical trial standard analgesic. If the pain score was rated 5 or was done following approval of the Dissertation more, intravenous tramadol 50 mg was given as a Committee of the Department of Anaesthesiology rescue medication. Any incidence of side effects such and Intensive Care, Universiti Kebangsaan Malaysia as nausea, vomiting, headache, somnolence, dizziness Medical Centre (UKMMC) and the Research Ethics and visual disturbance were documented. Committee of UKMMC (Research No. FF–444-2012). Based on previous study13, with the power of Forty nine, ASA I or II patients, aged 20 to 60 years 0.8, alpha value of 0.05 and dropout rate of 10%, the who were scheduled for elective mastectomy with or sample size calculated was 60. Statistical analysis without axillary lymph nodes dissection (ALND) were and calculations was performed using SPSS for included in the study. Informed and written consent Windows Version 12.0. VNRS pain score and amount was obtained from all patients during preoperative of intraoperative morphine used were analysed using anaesthetic assessment a day before surgery. Mann-Whitney U-test. Categorical variables such Exclusion criteria included, known contraindication to as number of patients needed rescue analgesic and Effect of preoperative oral pregabalin on postoperative pain after mastectomy 65

Table 1 Demographic data values are expressed as mean± SD or number(percentage)

Placebo Pregabalin

(n=24) (n=25)

Age 52.0 ± 8.4 51.5 ± 9.6

Weight (kg) 62.4 ± 8.0 60.2 ± 5.0

Height (cm) 156.9 ± 3.0 156.2 ± 2.8

Malay 12 (50) 17 (68) Race Chinese 8 (33.3) 5 (20) Indian 4 (16.7) 3 (12)

I 12 (50) 15 (60) ASA II 12 (50) 10 (40)

Mastectomy 6 (25) 6 (24) Type of operation Mastectomy with ALND 18 (75) 19 (76)

* p value = 0.024. “ p value = 0.006. ‘ p value = 0.003. incidence of side effects were evaluated with X2 test or 25 patients were in the pregabalin group. There were Fischer’s exact test. A p value of <0.05 was considered no statistical differences with regards to age, weight, statistically significant. height, race, ASA and type of operation (Table 1). Figure 1 showed VNRS at rest in pregabalin Results group compared to placebo. There were statistically significant differences at 2, 4 and 6 hours Forty nine patients were recruited in this study postoperatively. in which 24 patients were in the placebo group and Figure 2 showed VNRS on movement in

Fig. 1 postoperative VNRS. values are expressed as mea

* p value = 0.024. “ p value = 0.006. ‘ p value = 0.003.

M.E.J. ANESTH 23 (1), 2015 66 Mardhiah Sarah Harnani Mansor and Choy Yin Choy

Fig. 2 postoperative VNRS. values are expressed as mean

* p value = 0.005. “ p value = 0.016.

pregabalin group compared to placebo. There were Discussion statistically significant differences at 4 and 6 hours postoperatively. In this current study, we found that preoperative There was no statistically significant difference single dose of oral pregabalin 150 mg was effective in the mean intraoperative morphine consumption in in reducing both the resting and on movement both placebo group and pregabalin group. postoperative pain in patients undergoing mastectomy with or without ALND. Spreng et al, showed a Six patients from the placebo group and three reduction of postoperative pain at rest and morphine patients in the pregabalin group needed tramadol as consumption from 4 up to 24 hours postoperatively a rescue drug postoperatively, however the difference after lumbar discectomy with a single dose of oral was statistically not significant. There was no pregabalin 150 mg10. In another study, Agarwal et difference in postoperative oral analgesic consumption al used a single dose of oral pregabalin 150 mg and for both groups. effectively reduced postoperative pain and fentanyl Adverse effects postoperatively in both groups, consumption in patients undergoing laparoscopic which was statistically not significant are presented in cholecystectomy up to 24 hours11. Jokela et al used table 2. oral pregabalin 150 mg preoperative for day-case There was no documented incidence of gynecological laparoscopic surgery and had better somnolence or visual disturbances in any of the analgesia during the early recovery but not sustained up patients. to 24 hours12. A study by Kim et al where mastectomy patients received oral pregabalin 75 mg twice a day Table 2 showed that there was reduced postoperative pain and Incidence of side effects analgesic consumption respectively13. That study also Placebo Pregabalin showed the ability of divided doses of pregabalin to n = 24 n = 25 reduced pain after 48 hours up to 1 week after surgery. Nausea/vomiting 17 19 Ittichaikulthol et al used a higher dose of oral Headache 8 7 pregabalin 300 mg preoperatively and showed Dizziness 9 16 reduction of pain scores and morphine consumption Effect of preoperative oral pregabalin on postoperative pain after mastectomy 67 for abdominal hysterectomy with or without salphingo- are associated with increased frequencies of side oophorectomy up to 24 hours post operatively14. effects. The common adverse effects of pregabalin are However a study by Paech et al using a lower dose nausea and vomiting, visual disturbances, headache, of oral pregabalin 100 mg preoperatively was unable dizziness and somnolence. Most of the studies showed to reduce acute pain or improve recovery after minor no significant adverse effects when a lower dose of gynecological surgery15. Most of these studies also pregabalin was used10-14. Nausea and vomiting were showed comparable rescue analgesic needed similar the common side effects in the current study followed with the current study. by headache and dizziness. There were no documented side effects of somnolence or visual disturbances. A meta analysis on efficacy of pregabalin in acute postoperative pain by Zhang et al concluded There are a few limitations in study. The pain that postoperative opioid consumption and opioid score was assessed immediately in the postoperative period in the recovery area which makes it difficult to related side effects were reduced but pain scores were assess the effects of pregabalin at that point of time. not reduced. These conflicting results could possibly Another confounding factor is the use of IV tramadol be due to differences in dosage, dosing regimen, type as a rescue drug which may affect the assessment of surgery, the use of other analgesic regimes such as of pain score postoperatively and incidence of side opioid or non opioids, different anesthetic technique effects. and surgical procedure16.

Most studies showed pregabalin to be well Conclusion tolerated and associated with dose dependent adverse effects that are mild to moderate and usually In conclusion, single dose of 150 mg pregabalin transient11-15. Different doses of pregabalin have been given preoperatively compared to placebo significantly used in the literature and doses ranging from 75 mg reduced the postoperative pain scores after mastectomy. to 300 mg11-17. It has been shown that higher doses

M.E.J. ANESTH 23 (1), 2015 68 Mardhiah Sarah Harnani Mansor and Choy Yin Choy

References

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Deepak Gupta**, Vinay Pallekonda*, Ronald Thomas**, George Mckelvey** and Farhad Ghoddoussi**

Abstract

Background: The etiology of delirium in intensive care units (ICU) is usually multi-factorial. There is common “myth” that lunar phases affect human body especially human brains (and minds). Objective: In the absence of any pre-existing studies in ICU patients, the current retrospective study was planned to investigate whether lunar phases play any role in ICU delirium by assessing if lunar phases correlate with prevalence of ICU delirium as judged by the corresponding consumptions of rescue anti-psychotics used for delirium in ICU. Materials and Methods: After institutional review board approval with waived consent, the daily census of ICU patients from the administrative records was accessed at an academic university’s Non-Cancer Hospital in a Metropolitan City of United States. Thereafter, the ICU pharmacy’s electronic database was accessed to obtain data on the use of haloperidol and quetiapine over the two time periods for patients aged 18 years or above. Subsequently the data was analyzed for whether the consumption of haloperidol or quetiapine followed any trends corresponding to the lunar phase cycles. Results: A total of 5382 pharmacy records of haloperidol equivalent administrations were analyzed for this study. The cumulative prevalence of incidents of haloperidol equivalent administrations peaked around the full moon period and troughed around the new moon period. As compared to male patients, female patients followed much more uniform trends of haloperidol equivalent administrations’ incidents which peaked around the full moon period and troughed around the new moon period. Further sub-analysis of 70-lunar cycles across the various solar months of the total 68-month study period revealed that haloperidol equivalent administrations’ incidents peaked around the full moon periods during the months of November-December and around the new moon periods during the month of July which all are interestingly the major holiday months (a potential confounding factor) in the United States. Conclusion: Consumption trends of rescue anti-psychotics for ICU delirium revealed an influence by lunar phase cycles particularly that of full moon periods on female patients in the ICU.

Introduction

* * MD. ** PhD. Corresponding author: Vinay Pallekonda MD, Department of Anesthesiology, Wayne State University, School of Medicine. Box No 162, 3990 John R, Detroit, MI 48201. Tel: 313-745-7233, Facsimile: 313-993-3889. E-mail: [email protected]

69 M.E.J. ANESTH 23 (1), 2015 70 Gupta Deepak et. al

Critically ill patients in the Intensive Care Units delirium was instituted in our hospital). Since March (ICUs) frequently experience delirium which is an 2013, our hospital’s standardized protocol for ICU acute reversible dysfunction of the brain. The etiology delirium include (a) daily screening for delirium with of ICU delirium is usually multi-factorial1. There is Intensive Care Delirium Screening Checklist (ICDSC) common “myth” that lunar phases affect human body to recognize patients with positive ICDSC scores ≥4 especially human brains (and minds). This “myth” followed by (b) their initial non-pharmacological has often been studied in various scenarios including management with sleep promotion, ambient noise automobile accidents and injury accidents2, suicides3, reductions during night-time, early and aggressive peri-operative blood loss4, clustering of seizures5, ambulation, and circadian rhythm cycle promotion, mental status changes in schizophrenics6, and human and thereafter reserving (c) pharmacological treatment and animal behavior and physiology7. The results of for intractable cases in form of haloperidol 2.5mg these studies reveal much ambiguity of the issue due to every 6hrs as needed intravenous boluses (maximum poorly understood underlying mechanisms; and hence single dose 5mg and maximum daily dose 40mg) results of various studies have either supported5-7 or or quetiapine 25-50mg by mouth every 12hrs refuted2-4 this norm/”myth” altogether. The common (maximum dose 200mg every 12hrs) besides ensuring thread of this “myth” is that as lunar phases affect the maximization of pain management strategies and oceans (tidal forces), these phases may affect the human minimization of benzodiazepine use among the ICU body because it is composed of 70% water (fluids) that delirium patients. may result in “human tidal waves” generated by lunar Subsequently, the day-to-day lunar phases 8 influences . (from new moon to first quarter to full moon to third Based on this background and in the absence quarter) for these time periods were accessed from of any pre-existing studies in the ICU patients, the the freely available public domain web-address http:// current retrospective study was planned to investigate www.timeanddate.com/calendar/moonphases.html. whether lunar phases have any role in ICU delirium Thereafter, the daily prevalence of ICU delirium was by assessing if lunar phases correlate with prevalence adjudged by recording the daily percentage of ICU of ICU delirium as judged by the corresponding patients who had received haloperidol or quetiapine. consumptions of rescue anti-psychotic medications Subsequently, the data was analyzed for whether the used for delirium in ICU. incidents of haloperidol or quetiapine administrations followed any medication consumption trends Materials and Methods corresponding to the lunar phase cycles (any time- sensitive-trends across the 29-plus days of a standard After institutional review board approval with lunar cycle as described in Table 1). Additionally, the waived consent, the daily census of ICU patients from data was compared for patients’ age and sex, and their the administrative records was accessed at an academic actual haloperidol/quetiapine usage. For uniformity university’s Non-Cancer Hospital in a Metropolitan during comparisons, all anti-psychotic usage was City of United States. Thereafter, the ICU pharmacy’s equated to per mg oral haloperidol equivalents as per electronic database was accessed to obtain data on the the below-mentioned explanations for bio-equivalence. use of haloperidol and quetiapine over the two time Using a multiplication factor of 1.6, intravenous periods for patients aged 18 years or above. Haloperidol haloperidol dose was converted to oral haloperidol and quetiapine are the two rescue anti-psychotic equivalent as per the recommendations of the freely medications primarily used to manage ICU delirium available public domain web-address http://www. in our hospital. The two time periods analyzed in this globalrph.com/haloperidol_dilution.htm. Similarly, study were: 2008-2012 (five year period before the although Woods (2003)9 advised using a conversion standardized protocol for ICU delirium was instituted of 75mg quetiapine as equivalent to 2mg oral in our hospital) and March 2013-October 2013 (eight haloperidol, Andreasen et al (2010)10 described the month period after the standardized protocol for ICU changing arena of patients’ requirements for very Rescue anti-psychotics for delirium in ICU 71

Table 1 Nomenclature of Lunar Phases for the Study Popular Popular Explanation Nomenclature for Explanation for This Study Nomenclature This Study

New Moon Time when 0% Visible Moon New Moon Period 24-hr period in either direction of New Moon’s Time (Total 48-hr Period) First Quarter Time after New Moon when 50% NOT STUDIED NOT APPLICABLE Moon becomes Visible Full Moon Time when 100% Visible Moon Full Moon Period 24-hr period in either direction of Full Moon’s Time (Total 48-hr Period) Last Quarter Time after Full Moon when 50% Moon NOT STUDIED NOT APPLICABLE (also known as Third remains Visible Quarter)

Waxing Crescent Over 7-8 days when Moon becomes Lunar Phase 1 Time Zone from New Moon’s Time to First Visible from 0% to 50% Quarter’s Time Waxing Gibbous Over 7-8 days when Moon becomes Lunar Phase 2 Time Zone from First Quarter’s Time to Visible from 50% to 100% Full Moon’s Time Waning Gibbous Over 7-8 days when Moon looses Lunar Phase 3 Time Zone from Full Moon’s Time to Last Visibility from 100% to 50% Quarter’s Time Waning Crescent Over 7-8 days when Moon looses Lunar Phase 4 Time Zone from Last Quarter’s Time to Visibility from 50% to 0% New Moon’s Time

high doses of quetiapine for efficacy and hence were tabulated based on a minimally modified popular calculated and recommended the changed equivalent nomenclature of lunar phases (Table 1) where the doses as 151.97mg quetiapine equivalent to 2 mg oral focus was comparisons between new moon period vs. haloperidol. Therefore, for our retrospective study, we full moon period; and inter-phase comparisons among followed the latest 2010 recommendations and used 76 the four lunar phases. As shown in Table 2, although mg quetiapine per mg oral haloperidol equivalent for there were variations for ICU delirium incidence study results analysis. among lunar cycles with the widest values ranging For statistical analysis, ANOVA (Analysis of from one-in-four ICU patients to one-in-nine ICU Variance) tests (Repeated measures 2 way ANOVA patients receiving haloperidol equivalents (P <0.001), treatment) were used to compare the continuous data. most commonly every 5th or 6th ICU patient based on Fisher exact test and Chi square analysis were used to daily ICU census was receiving haloperidol equivalent compare categorical data. For post-hoc analyses, the during 2008-2013 combined period irrespective of Student Newman-Keuls test was used. P-values <0.05 lunar cycle phase. However, the cumulative prevalence were considered statistically significant. of incidents of haloperidol equivalent administrations (Table 2; Figure 2) were significantly different in both Results study periods (2008-2012 and 8-month 2013) wherein the incidents of haloperidol equivalent administrations As described in the CONSORT Diagram (Figure peaked around the full moon period and troughed 1), a total of 5382 pharmacy records of haloperidol around the new moon period. There was a significant equivalent administrations were analyzed for this study difference between the incidents of haloperidol (4734 administrations during 2008-2012 period and equivalent administrations based on the patients’ 648 administrations during 8-month period in 2013). sex (Table 3; Figure 3) wherein as compared to male The time-trends analysis for these administrations patients, female patients followed much more uniform

M.E.J. ANESTH 23 (1), 2015 72 Gupta Deepak et. al

Table 2 At any given time-point, each instance of haloperidol equivalent administration was representative as following LUNAR PERIOD Percentage Incidence Incidence of P Value Cumulative Prevalence P Value of Haloperidol Haloperidol (F-Test) of Incidents of (F-Test) Equivalent Equivalent Haloperidol Equivalent Administration per Administration per Administrations Daily Census Daily Census On Average COMBINED 2008-2013 COMBINED 2008-2013 New Moon Period 16.7% ±16.6% 1-in-6 Patients 0.88 n=337 0.006 Full Moon Period 16.9% ±14.7% 1-in-6 Patients n=412 Lunar Phase 1 18.3% ±18.3% 1-in-5 Patients 0.18 n=1194 <0.001* Lunar Phase 2 17.6% ±16.2% 1-in-6 Patients n=1453 Lunar Phase 3 17.5% ±14.5% 1-in-6 Patients n=1427 Lunar Phase 4 18.7% ±19.2% 1-in-5 Patients n=1308 2008-2012 2008-2012 New Moon Period 16.1% ±15.0% 1-in-6 Patients <0.001 n=309 0.03 Full Moon Period 17.8% ±15.4% 1-in-6 Patients n=361 2013 2013 New Moon Period 23.8% ±28.3% 1-in-4 Patients n=28 0.008 Full Moon Period 10.7% ±5.2% 1-in-9 Patients n=51 2008-2012 2008-2012 Lunar Phase 1 18.8% ±18.6% 1-in-5 Patients 0.16 n=1051 <0.001* Lunar Phase 2 18.3% ±17.1% 1-in-5 Patients n=1269 Lunar Phase 3 17.9% ±15.0% 1-in-6 Patients n=1248 Lunar Phase 4 19.6% ±20.0% 1-in-5 Patients n=1166 2013 2013 Lunar Phase 1 14.1% ±15.1% 1-in-7 Patients n=143 0.02* Lunar Phase 2 12.9% ±6.1% 1-in-8 Patients n=184 Lunar Phase 3 14.6% ±9.1% 1-in-7 Patients n=179 Lunar Phase 4 11.8% ±6.5% 1-in-8 Patients n=142 *All pair-wise post-hoc comparisons are significantly different (P<0.05) when compared to their expected frequencies trends of haloperidol equivalent administrations’ ICU census across all the lunar cycle phases (Table incidents which peaked around the full moon period 4: section B). Further sub-analysis of 70-lunar cycles and troughed around the new moon period during both across the various solar months of the total 68-month study periods (2008-2012 and 8-month 2013). On study period (Figure 4) revealed that haloperidol further analysis of the actual administered haloperidol equivalent administrations’ incidents peaked around mg equivalent doses, the statistical significance for the full moon periods during the months of November- differences in the administered doses across lunar December and around the new moon periods during cycle phases were only observed when the patient- the month of July; however, interestingly, the actual doses were compared across the combined 2008-2013 administered haloperidol mg equivalent average doses period (Table 4: section B); and even though there was were highest around the new moon periods during the a statistical significance, the average clinical doses months of November-December. were 0.6-0.7 haloperidol mg equivalent per daily Rescue anti-psychotics for delirium in ICU 73

