Portal de Periódicos da CAPES

Opioid-free anaesthesia

2019; Lippincott Williams & Wilkins; Volume: 36; Issue: 4 Linguagem: Inglês

10.1097/eja.0000000000000966

1365-2346

Patricia Lavand’homme,

Anesthesia and Sedative Agents

This Editorial is part of a Pro and Con debate and is accompanied by the following articles: Veyckemans F. Opioid-free anaesthesia. Still a debate? Eur J Anaesthesiol 2019; 36:245–246. Lirk P, Rathmell JP. Opioid-free anaesthesia. Con: it is too early to adopt opioid-free anaesthesia today. Eur J Anaesthesiol 2019; 36:250–254. A few years ago, a letter addressed to a medical journal was entitled 'Why doctors prescribe opioids to known opioid abusers?' questioning the well known abuse and diverted use of these medications among patients.1 Today, the 'US-opioid crisis' has confirmed earlier fears and moreover, has questioned the role of healthcare providers, including anaesthetists, in that disastrous situation. The morbidity and mortality associated with opioid medications has recently prompted the Centre for Disease Control and the Food and Drug Administration to provide new directives for opioids use for example reinforcing evidence-based approaches to treat pain in a manner that spares the use of opioids.2 However, in reality opioids too often 'remain the most comfortable choice of healthcare providers', including during the peri-operative period.3 The development of synthetic opioids like 'fentanyl' has revolutionised anaesthesia practice by allowing safer management of fragile patients. Later, even more potent synthetic opioids and also ultrashort lasting compounds have gained the favour of anaesthesiologists to promote easily controlled and stress-free 'opioid-based anaesthesia' (OBA).4 Although 20 years ago, Paul Janssens, the inventor of most synthetic opioids, warned against the risk of respiratory depression and other unknown adverse effects,4 it took several years to finally find out that opioids may slow patients' recovery and even may induce long-lasting pronociceptive effects that is opioid-induced hyperalgesia.5 These observations have prompted the development of 'balanced anaesthesia' where a combination of opioid and nonopioid analgesics are used to improve surgical outcome.6 Simultaneously, the interest for peri-operative analgesic adjuvants like ketamine, clonidine, lidocaine, magnesium sulphate or dexamethasone, among others, has increased, with reports of their beneficial analgesic and antihyperalgesic properties which extended into the postoperative period (Fig. 1).7Fig. 1: Evolution of opioid use in peri-operative medicine. OBA, opioid-based anaesthesia; OFA&A, opioid-free anaesthesia & analgesia; OFA, opioid-free anaesthesia. Adapted from.4We will discuss opioid-free anaesthesia (OFA) – not yet 'opioid-free anaesthesia & analgesia' which involves the total peri-operative period and still is a goal that remains difficult to achieve. We argue here that OFA is a new paradigm, by opposition to the old OBA dogma, and as an important step to a more rational use of peri-operative opioids. The concept of OFA perfectly fits with the hypothesis of Suzan et al.8 who, in a topical review, stated that the timing of administration crucially separates beneficial and counterproductive effects of opioids on postoperative pain. Why do (we think that) we need intra-operative opioids? Intra-operative opioids achieve haemodynamic stability. They block the sympathetic reaction to surgical injury while maintaining blood pressure and heart rate. Currently, we administer very specific drugs to blunt the sympathetic reaction to the surgical stress. Among these drugs which modulate the sympathetic nervous system, α2-adrenergic agonists (clonidine, dexmedetomidine) provide postoperative opioid-sparing and analgesic effects.7 More significantly, β-receptor antagonists (e.g. esmolol), which do not possess analgesic properties per se, reduce intra-operative and postoperative opioid consumption (without changes in postoperative pain scores) when they are used intra-operatively to treat the acute haemodynamic reaction to surgical stress.9 Intra-operative opioids are mandatory to control intra-operative pain. By definition, pain is an 'unpleasant sensory and emotional experience…', in other words, pain is a subjective phenomenon.10 Under anaesthesia, as under other conditions where a patient is unconscious (e.g. in a coma state), the term 'pain' should not be used and should be replaced by 'nociception' which relates to the neural processes of encoding and processing noxious stimuli. Consequently, are opioids the best drugs to control intra-operative