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Eur J Anaesthesiol 2019; 36:247–249


Opioid-free anaesthesia
Pro: damned if you don’t use opioids during surgery
Patricia Lavand’homme
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European Journal of Anaesthesiology 2019, 36:247–249 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
This Editorial is part of a Pro and Con debate and is long-lasting pronociceptive effects that is opioid-induced
accompanied by the following articles: hyperalgesia.5 These observations have prompted the
 Veyckemans F. Opioid-free anaesthesia. Still a development of ‘balanced anaesthesia’ where a combi-
debate? Eur J Anaesthesiol 2019; 36:245–246. nation of opioid and nonopioid analgesics are used to
 Lirk P, Rathmell JP. Opioid-free anaesthesia. improve surgical outcome.6 Simultaneously, the interest
Con: it is too early to adopt opioid-free anaesthe- for peri-operative analgesic adjuvants like ketamine,
sia today. Eur J Anaesthesiol 2019; 36:250–254. clonidine, lidocaine, magnesium sulphate or dexametha-
sone, among others, has increased, with reports of their
beneficial analgesic and antihyperalgesic properties
which extended into the postoperative period (Fig. 1).7
A few years ago, a letter addressed to a medical journal We will discuss opioid-free anaesthesia (OFA) – not yet
was entitled ‘Why doctors prescribe opioids to known ‘opioid-free anaesthesia & analgesia’ which involves the
opioid abusers?’ questioning the well known abuse and total peri-operative period and still is a goal that remains
diverted use of these medications among patients.1 difficult to achieve. We argue here that OFA is a new
Today, the ‘US-opioid crisis’ has confirmed earlier fears paradigm, by opposition to the old OBA dogma, and as an
and moreover, has questioned the role of healthcare important step to a more rational use of peri-operative
providers, including anaesthetists, in that disastrous situ- opioids. The concept of OFA perfectly fits with the
ation. The morbidity and mortality associated with opioid hypothesis of Suzan et al.8 who, in a topical review, stated
medications has recently prompted the Centre for Dis- that the timing of administration crucially separates ben-
ease Control and the Food and Drug Administration to eficial and counterproductive effects of opioids on
provide new directives for opioids use for example rein- postoperative pain.
forcing evidence-based approaches to treat pain in a
manner that spares the use of opioids.2 However, in
Why do (we think that) we need intra-
reality opioids too often ‘remain the most comfortable
operative opioids?
choice of healthcare providers’, including during the peri-
Intra-operative opioids achieve haemodynamic stability.
operative period.3
They block the sympathetic reaction to surgical injury
The development of synthetic opioids like ‘fentanyl’ has while maintaining blood pressure and heart rate. Cur-
revolutionised anaesthesia practice by allowing safer rently, we administer very specific drugs to blunt the
management of fragile patients. Later, even more potent sympathetic reaction to the surgical stress. Among these
synthetic opioids and also ultrashort lasting compounds drugs which modulate the sympathetic nervous system,
have gained the favour of anaesthesiologists to promote a2-adrenergic agonists (clonidine, dexmedetomidine)
easily controlled and stress-free ‘opioid-based anaesthe- provide postoperative opioid-sparing and analgesic
sia’ (OBA).4 Although 20 years ago, Paul Janssens, the effects.7 More significantly, b-receptor antagonists (e.g.
inventor of most synthetic opioids, warned against the esmolol), which do not possess analgesic properties per se,

From the Department of Anaesthesiology and Postoperative Pain Service, University Catholic of Louvain, Brussels, Belgium
Correspondence to Patricia Lavand’homme, MD, PhD, Department of Anaesthesiology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Brussels,

0265-0215 Copyright ß 2019 European Society of Anaesthesiology. All rights reserved. DOI:10.1097/EJA.0000000000000966

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.

248 Lavand’homme

Fig. 1

• beginning with ether administration in 1847

Inhalation • shift to "balanced general anesthesia" in 1946 with use of d-tubocurarine

• improvement of "balanced general anesthesia" with development of potent

synthetic opioids (e.g. fentanyl in 1962)
OBA • shift to "opioid low anesthesia" i.e. optimal balanced general anesthesia

• feasibility and safety of no intraoperative opioids

• opioid analgesics kept as rescue for postoperative analgesia

• the next (ultimate) step ?

