Controlled-release opioids cause harm and should be avoided in management of postoperative pain in opioid naïve patients

Abstract

In 2018 the Australian and New Zealand College of Anaesthetists (ANZCA) and its Faculty of Pain Medicine (FPM) released a Position statement on the use of slow-release opioid preparations in the treatment of acute pain, and stated that ‘Slow-release opioids are not recommended for use in the management of patients with acute pain’. This commentary discusses why and how controlled-release opioids were introduced into anaesthetic practice, and their subsequent contribution to the global prescribed opioid epidemic. Other concerns that are associated with the use of controlled-release opioids are also explored including opioid-induced hypoventilation impairment. The US response to the use of controlled-release opioids is examined, and the justification for ANZCA/FPM's position statement. This editorial then discusses current analgesic strategies that promote the rapid return of normal function (drinking, eating, and mobilisation), whilst reducing the potential for harm from acute opioid toxicity and chronic opioid dependence. The introduction of controlled-release oral opioids into postoperative pain control management began in the late 1990s. Before that analgesic techniques for major surgery were ‘unimodal’ (Kehlet and Dahl's1Kehlet H. Dahl J.B. The value of “multimodal” or “balanced analgesia” in postoperative pain treatment.Anesth Analg. 1993; 77: 1048-1056Crossref PubMed Scopus (1110) Google Scholar revolutionary paper on the benefits of ‘multimodal’ analgesia was published in 1993). There was a paucity of effective analgesic options, consequently, postoperative pain after surgery was common and frequently severe. The analgesic options were limited to ‘on demand’/‘pro re nata’ (prn) intramuscular and subcutaneous opioid injections, patient-controlled analgesia (PCA) and epidural analgesia. Standard practice was for opioids administered parenterally and ‘on demand’, and therefore patients would experience pain before analgesia and this was believed to confer a safety advantage. However a corollary of this is that patients suffer episodes of severe pain before assistance arrived and then delayed analgesia administration as trained staff prepared and checked the prescription and drugs.2Bourke M. Hayes A. Doyle M. McCarroll M. A comparison of regularly administered sustained release oral morphine with intramuscular morphine for control of postoperative pain.Anesth Analg. 2000; 90: 427-430PubMed Google Scholar, 3McCormack J.P. Warriner C.B. Levine M. Glick N. A comparison of regularly dosed oral morphine and on-demand intramuscular morphine in the treatment of postsurgical pain.Can J Anaesth. 1993; 40: 819-824Crossref PubMed Scopus (32) Google Scholar The concurrent use of simple analgesics (NSAIDs and paracetamol) was not routine practice as the concept of multimodal/balanced analgesia had not been developed.1Kehlet H. Dahl J.B. The value of “multimodal” or “balanced analgesia” in postoperative pain treatment.Anesth Analg. 1993; 77: 1048-1056Crossref PubMed Scopus (1110) Google Scholar, 4Dahl J.B. Kehlet H. Non-steroidal anti-inflammatory drugs: rationale for use in severe postoperative pain.Br J Anaesth. 1991; 66: 703-712Abstract Full Text PDF PubMed Scopus (408) Google Scholar Immediate-release oral opioids were available, and there was good evidence they were effective and safe for management of acute postoperative pain3McCormack J.P. Warriner C.B. Levine M. Glick N. A comparison of regularly dosed oral morphine and on-demand intramuscular morphine in the treatment of postsurgical pain.Can J Anaesth. 1993; 40: 819-824Crossref PubMed Scopus (32) Google Scholar; however, concerns about erratic absorption, high first pass metabolism, and short half-life hindered widespread adoption. The publicised death of a patient enrolled in a clinical study investigating controlled-release morphine in the postoperative period5Brahams D. Death of patient participating in trial of oral morphine for relief of postoperative pain.Lancet. 