Fig 1 CONSORT Diagram

Discussion lunar cycle trends; (e) after removing patients’ age as confounding factor, haloperidol mg equivalent doses’ To summarize the key points of the study results: trends were statistically different (though differences (a) ICU delirium events, as adjudged by haloperidol were clinically inconspicuous) in relation to lunar equivalent administrations’ incidents, occurred on an cycle phases; and (f) ICU delirium events happening in average in approximately 20% of ICU patients daily relation to lunar cycle phases were more common in the at our hospital during 2008-2013; (b) ICU delirium solar months of July, November and December which events peaked around full moon; (c) ICU delirium are interestingly the major holiday months (a potential events trended similarly across the lunar cycles during confounding factor) in the United States besides July pre-standardized protocol time period (2008-2012) as being first month-in-training for new resident/fellow well as during post-standardized protocol time period ICU physicians and November-December being (2013); (d) as compared to male patients, ICU delirium severe winter weather months in our Metropolitan city. events in female patients more uniformly followed The moon and its effects on animal and human

M.E.J. ANESTH 23 (1), 2015 74 Gupta Deepak et. al

Table 3 Demographics of Patients who received Haloperidol Equivalent Administrations LUNAR PERIOD Age (Mean ±SD) P Value Cumulative Prevalence Gender Distribution of P Value in years (F-Test) of Incidents of Incidents of Haloperidol (F-Test) Haloperidol Equivalent Equivalent Administrations Administrations COMBINED 2008-2013 New Moon Period 57.8 ±13.5 0.2 n=337 Females 39% <0.001 Males 61% Full Moon Period 59.1 ±14.2 n=412 Females 54% Males 46% Lunar Phase 1 58.3 ±13.7 0.15 n=1194 Females 43% <0.001 Males 57% Lunar Phase 2 57.6 ±15.2 n=1453 Females 50% Males 50% Lunar Phase 3 57.5 ±13.7 n=1427 Females 51% Males 49% Lunar Phase 4 58.5 ±13.8 n=1308 Females 45% Males 55% 2008-2012 New Moon Period 57.2 ±13.5 0.09 n=309 Females 39% Males 61% <0.001 Full Moon Period 59.0 ±14.0 n=361 Females 53% Males 47% 2013 New Moon Period 65.0 ±11.6 0.16 n=28 Females 50% 0.34 Males 50% Full Moon Period 60.1 ±16.0 n=51 Females 63% Males 37% 2008-2012 Lunar Phase 1 57.9 ±13.6 0.09 n=1051 Females 41% <0.001 Males 59% Lunar Phase 2 56.9 ±15.3 n=1269 Females 48% Males 52% Lunar Phase 3 57.4 ±13.9 n=1248 Females 49% Males 51% Lunar Phase 4 58.2 ±14.1 n=1166 Females 45% Males 55% 2013 Lunar Phase 1 61.3 ±14.5 0.009 n=143 Females 57% 0.03 Males 43% Lunar Phase 2 62.9 ±13.5 n=184 Females 60% Males 40% Lunar Phase 3 58.4 ±12.6 n=179 Females 63% Males 37% Lunar Phase 4 61.2 ±10.5 n=142 Females 47% Males 53% Rescue anti-psychotics for delirium in ICU 75

Table 4 Haloperidol mg Equivalent-Strength Administration Dose Per Daily Intensive Care Unit Census

Lunar Period Characteristic that Acted as P Value Confounding Factor/Covariate (F-Test)

A Study Period 2008-2012 Study Period 2013

Number of Haloperidol mg Number of Haloperidol mg Administrations (n) Equivalent (Mean Administrations (n) Equivalent (Mean ±SD) ±SD)

New Moon 309 0.6 ±1.0 28 0.4 ±0.7 0.85 Period

Full 361 0.6 ±0.7 51 0.4 ±0.4 Moon Period

Lunar Phase 1 1051 0.6 ±0.9 143 0.4 ±0.6 0.27

Lunar Phase 2 1269 0.6 ±1.0 184 0.4 ±0.5

Lunar Phase 3 1248 0.6 ±0.8 179 0.5 ±0.6

Lunar Phase 4 1166 0.7 ±1.1 142 0.4 ±0.7

B Patient’s Age as Co-Variate P Value (F-Test) Number of Administrations (n) Haloperidol mg Equivalent (Mean ±SD)

New Moon 337 0.6 ±1.0 0.006 Period

Full 412 0.6 ±0.7 Moon Period

Lunar Phase 1 1194 0.6 ±0.9 0.001

Lunar Phase 2 1453 0.6 ±0.9

Lunar Phase 3 1427 0.6 ±0.8

Lunar Phase 4 1308 0.7 ±1.1

C Patient’s Sex: Female Patient’s Sex: Male P Value (F-Test) Number of Haloperidol mg Number of Haloperidol mg Administrations (n) Equivalent (Mean Administrations (n) Equivalent (Mean ±SD) ±SD)

New Moon 133 0.4 ±0.5 204 0.6 ±1.2 0.17 Period

Full Moon 223 0.5 ±0.7 189 0.6 ±0.7 Period

Lunar Phase 1 509 0.5 ±0.8 685 0.6 ±0.9 0.74

Lunar Phase 2 721 0.6 ±0.9 732 0.6 ±1.0

Lunar Phase 3 728 0.6 ±0.8 699 0.6 ±0.8

Lunar Phase 4 591 0.6 ±0.9 717 0.7 ±1.2

M.E.J. ANESTH 23 (1), 2015 76 Gupta Deepak et. al

Fig. 2 Graphical Presentation of Haloperidol Equivalent Administrations’ Incidents across the Whole Study Period: New Moon vs. Full Moon AND Lunar Phases 1-4 (Comparative P-Values reported in Table 2)

Fig. 3 Graphical Presentation of Haloperidol Equivalent Administrations’ Incidents’ Distribution per Patients’ Sex/ Gender: New Moon vs. Full Moon AND Lunar Phases 1-4 (Comparative P-Values reported in Table 3) Rescue anti-psychotics for delirium in ICU 77

Fig. 4 Graphical Presentation of Haloperidol Equivalent Administrations’ Incidents across the 68-Solar Month Study Period: New Moon vs. Full Moon (F-Test P-Value <0.001 for Overall Solar Month Trends’ Effect) AND Lunar Phases 1-4 (F-Test P-Value <0.001 for Overall Solar Month Trends’ Effect)

behavior have fascinated mankind since ancient times. concluded that further investigations were required Similarly, the medical profession has not been naive to validate the findings. Zimecki (2006)7 further or immune to these discussions. Thakur and Sharma expanded these discussion by reviewing the lunar (1984)8 observed that crime rates in three different phase effects on the animal kingdom in regards to cities in India during 1978-1982 increased threefold phylogenesis, fishes’ fertility cycles, hormonal level from new moon period to full moon period; and the changes in birds, sensory system of rats, and human authors explained this effect secondary to “human tidal reproduction. Zimecki7 tried to explain lunar effects waves” in human physiology as similar to gravitational on animal physiology as due to possible induction effects of moon on the oceans. However, Laverty and of changes in electromagnetic milieu around animals Kelly (1998)2 reviewed a nine-year period with almost due to the periodic changes in the moon. Around 300,000 accidents and observed periodic changes same time, Polychronopoulos et al (2006)5 reported secondary to calendar changes and season changes but neurology emergency department experience over no relationship was apparent in relation to lunar cycle five year-period that as compared to 21.4% epileptic phases including full moon period. seizures that occurred during new moon period, 34.2% Barr (2000)6 revisited the historical aspect of term epileptic seizures occurred during full moon period. 5 “lunacy” wherein during pre-modern times, mentally They re-iterated the possibility of epileptic seizures ill patients were supposedly displaying behavior induction secondary to deprived sleep behavior during changes in accordance to the changes in moon (“lunar”) the full moon periods as an evolutionary learned phases. Among 100 patients who were followed for behavior in response to increased night-time ambient two-and-half years, Barr6 observed significant changes light during the full moon period. during full moon period in the schizophrenic patients Recently, Voracek et al (2008)3 reviewed over as compared to the non-schizophrenic patients; and 65,000 suicides in Austria from 1970-2006. They

M.E.J. ANESTH 23 (1), 2015 78 Gupta Deepak et. al did not find any significant difference in completed delirium, and (d) it does not differentiate the effects suicides’ incidence between new moon period vs. full of lunar phases (if any) on the ICU delirium patients moon period, and the completed suicides’ incidence was vs. their medical care providers who had diagnosed equally divided among the four lunar phases. Voracek ICU delirium and decided to administer haloperidol et al (2008)3 suggested that as compared to their almost equivalents. four-decade long study period, other researchers’ short duration study periods can be the reason for other Conclusion studies reporting lunar effects on human behavior events because they themselves also observed new In summary, consumption trends of rescue anti- moon as well as full moon sporadically affecting psychotics for ICU delirium revealed an influence completed suicide rates during a few individual years by lunar phase cycles particularly that of full moon among their cumulative 37-year long study period. periods on female patients in the ICU. Similarly, Schuld et al (2011)4 questioned the idea of patients scheduling their elective major surgeries in Acknowledgement accordance to avoid lunar phases like full moon period because their analysis of emergency surgeries’ ten- The authors are deeply indebted to the appreciative year data revealed absence of statistical significance in efforts of Ms. Connie Tourangeau, Pharmacist, and regards to any differences in peri-operative blood loss Mr. Xavier Bell, Field Engineer, Department of and complications when measured in concurrence to Pharmacy, Harper Hospital, Detroit Medical Center, lunar phases. Detroit, Michigan, United States in regards to their The limitations of our study are that (a) it is a retrospective enlisting of the ICU patients according retrospective analysis, (b) it measured primarily the to the medications that they had received per their action (rescue anti-psychotics use) and assumed the databases. The authors are also grateful to Ms Sapna corresponding cause (ICU delirium), (c) it puts forth Parmar, Information Systems Division Application only our observations but does not provide evidence for Staff, for her help in enlisting daily ICU patients’ the interpretation how (if any) lunar phases affect ICU census data for our retrospective study period. Rescue anti-psychotics for delirium in ICU 79

References

1. Banh HL: Management of delirium in adult critically ill patients: an and seizure occurrence: just an ancient legend? Neurology; 2006, overview. J Pharm Pharm Sci; 2012, 15:499-509. 66:1442-1443. 2. Laverty WH, Kelly IW: Cyclical calendar and lunar patterns in 6. Barr W: Lunacy revisited. The influence of the moon on mental automobile property accidents and injury accidents. Percept Mot health and quality of life. J Psychosoc Nurs Ment Health Serv; 2000, Skills; 1998, 86:299-302. 38:28-35. 3. Voracek M, Loibl LM, Kapusta ND, Niederkrotenthaler T, 7. Zimecki M: The lunar cycle: effects on human and animal behavior Dervic K, Sonneck G: Not carried away by a moonlight shadow: and physiology. Postepy Hig Med Dosw (Online); 2006, 60: 1-7. no evidence for associations between suicide occurrence and lunar 8. Thakur CP, Sharma D: Full moon and crime. Br Med J (Clin Res phase among more than 65,000 suicide cases in Austria, 1970-2006. Ed); 1984, 289:1789-1791. Wien Klin Wochenschr; 2008, 120:343-349. 9. Woods SW: Chlorpromazine equivalent doses for the newer atypical 4. Schuld J, Slotta JE, Schuld S, Kollmar O, Schilling MK, Richter antipsychotics. J Clin Psychiatry; 2003, 64:663-667. S: Popular belief meets surgical reality: impact of lunar phases, 10. Andreasen NC, Pressler M, Nopoulos P, Miller D, Ho BC: Friday the 13th and zodiac signs on emergency operations and Antipsychotic dose equivalents and dose-years: a standardized intraoperative blood loss. World J Surg; 2011, 35:1945-1949. method for comparing exposure to different drugs. Biol Psychiatry; 5. Polychronopoulos P, Argyriou AA, Sirrou V, Huliara V, Aplada 2010, 67:255-262. M, Gourzis P, Economou A, Terzis E, Chroni E: Lunar phases

M.E.J. ANESTH 23 (1), 2015

The Use of Paravertebral Blockade for Analgesia after Anterior-Approach Total Hip Arthroplasty.

Alberto E. Ardon* MD MPH, Roy A. Greengrass* MD, Upasna Bhuria* MBBS, Steven B. Porter* MD, Christopher B. Robards* MD and Kurt Blasser** MD

Abstract

Background: Anterior approaches for total hip arthroplasty (ATHA) are becoming increasingly popular. We postulated that the use of PVB of the T12, L1, and L2 roots would provide adequate analgesia for ATHA while allowing motor sparing. Methods: The medical records of 20 patients undergoing primary ATHA were reviewed. T12, L1 and L2 paravertebral blockade was accomplished with 3-4ml of 1% ropivacaine with epinephrine 1:200,000 and 0.5mg/ml of preservative-free dexamethasone per level. Primary outcomes were mean opioid consumption in intravenous morphine equivalents and worst recorded visual analog scale (VAS) pain scores during postoperative days 0 to 2 (POD 0 to 2). Results: Mean opioid consumption was 8.4mg on POD0, 16.6mg on POD1, and 9.8mg on POD2. Median worst VAS scores were 2 for all time intervals except POD 0, which had a median value of 0. All patients had full hip motor strength the evening of POD0. 19 patients were able to ambulate the afternoon of POD1. Conclusion: T12-L2 PVB, when utilized as part of a multimodal analgesic regimen, results in moderate opioid consumption, low VAS scores, preservation of hip motor function, and may be an effective regional anesthesia technique for ATHA. Keywords: Paravertebral blockade1, anterior total hip arthroplasty, multimodal analgesia, opioid consumption.

Introduction

Anterior approaches for total hip arthroplasty are becoming increasingly popular due to advantages of less muscle trauma, resulting in enhanced convalescence1.

* department of Anesthesiology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224. ** department of Orthopedic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224. Corresponding author: Alberto E. Ardon, Department of Anesthesiology, Mayo Clinic, Jacksonville, FL 4500 San Pablo Road, Jacksonville, FL 32224. Tel: 904-766-0738; 225-773-4407, Fax: 904-956-3332. E-mail: [email protected] Present academic appointment and address: Assistant Professor, University of Florida-Jacksonville, 2nd Floor, Clinical Center, Department of Anesthesiology, 655 West 8th Street, C72, Jacksonville, FL 32209. Tel: 904-244-4195; 225-773- 4407, Fax: 904-244-4908. E-mail [email protected]; [email protected] 1. PVB: paravertebral blockade. aTHA: anterior total hip arthroplasty. POD: postoperative day. vas: visual analog scale.

81 M.E.J. ANESTH 23 (1), 2015 82 Alberto Ardon et. al

Unfortunately, similar to posterior approaches, Anesthesiologists standard monitors and verification of anterior total hip arthroplasty (ATHA) is associated patient identity and laterality of the procedure. Sedation with significant pain requiring moderate to large doses was at the discretion of the attending anesthesiologist, of opioids with attendant side effects. Multimodal and included sedative doses of midazolam, fentanyl, analgesia including regional analgesic techniques such ketamine, and/or propofol. as posterior lumbar plexus block (psoas compartment For PVB placement, patients were positioned block) have been utilized to treat the pain of total hip in the sitting position. The T12, L1 and L2 spinous arthroplasty with encouraging results2. However, the processes were identified in the sitting position either motor weakness associated with psoas compartment by counting from the L4 spinous process at the level block may limit ambulation and decrease effective of iliac crest and/or from the T7 spinous process physiotherapy, possibly increasing the risk of falls3. It at the level of lower border of the scapulae. Needle is felt by many surgeons that motor sparing analgesic entry points were marked 2.5 cm lateral to the spinous techniques would be of benefit to patients. process as described previously by Greengrass et While opioids are commonly used for al5. After skin infiltration with 2% lidocaine with postoperative analgesia in hip arthroplasty patients, the epinephrine 1:200,000 at the marked sites, a sterile use of these medications is associated with a significant 22 G, 10 cm Tuohy needle (B Braun, Melsungen, negative side effect profile that includes nausea and DE) was introduced perpendicular to the skin until vomiting, respiratory depression, prolonged recovery the transverse process was contacted. The needle was room stay, increased healthcare burden, and decreased then redirected in a caudad direction and advanced 4 patient satisfaction . Consequently, the use of a 1-1.5 cm. After negative aspiration, 3-4 ml of 1% regional anesthetic technique as a part of a multimodal ropivacaine with epinephrine 1:200,000 and 0.5mg/ml analgesic plan aimed at reducing postoperative opioid of preservative free dexamethasone were injected per consumption would be advantageous. level. Injections were repeated at the other two levels. The paravertebral block (PVB) is a block of Sensory deficit in the distribution of T12, L1 and L2 the mixed nerve soon after it exits the intervertebral dermatomes were confirmed with ice testing prior to foramen5. It provides intense unilateral analgesia of surgical anesthesia. Absence of motor blockade upon long duration and has become the primary anesthetic hip flexion, assessed with the modified Bromage scale, for many applications6,7. We postulated that the use was also confirmed preoperatively. The modified of PVB of the T12, L1 and L2 roots would provide Bromage scale is defined as follows: 1 = unable to adequate analgesia for ATHA while allowing motor move foot or knee; 2 = able to move foot only; 3 = sparing. In this study we present our initial expanded just able to move knee; 4 = full flexion of knee; 5 = no case series of 20 patients who received PVB for ATHA. detectable weakness of hip flexion while supine. One patient required an additional injection at all levels to Methods establish appropriate sensory deficit. Surgical anesthesia was achieved with an The Institutional Review Board (IRB) approved intrathecal injection of 12.5 to 13mg of preservative- this study. From June 2013 to February 2014, the free isobaric 0.5% bupivacaine. The same surgeon medical records of 20 patients undergoing primary performed all surgeries utilizing a modified Smith- ATHA were reviewed. No patient had preoperative Peterson anterior approach. No patients had motor deficit or opioid consumption requiring long- intraoperative complications. At the discretion of the acting opioids. surgeon, patients received an intra-articular injection After a preoperative interview, informed consent consisting of morphine 10mg, ketorolac 30mg, and for both surgical anesthesia and peripheral nerve epinephrine 200mcg. Daily opioid and non-opioid blockade was obtained by an anesthesiologist. All analgesic consumption, visual analog scale (VAS) pain blocks were performed in the preoperative area in a scores, and length-of-stay data were extracted from the sterile fashion after placement of American Society of electronic medical record. Paravertebral block for hip arthroplasty 83

