- Email: [email protected]
Up-to-date or out-of-date: does thiopental have a future in obstetric general anaesthesia?
International Journal of Obstetric Anesthesia (2013) 22, 175–178 0959-289X/$ - see front matter c 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijoa.2013.03.015
EDITORIAL
www.obstetanesthesia.com
Up-to-date or out-of-date: does thiopental have a future in obstetric general anaesthesia? The unique nature of obstetric general anaesthesia (GA) places many demands on the properties of an induction agent. According to Chestnut’s Obstetric Anesthesia, the primary goals of an induction agent for caesarean section (CS) under GA are; ‘‘to preserve maternal blood pressure, cardiac output and uterine blood flow; minimise fetal and neonatal depression, and to ensure maternal hypnosis and amnesia’’.1 Furthermore, in many countries, it is the emergency CS for which GA is most frequently employed. At these times conditions may be adverse, time pressure extreme and these situational factors present other challenges. Can the induction agent be safely reconstituted in the time available or prepared in advance and stored safely for emergency use? Drug preparation and administration errors are more common in emergency situations,2 and are these influenced by our choice of induction agent? Other considerations include: cost, familiarity, shelf life, effect on intubating conditions, whether licensed for use in pregnancy and impact on maternal recovery. Finally, and arguably most importantly, the overall value of any drug is considerably influenced by its availability and reliability of supply. Many obstetric anaesthetists practicing in the UK will be familiar with a daily ritual that aims to mitigate some of the associated risks of emergency obstetric GA. Each day, an ampoule of thiopental is reconstituted and a syringe prepared, labelled, and placed in the drug fridge for use should an emergency present.3,4 At the end of a day (or a variable amount of time), if not administered, the syringe of thiopental is discarded and the ritual repeats itself over again. In a 2007 UK survey, routine pre-preparation of emergency drugs was reported in 87% of obstetric units,3 and although this practice may be on the decline, it still occurs in over half.4 Whether pre-prepared or not, it is clear that, in the UK at least, the popularity of thiopental in obstetric GA has waned little. A recent survey of UK consultant obstetric anaesthetists by Murdoch et al. found thiopental was routinely used by 93% of respondents for induction of GA for CS.5 The enduring popularity of thiopental in the UK is no doubt a consequence of the substantial body of evidence that supports its safety and efficacy in obstetric GA, but use in other parts of the world is less. Although accurate
information is limited, alternative agents are routinely used for CS under GA in many countries, including the USA, where thiopental was once considered the ‘drug of choice’.6,7 The shift away from thiopental has been a consequence of problems with drug supply, rather than of emerging clinical advantage of alternative drugs. UpToDateÒ, self-described as the ‘premier evidencebased clinical decision support resource’, concisely illustrates the current situation, by stating, in regard to obstetric GA that; ‘‘a once-popular induction agent, thiopental, is no longer available in the United States.’’7 This succinct observation fails to convey the perceived importance of the drug to anaesthetists in the USA; discontinuation of the domestic production of thiopental in 2011 prompted the American Society of Anesthesiologists to urge the Food and Drug Administration to import thiopental from foreign manufacturing sites, stating that, ‘‘in obstetric anesthesia, thiopental is still the drug of choice for induction of general anesthesia administered during cesarean delivery.’’6 Currently, thiopental remains available in the UK, but at the time of writing, its production by the sole UK manufacturer has temporarily ceased and UK supply is currently maintained by import from Germany on an unlicensed basis (personal communication, Archimedes Pharma Ltd., Reading, UK, March 2013). In light of the current situation affecting the UK and events elsewhere, perhaps