1984; 1: 1083Google Scholar contributed to the severely restricted licence that still applies to use of controlled-release morphine in the management of postoperative pain: controlled-release morphine is ‘not recommended in the first 24 h after operation or until normal bowel function has returned and the dosage is dependent upon the severity of the pain, the patient's age and previous history of analgesic requirements’.6Electronic Medicines Compendium Summary of product characteristics of MST continus tablets.https://www.medicines.org.uk/emc/product/7666/smpcDate accessed: September 6, 2018Google Scholar The increasing popularity of PCA and epidural analgesia was in part driven by the dearth of other analgesic options and also by technological advances in pump design that made them cheaper, safer, more portable, and therefore more accessible. These advanced analgesia delivery options resulted in improved patient satisfaction in comparison with prn intramuscular and subcutaneous opioid, but at the cost of increased nursing input managing the well-recognised complications of these techniques (e.g. reduced mobility, hypotension, increased observations, associated fluid therapy, sedation). Management of postoperative surgical pain was transformed in 1995 when Purdue Pharma (Stamford, Connecticut, USA) obtained US Food and Drug Administration (FDA) approval to market the controlled-release preparation of oral oxycodone (OxyContin®). Oxycodone was originally developed in Germany in 1917, and for many years was often marketed in combination with other drugs. During the Second World War it was formulated with scopolamine and ephedrine (ephedrine was added to reduce circulatory and respiratory effects). In 1950, Percodan®, a compound analgesic of oxycodone and aspirin was first marketed. In 1976, this was superseded by Perocet®, a compound analgesic containing oxycodone and paracetamol. The use and dose of Percodan® and Perocet® in the treatment of severe postoperative pain was limited by the risk of toxicity secondary to the non-opioid analgesic. In comparison with morphine, oxycodone has a more favourable pharmacokinetic profile with significantly higher oral bioavailability and less plasma level variability between individuals. Hallucinations, pruritus, and nausea and vomiting are also less frequently reported (albeit the research was undertaken in cancer patients).7Riley J. Eisenberg E. Müller-Schwefe G. Drewes A.M. Arendt-Nielsen L. Oxycodone: a review of its use in the management of pain.Current Med Res Opin. 2008; 24: 175-192Crossref PubMed Scopus (124) Google Scholar The production and marketing of OxyContin® (containing solely controlled-release oxycodone) by Purdue Pharma in 1995 resulted in the medical and commercial step change that led to the ubiquity of controlled-release oxycodone. Controlled-release oxycodone is designed to provide sustained delivery of oxycodone over a 12 h period and is indicated for the treatment of moderate to severe postoperative pain and cancer pain.8Electronic Medicines CompendiumSummary of product characteristics of OxyContin.https://www.medicines.org.uk/emc/product/3415/smpcDate accessed: September 6, 2018Google Scholar The controlled-release mechanism provides a biphasic absorption profile, characterised by an initial prompt release of drug, facilitating rapid absorption and an onset of action within 1 h for most patients, and a steady release over several hours.9Smith H.S. Enteral controlled-release opioid delivery systems.Pain Med. 2009; 10: S30-S38Google Scholar Its pharmacological properties allayed safety concerns about the variable peak and trough levels observed with morphine, and the belief that it was a ‘less addictive opioid’10deShazo R.D. Johnson M. Eriator I. Rodenmeyer K. Backstories on the U.S. opioid epidemic good intentions gone bad, an industry gone rogue and watch dogs gone to sleep.Am J Med. 2018; 131: 595-601Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar made it attractive to both physicians and patients. Ultimately this led to the advent of regular controlled-released oxycodone administration regimes, and the dose was not dependent on previous analgesic requirements in contrast with controlled-release morphine.6Electronic Medicines Compendium Summary of product characteristics of MST continus tablets.https://www.medicines.org.uk/emc/product/7666/smpcDate accessed: September 6, 2018Google Scholar, 7Riley J. Eisenberg E. Müller-Schwefe G. Drewes A.M. Arendt-Nielsen L. Oxycodone: a review of its use in the management of pain.Current Med Res Opin. 2008; 24: 175-192Crossref PubMed Scopus (124) Google Scholar, 8Electronic Medicines CompendiumSummary of product characteristics of OxyContin.https://www.medicines.org.uk/emc/product/3415/smpcDate accessed: September 6, 2018Google Scholar, 9Smith H.S. Enteral controlled-release opioid delivery systems.Pain Med. 2009; 10: S30-S38Google Scholar, 10deShazo R.D. Johnson M. Eriator I. Rodenmeyer K. Backstories on the U.S. opioid epidemic good intentions gone bad, an industry gone rogue and watch dogs gone to sleep.Am J Med. 2018; 131: 595-601Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar, 11Carli F. Charlebois P. Baldini G. Cachero O. Stein B. An integrated multidisciplinary approach to implementation of a fast-track program for laparoscopic colorectal surgery.Can J Anesth. 2009; 56: 837-842Crossref PubMed Scopus (71) Google Scholar, 12Tan M. Law L.S. Gan T.J. Optimizing pain management to facilitate enhanced recovery after surgery pathways.Can J Anesth. 