Eur J Anaesthesiol 2015; 32:517520
EDITORIAL
The current place of nitrous oxide in clinical practice
An expert opinion-based task force consensus statement of the
European Society of Anaesthesiology
The European Society of Anaesthesiology task force on the use of nitrous oxide in clinical
anaesthetic practiceM
European Journal of Anaesthesiology 2015, 32:517520
Published online 20 May 2015
Introduction
Nitrous oxide (N2O) has been used for years as an
essential part of general anaesthesia. During the past
few decades, however, its use in general anaesthesia
has steadily declined. Parallel to this evolution, we wit-
ness a growing interest in the use of N2O by nonanaesthe-
siologists, mainly as a sedative and adjuvant for pain
therapy during procedural interventions.14 In line with
this paradigm shift, heated debates, frequently blurred by
strong emotional viewpoints, are questioning the current
place of N2O during anaesthesia and during procedural
sedation.5
In an attempt to search for up-to-date answers to these
issues, the European Society of Anaesthesiology (ESA)
convened a number of clinical experts to debate specifi-
cally on the following questions.
(1) What is the place of N2O in todays perioperative
anaesthesia management?
(2) What is the place of N2O in procedural analgesia
and sedation?
(3) Is administration of N2O associated with a health risk
for patients and/or providers?
Members of the task force consisted of the chairs of the
ESA Scientific Committee and Research Committee,
and the chairs of the scientific subcommittees on
Pharmacology, Paediatrics, and Monitoring, Ultrasound
and Equipment. In addition, Western and Eastern Euro-
pean key opinion leaders on the use and place of N2O in
adult and paediatric anaesthesia were asked to join the
task force.
Correspondence to Stefan G. De Hert, MD, PhD, University of Ghent, Ghent, Belgium B-9000
E-mail: stefan.dehert@ugent.be

The members of the task force are listed at the end of the article.
0265-0215 Copyright 2015 European Society of Anaesthesiology. All rights reserved.
Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
The present consensus statement is the result of an
intensive debate based on the available literature and
the expert opinion of the task force members.
What is the place of N2O in todays
perioperative anaesthesia management?
Members of the task force agreed that, despite its con-
tinuously decreasing use in perioperative care, there are
no arguments to state that the use of N2O should be
abandoned.
This statement was primarily motivated by the known
basic physicochemical properties of N2O. In clinical
practice, these properties translate into potential benefits
at anaesthesia induction, maintenance and emergence.
Indeed, faster and smoother induction with improved
oxygenation has been reported in the presence of N2O.68
During maintenance, N2O is always combined with other
drugs, and the addition of N2O dose-dependently allows
the concentrations of the other drugs to be decreased,
which, in turn, may result in faster recovery at the end of
the procedure.911
The specific place of N2O in the context of anaesthesia
induction in children was discussed. The use of N2O is
still very common in todays clinical care and has been
generally considered to induce anxiolysis, thereby facil-
itating mask acceptance as well as peripheral venous
line insertion.1214 Nevertheless, members of the Task
Force agreed that these goals can also be achieved with
adequate child preparation, conversational hypnosis,
parental presence and/or pharmacological premedication.
DOI:10.1097/EJA.00000000000002
 518 The European Society of Anaesthesiology task force on the use of nitrous oxide in clinical anaesthetic practice
Although perioperative use of N2O may increase
the incidence of postoperative nausea and vomiting
(PONV),1519 it is, however, important to state that in
patients with a low risk for PONV, this nondesirable side
effect can easily be controlled with antiemetic prophy-
laxis.20 Moreover, the exposure time to N2O seems to be
an important factor, with no clinically significant effect of
this drug on the incidence of PONV when the duration of
exposure is less than 1 h.21
What is the place of N2O in procedural
analgesia and sedation?
Members of the task force agreed that there is a place for
N2O in procedural analgesia and sedation in both adult
and paediatric populations. The safety profile based on
existing clinical data suggests that N2O administered as
the sole sedation/analgesic agent can safely be provided
by nonanaesthesiologists who are appropriately trained in
the administration modalities of the drug. The members
of the task force agreed that thorough basic life support
training should be mandatory for anyone providing seda-
tion using N2O or any other sedative drug.
An extensive amount of clinical evidence indicates that
N2O can be used safely for procedural pain management
(in the emergency room, in the normal ward or in a
prehospital situation), for the management of labour
pain,2025 and for anxiolysis and sedation in dentistry.26
N2O continues to be the mainstay for paediatric pro-
cedural sedation in a large variety of clinical settings.
Administration of N2O appears to be well tolerated in this
setting and no major problems have been reported.27
However, although currently available work suggests that
N2O can be an effective agent to provide sedation in
procedures resulting in minor to moderate pain, it is
definitely insufficient as a sole agent in more painful
procedures.27 Given the variety of procedures performed
in paediatric patients, future research needs to define
the most appropriate procedure-related effective use of
N2O.
Is administration of N2O associated with a
health risk for patients and/or for providers?
Members of the task force agreed that, despite theoretical
concerns and laboratory data, there is no evidence indi-
cating that the use of N2O in a clinically relevant setting
would increase health risk in patients or providers
exposed to this drug.
