Opioids caught in the crosshairs: Towards smarter and safer use of opioids in daily clinical practice

It is nearly 50 years since the first edition of Anaesthesia and Intensive Care was published by the Australian Society of Anaesthetists (ASA) in August 1972. The first editor, Dr Benedict Barry, ASA Honorary Federal Secretary, envisioned the journal would ‘… provide a forum where new trends in Australian practice and research are presented. Typically Australian techniques, philosophies, clinical problems and researches will be communicated within the Asian-Australasian region, to foster greater exchange of ideas and personnel.’ ¹

Barry noted that there had been nine textbooks on the subject of anaesthesia published in English between 1929 and 1933. Thirty years later, similar publications had mushroomed to 93, and he noted that the growth in the world anaesthesia literature at that time was estimated at over 4000 articles annually. He posited that this was a ‘burden [for] every anaesthetist who is striving to keep abreast with modern trends …’. ¹

Fifty years on, besides championing Australian clinical practice and research, this special edition aims to put into action the inaugural editor’s plan for the journal’s content to include ‘review articles [that] will provide for busy anaesthetists a quick reference on important subjects.’ ¹

This issue celebrates the 50th volume of Anaesthesia and Intensive Care with a collection of articles about what could be considered one of the most pressing issues in contemporary medical practice in Australia and New Zealand, prescription opioids.

Along with several other developed countries, Australia and New Zealand, to a lesser extent, are facing two intimately related major public health issues: poorly managed pain and problematic opioid use causing the unintentional deaths of more than three Australians a day and three New Zealanders per month as well as a wider range of personal and societal harms.^2,3 The realisation some years ago that prescription opioids were major contributors to these harms raised alarms across many community sectors from governments to regulators, healthcare service providers to patients, their families and carers, and society at large.^{2,4 –7}

In response, opioid regulatory changes,^7,8 revised recommendations from medical colleges^{9 –12} and wide media coverage have raised awareness of the risk of harm, including dependence and substance use disorders.^13,14 Medical practitioners have been placed squarely in the centre of the conversation both as prescribers of opioids and the health professionals most expected to help manage all types of pain.

Conversations about opioids have waxed and waned over the centuries as prevailing societal attitudes have swung from excessive fear of harms to enthusiastic embrace. History has been repeated perhaps more quickly than usual in the past three decades. As opioid prescribing increased in the 1990s for acute pain management and pain in palliative care, the proposition that ‘pain relief is a basic human right’ was promulgated, fuelling an attitudinal change for people living with chronic non-cancer pain (CNCP), which was interpreted as having an equal right to receive opioids as well.^15,16 In fact, treating CNCP with opioids was deemed a moral imperative, and it was even proposed that medical practitioners who declined to prescribe should be prosecuted. ¹⁷ As a result, the conversation about opioids changed from relatively negative to positive. However, as the toll of harms from more liberal prescribing became apparent, the conversation turned around. As societal attitudes have changed again, so has the language of opioids and pain. In his review in this issue, Sussex explains the importance of language in developing community values and attitudes. ¹⁸ By applying a linguistics lens to the language found in standard English papers and online dictionaries and large text databases, including web-accessible journalism, Sussex skilfully demonstrates how terms that were once solely within the realm of the medical profession have become common parlance and undergone pejoration, imperceptibly changing our judgements towards people who take opioids and live with pain, particularly CNCP.

In retrospect, the confluence of doctors’ best intentions to manage pain optimally, technological advances in the pharmaceutical industry presenting them with new enticing but unfamiliar slow-release (SR) opioid formulations, and aggressive marketing strategies led to the perfect storm, the so-called ‘opioid epidemic’. ¹⁹ The many tragic consequences are now being played out in communities across the USA, including courtrooms.^20,21 Reflections on this recent history with salutary lessons for patient care now and into the future are offered in the review by Macintyre in this issue. ²²

However, this is not the first opioid epidemic nor the first time aggressive marketing to physicians of attractive opioid products of uncertain benefit has occurred. Glossy advertising materials promoting products, often unknowingly containing opium, direct to physicians, claiming to treat a wide range of conditions is recorded from the early 19th century in the USA. ²³ Aided by the isolation of morphine and the development of the hypodermic syringe and synthetic opioids, use became epidemic in proportion in the 1870s, ultimately leading to various approaches to control the emerging social disaster. In the cover note of this issue, Ball and Featherstone outline the interesting history of one of those approaches, the search for non-addictive opioids, in particular, the development of methadone and buprenorphine, forcibly using prison inmates as research subjects. ²⁴

Pattullo’s article in this issue looks back on another well-intended but ultimately disastrous attempt to influence clinical practice, the designation of pain as the ‘fifth vital sign’. ²⁵ It became an additional driver of excessive opioid prescribing in what became a unimodal response to a unidimensional assessment of pain relying on numerical rating scales. Pattullo offers a more nuanced approach to prescribing opioids in the acute pain setting for both opioid-naive and opioid-dependent patients. ²⁵ However, prescribing is only one aspect of a systemic problem, extending from within acute care hospitals out into communities everywhere.