Table 1 Patient characteristics Pt ID Age ASA Sex Operative Side Consistent Preoperative Day of Discharge opioid, if any 1 82 3 F Right No POD 3 2 64 2 M Right No POD 2 3 72 3 F Right No POD 3 4 56 1 M Right No POD 2 5 74 3 M Left No POD 3 6 76 2 F Left No POD 3 7 81 3 M Left No POD 3 8 65 2 M Left Oxycodone POD 3 9 72 2 M Right No POD 2 10 71 2 M Left No POD 3 11 69 2 M Left Oxycodone POD 2 12 61 2 F Right No POD 2 13 77 2 M Left No POD 3 14 91 3 M Right No POD 3 15 67 2 F Left No POD 3 16 70 2 F Right No POD 3 17 64 2 F Right Hydrocodone POD 3 18 70 3 M Right No POD 3 19 72 3 M Left No POD 3 20 83 3 M Left No POD 2

Postoperatively, patients received scheduled Secondary Outcomes intravenous acetaminophen every 6 hours for the first 24 hours, and thereafter on an as-needed basis. All Secondary outcomes included maximum opioid patients received oral celecoxib 200mg twice daily. consumption, non-opioid analgesic consumption, ability to ambulate, and distance ambulated. Primary Outcomes Results Mean opioid consumption in intravenous morphine equivalents during the time intervals of postoperative Patient characteristics are shown in Table 1. A total of 20 patients were included, all of whom day 0 (POD 0, defined as the period of time from surgi- received a spinal anesthetic. Mean operative time cal incision until 07:00 on postoperative day 1), post- was 78 minutes. Three patients had documented operative day 1 (POD 1, defined as 07:00 until 07:00 preoperative opioid consumption with short-acting on POD2), and postoperative day 2 (POD 2, defined as agents. However, none of these patients consumed .)07:00 on POD2 until 18:00 more than 30mg of oral morphine equivalents per day. Worst recorded visual analog scale (VAS) pain scores, The remaining patients denied use of preoperative rated from 0 - 10, during time intervals from POD 0 opioids. No patients developed complications from .to 2 the paravertebral blocks while hospitalized. No falls

M.E.J. ANESTH 23 (1), 2015 84 Alberto Ardon et. al

Table 2 Opioid consumption in IV morphine equivalents (mg) Patient ID POD 0 POD 1 POD 2 1 4 12 9 2 10 10 5 3 10 10 5 4 15 10 10 5 0 15 0 6 5 33.3 30 7 12 42.3 15.6 8 10 20 15 9 9 11.3 5 10 0 20 15 11 10 15 10 12 10 25 10 13 5.3 4 13.3 14 3.3 13.3 7.5 15 20.3 18.3 5.3 16 10 15 10 17 21.7 36.7 30 18 16.7 10 0 19 0 0 0 20 0 0 0 Mean 8.4 16.6 9.8 Median 9.5 15 9.5

Table 3 Visual analog pain scores Patient ID Worst VAS Worst VAS Worst VAS Worst VAS Worst VAS Worst VAS Worst VAS POD 0 to POD 0-1 POD 1 AM POD 1 PM POD 1-2 POD 2 AM POD 2 PM 19:00 overnight overnight 1 0 0 0 0 0 2 2 2 0 4 2 2 4 2 n/a 3 5 2 0 0 0 2 3 4 0 8 3 3 3 2 n/a 5 0 1 0 n/a 3 0.5 1 6 0 7 3 1 5 0 4 7 2 2 2 0 7 0 4 8 0 4 1 2 2 2 0 9 0 0 0 0 0 0 2 10 0 3 3 2 2 2 2 11 5 5 2 2 2 5 4 12 4 2 3 3 1 1 n/a 13 0 2 2 0 0 0 n/a 14 6 5 3 3 3 0 0 15 4 2 2 3 3 2 3 16 2.5 2 0 2 0 0 1.5 17 6 4 6 4 5 4 3 18 0 6 2 0 4 2 2 19 0 0 0 0 0 1 0 20 0 0 0 0 1 2 n/a n/a: not recorded secondary to lack of record or patient discharge Paravertebral block for hip arthroplasty 85 occurred during hospitalization. Six patients were All patients had modified Bromage scores of 5 discharged on POD 2. the evening of POD 0; 2 patients were able to ambulate Opioid consumption in IV morphine equivalents at that time. On the morning of POD 1, 15 patients by patient is shown in Table 2. Mean opioid consumption were able to ambulate, while 19 were able to do so by was 8.4mg on POD0, 16.6mg on POD1, and 9.8mg on that afternoon (Table 6). Median distances ambulated POD2. Median opioid consumption was 9.5mg, 15mg, on the morning and afternoon of POD1 were 30 feet and 9.5mg for POD0, POD1, and POD2, respectively. and 80 feet, respectively. Maximum opioid consumption was 21.7mg on POD0, Table 6 42.3mg on POD1, and 30mg on POD2. The three Ambulation among study patients, with distance ambulated in patients with documented preoperative opioid use had feet [median (range)] postoperative opioid consumption greater than the # of patients ambulated POD0 2 median on POD 0, 1 and 2. # of patients ambulated POD1 AM 15

Worst VAS scores recorded for each patient are # of patients ambulated POD1 PM 19 shown in Table 3; values ranged from 0 to 8. Median Distance ambulated POD1 AM 30 (1, 500) worst VAS scores, shown in Table 4, were 2 for all time intervals except POD0, which had a median value Distance ambulated POD1 PM 80 (5, 980) of 0. Table 4 Discussion Median worst visual analog pain scores (minimum, maximum) POD0 to 19:00 0 (0,6) Although the concept of the paravertebral th POD 0-1 overnight 2 (0,8) block (PVB) originated in the early 20 century, its popularity has waxed and waned. Recently, a renewed POD1 AM 2 (0,6) interest in the technique has developed, as it has been POD1 PM 2 (0,4) found to be an effective analgesic technique that POD 1-2 overnight 2 (0,7) minimizes hemodynamic compromise8,9. The injection POD2 AM 2 (0,5) of local anesthetic in the paravertebral space blocks POD2 PM 2 (0,4) conduction in the dorsal and ventral rami of the exiting spinal nerve root. Paravertebral blockade also inhibits Regarding non-opioid analgesics, median conduction through the sympathetic chain, resulting acetaminophen and celecoxib doses are shown in Table in only a unilateral sympathectomy. At the levels of 5. Median acetaminophen dose was highest on POD 0 thoracic vertebrae, the paravertebral space is a wedge (4000mg), while median celecoxib dose was higher on shaped space defined anterolaterally by the parietal POD1 and POD2 (400mg). pleura, posteriorly by the superior costotransverse ligament, and medially by the vertebral, vertebral Table 5 disk, and intervertebral foramina. The superior and Median acetaminophen and celecoxib consumption among inferior borders are provided by the heads of the ribs. patients (mg) In the lumbar vertebrae, the inter-transverse ligament Acetaminophen Consumption provides the posterior border of the paravertebral space. POD 0 4000 As explained by Greengrass et al, the paravertebral POD 1 2650 space provides an area where exiting spinal nerves are not tightly enveloped by fascia, possibly facilitating POD 2 1000 nerve blockade5. Celecoxib Consumption Paravertebral blockade is commonly used POD 0 200 for breast surgery, video-assisted thoracic surgery, POD 1 400 minimally invasive cardiac surgery, herniorrhaphy, and POD 2 400 hand-assisted laparoscopic nephrectomy7,8,9. To our

M.E.J. ANESTH 23 (1), 2015 86 Alberto Ardon et. al knowledge, use of this analgesic technique in anterior- respiratory depression after an intrathecal opioid approach hip arthroplasty has not been described injection is unnecessary when non-opioid modalities in the literature. While the use of PVB was reported are available. Bogoch et al’s study which used a by Bogoch and colleagues in 2002 for postoperative single-injection lumbar plexus block showed an opioid analgesia following total hip and knee arthroplasty, consumption of 18.7mg of morphine equivalents in the the technique described suggests a psoas compartment first 8 hours after surgery, which is significantly higher blockade, not a true paravertebral block, as the initial than our results10. Some studies contend that there is needle approach was made 4cm lateral to the spinous little difference in opioid consumption or pain scores process rather than 2.5cm10. Lee et al reported excellent when comparing an anterior approach hip arthroplasty analgesia in two patients who patients received L1/ to a classic posterior approach. Rodriguez et al found L2 paravertebral blocks along with local anesthetic no difference in either metric when comparing the infiltration of the joint for hip arthroscopy11. Wardhan two surgical methods16. Even with a lumbar plexus and colleagues described continuous L2 paravertebral catheter in place, opioid consumption may be high in blockade to be slightly inferior to a lumbar plexus the classic posterior approach. For example, Wilson catheter when comparing opioid consumption in et al documented a mean opioid consumption of posterior approach total hip arthroplasty patients, with 54.67mg of IV morphine equivalents in the first 24 12 no motor strength advantage . However, patients in hours after THA, even with a properly functioning that study received 15ml of local anesthetic during lumbar plexus catheter17. If indeed little difference in placement of the paravertebral catheter. Injection of a opioid consumption exists between the two surgical large amount of local anesthetic in the paravertebral techniques, our results suggest that multimodal space may result in epidural and/or unpredictable analgesia including a PVB at T12-L2 may decrease 5,13,14 spread . In one radiographic study, 25% of patients opioid consumption significantly in ATHA patients. who received 20ml injectate at a single paravertebral level had epidural spread evident on MRI13. Thus, During the time intervals studied, all median observed weakness in PVB patients after a large VAS scores were 2 or less. Reports of perioperative volume injection could be secondary to neuraxial or VAS scores for the ATHA patient population are extensive paravertebral spread of local anesthetics. limited. One study described mean POD 0, 1, and 2 In our current study, we have limited the injectate VAS scores to be (4.2 ± 1.4), (4.0 ± 1.0) and (3.8 ± 15 to a maximum of 4ml per level, which we believe 1.1), respectively . The low median VAS scores in our minimizes the risk of these complications. In our case study, combined with moderate opioid consumption, series, no patient had a modified Bromage score less are thus encouraging. than 5 the evening of POD 0. Additionally, no patient The potential efficacy of paravertebral blockade was noted by physical therapy as having significant in this study may be explained on anatomic grounds. ipsilateral lower extremity weakness that prevented First, the cutaneous analgesia provided by paravertebral full participation in physical activity. blocks at T12, L1 and L2 is suited for coverage of the Studies addressing opioid consumption among surgical incision. Second, as described by Wetheimer patients who undergo anterior approach total hip in 1952, the peripheral nerve innervation of the hip arthroplasty are limited. In a prospective study by joint is provided by the obturator nerve, femoral nerve, Barrett et al, ATHA patients consumed a mean of and branches of the sacral plexus18. The spinal nerves at 32.2mg, 50.7mg, and 33.7mg IV morphine equivalents the levels of T12, L1 and L2 provide sensory fibers to on POD 0, 1 and 2, respectively15. Another study by the iliohypogastric, ilioinguinal, genitofemoral, lateral Restrepo describes POD0, POD1, and POD2 mean femoral cutaneous, femoral and obturator nerves. intravenous morphine consumption as 11.2mg, Thus, a significant proportion of the sensory fibers 13.9mg, and 6.82mg, respectively. However, patients to the hip joint are affected by T12-L2 paravertebral in this study received intrathecal morphine as part of blockade. Lastly, the bony innervation of the hip their analgesic plan, thus our results are not directly joint may indeed be affected by this paravertebral comparable1. Additionally, the risk of postoperative approach. Although osteotomal anatomy of the hip Paravertebral block for hip arthroplasty 87 joint is much less well defined, Brown and colleagues VAS scores on POD1, suggest that paravertebral describe L2 as providing innervation to the medial blockade may provide significant analgesia to facilitate midshaft femur, iliac crest, and anterior superior iliac ambulation during the first 24 hours after surgery. spine; L3 provides innervation to the femoral neck and As mentioned previously, 13 patients received 19 acetabulum . In our study we did not conduct an L3 intraarticular morphine, ketorolac and epinephrine. block so as to decrease the total anesthetic dose and The evidence supporting the use of these medications minimize the risk of motor block. Based on our results, within the articular space without local anesthetic, separate blockade of L3 may indeed not be required for however, is not robust. While some studies do suggest adequate analgesia after ATHA. Femoral nerve fibers that the use of intraarticular local anesthetic may arise from L2, L3, and L4 nerve roots. Blockade with enhance postoperative analgesia22,23,24, the analgesic moderate volume only at L2, while giving sensory properties of intra-articular morphine or epinephrine block in that dermatomal distribution and having without local anesthetic are yet to be supported limited caudal spread, may allow full motor function by data. To our knowledge, there are no studies of the femoral nerve. We recognize, however, that until regarding the analgesic properties of sole epinephrine further studies delineating osteotomal hip innervation when injected into an articulation. Regarding opioids, are conducted, the exact contribution of PVB analgesia one murine-model study suggests that subcutaneous to the hip joint may not be well defined. administration of morphine may have some analgesic The patients in this case series received both properties at the site of injection, but these effects acetaminophen and celecoxib as part of a multimodal have not been validated in the intra-articular space 25 approach to postoperative analgesia. Acetaminophen in humans . Another study in patients undergoing use was highest on POD0-1, which may have knee surgery showed no difference in postoperative contributed to the low opioid consumption and very opioid consumption when morphine is added to intra- low median worst VAS of zero. Likewise, twice-daily articular bupivacaine in the presence of a femoral 26 celecoxib administration may also have contributed nerve block . The efficacy of ketorolac when injected into a joint without local anesthetic has also not been to decreasing the total opioid consumption among studied extensively. One small study by Vintar et these patients. While the exact contribution of al studied the impact of 10mg ketorolac on an on- acetaminophen and celecoxib in reducing opioid demand intraarticular bolus of 25mg ropivacaine requirements in these anterior hip arthroplasty patients and 2mg morphine available every 60 minutes. is not known, previous studies in total knee and Patients who received intraarticular ketorolac had posterior-lateral approach hip arthroplasty suggest that decreased opioid use 24 hours postoperatively27. multimodal analgesia reduces opioid burden20,21. The However, another study showed that patients who low overall pain scores and opioid consumption in this only received intraarticular ketorolac had higher case series certainly suggest that the use of multimodal pain scores and shorter time to first analgesic request analgesia may contribute to the analgesic efficacy of compared to patients who only received intraarticular paravertebral blockade. bupivacaine28. In our study, when patients who did All but two of the study patients were able to not receive this intra-articular injection are analyzed participate in physical therapy to some degree by the separately, mean and median opioid consumption are evening of their surgical day. The two patients who similar to those of the overall cohort (Table 7). Thus, did not were limited by a late discharge from the given these results and the paucity of evidence for recovery room, as they were both mid-afternoon cases. the efficacy of this intra-articular mixture, we do not By the morning of POD1, 15 of the 20 patients were believe this modality affected our primary outcome. able to ambulate. Median distance ambulated during However, as shown in Table 8, median worst VAS the morning physical therapy session was 30 feet. By scores did seem to be slightly higher in those patients. the afternoon of postoperative day 1, 19 patients were Thus, we realize that the theoretical possibility ambulating, with a median distance of 80 feet. These of a combined analgesic effect cannot entirely be results, when considered in the context of low median discounted.