now is an appropriate time to reappraise thiopental and its place in obstetric GA. In the survey by Murdoch, more than a third of respondents cited historical reasons for their routine use of thiopental.5 The time-tested routine of ‘thio, sux, tube’ has a long association with GA for patients considered at risk of pulmonary aspiration and a technique encompassing each of these three elements for obstetric practice was reported over 50 years ago.8 Thiopental’s long association with obstetric GA may, in some part, be a consequence of a lack of alternative induction agents with superior properties. Other drugs currently used for induction of GA for CS include; etomidate, ketamine and propofol, and the latter has generated debate as to its suitability for routine use at CS under GA.9 Propofol entered clinical practice in the late 1980s, rapidly gained popularity, and comparative studies with thiopental for obstetric GA soon
176 followed.10–16 Although these early studies produced conflicting findings, some uncertainty emerged regarding the safety of propofol with respect to both mother and baby.9 General anaesthesia for CS is associated with a higher incidence of intraoperative awareness than that reported in the general surgical population.17 Awareness is distressing and a prominent cause of obstetric GA-related litigation in the UK.18 A third of respondents in Murdoch’s survey based thiopental choice on the increased risk of awareness with alternative induction agents.5 These concerns may stem from a small study that found unacceptably high rates of awareness (40%) following propofol induction for elective CS.19 However, aspects of the anaesthetic technique in this study may have contributed to this finding since halothane, administered at 0.25–0.5% with 50% nitrous oxide in oxygen for maintenance of anaesthesia, was discontinued between uterine incision and delivery. Other comparative studies of thiopental and propofol found no difference in rates of awareness, although these and other studies of women undergoing elective surgery were not adequately powered to identify a difference in this complication, nor were standardised methods of identifying awareness employed.10,11,13,16 The lack of evidence of an increased risk of awareness with propofol and absence of accumulating clinical reports given the extensive worldwide use of propofol in obstetric anaesthesia, are no doubt reassuring. The clinical safety profile of maternal propofol administration on neonatal outcomes is perhaps less clear, and data from a range of studies using different methodology are mixed.9 Poorer Apgar scores were reported in neonates of women administered propofol for CS under GA compared to those with thiopental.10,12 In one study, propofol induction was associated with inferior neonatal neurobehavioural measures, but these effects were short-lived.12 In contrast, several comparative studies of propofol and thiopental have found no difference in neonatal outcomes.11,14–16 Importantly, there are no large-scale studies in the setting of emergency obstetric GA in which the fetus may be distressed but its exposure to anaesthetic drugs brief. There is emerging interest in the influence of fetal exposure to anaesthetic agents on early brain development, and animal studies clearly show an adverse effect, especially when exposure occurs in the second trimester.20 Human studies are limited, and there are no long-term neurodevelopment follow-up studies on infants exposed to maternally administered anaesthetic agents at CS. While there is no evidence that propofol for maternal induction conveys a clear advantage to the neonate over thiopental, evidence is lacking that propofol is more hazardous. What about the effects of propofol on maternal haemodynamics? Clearly, the period from induction to delivery represents the key interval for investigation, since pre-delivery hypotension may adversely affect neo-
