Correspondence Letter to the Canadian Journal of Anesthesia by Adrian Gelb and Eric Vreede discussing the impact of the cessation of halothane production on anaesthesia services in low-resource settings.
This correspondence was published on 10 September 2024 in the Canadian Journal of Anesthesia https://doi.org/10.1007/s12630-024-02836-9.
To the Editor,
Halothane was approved by the U.S. Food & Drug Administration in the USA and introduced into global clinical practice in 1958.1 It was initially hailed as inert, safe, and suitable for inhalational induction because of its sweetish odour without some of the disadvantages of diethyl ether. Nevertheless, within a decade it was shown that about 25% was metabolized, and in a small percentage of patients, this metabolism resulted in potentially lethal hepatitis, termed ‘‘halothane hepatitis.’’ A further concern was the high incidence of cardiac arrhythmias, as high as 20%, that were worsened by the use of catecholamines and the presence of hypoxia and/or hypercapnia.2 Over subsequent decades, halothane was largely replaced by enflurane, isoflurane, and currently sevoflurane—agents with progressively safer profiles.
Halothane’s clinical use in higher income countries disappeared decades ago. Nevertheless, halothane has not completely disappeared from clinical practice globally. Based largely on price and the ability to use it for inhalational induction of anesthesia in children, halothane has continued to be used, sometimes as the only available inhaled agent, in lower-resource countries, and especially in rural areas. For these reasons, it has remained on the World Health Organization Essential Medicines List but there has continued to be a dwindling number of manufacturers, often only producing for the local market. One of the larger purveyors to sub-Saharan Africa, Piramal Pharma Ltd., ceased production of halothane at the end of 2023.
The apparently sudden loss of a major halothane producer took the anesthesia community by surprise and appropriately created much concern in some countries. The World Federation of Societies of Anaesthesiologists (WFSA) conducted an informal survey of anesthesia societies to get a sense of the extent of the impact in sub- Saharan Africa (Table). Nevertheless, this is probably a huge underestimate as the smaller and more rural facilities are unlikely to be staffed by certified specialist anesthesiologists who are members of the national societies.
The smaller and more rural facilities are the ones that are most likely dependent on a supply of halothane as they are likely to be poorly equipped and staffed by less well trained anesthesia providers who often only know a single technique. Options to replace halothane at such facilities may only be the use of ketamine and/or isoflurane, which is unsuitable for inhalational induction in children. Isoflurane can be used in a halothane vaporizer as both agents have a similar saturated vapour pressure (SVP). Nevertheless, there are safety concerns including differences in the minimum alveolar concentration (MAC) resulting in lighter anesthesia with isoflurane at the same dial setting (halothane: MAC, 0.75; SVP, 243 mm Hg; isoflurane, MAC 1.17; SVP, 238 mm Hg), confusion about what is in the vaporizer, and compatibility of the vaporizer material with isoflurane.3
Manufacturers clearly have the autonomy to decide when to discontinue the production of medications. Nevertheless, we believe that they have a moral obligation to ensure that end-users of important medications are being appropriately informed—not merely their distributors. This could most easily be achieved by connecting with the relevant national society of anesthesia and/or critical care and concurrently informing the WFSA. National agencies for the regulation of medicines should also be informed, and national anesthesia societies should liaise with these agencies about propagating the message and the planning of timely solutions.
Meanwhile, many low-resource regions are facing a difficult situation by being forced to rapidly find alternatives, all of which will increase costs. Mobilizing the finances and required components will take time, years in some countries. This will possibly decrease access to safe anesthesia and surgery during that period. We regret that this has occurred and urge a manufacturer to continue or restart production and multinational distribution so that countries can transition safely in the near future. During this transition period, it is imperative for national and regional health authorities to rapidly budget for and implement a safe transition to isoflurane and/or sevoflurane to replace halothane.
Disclosures
Dr. Gelb is a Past President of the World Federation of Societies of Anaesthesiologists (WFSA) and the Director for Advocacy at the UCSF Center for Health Equity in Surgery and Anesthesia (San Francisco, CA, USA). Dr. Vreede is a member of the WFSA ad hoc committee for halothane, Chair of the World Federation of Societies of Anaesthesiologists (WFSA) – International Committee of the Red Cross (ICRC) Liaison Committee, Secretary of the Sierra Leone Society of Anaesthetists, and Secretary of the Faculty of Anaesthesia of the Sierra Leone College of Physicians and Surgeons.
References
- U.S. Food & Drug Administration. FDA-approved drugs. Available from URL: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=011338 (accessed July 2024).
- Black GW. A review of the pharmacology of halothane. Br J Anaesth 1965; 37: 688–705. https://doi.org/10.1093/bja/37.9.688
- Ebert TJ, Sawyer A. Chapter 18: Inhaled Anesthetics. In: Barash PG, Cullen BF, Stoelting RK, et al. (Eds.). Clinical Anesthesia, 8th
ed. Philadelphia: Wolters Kluwer; 2017: 459–85.
Further Resources
Information on end of halothane production for WFSA Member Societies