M.E.J. ANESTH 23 (1), 2015 88 Alberto Ardon et. al

Table 7 per regular protocol, without mention of activity status Mean and median opioid consumption in mg IV morphine during the patient’s self-assessment of pain. However, equivalents, patients who did not receive intra-articular since we have collected the worst recorded VAS injection rather than the entire range of pain scores, we hope to Mean Median capture as many VAS scores associated with activity POD 0 8.96 10 as possible. We also recognize that while appropriate sensory deficit was confirmed preoperatively, the POD 1 12.43 10 duration of this sensory deficit was not documented. POD 2 7.04 5 Thus, we can only speculate on the exact duration of the paravertebral block. Given the steady level of Table 8 opioid requirements throughout postoperative day 2, Median visual analog pain scores (minimum, maximum), though, we suspect that the analgesia associated with patients who did not receive intra-articular injection nerve blockade continued to some degree during this POD0 to 19:00 0 (0,5) time period. POD 0-1 overnight 5 (0,9) POD1 AM 0 (0,3) Conclusion POD1 PM 2 (0,6) POD 1-2 overnight 4 (0,6) T12 through L2 paravertebral blockade, when POD2 AM 5 (0,8) utilized as part of a multimodal pain management plan, POD2 PM 6 (0,7) results in low VAS scores, preservation of hip motor function, moderate opioid consumption, and may be an effective analgesic modality for patients undergoing The limitations in our case series include the anterior approach total hip arthroplasty. The outcomes retrospective nature of the study, the small number of of our retrospective case series are encouraging. patients, and the lack of randomization. Additionally, Prospective studies are warranted. the VAS scores were recorded by ward nursing staff Paravertebral block for hip arthroplasty 89

References

1. Restrepo C, Parvizi J, Pour AE, Hozack WJ: Prospective randomized 16. Rodriguez JA, Deshmukh AJ, Rathod PA, Greiz ML, Deshmane study of two surgical approaches for total hip arthroplasty. J of PP, Hepinstall MS, Ranawat AS: Does the direct anterior approach Arthroplasty; 2010, 25(5):671-80. in THA offer faster rehabilitation and comparable safety to the 2. Horlocker TT: Pain management in total joint arthroplasty: a posterior approach? Clin Orthop Rel Res; 2014, 472:455-63. historical review. Orthopedics; 2010, 33(9):supplement. 17. Wilson SH, Auroux AM, Eloy JD, Merman RB, Chelly JE: 3. Ilfeld BM, Mariano ER, Madison SJ, Loland VJ, Sandhu NS, Ropivacaine 0.1% versus 0.2% for continuous lumbar plexus nerve Suresh PJ, Bishop ML, Kim TE, Donohue MC, Kulidjian AA, Ball block infusions following total hip arthroplasty: a randomized, ST: Continuous femoral versus posterior lumbar plexus nerve blocks double blinded study. Pain Medicine; 2014, 15:465-472. for analgesia after hip arthroplasty: a randomized, controlled study. 18. Wertheimer LG: The sensory nerves of the hip joint. J of Bone and Anesth Analg; 2011, 113(4):897-903. Joint Surgery; 1952, 34(2):477-87. 4. Greenberg C: Practical, cost-effective regional anesthesia for 19. Brown DL, Boezaart AP, Galway UA, Rosenquist RW, Rathmell ambulatory surgery. J of Clinical Anesthesia; 1995, 7:614-21. JP, Sites BD, Spence BC: Atlas of Regional Anesthesia. 4th Ed. 5. Greengrass RA, Duclas R: Paravertebral blocks. International Philadelphia: Saunders Elsevier; 2010. Anesthesiology Clinics; 2012, 50(1):56-73. 20. Ittichaikulthol W, Prachanpanich N, Kositchaiwat C, Intapan T: 6. Akcaboy EY, Akcaboy ZN, Gogus N: Ambulatory inguinal The postoperative analgesic efficacy of celecoxib compared with herniorrhaphy: paravertebral block versus spinal anesthesia. placebo and parecoxib after total hip or knee arthroplasty. J Med Minerva Anestesiologica; 2009, 75(12):684-691. Assoc Thai; 2010, 93(8):937-42. 7. Schnabel A, Reichl SU, Kranke P, Pogatzki-Zahn EM, Zahn PK: 21. Peters CL, Shirley B, Erickson J: The effect of a new multimodal Efficacy and safety of paravertebral blocks in breast surgery: a meta- perioperative anesthetic regimen on postoperative pain, side effects, analysis of randomized controlled trials. British J of Anesthesia; rehabilitation, and length of hospital stay after total joint arthroplasty. 2010, 105(6):842-52. J of Arthroplasty; 2006, 21(6 Suppl 2):132-8. 8. Eason MJ, Wyatt R: Paravertebral thoracic block: a re-appraisal. 22. Chen LH, Huang QW, Wang WJ, He ZR, Ding WL: The applied Anesthesia; 1979, 34(7):638-42. anatomy of anterior approach for minimally invasive hip joint 9. Clendenen SR, Wehle MJ, Rodriguez GA, Greengrass RA: surgery. Clinical Anatomy; 2009, 22:250-55. Paravertebral block provides significant opioid sparing after hand- 23. Dobrydnjov I, Anderberg C, Olsson C, Shapurova O, Angel K, assisted laparoscopic nephrectomy: an expanded case report of 30 Bergman S: Intraarticular versus extraarticular ropivacaine infusion patients. J of Endourology; 2009, 23(12):1979-83. following high-dose local infiltration analgesia after total knee arthroplasty: a randomized double-blind study. Acta Orthopaedica; 10. Bogoch ER, Henke M, Mackenzie T, Olschewski E, Mahomed NN: Lumbar paravertebral nerve block in the management of pain after 2011, 82(6):692-98. total hip and knee arthroplasty. J of Arthroplasty; 2002, 17(4):398- 24. Axelsson K, Gupta A, Johanzon E, Berg E, Ekback G, Rawal N, Enstrom P, Nordensson U: Intraarticular administration of 401. ketorolac, morphine and ropivacaine combined with intraarticular 11. Lee EM, Murphy KP, Ben-David B: Postoperative analgesia for patient-controlled regional anesthesia for pain relief after shoulder hip arthroscopy: combined L1 and L2 paraverterbral blocks. J of surgery: a randomized, double-blind study. Anesth Analg; 2008, Clinical Anesthesia; 2008, 20:462-465. 106:328-33. 12. Wardhan R, Auroux AM, Ben-David B, Chelly JE: Is L2 25. Desroches J, Bouchard JF, Gendron L, Beaulieu P: Involvement of paravertebral block comparable to lumbar plexus block for cannabinoid receptors in peripheral and spinal morphine analgesia. postoperative analgesia after total hip arthroplasty? Clin Orthop Rel Neuroscience; 2014, 261:23-42. Res; 2014, 472(5):1475-81. 26. McCarty EC, Spindler KP, Tingstad E, Shyr Y, Higgins M: Does 13. Marhofer D, Marhofer P, Kettner SC, Fleischmann E, Prayer intraarticular morphine improve pain control with femoral nerve D, Schernthaner M, Lackner E, Willschke H, Schwetz P, block after anterior cruciate ligament reconstruction? American J of Zeitlinger M: Magnetic resonance imaging analysis of the spread Sports Med; 2001, 29(3):327-33. of local anesthetic solution after ultrasound-guided lateral thoracic 27. Vintar N, Rawal N, Veselko M: Intraarticular patient-controlled paravertebral blockade. Anesthesiology; 2013, 118(5):1106-12. regional anesthesia after arthroscopically assisted anterior cruciate 14. Richardson J, Jones J, Atkinson R: The effect of thoracic ligament reconstruction: ropivacaine/morphine/ketorolac versus paravertebral blockade on intercostal somatosensory evoked ropivacaine/morphine. Anesth Analg; 2005, 101:573-8. potentials. Anesth Analg; 1998, 87:373-6. 28. Reuben SS, Connelly NR: Postoperative analgesia for outpatient 15. Barrett WP, Turner SE, Leopold JP: Prospective randomized arthroscopic knee surgery with intraarticular bupivacaine and study of direct anterior vs postero-lateral approach for total hip ketorolac. Anesth Analg; 1995, 80:1154-7. arthroplasty. J of Arthroplasty; 2013, 28:1634-38.

M.E.J. ANESTH 23 (1), 2015

Subtenon bupivacaine injection for postoperative pain relief following pediatric strabismus surgery: A randomized controlled double blind trial

Radwa H Bakr** and Hesham M Abdelaziz*

Abstract

Background: Strabismus surgery in children is often associated with undesirable intraoperative and postoperative side effects including pain, postoperative nausea and vomiting (PONV), and occulocardiac reflex (OCR). Systemic analgesics have side effects and are contraindicated in some cases. We hypothesized that the preoperative subtenon injection of bupivacaine would reduce postoperative pain and the incidence of side effects adverse effects. Methods: Sixty children (2 to 6 years of age, ASA status I to II) were randomized to receive either subtenon bupivacaine 0.5% or a saline injection before the beginning of surgery in a double- blind manner. Pain scores using the Face, Legs, Cry, Activity, and Consolability (FLACC) scale, incidence of OCR and PONV, requirement of additional systemic analgesia, and time to discharge from the recovery room were compared. Results: The pain scores were significantly lower in the subtenon bupivacaine group at 0 min (p = 0.0056) and at 30 min (p = 0.013). There was no significant difference between the two groups at the other time intervals. There was a significant reduction in the incidence of occulocardiac reflex and the incidence of vomiting in the subtenon bupivacaine group. Eight of the 27 patients in the subtenon bupivacaine group required additional systemic analgesia compared to 19 of 29 controls. The time to discharge from recovery room was lower in the subtenon bupivacaine group. Conclusion: These data provide some evidence that a preoperative subtenon block with bupivacaine combined with general anesthesia allows efficient control of postoperative pain as well as a reduction in the incidence of OCR and PONV in young children undergoing strabismus surgery. Keywords: Bupivacaine, Pain, Pediatrics, Strabismus surgery, Subtenon anesthesia.

Introduction

Following strabismus surgery children often experience severe discomfort and are unable to open the operated eye. The surgical manipulation of the medial rectus muscle causes severe bradycardia because of the occulocardiac reflex1. The postoperative period is marked by frequent obvious discomfort, caused by a high frequency of postoperative nausea and vomiting and pain. Pain after strabismus correction is thought to be in the conjunctival area, but Tenon’s capsule, sclera, and stretched muscles may also contribute to its intensity1. This pain represents a source of distress to the child and the parents. Different modalities of treatment have been proposed and found to be variably effective. Opioids are helpful but carry the risk of nausea, vomiting, and drowsiness.

* ∗ MD. Department of anesthesia and intensive care, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

91 M.E.J. ANESTH 23 (1), 2015 92 Radwa Bakr et. al

Non-steroidal anti-inflammatory drugs (NSAIDs) and atropine (10 μg/kg) were given rectally 30 minutes remain controversial in small children. The side effects before anesthesia. EMLA (eutectic mixture of local of these agents are particularly undesirable in the anesthetics) cream was applied 30 min before anesthesia ambulatory surgery setting or are contraindicated in over two potential venipuncture sites. Induction was many children. Regional anesthesia has been proposed by sevoflurane inhalation and maintenance was by for management of postoperative pain following spontaneous ventilation of sevoflurane in oxygen and strabismus surgery. Topical amethocaine 1% drops nitrous oxide via laryngeal mask airway. Intraoperative and subconjunctival infiltration with bupivacaine analgesia was in the form of rectal paracetamol 20 0.5% administered at the conclusion of strabismus mg/kg. Patients were monitored intraoperatively by surgery have been shown to be effective in reducing electrocardiography, pulse oximetry, noninvasive 2,3,4 postoperative pain . Retrobulbur and peribulbar blood pressure, and end-tidal CO2 measurements. block have been explored in children with varying Heart rate and blood pressure were recorded before degrees of success5. Among the different techniques, induction and every 5 minutes during anesthesia and the subtenon eye block is widely used for anterior and surgery until the end of the procedure. After induction, posterior segment surgery in adults. A small quantity bupivacaine 0.5% or a placebo saline solution were of local anesthetic is injected in the subtenon space slowly injected in the subtenon space with a curved, by use of a smooth cannula after surgical incision blunt 25-mm 20 gauge cannula introduced through of the conjunctiva. This technique ensures adequate a small conjunctival and subtenon limbal aperture. postoperative analgesia in adults6,7 although it has not The dose of bupivacine was titrated according to the been sufficiently explored when used before the start child’s body weight to ensure a subtoxic dose of less of surgery in children. than 2.5 mg/kg. The efficacy of the block was judged satisfactory if the pupil was widely dilated and fixed, We performed a prospective, randomized, thus confirming ciliary ganglion blockade. double-blind, controlled study to determine the efficacy of subtenon’s bupivacaine injection at reducing The anesthesiologist, surgeon, and nurses were postoperative pain, the incidence of postoperative blinded to the nature of the injected solution. All complications, and the requirements of postoperative operations were performed by the same surgeon. analgesics in pediatric patients undergoing strabismus Surgery was started 5 minutes after the subtenon surgery. injection. The surgical protocol was standardized; for surgery on the vertical rectus muscles the conjunctiva was opened over the insertion. The inferior oblique was Patients and Methods approached via limbal peritomy if surgery on the lateral rectus was also being performed, or via a circumferential Approval to perform the study was granted by the conjunctival incision 10 mm from the limbus if not. The Institutional Review Board. Informed written consent conjunctiva was closed with 6-0 or smaller Vicryl®. was obtained from the parents prior to their children’s All patients received 1 drop of amethocaine 1% onto enrollment in the study. Sixty children aged 2-6 years the operated eye at the conclusion of surgery. After of age with ASA status I to II scheduled for primary emergence from anesthesia patients were transferred surgical correction of unilateral or bilateral strabismus to the recovery ward. On arrival in the recovery room, were included in the study. Patients were randomly the patient›s behavior was assessed by a nurse who allocated to one of 2 equal groups. The inclusion was not aware of the nature of the solution injected in criteria were: age 6 years or under, unilateral or bilateral the subtenon space. The pain scale used for assessment surgery, primary surgery or reoperation, horizontal, was the Face, Legs, Activity, Cry, Consolability scale vertical, or oblique muscle surgery. Exclusion criteria (FLACC)8 (Table 1). This behavioral pain assessment were: known drug sensitivity or body weight less than scale is widely accepted as a method of assessment 8 kg. for pain in children by direct observation. The scale A standard anesthetic protocol was used for all consists of 5 categories. Each category is scored on a children included in the studyMidazolam (0.3 mg/kg) 0-2 scale, which results in a total score of 0-10. A score Subtenon bupivacaine for pediatric strabismus surgery 93

Table 1 FLACC (face, legs, activity, cry, consolability) scale Face 0 1 2 No particular expression Occasional grimace or frown, Frequent to constant frown, or smile withdrawn, disinterested clenched jaw, quivering chin

Legs 0 1 2 Normal position or relaxed Uneasy, restless, tense Kicking or legs drawn up Activity Lying quietly, normal position, Squirming, shifting back and forth, Arched, rigid or jerking moves easily tense Cry 0 1 2 No cry (awake or asleep) Moans or whimpers Crying steadily, screams or sobs, frequent complaint Consolability 0 1 2 Content, relaxed Reassured by touch Difficult to console or comfort

The FLACC scale can be used in children up to 7 years and in children with cognitive impairment. Each of the five categories (faces, legs, activity, cry, consolability) is scored 0-2, and the scores are added to yield a total from 0 to 10. Each section above is scored and a total obtained. of 0 means relaxed and comfortable, 1-3 indicates Results mild discomfort, 4-6 indicates moderate pain, and 7-10 indicates severe discomfort or pain or both. Fifty six children completed the study. One child Pain assessment was performed after the removal of in the control group and three in the treatment group the laryngeal mask, and then at 30 min intervals until were excluded after recruitment due to incomplete discharge from the recovery ward. Children with a data. 46 (82.0%) underwent unilateral and 10 (18.0%) FLACC score equal to or higher than 4 were given 20 underwent bilateral surgery. 45 operations (81.1%) were mg/kg rectal paracetamol. The following parameters primary procedures and 11 (18.9%) were reoperations. were collected in the recovery room: Pain scores, at 0 27 children (48.6%) were randomized to the treatment min, 30 min, 1hr, 2hrs, 3hrs, incidence of occurrence of group and 29 (51.4%) were randomized to the control Occulo-cardiac reflex (indicated by a sudden decrease group. The groups were similar with regards to age, of the heart rate higher than 20% and concomitant with weight, sex, proportions having bilateral surgery or muscular traction), incidence of postoperative nausea reoperations, and number of muscles operated upon and vomiting, number of patients requiring additional (Table 2). systemic analgesia, and the mean time to first analgesia. The pain scores at each time interval are Statistical analysis was done using SPSS (version summarized in Table (3). The treatment group 14.0, SPSS Inc., Chicago, IL, USA). Continuous experienced significantly less pain than the control at data, such as age, weight, anesthetic duration, time the 0-h observation (P = 0.005) and at 30 min (P = to discharge from the recovery ward and time to eye 0.013). There was no significant difference between opening, were expressed as mean and SD and were the two groups at the other time intervals. There was analyzed using Student’s t-test. A chi-squared test was a significant reduction in the incidence of occurrence performed for the comparison between qualitative of occulocardiac reflex that required a temporary variables. A Mann-Whitney U test allowed intergroup interruption of traction on the muscles and the comparison between quantitative variables. A P value injection of atropine in the study group (5 patients) < 0.05 was considered as significant. Results were compared to (11 patients) in the control group. The expressed as mean ± SD. Confidence intervals of 95% incidence of nausea was not significantly decreased in are provided for statistically significant results. the study group (3 patients compared to 4 patients in

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Table 2 Patient characteristics: Data is presented as mean ± SD Subtenon Group Control Group P-value (N = 27) Mean (SD) (N = 29) Mean (SD) Age (years) 3.27 ± 1.69 3.37 ± 1.71 0.38 Weight (kg) 17.6 ± 3.6 17.9 ± 3.9 0.54 Sex ratio (male: female) 12:15 11:18 0.62 ASA I:II 18:1 18:1 1 Unilateral: Bilateral surgery 22:5 24:5 0.9 Primary surgery: reoperations 21:6 22:8 0.69 Number of operated muscles 2.2 ± 0.8 2.2 ± 0.8 1 Length of the operation 35.5 ± 10 36 ± 10.2 0.63 the control group); however, the incidence of vomiting proportion of children experience clinically significant was significantly lower in the study group (6 patients) pain after strabismus surgery9. Additionally, Pediatric than the control group (10 patients) (Table 4). Eight strabismus surgery often leads to postoperative of the 27 patients in the subtenons group required behavioral problems during the recovery period as a additional systemic analgesia (30%) compared to 19 result of pain, visual disturbances, nausea and vomiting, of 29 controls (65%). This difference was borderline and separation from parents. A study demonstrated with regards to statistical significance (P = 0.052). The that altered behavior was encountered on emergence median time to first analgesia was 2hrs 45min in the in 44% of operated children, and that 20% of them control group compared to 1 hour in the study group exhibited complex symptoms simulating delirium10. (Table 5). The length of stay in the recovery room Symptoms such as PONV and pain are the was reduced to a significant degree in the bupivacaine main cause of delayed discharge, contact with the group; two hours after the removal of the LMA, 22 hospital after discharge, and hospital readmission after of 29 children recruited in the control group were still outpatient surgery for these children11. present in the recovery room in contrast to 4 of the 27 Pain after strabismus surgery may be caused by children in the study group. sectioning and traction exerted on the extraoccular muscles. Many strategies have been proposed for Discussion treatment of the pain experienced by these children. Topical analgesia using drops containing a NSAID Strabismus surgery in children is frequently was efficient in some studies12, but not effective in performed as an outpatient procedure. A large others13,14.