Editorial natal condition and blood pressure elevation at laryngoscopy and intubation may have maternal implications. Several studies have found that propofol obtunds the increase in maternal blood pressure at laryngoscopy and intubation compared to thiopental.10,13–16 In one study, maximal maternal noradrenaline concentrations were found to be greater in women induced with thiopental, compared to propofol, however there was no difference in maternal adrenaline concentrations or neonatal outcome between groups.15 The clinical significance of these observations remains unclear. Despite the continuing popularity of thiopental for obstetric GA in the UK, other induction agents have largely replaced its use in emergency GA for non-obstetric patients considered at risk of pulmonary aspiration.21 In a survey of Welsh anaesthetists, thiopental was used by 88% of respondents for emergency obstetric GA but less frequently than other induction agents for nonobstetric cases requiring rapid sequence induction and intubation.21 Consequently, anaesthetists’ experience with thiopental is declining and, in the context of obstetric emergency GA that is infrequent and largely unpredictable, using an unfamiliar induction agent at such times is not ideal. Encouraging thiopental use outside obstetric practice to improve familiarity is an approach supported by some,5 but appropriate opportunities are likely to be infrequent. Infrequent use of thiopental presents other problems. Drug administration errors, including ‘syringe-swap’ (a drug administered from a syringe whose contents were correctly labelled but the drug was not the one intended) are an important cause of anaesthesia-related morbidity and inattention, haste, distraction and fatigue have been associated with their occurrence.2 These situational factors feature commonly at obstetric emergencies and it is no surprise that drug errors arise at these times.17,22,23 The most common serious drug error reported in UK surveys of obstetric anaesthetic practice is administration of thiopental instead of antibiotic (or vice-versa).4,24 The consequences, inadvertent GA or absence of intended GA with risk of awareness, are serious and potentially damaging. Although the true frequency of these events is unknown, their common reporting in surveys of drug errors in obstetric anaesthesia is concerning, and a recent UK patient safety report has highlighted this risk in obstetric practice.22 In addition to ‘syringe-swap’ errors, some drugs are prone to reconstitution error. This has been reported at emergency CS; failure to reconstitute thiopental led to administration of water for injection followed by suxamethonium and consequent awareness.17 Evidence-based strategies have been developed to reduce the risk of intravenous drug administration errors.25 However, it is clear that certain drugs, including thiopental and antibiotics, are more commonly implicated in obstetric anaesthesia-related drug error incidents, partly because of the frequency
Editorial with which they are used but no doubt because of their similarity in appearance to other drugs used in this setting.24 The summary of product characteristics (SPC) of thiopental recommends reconstituted drug is used within seven hours of preparation,26 but it is doubtful that this guidance is consistently followed in labour units that preprepare the drug for emergency use.3 Reconstituted thiopental has been found to be sterile for longer than seven days when stored at 3°C, but storage for longer than seven hours is clearly outside its SPC.27 The advantages of advanced reconstitution must be considered against the costs of drug wastage and potential safety hazards, including risk of drug tampering and contamination. Pre-filled drug syringes have been shown to reduce drug error in anaesthetic practice.25 Utilising thiopental in this way is attractive since it not only eliminates reconstitution errors but can reduce costs, and pre-filled thiopental formulations with an extended shelf life of up to 90 days are available.28 Despite these potential advantages, there are reports of failed induction of anaesthesia at CS with thiopental delivered from pre-filled syringes.29,30 Fortunately, in each of these cases the problem was detected before muscle relaxant administration, but the potential for harm is obvious. The SPC of thiopental states that it can be used ‘‘without adverse effects during pregnancy’’ however, this comes with the caveat that the total dose should not exceed 250 mg.26 Clearly, this dose is commonly, and justifiably exceeded. In