OFA&A • feasibility and safety ?

From Mulier & De Kock4. Opioid free general anesthesia, a new paradigm?

Evolution of opioid use in peri-operative medicine. OBA, opioid-based anaesthesia; OFA&A, opioid-free anaesthesia & analgesia; OFA, opioid-free
anaesthesia. Adapted from.4

reduce intra-operative and postoperative opioid con- Common adverse effects related to intra-operative opioid
sumption (without changes in postoperative pain scores) administration are well known. Among them, intrinsic
when they are used intra-operatively to treat the acute activation of specific pronociceptive processes such as
haemodynamic reaction to surgical stress.9 opioid-induced hyperalgesia which may lead to an exag-
geration of surgical injury-induced hyperalgesia, increas-
Intra-operative opioids are mandatory to control intra-
ing postoperative pain and perhaps underlying the
operative pain. By definition, pain is an ‘unpleasant
development of persistent pain in some patients.5 OFA
sensory and emotional experience. . .’, in other words,
may affect patients’ recovery in two ways. First, by less-
pain is a subjective phenomenon.10 Under anaesthesia, as
ening a patient’s exposure to opioids, OFA will decrease
under other conditions where a patient is unconscious
the risk of common opioid-related adverse effects like
(e.g. in a coma state), the term ‘pain’ should not be used
sedation, respiratory depression, nausea and vomiting in
and should be replaced by ‘nociception’ which relates to
the immediate postoperative period. OFA will also allow
the neural processes of encoding and processing noxious
sparing of the m-receptors for early postoperative analgesia
stimuli. Consequently, are opioids the best drugs to
by preventing the occurrence of an acute tolerance phe-
control intra-operative nociception? We are here facing
nomenon.2 Second, the more liberal utilisation of intra-
two problems which are key questions regarding OFA. It
operative ‘adjuvants’ during OFA may contribute to
is well established that nociceptive inputs reaching the
enhance recovery in relation to the specific analgesic
central nervous system trigger central sensitisation which
and antihyperalgesic properties of these drugs.7 Such
in turn participate in acute and persistent postoperative
benefits have already been highlighted in chronic pain
pain. However, we currently lack accurate and validated
and opioid dependent patients. A more widespread use of
monitoring to measure intra-operative nociception.11,12
nonopioid analgesics might reduce the risk of long-term
Instead, the sympathetic/parasympathetic balance is gen-
opioid dependency. On the contrary, to date, OFA use
erally used to address the adequacy of intra-operative
during enhanced recovery after surgery does not correlate
antinociception control. Second, endogenous nociceptive
with less opioid prescriptions at hospital discharge13 or
pathways involve many transmitters and there is no
patients’ 24-h predischarge opioid use.14 These observa-
reason to achieve antinociception only by interfering
tions really argue for better education of healthcare pro-
with enkephalins by using only opioids.12
viders about opioid prescribing.

What could be the benefits of opioid-free What are future challenges of opioid-free
anaesthesia for peri-operative patients? anaesthesia?
There is now sufficient evidence to question the fact that Today, OFA is feasible and safe. Small studies and case
intra-operative opioids contribute to improved postoper- reports are showing smooth and rapid awakening with
ative outcomes in terms of analgesia and recovery.6 less pain. However, there is an urgent need for larger,

Eur J Anaesthesiol 2019; 36:247–249

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
Opioid-free anaesthesia 249

well conducted clinical trials which focus on both imme- Associate Editor of the European Journal of Anaesthesiology. This
diate and delayed benefits after surgery. There is also a Editorial was checked by the editors but was not sent for external
need for more research on outcome differences between peer review.
opioid-low and zero-opioid (i.e. OFA) anaesthesia.4 Fur-
ther, the choice of adjuvants used for OFA also deserves
further study: should this choice be ‘procedure-specific’ References
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Comment from the Editor: this article is based on the lecture 15 Brummett CM, Clauw DJ. Flipping the paradigm: from surgery-specific to
‘Opioid-Free Anaesthesia: PRO’, delivered by PLdH at the 2018 patient-driven perioperative analgesic algorithms. Anesthesiology 2015;
Euroanaesthesia Congress, Copenhagen, Denmark. PLdH is an 122:731–733.

Eur J Anaesthesiol 2019; 36:247–249

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.