Table 3 Summary of pain scores, Mean ± SD

Subtenon Group Control Group P-value (N = 27) (N = 29) 0 min 1.77 ± 1.12 3.41 ± 1.12 0.005 30 min 1.66 ± 1 3.17 ± 1.04 0.013 1 hr. 2.11 ± 0.89 2.14 ± 0.1 0.91 2 hrs. 2.55 ± 0.89 2.86 ± 1.41 0.57 3 hrs. 3.04 ± 1.4 2.72 ± 1.47 0.38 Subtenon bupivacaine for pediatric strabismus surgery 95

Table 4 Incidence of side effects: Data is presented as n(%)

Subtenon Group (N = 27) Control Group (N = 29) P-value

OCR 5 (18%) 11 (38%) 0.003 Incidence of nausea 3 (11%) 4 (14%) 0.575 Incidence of vomiting 6 (22%) 10 (34%) 0.048

Opioid analgesia is frequently used to reduce appropriate for many children undergoing strabismus postoperative pain after strabismus surgery; however, surgery. these drugs often cause nausea, vomiting, and Different techniques of regional anesthesia drowsiness. A study showed that opioid analgesia is combined with general anesthesia have been proposed associated with more prolonged recovery times after for the young child undergoing strabismus surgery. In anesthesia, a longer stay in hospital, and delayed return addition to controlling postoperative pain, it has been 15 to normal activity when compared to other analgesics . suggested that suppression of the trigeminal reflex by Intravenous NSAID such as ketorolac have been regional anesthesia may correlate with a decrease in shown to be as effective as morphine and pethidine for the incidence of vomiting29. the relief of pain after strabismus surgery in children, These techniques have yielded conflicting and with a lower incidence of postoperative nausea reports. Postoperative topical tetracaine compared and vomiting16,17. with topical saline in pediatric strabismus surgery was Other studies showed that systemic NSAIDs shown to provide a short-lived but significantly better such as ketoprofen were efficient in reducing pain pain relief as judged by both pain score and analgesic after strabismus surgery in children when compared to requirement30. placebo18,19. Topical amethocaine 1% drops and subconjunctival On the other hand certain NSAIDs such as infiltration with bupivacaine 0.5% administered at the ibuprofen and simple analgesics such as paracetamol conclusion of strabismus surgery have been shown to 20 were shown to be less effective . be equally effective in reducing postoperative pain31, Asthma occurs in 30% to 40% of children, 20% although another study did not show any additional of those are sensitive to aspirin and other NSAIDs21,22. analgesic effect of either of these interventions when In addition, reactions to NSAIDs include urticaria, compared to placebo32. Similarly, a study showed that angioedema, rhinitis23, and exacerbation of asthma the subconjunctival injection of bupivacaine 0.5% as or bronchospasm24-27, which may be fatal28. These compared with a placebo decreased postoperative pain side effects occur after administration in common scores in 36 young children. Another study compared ophthalmic procedures and have been shown to occur subconjunctival bupivacaine to topical tetracaine in with NSAIDs such as ibuprofen, diclofenac, and children undergoing squint surgery, with both giving ketorolac28. Therefore the use of NSAIDs may not be effective analgesia.

Table 5 Requirements of additional systemic analgesia Subtenon Group (N = 27) Control Group (N = 29) P-value

Number of patients requiring additional 8 (30%) 19 (65%). 0.052 systemic analgesia n (%) Median time to first analgesia 2 hours 45 minutes 1 hour 0.05

M.E.J. ANESTH 23 (1), 2015 96 Radwa Bakr et. al

However, some investigators found no These nerves carry sensory fibers from the sclera, difference in pain score after pediatric squint cornea, and uveal tract. Spread of the drug into the surgery using postoperative topical saline, topical muscle sheaths and eyelids results in anesthesia of tetracaine or subconjunctival bupivacaine. Although these structures40. subconjunctival local anesthetics have had some The surgery is then started through the same success in the relief of postoperative pain, the source conjunctival incision which allows access to extraocular of pain after strabismus surgery is believed to be muscles. Therefore, application of anesthetics is no receptors in tenon’s fascia and muscle tendons as well more invasive than the operation itself. Moreover, as conjunctival receptors. the required volume of local anesthetics to provide Regional blocks have also been explored in adequate analgesia is less important and limits the risks children. Retrobulbar anesthesia by the administration of damage caused by rapid injection or myotoxicity of 2 mL of bupivacaine 0.5% before surgery was as from the anesthetic solution. effective as a subconjunctival injection given after the Complications after subtenons anesthesia are operation in 10 children5. However the block reduced uncommon but orbital hemorrhage41, extraocular the incidence of OCR from 60% (control group) to 4% muscle injury42,43, and globe perforation with scissors in children3. Similarly, a study proved that peribulbar during dissection of the subtenons space44 have all block (0.3 mL/kg of a bupivacaine 0.5% and lidocaine been reported. There is also a risk of damage to 2% mixture) reduced postoperative pain in 25 children structures crossing the subtenons space during rapid 5 to 14 years of age to a significant degree; two thirds or high volume injection, and of myotoxicity from of these children were operated on for strabismus33,34. the anesthetic agent, but neither of these has yet been The authors also reported a major reduction in the reported after subtenons administration. This was fully incidence of occulocardiac reflex and postoperative explained to parents at the time of consent. There were nausea and vomiting compared with the control group no complications resulting from subtenon injection in treated with pethidine35,36. this study. However, when comparing different eye blocks We chose to administer the block preoperatively in children, subtenon anesthesia seems to offer some rather than postoperatively since regional blocks advantages over retrobulbar or peribulbar blocks in are associated with fewer episodes of bradycardia pediatric strabismus surgery; All these techniques and hypertension intraoperatively caused by the require the cooperation of patients by asking them occulocardiac reflex which results from the traction to move their eyes laterally to exclude perforation on the extraoccular muscles45, this was evident in our of the globe or nerve injury during the procedure37. study where a significant difference in the occurrence Small children are unable to cooperate in this way, of occulocardiac reflex was observed. which leads to performance of the block under general Preoperative administration also offered the anesthesia, with poor clinical control. advantage of facilitation of surgical dissection and Thus, in the current study, we elected to perform delivery of a controlled volume. The administration of subtenon anesthesia in pediatric patients undergoing local anesthetic, postoperatively is usually associated squint surgery. Subtenon’s anesthesia results in with protrusion of Tenon fascia and leakage of excellent anesthesia and akinesia and is widely used anesthetic through the incision. The administration for adult anterior and posterior segment surgery38. The of a preoperative subtenon block did not result in any anesthetic agent is delivered into the subtenon’s space surgical difficulty from tissue distortion. posterior to the globe’s equator using a blunt cannula In this study we looked at the administration inserted through a conjunctival incision, usually of a long acting anesthetic; bupivacaine has an onset located in the inferonasal quadrant. The drug spreads of action of approximately 20 min45, preoperative rapidly through the subtenon’s space and anesthetizes administration ensures analgesic effectiveness as the the long and short ciliary nerves as they pierce Tenon’s general anesthetic wears off. We, found significant capsule around the optic nerve39. reduction in postoperative pain score as measured by Subtenon bupivacaine for pediatric strabismus surgery 97 the FLACC score. No data in the literature suggests the optimal Similar results have been obtained in a randomized volume to inject in the pediatric population. Use of a controlled trial that investigated the postoperative use large volume to produce akinesia is not essential, as of sub-Tenon lignocaine in 111 children undergoing general anesthesia is always used with young children, squint surgery. Pain was reduced significantly in the which allows satisfactory operating conditions by 49-52 first hour after surgery, but thereafter there was no itself . effect46. Lignocaine is a shorter-acting anesthetic with A significant reduction in PONV was observed a duration of 1-2h when given as a sub-Tenon block, in our study during the recovery period. This while the effect of bupivacaine lasts for 3-3.5h45. undesirable effect after strabismus surgery is caused Our findings are also similar to those obtained by pain, traction of the muscles, and perioperative use of opioids. A similar reduction in PONV was also by Steib et al. who explored the preoperative encountered in the study conducted by Steib et al47. administration of bupivacaine in 40 children the authors found a significant reduction in pain scores in In conclusion, a preoperative subtenon block the study group. The incidence of occulocardiac reflex with bupivacaine combined with general anesthesia and postoperative nausea and vomiting were also allowed efficient control of postoperative pain as well reduced in the study group47. as a reduction in the incidence of OCR and PONV in young children undergoing strabismus surgery. On the other hand, in a study by Morris et al the We recommend that further studies be conducted to authors used preoperative levobupivacaine to perform determine the optimal volume to inject in the subtenon subtenon block in 27 children undergoing strabismus space and to compare different local anesthetics. surgery and found no significant reduction in pain scores in the study group49. However, their study had several limitations; a placebo was not used in the Acknowledgements control group, and not all patients received exactly the same general anesthetic agents or additional analgesia The authors sincerely acknowledge the support of these two factors may have influenced the results the Ain Shams University Ophthalmology Department obtained by these investigators. These factors were in supporting this anesthesiology research. The authors avoided in our study which may explain our favorable also acknowledge the efforts of Mr. Deepak Gupta in results. However, the results obtained by these authors the statistical calculations and analysis. matched previous results obtained by Carden et al33.

M.E.J. ANESTH 23 (1), 2015 98 Radwa Bakr et. al

References

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M.E.J. ANESTH 23 (1), 2015

CASE REPORTS

Straight to Video: Tonsillar Injury During Elective GlideScopeÒ-Assisted Pediatric Intubation

Jason D. Rodney*, Zulfiqar Ahmed*, Deepak Gupta*, and Maria Markakis Zestos*

Abstract

Airway management in pediatric patients presenting for tonsillectomy and adenoidectomy may prove challenging given the enlarged upper airway structures. Video Laryngoscopy (VL) can be very helpful but it does not come without risks. In this case report, we report an unfavorable outcome of VL in a pediatric patient with adenotonsillar hypertrophy.

Introduction

Airway management in pediatric patients presenting for tonsillectomy and adenoidectomy may prove challenging given the enlarged upper airway structures. Video Laryngoscopy (VL) as a modality of airway instrumentation has the potential to facilitate an unobstructed view of the vocal cords in situations where the oral, pharyngeal and laryngeal axes are difficult to align. Such may be the case due to body habitus, trauma or neoplasm, among other indications. For this reason, VL is an important tool in the anesthesiologist’s armamentarium. It has been suggested that VL has earned a place high up in an algorithm for dealing with a difficult airway, particularly in a “can’t intubate/can’t ventilate” patient scenario1-4. VL may also be considered in patients where minimizing the force required during laryngoscopy is desirable such as a patient with loose teeth. Even though VL can be very helpful, it does not come without risks. There have been numerous case reports describing injury to various oropharyngeal structures. Hereby, we report an unfavorable outcome of VL in a pediatric patient with adenotonsillar hypertrophy undergoing tonsillectomy and adenoidectomy.

Case Presentation

A 6-year old female with comorbidities of sickle cell disease and a history of numerous blood transfusions presented for elective tonsillectomy-adenoidectomy due to obstructive sleep apnea. Preoperative airway examination revealed Mallampati Class I with full range of neck

* MD. Corresponding author: Maria Markakis Zestos, MD, Chief of Anesthesiology, Children’s Hospital of Michigan, Associate Professor, Wayne State University, 3901 Beaubien St, Suite 3B-17, Detroit Michigan 48201, United States. Office: 1-313- 745-5535, Fax: 1-313-745-5448. E-mail: [email protected]

101 M.E.J. ANESTH 23 (1), 2015 102 J.Rodney et. al and jaw mobility, adequate thyro-mental distance, Discussion and as expected, enlarged tonsils. In addition to tonsillar hypertrophy, it was noted that the patient Even though VL has been shown to improve the had loose upper incisors about which the parent was ability of novices to obtain laryngeal exposure when very concerned. The anesthesia team decided to use compared to Direct Laryngoscopy (DL) in adults5, GlideScopeÒ Cobalt AVL for endotracheal intubation there is evidence for and against ease of use with in an effort to avoid inadvertent pressure or traction on respect to pediatric patients. Fonte et al6 demonstrated the loose teeth. that pediatric residents, who were unfamiliar with VL, After the induction of anesthesia, endotracheal failed at tracheal intubations at a higher rate while using VL than when performing DL with a Miller intubation was attempted by the anesthesiology blade in pediatric patients with a normal airway or resident with the GlideScopeÒ. A Cormack Lehane tongue edema. Ilies et al7 found no difference between grade I laryngoscopic view was easily achieved with an attending physician’s and an experienced resident’s a size 2 GlideScopeÒ blade. A 6.0 internal diameter ability to obtain an improved view of vocal cords using (ID) oral RAE endotracheal tube, without stylet, was VL after DL. Despite a perceived disadvantage to using unsuccessfully introduced to the oropharynx. The VL for tracheal intubation by novices, it has been shown Ò rigid GlideRite stylet was not used during the initial that in the hands of experienced anesthesiologists, attempts to pass the endotracheal tube because when VL does improve the ability to successfully intubate inserted into the endotracheal tube, the tip of the stylet pediatric patients8-10. VL may prove to be a useful tool protruded beyond the end of the oral RAE endotracheal in obtaining laryngeal exposure, but there have been tube. The RAE endotracheal tube of ID 6.0 mm was numerous reports of injury to various oropharyngeal removed, and it was noted that blood was present on structures in adults including abrasion, perforation the tip of the endotracheal tube. and laceration of tonsils, palatopharyngeal wall, 11-18 Mask ventilation was resumed with oxygen lingual nerve as well as dental injury . It has been and sevoflurane and at this time, it was much more suggested that both the blind insertion and pathway of the endotracheal tube and the rigid stylet may be difficult to manually ventilate than during induction contributing factors to oropharyngeal injury during despite head-tilt-chin-lift and jaw thrust maneuvers. VL19-20. A subsequent attempt at VL by the supervising anesthesiologist revealed that the tonsils were almost Although the decision for airway instrument completely obstructing the laryngoscopic view. Further choice was ultimately influenced by the patient’s attempts at intubation were withheld, and assistance dentition rather than a perceived difficult airway (even though the loose tooth was eventually removed by a was sought from the otorhinolaryngology surgical dentist), this case shows one instance wherein use of team due to the apparent injury to the enlarged tonsils GlidescopeÒ for pediatric endotracheal intubation may during the initial intubation attempt. have contributed to more harm than good. Even if the The examination by the otorhinolaryngologist rigid stylet is not used to facilitate intubation, there is revealed Brodsky Grade 4+ tonsils with one an inherent risk of oropharyngeal injury when using partially detached tonsil having minimal mucosal the video laryngoscope due to the inability to visualize bleeding. Endotracheal intubation was achieved by the endotracheal tube passing from the opening of the an attending physician with a Miller 2 blade with no mouth to the point where it enters the field of focus of observable effect to the loose teeth. At this time, the the camera lens. decision was made to proceed with the tonsillectomy- The GlidescopeÒ has become a popular tool adenoidectomy as planned. After discussion with the among peri-operative, critical care and emergency concerned parent, the loose tooth was removed by the room care providers. Few would dispute that it attending dentist. The remainder of the peri-operative has earned a place in the American Society of course was unremarkable. Anesthesiologists’ Difficult Airway Algorithm21 which Injury with GlideScope pediatric intubation 103 states that providers managing difficult airway should the risk of oropharyngeal injury or failed intubation in give appropriate considerations to the comparative inexperienced hands. benefits vs. workability potential of options including 3 VL as the initial intubation attempt . In the presence of Conclusion a known pharyngeal mass it may be worth considering DL, flexible fiberoptic (FFO) bronchoscope ora In summary, operators’ tendency to direct and combination of VL and FFO used in conjunction as focus their attention ‘Straight To Video’ in VL should described by Weissbrod and Merati22. We would be cautioned against in order to avoid potential also recommend caution when using the video oropharyngeal injuries along the route of blind laryngoscope for educational purposes. Although VL insertion of the endotracheal tube from the angle of the may facilitate both trainer and trainee to visualize the mouth until it becomes visible on the screen of the VL. vocal cords in pediatric patients, its use may increase