The contraindications to the use of N2O are few: the pre-
sence of closed gas containing cavities (e.g. pneumothorax)
or abnormalities of the metabolism of vitamin B12
(e.g. vegetarianism, some rare metabolic disorders).13,28
However, whether a 5 to 10-min long single administration
Eur J Anaesthesiol 2015; 32:517520
Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
of 50% N2O is deleterious in these specific cases is cur-
rently unknown. The issue of repeated anaesthesia or
sedation with N2O is poorly studied. Cases of chronic
N2O abuse have shown that both polyneuropathy
and megaloblastic anaemia can occur and some groups
therefore recommend not to use N2O more than twice a
week.29
With the ubiquitous availability of scavenging systems in
the modern operating room, the health concern for
medical staff has decreased dramatically. Properly oper-
ating scavenging systems reduce N2O concentrations
by more than 70%, thereby efficiently keeping ambient
N2O levels well below official limits.3032 The National
Institute for Occupational Safety and Health (NIOSH)
recommends an exposure limit to N2O of 25 parts per
million (ppm) as a time-weighted average (TWA) during
the period of anaesthetic administration.33 The primary
intention of this exposure limit was to prevent the
possible decreases in mental performance, audiovisual
acuity and manual dexterity during exposure to N2O.
The limits of exposure were then established by different
health authorities and were expressed in ppm as 8-h
TWA (maximum allowed exposure during 8 h), although
in the setting of procedural sedation by nonanaesthesio-
logists, peak value limits would probably be more appro-
priate (e.g. in Germany, 200 ppm during 15 min for a
maximum of four times per day). Interestingly, the limit
for N2O TWA varies greatly from country to country: for
France 25 ppm, for the USA, Italy and Belgium 50 ppm,
and for Germany, Sweden and the UK 100 ppm.34 How-
ever, these limits do not take into account the variability
in the exposure throughout the different phases of anaes-
thesia, which may depend greatly on the breathing sys-
tem used for induction, the fresh gas flow rate, ventilation
rate of the operating room and on the use of a scavenging
system.35
The potential teratogenic effect of N2O observed
in experimental models cannot be extrapolated to
humans.29,36,37 There is a lack of evidence for an associ-
ation between N2O and reproductive toxicity.29,38 The
incidence of health hazards and abortion was not shown
to be higher in women exposed to, or spouses of men
exposed to N2O than those who were not so exposed.
Moreover, the incidence of congenital malformations
was not higher among women who received N2O for
anaesthesia during the first trimester of pregnancy39 nor
during anaesthesia management for cervical cerclage,
nor for surgery in the first two trimesters of preg-
nancy.40
Conclusion
Members of the task force agreed that there is currently
no clinically relevant evidence for the withdrawal of N2O
from the armamentarium of anaesthesia practice or pro-
cedural sedation. In procedural sedation, the use of N2O
should be limited to procedures resulting in minor to

moderate pain intensity. Finally, there is no evidence
indicating that the use of N2O in a modern clinically
relevant setting increases health risk in patients or
providers exposed to this drug.
Members of the ESA task force (in
alphabetical order)
Wolfgang Buhre, Department of Anaesthesia and Pain
Treatment, Department of Intensive Care, Maastricht
University Medical Centre MUMC, Maastricht, The
Netherlands.
Vladimir Cerny, Department of Anaesthesiology, Peri-
operative Medicine and Intensive Care, Masarik Hospi-
tal, Usti nad Labem, Czech Republic.
Stefan De Hert, Department of Anaesthesiology, Ghent
University Hospital, Ghent, Belgium.
Nicola Disma, Department of Paediatric Anaesthesia,
Istituto Giannina Gaslini, Genoa, Italy.
Walid Habre, Department of Anaesthesiology, Geneva
University Hospitals, Geneva, Switzerland.
Jan Hendrickx, Department of Anaesthesiology, Onze
Lieve Vrouw Hospital, Aalst, Belgium.
Markus W. Hollmann, Department of Anaesthesiology,
Academic Medical Center, Amsterdam, Netherlands.
Jan Jakobsson, Institution for Clinical Science, Karo-
linska Institute, Stockholm, Sweden.
Radmilo Jankovic, Department of Anaesthesiology and
Intensive Care, University of Nis, Nis, Serbia.
Mikhail Kirov, Department of Anaesthesiology and
Intensive Care Medicine, Northern State Medical
University, Arkhangelsk, Russian Federation.
Dusica Simic, Department of Anaesthesiology, Univer-
sity Childrens Hospital, Medical Faculty, University of
Belgrade, Serbia.
Francis Veyckemans, Department of Anaesthesiology,
Cliniques universitaires St Luc, UCL, Brussels, Belgium.
Sergey Vorotyntsev, Department of Anaesthesiology and
Intensive Care, Zaporozhye State Medical University,
Ukraine.
Laszlo Vutskits, Department of Anaesthesiology, Geneva
University Hospitals, Geneva, Switzerland.
Jorg Weimann, Department of Anaesthesiology and
Intensive Care Medicine, Sankt Gertrauden Hospital,
Berlin, Germany.
Magdalena Wujtewicz, Department of Ophthalmology,
Medical University of Gdansk, Gdansk, Poland.
Marzena Zielinska, Department of Anaesthesiology and
Intensive Care, Wroclaw Medical University, Wroclaw,
Poland.
Eur J Anaesthesiol 2015; 32:517520
Copyright European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
The current place of nitrous oxide in clinical practice 519
Acknowledgements relating to this article
Assistance with the study: none.
Financial support and sponsorship: ESA received an educational
grant from Air Liquide (France) to convene the task force. There
was no interference by industry in the choice of the experts or the
content of the consensus statement.
Conflicts of interest: JH has received meeting organisational sup-
port from Air Liquide; JW has received funding for lectures from
Linde Healthcare; JJ has received consultation fees from Linde
Healthcare.
Comment from the editor: FV, SDH and WH are associate editors
of the European Journal of Anaesthesiology.
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