Page 83 - JSOM Spring 2024

Deployed Combat Use of Methoxyflurane for Analgesia

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Steven G. Schauer, DO, MS *; Andrew D. Fisher, MD, MPAS ;
Michael D. April, MD, DPhil, MSc 3

ABSTRACT
Background: The U.S. Military needs fast-acting, non-opioid those experiencing hypotension and vasoconstriction. It was
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solutions for battlefield pain. The U.S. Military recently used never a recommended analgesic solution by the Committee on
morphine auto-injectors, which are now unavailable. Off-label Tactical Combat Casualty Care. 4
ketamine and oral transmucosal fentanyl citrate use introduces
challenges and is therefore uncommon among conventional As such, other solutions were sought, namely ketamine and
forces. Sublingual suftentanil is the only recent pain medication oral transmucosal fentanyl citrate (OTFC), primarily within
acquired to fill this gap. Conversely, methoxyflurane delivered the U.S. Special Operations Command (SOCOM). 5–12 While
by a handheld inhaler is promising, fast-acting, and available to previous studies demonstrated good clinical efficacy with
some partner forces. We describe methoxyflurane use reported these solutions, multiple issues made the expansion outside of
in the Department of Defense Trauma Registry (DODTR). SOCOM nearly nonexistent. Ketamine for analgesia is well
Methods: We requested all available DODTR encounters from described but remains off-label because the only on-label in-
2007 to 2023 with a documented intervention or assessment dication is anesthesia. The development of an auto-injector
within the first 72 hours of care. We analyzed casualties who remains challenging as the drug cannot be manufactured and
received methoxyflurane in the prehospital setting using de- sold for an off-label indication. Ketamine drawn from vi-
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scriptive statistics. Results: There were 22 encounters with als remains difficult to track and control, creating concerns
documented methoxyflurane administration. The median pa- about diversion and abuse. Oral transmucosal fentanyl ci-
tient age was 23 (range 21–31) years. All were men. The largest trate (OTFC) is easier to track, and the one-time use makes
proportion was partner force (50%), followed by U.S. Military diversion more difficult. However, OTFC carries a black box
(27%). Most (64%) sustained battle injuries. Explosives were warning from the FDA for outpatient use in opioid-naive pa-
the most common mechanism of injury (46%), followed by tients. There have been only a handful of cases of possible
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firearms (23%). The median injury severity score was 5 (range overdose in the prehospital setting and the black box warning
1–17). The most frequent injuries were serious injuries to the is not intended to apply to a setting with direct monitoring
extremities (27%), and 23% of patients (5) received a tour- by healthcare personnel. 11,13,14 Nevertheless, this warning has
niquet. One-half of the casualties received concomitant pain created anxiety related to the widespread use throughout the
medications. Only three casualties had multiple pain scores Force and remains a stop-gap solution. To date, the only offi-
measured, with a median pain score change of –3 on a scale cial solution in the deployed sets is the sublingual sufentanil
of 10. Conclusion: Methoxyflurane use in deployed combat (DSUVIA, AcelRx Pharmaceuticals, Inc., Redwood City, CA,
shows both feasibility and usability for analgesia. https://www.dsuvia.com/). While available to both SOCOM
and conventional forces, the efficacy of this solution for acute
Keywords: military; combat; trauma; pain; analgesia; meth- pain has limited data as it has been tested more in the post-
oxy flurane; penthrox operative setting. 15–18 Additionally, there are unpublished re-
ports of challenges with its delivery system. There was also
controversy with bringing a new opioid to market amid an
opioid crisis. 19,20
Introduction
The U.S. Military and Coalition partners have been involved Given the risks associated with opioids, even with single doses,
in combat operations for over two decades during the Global the U.S. Military desperately needs a non-opioid battlefield
War on Terrorism. Early in the recent conflicts, the U.S. mil- analgesia solution. Methoxyflurane is a volatile anesthetic
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itary relied on stockpiles of morphine auto-injectors until that is delivered through a handheld inhaler. It is known by
exhaustion (since they were no longer being actively manu- the brand name Penthrox (Medical Developments, Australia)
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factured). However, intramuscular morphine is not an ideal or the colloquial term “the green whistle.” The use of this
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battlefield pain solution; onset can take over 20 minutes to drug outside of the U.S. is well described, with high-quality
peak in healthy subjects, with even more variability among data supporting its use for analgesia. 22–26 It has a very rapid
*Correspondence to steven.g.schauer.mil@army.mil
1 LTC Steven Schauer is a Fellow in Anesthesia Critical Care Medicine in the Departments of Anesthesiology and Center for Combat and Bat-
tlefield (COMBAT) Research, University of Colorado School of Medicine, Aurora, CO, and an Associate Professor of Military and Emergency
Medicine at the Uniformed Services University of the Health Sciences, Bethesda, MD. MAJ Andrew Fisher is a general surgery resident physi-
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cian the Department of Surgery, University of New Mexico School of Medicine Albuquerque, NM, and the Texas National Guard, Austin, TX.
3 LTC Michael April is an Associate Professor of Military and Emergency Medicine at the Uniformed Services University of the Health Sciences,
Bethesda, MD.
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