2015; 62: 203-218Crossref PubMed Scopus (190) Google Scholar, 13Sunshine A. Olson N.Z. Colon A. et al.Analgesic efficacy of controlled-release oxycodone in postoperative pain.J Clin Pharmacol. 1996; 36: 595-603Crossref PubMed Scopus (83) Google Scholar, 14Reuben S.S. Connelly N.R. Maciolek H. Postoperative analgesia with controlled-release oxycodone for outpatient anterior cruciate ligament surgery.Anesth Analg. 1999; 88 ([retracted]): 1286-1291PubMed Google Scholar In 1996, Sunshine and colleagues13Sunshine A. Olson N.Z. Colon A. et al.Analgesic efficacy of controlled-release oxycodone in postoperative pain.J Clin Pharmacol. 1996; 36: 595-603Crossref PubMed Scopus (83) Google Scholar demonstrated that in patients undergoing open gynaecological procedures, pre-emptive controlled-release oxycodone was comparable in onset with Perocet® but superior in terms of quality of analgesia and duration. In 1999, Reuben and colleagues14Reuben S.S. Connelly N.R. Maciolek H. Postoperative analgesia with controlled-release oxycodone for outpatient anterior cruciate ligament surgery.Anesth Analg. 1999; 88 ([retracted]): 1286-1291PubMed Google Scholar were able to publish their findings from a study investigating the quality of analgesia after anterior cruciate ligament surgery. They concluded that controlled-release oxycodone was superior to prn oxycodone in terms of better analgesia and less sedation, and less overall oxycodone consumption. However, the paper subsequently had to be retracted because of falsification of results.14Reuben S.S. Connelly N.R. Maciolek H. Postoperative analgesia with controlled-release oxycodone for outpatient anterior cruciate ligament surgery.Anesth Analg. 1999; 88 ([retracted]): 1286-1291PubMed Google Scholar Before its retraction, the article had been cited 116 times, and was used to advocate use of controlled-release oxycodone in the management of acute postoperative pain. In 2001 Cheville and colleagues15Cheville A. Chen A. Oster G. McGarry L. Narcessian E. A randomized trial of controlled-release oxycodone during inpatient rehabilitation following unilateral total knee arthroplasty.J Bone Jt Surg Am. 2001; 83: 572Crossref PubMed Scopus (36) Google Scholar published a randomised study looking at two groups of patients undergoing unilateral knee arthroplasty. Group 1 received pre-emptive controlled-release oxycodone and the second group a placebo. Patients were able to request immediate-release oxycodone. The controlled-release oxycodone cohort received less oxycodone in total, mobilised quicker, and were discharged 2.3 days earlier. The conclusion was that pre-emptive use of controlled-release oxycodone leads to improved pain control, more rapid functional recovery, and a reduced need for expensive healthcare resources. In 2005 de Beer and colleagues16De Beer J. de V. Winemaker M.J. Donnelly G.A.E. et al.Efficacy and safety of controlled-release oxycodone and standard therapies for postoperative pain after knee or hip replacement.Can J Surg. 2005; 48: 277-283PubMed Google Scholar reported that controlled-release oxycodone provided superior pain relief in comparison with epidural and PCA analgesia in patients undergoing lower limb arthroplasty. In addition, hospital stay was shorter, resulting in hospital cost savings because of reduced use of healthcare resources. This highly cited study cemented the routine use of controlled-release oxycodone in fast-track surgery for joint arthroplasty. This study was funded by Purdue Pharma, and several of the authors were employees. A more detailed account of all of these studies can be found in the review that received an unrestricted educational grant from Mundipharma (Cambridge , UK), the European distributors of OxyContin.7Riley J. Eisenberg E. Müller-Schwefe G. Drewes A.M. Arendt-Nielsen L. Oxycodone: a review of its use in the management of pain.Current Med Res Opin. 2008; 24: 175-192Crossref PubMed Scopus (124) Google Scholar In 2009, Carli and colleagues11Carli F. Charlebois P. Baldini G. Cachero O. Stein B. An integrated multidisciplinary approach to implementation of a fast-track program for laparoscopic colorectal surgery.Can J Anesth. 2009; 56: 837-842Crossref PubMed Scopus (71) Google Scholar demonstrated that for selected patients, enrolled in an enhanced recovery programme for elective laparoscopic colorectal, controlled-release oxycodone was effective in managing postoperative pain and promoting rapid hospital discharge. On the basis of these and other studies,7Riley J. Eisenberg E. Müller-Schwefe G. Drewes A.M. Arendt-Nielsen L. Oxycodone: a review of its use in the management of pain.Current Med Res Opin. 2008; 24: 175-192Crossref PubMed Scopus (124) Google Scholar, 11Carli F. Charlebois P. Baldini G. Cachero O. Stein B. An integrated multidisciplinary approach to implementation of a fast-track program for laparoscopic colorectal surgery.Can J Anesth. 