Labour Analgesia - Epidural Or Alternatives ?

Labour analgesia - epidural or alternatives ?

Thierry Girard Basel, Switzerland CONFLICT OF INTEREST

Smiths-medical Cochrane Database Syst Rev. 2011;(12):CD000331.

Epidural versus non-epidural or no analgesia in labour (Review)

Anim-Somuah M, Smyth RMD, Jones L

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2011, Issue 12 http://www.thecochranelibrary.com

Inhaled analgesia for pain management in labour (Review) Authors’ conclusions

Klomp T, van Poppel M, Jones L, Lazet J, Di Nisio M, Lagro-Janssen ALM Inhaled analgesia appears to be effective in reducing pain intensity and in giving pain relief in labour. ... nitrous oxide appears to result in even more side effects such as nausea, vomiting, dizziness and drowsiness...

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2012, Issue 9 http://www.thecochranelibrary.com

Inhaled analgesia for pain management in labour (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. http://tinycheese.blogspot.com/2010_06_01_archive.html INCREDIBLE PAIN continued all night - I eventually got on Remifentanil - the new morphine based drug which you self-administer, dosing yourself when you need it. It was absolutely WONDERFUL.

Didn't actually stop you feeling pain but does stop you caring about it. I got absolutely sky high, thoroughly amused the midwife by talking utter rubbish, …., I even started seeing things - including Nelson Mandela on a bicycle... blooming weird but there you go. CE: Madhur; EJA/200723; Total nos of Pages: 9; EJA 200723

ORIGINAL ARTICLE

Remifentanil for labour analgesia: a meta-analysis of randomised controlled trials Alexander Schnabel, Niklas Hahn, Jens Broscheit, Ralf M. Muellenbach, Lorenz Rieger, Norbert Roewer and Peter Kranke CE: Madhur; EJA/200723; Total nos of Pages: 9; EJA 200723 Context Remifentanil is a potent short-acting m-opioid receptor had higher satisfaction scores (P < 0.05) in comparison with agonist which is rapidly metabolised in the mother and fetus and women receiving pethidine. Epidural analgesia decreased pain may be ideal for labour analgesia. scores compared with remifentanil (P 0.003). There was only ¼ Objectives To assess efficacy and safety of remifentanil a limited amount of data comparing remifentanil with nitrous compared with other analgesic techniques for labour pain. oxide or fentanyl. Serious maternal or fetal adverse outcomes ORIGINALData sources We ARTICLE systematically searched the central register were not reported in these trials. of controlled trials of the Cochrane Library (till August 2011) and Conclusion During labour, remifentanil-PCA provided superior MEDLINE (till August 2011). analgesia and higher patient satisfaction compared with RemifentanilEligibility criteria Randomised for controlled labour trials analgesia: investigating pethidine a meta-analysis with a comparable degree of adverse of events. Epidural randomisedefficacy and safety of remifentanil controlled administered trials via a patient- analgesia provided superior pain relief in comparison with Alexandercontrolled Schnabel, analgesia (PCA) Niklas device Hahn, compared Jens Broscheit, with any other Ralf M.remifentanil. Muellenbach, Due toLorenz a low number Rieger, of reported adverse events, analgesic technique for labour pain were included. the safety issue of remifentanil use in labour remains an open Norbert Roewer and Peter Kranke Results We finally included 12 randomised controlled trials question that needs to be addressed in future trials. (published from 2001 to 2011). Women treated with Eur J Anaesthesiol 2012; 29:000–000 Context Remifentanil is a potent short-acting m-opioid receptor had higher satisfaction scores (P < 0.05) in comparison with remifentanil had a lower risk of conversion to epidural analgesia Keywords: analgesia, epidural analgesia, labour, patient-controlled agonist(P < which0.001), is rapidly a lower metabolised mean pain score in the motherafter 1 h and (P < fetus0.001) and and womenanalgesia, receiving pethidine, pethidine. remifentanil Epidural analgesia decreased pain may be ideal for labour analgesia. scores compared with remifentanil (P 0.003). There was only ¼ Objectives To assess efficacy and safety of remifentanil a limited amount of data comparing remifentanil with nitrous compared with other analgesic techniques for labour pain. oxide or fentanyl. Serious maternal or fetal adverse outcomes DataIntroduction sources We systematically searched the central register wereRemifentanil not reported in is these an ultra-short-acting trials. m-1 opioid receptor of controlledSome of trials the of most the Cochrane common Library anaesthetic(till August procedures 2011) and per- ConclusionagonistDuring with an labour, onset remifentanil-PCA time of 30–60 provided s, and peak superior effect MEDLINEformed(till are August interventions 2011). to relieve labour pain. Several analgesiaafter and2.5 min. higher5 Due patient to satisfaction fast metabolism compared through with plasma Eligibilitysurveys criteria haveRandomised shown that thecontrolled right timing trials investigating and availability pethidineand tissue with a esterases, comparable remifentanil degree of adverse offers events. the advantage Epidural of efficacyof analgesia and safety – of independent remifentanil administered of the mode via a of patient- analgesia analgesiaa short provided half-life. superior6 Furthermore, pain relief in it comparison has a short with context- controlleditself –analgesia are very (PCA) important device factors compared for with maternal any other satisfac- remifentanil.sensitive Due half-life to a low (3.5 number min) ofand reported can be adverse used over events, a long analgesiction.1 techniqueAccording for labour to the pain guidelines were included. of the American the safetyperiod issue without of remifentanil fear of use accumulation. in labour remains7 Remifentanil an open ResultsSocietyWe finally of Anesthesiologists included 12 randomised (ASA) controlled and the trials American questionrapidly that crosses needs to the be placenta, addressed but in future it is trials. metabolised and (publishedCollege from of 2001 Obstetricians to 2011). Women and Gynecologists treated with (ACOG), Eurredistributed J Anaesthesiol very2012; quickly 29:000–000 by the fetus.8 Due to its remifentanilepidural had analgesia a lower risk is of recommended conversion to epidural in labour analgesia as the Keywords:unique analgesia, pharmacodynamic epidural analgesia, and labour, pharmacokinetic patient-controlled profile, (P <‘most0.001), flexible, a lower mean effective pain score and after least 1 h depressing (P < 0.001) and to the analgesia,remifentanil pethidine, remifentanil may be the best opioid for labour analgesia. central nervous system’ of the choices available.2 How- Its use during labour is gaining in popularity,9 although ever, obstetric anaesthesiologists are occasionally faced pethidine, despite its poor efficacy and known adverse with absolute or relative contraindications: women with effects on the newborn, remains the most popular Introductiona higher risk for thrombosis or thromboembolism (e.g. Remifentanilsystemic analgesic is an ultra-short-acting for labour pain.m-110,11 opioidThe receptor aim of this Somefactor of the V mutation) most common receiving anaesthetic prophylactic procedures anticoagulants per- agonistmeta-analysis with an onset was time to assess of 30–60 the efficacy s, and peak and effect safety of formedduring are interventions pregnancy or to with relieve former labour congenital pain. Several heart afterremifentanil 2.5 min.5 Due patient-controlled to fast metabolism infusion through compared plasma with surveyscorrection have shown surgery that who the rightneed timing lifelong and anticoagulation availability 3 andother tissue analgesic esterases, techniques remifentanil for offers labour the pain. advantage of of analgesiaor with obesity – independent and diabetes. of the4 Women mode may of analgesia also ask for a short half-life.6 Furthermore, it has a short context- itselfalternatives – are very to important central neuraxial factors for analgesia maternal because satisfac- they sensitiveMethods half-life (3.5 min) and can be used over a long tion.do1 notAccording (yet) want to this the type guidelines of pain relief. of the Therefore, American there periodThis without meta-analysis fear of was accumulation. in accord with7 Remifentanil the Preferred Societyis a need of Anesthesiologists for effective and well (ASA) tolerated and the systemic American analge- rapidlyReporting crosses Items the placenta, for Systematic but it is reviewsmetabolised and and Meta- Collegesics for of labour Obstetricians pain to andprovide Gynecologists an alternative (ACOG), to central redistributedAnalyses (PRISMA) very quickly statement. by the12 fetus.8 Due to its epiduralneuraxial analgesia analgesia. is recommended in labour as the unique pharmacodynamic and pharmacokinetic profile, ‘most flexible, effective and least depressing to the remifentanilSearch strategy may be the best opioid for labour analgesia. 2 9 centralFrom thenervous Department system’ of Anaesthesiology of the choices and Intensive available. Care, UniversityHow- Hospital of Its useThe during systematic labour search is gaining was in conducted popularity, byalthough two authors Mu¨nster, Mu¨nster (AS), Department of Anaesthesia and Critical Care (NH, RM, ever,NR, obstetric PK) and Department anaesthesiologists of Obstetrics and Gynaecology are occasionally (LR), University faced Hospital pethidine,(A.S., N.H.) despite in the its poor Central efficacy register and of known controlled adverse trials of withof absolute Wu¨rzburg, Wu or¨rzburg, relative Germany contraindications: women with effectsthe Cochrane on the newborn,Library (till remains August the 2011) most and popularMEDLINE 10,11 a higherCorrespondence risk for to thrombosis Professor Dr med. or thromboembolism Peter Kranke, MBA, Oberdu (e.g.¨rrbacher systemic(till 1 analgesic August 2011) for labour according pain. to theThe recommendations aim of this factorStreet V 6, mutation) 97080 Wu¨rzburg, receiving Germany prophylactic anticoagulants meta-analysis was to assess the efficacy and safety of Tel: +49 931 201 30050; fax: +49 931 201 30053; e-mail: [email protected] of the Cochrane Collaboration. The search strategy duringwuerzburg.de pregnancy or with former congenital heart remifentanilconsisted patient-controlled of a combination infusion of the compared free text with words correction surgery who need lifelong anticoagulation3 other analgesic techniques for labour pain. or with0265-0215 obesityß 2011 and Copyright diabetes. European4 Women Society of may Anaesthesiology also ask for DOI:10.1097/EJA.0b013e32834fc260 Copyrightalternatives © toEuropean central neuraxial Society analgesia of Anaesthesiology. because they Methods Unauthorized reproduction of this article is prohibited. do not (yet) want this type of pain relief. Therefore, there This meta-analysis was in accord with the Preferred is a need for effective and well tolerated systemic analge- Reporting Items for Systematic reviews and Meta- sics for labour pain to provide an alternative to central Analyses (PRISMA) statement.12 neuraxial analgesia. Search strategy From the Department of Anaesthesiology and Intensive Care, University Hospital of The systematic search was conducted by two authors Mu¨nster, Mu¨nster (AS), Department of Anaesthesia and Critical Care (NH, RM, NR, PK) and Department of Obstetrics and Gynaecology (LR), University Hospital (A.S., N.H.) in the Central register of controlled trials of of Wu¨rzburg, Wu¨rzburg, Germany the Cochrane Library (till August 2011) and MEDLINE Correspondence to Professor Dr med. Peter Kranke, MBA, Oberdu¨rrbacher (till 1 August 2011) according to the recommendations Street 6, 97080 Wu¨rzburg, Germany Tel: +49 931 201 30050; fax: +49 931 201 30053; e-mail: [email protected] of the Cochrane Collaboration. The search strategy wuerzburg.de consisted of a combination of the free text words

0265-0215 ß 2011 Copyright European Society of Anaesthesiology DOI:10.1097/EJA.0b013e32834fc260 Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited. CE: Madhur; EJA/200723; Total nos of Pages: 9; EJA 200723

8 Schnabel et al.

issues are lacking. These are urgently needed for an Acknowledgements appropriate risk to benefit analysis and for the creation This work was supported by the Department of of reasonable recommendations for monitoring to ensure Anaesthesia and Critical Care, University Hospital of the safety of this promising method of labour analgesia. Wu¨ rzburg, Wurzburg, Germany and the Department The analysis has clearly shown that remifentanil provides of Anaesthesiology and Intensive, University Hospital better pain relief than the frequently used pethidine. of Mu¨ nster, Munster, Germany. What is less clear is whether other opioids currently used Data from Tveit et al.,26 accepted for publication but in the postoperative pain setting, such as fentanyl, can not yet published when this systematic review was provide equivalent pain relief and could offer a better performed, were made available through the editors of safety profile for the mother and baby. the European Journal of Anaesthesiology. The authors have no conflicts of interest. Limitations The trials included in this systematic review are References subject to clinical heterogeneity, with different study 1RantaPO.Obstetricepiduralanalgesia.Curr Opin Anaesthesiol 2002; 15:525–531. protocols with respect to timing, dose, speed of appli- 2 ACOG committee opinion. #295: Pain relief during labor. Obstet Gynecol cation, lock-out intervals and comparative drugs. 2004; 104:213. Altogether, there are too few trials and patients, and 3MoghbeliN,PareE,WebbG.Practicalassessmentofmaternal cardiovascular risk in pregnancy. Congenit Heart Dis 2008; 3:308–316. insufficient events with respect to adverse outcomes. 4 Soens MA, Birnbach DJ, Ranasinghe JS, van Zundert A. Obstetric This means the calculated pooled RR or mean difference anesthesia for the obese and morbidly obese patient: an ounce of prevention is worth more than a pound of treatment. Acta Anaesthesiol should be interpreted with caution. We included Scand 2008; 52:6–19. randomised controlled trials comparing two different 5BabencoHD,ConardPF,GrossJB.Thepharmacodynamiceffectofa administration settings (e.g. PCA versus intramuscular remifentanil bolus on ventilatory control. Anesthesiology 2000; 92:393– 398. injection) which may have led to an overestimation of 6 Glass PS, Hardman D, Kamiyama Y, et al. Preliminary pharmacokinetics the treatment effect with remifentanil. However, as the and pharmacodynamics of an ultra-short-acting opioid: remifentanil intravenous or intramuscular route represents common (GI87084B). Anesth Analg 1993; 77:1031–1040. 7 Egan TD. Pharmacokinetics and pharmacodynamics of remifentanil: an clinical practice, these trials may inform opinion as to update in the year 2000. Curr Opin Anaesthesiol 2000; 13:449– whether pethidine, the current most popular form of 455. 8KanRE,HughesSC,RosenMA,et al. Intravenous remifentanil: placental labour analgesia, represents the best intervention in transfer, maternal and neonatal effects. Anesthesiology 1998; 88:1467– women who cannot have neuraxial analgesia, or if should 1474. be replaced by a better option, such as remifentanil. 9 Lavand’homme P, Roelants F. Patient-controlled intravenous analgesia as an alternative to epidural analgesia during labor: questioning the use of the Satisfaction was inconsistently measured and should be short-acting opioid remifentanil. Survey in the French part of Belgium further explored. Reports of higher or similar satisfaction (Wallonia and Brussels). Acta Anaesthesiol Belg 2009; 60:75–82. scores compared with other methods of pain relief 10 Tveit TO, Halvorsen A, Rosland JH. Analgesia for labour: a survey of Norwegian practice – with a focus on parenteral opioids. Acta have to be interpreted with caution. Patient preferences Anaesthesiol Scand 2009; 53:794–799. and patient choice in conjunction with the analgesic 11 Saravanakumar K, Garstang JS, Hasan K. Intravenous patient-controlled analgesia for labour: a survey of UK practice. Int J Obstet Anesth 2007; technique may prove a valuable area for research, as 16:221–225. many sources indicate that parturient women in general 12 Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for like having a second effective option for pain relief other reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009; Schnabel A etthan al. Eur central J Anaesthesiology. neuraxial analgesia. 2012;29(4):177-85 339:b2700. 13 Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of Conclusion randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17:1–12. There is good evidence that a remifentanil PCA 14 Popping DM, Elia N, Marret E, et al. Clonidine as an adjuvant to local provides better analgesia for labour than intramuscular anesthetics for peripheral nerve and plexus blocks: a meta-analysis of randomized trials. Anesthesiology 2009; 111:406–415. or intravenous pethidine with almost comparable 15 Douma MR, Verwey RA, Kam-Endtz CE, et al. Obstetric analgesia: a maternal adverse events. Epidural analgesia provided comparison of patient-controlled meperidine, remifentanil, and fentanyl better pain relief than remifentanil. The conclusions in labour. Br J Anaesth 2010; 104:209–215. 16 Douma MR, Middeldorp JM, Verwey RA, et al. A randomised comparison regarding the comparison of remifentanil with inhala- of intravenous remifentanil patient-controlled analgesia with epidural tional nitrous oxide and fentanyl are less clear due to ropivacaine/sufentanil during labour. Int J Obstet Anesth 2011; 20:118– limited data. As there were few randomised trials 123. 17 Blair JM, Dobson GT, Hill DA, et al. Patient controlled analgesia for labour: a included in this meta-analysis, with few adverse comparison of remifentanil with pethidine. Anaesthesia 2005; 60:22–27. events reported, an appropriate risk-to-benefit analysis 18 Evron S, Glezerman M, Sadan O, et al. Remifentanil: a novel systemic is currently not feasible. Large randomised controlled analgesic for labor pain. Anesth Analg 2005; 100:233–238. 19 Shahriari AKM. A randomzed controlled trial of intravenous remifentanil trials reporting on safety issues and patient satisfaction compared with intramuscular meperidine for pain relief in labor. JMedSci using appropriate administration modes are urgently 2007; 7:635–639. 20 Volmanen P, Akural E, Raudaskoski T, et al. Comparison of remifentanil and needed to complement our knowledge of this alternative nitrous oxide in labour analgesia. Acta Anaesthesiol Scand 2005; 49:453– method for pain relief during labour. 458.

FHR remained reactive in 90% in the remifentanil Table 3. Suggested Guidelines for Patient-Controlled IV group versus 38% in the meperidine group. Analgesia (PCIA) with Remifentanil No study has identified an increased incidence of Eligibility nonreassuring FHR recordings after remifentanil has Informed consent been used for labor analgesia. Apgar scores and No opioid use in the previous 4 h umbilical cord gases have all been within normal Dedicated IV cannula for remifentanil administration limits. Furthermore, no neonate has needed naloxone PCIA protocol PCIA bolus: 40 ␮g after delivery, confirming remifentanil’s rapid metab- Lockout interval: 2 min NOT in case of olism and redistribution in the neonate after placental Continuous observations intrauterine death transfer. SaO2 (pulse oximetry) Nursing supervision: one-to-one Concomitant Use of Nitrous Oxide During Remifentanil 30-min observations Labor Analgesia Respiratory rate Sedation score Remifentanil provided superior analgesia to 50% Pain score nitrous oxide (Entonox) when administered to women Indications for contacting the anesthesia provider in a small crossover study with a threefold reduction Excessive sedation score (not arousable to voice) in median pain scores (15 vs 5 mm).18 Two studies Respiratory rate Ͻ8 breaths/min SaO Ͻ90% while breathing room air comparing remifentanil PCIA with meperidine PCIA 2 Sample guidelines adapted from those used by the Ulster Community and Hospitals Trust, allowed parturients to use nitrous oxide to supple- Ulster, United Kingdom. Labor nurses must establish competency in the use of remifentanil ment opioid analgesia as part of the study proto- PCIA before providing care. col.15,16 Thurlow et al.16 found equal use of nitrous PCIA ϭ patient-controlled IV analgesia. oxide in the IM meperidine and remifentanil PCIA groups. Blair et al.15 derived a similar conclusion: 19 of 19 women in the meperidine group and 18 of 20 in the contraction pain. Although remifentanil provides only modest analgesia, it seems to be popular with partu- remifentanil group chose to continue to use nitrous 1 oxide. It seems that when given the choice, women rients enrolled in trials. An appropriate PCIA dose ␮ 9 frequently prefer to continue using nitrous oxide at regimen is a 40- g bolus with a 2-min lockout. the same time as remifentanil PCIA, although some Because of its side-effect profile, guidelines should be studies of systemic opioid analgesia have identified an in place to ensure routine oxygen saturation monitor- increased risk of hypoxemia with the addition of ing, oxygen supplementation if needed to treat mater- nitrous oxide.23 nal desaturation, and one-to-one nursing/midwife monitoring using trained personnel. The requirement Supervision and Monitoring for close monitoring is a potential drawback to routine The findings of various studies point to the need for use of the technique in a clinical setting. We believe close (one-to-one nursing/midwife) patient supervi- that remifentanil PCIA for labor analgesia is an im- sion, training for the caregiver such as the labor nurse, portant advance in the obstetric anesthesia armamen- continuous oxygen saturation monitoring, and a dedi- tarium, especially for parturients who do not want cated IV cannula while a parturient is receiving a neuraxial analgesia or when its use is contraindicated. remifentanil PCIA regimen. Suggested guidelines for REFERENCES the use of remifentanil PCIA for labor analgesia are 1. Saravanakumar K, Garstang JS, Hasan K. Intravenous patient- shown in Table 3. controlled analgesia for labour: a survey of UK practice. Int J Obstet Anesth 2007;16:221–5 Future Research 2. Tsui MH, Ngan Kee WD, Ng FF, Lau TK. A double blinded Optimal remifentanil PCIA regimens may well re- randomised placebo-controlled study of intramuscular pethidine for pain relief in the first stage of labour. BJOG 2004; quire titration against individual patient response as 111:648–55 well as a titration in dose requirements as labor 3. Belsey EM, Rosenblatt DB, Lieberman BA, Redshaw M, Cald- progresses. Further developments may include syn- well J, Notarianni L, Smith RL, Beard RW. The influence of maternal analgesia on neonatal behaviour: I. Pethidine. Br J chronization of the remifentanil PCIA bolus dose to Obstet Gynaecol 1981;88:398–406 the tocodynameter recording so that the maximum 4. Evron S, Ezri T. Options for systemic labor analgesia. Curr Opin analgesic effect of the drug can occur at the peak of the Anaesthesiol 2007;20:181–5 5. Nissen E, Widstrom AM, Lilja G, Matthiesen AS, Uvnas-Moberg uterine contraction. Administration of the bolus dur- K, Jacobsson G, Boreus LO. Effects of routinely given pethidine ing the period between contractions may also poten- during labour on infants’ developing breastfeeding behaviour. tially improve efficacy.24 Effects of dose-delivery time interval and various concentrations of pethidine/norpethidine in cord plasma. Acta Paediatr 1997;86:201–8 CONCLUSION 6. Glass PS, Hardman D, Kamiyama Y, Quill TJ, Marton G, Donn KH, Grosse CM, Hermann D. Preliminary pharmacokinetics There is evidence supporting the analgesic effects and pharmacodynamics of an ultra-short-acting opioid: and suitability of remifentanil for first-stage labor remifentanil (GI87084B). Anesth Analg 1993;77:1031–40 7. Egan TD. Pharmacokinetics and pharmacodynamics of remifen- analgesia, although the timing of the onset of action or tanil: an update in the year 2000. Curr Opin Anaesthesiol peak action cannot currently be matched to uterine 2000;13:449–55

1928 Remifentanil for Labor Pain ANESTHESIA & ANALGESIA Remifentanil PCA is perfectly safe for the baby

“Just make sure that mum doesn’t stop breathing !.”