M.E.J. ANESTH 23 (1), 2015 104 J.Rodney et. al

References

1. Caldiroli D, Cortellazzi P: A new difficult airway management 12. Cooper RM: Complications associated with the use of the algorithm based upon the El Ganzouri Risk Index and GlideScope® GlideScope videolaryngoscope. Can J Anaesth; 2007, 54:54-57. videolaryngoscope: a new look for intubation? Minerva Anestesiol; 13. Choo MK, Yeo VS, See JJ: Another complication associated with 2011, 77:1011-1017. videolaryngoscopy. Can J Anaesth; 2007, 54:322-324. 2. Frova G: Do videolaryngoscopes have a new role in the SIAARTI 14. Chin KJ, Arango MF, Paez AF, Turkstra TP: Palatal injury difficult airway management algorithm? Minerva Anestesiol; 2010, associated with the GlideScope. Anaesth Intensive Care; 2007, 76:637-640. 35:449-450. 3. Saxena S: The ASA difficult airway algorithm: is it time to include 15. Malik AM, Frogel JK: Anterior tonsillar pillar perforation during video laryngoscopy and discourage blind and multiple intubation GlideScope video laryngoscopy. Anesth Analg; 2007, 104:1610- attempts in the nonemergency pathway? Anesth Analg; 2009, 1611. 108:1052. 16. Vincent RD JR, Wimberly MP, Brockwell RC, Magnuson JS: Soft 4. Weiss M, Engelhardt T: Proposal for the management of the palate perforation during orotracheal intubation facilitated by the unexpected difficult pediatric airway. Paediatr Anaesth; 2010, GlideScope videolaryngoscope. J Clin Anesth; 2007, 19:619-621. 20:454-464. 17. Hsu WT, Tsao SL, Chen KY, Chou WK: Penetrating injury of 5. Cooper RM, Pacey JA, Bishop MJ, Mccluskey SA: Early clinical the palatoglossal arch associated with use of the GlideScope experience with a new videolaryngoscope (GlideScope) in 728 videolaryngoscope in a flame burn patient. Acta Anaesthesiol patients. Can J Anaesth; 2005, 52:191-198. Taiwan; 2008, 46:39-41. 6. Fonte M, Oulego-Erroz I, Nadkarni L, Sánchez-Santos L, 18. Leong WL, Lim Y, Sia AT: Palatopharyngeal wall perforation during Iglesias-Vásquez A, Rodríguez-Núñez A: A randomized comparison Glidescope intubation. Anaesth Intensive Care; 2008, 36:870-874. of the GlideScope videolaryngoscope to the standard laryngoscopy 19. Dupanovic M: Maneuvers to prevent oropharyngeal injury during for intubation by pediatric residents in simulated easy and difficult orotracheal intubation with the GlideScope video laryngoscope. J infant airway scenarios. Pediatr Emerg Care; 2011, 27:398-402. Clin Anesth; 2010, 22:152-154. 7. Ilies C, Fudickar A, Thee C, Dütschke P, Hanss R, Doerges V, Bein 20. Magboul MM, Joel S: The video laryngoscopes blind spots and B: Airway management in pediatric patients using the Glidescope possible lingual nerve injury by the Gliderite rigid stylet-case Cobalt®: a feasibility study. Minerva Anestesiol; 2012, 78:1019- presentation and review of literature. Middle East J Anesthesiol; 1025. 2010, 20:857-860. 8. Kim JT, Na HS, Bae JY, Kim DW, Kim HS, Kim CS, Kim SD: 21. Apfelbaum JL, Hagberg CA, Caplan RA, Blitt CD, Connis RT, GlideScope video laryngoscope: a randomized clinical trial in 203 Nickinovich DG, Hagberg CA, Caplan RA, Benumof JL, Berry paediatric patients. Br J Anaesth; 2008, 101:531-534. FA, Blitt CD, Bode RH, Cheney FW, Connis RT, Guidry OF, 9. Redel A, Karademir F, Schlitterlau A, Frommer M, Scholtz Nickinovich DG, Ovassapian A: American Society of LU, Kranke P, Kehl F, Roewer N, Lange M: Validation of the Anesthesiologists Task Force on Management of GlideScope video laryngoscope in pediatric patients. Paediatr the Difficult Airway: Practice guidelines for management Anaesth; 2009, 19:667-671. of the difficult airway: an updated report by the American Society 10. Xue FS, Liu HP, Liu JH, Liao X, Zhang YM: Facilitating of Anesthesiologists Task Force on Management of the Difficult endotracheal intubation using the GlideScope video laryngoscope in Airway. Anesthesiology; 2013, 118:251-270. children with difficult airways.Paediatr Anaesth; 2009, 19:918-919. 22. Weissbrod PA, Merati AL: Reducing injury during video-assisted 11. Cross P, Cytryn J, Cheng KK: Perforation of the soft palate using endotracheal intubation: the “smart stylet” concept. Laryngoscope; the GlideScope videolaryngoscope. Can J Anaesth; 2007, 54:588- 2011, 121:2391-2393. 589. Percutaneous Balloon Compression of Gasserian Ganglion for the treatment of Trigeminal Neuralgia: An Experience from India

Dr. Anurag Agarwal*, Dr. Vipin Dhama**, Dr. Yogesh K. Manik**, Dr. M. K. Upadhyaya**, Dr. C. S. Singh**and Dr. V. Rastogi**

Abstract

Trigeminal neuralgia (TN) is characterized by unilateral, lancinating, paroxysmal pain in the dermatomal distribution area of trigeminal nerve. Percutaneous balloon compression (PBC) of Gasserian ganglion is an effective, comparatively cheaper and simple therapeutic modality for treatment of TN. Compression secondary to PBC selectively injures the large myelinated A-alfa (afferent) fibers that mediate light touch and does not affect A-delta and C-fibres, which carry pain sensation. Balloon compression reduces the sensory neuronal input, thus turning off the trigger to the neuropathic trigeminal pain. In this current case series, we are sharing our experience with PBC of Gasserian Ganglion for the treatment of idiopathic TN in our patients at an academic university-based medical institution in India. During the period of August 2012 to October 2013, a total of twelve PBCs of Gasserian Ganglion were performed in eleven patients suffering from idiopathic TN. There were nine female patients and two male patients with the age range of 35-70years (median age: 54years). In all patients cannulation of foramen ovale was done successfully in the first attempt. In eight out of eleven(72.7%) patients ideal ‘Pear-shaped’ balloon visualization could be achieved. In the remaining three patients (27.3%), inflated balloon was ‘Bullet-shaped’. In one patient final placement of Fogarty balloon was not satisfactory and it ruptured during inflation. This case was deferred for one week when it was completed successfully with ‘Pear-shaped’ balloon inflation. During the follow up period of 1-13 months, there have been no recurrences of TN. Eight out of eleven patients (72.7%) are completely off medicines (carbamazepine and baclofen) and other two patients are stable on very low doses of carbamazepine. All patients have reported marked improvement in quality of life. This case series shows that percutaneous balloon compression is a useful minimally invasive intervention for the treatment of trigeminal neuralgia.

Introduction

Trigeminal neuralgia (TN) is characterized by unilateral, lancinating, paroxysmal pain in the dermatomal distribution area of trigeminal nerve1. According to International Headache Society (IHS) and International Association for Study of Pain (IASP) trigeminal neuralgia is

* md, PDCC. ** MD. Corresponding author:Anurag Agarwal, MD, PDCC, Pain Specialist & Associate Professor, Dept. of Anesthesiology & Pain Medicine, Lala Lajpat Rai Memorial Medical College, Meerut, Uttar Pradesh, India. Tel: 00-91-73889-70385. E-mail ID: [email protected]

105 M.E.J. ANESTH 23 (1), 2015 106 Anurag agarwal et. al painful, unilateral affliction of face, characterized by which carry pain sensation. Balloon compression brief, electric shock like pain limited to one or more reduces the sensory neuronal input, thus turning off divisions of trigeminal nerve, commonly evoked by the trigger to the neuropathic trigeminal pain. PBC is trivial stimuli like shaving, talking, washing of face not as selective for pain originating from a particular but may also occur spontaneously with abrupt onset trigeminal division as radiofrequency thermo- and termination2. Exact cause of TN is not known, and coagulation (RFTC) is10,11. multiple treatment options are available but there is no In this current case series, we are sharing our 3 ideal treatment available for all patients . Severity of experience with PBC of Gasserian ganglion for pain can result in poor health and deterioration of day- the treatment of idiopathic TN in our patients at an 4,5 to-day functional status . According to IHS, TN can academic university-based medical institution in India. be classified as classical or idiopathic and symptomatic or secondary6,7. In 2003, Burchiel classified TN on Case Series the basis of clinical features: Type 1 TN which is predominantly episodic and sharp; and Type 2 TN which is constant, dull, and burning in nature8. During the period of August 2012 to October 2013, a total of twelve PBCs of Gasserian Ganglion The American Academy of Neurology (AAN) were performed in the Department of Anesthesiology and the European Federation of Neurological and Pain Medicine at Lala Lajpat Rai Memorial Societies (EFNS) Guidelines on TN treatment (2008) Medical College, Meerut, India in eleven patients recommend medical treatment with carbamazepine suffering from idiopathic TN. There were nine female and oxcarbazepine or lamotrigine and baclofen as patients and two male patients with the age range of 7 first option for TN . In patients refractory to medical 35-70years (median age: 54years). All the patients treatment or in whom side effects of medications are were suffering from Burchiel Type 1 TN with the intolerable, other surgical treatments are recommended. classical features of idiopathic TN i.e., electric shock- Various modalities of surgical treatment are possible, like lancinting pain in the territory of trigeminal from major intracranial operation to minimally nerve (CN V). Two patients had involvement of invasive percutaneous techniques. Because of the both maxillary (V2) and mandibular (V3) divisions of achievable longest duration of pain relief, micro- Cranial Nerve V; three patients had involvement of vascular decompression (MVD) is recommended as V division only and remaining six patients had TN the first option, but it is a major intracranial operation, 2 alongV3 division only. The duration of the disease which may not be suitable for older, debilitated ranged from 2.5-12 years. Only three patients could patients. MVD is also complicated with the risk of undergo a magnetic resonance imaging because of major neurological morbidity and mortality. Due to financial constraints; all other patients were screened their minimally invasive nature and possibility to for any intra-cranial pathology by computerized repeat, percutaneous procedures are widely used for tomography scanning. None of our patients had the surgical treatment of TN, mostly in the patients bilateral TN; five patients had involvement of right who are not eligible for MVD, are not willing to side CN V and six patients had left-sided involvement. have MVD or are refractory to previous surgical All patients had been treated with carbamazepine and treatments. One of these procedures is percutaneous baclofen as part of failed medical management prior balloon compression (PBC) of Gasserian ganglion to PBC. One patient had already undergone retro- which was first introduced by Mullan and Lichtor in gasserian glycerol rhizotomy, which provided pain 9 1983 . relief for only five months. One patient underwent PBC is an effective, comparatively cheaper and PBC on two occasions secondary to non-satisfactory simple therapeutic modality for treatment of TN. placement of balloon inside the Meckel’s cave Compression secondary to PBC selectively injures the followed by rupture of balloon and venous bleeding. large myelinated A-alfa (afferent) fibers that mediate The case was deferred and performed again after one light touch and does not affect A-delta and C-fibres, week with satisfactory results. Compression in Gasserian ganglion in trigeminal neuralgia 107

Procedural Details of PBC: All the procedures Fig. 2 were performed under conscious sedation using two Modified Submental View with cannula in Foramen ovale dimensional C-arm fluoroscopic guidance. Patients were placed in supine position with slight extension of neck. C-arm fluoroscope was aligned to take a ‘Modified sub-mental view’, in which foramen ovale was visualized between mandible on the lateral side and maxilla on the medial side (Figure 1). In this view, a 14-gauge cannula with blunt trocar was used to enter the foramen ovale to reach the Meckel’s cave where the Gasserian ganglion is situated (Figure 2). Once entry was confirmed in the Meckel’s cave, lateral view was obtained wherein 4-Fr Fogarty catheter was gently threaded in to the Meckel’s cave up to the clivus. After confirmation of correct Procedural Results of PBC: In all patients position of the balloon in anterio-posterior and lateral cannulation of foramen ovale was done successfully in views, Fogarty balloon was inflated with 0.8-1 ml the first attempt. In eight out of eleven(72.7%) patients of water soluble contrast dye (Omnipaque-240, GE ideal ‘Pear-shaped’ balloon visualization could be Healthcare) for 1.5-3minutes. After completion of achieved (Figures 3-4). In the remaining three patients the intervention, Fogarty balloon was deflated and (27.3%), inflated balloon was ‘Bullet-shaped’. In one removed along with the cannula; and manual digital patient final placement of Fogarty balloon was not pressure was applied for five minutes against the satisfactory and it ruptured during inflation. This case maxilla to stop any bleeding and cerebrospinal fluid was deferred for one week when it was completed drainage. A small dressing was applied on the skin successfully with ‘Pear-shaped’ balloon inflation. In puncture site and patients were transferred to post- one patient, venous bleeding was detected on removal anesthesia care unit for observation. After regaining of trocar from cannula that ceased after placement of full consciousness, patients were examined for relief Fogarty catheter and successful PBC. In another patient, in pain, facial sensation and corneal reflex; and, after who had not been pre-medicated with atropine, there two to four hours, patients were discharged home on was sudden asystole on entering in to the foramen ovale, oral antibiotics and non-steroidal anti-inflammatory which responded to Inj. atropine 1.2mg intravenous drugs (NSAIDs). bolus with no post-operative sequelae. In all other

Fig. 1 patients, no episode of major bradycardia occurred due Submental View showing Foramen Ovale to pre-medication with atropine 0.4mg intravenously. All patients had complete relief of neuralgic pain in the immediate post-operative period. In nine out of eleven patients (81.81 %), there was mild to moderate facial hypoesthesia, which was more prominent with longer compression-duration (3 minutes vs. 1.5 minutes). This hypoesthesia improved within 6-8 weeks and did not cause appreciable discomfort to these patients. Five out of eleven patients (45.4%) complained about mild facial dysesthesias (continuous burning sensation in CN V distribution), which improved in 6-8 weeks with the use of neuro-modulatory drugs such as pregabalin. One patient complained of malocclusion of mandible and difficulty in chewing on the operated side, which

M.E.J. ANESTH 23 (1), 2015 108 Anurag agarwal et. al

Fig. 3 Fig. 4 Ideal Pear shaped balloon in Lateral View Anterio-Posterior view with Pear shaped balloon

Discussion

also improved in four weeks without any treatment. poorly myelinated A-delta fibers13. So it may be the

Four out of eleven (36.36%) patients revealed mild to best technique for addressing ophthalmic division (V1) moderate asymptomatic masseteric weakness on post- pain of TN6 and this observation has been confirmed operative physical examination that also improved in by Brown et al12. 4-6 weeks. None of the patients had loss of corneal Initially PBC was advocated for older age reflex and/or anesthesia dolorosa. In two out of eleven group and for those who were unfit for major surgical (18.2%) patients, there was eruption of herpes labialis procedure. Now it has been found useful even in on the ipsilateral side, which was treated with anti-viral many young patients, especially those who do not drugs with resolution of the lesions within two weeks. have any evidence of vascular malformation and/or All patients complained of temporal headache in the are unwilling to undergo major surgery. Strojnik and immediate post-operative period, which improved in Smigoc9 and Natrajan14 have used this technique in 24-48 hrs with the use of NSAIDs and ice fomentation. patients with aberrant basilar artery as well as in young None of the patients had any major complication such as patients. In our study, there was a female patients corneal ulcer, 4th or 6th cranial nerve palsy, meningitis preponderance, most patients were of advanced age or death. During the follow up period of 1-13 months, and there was almost equal distribution of right side there have been no recurrences of TN. Eight out of vs. left side involvement, although some authors have eleven patients (72.7%) are completely off medicines found preponderance of right sided involvement9. (carbamazepine and baclofen) and other two patients In all our patients, modified Mullan’s technique are stable on very low doses of carbamazepine. All was used9,11 for PBC. Though ‘Pear-shaped’ balloon is patients have reported marked improvement in quality considered to be the best in some studies9,10,15,16,17, this of life. shape was achieved in only eight out of eleven patients Minimally invasive pain interventions have in our series but we did not find any differences in found a niche among the available treatments for many the outcome, possibly due to shorter follow-up in our intractable, chronic painful conditions such as TN. study (1-13 months). Same can be true in regards to the PBC has been found to be an effective intervention in compression-duration wherein practitioners have used many studies3,6,10,12. PBC has an advantage of sparing compression time ranging from 1-20 minutes; some the corneal reflex over other percutaneous methods. It authors have reported correlation between the duration has a unique mechanism of action of selective injury of compression and duration of pain relief but with to large myelinated A-alfa and A-beta fibers and longer duration of compression, more complications relative sparing of small, unmyelinated C-fibers and like facial dysesthesias9,15,18have been reported. Compression in Gasserian ganglion in trigeminal neuralgia 109

Because there is no consensus on the optimal duration operative sequelae. Therefore, it is our suggestion to of compression during PBC, in our practice we have ensure premedication with atropine prior to penetration used the compression times of 1.5 minutes and 3 of foramen ovale before all percutaneous procedures minutes; and we have found that although the pain including PBC. Though review of medical literature relief was complete with both compression-duration, elicits rare incidences of anesthesia dolorosa, intra- incidence and magnitude of facial hypoesthesia and cranial fistula formation and cranial nerve injury, dysesthesia was more in patients who had received corneal ulceration and death during PBC, we did not compression for longer duration. encounter any such adverse effect. Prolonged masticatory weakness due to Recurrence of pain after successful PBC and masseter-pterygoid weakness has been reported initial pain relief has been reported very widely in the 20 after PBC11,15. We also encountered malocclusion literature, Baabor and Perez-Limonte had reported 17 on ipsilateral jaw in one patient and mild masseteric 15% recurrence after 3 years, and Skirving and Dan weakness in four patients, which was not bothersome had reported 31.9% recurrence in 20-years duration. to the patients because pre-procedure, they were In our moderate follow-up period of 1-13 months, we not chewing from that side any way due to the have not found any recurrence so far. precipitation of their neuralgic pain. In all patients, The major limitations in the present study were this weakness completely recovered in 4-6 weeks retrospective nature of the case series, small number without any intervention. In all patients in our series, of patients (n=11) and short duration of follow-up complete relief from neuralgic pain was observed, (1-13months). which is similar to other studies9,11,14. Autonomic changes such as bradycardia and hypotension have Conclusion been reported on entering the foramen ovale in more 14,19 than 50% of cases which was not observed in This case series shows that percutaneous our series because of pre-medication with atropine. balloon compression of Gasserian ganglion is a useful Though no mortality has been reported during PBC minimally invasive intervention for the treatment of in the literature, Natrajan had reported an incidence trigeminal neuralgia. If performed appropriately with of intra-operative myocardial infarction which was the help of anatomical landmarks and radiological managed successfully14. We also encountered a case guidance, it is a low risk procedure with high success of sudden asystole on foramen ovale penetration in a rate. Due to very low incidence of corneal anesthesia patient who was not given atropine pre-operatively in and anesthesia dolorosa, we recommend PBC as spite of our policy. It was recognized immediately due first choice among percutaneous interventions for to continuous electrocardiography and was managed TN especially involving V1division as well as in successfully with rescue dose of atropine with no post- multidivisional pain.