2009; 56: 837-842Crossref PubMed Scopus (71) Google Scholar, 13Sunshine A. Olson N.Z. Colon A. et al.Analgesic efficacy of controlled-release oxycodone in postoperative pain.J Clin Pharmacol. 1996; 36: 595-603Crossref PubMed Scopus (83) Google Scholar, 14Reuben S.S. Connelly N.R. Maciolek H. Postoperative analgesia with controlled-release oxycodone for outpatient anterior cruciate ligament surgery.Anesth Analg. 1999; 88 ([retracted]): 1286-1291PubMed Google Scholar, 15Cheville A. Chen A. Oster G. McGarry L. Narcessian E. A randomized trial of controlled-release oxycodone during inpatient rehabilitation following unilateral total knee arthroplasty.J Bone Jt Surg Am. 2001; 83: 572Crossref PubMed Scopus (36) Google Scholar, 16De Beer J. de V. Winemaker M.J. Donnelly G.A.E. et al.Efficacy and safety of controlled-release oxycodone and standard therapies for postoperative pain after knee or hip replacement.Can J Surg. 2005; 48: 277-283PubMed Google Scholar controlled-release oxycodone swiftly gained widespread credence as the safest, most effective, and most economic analgesic in the treatment of postoperative pain, and has become embedded as an integral part of enhanced recovery techniques and fast track surgery.12Tan M. Law L.S. Gan T.J. Optimizing pain management to facilitate enhanced recovery after surgery pathways.Can J Anesth. 2015; 62: 203-218Crossref PubMed Scopus (190) Google Scholar The first indication that there may be a problem with controlled-release oxycodone occurred as early as 2000 when the first reports of its use, misuse, and abuse began to appear in the US media and medical journals. The marketing techniques used by Purdue Pharma to promote OxyContin® have been extensively reviewed elsewhere, and it now recognised that Purdue Pharma misbranded OxyContin® and misled doctors and patients about the risk of addiction and potential for abuse of OxyContin®.10deShazo R.D. Johnson M. Eriator I. Rodenmeyer K. Backstories on the U.S. opioid epidemic good intentions gone bad, an industry gone rogue and watch dogs gone to sleep.Am J Med. 2018; 131: 595-601Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar To date, more than 600 000 deaths from opioid abuse have occurred in the USA with 180 000 more predicted by 2020. In 2015, 20.5 million US residents had substance use disorders and 2 million of these were addicted to prescription pain relievers. The US President's Council of Economic Advisers estimated that the opioid epidemic cost the US economy $504 billion in 2015. Opioids were involved in 42 249 deaths in 2016, the second successive year in which US life expectancy fell, and there were five times as many deaths from opioid overdose as in 1999.17Gostin L.O. Hodge J.G. Noe S.A. Reframing the Opioid Epidemic as a National Emergency.JAMA. 2017; 318: 1539-1540Crossref PubMed Scopus (162) Google Scholar Australia, Canada, and the UK also have a prescribed opioid epidemic, but on a smaller scale. About 5% of the UK population take regular opioids,18Farias J.C. Porter L. McManus S. et al.Prescribing patterns in dependence forming medicines.http://phrc.lshtm.ac.uk/papers/PHRC_014_Final_Report.pdfDate accessed: September 6, 2018Google Scholar and use in primary care is increasing in Scotland.19Torrance N. Mansoor R. Wang H. et al.Association of opioid prescribing practices with chronic pain and benzodiazepine co-prescription: a primary care data linkage study.Br J of Anaesth. 2018; 120: 1345-1355Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar Victoria, Australia saw opioid prescriptions increase by 78% between 2006 and 2014, and hospital-related opioid admissions increased by 7.8% in the same period.20Berecki-Gisolf J. Hassani-Mahmooei B. Clapperton A. McClure R. Prescription opioid dispensing and prescription opioid poisoning: population data from Victoria, Australia 2006 to 2013.Aust N Z J Public Health. 2017; 41: 85-91Crossref PubMed Scopus (36) Google Scholar After the USA, Canada has the highest consumption of opioid per capita, and the addition of controlled-release oxycodone to the drug formulary in Ontario in 2000 was associated with a five-fold increase in oxycodone-related mortality.21Dhalla I.A. Mamdani M.M. Sivilotti M.L. Kopp A. Qureshi O. Juurlink D.N. Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone.Can Med Assoc J. 2009; 181: 891-896Crossref PubMed Scopus (325) Google Scholar Opioid diversion and abuse occurred rapidly with the release of controlled-release oxycodone. The biphasic mechanism of absorption could be overcome by crushing and dissolving the tablets allowing the smoking, snorting, inhalation, or injection of the opioid. The addictive potential increases exponentially when opioids are administered via these routes as the rapid absorption produces a ‘high’. In 2010, Purdue Pharma reformulated OxyContin®, aiming to secure the biphasic absorption by altering the physiochemical properties of the extended-release mechanism.22Sessler N.E. Downing J.M. Kale H. Chilcoat H.D. Baumgartner T.F. Coplan P.M. Reductions in reported deaths following the introduction of extended-release oxycodone (OxyContin) with an abuse-deterrent formulation.Pharmacoepidemiol Drug Saf. 2014; : 1238-1246Google Scholar This reformulation did not overcome the other class intrinsic problems of controlled-release opioids in the management of acute pain, namely the inability to predict an individual patient's dose. This results in the dual requirement for both controlled- and immediate-release opioid preparations and consequently an increased risk of serious harm from postoperative opioid-induced respiratory depression.23Lee L.A. Caplan R.A. Stephens L.S. et al.Postoperative opioid-induced respiratory depression. A closed claims analysis.Anesthiology. 2015; 122: 659-665Crossref PubMed Scopus (294) Google Scholar Furthermore, the tapering and discontinuation of controlled-release opioid preparations is problematic, and thus the use of prescribed controlled-release opioid preparations is the single biggest risk factor for subsequent opioid dependence.24Shah A. Hayes C.J. Martin B.C. Characteristics of initial prescription episodes and likelihood of long-term opioid use-United States, 2006–2015.MMWR: Morb Mortal Wkly Rep. 2017; 66: 265-269Crossref PubMed Scopus (604) Google Scholar Between January 2010 and December 2012, there were 7433 patient safety incidents involving oral oxycodone medicines reported to the National Reporting and Learning System (NRLS) in the UK, with 801 (10.8%) of the incidents reporting actual harm to the patient.25Care quality commission Safer Use of Controlled Drugs. Preventing Harm From Oral Oxycodone Medicines.September 2014https://www.surreyandsussex.nhs.uk/wp-content/uploads/2013/04/CQC-Safer-use-of-Controlled-Drugs-Preventing-harm-from-Oral-Oxycodone-preparations.pdfDate accessed: September 6, 2018Google Scholar Subsequently, in 2014 NHS England's Care Quality Commission released a patient safety incident report on preventing harm from oral oxycodone medicines and recommended that ‘Oxycodone should only be used as a second-line strong opioid, if morphine is not suitable or cannot be tolerated’.25Care quality commission Safer Use of Controlled Drugs. Preventing Harm From Oral Oxycodone Medicines.September 2014https://www.surreyandsussex.nhs.uk/wp-content/uploads/2013/04/CQC-Safer-use-of-Controlled-Drugs-Preventing-harm-from-Oral-Oxycodone-preparations.pdfDate accessed: September 6, 2018Google Scholar However, this safety report was primarily aimed at reducing mis-selection of oxycodone products. Pedersen and colleagues26Pedersen L. Borchgrevink P.C. Riphagen I.I. Fredheim O.M. Long-or short-acting opioids for chronic non-malignant pain? A qualitative systematic review.Acta Anaesthesiol Scand. 2014; 58: 390-401Google Scholar in 2014 published a qualitative systematic review examining whether long-acting opioids in chronic non-malignant pain are superior to short-acting opioids in pain relief, physical function, sleep quality, quality of life, or adverse events. Although they identified 1851 publications, only six randomised trials fulfilled the criteria for evaluating efficacy and safety. They discovered that none of the studies demonstrated significantly better pain relief, significantly less consumption of rescue analgesia, improved quality of sleep, or improved physical function from the use of long-acting opioids. They concluded that contrary to many guidelines, there is no evidence supporting the superiority of long-acting over short-acting opioids in improving functional outcomes, reducing side-effects or reducing addiction. In 2012, the US FDA released a Risk Evaluation and Mitigation Strategy (REMS) on extended release opioid preparations. The REMS instructed opioid prescribers that modified-release opioid analgesics are ‘limited in use’ and are ‘not to be used in treating acute pain’.27FDA blueprint for prescriber education for extended-release and long-acting opioid analgesics. 