– Dr Bernard Norman, OAA 3day course, London 2011 Anaesthesia 2013 doi:10.1111/anae.12099 Case Report

Cardiac arrest in an obstetric patient using remifentanil patient-controlled analgesia

R. Marr,1 J. Hyams2 and V. Bythell1

1 Consultant Anaesthetist, 2 Specialty Trainee, The Royal Victoria Inﬁrmary, Newcastle upon Tyne, UK

Summary This case report describes the management of a patient, diagnosed with an intrauterine death at 31 weeks’ gestation, who suffered a cardiorespiratory arrest during her induced labour while using a remifentanil PCA. She made a full recovery from resuscitation which included a peri-mortem caesarean section...... Correspondence to: R. Marr Email: [email protected] Accepted: 1 November 2012

Remifentanil is an ultra-short acting l opioid receptor an uncomplicated emergency caesarean section for a agonist. It is thought to offer some advantages over previous delivery. She was not taking any regular med- conventional parenteral opioid analgesia for labour ication and had no allergies. and therefore to have a place in the management of She was given mifopristone 200 lg orally and was labour pain, despite the greater efﬁcacy of neuraxial booked to attend the labour ward 48 h later for induc- analgesia [1, 2]. We developed a local protocol for its tion of her labour. Induction of labour was com- use as intravenous patient-controlled analgesia (PCA) menced as per our local protocol with a misoprostol in labour based on that described by Hill [3]. Remifen- 100-lg pessary. The patient requested analgesia and tanil was offered to selected women as an alternative oral paracetamol 1 g was given. An hour later (time 0) to regional analgesia or to intramuscular diamorphine, she took oral codeine phosphate 60 mg, and 60 min which is the standard opioid used in our unit. It had, later she began to use Entonox (50:50 mixture of at the time of this reported incident, replaced intrave- nitrous oxide:oxygen). nous morphine PCA as the analgesic option most Two hours after the codeine, the midwife commonly used by women labouring with a non-via- requested an anaesthetic review to discuss further anal- ble fetus. gesia with the patient as she was complaining of increased pain. At that time the two anaesthetists on Case report labour ward were not able to attend within 30 min, so A 24-year-old woman with weight 87 kg, height the midwife gave her diamorphine 10 mg intramuscu- 2 169 cm, and BMI 29.4 kg.mÀ was diagnosed on ultra- larly and she continued to use Entonox. Following the sound scan with an intrauterine death at 31 weeks’ diamorphine, the patient was much more comfortable gestation. The patient was otherwise well. She had had and did not require additional analgesia; 90 min later

fits over other opioids in terms of Competing interests Anesthesia and Analgesia 1993; 77: 1031–40. fetal effects are not a consideration, No external funding or competing 10. Kan RE, Hughes SC, Rosen MA, Kessin needs to be questioned. All units interests declared. C, Preston PG, Lobo EP. Intravenous that offer remifentanil PCA on remifentanil: placental transfer, maternal and neonatal effects. Anesthesiol- labour ward should closely examine N. A. Muchatuta ogy 1998; 88: 1467–74. their practice, and should discon- S. M. Kinsella 11. Schnabel A, Hahn N, Broscheit J, et al. Remifentanil for labour analgesia: a tinue the service if appropriate Consultant Anaesthetists ’ meta-analysis of randomised con- monitoring and supervision of St Michael s Hospital trolled trials. European Journal of Ana- University Hospitals Bristol NHS patients cannot be guaranteed at all esthesiology 2012; 29: 177–85. Foundation Trust 12. Hinova A, Fernando R. Systemic remif- times. Bristol UK entanil for labor analgesia. Anesthesia The accumulated doses that Email: and Analgesia 2009; 109: 1925–9. 13. Volmanen P, Sarvela J, Akural EI, PCA regimens can deliver and the [email protected] Raudaskoski T, Korttila K, Alahuhta S. lockout interval between doses need Intravenous remifentanil vs. epidural careful consideration. Early investi- levobupivacaine with fentanyl for pain References relief in early labour: a randomised, gators warned against repeated 1. Thurlow JA, Waterhouse P. Patient-con- controlled, double-blinded study. Acta boluses less than 2.5 minutes apart trolled analgesia in labour using remif- Anaesthesiologica Scandinavica 2008; entanil in two parturients with platelet 52: 249–55. due to the risk of excessive respira- abnormalities. British Journal of Anaes- 14. Hodgkinson P, Hughes D. Audit of rem- tory depression [25]. We would rec- thesia 2000; 84: 411–3. ifentanil PCA in 612 labouring women. ommend that a three-minute 2. Howie KM, Millar S. Usage of remifen- International Journal of Obstetric Anes- tanil patient controlled analgesia in thesia 2008; 17: S10. lockout become the minimum stan- labour in the UK. International Journal 15. Harbers J, Drogtrop A, van Ieperen R. dard, as shorter lockouts allow of Obstetric Anesthesia 2011; 20: S36. Remifentanil is safe and effective for 3. Shen MK, Wu ZF, Zhu AB, et al. Remi- patient-controlled intravenous analge- additional doses to be received fentanil for labour analgesia: a double- sia during labour: the results in 305 before maximal side-effects – and blinded, randomised controlled trial of parturients. International Journal of peak analgesic effects – have maternal and neonatal effects of Obstetric Anesthesia 2008; 17: S52. patient-controlled analgesia versus 16. Laird R, Hughes D, Hill D. Audit of rem- occurred. Particular care is needed continuous infusion. Anaesthesia 2013; ifentanil patient-controlled analgesia when other opioids have previously doi: 10.1111/anae.12098 for labour. International Journal of 4. Jost A, Ban B, Kamenik M. Modified Obstetric Anesthesia 2007; 16: S43. been administered. Ultimately, it will patient-controlled remifentanil bolus 17. Saravanakumar K, Garstang JS, Hasan only be through a rigorous process delivery regimen for labour pain. K. Intravenous patient-controlled anal- of audit, appropriate supervision and Anaesthesia 2012; doi: 10.1111/anae. gesia for labour: a survey of UK prac- 12038 tice. International Journal of Obstetric co-ordinated adverse event monitor- 5. Marr R, Hyams J, Bythell V. Cardiac Anesthesia 2007; 16: 221–5. ing that we can make remifentanil a arrest in an obstetric patient using 18. Lavandhomme P, Roelants F. Patient- remifentanil patient-controlled analge- controlled intravenous analgesia as an safer option for women in labour. Anaesthesia 2013 sia. Anaesthesia 2013; doi: 10.1111/ Editorial alternative to epidural analgesia during Whatever our individual opin- anae.12099 labor: questioning the use of the fits over other opioids in terms of Competing6. Kinney interests MA, Rose CH, TraynorAnesthesia KD, and et Analgesia al. 1993; 77: short-acting opioid remifentanil. Survey ions of remifentanil in labour, the 1031–40. fetal effects are not a consideration, No external fundingEmergency or competing bedside10. cesarean Kan RE, Hughes delivery: SC, Rosen MA, Kessin in the French part of Belgium (Wallo- Anaesthesia 2013 recent casesneeds of to respiratory be questioned. All and units car-interestsdoi: 10.1111/anae.12153 declaredlessons. learned in teamworkC, Preston PG, Lobo and EP. Intravenous nia and Brussels). Acta Anaesthesio- that offer remifentanil PCA on remifentanil: placental transfer, mater- patient safety. BMC Researchnal and neonatal Notes effects. Anesthesiol- logica Belgica 2009; 60: 75–82. diac arrestlabour are ward a should timely closely reminder examine N. A. Muchatuta2012; 5: 412. ogy 1998; 88: 1467–74. 19. Hill D. Remifentanil patient-controlled Editorial their practice, and should discon- S. M. Kinsella 11. Schnabel A, Hahn N, Broscheit J, et al. that nothing we do in anaesthesia is 7. Pruefer C, Bewlay A. RespiratoryRemifentanil for arrest labour analgesia: a tinue the service if appropriate Consultant Anaesthetists analgesia should be routinely available ’ meta-analysis of randomised con- benign; riskmonitoring is a constant and supervision compan- of St Michael s Hospitalwith remifentanil patient-controlledtrolled trials. European Journal of Ana- for use in labour. International Journal University Hospitals Bristol NHS patients cannot be guaranteed at all analgesia – another case.esthesiologyAnaesthesia2012; 29: 177–85. of Obstetric Anesthesia 2008; 17: 336– Remifentanilion for labour to our analgesia: practice, time to and draw must breath?Foundation Trust 12. Hinova A, Fernando R. Systemic remif- – times. Bristol UK 2012; 67: 1044 5. entanil for labor analgesia. Anesthesia 9. and Analgesia 2009; 109: 1925–9. The use of remifentanilalways for labour besic thanconsideredThe other accumulated parenteral alongsideand inha- dosesmens that any describedEmail: allow8. doses Bonner similar JC, McClymont W. Respiratory 20. Volmanen P, Akural EI, Raudaskoski T, 13. Volmanen P, Sarvela J, Akural EI, PCA regimens can deliver and the [email protected] analgesia has grown over 12 years, lational alternativesfi [11]. Whilst to those given during generalarrest anaes- in an obstetricRaudaskoski patient T, Korttila using K, Alahuhta S. Alahuhta S. Remifentanil in obstetric from a few carefully selectedperceived cases epidurals bene mightts. provide betterWithout pain thesia due [21]. Indeed, using the most lockout interval between doses need remifentanil patient-controlledIntravenous remifentanil anal- vs. epidural analgesia: a dose-finding study. Anes- [1] to being available inrespect over a third forrelief,careful the remifentanil consideration. side-effects PCA is popular Early of investi-popular remi- PCA settings in the UK of levobupivacaine with fentanyl for pain of units in the UK [2]. As interest with parturients and both share a 40-lg bolusReferences with a two-minutegesia. Anaesthesia 2012;relief in67 early:538 labour:– a randomised, thesia and Analgesia 2002; 94: 913–7. gators warned against repeated among the anaesthetic community similar satisfaction scores [11, 12]. lockout [2],1. during Thurlow any given JA, Waterhouse three- P. Patient-con- controlled, double-blinded study. Acta fentanil, we risk sleepwalking into a trolled analgesia40. in labour using remif- 21. Sneyd R. Remifentanil on the labour has grown, articles have appeared Itboluses has euphoric less than side-effects 2.5 minutes that apartminute period a parturient weighing Anaesthesiologica Scandinavica 2008; entanil9. in two Glass parturients PS, with Hardman platelet D, Kamiyama52: 249–55. Y, et ward. Anaesthesia 2012; : 1045–6. in journals with increasing regular- maydue contribute to the risk to its of acceptability excessive respira-between 60 andabnormalities. 80 kg could readilyBritish Journal of Anaes- 67 maternal death related to its use in 1 14. Hodgkinson P, Hughes D. Audit of rem- ity. This issue of Anaesthesia con- withtory labouring depression women, [25]. with We some wouldreceive rec- 0.33thesia–0.442000;lg.kg.minal.84: 411À Preliminary. –3. pharmacokineticsifentanil PCA in 612 and labouring women.22. Volikas I, Butwick A, Wilkinson C, Ple- tains three reports on the use of studies demonstrating similar pain Despite the potentially large doses the nearommend future that– we a three-minute have been2. Howie KM, Millarpharmacodynamics S. Usage of remifen- ofInternational an ultra-short- Journal of Obstetric Anes- ming A, Nicholson G. Maternal and remifentanil during labour. Two are relief scores to epidural analgesia used, patientstanil can patient still rapidly controlled analgesia in thesia 2008; 17: S10. concerned with establishingwarned the best [21].[13].lockout Several become units have the published minimum stan-develop tolerance,labour with in several theacting UK. stud-International opioid: Journal remifentanil15. Harbers (GI87084B). J, Drogtrop A, van Ieperen R. neonatal side-effects of remifentanil method of administration: Shen et safedard, use in as hundreds shorter of cases lockouts [14– allowies showing a reductionof Obstetric in Anesthesia efficacy 2011; 20: S36. Remifentanil is safe and effective for 3. Shen MK, Wu ZF, Zhu AB, et al. Remi- al. compare patient-controlled anal- 16], and its application within the after 60 minutes of use [3, 22, 23]. patient-controlled intravenous analge- additional doses to be received fentanil for labour analgesia: a double- sia during labour: the results in 305 gesia (PCA) with continuous infu- UK and beyond has grown rapidly To take account for such wide vari- 4 before maximal side-effects – and blinded, randomised controlled trial of parturients.© 2013International The Association Journal of of Anaesthetists of Great Britain and Ireland sion [3], and Jost et al. demonstrate [2, 17, 18]. Some hospitals have ation, Jost et al. have developed a peak analgesic effects – have maternal and neonatal effects of Obstetric Anesthesia 2008; 17: S52. a novel approach of a patient- developed remifentanil analgesia variable dose regimenpatient-controlled whereby the analgesia versus 16. Laird R, Hughes D, Hill D. Audit of rem- altered variable PCA dose [4]. The eitheroccurred. for women Particular with contraindica- care is neededparturient cancontinuous increase the infusion. dose Anaesthesia 2013; ifentanil patient-controlled analgesia third article is a case report of cardio- tionswhen to regional other opioids analgesia haveor where previouslyadministereddoi: by 10.1111/anae.12098 pressing the for labour. International Journal of respiratory arrest associated with an ‘epidural on demand’ service is demand button4. Jost for longer A, Ban [4]. B, Kamenik M. Modified Obstetric Anesthesia 2007; 16: S43. been administered. Ultimately, it will patient-controlled remifentanil bolus remifentanil PCA [5]. This is now not provided [2]. Others allow rem- Neuraxial analgesia is currently 17. Saravanakumar K, Garstang JS, Hasan only be through a rigorous process delivery regimen for labour pain. K. Intravenous patient-controlled anal- the fourth case report of respiratory ifentanil as a routine analgesic the only method that potentially Anaesthesia 2012; doi: 10.1111/anae. gesia for labour: a survey of UK prac- and/or cardiac arrest related to option,of audit, which appropriate has been so supervision popular provides and absolute relief from con- 12038 tice. International Journal of Obstetric remifentanil in obstetrics published withco-ordinated women as to adverse lead to a event reduc- monitor-traction pain,5. Marr whereas R, Hyams all others J, Bythell V. Cardiac Anesthesia 2007; 16: 221–5. in the last year [5–8]. Why the sud- tioning in that the overallwe can uptake make of remifentanil regio- provide a partialarrest pain relief. in an Labour obstetric patient using 18. Lavandhomme P, Roelants F. Patient- den flurry? Has familiarity bred nal analgesia [19]. pain is unique inremifentanil the regular patient-controlled cycling analge- controlled intravenous analgesia as an safer option for women in labour. complacency? And where does this On the other hand, other evi- between intensesia. painAnaesthesia and none. The2013; doi: 10.1111/ alternative to epidural analgesia during leave remifentanil within our denceWhatever suggests that our remifentanil individual opin-doses of long-actinganae.12099 analgesics such labor: questioning the use of the 6. Kinney MA, Rose CH, Traynor KD, et al. armoury of labour analgesic tech- onlyions offers of remifentanil modest analgesia in labour, for as the pethidine and diamorphine have short-acting opioid remifentanil. Survey Emergency bedside cesarean delivery: in the French part of Belgium (Wallo- niques? labour [11, 12]. The optimum bolus to be balanced to provide analgesia recent cases of respiratory and car- lessons learned in teamwork and nia and Brussels). Acta Anaesthesio- Remifentanil has a substantial dose,diac duration arrest ofare bolus a timely delivery, reminderduring contractionspatient without safety. exces-BMC Research Notes logica Belgica 2009; 60: 75–82. body of evidence that supports its lockout interval and suitability of a sive effect between2012; 5: contractions. 412. 19. Hill D. Remifentanil patient-controlled use for labour analgesia. It is an backgroundthat nothing infusion we do all in remain anaesthesiaThe is ideal7. for Pruefer analgesic C, Bewlay methods A. Respiratory arrest analgesia should be routinely available ultra-short acting opioid that is rap- unknownbenign; [12]. risk Oneis a constantdose-finding compan-with a short durationwith remifentanil is to provide patient-controlled for use in labour. International Journal idly and efficiently metabolised by studyion found to our that practice, some women and mustan effect only whenanalgesia needed.– another In this case. Anaesthesia of Obstetric Anesthesia 2008; 17: 336– 2012; 67: 1044–5. both mother and fetus [9, 10]. A required an eight-fold higher dose respect, TENS – with its instant 9. always be considered alongside any 8. Bonner JC, McClymont W. Respiratory 20. Volmanen P, Akural EI, Raudaskoski T, recent meta-analysis confirms that than others to provide comparable onset and offset – is best, although fi arrest in an obstetric patient using Alahuhta S. Remifentanil in obstetric perceived bene ts. Without due fi it is a more effective labour analge- analgesia [20]. Many of the regi- unfortunately itremifentanil has low ef patient-controlledcacy. anal- analgesia: a dose-finding study. Anes- respect for the side-effects of remi- gesia. Anaesthesia 2012; 67:538– thesia and Analgesia 2002; 94: 913–7. © 2013 The Association of Anaesthetists of Great Britain andfentanil, Ireland we risk sleepwalking into a 40. 1 21. Sneyd R. Remifentanil on the labour maternal death related to its use in 9. Glass PS, Hardman D, Kamiyama Y, et ward. Anaesthesia 2012; 67: 1045–6. al. Preliminary pharmacokinetics and 22. Volikas I, Butwick A, Wilkinson C, Ple- the near future – we have been pharmacodynamics of an ultra-short- ming A, Nicholson G. Maternal and warned [21]. acting opioid: remifentanil (GI87084B). neonatal side-effects of remifentanil

CURRENT OPINION Patient-controlled intravenous analgesia remifentanil for labor analgesia: time to stop, think and reconsider

Marc Van de Veldea,b

Purpose of review Remifentanil is a relatively new but commonly used opioid alternative in the management of labor pain relief. The present article evaluates efficacy and safety of patient-controlled intravenous analgesia (PCIA) with remifentanil in the management of labor pain relief. Recent findings Remifentanil PCIA provides analgesia that is superior to nitrous oxide or other opioids such as meperidine, but is less effective when compared with epidural analgesia. Recent evidence suggests it produces significant respiratory depression making routine use as first line analgesia strategy virtually impossible. Summary Remifentanil PCIA is a valuable analgesic strategy whenever regional analgesia is contraindicated. Using it as first line strategy seems to be contraindicated because of significant respiratory side-effects to the mother. Whenever used advanced and continuous monitoring using capnography, saturation monitoring and one-to-one midwifery care are mandatory! Keywords labor, pain relief, patient-controlled intravenous analgesia, remifentanil

INTRODUCTION The present article will evaluate recent data on Over the last two decades, remifentanil patient-con- efficacy and safety of PCIA remifentanil for labor trolled intravenous analgesia (PCIA) has rapidly analgesia. gained popularity as labor analgesic both as an alternative whenever regional analgesia is contra- Analgesic efficacy indicated and as first line strategy to manage labor pain. Theoretically, the fast onset and offset of When performing a literature search in January remifentanil with effect-site concentration peaking 2015, 36 original studies were identified which at 1–2 min might make the drug suitable for labor evaluated the use of remifentanil PCIA for labor analgesia, especially if timing of remifentanil peak analgesia in humans. These studies were feasibility studies (n 9), comparisons with other opioids effect can be matched to the uterine contractions. ¼ However, the peak remifentanil effect might only be (n 8), comparisons with nitrous oxide (n 2), comparisons¼ with epidural analgesia (n 10) and¼ studies achieved upon the next contraction. Nevertheless in ¼ a pattern of regular labor, it is still possible to match bolus dosing with uterine contractions albeit with a b the second or subsequent contraction. Of note, Department of Cardiovascular Sciences and Department of Anesthesi- ology, UZ Leuven, Leuven, Belgium intravenously administered remifentanil exten- Correspondence to Marc Van de Velde, MD, PhD, EDRA, Professor of sively crosses the placenta [1]. Anesthesiology, Department of Cardiovascular Sciences, Section Importantly, intravenous remifentanil is a Anaesthesiology, Catholic University Leuven and University Hospitals potent respiratory depressant that might cause Leuven, Herestraat 49, B - 3000 Leuven, Belgium. Tel: +32 16 34 42 70; serious maternal morbidity and even mortality fax: +32 16 34 42 45; e-mail: [email protected] when used in a labor ward. Hence, the use of remi- Curr Opin Anesthesiol 2015, 28:237–239 fentanil PCIA is heavily debated [2,3] in literature. DOI:10.1097/ACO.0000000000000191

0952-7907 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. www.co-anesthesiology.com Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. International Journal of Obstetric Anesthesia (2016) 25, 66–74 0959-289X/$ - see front matter Ó 2015 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijoa.2015.12.004

REVIEW ARTICLE www.obstetanesthesia.com Remifentanil for labor analgesia: an evidence-based narrative review

M. Van de Velde,a B. Carvalhob aDepartment of Cardiovascular Sciences, Katholieke Universiteit Leuven and Department of Anaesthesiology, University Hospitals Gasthuisberg, Leuven, Belgium bDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, CA, USA

ABSTRACT This manuscript reviews the available literature on remifentanil patient-controlled intravenous analgesia in labor focusing on efficacy and safety. Remifentanil compares favorably to other potent systemic opioids but with fewer opioid-related neonatal effects. However, remifentanil provides modest and short-lasting labor analgesia that is consistently inferior when compared to neuraxial analgesia. The initial analgesic effect provided with remifentanil also diminishes as labor progresses. In several studies, remifentanil induced significant respiratory depressant effects in laboring women with episodes of desaturation, hypoventilation and even apnea. Given the safety concerns, we recommend that remifentanil patient-controlled intravenous analgesia should not be a routine analgesia technique during labor. In cases where neuraxial analgesia is refused or contraindicated and the use of remifentanil justified, continuous and careful monitoring is required to detect respiratory depression to provide safe care of both the pregnant woman and unborn child. Ó 2015 Elsevier Ltd. All rights reserved.

Introduction pregnancy. Additionally, the manufacturers state ‘‘the safety of remifentanil during labor or delivery has not Neuraxial labor analgesia is well established worldwide, been demonstrated” and ‘‘the drug should be given to especially in developed countries. However, many a pregnant woman only if clearly needed benefit justifies women, even in the developed world, do not opt for the potential risk to the fetus.” (UltivaÒ (remifentanil) neuraxial analgesia, have no access to this form of pain package insert 2013, Mylan Institutional LLC, Rock- relief, or have contraindications to its use. Many labor- ford, IL, USA). ing women therefore receive parenteral opioid-based For this review, we conducted a literature search with analgesia using pethidine (meperidine), fentanyl, butor- no language restriction on 31 December 2014. Searches phanol, nalbuphine, tramadol, morphine, alfentanil or were performed in PubMed using the terms ‘‘remifen- sufentanil. Remifentanil is a potent opioid with pharma- tanil” and ‘‘labor analgesia” or ‘‘PCIA remifentanil cological properties that potentially makes it an ideal and labor analgesia”. The results of the search are parenteral analgesic for labor. For the last two decades, reported in Table 1. Articles were selected based on rel- remifentanil has been studied as either an alternative to evance to this narrative review on the efficacy and safety neuraxial analgesia or as the preferred parenteral opioid of remifentanil for the provision of labor analgesia. The to treat labor pain. Despite the increased use of remifen- class of recommendation and level of evidence is stated tanil patient-controlled intravenous analgesia (PCIA) to for each recommendation. provide labor analgesia, this indication is considered off-label use. Remifentanil carries a Category C label Remifentanil pharmacokinetics (unknown whether the drug can cause fetal harm when administered to a pregnant woman) for use in Remifentanil has a very short context-sensitive half- time in non-pregnant humans of three minutes,1 Accepted December 2015 regardless of the duration of infusion. It is rapidly bro- Correspondence to: Dr Marc Van de Velde, MD, PhD, EDRA, ken down to non-active metabolites by non-specific Department of Anaesthesiology, University Hospitals Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. plasma esterases independent of organ metabolism. E-mail address: [email protected] Kan et al. demonstrated that remifentanil rapidly and International Journal of Obstetric Anesthesia (2016) 27, 89–96

CORRESPONDENCE www.obstetanesthesia.com Remifentanil patient-controlled a large number of the prescriptions we provide are in fact analgesia for labour: learning points OLDU.5 In obstetric anaesthesia, for example, epidural from a registry or intrathecalSAOA clonidine and fentanyl are OLDU, yet many of us administer them on a regular basis. Off-label The board of the Swiss Association of Obstetric drug usewww.remipca.org is acceptable and should be part of clinical prac- Anaesthesia (SAOA) read with interest the narrative tice only for indications that clinicians believe are in the review on remifentanil patient-controlled analgesia best interest of their patients.5 The SAOA believes that (PCA) for labour.1 This review raises important the safe application of remifentanil for labour analgesia issues. We appreciate that the Swiss RemiPCA SAFE can fulfil these requirements in certain circumstances. Network was specifically acknowledged and would Safe prescription of remifentanil not only depends on like to share results from this database.2 Results patient selection but also on the medical resources at are based on different settings from various hospitals hand. Routine use of remifentanil PCA in large teaching (large teaching-, small regional- and private hospitals) hospitals with numerous residents, midwives and limited where remifentanil labour analgesia is, depending on possibilities to guarantee continuous clinical monitoring the institution, either used as a first-line treatment or to all patients is probably inappropriate. However, if a when neuraxial analgesia is contraindicated. The board thorough selection of the right patients (low-risk) takes of the SAOA would like to add some considerations place in a well-staffed hospital, where safety require- and narrative inputs. ments are a priority, remifentanil might be a valuable We agree completely with the concerns about safety, option for some labouring women. the risk of hypoxia and apnoea underlying this analgesic Finally, mandatory reporting of all applications of method. However, it is possible that the use of remifen- remifentanil for labour analgesia in a central register tanil may in counterpart provide some benefits. In a would be more than welcome. The RemiPCA SAFE Net- recent study from Douma et al., remifentanil was less work has been operating for more than six years, and we frequently associated with fever than epidural analge- have already adjusted our regimen several times based not sia.3 In addition, in Douma’s study and that by Stocki only on the actual literature and discussion with experts, et al., remifentanil groups needed less oxytocin for aug- but also according to the reported results available on the mentation of labour;3,4 we can confirm this finding with registry. Now is an ideal moment to start a joint effort of our registry data.2 Duration of labour was also shorter. scientists and clinical practitioners for a safe application Looking further at the Stocki’s remifentanil regimen, of remifentanil in order to tailor the right analgesic bolus doses as high as 60 lg with a lockout interval as method sensibly and responsibly to our patients. low as 1 min were used.4 Although side effects (hypoxia and apnoea) are well documented, such a dose/lockout A. Melber, T. Girard, M. Baeriswyl, combination might not be completely transferable to P. Knessl, G. Savoldelli clinical settings outside the context of a clinical trial. Board Members of the Swiss Association of Obstetric In Switzerland, RemiPCA SAFE Network recommends Anaesthesia bolus doses of 20 lg (with a rare escalation up to 30 lg) E-mail address: [email protected] with a lockout interval of 2 min. Registry data show good satisfaction rate (>80% of women satisfied or very satisfied) with this dosing. Among the 6000 datasets, no References serious maternal event (ventilation/resuscitation/ emergency caesarean section linked to remifentanil 1. Van de Velde M, Carvalho B. Remifentanil for labor analgesia: an use) was reported, although these may have been evidence-based narrative review. Int J Obstet Anesth 2016;25:66–74. 2 2. RemiPCA SAFE Network https://www.remipca.org. [accessed under-reported. We are well aware of the fact that an April 2016]. observational register is not comparable with a random- 3. Douma MR, Stienstra R, Middeldorp JM, et al. Differences in ized controlled trial, but the clinical experience it offers maternal temperature during labour with remifentanil patient- strongly supports further studies to investigate similar controlled analgesia or epidural analgesia: a randomised con- dosage in order to better define a possibly safer regimen. trolled trial. Int J Obstet Anesth 2015;24:313–22. 4. Stocki D, Matot I, Einav S, et al. A randomized controlled trial of We would also like to comment on the use of remifen- the efficacy and respiratory effects of patient-controlled intra- tanil in obstetrics, which indeed is an off-label drug use venous remifentanil analgesia and patient-controlled epidural (OLDU). It is important for the reader to consider that analgesia in laboring women. Anesth Analg 2014;118:589–97. BMJ 2015;350:h846 doi: 10.1136/bmj.h846 (Published 23 February 2015) Page 1 of 14