nociception? We are here facing two problems which are key questions regarding OFA. It is well established that nociceptive inputs reaching the central nervous system trigger central sensitisation which in turn participate in acute and persistent postoperative pain. However, we currently lack accurate and validated monitoring to measure intra-operative nociception.11,12 Instead, the sympathetic/parasympathetic balance is generally used to address the adequacy of intra-operative antinociception control. Second, endogenous nociceptive pathways involve many transmitters and there is no reason to achieve antinociception only by interfering with enkephalins by using only opioids.12 What could be the benefits of opioid-free anaesthesia for peri-operative patients? There is now sufficient evidence to question the fact that intra-operative opioids contribute to improved postoperative outcomes in terms of analgesia and recovery.6 Common adverse effects related to intra-operative opioid administration are well known. Among them, intrinsic activation of specific pronociceptive processes such as opioid-induced hyperalgesia which may lead to an exaggeration of surgical injury-induced hyperalgesia, increasing postoperative pain and perhaps underlying the development of persistent pain in some patients.5 OFA may affect patients' recovery in two ways. First, by lessening a patient's exposure to opioids, OFA will decrease the risk of common opioid-related adverse effects like sedation, respiratory depression, nausea and vomiting in the immediate postoperative period. OFA will also allow sparing of the μ-receptors for early postoperative analgesia by preventing the occurrence of an acute tolerance phenomenon.2 Second, the more liberal utilisation of intra-operative 'adjuvants' during OFA may contribute to enhance recovery in relation to the specific analgesic and antihyperalgesic properties of these drugs.7 Such benefits have already been highlighted in chronic pain and opioid dependent patients. A more widespread use of nonopioid analgesics might reduce the risk of long-term opioid dependency. On the contrary, to date, OFA use during enhanced recovery after surgery does not correlate with less opioid prescriptions at hospital discharge13 or patients' 24-h predischarge opioid use.14 These observations really argue for better education of healthcare providers about opioid prescribing. What are future challenges of opioid-free anaesthesia? Today, OFA is feasible and safe. Small studies and case reports are showing smooth and rapid awakening with less pain. However, there is an urgent need for larger, well conducted clinical trials which focus on both immediate and delayed benefits after surgery. There is also a need for more research on outcome differences between opioid-low and zero-opioid (i.e. OFA) anaesthesia.4 Further, the choice of adjuvants used for OFA also deserves further study: should this choice be 'procedure-specific' or rather be 'patient-specific'? The trend in peri-operative management is currently in favour of individualised treatments based on endogenous processing of nociceptive inputs, but objective guidelines are still missing.15 Indirectly, this raises questions as to the identification of patients who will or will not benefit from OFA.4 The use of OFA in patients with comorbidities like obesity, obstructive sleep apnoea syndrome or opioid dependence seems logical. In contrast, contraindications for the use of OFA are less clear. Finally, there is an urgent need to develop reliable tools to monitor intra-operative nociception under both OBA and OFA conditions.12 In conclusion, OFA is certainly more than 'the dream of some opioid-phobic doctors'. It stands as a new paradigm and invites anaesthetists and healthcare providers to reflect on current practice. Future OFA challenges include an objective documentation of both short-term and long-term benefits using large databases, the development of accurate monitoring to assess intra-operative nociception, as well as the implementation of surgery-specific and patient-specific protocols that should allow for a rational use of nonopioid adjuvants. Acknowledgements relating to this article Assistance with the Editorial: none. Financial support and sponsorship: none. Conflicts of interest: none. Comment from the Editor: this article is based on the lecture 'Opioid-Free Anaesthesia: PRO', delivered by PLdH at the 2018 Euroanaesthesia Congress, Copenhagen, Denmark. PLdH is an Associate Editor of the European Journal of Anaesthesiology. This Editorial was checked by the editors but was not sent for external peer review.