contrast, the SPC of propofol advises that it ‘‘should not be used for obstetric anaesthesia unless clearly necessary’’.31 Relatively few drugs possess a license for use in pregnancy and several drugs commonly used in obstetric anaesthesia are prescribed outside the stipulations of their SPC.9 Anaesthetists working in countries where thiopental is no longer available may reasonably argue that, in its absence, use of propofol for obstetric GA has now become ‘clearly necessary’. Worldwide, propofol is used extensively for obstetric GA and the scientific literature does not demonstrate a clear disadvantage over thiopental to either mother or baby. The absence of accumulating reports of maternal or neonatal harm provides further reassurance that it is safe in this setting, and at present there may be an appetite for change; a majority of the UK consultant obstetric anaesthetists in Murdoch’s survey supported a move to propofol as the induction agent of choice.5 Whatever our individual opinion, it is clear that within the UK, and perhaps elsewhere, an increasingly unfamiliar drug is in use for an infrequent and often challenging procedure. The supply and long-term availability of thiopental is unpredictable, it features prominently in cases of serious obstetric anaesthesia-related drug error, and it requires storage once reconstituted, with potential additional risks that cannot necessarily be mitigated by the use of pre-filled syringes. If we return to where we
177 started in considering the ideal properties of an induction agent for obstetric GA, it is clear that thiopental is far from perfect. For those in the UK and other countries where thiopental remains available but the long-term supply is unreliable, consideration and understanding of alternative agents for obstetric anaesthesia is now prudent. Our relationship with this valuable drug has been long and for the most part fulfilling, but if the love is waning, perhaps now is the time for a considered and amicable separation, rather than an unplanned and messy break-up brought on by events beyond our control. Perhaps in time, we may even grow to love an alternative that will continue the challenge in keeping our pregnant patients and their babies safe during obstetric GA. Matthew Rucklidge Department of Anaesthesia Royal Devon and Exeter NHS Foundation Trust Exeter, UK E-mail address: [email protected]
References 1. Kuczkowski KM, Reisner LS, Lin D. Anesthesia for caesarean section. In: Chestnut DH, Polley LS, Tsen LC, Wong CA, editors. Chestnut’s Obstetric Anesthesia: Principles and Practice. 3rd ed. Philadelphia: Elsevier Mosby; 2004.. P. 434. 2. Abeysekera A, Bergman IJ, Kluger MT, Short TG. Drug error in anaesthetic practice: a review of 896 reports from the Australian Incident Monitoring Study database. Anaesthesia 2005;60:220–7. 3. Stone JP, Fenner LB, Christmas TR. The preparation and storage of anaesthetic drugs for obstetric emergencies: a survey of UK practice. Int J Obstet Anesth 2009;18:242–8. 4. Eason S, Misra U. Drug errors in obstetric anaesthesia: a national survey. OAA survey 108. Poster presentation OAA 2011 Edinburgh. http://www.oaa-anaes.ac.uk/assets/_managed/editor/File/ Courses/2011/11.92_non-IJOA_abstracts.pdf [accessed March 2013]. 5. Murdoch H, Scrutton M, Laxton CH. Choice of anaesthetic agents for caesarean section: a UK survey of current practice. Int J Obstet Anesth 2013;22:31–5. 6. ASA letter to FDA on thiopental shortage. http://www.asahq.org/ For-members/Advocacy/Washington-Alerts/asa-letter-to-fda-onthiopental-shortage.aspx [accessed March 2013]. 7. UpToDateÒ. Anesthesia for cesarean delivery. http://www.Uptodate.com/contents/anesthesia-for-cesarean-delivery [accessed March 2013]. 8. Hamer Hodges RJ, Bennett JR, Tunstall ME, Knight RF. General anaesthesia for operative obstetrics. With special reference to the use of thiopentone and suxamethonium. Br J Anaesth 1959;31:152–63. 9. Duggal K, Russell R. Propofol should be the induction agent of choice for caesarean section under general anaesthesia. Int J Obstet Anesth 2003;12:275–9. 10. Capogna G, Celleno D, Sebastiani M, et al. Propofol and thiopentone for caesarean section revisited: maternal effects and neonatal outcome. Int J Obstet Anesth 1991;1:19–23.