Research

RESEARCH

Patient controlled analgesia with remifentanil versus epidural analgesia in labour: randomised multicentre equivalence trial OPEN ACCESS

1 1 Liv M Freeman gynaecologist , Kitty W Bloemenkamp gynaecologist , Maureen T Franssen 2 3 4 gynaecologist , Dimitri N Papatsonis gynaecologist , Petra J Hajenius gynaecologist , Markus W 5 6 Hollmann professor of anaesthesiology , Mallory D Woiski gynaecologist , Martina Porath 7 8 9 gynaecologist , Hans J van den Berg anaesthesiologist , Erik van Beek gynaecologist , Odette W 10 11 H M Borchert anaesthesiologist , Nico Schuitemaker gynaecologist , J Marko Sikkema 12 13 14 gynaecologist , A H M Kuipers anaesthesiologist , Sabine L M Logtenberg midwife/PhD candidate , 15 4 Paulien C M van der Salm gynaecologist , Katrien Oude Rengerink epidemiologist , Enrico Lopriore 16 17 neonatologist , M Elske van den Akker-van Marle assistant professor of health economics , Saskia 18 1 le Cessie associate professor of medical statistics , Jan M van Lith professor of obstetrics , Michel 19 20 M Struys professor of anaesthesiology , Ben Willem J Mol professor of obstetrics , Albert Dahan 21 1 professor of anaesthesiology , Johanna M Middeldorp gynaecologist

1Obstetrics, Leiden University Medical Centre, Leiden, Netherlands; 2Obstetrics and Gynaecology, University Medical Centre Groningen, Groningen, Netherlands; 3Obstetrics and Gynaecology, Amphia Hospital, Breda, Netherlands; 4Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, Netherlands; 5Anaesthesiology, Academic Medical Centre, Amsterdam, Netherlands; 6Obstetrics and Gynaecology, Radboud University Medical Centre, Nijmegen, Netherlands; 7Obstetrics and Gynaecology, Maxima Medical Centre, Veldhoven, Netherlands; 8Anaesthesiology, Maxima Medical Centre, Veldhoven, Netherlands; 9Obstetrics and Gynaecology, Saint Antonius Hospital, Nieuwegein, Netherlands; 10Anaesthesiology, Saint Antonius Hospital, Nieuwegein, Netherlands; 11Obstetrics and Gynaecology, Diakonessen Hospital, Utrecht, Netherlands; 12Obstetrics and Gynaecology, Hospital Group Twente, Almelo, Netherlands; 13Anaesthesiology, Hospital Group Twente, Almelo, Netherlands; 14Obstetrics and Gynaecology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands; 15Obstetrics and Gynaecology, Meander Medical Centre, Amersfoort, Netherlands; 16Paediatrics, Leiden University Medical Centre, Leiden, Netherlands; 17Medical Decision Making, Leiden University Medical Centre, Leiden, Netherlands; 18Medical Statistics and Clinical Epidemiology, Leiden University Medical Centre, Leiden, Netherlands; 19Anaesthesiology, University of Groningen and University Medical Centre Groningen, Groningen, Netherlands; 20Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Australia; 21Anaesthesiology, Leiden University Medical Centre, Leiden, Netherlands

Abstract Participants Women with an intermediate to high obstetric risk with an Objective To determine women’s satisfaction with pain relief using intention to deliver vaginally. To exclude a clinically relevant difference patient controlled analgesia with remifentanil compared with epidural in satisfaction with pain relief of more than 10%, we needed to include analgesia during labour. 1136 women. Because of missing values for satisfaction this number was increased to 1400 before any analysis. We used multiple imputation Design Multicentre randomised controlled equivalence trial. to correct for missing data. Setting 15 hospitals in the Netherlands.

Correspondence to: L M Freeman [email protected] Extra material supplied by the author (see http://www.bmj.com/content/350/bmj.h846?tab=related#datasupp) Appendix: Patients information visual analogue scale Appendix: Supplementary tables A-D Appendix: Supplementary figures A-D

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RESEARCH Freeman et al. BMJ. 2015;350:h846.

Figure

402 296

13 % 1 %

Randomisation and flow of pregnant women allocated to patient controlled remifentanil or epidural analgesia in labour

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RESEARCH Freeman et al. BMJ. 2015;350:h846.

Table 3| Area under curve for satisfaction with pain relief and pain scores during active labour and after start pain relief in pregnant women allocated to patient controlled remifentanil or epidural analgesia in labour

Mean area under curve Measure (No of women per group) Remifentanil Epidural analgesia Difference (95% CI) With missing AUC values imputed

Satisfaction with pain relief during active labour (687/671) 30.9 33.7 −2.8 (−6.9 to 1.3) Satisfaction with pain relief after pain relief (447/347*) 25.6 36.1 −10.4 (−13.9 to −7.0) Pain during active labour (687/671) 30.9 27.2 3.8 (0.92 to 6.6) Pain score after pain relief (447/347*) 26.7 20.3 6.4 (3.5 to 9.4) Missing AUC values not imputed

Satisfaction with pain relief during active labour (394/290) 27.2 37.6 −10.3 (−14.6 to −6.1) Satisfaction with pain relief after pain relief (316/198†*) 25.5 41.3 −15.7 (−20.2 to −11.2) Pain during active labour (438/354) 29.7 24.9 4.9 (1.7 to 8.1) Pain score after pain relief (345/220†) 27.8 21.0 7.0 (3.3 to 10.7)

*No who actually received pain relief. †No who reported sufficient scores to calculate AUC and received pain relief.

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BMJ 2015;350:h846 doi: 10.1136/bmj.h846 (Published 23 February 2015) RESEARCHPage 12 of 14 RESEARCH

BMJTable2015;350:h8465| Characteristicsdoi:of10.1136/bmj.h846labour in pregnant(Publishedwomen allocated23 Februaryto patient2015) controlled remifentanil or epidural analgesia accordingPageto intention12 of 14 to treat analysis. Figures are numbers (percentage) unless otherwise indicated Table 5| Characteristics of labour in pregnant women allocated to patient controlled remifentanil or epidural analgesia accordingRESEARCHto intention to treat analysis. Figures are numbers (percentage)Remifentanilunless otherwise(n=687) Epiduralindicatedanalgesia (n=671) Relative risk (95% CI) P value

Median (IQR) gestational age at delivery (weeks) Remifentanil39.7 (38.3-40.7)(n=687) Epidural39.7analgesia(38.3-40.7)(n=671) Relative risk— (95% CI) P0.37value MedianOnset of(IQR)labour:gestational age at delivery (weeks)Freeman et39.7 al.(38.3-40.7) BMJ. 2015;350:h846.39.7 (38.3-40.7) — 0.37 Spontaneous 282 (41) 281 (42) 0.98 (0.88 to 1.09) 0.76 TableOnset 5of| Characteristicslabour: of labour in pregnant women allocated to patient controlled remifentanil or epidural analgesia according to intention toSpontaneousInducedtreat analysis. Figures are numbers (percentage) unless282405 (41)(59)otherwise indicated281390 (42)(58) 0.981.02 (0.88(0.91 to 1.09)1.32) 0.76 RequestedInduced pain relief 405447 (59)(65) 390347 (58)(52) 1.021.32 (0.91(1.18 to 1.32)1.48) <0.0010.76 Remifentanil (n=687) Epidural analgesia (n=671) Relative risk (95% CI) P value RequestedMedian (IQR)paindilationrelief (cm) at request 4474 (3-5)(65) 3474 (3-5)(52) 1.32 (1.18— to 1.48) <0.0010.94 Median (IQR) gestational age at delivery (weeks) 39.7 (38.3-40.7) 39.7 (38.3-40.7) — 0.37 MedianFetal condition(IQR) dilationat start(cm)painatreliefrequest(cardiotocography) (n=794): 4 (3-5) 4 (3-5) — 0.94 Onset of labour: FetalOptimalcondition at start pain relief (cardiotocography) (n=794): 400 (90) 315 (91) 0.96 (0.80 to 1.17) 0.71 Spontaneous 282 (41) 281 (42) 0.98 (0.88 to 1.09) 0.76 OptimalNot optimal 40044 (10)(90) 31532 (91)(9) 0.96 (0.80— to 1.17) 0.71 Induced 405 (59) 390 (58) 1.02 (0.91 to 1.32) 0.76 MeconiumNot optimalstained amniotic fluid 7644(11)*(10) 8032(12)†(9) 0.95 (0.80— to 1.13) 0.57 Requested pain relief 447 (65) 347 (52) 1.32 (1.18 to 1.48) <0.001 MeconiumAugmentationstainedwith amnioticoxytocin fluid 39476 (11)*(58) 80391(12)†(58) 0.950.97 (0.80(0.87 to 1.13)1.08) 0.570.61 Median (IQR) dilation (cm) at request 4 (3-5) 4 (3-5) — 0.94 Augmentation>24 hours sincewithruptureoxytocinof membranes 39450 (58)(7) 39148 (58)(7) 0.971.01 (0.87(0.83 to 1.08)1.24) 0.610.92 Fetal condition at start pain relief (cardiotocography) (n=794): >24Medianhours(IQR)sincetimerupture(min)offrommembranesrequest to start analgesia 2850(15-45)(7) 5548(32-80)(7) 1.01 (0.83— to 1.24) <0.0010.92 Optimal 400 (90) 315 (91) 0.96 (0.80 to 1.17) 0.71 Median (IQR) timeduration(min)offromanalgesiarequest(min)to start analgesia 23628(128-376)(15-45) 30955(181-454)(32-80) — <0.001 Not optimal 44 (10) 32 (9) — Median (IQR) duration ofsecondanalgesiastage(min)(min) 23620(128-376)(10-46) 30924(181-454)(10-53) — <0.0010.09 Meconium stained amniotic fluid 76 (11)* 80 (12)† 0.95 (0.80 to 1.13) 0.57 MedianMode of(IQR)delivery:duration second stage (min) 20 (10-46) 24 (10-53) — 0.09 Augmentation with oxytocin 394 (58) 391 (58) 0.97 (0.87 to 1.08) 0.61 ModeSpontaneousof delivery: 518 (75) 501 (75) 1.01 (0.90 to 1.15) 0.75 >24 hours since rupture of membranes 50 (7) 48 (7) 1.01 (0.83 to 1.24) 0.92 SpontaneousVaginal instrumental 51863 (75)(9) 50170 (10)(75) 1.010.93 (0.90(0.77 to 1.15)1.13) 0.750.45 Median (IQR) time (min) from request to start analgesia 28 (15-45) 55 (32-80) — <0.001 VaginalCaesareaninstrumentalsection 10663 (9)(15) 10070 (10)(15) 0.931.01 (0.77(0.88 to 1.13)1.17) 0.450.87 Median (IQR) duration of analgesia (min) 236 (128-376) 309 (181-454) — <0.001 PostpartumCaesareanhaemorrhagesection (≥1000 mL) 10652 (8)‡(15) 10066 (10)§(15) 1.010.86 (0.88(0.69 to 1.17)1.06) 0.870.13 Median (IQR) duration second stage (min) 20 (10-46) 24 (10-53) — 0.09 PostpartumApgar scorehaemorrhage<7 at 5 min twin(≥10001 mL) 529 (8)‡(1) 6615(10)§(2) 0.860.74 (0.69(0.44 to 1.06)1.25) 0.130.20 Mode of delivery: ApgarTwin 1scorepHa <7.10<7 at 5 min twin 1 229 (1)(5)¶ 2815(6)**(2) 0.740.86 (0.44(0.63 to 1.25)1.19) 0.200.34 Spontaneous 518 (75) 501 (75) 1.01 (0.90 to 1.15) 0.75 TwinSpinal1headachepHa <7.10 122(0.1)††(5)¶ 428(0.6)‡‡(6)** 0.860.24 (0.63(0.03 to 1.19)2.18) 0.340.21 Vaginal instrumental 63 (9) 70 (10) 0.93 (0.77 to 1.13) 0.45 SpinalMajor maternalheadachecomplication 12(0.1)††(0.3) 46(0.6)‡‡(0.9) 0.240.33 (0.03(0.07 to 2.18)1.61) 0.210.17 Caesarean section 106 (15) 100 (15) 1.01 (0.88 to 1.17) 0.87 MajorMaternalmaternaladmissioncomplication 4192 (0.3)(61) 4166 (0.9)(62) 0.330.98 (0.07(0.88 to 1.61)1.09) 0.170.70 Postpartum haemorrhage (≥1000 mL) 52 (8)‡ 66 (10)§ 0.86 (0.69 to 1.06) 0.13 MaternalMedian (IQR)admissionlength of admission (days) 4191 (1-3)(61) 4161 (1-3)(62) 0.98 (0.88— to 1.09) 0.700.24 Apgar score <7 at 5 min twin 1 9 (1) 15 (2) 0.74 (0.44 to 1.25) 0.20 MedianNeonatal(IQR)admissionlength of admission (days) 3901 (1-3)(57) 3851 (1-3)(57) 0.99 (0.89— to 1.10) 0.240.82 Twin 1 pHa <7.10 22 (5)¶ 28 (6)** 0.86 (0.63 to 1.19) 0.34 NeonatalMedian (IQR)admissionlength of admission twin 1 (days) 3901 (1-3)(57) 3851 (1-3)(57) 0.99 (0.89— to 1.10) 0.820.13 Spinal headache 1 (0.1)†† 4 (0.6)‡‡ 0.24 (0.03 to 2.18) 0.21 Median (IQR) length of admission twin 12 (days) 3 1(2-5.75)(1-3) 4.5 (2.25-13.25)1 (1-3) — 0.130.42 Major maternal complication 2 (0.3) 6 (0.9) 0.33 (0.07 to 1.61) 0.17 Median (IQR) length of admission twin 2 (days) 3 (2-5.75) 4.5 (2.25-13.25) — 0.42 Maternal*3.2% (21)admissionmissing. 419 (61) 416 (62) 0.98 (0.88 to 1.09) 0.70 †4.2% (28) missing. *3.2%Median(21)(IQR)missing.length of admission (days) 1 (1-3) 1 (1-3) — 0.24 ‡2% (14) missing. Neonatal†4.2% (28)admissionmissing. 390 (57) 385 (57) 0.99 (0.89 to 1.10) 0.82 §2.8% (19) missing. Median‡2% (14)(IQR)missing.length of admission twin 1 (days) 1 (1-3) 1 (1-3) — 0.13 ¶28.7% (197) missing. §2.8% (19) missing. **28.8%Median (IQR)(193)lengthmissing.of admission twin 2 (days) 3 (2-5.75) 4.5 (2.25-13.25) — 0.42 ¶28.7% (197) missing. ††5.3% (23/447) missing. *3.2%**28.8%(21)(193)missing.missing. ‡‡6.6% (22/347) missing. †4.2%††5.3%(28)(23/447)missing.missing. ‡2%‡‡6.6%(14)(22/347)missing.missing. §2.8% (19) missing. ¶28.7% (197) missing. **28.8% (193) missing. ††5.3% (23/447) missing. ‡‡6.6% (22/347) missing.

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RESEARCH

Table 6| Maternal side effects during administration of analgesia in pregnant women allocated to patient controlled remifentanil or epidural analgesia in labour. Figures areFreemannumbers et(percentage) al. BMJ. unless2015;350:h846.otherwise indicated

No (%) with missing data Remifentanil (n=447) Epidural analgesia (n=347) Relative risk (95% CI) P value Remifentanil Epidural

Temperature °C during labour: >38 °C 35 (9) 55 (18) 0.66 (0.50 to 0.86) <0.001 41 (9.2) 35 (10.1) Maximum reported: Median (IQR) 37.0 (36.6-37.4) 37.3 (36.7-37.8) — <0.001 41 (9.2) 35 (10.1) Range 35.0-39.4 35.1-40.4 — — — — Saturation %: <95% 154 (37) 37 (12) 1.63 (1.46 to 1.82) <0.001 32 (7.2) 45 (13.0) <92% 71 (18) 14 (5) 1.52 (1.35 to 1.71) <0.001 58 (13) 73 (21) Minimum reported: Median (IQR) 95 (93-97) 97 (96-98) — <0.001 58 (13) 73 (21) Range 50-100 76-100 — — — — Hypotension (<90 mm Hg systolic) 29 (7) 38 (12) 0.75 (0.57 to 1.00) 0.03 26 (5.8) 19 (5.5) Respiratory depression 4 (1) 0 (0) — 0.15 83 (18.6) 99 (28.5) Nausea 62 (21) 25 (12) 1.27 (1.09 to 1.49) 0.01 150 (33.6) 138 (39.8) Vomiting 55 (18) 28 (13) 1.16 (0.97 to 1.38) 0.12 145 (32.4) 134 (38.6) Itching 17 (6) 20 (10) 0.77 (0.54 to 1.10) 0.1 156 (34.9) 144 (41.5)

No commercial reuse: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe Anaesthesia 2016, 71, 171–176 doi:10.1111/anae.13329 Original Article

A prospective observational study of maternal oxygenation during remifentanil patient-controlled analgesia use in labour* 1 2 3 87 % A. A. Messmer, J. M. Potts and C. E. Orlikowski

1 Consultant, Department of Anaesthesia, 3 Consultant, Department of Persistent Pain, Royal Hobart Hospital, Hobart, Tasmania, Australia 270 Statistician, The Analytical % Edge, Hobart, Tasmania, Australia16 s Summary Numerous studies of remifentanil patient-controlled analgesia during labour have shown high levels of maternal satisfaction, but concerns remain, especially over the side-effects of sedation and respiratory depression. We conducted a prospective observational study of maternal oxygen desaturation during remifentanil patient-controlled analgesia. Pulse oximetry values were recorded every eight s and later downloaded for analysis. A desaturation episode was defined as oxygen saturation < 90%. We collected 148 h of data in 61 women, during which we observed 176 desaturation episodes. These episodes occurred in 43 (70%) women. The median (IQR [range]) of the lowest saturation during each episode was 87 (85–89 [68–89])% with duration 16 (8–24 [8–104]) s. Supplementary oxygen reduced the time per hour spent with saturation < 90%, but not the depth or duration of individual episodes. Desaturation episodes were twice as common during the second stage of labour as compared with the first stage. Prior opioid administration, bolus size and use of nitrous oxide during patient-controlled analgesia use were not found to influence frequency, depth or duration of desaturation episodes. Although these findings suggest desaturation occurs more frequently during remifentanil patient-controlled analgesia than previously reported, the results are comparable with earlier oximetry studies of women who received nitrous oxide and pethidine during labour...... Correspondence to: A. A. Messmer Email: [email protected] Accepted: 21 October 2015 *Presented in part at the Annual Scientific Meeting of the Australian and New Zealand College of Anaesthetists, Adelaide, Australia, May 2015.

Introduction noted that 32% of women experienced some degree of Remifentanil patient-controlled analgesia (PCA) has respiratory depression [4]. Case reports of cardiac and been in use for over 15 years, but uncertainty still respiratory arrest associated with remifentanil PCA exists over its place in the provision of analgesia for have further accentuated these concerns [5–7]. In women during labour [1, 2]. Concerns over its safety, response to these concerns and as recommended in particularly regarding respiratory depression, have lim- editorial commentary [2], we conducted a prospective ited its widespread adoption. In 2005, a study reported observational review of our own practice of remifen- that women using remifentanil PCA spent 5% of the tanil PCA during labour, using pulse oximetry as a time with an oxygen saturation < 90% [3], and in a simple measure of maternal oxygenation. Our protocol summary of ten studies of remifentanil PCA, it was has been in place since 2007 and has been used in

Zu beachten! Remifentanil-PCA 1. Hebamme soll den Gebärsaal nicht verlassen. 2. Der PCA Bolus darf ausschliesslich durch die Patientin bedient werden. 3. Atemfrequenz, Sauerstoffsättigung und Schmerzen (VAS) sind alle 30 min. zu protokollieren Einleitung! 4. Installation durch Anästhesie nur mit CADD Pumpe und Remifentanil-Programm. Remifentanil ist ein kurzwirksames Opiat mit einer reinen µ-agonistischen Wirkung. Remifentanil- PCA ist nach der neuraxialen Analgesie die aktuell effektivste Methode zur geburtshilflichen Alarmierung Anästhesie 86600! Analgesie. Die Analgesie ist jedoch deutlich schwächer und nach 2-3 Stunden kommt es in der Regel zur Wirkungsabnahme. Die Nebenwirkung entspricht derjenigen anderer Opioide: 1. Tiefe Sedation der Patientin (auf Ansprechen nicht weckbar) Übelkeit, Erbrechen, Atemdepression u.a. 2. Atemfrequenz unter 8/min Es sind verschiedene Fälle von Atemdepression bis zum Atemstillstand beschrieben worden. Aus 3. Sättigung <90% bei Raumluft oder <95% mit Sauerstoff. diesem Grund sind entspechenden Vorsichtsmassnahmen zu treffen. Wir setzen Remifentanil-PCA im Gebärsaal ausschliesslich dann ein, wenn es eine Kontraindikation gegen ein neuraxiales ! Verfahren gibt.

Voraussetzungen! Indikation: Unmöglichkeit einer neuraxialen Analgesie (zum Beispiel):! • Gerinnungsstörung (angeboren, erworben, iatrogen) • Anatomische Besonderheit (schwere Skoliose etc.) • Infekt über der Einstichstelle / Sepsis (Chorioamnitis unter Antibiose ist keine KI für PDA) • Punktionsunmöglichkeit • Ablehnung der Patientin

Relative Kontraindikationen! • BMI > 40 • Epilepsie • Herz/Kreislauferkrankung, Schwere Pneumopathie • Schlafapnoesyndrom

Absolute Kontraindikation! • Intrauteriner Fruchttod • Abortinduktion

Weitere Voraussetzungen! • Indikation muss mit Oberarzt/ärztin Geburtshilfe und Oberarzt/ärztin Anästhesie abgesprochen sein. • Informed consent mit der Notiz, dass Remifentanil-PCA off-label ist • Eigener venöser Zugang für Remifentanil-PCA mit Rückschlagventil und langsamer Hintergrundinfusion von Ringer-Lactat • Kontinuierliche Messung der Sauerstoffsättigung • Nasenbrille zur Sauerstoffgabe liegt bereit. • Beatmungsbeutel ist bereit. • 1:1 Betreuung durch die Hebamme Th. Girard 20.4.2014 Th. Girard 20.4.2014 Epidural versus non-epiduralCochrane or no analgesia Database in labour Syst Rev. 2011;(12):CD000331. (Review)

Anim-Somuah M, Smyth RMD, Howell CJ

Epidural versus non-epidural or no analgesia in labour (Review)

Anim-Somuah M, Smyth RMD, Howell CJ

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2010, Issue 8 http://www.thecochranelibrary.com risk 95% CI NNT ratio

backpain 1 0.89 - 1.12

instrumented 1.42 1.28 - 1.57 20 delivery

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2010, Issue 8 http://www.thecochranelibrary.com

The new england journal of medicine

established in 1812 february 17, 2005 vol. 352 no. 7

The Risk of Cesarean Delivery with Neuraxial Analgesia Given Early versus Late in Labor

Cynthia A. Wong, M.D., Barbara M. Scavone, M.D., Alan M. Peaceman, M.D., Robert J. McCarthy, Pharm.D., John T. Sullivan, M.D., Nathaniel T. Diaz, M.D., Edward Yaghmour, M.D., R-Jay L. Marcus, M.D., Saadia S. Sherwani, M.D., Michelle T. Sproviero, M.D., Meltem Yilmaz, M.D., Roshani Patel, R.N., Carmen Robles, R.N., and Sharon Grouper, B.S.

abstract background Epidural analgesia initiated early in labor (when the cervix is less than 4.0 cm dilated) From the Departments of Anesthesiology has been associated with an increased risk of cesarean delivery. It is unclear, however, (C.A.W., B.M.S., R.J.M., J.T.S., N.T.D., E.Y., R.L.M., S.S.S., M.T.S., M.Y., R.P., C.R., S.G.) whether this increase in risk is due to the analgesia or is attributable to other factors. and Obstetrics and Gynecology (A.M.P.), Feinberg School of Medicine, Northwest- methods ern University, Chicago. Address reprint requests to Dr. Wong at the Department We conducted a randomized trial of 750 nulliparous women at term who were in spon- of Anesthesiology, Feinberg School of taneous labor or had spontaneous rupture of the membranes and who had a cervical di- Medicine, Northwestern University, 251 latation of less than 4.0 cm. Women were randomly assigned to receive intrathecal fen- E. Huron, F 5-704, Chicago, IL 60611, or at [email protected]. tanyl or systemic hydromorphone at the first request for analgesia. Epidural analgesia was initiated in the intrathecal group at the second request for analgesia and in the sys- N Engl J Med 2005;352:655-65. temic group at a cervical dilatation of 4.0 cm or greater or at the third request for anal- Copyright © 2005 Massachusetts Medical Society. gesia. The primary outcome was the rate of cesarean delivery. results The rate of cesarean delivery was not significantly different between the groups (17.8 percent after intrathecal analgesia vs. 20.7 percent after systemic analgesia; 95 percent confidence interval for the difference, ¡9.0 to 3.0 percentage points; P=0.31). The median time from the initiation of analgesia to complete dilatation was significantly shorter after intrathecal analgesia than after systemic analgesia (295 minutes vs. 385 minutes, P<0.001), as was the time to vaginal delivery (398 minutes vs. 479 minutes, P<0.001). Pain scores after the first intervention were significantly lower after intrathecal analgesia than after systemic analgesia (2 vs. 6 on a 0-to-10 scale, P<0.001). The incidence of one-minute Apgar scores below 7 was significantly higher after systemic analgesia (24.0 percent vs. 16.7 percent, P=0.01). conclusions Neuraxial analgesia in early labor did not increase the rate of cesarean delivery, and it provided better analgesia and resulted in a shorter duration of labor than systemic analgesia.

