Beyond Ether and Chloroform-A Major Breakthrough With Halothane

UMMS Affiliation

School of Medicine; Department of Anesthesiology

Publication Date


Document Type



Anesthesia and Analgesia | Anesthesiology | Health Services Administration | History of Science, Technology, and Medicine


BACKGROUND: The use of equipment powered by electricity in the operating room increased the risk of fires in the presence of flammable agents such as ether and cyclopropane. Chloroform was associated with cardiac arrhythmias and liver damage. The introduction of halothane in the late 1950s was heralded as a solution to many problems facing the specialty of anesthesia. We explore whether the manufacturer promptly reported halothane's adverse effects to regulatory agencies and practitioners.

SOURCES: We consulted documents submitted by Ayerst Laboratories to federal authorities through the Freedom of Information Act, promotional advertisements, package inserts, published articles, and textbooks.

RESULTS: Two major complications associated with the use of halothane, cardiac arrhythmias and the risk of hepatotoxicity, were disclosed by the manufacturer when the drug was first introduced to the US market. Reports appeared timely and complete; there was no apparent attempt to conceal or otherwise downplay these risks.

CONCLUSION: The process of drug discovery and approval for clinical use has always been a lengthy, complex, and extremely expensive undertaking, with only a small minority of compounds receiving approval. The risk of adverse effects or drug interaction directly impacts commercial viability. In the case of halothane, the manufacturer disclosed major adverse effects, and the drug enjoyed decades of popularity until it was replaced by agents with a better drug profile.


Adverse effects, Halothane, Hepatitis, Myocardial sensitization, Side effects

DOI of Published Version



J Anesth Hist. 2017 Jul;3(3):87-102. doi: 10.1016/j.janh.2017.05.003. Epub 2017 Jun 3. Link to article on publisher's site

Journal/Book/Conference Title

Journal of anesthesia history

Related Resources

Link to Article in PubMed

PubMed ID