178 11. Valtonen M, Kanto J, Rosenberg P. Comparison of propofol and thiopentone for induction of anaesthesia for elective caesarean section. Anaesthesia 1989;44:758–62. 12. Celleno D, Capogna G, Tomassetti M, Costantino P, Di Feo G, Nisini R. Neurobehavioural effects of propofol on the neonate following elective caesarean section. Br J Anaesth 1989;62:649–54. 13. Yau G, Gin T, Ewart MC, Kotur CF, Leung RK, Oh TE. Propofol for induction and maintenance of anesthesia at caesarean section. A comparison with thiopentone/enflurane. Anaesthesia 1991;46:20–3. 14. Moore J, Bill KM, Flynn RJ, McKeating KT, Howard PJ. A comparison between propofol and thiopentone as induction agents in obstetric anaesthesia. Anaesthesia 1989;44:753–7. 15. Gin T, O’Meara ME, Kan AF, Leung RKW, Tan P, Yau G. Plasma catecholamines and neonatal condition after induction of anaesthesia with propofol or thiopentone at caesarean section. Br J Anaesth 1993;70:311–6. 16. Gin T, Gregory MA, Oh TE. The haemodynamic effects of propofol and thiopentone for induction of caesarean section. Anaesth Intensive Care 1990;18:175–9. 17. Paech MJ, Scott KL, Clavisi SC, Chua S, McDonnell N; The ANZCA Trials Group. A prospective study of awareness and recall associated with general anaesthesia for caesarean section. Int J Obstet Anesth 2008;17:298–303. 18. Ashpole KJ, Cook TM. Litigation in obstetric general anaesthesia: an analysis of claims against the NHS in England 1995–2007. Anaesthesia 2010;65:529–30. 19. Dailland P, Cockshott ID, Lirzin JD, et al. Intravenous propofol during cesarean section: placental transfer, concentrations in breast milk, and neonatal effects. A preliminary study. Anesthesiology 1989;71:827–34. 20. Palanisamy A. Maternal anesthesia and fetal neurodevelopment. Int J Obstet Anesth 2012;21:152–62.
Editorial 21. Koerber JP, Roberts GE, Whitaker R, Thorpe CM. Variation in rapid sequence induction techniques: current practice in Wales. Anaesthesia 2009;64:54–9. 22. AAGBI. Safe Anaesthesia Liaison Group. Patient Safety Update. Including the summary of reported incidents relating to anaesthesia 1 Oct 2011 to 31 Dec 2011. http://www.rcoa.ac.uk/system/files/ CSQ-PS-PSU-DEC2011.pdf [accessed March 2013]. 23. Marr R, Boyle G, Bythell V. Antibiotic prophylaxis for caesarean section: exchanging one risk for another? Anaesthesia 2012;67:678–9. 24. Yentis SM, Randall K. Drug errors in obstetric anaesthesia: a national survey. Int J Obstet Anesth 2003;12:246–9. 25. Jensen LS, Merry AF, Webster CS, Weller J, Larsson L. Evidencebased strategies for preventing drug administration errors during anaesthesia. Anaesthesia 2004;59:493–504. 26. Summary of product characteristics for thiopental sodium. http:// www.medicines.org.uk/EMC/medicine/14338/SPC/Thiopental+injection [accessed March 2013]. 27. Haws JL, Herman N, Clark Y, Bjoraker R, Jones D. The chemical stability and sterility of sodium thiopental after preparation. Anesth Analg 1998;86:208–13. 28. Murdoch H, Jordan L, Tuckey J. Pre-filled thiopental syringes reduce cost and wastage whilst improving safety. Int J Obstet Anesth 2012;21:384–5. 29. Quinn L, Furness G. Antibiotic or induction agent? Another problem from a possible solution. Anaesthesia 2012;67:1048–9. 30. Stewart PJ, Laird R. Failure of prefilled thiopental to induce anaesthesia. Anaesthesia 2013;68:308. 31. Summary of product characteristics for Diprivan 1%. http:// www.medicines.org.uk/emc/medicine/2275/SPC [accessed March 2013].