M.E.J. ANESTH 23 (1), 2015 110 Anurag agarwal et. al

References

1. Edlich RF, Winters KL, Britt L, Long WB 3rd: Trigeminal the trigeminal ganglion for trigeminal neuralgia. Journal of neuralgia. J Long Term Eff Med Implants; 2006, 16:185-192. Neurosurgery; 1983, 59:1007-1012. 2. Merskey H, Bogduk N: Classification of chronic pain. Descriptions 12. Brown JA, McDaniel MD, Weaver MT, Burchiel KJ, Young of Chronic Pain Syndromes and Definitions of Pain Terms. Seattle: RF:Percutaneous trigeminal nerve compression for treatment of IASP Press; 1994, 59-71. trigeminal neuralgia: results in 50 patients. Neurosurgery; 1993, 3. Tattli M, Satici O, Kanpolat Y, Sindou M: Various surgical 32:570-573. modalities for trigeminal neuralgia: literature study of retrospective 13. Brown JA, Hoeflinger B, Long PB, Gunning WT, Rhoades R, long-term outcomes. ActaNeurochirurgica; 2008, 150:243-255. Bennett-Clarke CA, Chiaia NL, Weaver MT:Axon and ganglion 4. Pollock BE, Stein KJ: Surgical management of trigeminal neuralgia cell injury in rabbits after percutancous trigeminal balloon patients with recurrent or persistent pain despite three or more prior compression. Neurosurgery; 1996, 38:993-1004. operations. World Neurosurgery; 2010, 73:523-528. 14. Natarajan M: Percutaneous trigeminal ganglion balloon compression: experience in 40 patients. Neurol India; 2000, 48:330. 5. Tölle T, Dukes E, Sadosky A: Patient burden of trigeminal neuralgia: 15. Kouzounias K, Schechtmann G, Lind G, Winter J, Linderoth results from a cross-sectional survey of health state impairment and B:Factors that influence outcome of percutaneous balloon treatment patterns in six European countries. Pain Practice; 2006, compression in the treatment of trigeminal neuralgia. Neurosurgery; 6:153-160. 2010, 67:925-934. 6. Campos WK, Linhares MN: A prospective study of 39 patients with 16. Park SS, Lee MK, Kim JW, Jung JY, Kim IS, Ghang CG:Percutaneous trigeminal neuralgia treated with percutaneous balloon compression. Balloon Compression of Trigeminal Ganglion for the Treatment ArqNeuropsiquiatr; 2011, 69:221-226. of Idiopathic Trigeminal Neuralgia: Experience in 50 Patients. J 7. Cruccu G, Gronseth G, Alksne J, Argoff C, Brainin M, Burchiel Korean NeurosurgSoc; 2008, 43:186-189. K, Nurmikko T, Zakrzewska JM: AAN-EFNS guidelines on 17. Skirving DJ, Dan NG:A 20-year review of percutaneous balloon trigeminal neuralgia management. European Journal of Neurology; compression of the trigeminal ganglion. Journal of Neurosurgery; 2008, 15:1013-1028. 2001, 94:913-917. 8. Burchiel J: A new classification for facial pain.Neurosurgery ; 2003, 18. Lichtor T, Mullan JF: A 10-year follow-up review of percutaneous 53:1164-1167. microcompression of the trigeminal ganglion. J Neurosurg; 1990, 9. Strojnik T, Ŝmigoc T: Percutaneous Trigeminal Ganglion Balloon 72:49- 54. Compression Rhizotomy: Experience in 27 Patients. The Scientific 19. Brown JA, Preul MC: Trigeminal ganglion compression for World Journal; Article ID 328936, 2012,6 pages. trigeminal neuralgia: experience in 22 patients and review of the 10. Linderoth B, Bergenheim AT:The predictive power of balloon literature. J Neurosurg; 1989, 70:900-904. shape and change of sensory functions on outcome of percutaneous 20. Baabor MG, Perez-Limonte L: Percutaneous balloon balloon compression for trigeminal neuralgia: clinical article. compression of the gasserian ganglion for the treatment of Journal of Neurosurgery; 2010, 113:498-507. trigeminal neuralgia: personal experience of 206 patients. 11. Mullan S, Lichtor T: Percutaneous microcompression of ActaNeurochirurgicaSupplementum; 2011, 108:251-254. Bedside retained radial artery catheter removal in a hemodynamically unstable neurocritically-ill patient: a case report.

Christa O’Hana V. San Luis* and Athir H. Morad*

Abstract

Radial artery insertion is a common procedure in intensive care units. We describe a case of a critically-ill 73-year-old man in the neurocritical care unit with a subarachnoid hemorrhage whose radial arterial catheter tip was transected from the main line and was successfully managed with bedside retrieval of the catheter.

Introduction

Radial artery insertion is usually done in the neurocritical care unit (NCCU) for the purposes of blood pressure monitoring and arterial blood sampling. Several complications are known such as temporary occlusion, thrombosis, pseudoaneurysm formation, hematoma formation, abscess, cellulitis, median nerve involvement and air embolism. Retained radial artery catheter is rare but has been reported in literature. Several causes have been mentioned such as accidental transection, repeated catheterization and repeated wrist movements. Several modalities have been mentioned to confirm the location of the arterial catheter as well as different methods to remove the catheter. We describe a case of a 73-year-old man who presented with aneurysmal subarachnoid hemorrhage due to an anterior communicating aneurysm and underwent aneurysmal clipping. His course was complicated by cardiopulmonary instability. On his first post-operative day, the radial arterial catheter tip on his left wrist was fractured from the main line as it was being removed. He then underwent a bedside vascular exploration and removal of the foreign body. We also present a review and summary of the available literature regarding retained radial catheters and the available modes of image confirmation and options for treatment.

Case

A 73-year-old man was admitted in our Neurosciences critical care unit (NCCU) for an aneurysmal subarachnoid hemorrhage (ASAH), Hunt and Hess 3, Modified Fischer Scale 3. He underwent aneurysmal clipping after a four vessel angiogram revealed a 3-millimeter irregular and superiorly projecting anterior communicating artery aneurysm. Post-operatively day 1, he was very agitated and his left radial arterial catheter was discontinued due to very poor waveform. As it was being pulled out, the nurse noticed that the long portion of the distal cannula was not there. It was highly suspected that it was still in the vessel. Pulses and perfusion distally were adequate. A

* m.D, Department of Anesthesia and Critical Care Medicine, Division of Neurosciences critical care, Johns Hopkins University School of Medicine Baltimore, MD 21287, USA. Corresponding author: Christa O’Hana V. San Luis, M.D, 600 N Wolfe Street, Phipps 455, Baltimore, MD, 21287. Tel: (949)8780490, Fax: (410)6147903. [email protected]

111 M.E.J. ANESTH 23 (1), 2015 112 Christa San Luis et. al stat portable 3-view X-ray of the wrist and hand done Fig. 2 visualized a 4cm catheter fragment in the anterolateral Proximal part of the radial arterial catheter without the soft tissue aspect of the distal forearm proximal to retained distal catheter tip the left wrist (Figure 1). A vascular surgery consult was placed and surgical removal and exploration was planned the following day. His family was informed of the incident and consented for the procedure. On the day of the planned exploration, the patient had acute respiratory failure further complicated by an asystolic event. He was immediately resuscitated and was started on norepinephrine, dopamine, epinephrine to maintain his mean arterial pressure. The surgical procedure was postponed due to hemodynamic instability. Three days after, it was deemed that due to the patient’s continued hemodynamic instability, he was not a good surgical candidate to transport to the operating room. The bedside exploration of the left radial artery and Discussion the removal of the distal catheter tip were then done with local anesthesia under ultrasound guidance. The The radial arterial line for this patient was for incision was made at the top of the radial artery on strict blood pressure monitoring which is one of the the left forearm. The catheter was identified right at most common reasons for its placement1,2. The reason the entry site of the radial artery. DeBakey pickups for the radial artery catheter breakdown in this patient were used to extract the catheter out of the radial is unclear. Several reasons for this type of breakdown artery (Figure 2). The radial artery was found to be have been reported in the past including accidental thrombosed at that location. Dopplers were performed transection while separating the arterial line from after the procedure to assure adequate pulses and the intravenous line3, possible damage to the catheter perfusion distally. The procedure was tolerated well sheath due to repeated catheterization attempts4, and perfusion was maintained throughout the hospital transection while suturing5, shearing off of the cannula stay. due to repeated wrist movement postoperatively during 6-8 9 Fig. 1 recovery , reinsertion of the stylet needle , accidental Plain left hand and wrist x-ray. Panel A is the PA (postero- cutting during suture removal10,11 and dressing anterior) view. Panel B is the lateral view. Encircled in red is removal12. In our case, our suspicion is that the patient the retained radial artery catheter fragment was probably moving his wrist repeatedly during his post-operative agitation. Prompt vascular surgery consult for possible exploration is very important to prevent the possibility of distal embolization and distal migration with thrombosis. There is also a possibility of proximal migration4 and the use of ultrasound to confirm the location of the catheter preoperatively is recommended. Described by Aslam et al.1, this proximal migration, although unlikely, may occur because of arterial spasm distally. Several imaging modalities may be used to confirm the location of the retained fragment (Table 1). In this patient, the most rapid way to confirm the imaging late at night was a plain radiograph. With the vascular surgery team Bedside retained radial artery catheter removal 113

Table 1 Summary of causes, diagnostic imaging and approach to removal of retained radial artery catheters (CT = computed tomography, OR = operating room)

Source Patient Cause of cannula transection Diagnostic Consulting service/ Outcome characteristic procedure for Procedure for removal confirmation

Moon et al.3 69 y.o., Accidental 7.5 MHz high- Plastic surgery/OR Surgical Recovered, no Male transection by scissors while frequency exploration and removal of residual sequelae separating intravenous and arterial ultrasonography, fragment by microforceps catheter 3-D CT Lee SY 69 y.o., Reinsertion may have damaged Wrist CT Service not mentioned/OR et al.4 Male the catheter sheath, manufacturing surgical exploration and defect of angiocatheter is removal of fragment suggested Ho KS 20 y.o., Repeated wrist movement Not mentioned Vascular surgery/OR surgical Recovered, no et al.6 Female exploration under local residual sequelae anesthesia Aslam M 63 y.o., Not mentioned ultrasound Vascular surgery/OR surgical et al.1 Female exploration under local anesthesia Shah U.S. 72 y.o., Transected while securing the none Vascular surgery/OR surgical et al.5 Female arterial catheter with suture. exploration simultaneous with planned indicated surgery Bengezi OA 58 y.o., Male Hypothesized to be repeated Plain X-ray of Vascular surgery/OR surgical Excellent flow with et al.7 flushing and manipulation created wrist and hand exploration with arteriotomy good capillary refill a vulnerable point along the with ultrasound in all fingers. catheter length confirmation pre- and intraoperatively Kim IS 74 y.o., Male Reinsertion of stylet needle Portable X-ray Unclear if vascular surgery Recovered et al.9 through the embedded catheter involved/OR Exploration and uneventful sheath intraoperatively for pleural removal during scheduled decortication primary surgery Moody C Unknown Accidental cutting of the plastic Ultrasound Surgical team involved/OR Recovered et al.10 elderly cannula imaging pre-and exploration with arteriotomy uneventful intraoperatively and removal of catheter Ferguson E et 62 y.o., Male Accidental cutting of catheter Portable X-ray Vascular surgery/OR Uneventful al.11 fragment arteriotomy and removal of catheter Mayne D and 64 y.o., Male Repeated flexion and extension Portable X-ray Unclear if vascular surgery Uneventful Kharwar F8 involved/Unclear if OR Exploration and removal or bedside Hamid unknown Accidental transection with Sonosite, X-ray Percutaneous approach using Some spasm et al.12 dressing removal a snare on angiography however no complications after removal

M.E.J. ANESTH 23 (1), 2015 114 Christa San Luis et. al on board, they were able to perform their bedside mechanisms by which the catheter may be transected ultrasound localization both preoperatively and during so precautions can be observed. Appropriate wrist the surgery itself. Ideally, patients are taken to the stabilization, careful suture placement and removal and operating room for surgical exploration and removal avoidance of multiple stylet needle reinsertion are the of the fragment with generally good outcome (Table suggested ways to prevent this complication. Prompt 1). However that is not always possible as in our case. confirmation of the location of the retained fragment The patient was hemodynamically unstable and was is indicated with simultaneous vascular surgery unable to tolerate repeated position changes even just consultation for timely exploration and removal. for transportation. However, as soon as the patient Intraoperative confirmation of the catheter may be was deemed able to tolerate the surgical exploration needed. If the patient is unable to tolerate transport at bedside, it was immediately arranged and another to the operating room, it is feasible to perform the ultrasound was performed preoperatively. The procedure at bedside. To the authors’ knowledge this procedure was performed in our NCCU. is the first report of a bedside surgical exploration for a Retained radial artery catheter is rare but has been retained radial arterial catheter in a hemodynamically reported. Clinicians should be aware of the various unstable patient. Bedside retained radial artery catheter removal 115

References

1. Aslam M, Sarker B, Bhattacharya V: A Rare Complication of 7. Bengezi OA, Dalcin A, Al-Thani H and Bain J: Unusual Radial Artery Cannulation. J Med Ultrasound; 2012, 20(3):183-185. complication of radial artery cannulation. Can J Plast Surg; 2003, 2. Scheer BV, Perel A and Pfeiffer U: Clinical review: Complications 11(4): 213-215. and risk factors of peripheral arterial catheters used for 8. Mayne D and Kharwar F: Another complication of radial artery haemodynamic monitoring in anaesthesia and intensive care cannulation. Anaesthesia; 1997 Jan, 52(1):89-90. medicine. Crit Care; 2002, 6(3):199-204. 9. Kim IS, Shin HK and Dae YK: Iatrogenic catheter sheath shearing 3. Moon S, Gong J, Kim J, Lee KC, K HY, Choi EK and Lee MJ: A during radial artery cannulation. Korean J Anesthesiol; 2013 Dec, retained catheter fragment in radial artery caused by accidental 65(6 Suppl):S12-S13. catheter transection during arterial catheter removal. J Anesth; 2012, 10. Moody C, Bhimarasetty C and Deshmukh S: Ultrasound guided 26:625-626. location and removal of retained arterial cannula fragment. 4. Lee S, Na H, Kim M, Kim C, Jeon Y, Hwang J and Do S: A Sheared Anesthesia; 2009 Mar, 64(3):338-9. catheter fragment in the wrist after arterial cannulation attempt-a 11. Ferguson E, Baumgartner P and Hamilton M: Accidental case report. Korean J Crit Care Med; 2010, 25:118-21. transection of radical artery cannula. Anaesth and Intensive Care; 5. Shah US, Downing R and Davis I: An iatrogenic arterial foreign 2005 Feb, 33(1):142-3. body. Br J Anaesth; 1996, 77:430-431. 12. Hamid UI, Collins A, McConkey C and Sidhu P: Accidental 6. Ho KS, Chia KH and Teh LY: An unusual complication of radial transection of a radial artery cannula. BMJ Case Reports; 2012, artery cannulation and its management: a case report. J Oral doi:10.1136/bcr-2012-006753. Maxillofac Surg; 2003, 61:955-7.

M.E.J. ANESTH 23 (1), 2015

Esophageal perforation following orogastric suction catheter insertion in an elderly patient

Roland N. Kaddoum*, Fadi Farah**, Rita W. Saroufim*** and Salah M. Zeineldine****

Abstract

Esophageal rupture has been described following iatrogenic manipulation. In this report, we present an elderly lady admitted to the operative theater for laparoscopic cholecystectomy. Multiple intra-operative attempts to place a flexible orogastric tube were unsuccessful because of failure to advance. Post-operatively, the patient developed sepsis and a right pleural effusion. She was transferred to the Intensive Care Unit and she was treated with antibiotics. Radiologic evaluation confirmed an esophago-pleural fistula. Surgical repair was urgently performed for closure of fistula and lung decortication. The patient recovered and was discharged home.

Introduction

Esophageal perforation is a serious complication of procedures performed on or around the esophagus and is mainly iatrogenic1,2. Esophageal perforation is most frequently encountered during endoscopic procedures3 but also during nasogastric tube placement4-9, endotracheal intubation10-14, stricture dilation15,16 and during the use of oesophageal bougies17. This complication has a poor prognosis with inadequate management3. While providing anesthesia to surgical patients, anesthesists frequently insert esophageal dilators, nasogastric tubes or orogastric tubes/suction catheters. Such interventions may cause trauma to soft tissue structures. We describe a case of esophageal perforation secondary to the orogastric insertion of a simple 14 french suction catheter used routinely to deflate the stomach during laparoscopic cholecystectomy. To our knowledge, this is the first case report describing esophageal perforation following the insertion of a flexible orogastric 14Fr suction catheter in an adult patient undergoing laparoscopic cholecystectomy.

