Eur J Anaesthesiol 2019; 36:247–249
EDITORIAL
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
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 anaesthe-
sia 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 situ-
ation. The morbidity and mortality associated with opioid
medications has recently prompted the Centre for Dis-
ease Control and the Food and Drug Administration to
provide new directives for opioids use for example rein-
forcing 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 anaesthe-
sia’ (OBA).4 Although 20 years ago, Paul Janssens, the
inventor of most synthetic opioids, warned against the
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,
Belgium
E-mail: patricia.lavandhomme@uclouvain.be
0265-0215 Copyright ß 2019 European Society of Anaesthesiology. All rights reserved.
Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
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 combi-
nation 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 dexametha-
sone, among others, has increased, with reports of their
beneficial analgesic and antihyperalgesic properties
which extended into the postoperative period (Fig. 1).7
We 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 ben-
eficial 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. Cur-
rently, we administer very specific drugs to blunt the
sympathetic reaction to the surgical stress. Among these
drugs which modulate the sympathetic nervous system,
a2-adrenergic agonists (clonidine, dexmedetomidine)
provide postoperative opioid-sparing and analgesic
effects.7 More significantly, b-receptor antagonists (e.g.
esmolol), which do not possess analgesic properties per se,
DOI:10.1097/EJA.0000000000000966
 248 Lavand’homme

Fig. 1

• beginning with ether administration in 1847

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

• 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
OFA

• 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
anaesthesia for peri-operative patients?
There is now sufficient evidence to question the fact that
intra-operative opioids contribute to improved postoper-
ative outcomes in terms of analgesia and recovery.6
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,

Eur J Anaesthesiol 2019; 36:247–249

Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.

well conducted clinical trials which focus on both imme-
diate 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 Fur-
ther, 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-opera-
tive management is currently in favour of individualised
treatments based on endogenous processing of nocicep-
tive 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 nocicep-
tion 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 devel-
opment 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
Eur J Anaesthesiol 2019; 36:247–249
Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
Opioid-free anaesthesia 249
Associate Editor of the European Journal of Anaesthesiology. This
Editorial was checked by the editors but was not sent for external
peer review.
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