n engl j med 352;7 www.nejm.org february 17, 2005 655

Downloaded from www.nejm.org at UNIVERSITY OF BASEL on January 17, 2010 . Copyright © 2005 Massachusetts Medical Society. All rights reserved. Smombie http://blogbuzzter.de/wp-content/uploads/2015/11/Verkehrsschilder-in-Stockholm-warnen-vor-Menschen-mit-Smarthphone-5.jpg Epidural labour analgesia

Low concentration of local anaesthetic • Bupivacaine (0.125%), 0.1%, 0.0625% • Ropivacaine (0.175%), 0.125%, 0.1% combined with lipophilic opioid • Fentanyl 1-2 µg / ml • Sufentanil 0.5-1 µg / ml Acta Anaesthesiol Scand 2003; 47: 1085—1090 Copyright # Acta Anaesthesiol Scand 2003 Printed in Denmark. All rights reserved ACTA ANAESTHESIOLOGICA SCANDINAVICA ISSN 0001-5172

PCEA compared to continuous epidural infusion in an ultra-low-dose regimen for labor pain relief: a randomized study

1 2 3 S. LEDIN ERIKSSON ,C.GENTELE and C. H. OLOFSSON 1Department of Anaesthesiology and Intensive Care, Ga¨vle-Sandviken County Hospital, Ga¨vle, 2Department of Anaesthesiology and Intensive Care, So¨der Hospital, Stockholm, and 3Department of Anaesthesiology and Intensive Care, Karolinska Hospital, Stockholm, Sweden

Background: Patient-controlled epidural analgesia, PCEA, has Results: The PCEA group consumed 33% less of the study been introduced in obstetric analgesia during the past decade. solution than the CEI group. Mean total consumption was Many studies have shown that the consumption of analgesic is 35ml (SD 18.0) and 52ml (SD 19.6), respectively. Mean hourly 1 reduced when the parturient requests her own doses. This consumption was 5.2 ml hÀ (SD 2.54) in the PCEA group and 1 study investigates whether this is also true when using an 6.9 ml hÀ (SD 1.31) in the CEI group. There were no significant ultra-low-dose regimen. differences between the two groups in pain relief, epidural Methods: Eighty parturients were prospectively randomized to efficacy, side-effects or obstetric outcome. have either continuous epidural infusion (CEI) with ropivacaine Conclusion: PCEA reduces doses compared to continuous 1 1 1 1 mg mlÀ and sufentanil 0.5 mg mlÀ , 6 ml hÀ , or patient- infusion even when ultra-low-dose local anesthetic with opioid controlled epidural analgesia (PCEA) with 4 ml demand doses is used. The PCEA technique provides individual titration of with 20 min’ lockout. The epidural start dose was the same for the doses to an acceptable degree of pain relief. two groups, 8 ml of the study solution. Rescue bolus doses were given when needed and the continuous infusion could be increased, which gave the two groups the same maximum possible dose. The consumption of local ropivacaine in combination with sufen- Accepted for publication 22 May 2003 tanil during labor was registered. Hourly assessments made throughout labor included pain intensity documented with visual Key words: Epidural; labor; obstetric analgesia; PCEA. analog score, VAS, the patient’s opinion on epidural efficacy, motor block, pruritus and need for nitrous oxide. # Acta Anaesthesiologica Scandinavica 47 (2003)

ATIENT-CONTROLLED epidural analgesia, PCEA, for Methods and material P labor pain relief has been introduced during the past decade (1—3). Many studies have shown This prospective randomized non-blinded study was a decrease in drug consumption when compared to approved by the Ethics Committee of Uppsala Uni- continuous epidural infusion, CEI (3, 4). In these versity and Huddinge Hospital. It was a multicenter studies the epidural block was established with study performed in Ga¨vle County Hospital and So¨der high-dose local anesthetic and then maintained Hospital in Stockholm. The parturients had received with low-dose local anesthetic with opioid. The verbal and written information about the study dur- present aim was to investigate whether an ultra- ing their antenatal visits. A power calculation showed low-dose local anesthetic with opioid regimen that a total sample size of 80 parturients would dis- could be used throughout and still decrease drug cover a 25% reduction in analgesic requirement with consumption with PCEA compared to continuous apowerof81%. infusion. Studied consecutively, the parturients were all Ropivacaine is a local anesthetic which has been healthy with singleton pregnancies, ASA classification gradually introduced in obstetric anesthesia (5—7). I-II. None had received systemic opioids for 6 h before The present study also aimed to try the drug combin- entering the study. Exclusion criteria were ASA clas- 1 ation ropivacaine 1 mg mlÀ with sufentanil sification III—IV, breech presentation and existing lan- 1 0.5 mgmlÀ in an ultra-low-dose protocol. guage barrier that would have precluded instruction 1085 CSEA Int J Obstet Anesth. 2000;9(1):3–6.

ORIGINAL ARTICLE

Are combined spinal-epidural catheters reliable?

M. C. Norris Department of Anesthesiology, Section of Obstetric Anesthesia, Washington University School of Medicine, Missouri, USA.

SUMMARY. The combined spinal-epidural (CSE) technique can rapidly relieve labor pain. However, the location of the epidural catheter is initially uncertain. In an emergency, this untested catheter may fail to provide adequate anesthesia. This study compared the efﬁcacy of catheters placed as a part of an epidural or needle-through-needle CSE technique in laboring women. Patients requesting pain relief received either epidural (n=601) or CSE (n=1061) analgesia. All patients had a 20 gauge, closed tip multi-holed polyamide catheter (B. Braun Medical, Inc.) inserted 2–8 cm into the epidural space. Catheters were tested to rule out intrathecal and intravascular location. Then, epidural patients received 10–20 mL local anesthetic ± opioid in divided doses. CSE patients received an infusion of 0.083% bupivacaine with opioid at 10–15 mL/h. Of the 1495 catheters that were adequately tested, those inserted as part of a CSE technique were more likely to produce bilateral sensory change and adequate analgesia than were those inserted without prior spinal analgesia (98.6% vs 98.2%, P<0.02). Stand-alone epidural catheters were more likely to produce neither sensory change nor analgesia than those inserted as part of CSE technique (1.3% vs 0.2%, P<0.02). The only catheters that failed completely and were not intravascular were stand-alone epidural catheters. In this clinical setting, catheters inserted as part of a CSE technique had a high probability of being in the epidural space and functioning appropriately. © 2000 Harcourt Publishers Ltd

INTRODUCTION METHODS This report represents a secondary analysis of data The combined spinal-epidural (CSE) technique can from two systematic evaluations of the efficacy of relieve labor pain rapidly. However, the precise loca- multi-orifice epidural catheters in laboring women.2,3 tion of the inserted catheter is initially uncertain. In Women requesting neuraxial labor analgesia partici- an acute emergency, this untested catheter may fail to pated in these Human Studies Committee approved provide adequate anesthesia. Some even recommend protocols. One study involved collecting data about a avoiding the use of the needle-through-needle tech- standardized, accepted clinical practice.2 As such, nique of CSE in laboring women at increased risk for there was no additional risk to the subjects. Therefore, cesarean section.1 The following study examines this the Human Studies Committee waived the require- issue by comparing the efficacy of catheters placed as ment for obtaining informed consent in accordance a part of an epidural or needle-through-needle CSE with the Title 45 of the Code of Federal Regulations, technique in laboring women. Part 46–Protection of Human Subjects.4 Patients gave verbal consent to participate in the other protocol.3 Blocks were performed by residents at all levels of training, student registered nurse anesthetists, certi- fied registered nurse anesthetists with up to 30 years of Accepted January 1999 experience or by anesthesiologists. The majority of Mark C. Norris MD, Department of Anesthesiology, Section of blocks were directly supervised by an anesthesiologist. Obstetric Anesthesia, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8054, St. Louis, Missouri Patients received either epidural or CSE analgesia at 63110, USA. Fax: + 001 314 747 1716 the discretion of the anesthetist and supervising Supported by the Department of Anesthesiology, Washington anesthesiologist. CSE patients received an intrathecal University School of Medicine, St. Louis, Missouri, USA injection of 10 µg sufentanil as part of a needle-

3 Int J Obstet Anesth. 2000;9(1):3–6.

Epidural CSEA Int J Obstet Anesth. 2004;13(4):227–33.

Incidence and characteristics of failures in obstetric neuraxial analgesia and anesthesia: a retrospective analysis of 19,259 deliveries

P. H. Pan, T. D. Bogard, M. D. Owen Department of Anesthesiology, Division of Obstetric Anesthesia, Wake Forest University School of Medicine, Winston-Salem, NC, USA

SUMMARY. A retrospective analysis was performed on 19,259 deliveries that occurred in our institution from January 2000 to December 2002. Anesthesia records and quality assurance data sheets were reviewed for the characteristics and failure rates of neuraxial blocks performed for labor analgesia and anesthesia. The neuraxial labor analgesia rate was 75% and the overall failure rate was 12%. After adequate analgesia from initial placement, 6.8% of patients had subsequent inadequate analgesia during labor that required epidural catheter replacement. Ultimately 98.8% of all patients received adequate analgesia even though 1.5% of patients had multiple replacements. Six percent of epidural catheters had initial intravenous placement but 46% were made functional by simple manipulations without higher subsequent failure. Unintended dural puncture occurred in 1.2% of labor neuraxial analgesia. The incidences of overall failure, intravenous epidural catheter, wet tap, inadequate epidural analgesia and catheter replacement were lower in patients receiving combined spinal-epidural versus epidural analgesia. For cesarean section, 7.1% of pre-existing labor epidural catheters failed and 4.3% of patients required conversion to general anesthesia. Spinal anesthesia for cesarean section had a lower failure rate of 2.7%, with 1.2% of the patients requiring general anesthesia. The overall use of general anesthesia decreased from 8% to 4.3% over the three-year period. Furthermore, regional anesthesia was used in 93.5% of cesarean deliveries with no anesthetic-related mortalities. Future investigations should identify acceptable international standards, risk factors associated with failure and methods to reduce failure before cesarean section. Ó 2004 Elsevier Ltd. All rights reserved.

Keywords: Obstetric; Epidural; Spinal; Combined spinal-epidural; Failures; Complications; Neuraxial analgesia

INTRODUCTION and failure trends can help identify problems that are potentially correctable, leading to improvements in Lumbar epidural and combined spinal-epidural (CSE) patient care. An understanding of failure trends can help analgesia are commonly used for labor pain relief due shape future prospective studies aimed at improving to their effectiveness and safety.1,2 The incidence and patient safety and outcomes. Through an ongoing pro- reasons for failure of obstetric neuraxial analgesia and spective quality assurance (QA) program, a retrospective anesthesia, however, are not well characterized and vary analysis was performed on a three-year database to widely among previous reports.3–9 Analysis of failure evaluate the incidences and characteristics of failures in obstetric neuraxial analgesia and anesthesia. Accepted April 2004

Presented in part as a poster at the annual meeting of the Society of Obstetric Anesthesia and Perinatology, Phoenix, AZ, May 2003, and at the annual meeting of the American Society of Anesthesiology, METHODS San Francisco, CA, October 2003. Correspondence to: Dr. Peter Pan, Department of Anesthesiology, After Institutional Review Board approval, a retrospec- Division of Obstetric Anesthesia, Wake Forest University School of tive analysis of obstetric anesthesia and analgesia out- Medicine, Medical Center Boulevard, Winston-Salem, NC 27157- 1009, USA. Tel.: +1 336 718 8272; Fax: +1 336 718 9271; comes was conducted on data collected prospectively E-mail: [email protected] between January 2000 and December 2002 as part of

227 Failures in obstetric neuraxial analgesia 229

Table 1. Characteristics of neuraxial labor analgesia

Year 2000 Year 2001 Year 2002 Total Number of deliveries (n) 6563 6498 6198 19259 Vaginal deliveries (n) 5195 5082 4792 15069 Labor with epidural or CSE (%) 69* 73* 83* 75 Labor with epidural (%) 44 42 54 47 Labor with CSE (%) 25 31 29 28 Cesarean section in labor with epidural or CSE (%) 14 13 13 14

Data are presented numerically or as percentage. CSE = combined spinal-epidural. *P < 0.0001 for neuraxial analgesia rate among years 2000, 2001 and 2002. deliveries and 4190 (22%) cesarean sections. Table 1 intravenously and none migrated intrathecally. The inci- shows the characteristics of neuraxial labor analgesia dence of overall failure, intravenous catheter, inadequate over the study period. The neuraxial labor analgesia rate analgesia and catheter replacement was significantly increased yearly from 69% to 83% (P < 0.0001), while lower with the CSE than with the epidural technique. the cesarean section rate for labor patients with neurax- On average, our second year anesthesiology residents ial analgesia remained 13% to 14%. Table 2 character- performed 12% of all CSE and 31% of all epidural pro- izes the failed labor neuraxial blocks. The overall cedures, while third and fourth year residents performed failure rate was 12% in patients receiving either epidural 57% and 31% of the CSE; and 37% and 32% of the epi- or CSE. After initial adequate analgesia at placement, dural procedures, respectively. 6.8% of patients had inadequate analgesia subsequently Table 3 depicts labor neuraxial block function for during labor, despite adequate dosing. Nevertheless, cesarean sections. The labor epidural catheters failed 98.8% of the patients ultimately received adequate pain in 7.1% of patients at or during cesarean section relief from neuraxial analgesia. Six percent of epidural and 4.3% of the patients required conversion to gen- catheters were initially placed intravenously but 46% eral anesthesia (Table 3). For planned spinal anesthe- of them were cleared with simple manipulation and sia for cesarean section, the failure rate and functioned well subsequently (Table 2). Of the epidural conversion rate to general anesthesia were 2.7% and catheters that functioned well initially, 0.25% migrated 1.2%, respectively (Table 4). Of note is that labor

Table 2. Characteristics of neuraxial labor analgesia failures

Types of failures Epidural CSE Total P value Neuraxial labor analgesia (n) 7849 4741 12590 Overall failure rate (%) 14 10 12 <0.000001 Initial placement failure Intravenous epidural catheter (%) 7 5 6 <0.0003 aCleared with manipulation (%) 46 48 46 NS Known wet tap or intrathecal catheter (%) 1.4 0.8 1.2 <0.002 Known wet tap required EBP (%) 31 28 30 NS bOccult wet tap (%) 0.45 0.4 0.43 NS bOccult wet tap required EBP (%) 83 79 82 NS Subsequent failure cCatheter migrated i.v. (%) 0.24 0.25 0.25 NS aCleared with manipulation (%) 21 8 16 NS cCatheter migrated intrathecally (%) 0 0 0 NS Other failure dNo CSF or spinal analgesia (%) 2.4 Inadequate analgesia with epidural catheter (%) 8.4 4.2 6.8 <0.000001 eCatheter replacement for poor analgesia (%) 7.1 3.2 5.6 <0.000001 Multiple replacement of epidural (%) 1.9 0.65 1.5 <0.000001

P value: comparison between epidural and CSE techniques. EBP = epidural blood patch; CSF = cerebral spinal fluid; CSE = combined spinal epidural. aIntravenous epidural catheters were made functional by withdrawing catheter in increments and/or flushing with saline. bWet tap was not identified during labor neuraxial analgesia but a postpartum postural headache developed. cEpidural catheters that were initially functional but migrated intravenously or subarachnoid during the course of labor analgesia. dInadequate analgesia includes no CSF or failure of spinal analgesia in the cases of CSE. eIn patients with inadequate analgesia, some catheters were not replaced due to patient refusal, imminent delivery or the use of an alternative technique (usually intravenous medication). Int J Obstet Anesth. 2016;26:4–7.

ORIGINAL ARTICLE www.obstetanesthesia.com Catheter failure rates and time course with epidural versus combined spinal-epidural analgesia in labor

J. Groden, A. Gonzalez-Fiol, J. Aaronson, A. Sachs, R. Smiley Department of Anesthesiology, Columbia University College of Physicians and Surgeons, New York, NY, USA

ABSTRACT Background: The combined spinal-epidural technique for labor analgesia has several advantages over the traditional epidural technique, including faster onset, greater maternal satisfaction, and decreased need for physician boluses. Proponents of the epidural technique criticize the combined spinal-epidural technique, arguing that the epidural catheter remains untested and thus may not be reliable if needed for surgical intervention. We compared failure rates and time of failure between techniques in our tertiary-care academic practice. Methods: Data regarding failed catheters were collected from October 2012 to September 2014 as part of our Quality Assurance program. Failed catheters were defined as any catheter replaced after it was considered to be properly placed and then determined to be intravascular, one sided or resulting in poor maternal analgesia or anesthesia. Results: A total of 5487 analgesics were performed (3980 combined spinal-epidural; 1507 epidural). Eighty-five combined spinal- epidural catheters (2.1%) and 59 epidural catheters (3.9%) were replaced during labor (P<0.001). Mean time to replacement was 512 ± 422 min and 354 ± 300 min for the combined spinal-epidural (n=80) and epidural (n=57) groups, respectively (P=0.02). Median time to replacement was 398 [IQR 131–578] min and 281 [IQR 186–767] min for combined spinal-epidural and epidural groups, respectively (P<0.0001). Conclusion: We were able to demonstrate that catheters placed using a combined spinal-epidural technique were less likely to fail during labor and that the time to detection of a failed catheter was significantly longer in the combined spinal-epidural group. Our findings validate the combined spinal-epidural technique as reliable for labor analgesia and tend to refute the theory of the untested catheter. Ó 2016 Elsevier Ltd. All rights reserved.

Keywords: Labor analgesia; Epidural; Combined spinal-epidural; Failed analgesia

Introduction placed using a CSE technique are less reliable than those placed in the traditional manner. The argument is that The combined spinal-epidural (CSE) technique for labor with the CSE technique, direct assessment of epidural analgesia has several advantages over the traditional catheter function is delayed secondary to intrathecal epidural technique. These include faster onset, better drug administration at the time of catheter placement.2,9 first-stage analgesia, greater maternal satisfaction, Therefore, the technique should not be chosen for decreased motor weakness and decreased need for patients with a high chance of needing the catheter for physician boluses.1–5 Previous studies have found that surgical anesthesia or for whom the failure of surgical catheters placed with a CSE technique are at least as anesthesia is of higher risk. Alternatively, detection of reliable as those placed by an epidural technique for cerebrospinal fluid (CSF) via the spinal needle during both labor analgesia and surgical anesthesia.1,2,6–9 a CSE technique can confirm correct placement of the Despite this, many proponents of traditional epidural epidural needle, especially in the setting of a question- analgesia criticize the CSE technique using the argument able loss of resistance, perhaps even more reliably than of the untested catheter, which suggests that catheters the achievement of labor analgesia.2 We have compared failure rates and time of failure between catheters placed via the CSE and traditional epidural techniques in our Accepted January 2016 Correspondence to: Jonathan Groden MD, Department of Anesthe- tertiary-care academic practice. siology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, PH-5, New York, NY 10032, USA. E-mail address: [email protected] 6 Epidural and CSE catheter failures

Table 1 Comparison of combined spinal-epidural and traditional epidural catheters CSE Epidural Overall P value Number 85 59 144 Age (years) 31.3 ± 5.6 30.2 ± 6.3 30.8 ±5.9 0.27 Body mass index (kg/m2) 32.0 ± 7.2 32.0 ± 7.7 32.0 ± 7.5 1.0 Nulliparous 55 34 89 0.49 No. of physician boluses pre replacement 2.28 ± 1.74 2.02 ± 1.47 2.17 ± 1.63 0.35 Initiation of analgesia to delivery (min) 788 ± 455 633 ± 420 724 ± 446 0.04 Loss of resistance (cm) 5.8 ± 1.5 6.1 ± 1.4 5.9 ± 1.4 0.23 Depth catheter ﬁxed (cm) 10.9 ± 1.50 11.4 ± 1.97 11.1 ± 1.69 0.10 Catheter failure rateInt J Obstet Anesth. 2016;26:4–7. 2.1% 3.9% 2.6% <0.001 Time to replacement (min) 512 ± 422 354 ± 300 446 ± 383 0.02 Data are number, percentage, mean ± SD.

the failure rates of the two techniques diverging early and then approximately parallel later, suggests that the 2.1 % vs. 3.9 % earlier median failure time in the epidural group may be explained by early failures (before 3–4 h) due to faulty initial placement, with a higher rate associated with the epidural technique. Later failures may reflect catheter movement or blood vessel entry or some other mechanism of late failure after initial correct placement. The later failures would presumably occur in both groups equally. Patients in the CSE group had a longer time from catheter placement to delivery. While this suggests that patients in the CSE group received catheters earlier in labor, it is difficult to draw any conclusions from this finding, as we do not have information regarding labor Fig. 1 Survival curves of catheters placed via epidural and progress or cervical examination at the time of catheter combined spinal-epidural technique. CSE: combined spinal- placement. It is important to note that in our practice, epidural the decision to place a catheter via CSE or epidural technique is generally not based on patient-related factors or labor progress but rather on attending preference. As such, we cannot necessarily attribute the longer time from CSE placement to delivery to the preferential placement of CSEs early in labor to facilitate artificial rupture of membranes or labor augmentation with oxytocin. Among those faculty members who generally favor epidurals, CSE is still frequently performed in women who are late in the first stage or in the second stage of labor. Lastly, our study indicates that catheters placed by CSE and epidural techniques were equally successful for conversion from labor analgesia to surgical anesthesia for CD. These results corroborate results previously reported by Riley et al.10 and refute the theory of the untested CSE catheter being more likely to fail at CD. In fact, Lee et al. found an increased rate of failed conversion 11 Fig. 2 Survival curves of catheters placed via epidural and with epidural when compared with CSE catheters. combined spinal-epidural technique for first 500 min. CSE: A limitation of this study is the lack of patient ran- combined spinal-epidural domization. In our practice, attending anesthesiologists choose between CSE and epidural technique based on correctly be viewed as untested.2 Thus, few of the CSE personal preference, not necessarily on patient-related failures were likely due to initial malposition masked factors. As such, we do not believe the populations of by the initial analgesia from the intrathecal dose. Inspec- women receiving the different techniques were likely to tion of the survival curve (Figs. 1 and 2), which shows be very different. It is important to consider that most Anesthesiology. 2016;125(3):516–24.

Combined Spinal Epidural Technique for Labor Analgesia Does Not Delay Recognition of Epidural PERIOPERATIVE MEDICINE Catheter Failures A Single-center Retrospective Cohort Survival Analysis

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This article has been selected for the ANESTHESIOLOGY CME Program. Learning objectives and disclosure and ordering information can be found in the CME section at the front of this issue.

ABSTRACT

Background: It is unclear whether recognition of epidural catheter failures is delayed with combined spinal epidural technique (CSE) compared to traditional epidural technique (EPID) when used for labor analgesia. Te authors hypothesized that recognition of failed catheters is not delayed by CSE. Methods: Anesthetic, obstetric, and quality assurance records from 2,395 labor neuraxial procedures (1,440 CSE and 955 EPID) performed at Forsyth Medical Center (Winston-Salem, North Carolina) between June 30 and December 31, 2012, were retrospectively analyzed. Te primary outcome was catheter survival (failure-free) time during labor analgesia. A proportional hazards model with the counting method was used to assess relationships between the techniques and survival (failure- free) time of catheters, while controlling for subjects’ body mass index and providers’ level of training in the fnal best-ft multivariable regression model. Results: Cumulative incidence of epidural catheter failures was 6.6% for CSE and 11.6% for EPID (P = 0.001). In the multivariable regression model, catheters placed with CSE versus epidural were less likely to fail (hazard ratio, 0.58; 95% CI, 0.43 to 0.79; P = 0.0002) for labor analgesia. Among the catheters that failed, there was no overall diference in failure time course between the techniques (hazard ratio, 1.17; 95% CI, 0.89 to 1.54; P = 0.26) even though more failed catheters with CSE (48.4%) than with EPID (30.6%) were recognized within the frst 30 min of placement (P = 0.009). Conclusions: In this cohort, CSE has a signifcantly lower risk of overall epidural catheter failures than EPID and does not delay recognition of epidural catheter failures. Choice of CSE versus EPID should be based on overall risk of failure, efcacy, and side efects. (ANESTHESIOLOGY 2016; 125:516-24)

PIDURAL analgesia has long been the mainstay of labor What We Already Know about This Topic Eanalgesia because it allows efective drug delivery throughout the course of labor, including cesarean delivery if necessary. t $PNCJOFETQJOBMFQJEVSBMBOBMHFTJBIBTCFDPNFBDPNNPO UFDIOJRVFGPSBOBMHFTJBJOUIFMBCPSJOHQBUJFOUEVFUPJUTNPSF Furthermore, epidural analgesia has a long-standing history of SBQJEPOTFUDPNQBSFEXJUIFQJEVSBMBOBMHFTJBBMPOF superior maternal and fetal safety compared to other forms of t )PXFWFS DPODFSOFYJTUTUIBUDPNCJOFETQJOBMFQJEVSBMDPVME analgesia and anesthesia. Initially, combined spinal epidural EFMBZSFDPHOJUJPOPGGBJMFEFQJEVSBMDBUIFUFSQMBDFNFOU technique (CSE) began as a refnement of traditional epidural What This Article Tells Us That Is New technique (EPID).1 Over the last two decades, CSE for labor t "TJOHMFDFOUFSSFUSPTQFDUJWFBOBMZTJTPG OFVSBYJBMQSPDF analgesia has become popular because of its advantages over EVSFTGPSMBCPSBOBMHFTJBGPVOEUIBUDPNCJOFETQJOBMFQJEVSBM EPID. A Cochrane systematic review2 comparing CSE and EJEOPUEFMBZSFDPHOJUJPOPGGBJMFEFQJEVSBMDBUIFUFSQMBDFNFOUT EPID indicated that the onset of completed analgesia was t .PSFPWFS UIFSJTLPGFQJEVSBMBOBMHFTJBGBJMVSFXBTMPXFSGPS signifcantly faster with CSE (−5.42 min [95% CI, −7.26 to DPNCJOFETQJOBMFQJEVSBMUIBOGPSFQJEVSBMBMPOF −3.59]), and more women with CSE achieved efective analgesia at 10 min (relative risk, 1.94 [95% CI, 1.49 to 2.54]). during labor or at least have a better sense of motor control.3 In addition, motor blockade and risk of hypotension may be Compared to EPID, CSE also has been associated with a lower lower with CSE; in turn, patients may be able to ambulate cumulative incidence of epidural catheter failures during labor

This article is featured in “This Month in Anesthesiology,” page 1A. Submitted for publication September 28, 2015. Accepted for publication June 6, 2016. From the Section of Obstetric Anesthesia, Depart- ment of Anesthesiology (J.M.B., J.C.P., V.H.R., L.C.H., P.H.P.) and Department of Biostatistical Sciences (G.B.R.), Wake Forest School of Medicine, Winston-Salem, North Carolina.