2012https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/OpioidREMJuly2012.pdfDate accessed: September 6, 2018https://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM515636.pdfGoogle Scholar This REMS therefore acknowledged the existence of the prescribed opioid epidemic, and recognised that long-term opioid use often begins with treatment of acute pain and the need for healthcare providers to modify their prescribing habits. In 2013, the American Academy of Pain Medicine published eight principles for safe opioid prescribing, and the eighth recommendation was to ‘Avoid using long-acting opioid formulations for acute, postoperative or trauma related pain’.28Webster L. President’s message eight principles for safer opioid prescribing.Pain Med. 2013; 14 (Available from:): 959-961http://onlinelibrary.wiley.com/doi/10.1111/pme.12194/pdfGoogle Scholar In 2016, the American Pain Society in their guidelines on the management of postoperative pain stated ‘Long-acting oral opioids are generally not recommended or labelled for use in the immediate postoperative period’.29Chou R. Gordon D. de Leon-Casasola O. et al.Guidelines on the management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council.J Pain. 2016; 17: 131-157http://www.jpain.org/article/S1526-5900(15)00995-5/pdfAbstract Full Text Full Text PDF PubMed Scopus (1550) Google Scholar Furthermore in 2016 the US Centers for Disease Control and Prevention (CDC) released guidance stating ‘When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids’.30Dowell D. Tamara M.H. Chou R. CDC guideline for prescribing opioids for chronic pain – United States 2016.MMWR Recomm Rep. 2016; 65 (Available from:): 1-49https://www.cdc.gov/mmwr/volumes/65/rr/pdfs/rr6501e1.pdfCrossref PubMed Scopus (2030) Google Scholar In 2015, the ANZCA and its FPM released the fourth edition of the compendium of acute pain management, and having systematically reviewed the evidence concluded that ‘The use of controlled-release opioid preparations as the sole agents for the early management of acute pain is discouraged because of difficulties in short-term dose adjustments needed for titration’.31Schug S.A. Palmer G.M. Scott D.A. Halliwell R. Trinca J. APM:SE working group of the Australian and New Zealand College of anaesthetists and faculty of pain medicine.in: Acute pain management: scientific evidence. 4th ed. ANZCA & FPM, Melbourne2015https://fpm.anzca.edu.au/resources/publicationsGoogle Scholar Despite all these recommendations, use of controlled-release opioid preparations continued, as did the deaths of patients from opioid-induced ventilatory impairment (OIVI).23Lee L.A. Caplan R.A. Stephens L.S. et al.Postoperative opioid-induced respiratory depression. A closed claims analysis.Anesthiology. 2015; 122: 659-665Crossref PubMed Scopus (294) Google Scholar, 32Hattingh K. Macintyre P. Schug Stephan Craigie M. Hore P. Slow Release opioids-the need for a statement. ANZCA Bulletin, March 2018: 14-17http://www.anzca.edu.au/documents/anzca-bulletin-march-2018-web-version.pdfDate accessed: September 8, 2018Google Scholar The closed claims analysis into deaths and brain damage caused by postoperative opioid-induced respiratory depression highlighted the dangers of the simultaneous administration of multiple preparations of opioids.23Lee L.A. Caplan R.A. Stephens L.S. et al.Postoperative opioid-induced respiratory depression. A closed claims analysis.Anesthiology. 2015; 122: 659-665Crossref PubMed Scopus (294) Google Scholar Subsequently, in March 2018, ANZCA and its FPM released a joint position statement on the use of slow release opioid preparations in the treatment of acute pain: ‘Slow-release opioids are not recommended for use in the management of patients with acute pain’.33Australia and New Zealand College of Anaesthesia Position statement on the use of slow-release opioid preparations in the treatment of acute pain.http://www.anzca.edu.au/resources/endorsed-guidelines/position-statement-on-the-use-of-slow-release-opioDate accessed: August 5, 2018Google Scholar The evidence to support this statement is provided in the position statement. Sedation and respiratory depression are more common with the inappropriate use of controlled-release opioids. There is significant variation in opioid responsiveness between individuals making accurate dose prediction difficult. Acute pain intensity normally reduces rapidly over a few days, and so should opioid doses, and controlled-release preparations do not allow for this rapid tapering. There is also the acknowledgment and acceptance that the use of controlled-release opioids is the single most important risk factor and facilitator of subsequent prescribed opioid dependence.24Shah A. Hayes C.J. Martin B.C. Characteristics of initial prescription episodes and likelihood of long-term opioid use-United States, 2006–2015.MMWR: Morb Mortal Wkly Rep. 2017; 66: 265-269Crossref PubMed Scopus (604) Google Scholar In addition the position statement also makes recommendations based on the latest scientific evidence on acute postoperative pain management, including advocating when opioids are indicated, and if oral route is available titration of an age-based