Page 82 - JSOM Summer 2025

An Ongoing Series

Proof of Concept

Is Small-scale Production of Diethyl Ether for Anesthetic Use Possible?

Sandeep T. Dhanjal, MD *; Katelyn M. Kitzinger, PhD ;
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Dennis Jarema, RN, ATP ; Jeffrey S. Johnson, PhD 4
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ABSTRACT
Background: Clinicians face numerous challenges when pro- more recent conflicts. Lack of air superiority, robust resources,
viding effective anesthesia in the setting of humanitarian crisis frequent resupply, and delayed evacuation are expected to
or armed conflict. Anesthetic supply limitations often stand as plague healthcare systems in such situations. One particular
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a critical gap in these environments. Due to its clinical safety field of medicine that tends to be drastically impacted by such
profile and relatively simple production, diethyl ether (Et O) catastrophes is the provision of safe anesthesia. While surgical
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may offer a solution in such situations. Methods: The dehydra- care in these settings has been well described in the literature,
tion of ethanol (EtOH) using an acid-catalyzed reaction was there is little documentation describing the provision of anes-
conducted twice. Sulfuric acid was added to a solution of eth- thesia under such circumstances. Previous reports suggest that
anol in a glass flask that was heated to approximately 145 °C, use of inhaled anesthetics in these challenging environments is
promoting the formation of Et O and water. At this tempera- often limited simply by supply shortages of such medications.
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ture, Et O was isolated from the solution through fractional Unfortunately, this often results in insufficient availability of
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distillation and collected in a flask that was cooled in an ice anesthesia and analgesia or the inability to perform needed
bath. The distillate was analyzed using proton nuclear mag- operations for many patients. Experience has led many experts
netic resonance ( H NMR) spectroscopy. Results: Two samples to believe that in order to continue to provide effective clinical
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of Et O were obtained using an acid-promoted dehydration care when resources are restricted, clinicians must revert to
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of ethanol. Analysis of the samples using H NMR spectros- techniques that were safely used in the past. 3
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copy led to the identification of two components, Et O and
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EtOH, whose identities were confirmed by comparison of the Diethyl ether (Et O), a once commonly used anesthetic, has
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constituent peaks to known chemical shifts. Integration of the been replaced with inhaled general anesthetics that are far less
relevant peaks suggested a Et O purity of approximately 97%. flammable. Its previously demonstrated safety profile and
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Conclusion: This proof-of-concept study demonstrates that simple production suggest that this agent may once again have
relatively pure Et O can feasibly be produced and isolated on a value in resource-constrained environments. Natural disas-
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small scale using an acid-catalyzed dehydration reaction with ters, armed conflict, and remote settings may force clinicians
fractional distillation. to provide prolonged field care, where conventional general
anesthetic techniques may not last for necessary time periods,
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Keywords: ether anesthesia; austere; ether; diethyl ether; especially when numerous casualties are expected. Addition-
inhalation agents ally, smaller, more mobile surgical teams are likely to become
“mission incapable” if evacuation or resupply are not avail-
able. Yet, history has shown that conflict will likely limit both
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capabilities. As identified by previous literature, the ability to
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Background
produce Et O, using common reagents, would certainly fill this
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When considering healthcare in future disasters, humanitarian gap. The present study aims to establish a proof of concept
crises, or armed conflict with peer or near-peer adversaries, the for producing diethyl ether using ethanol (EtOH) and sulfuric
U.S. Military will likely face challenges that were not present in acid.
*Correspondence to Sandeep_Dhanjal@med.unc.edu
1 Dr. Sandeep T. Dhanjal is associated with the Department of Anesthesiology, University of North Carolina at Chapel Hill School of Medicine,
Chapel Hill, NC and the Special Warfare Medical Group (Airborne), Joint Special Operations Medical Training Center, Fort Bragg, Fayetteville,
NC. Dr. Katelyn M. Kitzinger is associated with the Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC.
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3 Dennis Jarema is associated with the Special Warfare Medical Group (Airborne), Joint Special Operations Medical Training Center, Fort Bragg,
Fayetteville, NC. Dr. Jeffrey S. Johnson is associated with the Department of Chemistry, University of North Carolina at Chapel Hill, Chapel
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Hill, NC.
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