Summary of evidence and Expert Committee recommendations
Following suggestions concerning the listing of different inhalational anaesthetic
medicines, a review of Section 1 and Section 20 of the EML was prepared by
Dr Tim Robertson (University of Newcastle, Australia) and Dr Anna Louise
Ridge (WHO Department of Essential Medicines and Pharmaceutical Policies)
to allow the Committee to update the section. The proposals were:
(1) add isoflurane (as a cost-effective alternative to halothane), propofol
(for both induction and maintenance of anaesthesia), midazolam
(more effective than promethazine or diazepam for sedation), and
atracurium (superior to alcuronium); and
(2) delete thiopental, diazepam, promethazine (less effective than
midazolam), and alcuronium.
Expert reviews were provided by Professor Abdol Majid Cheraghali and
Dr Gregory L Kearns. Comments were received from Médecins Sans Frontières
supporting the review, but proposing retention of thiopental as a useful and
cost-effective alternative to propofol.
The Committee noted that in the developing world anaesthesia is
often delivered by non-medical staff or medical staff with limited training and
resources with respect to facilities and equipment.
The Committee reviewed the evidence on inhalational anaesthetics.
Currently halothane (square box) and nitrous oxide are the only
inhalational anaesthetics on the EML. Halothane is widely used in both induction
and maintenance, in adults and children but has been gradually replaced in
developed countries by isoflurane, enflurane, desflurane, and sevoflurane for
safety reasons. Ensuring availability of halothane is increasingly problematic in
many settings. None of these medicines is best in all situations and the choice is
determined by the availability of the medicines and specific vaporizers.
While isoflurane causes less hepatic failure than halothane (1), and
has advantages for maintenance, it is unsuitable for induction. Enflurane
also has a lower rate of hepatic failure and less cardiovascular toxicity than
halothane, but increases the risk of seizure, and has to be avoided in patients
with epilepsy. Isoflurane and enflurane have more rapid onset and recovery
times than halothane. Sevoflurane and desflurane have the most rapid onset and
offset of action and few adverse effects, such as airways irritation for desflurane
(2), agitation in more than 20% of children during recovery, and convulsions
with sevoflurane. Both sevoflurane and desflurane are more expensive than
halothane, isoflurane, or enflurane.
The Committee decided to include isoflurane but not enflurane (due to
the risks of convulsions) or sevoflurane (due to cost). Halothane should remain,
but without a square box, as this would not be listed as the examplar of all
inhalation agents. Where available, halothane provides an affordable option for
induction and maintenance. However, where availability is an issue, isoflurane
provides an acceptable option for maintenance. The Committee also decided to
divide this section between injectable and inhalational agents (and oxygen).
The Committee noted that nitrous oxide can be used as a single agent
where general anaesthesia is not required, or in combination with inhalational
anaesthetics. Use in combination reduces the dose, toxicity, and costs of
inhalational drugs. The Committee therefore decided to retain nitrous oxide in
The Committee reviewed the evidence on IV anaesthetics. Ketamine and
thiopental () are on the current EML. A comparison of IV anaesthetics was
provided in the application (Table 5).
Ketamine is the most widely used in developing countries. It has few
effects on the cardiovascular system, and although apnoea can occur after
injection, airways reflexes are preserved and respiratory depression does
not occur. Ketamine is associated with hallucinations and vivid dreams at
The Committee considered that thiopental, propofol, and etomidate
have been shown to be safe induction agents (4). For thiopental, repeat dosing
can induce prolonged somnolence and has a hang-over effect. The Committee
noted that there is conflicting information on different haemodynamic effects
of propofol and thiopental. A 2001 systematic review concluded that there were
no differences in safety and efficacy between propofol and thiopental based on
evidence obtained in stable patients in non-emergency department settings
(5). While etomidate has possible advantages for use in patients in shock – as it
does not produce cardiovascular depression (4) – it is associated with adrenal
suppression even after single use, which limits its use. Etomidate was therefore
not added to the EML.
The Committee was of the opinion that thiopental could be deleted due
to its safety profile and predictable difficulties in supply in the future, but that it
needed to be retained as an alternative to propofol.
1. Stachnik J, Bonk ME. Inhaled anesthetic agents. American Journal of Health-System Pharmacy,
2. Gupta A et al. Comparison of recovery profile after ambulatory anesthesia with propofol,
isoflurane, sevoflurane and desflurane: a systematic review. Anesthesia and Analgesia, 2004,
3. Lupton T, Pratt O. Intravenous drugs used for the induction of anaesthesia [Online]
Anaesthesia.pdf, accessed 21 September 2011).
4. Nathan N, Odin I. Induction of anaesthesia: A guide to drug choice. Drugs, 2007, 67:701–723.
5. Wilbur K, Zed PJ. Is propofol an optimal agent for procedural sedation and rapid sequence
intubation in the emergency department? Canadian Journal of Emergency Medicine, 2001,