Australasian Anaesthesia 2011 - Australian and New Zealand ...

Pethidine: the case for its withdrawal 17Pethidine: the case for its withdrawalGAVIN PATTULLO, BMEDSCI, MBBS (HONS), FANZCA, FFPMANZCADepartment of Anaesthesia and Pain Management,Royal North Shore Hospital, St Leonards NSW 2065Dr Pattullo is a Senior Staff Specialist Anaesthetist and Specialist Pain Medicine Physician. He recently completeda 2 year Fellowship in Anaesthesia in Toronto, Canada where he took a keen interest in ultrasound guided regionalanaesthesia. As the Director of the Acute Pain Service his interests are in the evidence-based application ofcontemporaneous pain management.ROSS MACPHERSON, MSC, PHD, FANZCADepartment of Anaesthesia and Pain Management,Royal North Shore Hospital, St Leonards NSW 2065Dr MacPherson is a Senior Staff Specialist and Clinical Associate Professor in the Department of Anaesthesia andPain Management at Royal North Shore Hospital, Sydney. Apart from clinical anaesthesia, Ross is also interestedin peri-operative assessment and is a member of the Hospital’s Acute Pain Management team. He is also currentlyChairman of the Primary Examination Committee.INTRODUCTIONSeventy years after pethidine became available it is time to critically challenge its continued use. Numerous drugsof similar vintage have long since been eliminated from anaesthetic practice. There are notably other opioids evenolder than pethidine still in widespread use – such as hydromorphone and morphine. However, in contrast to thesetwo examples, only with pethidine is it now appreciated that use brings an excess of worrying side effects. Expertsin the fields of anaesthesia, pain management and addiction medicine calling for the curbing of pethidine use haveoverwhelmed the weak or even absent arguments in support of its ongoing use. 1-3 This calls into question theappropriateness of continued pethidine use.Pethidine can be viewed as having lived somewhat of a charmed life. It was born in 1939 originally out of thesearch for an agent with atropine-like activity. Serendipity intervened with pethidine being found to possess analgesicqualities. Much of the promotion of pethidine in its early years is ascribed by historians to the need for Alliedcountries to have ready access to an alternative opioid analgesic, since Germany dominated morphine manufactureat the time. Good fortune continued with pethidine arriving at a time when both an exciting new opioid was longedfor and one that was hoped to be devoid of typical opioid side effects was keenly sought, and it must be rememberedthat pethidine was essentially the first new opioid on the scene for the last two thousand years! The promotion ofpethidine as being a better choice in a number of key areas such as labour and biliary disease was often conductedwith disregard to the evidence at the time, or was accompanied by an unfair demonisation of morphine.The oft-encountered belief of pethidine’s absence of an emetogenic effect spread by rumour and an almostmystical reverence.ADVANTAGES OF PETHIDINE (?)The use of pethidine brings to patients a unique set of harms without any clear benefit over other opioids. Anextensive discussion of the harms of pethidine will be presented. There are however a number of areas in whichpethidine is commonly held to offer benefit, being a combination of those stated in texts or mentioned by colleagues;the evidence base (or rather the lack of evidence) in support of pethidine will be reviewed.Reduction in Nausea and VomitingPerhaps the best way to answer this assertion is to analyse patient controlled analgesia (PCA) studies comparingoutcomes for the use of pethidine with the commonly available alternatives. PCA studies allow the simplest meansto control for differences in analgesic potency otherwise complicating the interpretation of single-dose studies, andare also more likely to reflect opioid-induced side effects in the purest sense, being more remote on a time basisto the muddying influence of postoperative nausea and vomiting. There have been a number of studies comparingthe PCA use of pethidine with alternatives of morphine, fentanyl or oxymorphone. 4-6 None of these reported astatistically significant difference in nausea and vomiting rates between pethidine and the alternatives available inAustralia of fentanyl or morphine. Woodhouse et al’s study comparing fentanyl, morphine and pethidine foundpatients who were blinded to treatment allocation did not report greater satisfaction with the use of one opioid overanother. Similarly, a blinded medical observer was unable to identify a discernable difference between opioidtreatment groups. 7It is worthy of comment these PCA studies were not designed to have nausea and vomiting rates as their primaryendpoint, and were therefore underpowered to demonstrate significant differences in the occurrence of theseadverse events. However, this lack of evidence of such a benefit becomes salient when we broaden the view toweighing up purported benefits of pethidine against the known harm.There is a suspicion of interindividual susceptibility to the emetogenic effect of a given opioid. This is oftenbased on the observation in PCA managed patients who have a resolution of nausea and vomiting when the opioidis changed to an alternative. Which of the myriad possibilities is responsible for this, including simply a resolutionwith time, is unclear. 8