EDITORIAL
www.obstetanesthesia.com
Up-to-date or out-of-date: does thiopental have a future in obstetric general anaesthesia? The unique nature of obstetric general anaesthesia (GA) places many demands on the properties of an induction agent. According to Chestnut’s Obstetric Anesthesia, the primary goals of an induction agent for caesarean section (CS) under GA are; ‘‘to preserve maternal blood pressure, cardiac output and uterine blood flow; minimise fetal and neonatal depression, and to ensure maternal hypnosis and amnesia’’.1 Furthermore, in many countries, it is the emergency CS for which GA is most frequently employed. At these times conditions may be adverse, time pressure extreme and these situational factors present other challenges. Can the induction agent be safely reconstituted in the time available or prepared in advance and stored safely for emergency use? Drug preparation and administration errors are more common in emergency situations,2 and are these influenced by our choice of induction agent? Other considerations include: cost, familiarity, shelf life, effect on intubating conditions, whether licensed for use in pregnancy and impact on maternal recovery. Finally, and arguably most importantly, the overall value of any drug is considerably influenced by its availability and reliability of supply. Many obstetric anaesthetists practicing in the UK will be familiar with a daily ritual that aims to mitigate some of the associated risks of emergency obstetric GA. Each day, an ampoule of thiopental is reconstituted and a syringe prepared, labelled, and placed in the drug fridge for use should an emergency present.3,4 At the end of a day (or a variable amount of time), if not administered, the syringe of thiopental is discarded and the ritual repeats itself over again. In a 2007 UK survey, routine pre-preparation of emergency drugs was reported in 87% of obstetric units,3 and although this practice may be on the decline, it still occurs in over half.4 Whether pre-prepared or not, it is clear that, in the UK at least, the popularity of thiopental in obstetric GA has waned little. A recent survey of UK consultant obstetric anaesthetists by Murdoch et al. found thiopental was routinely used by 93% of respondents for induction of GA for CS.5 The enduring popularity of thiopental in the UK is no doubt a consequence of the substantial body of evidence that supports its safety and efficacy in obstetric GA, but use in other parts of the world is less. Although accurate
information is limited, alternative agents are routinely used for CS under GA in many countries, including the USA, where thiopental was once considered the ‘drug of choice’.6,7 The shift away from thiopental has been a consequence of problems with drug supply, rather than of emerging clinical advantage of alternative drugs. UpToDateÒ, self-described as the ‘premier evidencebased clinical decision support resource’, concisely illustrates the current situation, by stating, in regard to obstetric GA that; ‘‘a once-popular induction agent, thiopental, is no longer available in the United States.’’7 This succinct observation fails to convey the perceived importance of the drug to anaesthetists in the USA; discontinuation of the domestic production of thiopental in 2011 prompted the American Society of Anesthesiologists to urge the Food and Drug Administration to import thiopental from foreign manufacturing sites, stating that, ‘‘in obstetric anesthesia, thiopental is still the drug of choice for induction of general anesthesia administered during cesarean delivery.’’6 Currently, thiopental remains available in the UK, but at the time of writing, its production by the sole UK manufacturer has temporarily ceased and UK supply is currently maintained by import from Germany on an unlicensed basis (personal communication, Archimedes Pharma Ltd., Reading, UK, March 2013). In light of the current situation affecting the UK and events elsewhere, perhaps now is an appropriate time to reappraise thiopental and its place in obstetric GA. In the survey by Murdoch, more than a third of respondents cited historical reasons for their routine use of thiopental.5 The time-tested routine of ‘thio, sux, tube’ has a long association with GA for patients considered at risk of pulmonary aspiration and a technique encompassing each of these three elements for obstetric practice was reported over 50 years ago.8 Thiopental’s long association with obstetric GA may, in some part, be a consequence of a lack of alternative induction agents with superior properties. Other drugs currently used for induction of GA for CS include; etomidate, ketamine and propofol, and the latter has generated debate as to its suitability for routine use at CS under GA.9 Propofol entered clinical practice in the late 1980s, rapidly gained popularity, and comparative studies with thiopental for obstetric GA soon