"OFTUIFTJPMPHZ 7t/P 516 September 2016

Table 3. Univariate Models of Covariates

Parameter df Parameter Estimate SE Chi-square P Value Hazard Ratio 95% CI

Procedure 1 −0.543 0.142 14.630 0.0001 0.58 0.44–0.77 BMI (kg/m2) 1 0.035 0.009 15.883 < 0.0001 1.04 1.02–1.05 Provider 3 0.97 Provider 1 1 −0.070 0.275 0.066 0.78 0.93 0.54–1.60 Provider 2 1 −0.088 0.193 0.208 0.65 0.92 0.62–1.34 Provider 3 1 −0.067 0.172 0.152 0.70 0.94 0.67–1.31 Gestational age (wk) 1 −0.040 0.022 3.337 0.07 0.96 0.92–1.003 Parity 1 0.038 0.059 0.406 0.52 1.04 0.92–1.17

Total numbers of cathetersAnesthesiology. analyzed for each 2016;125(3):516–24. covariate’s univariate model: procedure = 2,395; body mass index (BMI) = 2,362; provider = 2,388; gestational age = 2,388; parity = 2,393. Provider = providers’ level of training: 1 = clinical anesthesia training year (CA) 1, 2 = CA2, 3 = CA3, 4 = CA4 and attending combined, where 4 is the referent group. Referent group for procedure is traditional epidural technique, while exposure group is combined spinal epidural technique. For hazard ratios, a value below 1 indicates a lower risk of catheter failures, while a value above 1 indicates an increased risk of catheter failures. df = degrees of freedom. 6.6 % vs. 11.6 % Consistency of the Model Te proportional hazards model (PROC PHREG) used correctly accounted for repeated procedures within the same patients. Results did not change in a sensitivity analysis when only the frst procedure of each patient was included. When the primary analysis (catheter failures between techniques) was performed including only the frst procedure for each patient, results for the primary outcome from the single-variable model (HR, 0.63; 95% CI, 0.47 to 0.84; P = 0.002) and the all-inclusive multivariable model (HR, 0.65; 95% CI, 0.47 to 0.91; P = 0.01) were consistent with results from models that included repeated procedures within the same patients (tables 3 and 4). Similarly, when catheters needed for CD were excluded from the fnal best-ft multivariable model, the primary outcome (HR, 0.58; 95% CI, Fig. 1. Kaplan–Meier survival analysis of all epidural catheters 0.42 to 0.80; P = 0.0009) remained essentially unchanged. placed with combined spinal epidural technique (CSE, n = 1,440) Finally, even when ASA PS and CD were included to the versus traditional epidural technique (EPID, n = 955) in a univari- covariates (procedure type, BMI, providers’ level of training, ate model. HR = hazard ratio; survival time = duration of catheter remained failure free or until end of functional usage. gestational age, and parity) of the all-inclusive multivariable model, the primary outcome fndings (HR, 0.61; 95% CI, 0.44 to 0.83; P = 0.002) were consistent and the conclusion controlled for in the fnal model. Gestational age met the was the same. inclusion threshold in the univariate analysis but became insignifcant and was removed in the stepwise algorithm of the fnal best-ft multivariable model. Te cumulative inci- Failure Pattern and Analyses of Only Failed Catheters dence of epidural catheter failures was 8.5% overall, 6.3% (Failure-only Model) for CSE, and 11.7% for EPID (P < 0.000001). When only Figure 3A shows the survival curve in a univariate model of nontechnical failures were considered in the multivari- only all failed catheters. Tere were no overall diferences in able model, catheters placed with CSE remained less likely the catheter failure time between CSE and EPID (HR, 1.17; (HR, 0.49; 95% CI, 0.33 to 0.73; P = 0.0004) to fail 95% CI, 0.89 to 1.54; P = 0.26; fg. 3A). When the survival over the course of labor and delivery. However, when only time for the frst 120 min of catheter placement was ana- technical failures are considered, the overall likelihood of lyzed, only the survival time during the frst 30 min difered failures did not difer between techniques (HR, 0.94; 95% between CSE and EPID (HR, 1.86; 95% CI, 1.19 to 2.90; CI, 0.60 to 1.46; P = 0.78). In addition, when all consid- P = 0.005). Beyond 30 min, there was no overall diference ered covariates were modeled in an all-inclusive multivari- in survival time between procedure types (fg. 3B). Similar able model regardless of their inclusion threshold or P value, results were seen with ORs (CSE vs. EPID as referent) when the results for the primary outcome (HR, 0.60; 95% CI, looking at failure proportions, rather than length of survival, 0.44 to 0.82; P = 0.001) were consistent with those in our in 15-min intervals. Among catheters that eventually failed, fnal multivariable model and did not add any statistically the ORs of catheter failures (CSE vs. EPID as referent) at signifcant variables to it. the frst three 15-min interval time points after catheter

Anesthesiology 2016; 125:516-24 521 Booth et al. Copyright © 2016, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. CSE Does Not Delay Epidural Catheter Failure Recognition

Fig. 2. (A) Kaplan–Meier survival analysis of all epidural catheters placed with combined spinal epidural technique (CSE) versus traditional epidural technique (EPID), including only nontechnical failures in a univariate model (47 and 77 nontechnical failures occurred with CSE and EPID, respectively).Anesthesiology. (B) Kaplan–Meier 2016;125(3):516–24. survival analysis of all epidural catheters placed with CSE versus EPID, including only technical failures in a univariate model (48 and 34 technical failures occurred with CSE and EPID, respectively). HR = hazard ratio; nontechnical failures = no block or inadequate analgesia; survival time = duration of catheter remained failure free or until end of functional usage; technical failures = inadvertent intravenous or intrathecal catheter, or other technical failures such as obstructed or dislodged catheter.

Table 4. Final Multivariable Model for Survival Analyses of All Catheters with Procedural Type, BMI, and Provider Experience Level Controlled in the Model

Parameter df Parameter Estimate SE Chi-square P Value Hazard Ratio 95% CI

Procedure 1 0.544 0.154 12.430 0.0002 0.58 0.43–0.79 BMI (kg/m2) 1 0.026 0.009 8.573 0.003 1.03 1.02–1.04 Provider 3 0.75 Provider 1 1 −0.298 0.284 1.102 0.29 0.74 0.43–1.30 Provider 2 1 −0.117 0.196 0.360 0.55 0.89 0.61–1.31 Provider 3 1 −0.058 0.175 0.109 0.74 0.94 0.67–1.33

Number of catheters in the model = total 2,355: combined spinal epidural technique (CSE) is 1,416 and traditional epidural technique (EPID) is 939. Num- ber of unique subjects in the model = total 2,174: CSE 1,384 and EPID 790. Provider = providers’ level of training: 1 = clinical anesthesia training year (CA) 1, 2 = CA2, 3 = CA3, 4 = CA4 and attending combined, where 4 is the referent group. Referent group for procedure is EPID, while exposure group is CSE. For hazard ratios, a value below 1 indicates lower risk of catheter failures; a value above 1 indicates increased risk of catheter failures. BMI = body mass index; df = degrees of freedom.

placement were 2.25 at 15 min (95% CI, 1.25 to 4.06; P suggest that the time to recognizing catheter failures was not = 0.008) and 2.13 at 30 min (95% CI, 1.20 to 3.76; P = delayed by CSE. When only failures occurring during the 0.010), with nonsignifcant diferences between CSE and frst 120 min after placement were analyzed in 15-min inter- EPID (referent) starting at 45 min (OR, 1.39; 95% CI, 0.80 vals, more failed catheters from CSE than from EPID were to 2.41; P = 0.26). Furthermore, during the frst 30 min after recognized in the frst 30 min from placement; however, no catheter placement, 91.3 and 91.2% of the epidural cath- diferences were seen beyond the frst 30 min. eter failures from CSE and EPID, respectively, were tech- Although technical failures predominated during the nical failures, and frequency did not difer between groups frst 30 min after placement for both CSE and EPID, a few (P = 0.31; table 2). nontechnical (inadequate analgesia or no block) failures also occurred; their incidence did not difer between groups. With group assignment based on intended procedure in this study, Discussion nontechnical failures were recognized with CSE when EPID Compared to EPID, catheters placed via CSE were associ- catheters were used within the frst 30 min if the spinal dose ated with a 0.58-times overall likelihood of failures through- did not provide adequate analgesia, as reported elsewhere.9,12,17 out the course of labor neuraxial analgesia. When only failed Te proportions of nontechnical (inadequate analgesia or no catheters were compared, there was no overall diference block) failures were similarly small for both CSE and EPID between the two techniques in their proportion of survival during the frst 30 min of placement. Tis result also sug- (or failure) over the full-time course of usage. Tese results gests that CSE did not increase or delay unrecognized poorly

Anesthesiology 2016; 125:516-24 522 Booth et al.

The Effect of Combined Spinal–Epidural Versus Epidural Analgesia in Laboring Women on Nonreassuring Fetal Heart Rate Tracings: Systematic Review and Meta-analysis

Judith Hattler, MD, Markus Klimek, MD, PhD, DEAA, EDIC, Rolf Rossaint, MD, PhD, and Michael Heesen, MD, PhD * † ‡ * BACKGROUND: Combined spinal–epidural labor analgesia has gained popularity, but it is unclear whether this technique is associated with a higher incidence of nonreassuring fetal heart rate (FHR) tracings compared with epidural analgesia. Our meta-analysis aimed at comparing the incidence of nonreassuring FHR tracings between the 2 neuraxial techniques. METHODS: Databases were searched to identify randomized controlled trials that compared the incidence of nonreassuring FHR tracings, as defned in the individual studies, after combined spinal–epidural versus epidural analgesia in laboring women. Risk ratios (RRs) and 95% confdence intervals (CIs) were calculated using the random-effects model. We performed a subgroup analysis for studies using low-dose epidural bupivacaine concentrations (≤0.125%) for epidural analgesia. RESULTS: Seventeen trials including 3947 parturients were retrieved that compared the 2 neuraxial techniques. All trials used intrathecal opioids in 1 study arm. The pooled effect estimate of low- and high-dose epidural bupivacaine studies together showed a signifcantly increased risk of nonreassuring FHR tracings with the combined technique (RR 1.31, 95% CI 1.02–1.67, P = .03, I2 = 18%). A subgroup analysis of 10 trials using low-dose epidural bupivacaine found a RR for nonreassuring FHR tracings between combined spinal–epidural and epidural analgesia of 1.12, 95% CI 0.93–1.34, P = .18. In a sensitivity analysis of those low-dose epidural bupivacaine studies that ensured blinding of the outcome assessor, the RR was 1.41, 95% CI 0.99–2.02, P = .06. CONCLUSIONS: Combined spinal–epidural labor analgesia was associated with a higher risk of nonreassuring FHR tracings than epidural analgesia alone. In the subgroup analysis comparing combined spinal–epidural with low-dose epidural labor analgesia, the 95% CI contains a clinically signifcant difference between groups; moreover, the 95% CI overlaps with the 95% CI of the comparison of the combined low- and high-dose epidural techniques. Therefore, it cannot be concluded that there was no difference between combined spinal–epidural and low-dose epidural techniques. (Anesth Analg 2016;XXX:00–00)

euraxial analgesia is the most effective way to with epidural analgesia, a fnding that was not corroborated provide labor pain relief. Epidural analgesia and in a recent trial by Patel et al.3 A meta-analysis from 20024 Ncombined spinal–epidural (CSE) analgesia are both reported that the incidence of fetal bradycardia was sig- recommended by the UK National Institute for Health and nifcantly increased in parturients receiving an intrathecal Clinical Excellence.1 Usually, local anesthetics are used in opioid compared with any nonintrathecal opioid neuraxial combination with lipid-soluble opioids for both the epi- technique. The risk for cesarean delivery because of FHR dural and the intrathecal route. abnormalities was not greater with intrathecal opioids.4 Abrão et al2 reported a higher incidence of fetal heart Moreover, intrathecal opioids had no effect on the instru- rate (FHR) abnormalities after CSE analgesia compared mental vaginal or cesarean delivery rates or oxytocin use during labor.4

From the Department of Anaesthesia, Kantonsspital Baden, Baden, We therefore aimed to perform a systematic review and Switzerland; Department of Anaesthesiology, Erasmus University Medical meta-analysis of randomized controlled trials that com- Center, Rotterdam,* The Netherlands; and Department of Anaesthesia, pared the incidence of nonreassuring FHR tracings in par- University Hospital† RWTH Aachen, Aachen, Germany. ‡ turients who received labor analgesia initiated by a CSE Accepted for publication April 11, 2016. versus epidural analgesia technique. Funding: This study was supported by departmental funds only. The authors declare no conficts of interest. This report is a systematic review and meta-analysis. The author states METHODS that the report includes every item in the PRISMA checklist for systematic This analysis was conducted in accordance with the reviews and meta-analysis clinical studies. Preferred Reporting Items for Systematic Reviews and Reprints will not be available from the authors. Meta-analyses (PRISMA) guidelines.5 We searched the data- Address correspondence to Michael Heesen, Department of Anaesthesia, bases PubMed, Embase, CINAHL, LILACS, CENTRAL, Kantonsspital Baden, Im Ergel 1, 5404 Baden, Switzerland. Address e-mail to [email protected]. Clinicaltrials.gov, and ISI WOS to identify randomized con- Copyright © 2016 International Anesthesia Research Society trolled trials that assessed the incidence of nonreassuring DOI: 10.1213/ANE.0000000000001412 FHR tracings in laboring women undergoing CSE versus

Number XXX www.anesthesia-analgesia.org 1 ڇ Volume XXX ڇ XXX 2016 Copyright © 2016 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited. Abnormal Fetal Heart Rate Tracings and Neuraxial Analgesia

Hattler et al. Anesth Analg. 2016 ahead of print Fetale bradycardia

Figure 2. Incidence of nonreassuring fetal heart rate tracings during combined spinal–epidural analgesia versus epidural analgesia. A, Incidence of nonreassuring fetal heart rate tracings, all studies. B, Incidence of fetal bradycardia, all studies. C, Incidence of nonreassuring fetal heart rate tracings in studies using low-dose epidural bupivacaine. CI indicates confdence interval; IV, inverse variance; M-H, Mantel– Haenszel; PCEA, patient-controlled epidural analgesia; PCEA+CI, patient-controlled epidural analgesia with continuous infusion; Random, random-effects model.

DISCUSSION paucity of data on nonreassuring FHR tracings as indication A signifcantly increased risk for nonreassuring FHR trac- for cesarean delivery; only 2 studies reported this outcome. ings with CSE analgesia compared with epidural analgesia Nonreassuring FHR tracings were not analyzed in was observed in this meta-analysis. This result was found a 2012 Cochrane review comparing CSE with epidural when studies not blinding the outcome assessor were analgesia.25 Our analysis thus provides additional data included and also in a sensitivity analysis that excluded that may help the clinician to make an informed choice studies without blinding of the outcome assessor. Fetal between the 2 neuraxial techniques. In 2002, Mardirosoff bradycardia, a type of nonreassuring FHR tracing, was et al4 reported that intrathecal opioids were associated reported in only 4 studies, and the RR was signifcantly with an increased risk for fetal bradycardia compared with higher in parturients receiving CSE analgesia. There was a nonintrathecal opioid neuraxial techniques; no difference

Sia et al. | Comparison of variable-frequency mandatory boluses with basal infusion for PCEA Anaesthesia 2012

Table 2 Analgesic and obstetric proﬁle of parturients assigned to PCEA with an automated bolus or basal infusion, at the time that breakthrough pain was experienced. Values are median (IQR [range]).

Automated Infusion bolus (n = 3) (n = 12) p value* Time to 1st breakthrough pain; min 205 (139–555 [139–555]) 286.5 (164–391 [145–630]) 0.99 Volume of epidural solution infused 25 (15–65 [15–65]) 47.5 (34–65 [20–100]) 0.25 at 1st breakthrough pain; ml Cervical dilation at 1st breakthough pain; cm 6 (3–7 [3–7]) 6.5 (5–8 [3–10]) 0.42 VAS at 1st breakthrough pain; cm 6 (6–6 [6–6]) 7.5 (6–9 [5–10]) 0.12 1 Oytocin infusion at 1st breakthrough pain; ml.hÀ 18 (12–42 [12–42]) 12 (0–27 [0–72]) 0.30 Sensory level at 1st breakthrough pain T8 (T6–T10 [T6–T10]) T8 (T7–T10 [T6–T10]) 0.89 Bromage score at 1st breakthrough pain 0 [0–0] 0 [0–0] 1.0

*Non-parametric tests were applied owing to the small number of patients with breakthrough pain.

Table 3 Side-effects of combined spinal–epidural in at full cervical dilation (p < 0.001). Two parturients in 102 parturients assigned to PCEA with an automated the Infusion group had their epidural infusion stopped bolus or basal infusion. Values are number (propor- by the obstetrician during the second stage of labour tion). and their data were analysed up to the point of Automated Infusion cessation of analgesia. Neonatal outcomes such as birth bolus (n = 51) (n = 51) p value weightAnaesthesia. and Apgar 2013;68(3):267–75. scores were similar (Table 4). Shivering 23 (45.1%) 26 (51.0%) 0.69 When asked to rate their overall labour analgesia Pruritus 29 (56.9%) 27 (52.9%) 0.84 Nausea 1 (2.0%) 1 (2.0%) 1.0 experience, parturients in the Automated bolus group Vomiting 1 (2.0%) 2 (3.9%) 1.0 reported higher satisfaction scores compared with Maternal pyrexia 3 (5.9%) 4 (7.8%) 1.0 those in the Infusion group, 96.5 (5.0) vs 89.2 (9.4) Maternal 0 1 (2.0%) 1.0 hypotension respectively (p < 0.001). Fetal bradycardia 2 (3.9%) 2 (3.9%) 1.0 Discussion In this study, we demonstrated that using variable- medication in the Automated bolus group, 10.9 frequency automated intermittent boluses in place of a 1 (4.5) ml.hÀ compared with the mean background continuous basal infusion in PCEA for labour analge- 1 infusion rate of 4.8 (1.0) ml.hÀ in the Infusion group sia resulted in a reduced incidence of breakthrough

Table 4 Obstetric and neonatal outcomes in 102 parturients. Values are mean (SD), number (proportion) or median (IQR [range]).

Automated Infusion bolus (n = 51) (n = 51) p value Duration of labour; min 389.4 (202.9) 414.2 (181.3) 0.52 Duration of 2nd stage; min 69.8 (48.9) 84.9 (57.9) 0.22 Rate of machine-delivered 10.9 (4.5) 4.8 (1.0) < 0.001 epidural medication during 2nd 1 stage of labour; ml.hÀ Mode of delivery Normal 33 (64.7%) 32 (62.7%) 0.65 Instrumental 5 (9.8%) 8 (15.7%) Caesarean 13 (25.5%) 11 (21.6%) Neonatal birthweight; g 3244.4 (392.5) 3083.5 (502.9) 0.08 Neonatal Apgar score at 5 min 9 (9–9 [7–9]) 9 (9–9 [9–9]) 1.00 Satisfaction score 96.5 (5.0) 89.2 (9.4) < 0.001

© 2012 The Authors Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland 7 Obstetric Anesthesiology ObstetricSection Editor: AnesthesiologyCynthia A. Wong Section Editor: Cynthia A. Wong Focused Review Focused Review Anesth Analg. 2009;108(3):921–8. Patient-Controlled Epidural Analgesia for Labor Patient-Controlled Epidural Analgesia for Labor Stephen H. Halpern, MD, MSc, Patient-controlled epidural analgesia (PCEA) for labor was introduced into clinical Stephen H. Halpern, MD,FRCPC* MSc, Patient-controlledpractice 20 yr ago. Theepidural PCEA analgesia technique (PCEA) has been for shown labor was to have introduced significant into benefits clinical when compared with continuous epidural infusion. We conducted a systematic FRCPC* practice 20 yr ago. The PCEA technique has been shown to have significant benefits Brendan Carvalho, MBBCh, whenreview compared using MEDLINE with continuous and EMBASE epidural (1988–April infusion. 1,We 2008) conducted of all randomized, a systematic FRCA† reviewcontrolled using trials MEDLINE in parturients and EMBASE who received (1988–April PCEA in 1, labor 2008) in of which all randomized, one of the Brendan Carvalho, MBBCh, following comparisons were made: background infusion versus none; ropivacaine FRCA† controlled trials in parturients who received PCEA in labor in which one of the followingversus bupivacaine; comparisons high were versus made: low background concentrations infusion of local versus anesthetics; none; ropivacaine and new versusstrategies bupivacaine; versus standard high versus strategies. low concentrations The outcomes of of local interest anesthetics; were maternaland new strategiesanalgesia, versus satisfaction, standard motor strategies. block, and The the outcomes incidence of of interest unscheduled were maternal clinician analgesia,interventions. satisfaction, motor block, and the incidence of unscheduled clinician interventions.A continuous background infusion improved maternal analgesia and reduced unscheduledA continuous clinician background interventions. infusion Larger improved bolus maternal doses (more analgesia than and 5 mL) reduced may unscheduledprovide better clinician analgesia interventions. compared with Larger small bolus boluses. doses (more Low concentrations than 5 mL) may of providebupivacaine better or ropivacaineanalgesia compared provide excellent with small analgesia boluses. without Low concentrations significant motor of bupivacaineblock. Many or strategies ropivacaine with provide PCEA excellent can provide analgesia effective without labor significant analgesia. motor High block.volume, Many dilute strategies local anesthetic with PCEA solutions can provide with a continuous effective labor background analgesia. infusion High volume,appear to dilute be the local most anesthetic successful solutions strategy. with Research a continuous into new background delivery strategies, infusion appearsuch as to mandatory be the most programmed successful intermittent strategy. Research boluses into and new computerized delivery strategies, feedback suchdosing, as ismandatory ongoing. programmed intermittent boluses and computerized feedback dosing,(Anesth Analg is 2009;108:921–8) ongoing. (Anesth Analg 2009;108:921–8)

Patient-controlled epidural analgesia for labor clinically significant impact on obstetric or neonatal 5 (PCEA)atient-controlled was first introduced epidural into analgesia clinical practice for labor by clinicallyoutcomes. significant impact on obstetric or neonatal P 1 (PCEA)Gambling was et al. firstin introduced 1988. It has into proven clinical to be practice both safe by outcomes.Clinical5 research has focused on refining PCEA andGambling effective. et al. PCEA1 in 1988. has many It has advantages proven to be when both com- safe techniquesClinical to research further hasimprove focused analgesia, on refining reduce PCEAmotor andpared effective. with continuous PCEA has epidural many advantages infusion when(CEI) com-tech- techniquesblock, and increase to further maternal improve satisfaction, analgesia, reduce while reduc- motor paredniques. with Although continuous the analgesia epidural provided infusion (CEI) is similar, tech- block,ing the and frequency increase of maternal unscheduled satisfaction, clinician while interven- reduc- niques.PCEA reduces Although the the incidence analgesia of unscheduled provided is clinician similar, ingtions. the In frequency this overview, of unscheduled we will systematically clinician interven- review PCEAinterventions reduces and the the incidence total dose of unscheduled of local anesthetic. clinician2 tions.the current In this evidence overview, to we answer will systematically the following review questions: 1) Should a background infusion be used? 2) Is interventionsPCEA also reduces and the the total incidence dose of of local lower anesthetic. extremity2 the current evidence to answer the following ques- 3 ropivacaine superior to bupivacaine when used for PCEAmotor also block. reducesAlthough the incidence PCEA has of notlower consistently extremity tions: 1) Should a background infusion be used? 2) Is PCEA in labor? 3) Can the volume of the PCEA bolus beenmotor associated block.3 Although with increased PCEA maternal has not consistentlysatisfaction, ropivacaine superior to bupivacaine when used for dose and lockout interval be manipulated to optimize beenthis may associated be due with to a increased lack of appropriate maternal satisfaction, measuring PCEA in labor? 3) Can the volume of the PCEA bolus doseanalgesia? and lockout and 4) interval What is be the manipulated impact of to new optimize tech- thistools. may Theoretically, be due to amaternal lack of satisfactionappropriate may measuring be in- analgesia?niques and and technologies 4) What on is current the impact PCEA of practice? new tech- In tools.creased Theoretically, by allowing the maternal parturient satisfaction greater control may be over in- 4 niquesanswering and technologiesthese questions, on current we hope PCEA to practice? be able Into creasedher analgesia. by allowingCompared the parturient with CEI, greater PCEA control has over no suggest a range of appropriate settings for labor PCEA 4 answering these questions, we hope to be able to her analgesia. Compared with CEI, PCEA has no suggestand present a range a glimpse of appropriate into future settings techniques for labor of PCEA labor From the *Department of Anesthesia, Sunnybrook Health Sciences andanalgesia present maintenance. a glimpse into future techniques of labor Centre, University of Toronto, Toronto, Canada; and †Department From the *Department of Anesthesia, Sunnybrook Health Sciences analgesiaTo answer maintenance. the above questions, we systematically of Anesthesia, Stanford University School of Medicine, Stanford, Centre, University of Toronto, Toronto, Canada; and †Department California. reviewedTo answer all published, the above questions, randomized, we systematically controlled tri- of Anesthesia, Stanford University School of Medicine, Stanford, als on PCEA for labor. Studies were obtained from California.Accepted for publication September 28, 2008. reviewed all published, randomized, controlled tri- MEDLINE and EMBASE, published in English before AcceptedSupported for by publication Departmental September Sources. 28, 2008. als on PCEA for labor. Studies were obtained from April 1, 2008. We included studies that have the SupportedReprints will by not Departmental be available Sources. from the author. MEDLINE and EMBASE, published in English before following intervention and control groups: 1) back- ReprintsAddress willcorrespondence not be available to Dr. from Stephen the author. Halpern, Sunnybrook April 1, 2008. We included studies that have the Health Sciences Centre/Women’s College Hospital, 76 Grenville ground infusion versus no background infusion; 2) Address correspondence to Dr. Stephen Halpern, Sunnybrook following intervention and control groups: 1) back- St., Toronto, Ontario, Canada M5S 1B2. Address e-mail to Health Sciences Centre/Women’s College Hospital, 76 Grenville groundropivacaine infusion versus versus bupivacaine; no background 3) high-volume infusion; bolus 2) [email protected]. St., Toronto, Ontario, Canada M5S 1B2. Address e-mail to ropivacaineversus low-volume versus bupivacaine; bolus and/or 3) longer high-volume lockout bolusinter- [email protected] © 2009 International Anesthesia Research Society val versus shorter lockout interval; and 4) a novel DOI: 10.1213/ane.0b013e3181951a7f versus low-volume bolus and/or longer lockout inter- Copyright © 2009 International Anesthesia Research Society valapproach versus to shorter PCEA lockout versus standard interval; treatment. and 4) a novel Each DOI: 10.1213/ane.0b013e3181951a7f approach to PCEA versus standard treatment. Each Vol. 108, No. 3, March 2009 921 Vol. 108, No. 3, March 2009 921 Anesth Analg. 2009;108(3):921–8.

motor block

local anaesthetics Anesth Analg. 2009;108(3):921–8.

clinican interventions PIEB

1 hour

20min Curr Opin Anaesthesiol. 2013;26(3):261–7.