dose of immediate-release oral opioid is the most appropriate initial treatment; controlled-released opioids should only be used if the patient was previously established on controlled-released opioid or if the patient experiences a prolonged pain state. Furthermore, patients starting opioids perioperatively should receive a weaning and deprescribing plan that is the responsibility of the person who initiated the opioid prescription.33Australia and New Zealand College of Anaesthesia Position statement on the use of slow-release opioid preparations in the treatment of acute pain.http://www.anzca.edu.au/resources/endorsed-guidelines/position-statement-on-the-use-of-slow-release-opioDate accessed: August 5, 2018Google Scholar Thus Australia and New Zealand are aligned with the US position. It is important to note that none of the aforementioned US and antipodean organisations are suggesting that acute pain should not be appropriately treated,27FDA blueprint for prescriber education for extended-release and long-acting opioid analgesics. 2012https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/OpioidREMJuly2012.pdfDate accessed: September 6, 2018https://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM515636.pdfGoogle Scholar, 28Webster L. President’s message eight principles for safer opioid prescribing.Pain Med. 2013; 14 (Available from:): 959-961http://onlinelibrary.wiley.com/doi/10.1111/pme.12194/pdfGoogle Scholar, 29Chou R. Gordon D. de Leon-Casasola O. et al.Guidelines on the management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council.J Pain. 2016; 17: 131-157http://www.jpain.org/article/S1526-5900(15)00995-5/pdfAbstract Full Text Full Text PDF PubMed Scopus (1550) Google Scholar, 30Dowell D. Tamara M.H. Chou R. CDC guideline for prescribing opioids for chronic pain – United States 2016.MMWR Recomm Rep. 2016; 65 (Available from:): 1-49https://www.cdc.gov/mmwr/volumes/65/rr/pdfs/rr6501e1.pdfCrossref PubMed Scopus (2030) Google Scholar, 31Schug S.A. Palmer G.M. Scott D.A. Halliwell R. Trinca J. APM:SE working group of the Australian and New Zealand College of anaesthetists and faculty of pain medicine.in: Acute pain management: scientific evidence. 4th ed. ANZCA & FPM, Melbourne2015https://fpm.anzca.edu.au/resources/publicationsGoogle Scholar, 32Hattingh K. Macintyre P. Schug Stephan Craigie M. Hore P. Slow Release opioids-the need for a statement. ANZCA Bulletin, March 2018: 14-17http://www.anzca.edu.au/documents/anzca-bulletin-march-2018-web-version.pdfDate accessed: September 8, 2018Google Scholar, 33Australia and New Zealand College of Anaesthesia Position statement on the use of slow-release opioid preparations in the treatment of acute pain.http://www.anzca.edu.au/resources/endorsed-guidelines/position-statement-on-the-use-of-slow-release-opioDate accessed: August 5, 2018Google Scholar or that we should disregard the considerable body of evidence that demonstrates that inadequately treated acute pain inhibits functional return, predisposes to chronic pain states or is unhumanitarian.29Chou R. Gordon D. de Leon-Casasola O. et al.Guidelines on the management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council.J Pain. 2016; 17: 131-157http://www.jpain.org/article/S1526-5900(15)00995-5/pdfAbstract Full Text Full Text PDF PubMed Scopus (1550) Google Scholar, 31Schug S.A. Palmer G.M. Scott D.A. Halliwell R. Trinca J. APM:SE working group of the Australian and New Zealand College of anaesthetists and faculty of pain medicine.in: Acute pain management: scientific evidence. 4th ed. ANZCA & FPM, Melbourne2015https://fpm.anzca.edu.au/resources/publicationsGoogle Scholar These organisations recommend that where indicated, acute pain is treated with immediate-release opioids rather than controlled-release opioids, as immediate-release preparations reduce the potential for harm. Furthermore, the need for effective opioid stewardship is recognised even with immediate-release preparations.28Webster L. President’s message eight principles for safer opioid prescribing.Pain Med. 2013; 14 (Available from:): 959-961http://onlinelibrary.wiley.com/doi/10.1111/pme.12194/pdfGoogle Scholar, 29Chou R. Gordon D. de Leon-Casasola O. et al.Guidelines on the management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council.J Pain. 2016; 17: 131-157http://www.jpain.org/article/S1526-5900(15)00995-5/pdfAbstract Full Text Full Text PDF PubMed Scopus (1550) Google Scholar, 30Dowell D. Tamara M.H. Chou R. CDC guideline for prescribing opioids for chronic pain – United States 2016.MMWR Recomm Rep. 2016; 65 (Available from:): 1-49https://www.cdc.gov/mmwr/volumes/65/rr/pdfs/rr6501e1.pdfCrossref PubMed Scopus (2030) Google Scholar, 31Schug S.A. Palmer G.M. Scott D.A. Halliwell R. Trinca J. APM:SE working group of the Australian and New Zealand College of anaesthetists and faculty of pain medicine.in: Acute pain management: scientific evidence. 