176 followed.10–16 Although these early studies produced conflicting findings, some uncertainty emerged regarding the safety of propofol with respect to both mother and baby.9 General anaesthesia for CS is associated with a higher incidence of intraoperative awareness than that reported in the general surgical population.17 Awareness is distressing and a prominent cause of obstetric GA-related litigation in the UK.18 A third of respondents in Murdoch’s survey based thiopental choice on the increased risk of awareness with alternative induction agents.5 These concerns may stem from a small study that found unacceptably high rates of awareness (40%) following propofol induction for elective CS.19 However, aspects of the anaesthetic technique in this study may have contributed to this finding since halothane, administered at 0.25–0.5% with 50% nitrous oxide in oxygen for maintenance of anaesthesia, was discontinued between uterine incision and delivery. Other comparative studies of thiopental and propofol found no difference in rates of awareness, although these and other studies of women undergoing elective surgery were not adequately powered to identify a difference in this complication, nor were standardised methods of identifying awareness employed.10,11,13,16 The lack of evidence of an increased risk of awareness with propofol and absence of accumulating clinical reports given the extensive worldwide use of propofol in obstetric anaesthesia, are no doubt reassuring. The clinical safety profile of maternal propofol administration on neonatal outcomes is perhaps less clear, and data from a range of studies using different methodology are mixed.9 Poorer Apgar scores were reported in neonates of women administered propofol for CS under GA compared to those with thiopental.10,12 In one study, propofol induction was associated with inferior neonatal neurobehavioural measures, but these effects were short-lived.12 In contrast, several comparative studies of propofol and thiopental have found no difference in neonatal outcomes.11,14–16 Importantly, there are no large-scale studies in the setting of emergency obstetric GA in which the fetus may be distressed but its exposure to anaesthetic drugs brief. There is emerging interest in the influence of fetal exposure to anaesthetic agents on early brain development, and animal studies clearly show an adverse effect, especially when exposure occurs in the second trimester.20 Human studies are limited, and there are no long-term neurodevelopment follow-up studies on infants exposed to maternally administered anaesthetic agents at CS. While there is no evidence that propofol for maternal induction conveys a clear advantage to the neonate over thiopental, evidence is lacking that propofol is more hazardous. What about the effects of propofol on maternal haemodynamics? Clearly, the period from induction to delivery represents the key interval for investigation, since pre-delivery hypotension may adversely affect neo-
Editorial natal condition and blood pressure elevation at laryngoscopy and intubation may have maternal implications. Several studies have found that propofol obtunds the increase in maternal blood pressure at laryngoscopy and intubation compared to thiopental.10,13–16 In one study, maximal maternal noradrenaline concentrations were found to be greater in women induced with thiopental, compared to propofol, however there was no difference in maternal adrenaline concentrations or neonatal outcome between groups.15 The clinical significance of these observations remains unclear. Despite the continuing popularity of thiopental for obstetric GA in the UK, other induction agents have largely replaced its use in emergency GA for non-obstetric patients considered at risk of pulmonary aspiration.21 In a survey of Welsh anaesthetists, thiopental was used by 88% of respondents for emergency obstetric GA but less frequently than other induction agents for nonobstetric cases requiring rapid sequence induction and intubation.21 Consequently, anaesthetists’ experience with thiopental is declining and, in the context of obstetric emergency GA that is infrequent and largely unpredictable, using an unfamiliar induction agent at such times is not ideal. Encouraging thiopental use outside obstetric practice to improve familiarity is an approach supported by some,5 but appropriate opportunities are likely to be infrequent. Infrequent use of thiopental presents other problems. Drug administration errors, including ‘syringe-swap’ (a drug administered from a syringe whose contents were correctly labelled but the drug was not the one intended) are an important cause of anaesthesia-related morbidity and inattention, haste, distraction and fatigue have been associated with their occurrence.2 These situational factors feature commonly at obstetric emergencies and it is no surprise that drug errors arise at these times.17,22,23 The most common serious drug error reported in UK surveys of obstetric anaesthetic practice is administration of thiopental