REVIEW

CURRENT OPINION Techniques for the maintenance of epidural labor analgesia

Giorgio Capogna and Silvia Stirparo

Purpose of review After initiating neuraxial labor analgesia, there are many techniques that can be used to maintain analgesia for the duration of labor. In this review, we have examined the new techniques of maintenance of epidural labor analgesia recently proposed to overcome the undesirable effects of continuous infusion and patient-controlled epidural analgesia (PCEA). Recent findings As labor progresses, there is a greater need for analgesia. PCEA with basal infusion, automated intermittent mandatory boluses, programmed intermittent epidural boluses and computer-integrated PCEA have been introduced to combine the advantages of a manual bolus and continuous infusion, thus matching infusion rate and bolus modality to the patient’s analgesic needs. Increased maternal satisfaction, reduced anesthetic consumption and decreased incidence of motor block are features of these new maintenance techniques. Summary Technology has now provided us with more advanced drug delivery systems that may have the potential to fulfill the maternal requirements of a safe, natural, and painless childbirth, tailoring the analgesic regimen for each parturient’s need. Keywords childbirth pain relief, continuous techniques, epidural, labor analgesia, labor pain, maintenance of labor analgesia, patient controlled epidural analgesia, programmed intermittent bolus

INTRODUCTION Maintenance of analgesia with CEI results in the Neuraxial labor analgesia is initiated using an frequent need for rescue boluses. Higher infusion epidural or a combined spinal–epidural (CSE) rates, which decrease the need for rescue boluses, technique [1,2]. Analgesia is usually maintained result in motor block in a relatively high percentage with the epidural administration of a local anes- of patients [3,4]. PCEA has been associated with thetic or opioid solution. The methods used to a lower consumption of local anesthetic with less administer this solution into the epidural space motor block [1,2,5,6]; however, its principle depends can be classified into two major techniques. The on the response of the parturient when she feels the first category is a ‘top-up’ technique, in which need for analgesia. Thus, the parturient experiences either the anesthesia provider (manual top-ups) or short periods of pain as analgesia wanes and she must the patient [patient-controlled epidural analgesia actively re-establish analgesia by self-administering (PCEA)] administers a bolus dose at irregular inter- a bolus anesthetic dose. Cultural factors, maternal vals as analgesia wanes and pain returns. The second training, and expectations have a bearing on the category includes techniques that prevent pain re- efficacy of this technique. occurrence by administering the anesthetic solution before the pain returns. These techniques include Department of Anesthesia, Citta` di Roma Hospital, Rome, Italy continuous epidural infusion (CEI), PCEA with Correspondence to Giorgio Capogna, MD, Head, Department of basal infusion, automated intermittent mandatory Anesthesiology, Citta` di Roma Hospital, Via Maidalchini, 20, 00151 boluses (AMBs) or continuous intermittent bolus Rome, Italy. Tel: +39 658 472 04; e-mail: dipartimento.anestesia@ (CIB), programmed intermittent epidural boluses gruppogarofalo.com (PIEBs), and computer-integrated PCEA (CIPCEA) Curr Opin Anesthesiol 2013, 26:261–267 and its associated settings. DOI:10.1097/ACO.0b013e328360b069

0952-7907 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-anesthesiology.com Maintenance of epidural labor analgesia Capogna and Stirparo

Pressure 30 (mmHg) 25

0 2468101214 Time (s)

FIGURE 2. Pressure waveforms produced by CEI 10 ml/h. Data from [20]. CEI, continuous epidural infusion. Curr Opin Anaesthesiol. 2013;26(3):261–7. with the initiation of labor augmentation regimens. devising a program based on a new clinical algor- If a PCEA pump could allow for a variable basal ithm. Depending on the number of PCEA patient infusion rate and could be responsive to the requests over the previous hour, this interactive demands of the patient, the parturient may be able pump automatically adjusts the basal infusion to experience more effective analgesia. Sia et al. [23] rate, continually recording the patient’s analgesic have created just such a pump by converting an requirements and modifying the basal infusion rate ordinary infusion pump into a CIPCEA pump by depending on whether the parturient needs one, intermittend bolus Obstetric and gynecological anesthesiacontinuous infusion

FIGURE 3. Analgesia and motor block are produced by the movement of local anesthetic fromFIGURE the extraneural 4. In the space case of into continuous the infusion, the extraneural concentration of local anesthetic is generally persistently higher nerve along a diffusion gradient. Over time, the extraneural concentration equals the intraneuralthan concentration in the intraneural of local space, and the total concentration inside the nerve is increased and may reach the threshold for motor anesthetic, establishing a steady state. Nerve blockade is eventually overcome when the intraneuralfiber block. concentration This may exceeds explain the the frequent occurrence and intensification of motor block during continuous infusion. extraneural concentration and the diffusion gradient is reversed. If low concentrations of local anesthetic are given in intermittent boluses, blockade of motor fibers is unlikely, as the total amount of local anesthetic inside the nerve is insufficient.

two, or three demand boluses, respectively, in the techniques than with CEI. However, because 0952-7907 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-anesthesiology.com 265 previous hour. Should there be no demands in unidimensional scales are used to measure this hour, the pump lowers the basal infusion rate satisfaction, it is hard to arrive at particular con- by decrements of 5 ml/h. Although consumption of clusions. Stirparo et al. [26] evaluated the difference local anesthetic has been reported to be the same in maternal satisfaction between labor analgesia in both CIPCEA and PCEA in one study [24], provided by PIEB or CEI in nulliparous women in another [25], CIPCEA had higher infusion rate using a multidimensional questionnaire and then during the second stage of labor. Thus, the semi-structured interviews. With CEI, the women CIPCEA can meet this requirement for higher doses experienced more motor block, numbness and of anesthetic solution as labor progressed by match- feeling of loss of control, and subsequent negative ing the basal infusion rate to the patient’s analgesic feelings because of their reduced ambulatory ability needs. and capacity to cope with labor and delivery. They indicated less satisfaction with CEI than PIEB. NEW MAINTENANCE TECHNIQUES AND MATERNAL SATISFACTION CONCLUSION Maternal satisfaction is one of the secondary Labor pain is dynamic and intensely personal, and outcomes indicated in the results of many studies with this understanding clinicians must ‘tailor’ the which contrast differing new techniques of analgesic regimen for each of their parturients so labor analgesia maintenance [1,2,6,16&&]. Although that the birthing experience can be pleasant and patient satisfaction is generally high with all memorable. Medical technology has now provided neuraxial analgesia techniques (>80%), satisfaction us with more advanced drug delivery systems that may be higher with PCEA or automated bolus have promising, but to be confirmed, potential to

266 www.co-anesthesiology.com Volume 26 Number 3 June 2013 Society for ObstetricAnesth Anesthesia Analg. and 2011;112(4):904–11. Perinatology

Section Editor: Cynthia A. Wong

The Effect of Manipulation of the Programmed Intermittent Bolus Time Interval and Injection Volume on Total Drug Use for Labor Epidural Analgesia: A Randomized Controlled Trial

Cynthia A. Wong, MD, Robert J. McCarthy, PharmD, and Bradley Hewlett, MD

BACKGROUND: Programmed intermittent bolus administration of epidural anesthetic solution compared with continuous infusion results in decreased anesthetic consumption and increased patient satisfaction. In this randomized300150 and blinded study, we evaluated ml/hml/h bupivacaine consump- pump that can be programmed to administer intermittent Tabletion and other 1. analgesic Study outcomes Group when the Allocation programmed intermittent bolus time interval and volume were manipulated during the maintenance of epidural labor analgesia. boluses and patient-controlled boluses, 2 pumps were METHODS: Healthy, term, nulliparous women in spontaneous labor had combined spinal- Groupepidural labor analgesia Programmed initiated with interval intrathecal (min) bupivacaine 1.25 Bolus mg and fentanylvolume 15 (mL)␮g, prepared for each subject with the same epidural solution. 2.5/15followed by an epidural test dose (lidocaine 15 45 mg with epinephrine 15 ␮g). Subjects 2.5 were randomized to 1 of 3 programmed intermittent bolus dose regimens for maintenance of One pump was programmed to administer the pro- 5/30analgesia:single 2.5 mL every 15 minutes (2.5/15), 30 5 mL every 30 minutesorifice (5/30), or 10 5 mL every 60 minutes (10/60). The maintenance epidural solution consisted of bupivacaine 0.625 mg/mL grammed intermittent bolus at a rate of 300 mL/h at 10/60with fentanyl 1.95 ␮g/mL. Breakthrough 60 pain was treated initially with patient-administered 10 epidural bolus doses, followed by manual boluses administered by the anesthesiologist if regular intervals. The second pump was programmed to necessary. The primary outcome was total bupivacaine consumption per hour of labor. A linear mixed-effects model was used to model each patient’s overall bupivacaine consumption per administer patient-controlled epidural analgesia (PCEA) hour; the fixed effect was basal bupivacaine administration rate and the random effect was the (bolus dose 5 mL delivered at 150 mL/h, lockout interval 10 laborarea under or the with pain score spontaneous versus time curve. rupture of membranes who RESULTS: One hundred ninety women were studied. The median (interquartile range) adjusted minutes, basal infusion rate 0 mL/h, maximum dose 15 plannedbupivacaine consumption neuraxial per hour labor of labor analgesia was 8.8 mg (8.0–9.7 were mg) eligible in group 10/60 to compared partici- patewith 10.0 in mg the (9.3–10.8 study. mg) in group Exclusion 5/30 and 10.4 criteria mg (9.6–11.2 included mg) in group 2.5/15 systemic (P ϭ mL/h). A 3-way stopcock was connected to the epidural 0.005). There were no differences in area under the pain score versus time curve, pain scores diseaseat delivery, (e.g.,patient-controlled diabetes epidural mellitus, analgesia requests hypertension, or administrations, number preeclamp- of manual catheter connector, and the infusion tubing from both bolus doses for breakthrough pain, time to first patient-controlled epidural analgesia or manual sia),bolus use dose, ofor patient chronic satisfaction analgesic with labor analgesia. medications, systemic opioid pumps was connected to the stopcock. The programmed CONCLUSIONS: Extending the programmed intermittent bolus interval and volume from 15 laborminutes analgesia to 60 minutes, and before 2.5 mL to the 10 mL, request respectively, for decreased neuraxial bupivacaine labor consumption anal- intermittent bolus pump was covered with an opaque bag gesia,without decreasing or cervical patient comfort dilation or satisfaction.Ͻ2 (Anesth cm or AnalgϾ 2011;112:904–11)5 cm at time of to maintain blinding. The parturient was instructed to push the PCEA de- tudiesinitiation suggest that administration of combined of maintenance spinal-epiduralvolume and dosing (CSE) interval has analgesia. not been determined. At epiduralSubjects solutions as were programmed excluded or automated from in- dataone end analysis of the spectrum, after a small random- volume and short bolusmand button whenever she felt uncomfortable. Therefore, Stermittent boluses, rather than continuous infusions, dose interval will likely behave similar to a continuous results in lowerization bupivacaine if they consumption, delivered decreased within need infusion. 90 minutes At the other of end theof the intrathe-spectrum, a large volumethe maximum volume per hour administered by the epi- for manualcal “top-up” injection boluses by the (assumption anesthesiologist, and thatand analgesia long bolus dose for interval the may first lead to 90 an increaseddural pumps was 25 mL in all groups. If the patient higher patient satisfaction.1–6 In this technique, the epidu- incidence of breakthrough pain. The purpose of this ran- ral maintenanceminutes dose is administered was provided as a bolus by by the thedomized, intrathecal double-blind trial injection was to determine and how manipu-continued to have breakthrough pain after 2 PCEA boluses, infusion pump at regular intervals instead of as a continu- lation of the programmed intermittent time interval andthe anesthesiologist was called to evaluate the patient, and ous infusion.epidural However, the analgesia optimal combination had of a bolus minimalvolume role). influences total drug use, quality of analgesia, and Eligible women were askedpatient to participate satisfaction during shortly maintenance after of labor analgesia.if appropriate, administer bupivacaine 1.25 mg/mL in From the Department of Anesthesiology, Northwestern University Feinberg We hypothesized that manipulation of the programmed School of Medicine,admission Chicago, Illinois. to the Labor & Deliveryintermittent Unit bolus at Prentice time interval Women’s and volume during5-mL the aliquots (total 5–15 mL) to reestablish analgesia (VAS Accepted for publication December 13, 2010. maintenance of epidural labor analgesia influences total Supported by theHospital Department of Anesthesiology, and informed, Northwestern University writtendrug consent use (primary was outcome), obtained. quality of At analgesia, andscore Յ10 mm). VAS scores for pain were determined every Feinberg School of Medicine, Chicago, IL. The Gemstar epidural pumps patient satisfaction. used for the studythe were time provided by of Hospira, request Inc. (Lake Forest, for IL). labor analgesia, the cervix was 120 minutes until delivery beginning 60 minutes after the The authors declare no conflicts of interest. Address correspondenceexamined and reprint and requests a to baseline Cynthia A. Wong, visual MD, METHODS analog scale (VAS) score for intrathecal injection. A modified Bromage score was deter- Department of Anesthesiology, Northwestern University Feinberg School of The study was approved by the Northwestern University Medicine, 251 Eastpain Huron (100-mm St., F5-704, Chicago, unmarked IL 60611. Address e-mail line to with the end points labeled mined every 120 minutes during the first stage of labor (0 ϭ [email protected]. IRB. The study was registered (identifier: NCT00417027) at Copyright © 2011“no International pain” Anesthesia and Research “worst Society pain imaginable”)ClinicalTrials.gov on was December determined. 27, 2006. Healthy, termno motor paralysis; 1 ϭ inability to raise extended leg, but DOI: 10.1213/ANE.0b013e31820e7c2f (Ն37 weeks’ gestation), nulliparous women in spontaneous Labor analgesia was initiated using a CSE technique in the able to move knee and foot; 2 ϭ inability to raise extended 904 www.anesthesia-analgesia.org April 2011 Volume 112 Number 4 sitting position at the L3–4 or L2–3 interspace• using a• leg and to move knee, but able to move foot; 3 ϭ inability loss-of-resistance technique to identify the epidural space to raise extended leg or to move knee and foot). Bilateral and a 27-gauge pencil-point spinal needle to puncture the dermatomal sensory level to ice was determined at 15 dura-arachnoid and administer the spinal dose. After injec- minutes and 3 hours after the intrathecal injection. Sensory tion of intrathecal bupivacaine 1.25 mg and fentanyl 15 ␮g, threshold to a rigid von Frey filament was determined a single-orifice epidural catheter was secured 4 to 5 cm in bilaterally at baseline (immediately before the initiation of the epidural space. A test dose of lidocaine 45 mg with CSE analgesia), and 3 hours after the intrathecal injection at epinephrine 15 ␮g was administered through the epidural the T12, T10, T7, and T4 dermatomes (IITC Life Science, catheter, and the parturient was placed in the lateral Inc., Woodland Hills, CA). The system uses a calibrated position. internal load cell to measure and display force (in grams) The VAS score for pain was determined 10 minutes after exerted against the tip of the probe. Pressure was applied the intrathecal injection. If the VAS score was Յ10 mm, the with the rigid tip until the subject reported feeling the parturient was randomized (by a computer-generated ran- pressure. Epidural analgesia was discontinued shortly after dom number table) to 1 of 3 programmed intermittent delivery. Before discharge from the Labor & Delivery Unit, epidural bolus analgesia maintenance techniques: 2.5 mL the parturient was asked to mark her overall satisfaction every 15 minutes (2.5/15), 5 mL every 30 minutes (5/30), or with labor analgesia using a 100-mm unmarked line with 10 mL every 60 minutes (10/60) (Table 1). Group assign- the left end labeled “not satisfied at all” and the right end ments were sealed in sequentially numbered opaque enve- labeled “extremely satisfied.” lopes that were opened by an anesthesia research nurse Additional recorded data included maternal age, height, after successful initiation of CSE analgesia. The mainte- weight, cervical dilation at initiation of CSE analgesia, nance epidural solution for all 3 groups consisted of duration of labor (initiation of analgesia to delivery), maxi- bupivacaine 0.625 mg/mL with fentanyl 1.95 ␮g/mL; the mum oxytocin infusion rate during labor, and mode of total programmed maintenance dose was 10 mL/h. The delivery. Analgesia data included maintenance epidural initial programmed intermittent bolus dose was initiated solution volume administered from the programmed inter- 30 minutes after the intrathecal injection in all groups mittent bolus pump, time of first PCEA bolus request, (time zero). number of PCEA bolus requests and delivered doses, Programmed intermittent epidural doses were adminis- PCEA bupivacaine dose, time to first request for manual tered via a Hospira Gemstar infusion pump (Hospira, Inc., rebolus, number of manual bolus doses, manual bolus Lake Forest, IL). The patient, anesthesiologist, and research bupivacaine dose, total bupivacaine dose, and total fenta- nurse recording data were blinded to group assignment. nyl dose. The unblinded anesthesia research nurse programmed the The primary outcome was total bupivacaine consump- pumps and initiated maintenance epidural analgesia accord- tion per hour of labor analgesia. In our previous study, the ing to group assignment. Because there is no commercial median bupivacaine consumption was 12.3 mg/h (95%

April 2011 Volume 112 Number 4 www.anesthesia-analgesia.org 905 • • B

mg/h UPIVACAIN D Anesth Anesth Analg. 2011;112(4):904–11. OSE Anesth Analg. 2013;116(1):133–44.

Intermittent Epidural Bolus Compared with Continuous Epidural Infusions for Labor Analgesia: A Systematic Review and Meta-Analysis

Ronald B. George, MD, FRCPC,* Terrence K. Allen, MBBS, FRCA,† and Ashraf S. Habib, MB, ChB, MSc, MHS, FRCA‡

BACKGROUND: The current standard labor epidural analgesic regimens consist of a local anesthetic in combination with an opioid delivered via continuous epidural infusion (CEI). With CEI local anesthetic, doses may be large with resulting profound motor blockade potentially affecting the incidence of instrumental deliveries. In this systematic review of randomized controlled trials (RCTs), we compared the effect of intermittent epidural bolus (IEB) to standard CEI dosing with or without patient-controlled epidural analgesia on patient satisfaction, the need for manual anesthesia interventions, labor progression, and mode of delivery in healthy women receiving labor epidural analgesia. METHODS: A systematic review of RCTs that compared CEI with IEB for labor analgesia was performed. The articles were evaluated for validity, and data were extracted by the authors and summarized using odds ratios (ORs), mean differences (MDs), and 95% confdence intervals (CIs). RESULTS: Nine RCTs were included in this systematic review. Three hundred forty-four subjects received CEI, whereas 350 subjects received IEB labor analgesia. All 9 studies were deemed to be low risk of bias. There was no statistical difference detected between IEB and CEI in the rate of cesarean delivery (OR, 0.87; 95% CI, 0.56–1.35), duration of labor (MD, −17 minutes; 95% CI, −42 to 7), or the need for anesthetic intervention (OR, 0.56; 95% CI, 0.29–1.06). IEB did result in a small but statistically signifcant reduction in local anesthetic usage (MD, −1.2 mg bupivacaine equivalent per hour; 95% CI, −2.2 to −0.3). Maternal satisfaction score (100-mm visual analog scale) was higher with IEB (MD, 7.0 mm; 95% CI, 6.2–7.8). CONCLUSIONS: IEB is an appealing concept; current evidence suggests IEB slightly reduces local anesthetic usage and improves maternal satisfaction. Given the wide CIs of the pooled results for many outcomes, defnite conclusions cannot be drawn for those outcomes, but there is also a potential that IEB improves instrumental delivery rate and need of anesthesia interventions. More study is required to conceptualize the ideal IEB regimen and investigate its effect on labor analgesia and obstetric outcomes. (Anesth Analg 2013;116:133–44)

hildbirth is arguably one of the most painful expe- The current standard labor epidural analgesic regimens riences a woman can undergo.1 The degree of pain in many institutions in North America and Europe consist Cexperienced and the quality of pain relief affect of a local anesthetic in combination with an opioid deliv- patients’ satisfaction with the birthing process and may have ered via continuous epidural infusion (CEI) with or with- long-term emotional and psychological effects.2 The quality out patient-controlled epidural analgesia (PCEA) boluses. of labor neuraxial analgesia has surpassed parenteral opi- Despite improved analgesia with CEI with or without oids, nitrous oxide, and nonpharmacologic measures, with PCEA compared with nonneuraxial analgesia, local anes- limited effect on the mode of delivery and maternal and thetic doses may be large with resulting profound motor 4 neonatal outcomes.3 blockade. This reduces mobility, pelvic muscle tone, and may impair the ability to “bear down” during the second stage of labor, potentially resulting in increased rates of dys- 5 From the *IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, tocia and instrumental deliveries. Canada; †Division of Women’s Anesthesia, Duke University Medical Cen- In the continuing evolution of labor analgesia, rather ter, Durham; and ‡Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina. than delivering the local anesthetic continuously, small Accepted for publication August 14, 2012. regularly spaced intermittent boluses may lead to a more 6 Reprints will not be available from the authors. extensive spread of local anesthetic in the epidural space. Dr. George acknowledges the Canadian Anesthesiologists Research Founda- Therefore, the same dose of local anesthetic given via inter- tion for the 2011 CAS Career Scientist Award in Anesthesia. mittent epidural bolus (IEB) may provide improved analge- The authors declare no conﬂicts of interest. sia. Research into IEB is growing, and medical devices are in This report was previously presented, in part, at the Society of Obstetric development. A shift in current practice from CEI (with or Anesthesia and Perinatology Annual Meeting 2011, Canadian Anesthesiolo- gists’ Society Annual Meeting 2011. without PCEA) to IEB (with or without PCEA) will require Address correspondence to Ronald B. George, MD, FRCPC, Department of enhanced pump technology and acceptance by obstetric Women and Obstetric Anesthesia, IWK Health Centre, Dalhousie University, anesthesiologists to justify the cost of pump replacement to 5850/5980 University Avenue, PO Box 9700, Halifax, NS, Canada B3K 6R8. Address e-mail to [email protected]. hospital administration. Previous systematic reviews have Copyright © 2012 International Anesthesia Research Society addressed labor epidural analgesia versus no analgesia DOI: 10.1213/ANE.0b013e3182713b26 and alternate forms of neuraxial analgesia.7–9 van der Vyver

Number 1 www.anesthesia-analgesia.org 133 ڇ Volume 116 ڇ January 2013 Intermittent Epidural Bolus: A Systematic Review

Intermittent Epidural Bolus: A Systematic Review

Anesth Analg. 2013;116(1):133–44. Figure 2. Forest plot for mode of delivery (cesarean). CEI = continuous epidural infusion; IEB = intermittent epidural bolus. ASSISTED VAGINAL DELIVERY

Figure 2. Forest plot for mode of delivery (cesarean). CEI = continuous epidural infusion; IEB = intermittent epidural bolus.