Although awareness of the risks of taking opioids long term has risen considerably over the past decade, up to 10% of people legitimately prescribed an opioid in hospital postoperative care settings are at increased risk of continued use, frequently regardless of the type of surgery.^{26 –29} An estimated 13,000 Australians are likely to become opioid dependent annually following elective surgery alone. ²⁷ Anaesthetists and pain medicine physicians have played a role in addressing this problem, trying various strategies such as hospital-based academic detailing with junior doctor education, ³⁰ and opioid-free anaesthesia. ³¹ Opioid stewardship programmes have emerged as another method of reducing opioids on hospital discharge. Several programmes have been trialled with limited success, indicative of the complexity of the problem.^{29,32 –34} Despite the lack of proven approaches, opioid stewardship is still considered a valuable adjunct to prescriber and consumer education.^22,35

While strategies to improve the transitional care arrangements for people discharged from hospital acute care on opioids remain to be optimised, in-hospital care has also been under scrutiny. In response to concerns about the increasing use and consequent harms from SR opioids in acute postoperative pain management, the Australian and New Zealand College of Anaesthetists (ANZCA) issued a position statement urging caution when prescribing these formulations, especially for opioid-naive patients. ³⁶ Despite use in acute pain being explicitly recommended against in the product information of several common SR opioid products,^{37 –39} it had become common practice in some surgical settings. A number of anaesthetists raised concerns about the evidence base for the ANZCA statement. ⁴⁰ However, early in 2021, an international multidisciplinary consortium published a comparable statement listing ten strategies aimed at preventing opioid-related harms in adult surgical patients. ⁴¹ Stevens and Findlay highlight the gaps between the theory underpinning these recommendations and current clinical practice in their opinion piece in this issue, ³⁵ proposing a range of practical options for closing those gaps that are well within the skills and resources of most anaesthetists and other hospital doctors.

Despite two decades of warning, ⁴² opioid-induced ventilatory impairment remains problematic, still causing unexpected serious harms in the acute care setting. The complex mechanisms involving multiple brain and airway sites and the impact of exogenous opioid administration on them to create the conditions for opioid-induced ventilatory impairment are outlined in a second review in this issue by Pattullo. ⁴³ This review provides explanations for the failure of supplemental oxygen and current bedside monitoring strategies to prevent all unanticipated deaths, ending with a consideration of implications for the future.

Some groups of patients are easily left out of conversations about opioids. Recognising that pain is multidimensional, influenced by the context and meaning of this episode of pain for the individual and their carers, along with many other factors, can inform a more considered ‘whole-person’ approach to pain management, especially for those whose voices may not be heard. ⁴⁴ One review in this issue by Rosen and colleagues addresses the place of opioids in contemporary pain management for children and adolescents ⁴⁵ and another by Moran et al. reviews opioid use in the complex environments experienced by the seriously ill in intensive care settings, especially those who are heavily sedated. ⁴⁶ Perhaps the most challenging group to interact with and manage well, those with opioid use disorder, are the subject of the review by Murnion and Demirkol in this issue. ⁴⁷

Finally, understanding opioid pharmacology is fundamental to safe opioid prescribing. Somogyi et al. explain in their review in this issue that differences matter when considering current and emerging opioids, especially now genetic polymorphisms affecting receptor structure and expression and drug metabolism are better known. ⁴⁸ Their insights offer hope that newer classes of drugs relying less on mu opioid receptor activation alone and more on multiple sites of action will enable us to manage pain better and keep our patients safe using personalised pain management plans.

Not surprisingly, opioids alone were never going to be the panacea for all pain needs; however, they will continue to be important medicines for managing acute pain well into the future. ⁴⁹ The question for anaesthetists, intensive care physicians and other opioid prescribers in 2022 is whether we can stay abreast of emerging understandings of the dynamic interplay between opioids and human experiences of pain, and be smarter and safer when using opioids in our daily clinical practice.

By offering this themed edition, Anaesthesia and Intensive Care carries on one of Ben Barry’s original intentions that ‘This journal will be a catalyst to development, and as a consequence the quality and standard of clinical practice, teaching and training will benefit.’ ¹