* MD, Assistant Professor of Anesthesiology, American University of Beirut Medical Center, Department of Anesthesiology, Beirut, Lebanon (Riad Solh 1107-2020). ** MD, Anesthesiology resident, Formerly of: American University of Beirut Medical Center, Department of Anesthesiology, Beirut Lebanon (Riad Solh 1107-2020). Current Department: St. Elizabeth's Medical Center, Department of Anesthesiology, Critical Care and Pain Medicine, 736 Cambridge Street, #213, Brighton, MA 02135. *** Medicine III student, Bachelor degree in Biology, American University of Beirut Medical Center, Department of Anesthesiology, Beirut, Lebanon (Riad Solh 1107-2020). **** MD, Assistant Professor of Clinical Medicine, American University of Beirut Medical Center, Department of Internal Medicine, Beirut, Lebanon (Riad Solh 1107-2020). Corresponding author: Salah M. Zeineldine, MD, Assistant Professor of Clinical Medicine, American University of Beirut Medical Center, Department of Internal Medicine, Beirut, Lebanon (Riad Solh 1107-2020). Tel: +961-1-350 000 x 4706, Fax: +961-1-744 489. E-mail: [email protected]

117 M.E.J. ANESTH 23 (1), 2015 118 Roland Kaddoum et. al

Case Report was uneventful. The patient was transferred to the recovery room. She was fully awake and asymptomatic. A 79 year old, 70 kg lady known hypertensive On post-op day one, the patient complained and dyslipidemic presented for laparoscopic of dry cough and dyspnea after her first meal. On cholecystectomy and intraoperative cholangiogram physical exam, she had scattered wheezes and right secondary to an acute cholecystitis. The patient denied field crakles. She was afebrile. Chest X ray (CXR) any symptoms or history of dysphagia, odynophagia, revealed opacification on the right lower and right gatroesophageal reflux or chest pain. Difficult middle fields. A diagnosis of pulmonary aspiration intubation was anticipated due to short neck and a was suspected and Solumedrol, Combivent, pulmicort glidescope assisted intubation was planned. and Tazocin were started. The CXR improved in the In the operating room, after lung denitrogenation afternoon. However, clinically the patient was getting with 100% oxygen, rapid sequence induction was worse the following day with progressive desaturation performed using lidocaine 100 mg (1.5 mg/kg), down to 90% and became hypotensive with systolic propofol 140 mg (2 mg/kg) and succinylcholine 100 pressure of 80 mmHg. The patient was transferred mg (1.5 mg/kg) intravenously. No bag ventilation to the intensive care unit and Tazocin was shifted was performed. The trachea was intubated by an to broad spectrum antibiotic coverage consisting of endotracheal tube (ETT) size 8.0 using the Glidesscope Meropenem, Levofloxacin and Metronidazole. The and a 10Fr intubating stylet (Unomedical). Several patient symptoms improved, however the cough and attempts to insert a well lubricated 14 Fr suction wheezes persisted. A CT chest was done on post op catheter failed (Bicakcilar, suction catheter w/ day 7 revealing an air pocket posterior to the carina vakon connector ideal tip 4.7 mm x 600mm). The in continuity with the right lower lobe. A diagnosis catheter would not advance even with an index finger of esophageo-pleural fistula in the lower esophagus inserted in the patient mouth guiding the catheter was suspected and was confirmed with Gastrograffin into the pharynx. After multiple attempts using the swallow. On post-op day 9, a thoracotomy for right laryngoscope to have better visualization, the insertion lung decortication and closure of fistula was performed. of the orogastric tube was not successful. During The patient was kept intubated and extubation was the procedure, the surgeon noted that the stomach done on the following day. Antibiotics were continued was inflated and insisted on the placement of an for 14 days post-op. The radiological findings on CXR orogastric tube to suction the stomach. We elected resolved on post-op day 17. then to place an ETT size 7.0 that we advanced in the A repeated gastrograffin swallow was performed esophagus and inserted the orogastric tube through it. on post-op day 20 showing an outpouching at the The advancement of the catheter would always stop level of the fistula but no leak. Another gastrograffin at the same level as previously tried with or without swallow was performed on post-op day 27 showed no the laryngoscope attempts. The resistance upon the leak. insertion of the catheter was encountered at a distance of about 25 cm from the lips. No forceful maneuvers The patient was discharged from the hospital on were performed and no blood was recovered over the post-op day 33. suction catheter. We decided to abort the placement of the orogastric tube and the surgeon was advised so. His Discussion concern was a fully inflated stomach that he is showing us on the video camera. We explained that placement Perforation of the esophagus due to of orogastric tube was difficult, and will treat his instrumentation in the adult is a rare yet potentially concern by extubating the trachea when the patient is devastating event associated with high morbidity and fully awake. mortality3. The mortality has decreased from 38.7% After the surgical procedure ended, extubation in the 1970s to 8.3% today18. The leading cause of Esophageal perforation in laparoscopy 119 esophageal perforation is mainly iatrogenic with However if delayed diagnosis beyond 48h was made, perforations at the thoracic level being the highest19. no patient with esophageal perforation should be Most of perforations occur during instrumentation deprived from surgical repair28. Mortality is decreased of the esophagus i.e. endoscopy procedures, in surgical repair versus conservative treatment29, for transesophageal echocardiography, esophageal varices that reason, our patient underwent thoracotomy for sclrerotherapy, stricture dilatation, using relatively fistula closure and repair of esophageal tear. large stiff probes (endoscope, TEE probe, Sengstaken- In any patient with a recent history of esophageal Blakemore (SB) tube, bougie). Several risk factors instrumentation, the diagnosis of esophageal injury have been described for esophageal perforation such should be suspected in the presence of any of the as pre-existing esophageal abnormalities (carcinoma, symptoms encountered by our patient. Also, the stricture, diverticuli)20 and cervical osteophytes21. absence of gastric content on naso/orogastric tube or Esophagogastroduodenoscopy was the most the presence of blood on the catheter elicit a possible commonly litigated procedure, followed by intubation diagnosis of perforation. Nevertheless blood was not and Nissen fundoplication22. But there have been few noted on the suction catheter in our case. reported cases of iatrogenic esophageal perforations by a flexible nasogastric tube occurring mainly in For the first 24 hours following the laparoscopic neonates or infants4-6,9,23. cholecystectomy, our patient’s only complain was pain over the incision and a mild shoulder pain attributed to In our patient the perforation occurred the laparoscopic procedure. This pain was controlled after multiple attempts at inserting the orogastric by analgesics. She denied any complain or history suction catheter where the obstruction was faced of dysphagia, odynophagia, dysphonia or dyspnea. at 25cm distal to the lips. The most common areas However, after her first meal she complained of of instrumental esophageal perforation are the sudden dry cough and severe dyspnea. Taking into relatively narrow portions at the distal esophagus. consideration the fact that the patient was extubated The perforation is complicated by an inflammatory with a distended stomach, pulmonary aspiration was process and communication with the pleura in 80% of the most probable diagnosis. the cases24. The thin mediastinal pleura is ruptured by the inflammatory process, producing contamination It was the persistence of the cough and dyspnea of the pleural space and a pleural effusion. Then, and the worsening of these symptoms following gastric contents and fluids are drawn into the pleural meals, along with a problematic naso/orogastric tube space by the negative intrathoracic pressure resulting insertion that made the suspiscion of esophageal in further inflammation and fluid sequestration, perforation high. Because of the failure of insertion of hypovolemia, and the early appearance of tachycardia the orogastric catheter and the occurrence of resistance and systemic sepsis. In our patient the CXR revealed at 25 cm from the lips, an intrathoracic esophageal opacifications which reflect consolidation of the lungs injury in our case was suspected. The CT chest showed that is due to an accumulation of fluids that is most an air pocket adjacent to the carina in continuity with probably edema and inflammation. This explains the the right lower lobe. This prompted us to perform scattered wheezes and crackles that were heard on esophagogram to confirm the diagnosis of esophageal post op day one. In addition, esophageal perforation perforation. allows bacteria, usually polymicrobia flora to spread The presence of underlying esophageal pathology into the mediastinum and subphrenic space leading could explain the difficulty in advancing the orogastric 18,25-27 to mediastinitis . This explains the septic picture tube. As anesthesiologists we are the experts in inserting of our patient that was revealed by hypotension and orogastric tubes or suction catheters, a maneuver that progressive oxygen desaturation. we perform almost every day in our practice. The Literature showed a better outcome with primary advancement of the catheter was impossible past 25cm surgical closure if diagnosed in less than 24 hours. of the lips despite so many attempts. This could be

M.E.J. ANESTH 23 (1), 2015 120 Roland Kaddoum et. al explained by a pre-existing esophageal pouch that the Conclusion patient is unaware of or by an osteophytic compression of the esophagus due to the patient age, which made The lesson taken from this case report is not to the advancement of the catheter impossible. Forcing force the advancement of an orogastric/nasogstric the catheter insertion through multiple attempts lead suction catheter especially when different techniques to the perforation. On another note, the deviation from and multiple attempts fail. The other lesson taken is our current practice of inserting a suction catheter to have a very high threshold inserting an ETT in the through an ETT placed in the esophagus is a very rare esophagus to facilitate the suction catheter insertion maneuver that we perform in extreme situations. This by advancing the catheter through the ETT since this also could be the reason of the perforation. could also be a risk factor for esophageal perforation. Esophageal perforation in laparoscopy 121

References

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Liu J, Zhang X, Xie D, Peng A, Yang X, Yu F, et al: Acute surgery; 2010, 147(3):e117-28. mediastinitis associated with foreign body erosion from the 4. Ahmed A, Aggarwal M, Watson E: Esophageal perforation: a hypopharynx and esophagus. Otolaryngology--head and neck complication of nasogastric tube placement. The American journal surgery. Official Journal of American Academy of Otolaryngology- of emergency medicine; 1998, 16(1):64-6. Head and Neck Surgery; 2012, 146(1):58-62. 5. de Dominicis F, Rekik R, Merlusca G, Deguines JB, Gamain 19. Eroglu A, Turkyilmaz A, Aydin Y, Yekeler E, Karaoglanoglu N: J, Berna P: [Esophageal perforation during nasogastric tube Current management of esophageal perforation: 20 years experience. insertion in a patient with right-sided aortic arch and thoracic aorta. Diseases of the esophagus. Official Journal of the International Pathophysiology and surgical implications]. 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M.E.J. ANESTH 23 (1), 2015

LETTER TO THE EDITOR

Pediatric Endotracheal Intubation

Claude Abdallah*

Dear Editor, I have read with interest the manuscript: ”Simulation training in endotracheal intubation in a pediatric residency” M. E. J. Anesth 22(5) 2014, by Drs. Sharara-Chami, Taher, Kaddoum, Tamim and Charafeddine. The authors are to be congratulated for taking the time to analyze and publish the study, the discussion highlights interesting points. Tracheal intubation in pediatric patients is an essential tool in anesthesiology, traditionally acquired in a clinical setting. Factors related to the patient such as the age of the patient and the level of experience of the trainee may be determinant factors in the decision of the anesthesiologist to make a first attempt at tracheal intubation. Learning curves exist for practical skills and despite useful tools to monitor the learning process; competency is difficult to assess by the anesthesiologist in the absence of adequate exposure with the trainee or a previous documentation of the level of execution of involved skills. Literature review shows the advantage of preparing trainees outside the operating room so that clinical training opportunities can be used most effectively when they arise. Scientific reports documenting the effects of simulation training on learning and updating knowledge about airway management showed improvement in decision-making, communication capabilities1-4 and a better learning of crisis management and endotracheal intubation5. Residents achieve proficiency levels in a smaller number of elapsed days of training and in a smaller number of trials in the operating room6. Simulation would represent also an additional tool for assessing the performance of procedures in anesthesia, such as rapid sequence induction, since it represents more clearly behaviors used in clinical practice than is possible to demonstrate using evaluation by questionnaires7. This may be particularly interesting since theoretical lectures and standard mannequin-based driven workshops have shown to improve overall theoretical knowledge but not to translate to practical skill during realistic mannequin-based simulations8. As discussed by the authors, future studies pertaining to documentation of the trainee’s perspective when faced with a pediatric tracheal intubation with teaching of pediatric endotracheal intubation with and without simulation training would be useful to perform.

* MD, MSc, Children’s National Medical Centre, Division of Anesthesiology, 111 Michigan Ave. NW, Washington DC, 20010 USA, (202) 476-2407. E-mail: [email protected]

123 M.E.J. ANESTH 23 (1), 2015 124 Claude Abdallah

References

1. Russo SG, Eich C, Barwing J, Nickel EA, Braun U, Graf BM, and human-patient simulation. Ann Acad Med Singapore; 2006, Timmermann A: Self-reported changes in attitude and behaviour 35:619-23. after attending a simulation-aided airway management course. J 6. Abrahamson S, Denson JS, Wolf RM: Effectiveness of a simulator Clin Anesth; 2007, 19:517-22. in training anesthesiology residents. Qual Saf Health Care; 2004, 2. Schaefer JJ 3rd: Simulators and difficult airway management skills. 13:395-7. Paediatr Anaesth; 2004, 14:28-37. 7. Zausig YA, Bayer Y, Hacke N Sinner B, Zink W, Grube C, 3. Owen H, Plummer JL: Improving learning of a clinical skill: the first Graf BM: Simulation as an additional tool for investigating the year’s experience of teaching endotracheal intubation in a clinical performance of standard operating procedures in anaesthesia. Br J simulation facility. Med Educ; 2002, 36:635-42. Anaesth; 2007, 99:673-8. 4. Rowe R, Cohen RA: An evaluation of a virtual reality airway 8. Wiel E, Lebuffe G, Erb C Assez N, Menu H, Facon A, Goldstein P: simulator. Anesth Analg; 2002, 95:62-6. Mannequin-based simulation to evaluate difficult intubation training 5. Ti LK, Tan GM, Khoo SG, Chen FG: The impact of experiential for emergency physicians. Ann Fr Anesth Reanim; 2009, 28:542-8. learning on NUS medical students: our experience with task trainers Erratum

The correct spelling name of the first author of the Letter-to-Editor entitled “Anesthetic management of a patient after functional hemispherectomy using bilateral bispectral index monitoring” and published in the October 2014 issue of the Middle East Journal of Anesthesiology (pp. 627-628) is “Shinichiro Kira” and not “Shinichiri Kira”.

125 M.E.J. ANESTH 23 (1), 2015 GUIDELINES FOR AUTHORS

The Middle East of Anesthesiology publishes original Clinical or laboratory investigations: work in the fields of anesthesiology, intensive care, pain, and The following structured format is required: emergency medicine. This includes clinical or laboratory investigations, review articles, case reports and letters to the 1. Cover Letter 7. Discussion Editor. 2. Title page 8. Acknowledgements Submission of manuscripts: 3. Abstract 9. References The Middle East Journal of Anesthesiology accepts electronic submission of manuscripts as an e-mail attachment 4. Introduction 10. Tables only. 5. Methods 11. Figures 6. Results Manuscripts must be submitted via email attachment to: Editor-In-Chief, 1. Cover Letter Department of Anesthesiology, Manuscripts must be accompanied by a cover letter, American University of Beirut Medical Center signed by all authors and stating that: Beirut, Lebanon - All authors have contributed intellectually to the manuscript and the manuscript has been read and E-mail: [email protected] approved by all the authors. - The manuscript has not been published, simultaneously Human Subjects submitted or accepted for publication elsewhere. Manuscripts describing investigations performed in humans must state that the study was approved by the appropriate Institutional Review Board and written informed consent was 2. Title Page obtained from all patients or parents of minors. Starts at page 1 and includes: Language: - A concise and informative title (preferably less than 15 words). Authors should include all information in the Articles are published in English. title that will make electronic retrieval of the article both sensitive and specific. Manuscript Preparation - Authors listing: first name, middle initial and last name with a superscript denoting the academic degrees as Manuscript format required: footprints. Double-spaced lines - The name of the department(s) and institutions(s) to Wide margins (1.5 inches or 3.8 cm) which the work should be attributed. Page numbers start on title page - The name, address, telephone, fax numbers and e-mail Word count should reflect text only (excluding abstract, address of the corresponding author. references, figures and tables). - Disclose sources of financial support (grants, equipment, drug etc…). Editorial 1500 - Conflict of interest: disclosure of any financial relationships between authors and commercial interests Abstract 250 (General articles) with a vested interest in the outcome of the study. 100 (Case Reports) - A running head, around 40 characters. Review article 4000 - Word count of the text only (excluding abstract, acknowledgements, figure legends and references). Original article 3000 Case Reports 800 3. Abstract Letter to Editor 500 Abstract should follow the title page. It should be structured with background, methods, results and conclusion.

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B. Technical information: Example: (1) from a journal (2) from a book. - Identify the methods, apparatus (give the 1. SHAWW: AND ROOT B: Brachial plexus anesthesia manufacturer’s name and address in parentheses), Comparatives study of agents and techniques. Am. J. and procedure in sufficient detail to allow others Surg.; 1951, 81:407. to reproduce the results. Give references to 2. ROBINSON JS: Modern Trends in Anaesthesia, Evans established methods. Provide references and brief and Gray Ch. 8, Butterworth Pub. Co., London 1967. descriptions for methods that have been published. Identify precisely all drugs and chemicals used, including generic names(s), dose(s) ands routes(s) 10. Tables of administration. Tables capture information concisely and display it C. Statistics-describe statistical methods with enough efficiently: They also provide information at any desired level detail to enable a knowledgeable reader with access to of details and precision. Including data in tables rather than text the original date to verify the reported results. Define frequently makes it possible to reduce the length of the text. statistical terms, abbreviations and most symbols. - Type or print each table with double spacing on a separate Specify the computer software used. Provide a power sheet of paper. analysis for the study. - Number tables consecutively in the order of their first citation in the text. 6. Results - Supply a brief title for each. Present your results in logical sequence in the text, tables - Place explanatory matter in footnotes, not in the and illustrations, giving the main or most important findings heading. first. Do not repeat all the data in the tables or illustrations - Explain all nonstandard abbreviations in footnotes. in the text: emphasize or summarize only the most important - Identify statistical measures of variations, such as observations. Extra or supplementary materials and technical standard deviation and standard error of the mean. details can be placed in an appendix. 11. Figures 7. Discussion - Figures should be submitted in JPEG or TIFF format Emphasize the new and important findings of the study with a minimum of 150 DPI in resolution. and the conclusions that may be drawn. - Colored data if requested by author is chargeable. Do not repeat in details data or other information given - If a figure has been published previously, acknowledge in the Introduction or the Results sections. For experimental the original source and submit written permission from studies, it is useful to begin the discussion by summarizing the copyrights holder to produce the figure. briefly the main findings, then explore possible mechanisms or Abbreviations and symbols: explanations for these findings, compare and contrast the results with other relevant studies. State the limitations of the study, - Use only standard abbreviations. and explore the implications of the findings for future research - Avoid abbreviations in the title of the manuscript. and for clinical practice. Link the conclusions with the goals of - The spelled-out abbreviations followed by the the study, but avoid unjustified statements and conclusions not abbreviation in parenthesis should be used in first adequately supported by the data. mention. Printed by Arab Scientific Publishers Ain Al-Tineh, Beirut, Lebanon Telefax: + 961 (1) 785107 / 8 Email: [email protected] www.asp.com.lb