Figure 3. Forest plot for mode of delivery (instrumental). CEI = continuous epidural infusion; IEB = intermittent epidural bolus.

was shorter with IEB22,24 (MD, −61 minutes; 95% CI, −129 their study to detect a clinically significant degree of motor to 6; Fig. 9). The total duration of labor was reduced with blockade measured with the Bromage score modified by IEB when PCEA was not used22,24,25 (MD, −86 minutes; 95% Breen et al.41 In their study, the incidence of motor block CI, −146 to −27), but not when it was used20,23,26–28 (MD, −4 (defined as modified Bromage score 41 <6, i.e., the inability minutes; 95% CI, −26 to 17; Fig. 4A). to stand and complete a partial knee bend) at least once during labor was significantly increased in the CEI group Figure 3. Forest plot for mode of delivery (instrumental). CEI = continuous epidural infusion; IEB = intermittentcompared with theepidural IEB group bolus.(26/70 vs 2/75, P < 0.001). Additional Outcomes Assuming the modified Bromage score <620 is equivalent to Other than dose of local anesthetic, most of the secondary a traditional Bromage score >1,21,27,28 then the pooled results outcomes were infrequently reported. A meta-analysis was are not statistically significant (Table 3). completed on specific outcomes that contained data from was shorter with IEB22,24 (MD, −61 minutes; 95% CI,more −129 than 1 study.their There werestudy no significant to detect differences a clinicallyDISCUSSION significant degree of motor between the groups with respect to these outcomes. The Nine high-quality low risk of bias RCTs have evaluated IEB to 6; Fig. 9). The total duration of labor was reducedresults with are summarizedblockade in Table 3. measured withversus the CEI Bromagein laboring women. score In healthy modified women requesting by 22,24,25 Umbilical pH values and 1-minute Apgar41 scores were labor epidural analgesia, the mode of maintenance of IEB when PCEA was not used (MD, −86 minutes;only 95% reported in 1 Breen study (no significant et al. difference). In their22 The study,epidural the analgesia incidence may not affect of the motor mode of delivery. block 20,23,26–28 5-minute Apgar was reported in 4 studies,22–25 in which the However, intermittent 41bolus dosing of local anesthetic may CI, −146 to −27), but not when it was used (MD,MD was − 4− 0.04 with(defined a 95% CI of − 0.2as to modified0.1. The degree ofBromage be associated score with reduced <6, local i.e., anesthetic the consumption, inability minutes; 95% CI, −26 to 17; Fig. 4A). sensory block was toquantified stand in 4 studies. and Leo complete et al.23 and adecreased partial anesthetic knee interventions, bend) and at an least improvement once Lim et al.24 reported the sensory block level at the first in maternal satisfaction when compared with those women request for additionalduring analgesia. laborChua et al. was21 reported significantly the receiving CEI. increased The 2 techniques in of local the anesthesia CEI deliverygroup maximal sensory block level within the first 3 hours of appear to be comparable in terms of total duration of labor, analgesia, while Siacompared et al.27 reported thewith maximal the sensory IEB butgroup there was (26/70 a statistically vs significant2/75, reductionP < 0.001). in the block during the entire study period. Within these studies, length of the second stage of labor20 with IEB. The duration of Additional Outcomes there was no significantAssuming difference between the modified CEI and IEB Bromagethe second stage wasscore a much <6 as 22 minutes is equivalent shorter with IEB. to 20 Other than dose of local anesthetic, most of the secondarywith respect to sensorya traditional blockade. Capogna Bromage et al. designed scoreArguably, >1, this21,27,28 may enter then the realm the of pooled clinically significant, results are not statistically significant (Table 3). outcomes were infrequently reported. A meta-analysis138 was www.anesthesia-analgesia.org ANESTHESIA & ANALGESIA completed on specific outcomes that contained data from more than 1 study. There were no significant differences DISCUSSION between the groups with respect to these outcomes. The Nine high-quality low risk of bias RCTs have evaluated IEB results are summarized in Table 3. versus CEI in laboring women. In healthy women requesting Umbilical pH values and 1-minute Apgar scores were labor epidural analgesia, the mode of maintenance of only reported in 1 study (no significant difference).22 The epidural analgesia may not affect the mode of delivery. 5-minute Apgar was reported in 4 studies,22–25 in which the However, intermittent bolus dosing of local anesthetic may MD was −0.04 with a 95% CI of −0.2 to 0.1. The degree of be associated with reduced local anesthetic consumption, sensory block was quantified in 4 studies. Leo et al.23 and decreased anesthetic interventions, and an improvement Lim et al.24 reported the sensory block level at the first in maternal satisfaction when compared with those women request for additional analgesia. Chua et al.21 reported the receiving CEI. The 2 techniques of local anesthesia delivery maximal sensory block level within the first 3 hours of appear to be comparable in terms of total duration of labor, analgesia, while Sia et al.27 reported the maximal sensory but there was a statistically significant reduction in the block during the entire study period. Within these studies, length of the second stage of labor with IEB. The duration of there was no significant difference between CEI and IEB the second stage was a much as 22 minutes shorter with IEB. with respect to sensory blockade. Capogna et al.20 designed Arguably, this may enter the realm of clinically significant,

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Programmed Intermittent Epidural Bolus Versus Continuous Epidural Infusion for Labor Analgesia: The Effects on Maternal Motor Function and Labor Outcome. A Randomized Double-Blind Study in Nulliparous Women

Giorgio Capogna, MD, Michela Camorcia, MD, Silvia Stirparo, MD, and Alessio Farcomeni, PhD

BACKGROUND: Programmed intermittent epidural anesthetic bolus (PIEB) technique may result in reduced total local anesthetic consumption, fewer manual boluses, and greater patient satisfaction compared with continuous epidural infusion (CEI). In this randomized, double-blind study, we compared the incidence of motor block and labor outcome in women who received PIEB or CEI for maintenance of labor analgesia. The primary outcome variable was maternal motor function and the secondary outcome was mode of delivery. METHODS: Nulliparous, term women with spontaneous labor and cervical dilation Ͻ4 cm were eligible to participate in the study. Epidural analgesia was initiated and maintained with a solution of levobupivacaine 0.0625% with sufentanil 0.5 ␮g/mL. After an initial epidural loading dose of 20 mL, patients were randomly assigned to receive PIEB (10 mL every hour beginning 60 minutes after the initial dose) or CEI (10 mL/h, beginning immediately after the initial dose) for the maintenance of analgesia. Patient-controlled epidural analgesia (PCEA) using a second infusion pump with levobupivacaine 0.125% was used to treat breakthrough pain. The degree of motor block was assessed in both lower extremities using the modiﬁed Bromage score at regular intervals throughout labor; the end point was any motor block in either limb. We also evaluated PCEA bolus doses and total analgesic solution consumption. RESULTS: We studied 145 subjects (PIEB ϭ 75; CEI ϭ 70). Motor block was reported in 37% in the CEI group and in 2.7% in the PIEB group (P Ͻ 0.001; odds ratio ϭ 21.2; 95% CI: 4.9–129.3); it occurred earlier (P ϭ 0.008) (hazard ratio ϭ 7.8; 95% CI: 1.9–30.8; P ϭ 0.003) and was more frequent at full cervical dilation in the CEI group (P Ͻ 0.001). The incidence of instrumental delivery was 20% for the CEI group and 7% for the PIEB group (P ϭ 0.03). Total levobupivacaine consumption, number of patients requiring additional PCEA boluses, and mean number of PCEA boluses per patient were lower in the PIEB group (P Ͻ 0.001). No differences in pain scores and duration of labor analgesia were observed. CONCLUSIONS: Maintenance of epidural analgesia with PIEB compared with CEI resulted in a lower incidence of maternal motor block and instrumental vaginal delivery. (Anesth Analg 2011; 113:826–31)

euraxial analgesic techniques, such as epidural Continuous infusion results in a smoother analgesic expe- and combined spinal-epidural (CSE) analgesia, are rience for the parturient with fewer medical interventions, Nthe most effective modalities for pain relief in but total anesthetic doses are usually larger and motor labor. Once analgesia has been established, either by using block may be more profound.1 There is some evidence from an epidural or a CSE technique, the maintenance of anal- anatomical and in vitro studies2,3 that uniform diffusion of gesia throughout labor until delivery may be obtained with local anesthetic in the epidural space, which leads to different techniques. With intermittent epidural bolus in- greater efficacy, is better obtained by the administration of jection (top-up) of the analgesic solution, frequent provider bolus rather that continuous infusion. interventions are required, and the parturient may experi- Automated systems designed to administer a bolus at ence intervals of analgesia after the dose takes effect programmable intervals (programmed intermittent epidu- alternating with intervals of pain as the analgesia wanes. ral anesthetic bolus [PIEB] technique) to combine the advantages of both manual bolus and continuous infusion, have recently been introduced. Wong et al.4 compared PIEB From the Department of Anesthesia, Citta`di Roma Hospital, Rome, Italy. versus continuous epidural infusion (CEI) in induced Accepted for publication May 25, 2011. parous women. They reported less total local anesthetic Funding: No funding. consumption, fewer manual bolus doses because of break- The authors declare no conflicts of interest. through pain, and greater patient satisfaction with the PIEB Reprints will not be available from the authors. technique. In their study, they noticed that the beneficial Address correspondence to Giorgio Capogna, MD, Department of Anesthe- effect of PIEB was significant in women with longer labors, sia, Citta`di Roma Hospital, Via Maidalchini 20, 00151 Roma, Italy. Address e-mail to [email protected]. and therefore, they hypothesized that PIEB would be of Copyright © 2011 International Anesthesia Research Society greater value in parturients with longer labors such as DOI: 10.1213/ANE.0b013e31822827b8 spontaneously laboring nulliparous women.

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at that time. It is likely that at the time of analgesic request, Table 1. Subject and Labor Characteristics any motor block, if present, had already resolved. Fettes et -P value al.,15 in comparing programmed intermittent bolus admin (75 ؍ PIEB (n (70 ؍ CEI (n Age (y) 27 Ϯ 5 29 Ϯ 5 Ͻ0.01 istration with continuous infusion, reported a frequent Weight (kg) 72 Ϯ 9 74 Ϯ 11 0.2 Height (cm) 164 Ϯ 6 165 Ϯ 6 0.2 incidence of motor block in both groups with no difference Gestational age (wk) 38.7 Ϯ 0.7 38.9 Ϯ 0.7 0.2 in motor block between groups, although the trend was Cervical dilatation at 2.0 (1.0–3.0) 2.0 (2.0–3.0) 0.6 toward less motor block in the intermittent bolus group. epidural request (cm) However, they used a higher local anesthetic concentration Duration of labor 332 (318–380) 335 (326–358) 0.9 (ropivacaine 0.2%) than other studies, and this may have analgesia (min) masked differences between the groups. Data are presented as mean Ϯ SD or median (interquartile range) (cervical Another reason for the difference in results among studies dilation) or median (95% conﬁdence interval) (duration of labor analgesia). CEI ϭ continuous epidural infusion; PIEB ϭ programmed intermittent epidural is that some of the previous studies used different local Anesthesia andbolus. Analgesia 2011;113:826 anesthetic concentrations and total anesthetic dose from those used in our study. Furthermore, the scale we used to evaluate motor block is more sensitive than that used in previous studies,9 and therefore the probability of diagnosing minor degrees of motor block was probably greater in our patients. In addition, the primary end point of previous studies was not motor block or mode of delivery, and therefore previous

motor block studies were not adequately powered to address these issues. Finally, we used an epidural rather than a subarachnoid initial loading dose,4–6 and we set the PIEB pump to deliver a larger volume of local analgesic solution at longer time intervals relative to previous studies.4,5 In our study, we noted a lower incidence of instrumental vaginal delivery in parturients receiving PIEB compared with CEI. Recently, Leo et al.16 also reported a trend toward a decreased incidence of instrumental vaginal delivery with automated intermittent boluses when compared with CEI, but, unfortunately, this result did not reach statistical signifi- cance, most likely because of the small sample size. In addition, Leo et al.16 did not report the incidence of motor block, nor did they correlate motor block with instrumental Figure 2. Percentage of patients from programmed intermittent delivery. epidural bolus (PIEB) or continuous epidural infusion (CEI) groups It is hypothesized that excessive motor block caused by who had any motor block versus time after induction of labor the epidural local anesthetic is undesirable because it may analgesia. Data were censored for delivery. The groups were signiﬁ- lead to decrease of pelvic muscle tone and difficulties in cantly different, P Ͻ 0.001. internal rotation of the fetal head, and therefore to a potential increase in the incidence of instrumental vaginal Table 2. Labor Analgesia delivery, although this assertion remains unproven. In our study, parturients who had longer labors and P value (75 ؍ PIEB (n (70 ؍ CEI (n motor block at full cervical dilation had a greater risk of Total dose of 37 (31–44) 31 (25–38) 0.001 levobupivacaine (mg) instrumental delivery. Our results suggest that PIEB, by Total dose of 28 (24–34) 25 (20–30) 0.009 reducing the incidence of motor block, contributes to sufentanil (␮g) reduction in instrumental deliveries in nulliparous women. Patients requiring 28 6 Ͻ0.001 Although local anesthetic consumption was higher in PCEA boluses (n) the CEI group, and we observed a difference in motor block PCEA boluses for 1 (1–2) 1 (1–1) Ͻ0.001 each patient (n) between parturients receiving PIEB and CEI, the dose difference between groups was modest. Therefore, we Data are presented as median (interquartile range) or number. suggest that the increased frequency of motor block in CEI ϭ continuous epidural infusion; PCEA ϭ patient-controlled epidural analgesia; PIEB ϭ programmed intermittent epidural bolus. parturients receiving CEI cannot merely be explained by the larger local anesthetic dose. It is hypothesized that the reason for the analgesic success of intermittent boluses labors. Chua and Sia5 reported a very low incidence of compared with continuous administration may be related motor block in their study of nulliparous parturients, but to differences in the dispersion of solutions in the epidural they terminated their study when patients requested space. Solutions injected into the epidural space tend to supplemental analgesia (on average after 4 hours), and spread more evenly when injected as a bolus, as compared therefore they were unable to observe any motor block. Lim with a continuous infusion.2,3 We have hypothesized that et al.6 studied programmed intermittent boluses versus differences in the dynamics of nerve block with intermit- CEI. They ended their study when the parturient com- tent or continuous infusion administration may contribute plained of breakthrough pain and reported no motor block to the explanation of our findings.17

830 www.anesthesia-analgesia.org ANESTHESIA & ANALGESIA Anesthesia and Analgesia 2011;113:826

continuous background infusion PIEB n=70 n=75

c/s instrumented spontaneous Risk Factors for Unintended Dural Puncture in Obstetric Patients: A Retrospective Cohort Study

Sharon Orbach-Zinger, MD, Eran Ashwal, MD, Lilach Hazan, MD, Danielle Bracco, BA, Alex Ioscovich, MD, Liran Hiersch, MD, Andrey Khinchuck, MD, Amir Aviram, MD, and Leonid A. Eidelman, MD* † * ‡ ‡ † *† † * BACKGROUND: Unintended dural puncture (UDP) is one of the main risks of epidural analgesia, with a reported incidence of approximately 1.5% among the obstetric population. UDP«In is associatedour hospital, with maternal anesthesiologists adverse outcomes, with the most begin frequent adverse outcome being postdural puncture headache (PDPH). Our retrospective cohort study objective workingwas to identify indemographic the delivery and obstetric suite risk factors only that afterincrease theythe risk of uninten- SOCIETY FOR OBSTETRIC ANESTHESIA AND PERINATOLOGYRESEARCH REPORT tional dural puncture as well as describing the obstetric outcome once a dural puncture havehas occurred. completed at least 2 years of residency METHODS: We retrospectively reviewed all cases of UDPs during attempted vaginal delivery between the years 2004 and 2013 in a single Israeli hospital. Each UDP case was matched andwith the have2 parturients previously who received epidural performed analgesia before 300and 2 parturients to 500 after performed by the same anesthesiologist (control group). Demographic, anesthetic, and obstetric variables werespinal compared anesthetic between the UDP andprocedures control groups. for cesarean RESULTS: Out of 46,668 epidural procedures, 177 cases of UDPs were documented (0.4%). Onedelivery hundred seven and women a large (60.5%) developednumber PDPH, of and supervised 38 (35.5%) required an epidural blood patch. In multivariate logistic regression, the degree of cervical dilation in centimeters at theepidurals time of epidural oninsertion non-obstetric was associated with an patients. increased rate of» UDP (P < .001). Multiparity was associated with PDPH after UDP (P = .004). Women with UDP had longer length of hospital stay than those without UDP (P < .001). CONCLUSIONS: UDP, an uncommon complication, is associated with obstetric factors. Nevertheless, it does not seem to be associated with adverse obstetric outcomes except for prolonged duration of hospital stay. (Anesth Analg 2016;XXX:00–00)

he incidence of unintended dural puncture (UDP) dur- Most of the published data only address anesthesiology ing attempted epidural insertion among the obstet- factors predisposing to UDP, rather than identifying obstetric population has been found to be approximately ric factors that may increase the risk for UDP. Additionally, T1 1.5%. This complication may be associated with a high data regarding the association between UDP and pregnancy rate of postdural puncture headache (PDPH),2 prolonged outcomes are scarce. hospitalization,3and possibly even chronic headache.2 Less- Therefore, we primarily aimed to identify which demo- frequent complications may include posterior reversible graphic and obstetric factors are associated with risk for encephalopathy syndrome,4–6 pneumocephalus,7and sub- UDP in parturients. We hypothesized that specifc obstetric dural hematoma.8 characteristics such as high parity or advanced cervical dila- The risk factors for UDP are unclear. Recent studies tion at the time of initiation of epidural analgesia are associ- reported several risk factors, including the anesthesiologist’s ated with risk for UDP. Second, we aimed to evaluate the experience and time of day.9,10 Another study in a training labor and delivery outcomes (ie, mode of delivery) in cases institution found an increased incidence of UDP in parturi- of witnessed UDP. ents undergoing epidural placement during the beginning of month, which coincided with the start of the month-long METHODS 11 obstetric anesthesia resident rotation. We conducted a retrospective study of all UDPs during attempted vaginal delivery between the years 2004 and From the Departments of Anesthesia and Obstetrics and Gynecol- 2013, at a single tertiary, university-affliated medical cen- ogy, Rabin Medical Center, Beilinson Hospital, Petach Tikvah, Israel; and ter with approximately 10,000 annual deliveries. Labor and Department of Anesthesia, Shaare* Zedek Medical† Center, Jerusalem, Israel. delivery outcome of women with UDPs was compared Accepted for publication June 27, 2016. ‡ with that of women who received uncomplicated epidural Funding: Departmental. analgesia. For each case in the study group (UDP), 2 previ- The authors declare no conficts of interest. ous and 2 consecutive deliveries of women who received The frst two authors are equal co-authors. epidural analgesia performed by the same anesthesiologist Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of (control group) were matched. This study was approved by this article on the journal’s website (www.anesthesia-analgesia.org). the Institutional Review Board of Rabin Medical Center – Reprints will not be available from the authors. Beilinson Campus. Address correspondence to Sharon Orbach-Zinger, MD, Department of An- In our hospital, anesthesiologists begin working in esthesia, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky St, Petach Tikva, Israel. Address email to [email protected]. the delivery suite only after they have completed at least Copyright © 2016 International Anesthesia Research Society 2 years of residency and have previously performed 300 to DOI: 10.1213/ANE.0000000000001510 500 spinal anesthetic procedures for cesarean delivery and

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Risk of accidental dural puncture

Table 1. Demographic and Baseline Obstetric Data Table 3. Obstetric Characteristics of the Study and UDP Epidural Control Groups (N = 177) (N = 708) P UDP Epidural Maternal age (years)a 30.7 ± 5.1 30.1 ± 4.8 0.15 (N = 177) (N = 708) P Pregestational body mass index 28.7 ± 5.4 28.1 ± 4.6 0.24 VNS pain score 4.71 ± 13.7 10.10 ± 15.7 0.001 (kgs)a postanesthesia (0–100)a Gravidityb 2 (1–3) 2 (1–3) 0.22 Mode of delivery Parityb 1 (0–1) 1 (0–2) 0.46 Spontaneous vaginalb 142 (80.2) 580 (81.9) 0.59 Nulliparityc 72 (40.7) 300 (42.4) 0.81 Instrumental vaginalb 25 (14.1) 108 (15.3) 0.81 Chronic hypertensionc 2 (1.1) 13 (1.8) 0.74 Cesarean deliveryb 12 (6.8) 32 (4.5) 0.24 Preeclampsiac 3 (1.7) 11 (1.6) >.99 Neuraxial-delivery interval (h)a 5.8 ± 4.8 5.4 ± 3.8 0.28 Gestational diabetesc 9 (5.1) 33 (4.7) 0.74 Maternal length of stay (d)a 3.3 ± 1.4 2.7 ± 0.8 <.001 Pre-gestational diabetes mellitusc 0 (0) 8 (1.1) 0.37 Prolonged hospitalizationb 46 (26.0) 81 (11.4) <.001 Gestational age at delivery (wks)a 39.1 ± 1.9 40.1 ± 1.5 0.47 Apgar 5-min < 7b 1 (0.6) 1 (0.1) 0.36 Preterm delivery (<37 wks)c 7 (4.0) 30 (4.2) 1.0 NICU admissionb 2 (1.1) 16 (2.3) 0.55 Premature rupture of membranesc 29 (16.4) 166 (23.4) 0.04 Values are presented as mean ± standard deviation or number (%). c Induction of labor 26 (14.7) 82 (11.6) 0.47 Abbreviations: NICU, neonatal intensive care unit; UDP, unintended dural c Oxytocin augmentation 17 (9.6) 91 (12.9) 0.30 puncture; VNS, verbal numeric scale (0–100). Cervical dilation at analgesia (cm)b 4 (3–4) 3 (3–4) <.001 Prolonged hospitalization was defned as hospitalization duration of more Values are listed as mean ± standard deviation or n (%). than 48 h and 96 h after vaginal and cesarean deliveries, respectively. aNormal distribution – t test was performed. Abbreviation: UDP, unintended dural puncture. b aNormal distribution: t test was performed. Fisher exact test. bNonnormal distribution: Mann-Whitney U test. cFisher exact test. Table 4. Unintended Dural Puncture: Complications Postdural puncture headachea 107 (60.5) Average time until onset of headache (h)b 23.7 ± 9.9 Table 2. Epidural Catheter Insertion Average VNS pain score (sitting)b 71.1 ± 22.9 Characteristics of the Study and Control Groups Tinnitusa 1 (0.9) Epidural Photophobiaa 3 (2.8) UDP (N = 177) (N = 708) P Nauseaa 6 (5.6) Interspace L4–L5 L4–L5 0.28 Back paina 17 (15.9 Loss of resistance to air 103/130 (79.2) 531/657 0.72 Epidural blood patcha 38 (35.5) (80.8) Average time from dural puncture until blood patch (h)b 56.9 ± 54.7 Epidural needle depth (cm) 5 (5–6) 5 (4–5) 0.001 Average blood volume injected for blood patch (mL)b 27.3 ± 7.7 Catheter depth (cm) 5 (5–5) 5 (5–5) 0.77 Women requiring second epidural blood patcha 1 (2.6) Values are listed as mean ± standard deviation or n (%). Nonnormal Values are presented as mean ± standard deviation or number (percent). distribution: Mann-Whitney U test. Abbreviation: VNS, verbal numeric scale (0–100 scale)—mean of scores Abbreviation: UDP, unintended dural puncture. assessed twice per day. aNon-normal distribution: Mann-Whitney U test. bNormal distribution: t test was performed. who had UDP had a longer mean length of hospital stay. There were no infectious complications because of spinal catheterization. In multivariable logistic regression analysis, after we con- Data regarding the management and complications after trolled for possible factors affecting PDPH (maternal age, UDP are listed in Table 4. Ten epidural catheters were res- BMI, parity, cervical dilation before anesthesia, VNS pain ited in the epidural space at a different interspinous space values postanesthesia, loss of resistance technique, needle because of technical complications. One hundred seven depth and catheter depth, and mode of delivery), multipar- women (60.5%) developed PDPH; 38 (35.5%) received an ity was associated with PDPH after UDP (aOR 20; 95% CI epidural blood patch. One of these women had persistent 3–100, P = .004). In multivariable logistic regression analy- pain after receiving blood patch and received a repeat blood sis, after controlling for possible factors affecting prolonged patch. In multivariable logistic regression analysis, after we hospitalization (maternal age, parity, induction of labor, ges- controlled for possible factors affecting UDP (maternal age, tational week at delivery and mode of delivery), UDP was BMI, parity, degree of cervical dilation at time of initiation associated with signifcantly increased odds of prolonged of analgesia, premature rupture of membranes, induction hospitalization (aOR 2.82; 95% CI 1.85–4.28, P < .001). of labor, oxytocin administration), premature rupture of membranes was associated negatively with the rate of UDP DISCUSSION (adjusted odds ratio [aOR] 0.55; 95% confdence interval In this study, we aimed to identify obstetric risk factors for [95% CI] 0.32–0.93, P = .02), whereas the degree of cervical UDP and to report obstetric variables associated with this dilation in centimeters at the time of epidural insertion was complication in a retrospective case control study design. associated positively with the risk of UDP (aOR 1.23; 95% CI Our main result is that after we controlled for obstetric and 1.04–1.42, P = .01) (Table 5); however, in a model with only anesthetic factors, the degree of cervical dilation in centime- cervical dilation at the time of epidural insertion and pre- ters before epidural analgesia was signifcantly and inde- mature rupture of membranes, cervical dilation remained pendently associated with the risk of UDP. associated with UDP (P < .001), but premature rupture of We found a low UDP rate, compared with previous studies membranes did not (P = .073) (Table 6). that described a rate of 0.5–1.5%.1 One possible explanation

