UMMS Affiliation

Department of Anesthesiology; School of Medicine

Publication Date

2018-07-29

Document Type

Article Postprint

Disciplines

Anesthesia and Analgesia | Anesthesiology | Health Services Administration | History of Science, Technology, and Medicine | Nutritional and Metabolic Diseases | Pathological Conditions, Signs and Symptoms

Abstract

Background: New therapies are created to address specific problems and enjoy popularity as they enter widespread clinical use. Broader use can reveal unknown adverse effects and impact the life cycle significantly. Succinylcholine, a depolarizing neuromuscular blocker, was the product of decades of research surrounding the ancient compound, curare. It was introduced into practice in the 1940s by Burroughs Wellcome and Company (BW Co.) and was welcomed due to its rapidly acting muscle relaxation effects. Global clinical use revealed adverse effects, both minor and major, in particular, hyperkalemia and malignant hyperthermia. We investigated when practitioners and the manufacturer became aware of these adverse effects, how information about these side effects were disseminated, and whether the manufacturer met the regulatory requirements of the time, specifically regarding the timely reporting of adverse effects.

Sources: Primary literature search using online and archived documents was conducted at the Wood Library-Museum of Anesthesiology, Schaumburg, Illinois. We consulted documents submitted by BW Co. to federal authorities, through the Freedom of Information Act (FOIA), Food and Drug Administration (FDA) reports, promotional advertisements, package inserts, published articles, and textbooks.

Results: Initial clinical testing in humans in 1952 found no adverse effects on cardiovascular or respiratory systems. Fasciculations and myalgia were early side effects described in case reports in 1952. Large-scale clinical trials in 1953 found abnormally long recovery times among some patients; the discovery of abnormal pseudocholinesterase enzyme activity was not fully demonstrated until the early 1960s. Bradycardia was first reported in 1957 in children, and in 1959 in adults. In 1960, animal studies reported a transient increase in plasma potassium; further experiments in 1969 clearly demonstrated succinylcholine-induced hyperkalemia in burn patients. Malignant hyperthermia was first described in 1966. Similar cases of elevated temperatures and muscle rigidity were described globally but the underlying mechanism was not elucidated until the 1990s. Standard anesthesia textbooks did not report major side effects of succinylcholine until 1960 and included newly documented side effects with each edition. BW Co.'s packaging contained warnings as early as the 1950's but were later updated in 1962 and beyond to reflect the newly discovered hyperkalemia and malignant hyperthermia.

Conclusion: Particularly given the regulatory environment of the time, BW Co. appropriately reported the adverse effects of succinylcholine after market entry; it updated promotional and packaging material in a timely manner to reflect newly discovered adverse effects. The toxicity, though alarming and put clinicians on alert, did not seem to heavily impact succinylcholine's use, given its various desirable properties. It is still a choice muscle relaxant used today, although there are efforts to develop superior agents to replace succinylcholine.

Keywords

Adverse effects, Side effects, Succinylcholine

Rights and Permissions

© 2018 Published by Elsevier Inc. on behalf of Anesthesia History Association. Accepted manuscript posted after 12 months with a CC-BY-NC-ND license as allowed by publisher's article sharing policy at https://www.elsevier.com/about/policies/sharing.

DOI of Published Version

10.1016/j.janh.2018.07.003

Source

Lisa Huang, Christine N. Sang, Manisha S. Desai , A Chronology for the Identification and Disclosure of Adverse Effects of Succinylcholine. Journal of Anesthesia History (2018), doi:10.1016/j.janh.2018.07.003. Link to article on publisher's site

Journal/Book/Conference Title

Journal of Anesthesia History

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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