instead of antibiotic (or vice-versa).4,24 The consequences, inadvertent GA or absence of intended GA with risk of awareness, are serious and potentially damaging. Although the true frequency of these events is unknown, their common reporting in surveys of drug errors in obstetric anaesthesia is concerning, and a recent UK patient safety report has highlighted this risk in obstetric practice.22 In addition to ‘syringe-swap’ errors, some drugs are prone to reconstitution error. This has been reported at emergency CS; failure to reconstitute thiopental led to administration of water for injection followed by suxamethonium and consequent awareness.17 Evidence-based strategies have been developed to reduce the risk of intravenous drug administration errors.25 However, it is clear that certain drugs, including thiopental and antibiotics, are more commonly implicated in obstetric anaesthesia-related drug error incidents, partly because of the frequency
Editorial with which they are used but no doubt because of their similarity in appearance to other drugs used in this setting.24 The summary of product characteristics (SPC) of thiopental recommends reconstituted drug is used within seven hours of preparation,26 but it is doubtful that this guidance is consistently followed in labour units that preprepare the drug for emergency use.3 Reconstituted thiopental has been found to be sterile for longer than seven days when stored at 3°C, but storage for longer than seven hours is clearly outside its SPC.27 The advantages of advanced reconstitution must be considered against the costs of drug wastage and potential safety hazards, including risk of drug tampering and contamination. Pre-filled drug syringes have been shown to reduce drug error in anaesthetic practice.25 Utilising thiopental in this way is attractive since it not only eliminates reconstitution errors but can reduce costs, and pre-filled thiopental formulations with an extended shelf life of up to 90 days are available.28 Despite these potential advantages, there are reports of failed induction of anaesthesia at CS with thiopental delivered from pre-filled syringes.29,30 Fortunately, in each of these cases the problem was detected before muscle relaxant administration, but the potential for harm is obvious. The SPC of thiopental states that it can be used ‘‘without adverse effects during pregnancy’’ however, this comes with the caveat that the total dose should not exceed 250 mg.26 Clearly, this dose is commonly, and justifiably exceeded. In contrast, the SPC of propofol advises that it ‘‘should not be used for obstetric anaesthesia unless clearly necessary’’.31 Relatively few drugs possess a license for use in pregnancy and several drugs commonly used in obstetric anaesthesia are prescribed outside the stipulations of their SPC.9 Anaesthetists working in countries where thiopental is no longer available may reasonably argue that, in its absence, use of propofol for obstetric GA has now become ‘clearly necessary’. Worldwide, propofol is used extensively for obstetric GA and the scientific literature does not demonstrate a clear disadvantage over thiopental to either mother or baby. The absence of accumulating reports of maternal or neonatal harm provides further reassurance that it is safe in this setting, and at present there may be an appetite for change; a majority of the UK consultant obstetric anaesthetists in Murdoch’s survey supported a move to propofol as the induction agent of choice.5 Whatever our individual opinion, it is clear that within the UK, and perhaps elsewhere, an increasingly unfamiliar drug is in use for an infrequent and often challenging procedure. The supply and long-term availability of thiopental is unpredictable, it features prominently in cases of serious obstetric anaesthesia-related drug error, and it requires storage once reconstituted, with potential additional risks that cannot necessarily be mitigated by the use of pre-filled syringes. If we return to where we
177 started in considering the ideal properties of an induction agent for obstetric GA, it is clear that thiopental is far from perfect. For those in the UK and other countries where thiopental remains available but the long-term supply is unreliable, consideration and understanding of alternative agents for obstetric anaesthesia is now prudent. Our relationship with this valuable drug has been long and for the most part fulfilling, but if the love is waning, perhaps now is the time for a considered and amicable separation, rather than an unplanned and messy break-up brought on by events beyond our control. Perhaps in time, we may even grow to love an alternative that will continue the challenge in keeping our pregnant patients and their babies safe during obstetric GA. Matthew Rucklidge Department of Anaesthesia Royal Devon and Exeter NHS Foundation Trust Exeter, UK E-mail address: [email protected]
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