Number XXX www.anesthesia-analgesia.org 3 ڇ Volume XXX ڇ XXX 2016 Copyright © 2016 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited. Orbach-Zinger et al. Anesth Analg. 2016 ahead of print

Impact of accidental dural puncture

Table 1. Demographic and Baseline Obstetric Data Table 3. Obstetric Characteristics of the Study and UDP Epidural Control Groups (N = 177) (N = 708) P UDP Epidural Maternal age (years)a 30.7 ± 5.1 30.1 ± 4.8 0.15 (N = 177) (N = 708) P Pregestational body mass index 28.7 ± 5.4 28.1 ± 4.6 0.24 VNS pain score 4.71 ± 13.7 10.10 ± 15.7 0.001 (kgs)a postanesthesia (0–100)a Gravidityb 2 (1–3) 2 (1–3) 0.22 Mode of delivery Parityb 1 (0–1) 1 (0–2) 0.46 Spontaneous vaginalb 142 (80.2) 580 (81.9) 0.59 Nulliparityc 72 (40.7) 300 (42.4) 0.81 Instrumental vaginalb 25 (14.1) 108 (15.3) 0.81 Chronic hypertensionc 2 (1.1) 13 (1.8) 0.74 Cesarean deliveryb 12 (6.8) 32 (4.5) 0.24 Preeclampsiac 3 (1.7) 11 (1.6) >.99 Neuraxial-delivery interval (h)a 5.8 ± 4.8 5.4 ± 3.8 0.28 Gestational diabetesc 9 (5.1) 33 (4.7) 0.74 Maternal length of stay (d)a 3.3 ± 1.4 2.7 ± 0.8 <.001 Pre-gestational diabetes mellitusc 0 (0) 8 (1.1) 0.37 Prolonged hospitalizationb 46 (26.0) 81 (11.4) <.001 Gestational age at delivery (wks)a 39.1 ± 1.9 40.1 ± 1.5 0.47 Apgar 5-min < 7b 1 (0.6) 1 (0.1) 0.36 Preterm delivery (<37 wks)c 7 (4.0) 30 (4.2) 1.0 NICU admissionb 2 (1.1) 16 (2.3) 0.55 Premature rupture of membranesc 29 (16.4) 166 (23.4) 0.04 Values are presented as mean ± standard deviation or number (%). c Induction of labor 26 (14.7) 82 (11.6) 0.47 Abbreviations: NICU, neonatal intensive care unit; UDP, unintended dural c Oxytocin augmentation 17 (9.6) 91 (12.9) 0.30 puncture; VNS, verbal numeric scale (0–100). Cervical dilation at analgesia (cm)b 4 (3–4) 3 (3–4) <.001 Prolonged hospitalization was defned as hospitalization duration of more Values are listed as mean ± standard deviation or n (%). than 48 h and 96 h after vaginal and cesarean deliveries, respectively. aNormal distribution – t test was performed. Abbreviation: UDP, unintended dural puncture. bFisher exact test. aNormal distribution: t test was performed. bNonnormal distribution: Mann-Whitney U test. cFisher exact test. Table 4. Unintended Dural Puncture: Complications Postdural puncture headachea 107 (60.5) Average time until onset of headache (h)b 23.7 ± 9.9 Table 2. Epidural Catheter Insertion Average VNS pain score (sitting)b 71.1 ± 22.9 Characteristics of the Study and Control Groups Tinnitusa 1 (0.9) Epidural Photophobiaa 3 (2.8) UDP (N = 177) (N = 708) P Nauseaa 6 (5.6) Interspace L4–L5 L4–L5 0.28 Back paina 17 (15.9 Loss of resistance to air 103/130 (79.2) 531/657 0.72 Epidural blood patcha 38 (35.5) (80.8) Average time from dural puncture until blood patch (h)b 56.9 ± 54.7 Epidural needle depth (cm) 5 (5–6) 5 (4–5) 0.001 Average blood volume injected for blood patch (mL)b 27.3 ± 7.7 Catheter depth (cm) 5 (5–5) 5 (5–5) 0.77 Women requiring second epidural blood patcha 1 (2.6) Values are listed as mean ± standard deviation or n (%). Nonnormal Values are presented as mean ± standard deviation or number (percent). distribution: Mann-Whitney U test. Abbreviation: VNS, verbal numeric scale (0–100 scale)—mean of scores Abbreviation: UDP, unintended dural puncture. assessed twice per day. aNon-normal distribution: Mann-Whitney U test. bNormal distribution: t test was performed. who had UDP had a longer mean length of hospital stay. There were no infectious complications because of spinal catheterization. In multivariable logistic regression analysis, after we con- Data regarding the management and complications after trolled for possible factors affecting PDPH (maternal age, UDP are listed in Table 4. Ten epidural catheters were res- BMI, parity, cervical dilation before anesthesia, VNS pain ited in the epidural space at a different interspinous space values postanesthesia, loss of resistance technique, needle because of technical complications. One hundred seven depth and catheter depth, and mode of delivery), multipar- women (60.5%) developed PDPH; 38 (35.5%) received an ity was associated with PDPH after UDP (aOR 20; 95% CI epidural blood patch. One of these women had persistent 3–100, P = .004). In multivariable logistic regression analy- pain after receiving blood patch and received a repeat blood sis, after controlling for possible factors affecting prolonged patch. In multivariable logistic regression analysis, after we hospitalization (maternal age, parity, induction of labor, ges- controlled for possible factors affecting UDP (maternal age, tational week at delivery and mode of delivery), UDP was BMI, parity, degree of cervical dilation at time of initiation associated with signifcantly increased odds of prolonged of analgesia, premature rupture of membranes, induction hospitalization (aOR 2.82; 95% CI 1.85–4.28, P < .001). of labor, oxytocin administration), premature rupture of membranes was associated negatively with the rate of UDP DISCUSSION (adjusted odds ratio [aOR] 0.55; 95% confdence interval In this study, we aimed to identify obstetric risk factors for [95% CI] 0.32–0.93, P = .02), whereas the degree of cervical UDP and to report obstetric variables associated with this dilation in centimeters at the time of epidural insertion was complication in a retrospective case control study design. associated positively with the risk of UDP (aOR 1.23; 95% CI Our main result is that after we controlled for obstetric and 1.04–1.42, P = .01) (Table 5); however, in a model with only anesthetic factors, the degree of cervical dilation in centime- cervical dilation at the time of epidural insertion and pre- ters before epidural analgesia was signifcantly and inde- mature rupture of membranes, cervical dilation remained pendently associated with the risk of UDP. associated with UDP (P < .001), but premature rupture of We found a low UDP rate, compared with previous studies membranes did not (P = .073) (Table 6). that described a rate of 0.5–1.5%.1 One possible explanation

Table 1. Demographic and Baseline Obstetric Data Table 3. Obstetric Characteristics of the Study and UDP Epidural Control Groups (N = 177) (N = 708) P UDP Epidural Maternal age (years)a 30.7 ± 5.1 30.1 ± 4.8 0.15 (N = 177) (N = 708) P Pregestational body mass index 28.7 ± 5.4 28.1 ± 4.6 0.24 VNS pain score 4.71 ± 13.7 10.10 ± 15.7 0.001 (kgs)a postanesthesia (0–100)a Gravidityb 2 (1–3) 2 (1–3) 0.22 Mode of delivery Parityb 1 (0–1) 1 (0–2) 0.46 Spontaneous vaginalb 142 (80.2) 580 (81.9) 0.59 Nulliparityc 72 (40.7) 300 (42.4) 0.81 Instrumental vaginalb 25 (14.1) 108 (15.3) 0.81 Chronic hypertensionc 2 (1.1) 13 (1.8) 0.74 Cesarean deliveryb 12 (6.8) 32 (4.5) 0.24 Preeclampsiac 3 (1.7) 11 (1.6) >.99 Neuraxial-delivery interval (h)a 5.8 ± 4.8 5.4 ± 3.8 0.28 Gestational diabetesc 9 (5.1) 33 (4.7) 0.74 Maternal length of stay (d)a 3.3 ± 1.4 2.7 ± 0.8 <.001 Pre-gestational diabetes mellitusc 0 (0) 8 (1.1) 0.37 Prolonged hospitalizationb 46 (26.0) 81 (11.4) <.001 Gestational age at delivery (wks)a 39.1 ± 1.9 40.1 ± 1.5 0.47 Apgar 5-min < 7b 1 (0.6) 1 (0.1) 0.36 Preterm delivery (<37 wks)c 7 (4.0) 30 (4.2) 1.0 NICU admissionb 2 (1.1) 16 (2.3) 0.55 Premature rupture of membranesc 29 (16.4) 166 (23.4) 0.04 Values are presented as mean ± standard deviation or number (%). c Induction of labor 26 (14.7) 82 (11.6) 0.47 Abbreviations:Orbach-Zinger NICU, neonatal et al. intensive Anesth Analg. care unit; 2016 UDP, ahead unintended of print dural c Oxytocin augmentation 17 (9.6) 91 (12.9) 0.30 puncture; VNS, verbal numeric scale (0–100). Cervical dilation at analgesia (cm)b 4 (3–4) 3 (3–4) <.001 Prolonged hospitalization was defned as hospitalization duration of more Values are listed as mean ± standard deviation or n (%). Impactthan 48 hof and accidental 96 h after vaginal dural and cesarean puncture deliveries, respectively. aNormal distribution – t test was performed. Abbreviation: UDP, unintended dural puncture. bFisher exact test. aNormal distribution: t test was performed. bNonnormal distribution: Mann-Whitney U test. cFisher exact test. Table 4. Unintended Dural Puncture: Complications Postdural puncture headachea 107 (60.5) Average time until onset of headache (h)b 23.7 ± 9.9 Table 2. Epidural Catheter Insertion Average VNS pain score (sitting)b 71.1 ± 22.9 Characteristics of the Study and Control Groups Tinnitusa 1 (0.9) Epidural Photophobiaa 3 (2.8) UDP (N = 177) (N = 708) P Nauseaa 6 (5.6) Interspace L4–L5 L4–L5 0.28 Back paina 17 (15.9 Loss of resistance to air 103/130 (79.2) 531/657 0.72 Epidural blood patcha 38 (35.5) (80.8) Average time from dural puncture until blood patch (h)b 56.9 ± 54.7 Epidural needle depth (cm) 5 (5–6) 5 (4–5) 0.001 Average blood volume injected for blood patch (mL)b 27.3 ± 7.7 Catheter depth (cm) 5 (5–5) 5 (5–5) 0.77 Women requiring second epidural blood patcha 1 (2.6) Values are listed as mean ± standard deviation or n (%). Nonnormal Values are presented as mean ± standard deviation or number (percent). distribution: Mann-Whitney U test. Abbreviation: VNS, verbal numeric scale (0–100 scale)—mean of scores Abbreviation: UDP, unintended dural puncture. assessed twice per day. aNon-normal distribution: Mann-Whitney U test. bNormal distribution: t test was performed. who had UDP had a longer mean length of hospital stay. There were no infectious complications because of spinal catheterization. In multivariable logistic regression analysis, after we con- Data regarding the management and complications after trolled for possible factors affecting PDPH (maternal age, UDP are listed in Table 4. Ten epidural catheters were res- BMI, parity, cervical dilation before anesthesia, VNS pain ited in the epidural space at a different interspinous space values postanesthesia, loss of resistance technique, needle because of technical complications. One hundred seven depth and catheter depth, and mode of delivery), multipar- women (60.5%) developed PDPH; 38 (35.5%) received an ity was associated with PDPH after UDP (aOR 20; 95% CI epidural blood patch. One of these women had persistent 3–100, P = .004). In multivariable logistic regression analy- pain after receiving blood patch and received a repeat blood sis, after controlling for possible factors affecting prolonged patch. In multivariable logistic regression analysis, after we hospitalization (maternal age, parity, induction of labor, ges- controlled for possible factors affecting UDP (maternal age, tational week at delivery and mode of delivery), UDP was BMI, parity, degree of cervical dilation at time of initiation associated with signifcantly increased odds of prolonged of analgesia, premature rupture of membranes, induction hospitalization (aOR 2.82; 95% CI 1.85–4.28, P < .001). of labor, oxytocin administration), premature rupture of membranes was associated negatively with the rate of UDP DISCUSSION (adjusted odds ratio [aOR] 0.55; 95% confdence interval In this study, we aimed to identify obstetric risk factors for [95% CI] 0.32–0.93, P = .02), whereas the degree of cervical UDP and to report obstetric variables associated with this dilation in centimeters at the time of epidural insertion was complication in a retrospective case control study design. associated positively with the risk of UDP (aOR 1.23; 95% CI Our main result is that after we controlled for obstetric and 1.04–1.42, P = .01) (Table 5); however, in a model with only anesthetic factors, the degree of cervical dilation in centime- cervical dilation at the time of epidural insertion and pre- ters before epidural analgesia was signifcantly and inde- mature rupture of membranes, cervical dilation remained pendently associated with the risk of UDP. associated with UDP (P < .001), but premature rupture of We found a low UDP rate, compared with previous studies membranes did not (P = .073) (Table 6). that described a rate of 0.5–1.5%.1 One possible explanation

Risk factors Obstetric Risk Factors for Inadvertent Dural Puncture

risk for UDP (P = .41); however, it is possible that the study Table 5. Multivariable Logistic Regression Model: was underpowered for this analysis. Factors Associated With Unintentional Dural Puncture Other variables such as BMI or loss of resistance to air OR (95% CI) P versus saline were not found to infuence the rate of dural Maternal age 1.01 (0.96–1.06) 0.64 puncture. This fnding differs from a 1993 study by Hood 18 Pregestational BMI 1.02 (0.98–1.07) 0.23 et al in which a greater rate of UDP was found in mor- Nulliparity 0.99 (0.63–1.55) 0.98 bidly obese parturients. Of note, a newer study found no PROM 0.55 (0.32–0.93) 0.02 difference in UDP rates between obese and normal-weight Induction of labor 1.31 (0.71–2.41) 0.38 women.19 Our study corroborates a Cochrane review, which Oxytocin augmentation 0.76 (0.41–1.56) 0.39 found that there was no difference in UDP rates using loss Degree of cervical dilation (cm) 1.23 (1.04–1.42) 0.01 20 VNS pain score before analgesia 0.99 (0.98–1.01) 0.08 of resistance to air or saline. Epidural needle depth 1.48 (1.08–2.03) 0.02 Previous articles addressing the risk for PDPH after dural puncture have shown a decreased PDPH incidence after unin- Abbreviations: BMI, body mass index; CI, confdence interval; OR, odds ratio; PROM, premature rupture of membranes; VNS, verbal numerical scale tentional dural puncture in parturients with an increased BMI, (0–100). even after controlling for pushing during labor.15,21 Our study found that only multiparity was a risk factor to develop PDPH Table 6. Multivariable Logistic Regression Model after UDP. We are unsure of the reason for this, although for Risk of Unintentional Dural Puncture With women with small children at home may need to be more Cervical Dilation at Time of Epidural Analgesia and active and need to spend more time in the upright position. Premature Rupture of Membranes The rate of PDPH after UDP was 60.5%, which is similar Hosmer & to the rate previously reported.22 Recent articles, however, Model Variable OR P Lemeshow showed lower rates of PDPH when continuous spinal analge- Main effect Cervical dilation(cm) 1.270 P < .001 P = 0.661 sia was performed after UDP when compared with our rate.23 PROM 0.656 P = .073 Our study did not corroborate this low rate, although it must Main effect and Cervical dilation (cm) 1.262 0.002 P = 0.657 interactions PROM 0.591 0.399 be noted that 10 of our 177 parturients did have their epidural Interaction 1.030 0.856 replaced as opposed to having continuous spinal analgesia. The weakness of this study includes its retrospective The interaction of premature rupture of membranes and with degree of cervical dilation at the time of epidural analgesia is explored further in design and the relatively low rate of recognized UDP. Supplementary Digital Content Collinearity Statistics and Variable Infation Possible confounding factors for UDP such as needle bevel factor. 24 Abbreviations: OR, odds ratio; PROM, premature rupture of membrane. direction and patient cooperation were not recorded. An additional limitation of this study is the fact that parturients in our hospital are relatively lean; results may be different in is anesthesiologist experience. Previous studies included areas where obesity is more prevalent. procedures performed by residents in their frst year of resi- In conclusion, women with a greater degree of cervical dency, whereas in our study only residents who performed dilation in centimeters at the time of initiation of epidural a large number of epidurals on non-obstetric patients and labor analgesia are at greater risk for UDP. Unintentional who completed at least 2 years of residency were allowed dural puncture does not seem to be associated with adverse to begin supervised work in the delivery ward. In addi- obstetric outcomes except for prolonged length of hospital tion, because of the large parturient population and limited stay. There was a high rate of PDPH after UDP. E anesthesiologist workforce, anesthesiology residents perform, at a minimal, four 24-hour shifts in the delivery ward DISCLOSURES every month, with approximately 15–20 epidurals per shift. Name: Sharon Orbach-Zinger, MD. Therefore, residents are highly experienced in performing Contribution: This author helped design the study, conduct the epidurals. Additionally, in 2 studies published in 2001, there study, analyze the data, and write the manuscript. was a dural puncture rate of less than 1%13,14 Similarly, in a Confict of Interest: Sharon Orbach-Zinger declares no conficts of interest. retrospective study conducted in Northwestern University Name: Eran Ashwal, MD. during the years 2004–2013, the UDP rate was 0.53%, only Contribution: This author helped conduct the study, analyze the slightly greater than our reported incidence.15 data, and write the manuscript. We found that the group of parturients with UDP had Confict of Interest: Eran Ashwal declares no conficts of interest. Name: Lilach Hazan, MD. greater degree of cervical dilation at the time of epidural Contribution: This author helped conduct the study. insertion. The greater degree of cervical dilation was dem- Confict of Interest: Lilach Hazan declares no conficts of interest. onstrated among parturients with and without premature Name: Danielle Bracco, BA. rupture of membranes (P = .0011, P = .0098, respectively, Contribution: This author helped conduct the study and write the Mann Whitney U). This fnding is reasonable as greater manuscript. Confict of Interest: Danielle Bracco declares no conficts of interest. degree of cervical dilation is associated with more frequent Name: Alex Ioscovich, MD. and painful contractions, making patient co-operation with Contribution: This author helped design the study and write the the procedure more diffcult. In addition, at greater degree manuscript. of cervical dilation, there may be pressure by the spouse or Confict of Interest: Alex Ioscovich declares no conficts of interest. Name: Liran Hiersch, MD. midwife to perform epidural analgesia before the parturient Contribution: This author helped design the study and conduct the 16 17 delivers. In contrast, Hollister et al found no evidence of study. an association between degree of cervical dilation and the Confict of Interest: Liran Hiersch declares no conficts of interest.

Anesth & Analg. 2016 ahead of print

Active Management of Labor Epidural Analgesia Is the Key to Successful Conversion of Epidural Analgesia to Cesarean Delivery Anesthesia Melissa E. Bauer, DO, and Jill M. Mhyre, MD

* † afe, reliable, and timely conversion of epidural anal- example, obstetric anesthesiologists are more likely to gesia to cesarean delivery anesthesia can be among withdraw an epidural catheter to improve anesthetic block Sthe most«Three challenging aspectsmajor of obstetric risk anesthesia factors quality. are4 However, consistently we believe a complete explanation lies practice. It is also one of the most important. When con- beyond clinical technique; obstetric anesthesiologists version fails, the risks of anesthesia-related complications focus more intensely on analgesic quality before cesarean escalate. Spinalassociated anesthesia injected afterwith failed conversionfailed to epiduraldelivery is declared. conversion: Active management of labor analge- cesarean delivery anesthesia risks high neuraxial blockade.1 sia is a care philosophy in which the anesthesiologist inte- Unplanned conversioncare to general providedanesthesia risks failed by air- agrates nonobstetric information about block quality, progress of labor, way management, which remains a serious safety concern maternal and fetal well-being, and maternal and obstetric despite decades of improvements in equipment and man- decision-making to optimize block quality and density agement anesthesiologist,protocols.2 Beyond ensuring maternal safety,increased suc- before a decisionboluses for cesarean during delivery is declared. Active cessful conversion enhances experience of care. Unplanned management of labor analgesia enhances conversion to cesarean deliverylabor in labor ascan be atraumatic; result the added of stress pain, epidural and anesthesia urgency (ie, limiting use of general anesthesia), of operative delay, intraoperative pain, or unplanned con- but it also targets improved experience of care, which is version to general anesthesia can make the experience of emerging as an important quality measure for obstetric care even worse. cesarean delivery.anesthesia.5 » In the current issue of Anesthesia and Analgesia, a focused Obstetric anesthesiologists may be more likely to work review by Mankowitz et al3 surveys the literature to identify in hospitals that ensure dedicated staffng for the labor and risk factors for failure to extend epidural labor analgesia to delivery unit. Free from duties outside of the unit, dedi- cesarean delivery anesthesia and evidence-based strategies cated staff are best able to maintain ongoing communica- to improve the rate of successful conversion to cesarean tion with the obstetric team, to provide active management delivery anesthesia. The authors are to be congratulated for of labor analgesia, and to identify those women most likely providing an evidence-based and clinically practical review to require cesarean delivery. Dedicated staffng also ensures on an important topic in obstetric anesthesiology. immediate availability for emergency cesarean delivery. Three major risk factors are consistently associated with Despite its many benefts, dedicated staffng may only be failed epidural conversion: care provided by a nonobstetric practical in a minority of delivery units with suffcient vol- anesthesiologist, increased boluses during labor as a result ume to support the service. According to the Centers for of pain, and urgency of cesarean delivery. Clinical strategies Medicare and Medicaid Services medical direction rules, to mitigate these risks are provided here. even a high-volume labor epidural service is not consid- Obstetric anesthesiologists facilitate high rates of suc- ered an anesthetizing location; this reduces the incentive for cessful conversion from epidural analgesia to cesarean many practices to provide dedicated coverage. delivery anesthesia.3 Differences in anesthetic technique Breakthrough pain that requires clinician-administered may partially explain these high rates of success. For bolus dosing during labor is an important risk factor for failed conversion of epidural analgesia to anesthesia. Analgesic dosing requirements and breakthrough pain have From the Division of Obstetric Anesthesiology, Department of also been associated with dysfunctional labor and cesarean Anesthesiology, University of Michigan Health System, Ann Arbor, Michigan; delivery,6 so prompt diagnosis of the cause of breakthrough and Division* of Obstetric Anesthesiology, Department of Anesthesiology, University of Arkansas, Little Rock, Arkansas. pain, targeted treatment, and timely replacement will help † Funding: Department of Anesthesiology, University of Michigan Health facilitate safe conversion if it is needed. In a retrospective System. review of cesarean delivery cases at Brigham and Women’s The authors declare no conficts of interest. Hospital from 2000 to 2005, the low rate of cesarean deliv- Reprints will not be available from the authors. ery requiring general anesthesia was partially attributed Address correspondence to Melissa E. Bauer, DO, L3622 UH South, 1500 E. to aggressive replacement of epidural catheters providing Medical Center Dr, Ann Arbor, MI 48009. Address e-mail to mbalun@med. 7 umich.edu. suboptimal labor analgesia. Copyright © 2016 International Anesthesia Research Society Labor analgesia infusion pump technology may also DOI: 10.1213/ANE.0000000000001582 play a role. Although a meta-analysis of studies comparing

Active management of labor analgesia

«….is a care philosophy in which the anesthesiologist integrates information about block quality, progress of labor, maternal and fetal well-being, and maternal and obstetric decision-making to optimize block quality and density before a decision for cesarean delivery is declared.» Anesth & Analg. 2016 ahead of print

Replacement of labor epidural

«…. timely replacement will help facilitate safe conversion…»

«….aggressive replacement of epidural catheters providing suboptimal labor analgesia…» Anesth & Analg. 2016 ahead of print

Labour anaesthesia

«Despite its many benefits, dedicated staffing may only be practical in a minority of delivery units with sufficient volume to support the service…»

…even a high-volume labor epidural service is not considered an anesthetizing location; this reduces the incentive for many practices to provide dedicated coverage…» [email protected]