4th ed. ANZCA & FPM, Melbourne2015https://fpm.anzca.edu.au/resources/publicationsGoogle Scholar The ANZCA/FPM's position statement and review of the evidence, when considered alongside modern anaesthetic and surgical techniques, finally allows for the previous concerns about the routine use of immediate-release oral opioids to be assuaged. The goal of modern anaesthesia is to promote early drinking, eating, and mobilising (DrEaMing),34Levy N. Mills P. Mythen M. Is the pursuit of DREAMing (drinking, eating and mobilising) the ultimate goal of anaesthesia?.Anaesthesia. 2016; 71: 1008-1012Crossref PubMed Scopus (36) Google Scholar with restoration of baseline function and all unnecessary medication deprescribed.35Levy N. Sturgess J. Mills P. “Pain as the fifth vital sign” and dependence on the “numerical pain scale” is being abandoned in the US: Why?.Br J Anaesth. 2018; 120: 435-438Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar This is achieved through the use of shared decision making, along with functional pain scores to establish realistic expectations and goals; procedure-specific analgesic techniques; multimodal analgesia; and the titration and subsequent tapering of immediate-release opioids.28Webster L. President’s message eight principles for safer opioid prescribing.Pain Med. 2013; 14 (Available from:): 959-961http://onlinelibrary.wiley.com/doi/10.1111/pme.12194/pdfGoogle Scholar, 29Chou R. Gordon D. de Leon-Casasola O. et al.Guidelines on the management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council.J Pain. 2016; 17: 131-157http://www.jpain.org/article/S1526-5900(15)00995-5/pdfAbstract Full Text Full Text PDF PubMed Scopus (1550) Google Scholar, 30Dowell D. Tamara M.H. Chou R. CDC guideline for prescribing opioids for chronic pain – United States 2016.MMWR Recomm Rep. 2016; 65 (Available from:): 1-49https://www.cdc.gov/mmwr/volumes/65/rr/pdfs/rr6501e1.pdfCrossref PubMed Scopus (2030) Google Scholar, 31Schug S.A. Palmer G.M. Scott D.A. Halliwell R. Trinca J. APM:SE working group of the Australian and New Zealand College of anaesthetists and faculty of pain medicine.in: Acute pain management: scientific evidence. 4th ed. ANZCA & FPM, Melbourne2015https://fpm.anzca.edu.au/resources/publicationsGoogle Scholar, 32Hattingh K. Macintyre P. Schug Stephan Craigie M. Hore P. Slow Release opioids-the need for a statement. ANZCA Bulletin, March 2018: 14-17http://www.anzca.edu.au/documents/anzca-bulletin-march-2018-web-version.pdfDate accessed: September 8, 2018Google Scholar, 33Australia and New Zealand College of Anaesthesia Position statement on the use of slow-release opioid preparations in the treatment of acute pain.http://www.anzca.edu.au/resources/endorsed-guidelines/position-statement-on-the-use-of-slow-release-opioDate accessed: August 5, 2018Google Scholar, 34Levy N. Mills P. Mythen M. Is the pursuit of DREAMing (drinking, eating and mobilising) the ultimate goal of anaesthesia?.Anaesthesia. 2016; 71: 1008-1012Crossref PubMed Scopus (36) Google Scholar, 35Levy N. Sturgess J. Mills P. “Pain as the fifth vital sign” and dependence on the “numerical pain scale” is being abandoned in the US: Why?.Br J Anaesth. 2018; 120: 435-438Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar As controlled-release opioid preparations have no benefit and are harmful, there is no longer a routine role for them in contemporary anaesthetic practice. Note: The term ‘controlled-release’ is used in this commentary and covers all opioid medications that may be referred to as slow-release, sustained-release, extended-release, modified-release, and long-acting. In the ANZCA/FPM's position statement, the term ‘slow-release’ also refers to transdermal opioid patches and methadone. The authors worked together to draft, produce, approve, and make subsequent revisions to the manuscript. The authors declare that they have no conflicts of interest. The good, the bad, and the ugly: the many faces of opioidsBritish Journal of AnaesthesiaVol. 122Issue 6PreviewOpium, an extract of the poppy Papaver somniferum, has been used for centuries for the alleviation of pain and suffering. This beneficial effect, as with most medications, is offset by a number of serious side-effects including respiratory depression, constipation, tolerance, and dependence.1 Tolerance and dependence unmask a darker side to opioids that has fuelled two historic opium wars in China, the current worldwide opioid ‘epidemic’, and a general vilification of the opioid drug class. This issue of British Journal of Anaesthesia includes a special section after a call for papers on this subject. Full-Text PDF Open Archive