Frozen in Time: A History of the Synthesis of Nitrous Oxide and How the Process Remained Unchanged for Over 2 Centuries

Three major factors have contributed to the unrivaled popularity of nitrous oxide (N2O) among anesthetists in the 20th century and beyond: its impressive safety profile, its affordability, and its rapid induction and emergence times. These 3 characteristics of N2O have been discussed and written about extensively throughout the medical literature. Nonetheless, the characteristic that contributed most to N2O's initial discovery—the elegance and simplicity of its synthesis—has received substantially less attention. Although N2O was first used as an anesthetic in Hartford, CT, in 1844, it had been identified and synthesized as a distinct gas in the late 18th century. In this article, we track the developments in the recognition and early synthesis of N2O, highlight the major players credited with its discovery, and examine its evolution from the late 1700s to today. The discovery and assimilation of N2O into common medical practice, alongside ether and chloroform, heralded a new paradigm in surgical medicine—one that no longer viewed pain as a fundamental component of surgical medicine. Its continued usage in modern medicine speaks to the brilliance and skill of the chemists and scientists involved in its initial discovery. Accepted for publication March 30, 2018. Funding: Intramural. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Manisha S. Desai, MD, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655. Address e-mail to manisha.desai@umassmemorial.org. © 2018 International Anesthesia Research Society

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