Page 51 - 2022 Spring JSOM

The Myths of Uncontrolled Emergence Reactions

and Consideration to Stop Mandatory, Protocolled Midazolam
Coadministration With Ketamine

Hugh Hiller, MD *; Brendon Drew, DO ; Andrew Fisher, MD ;
1
3
2
Matthew Cuthrell, PA-C ; James Spradling, CRNA 5
4

ABSTRACT
Ketamine continues to demonstrate its utility and safety in the of literature discussing the incompletely dissociated ketamine
austere and prehospital environment, but myths persist re- patient. Additionally, midazolam is not a benign drug, as its
garding the frequency of behavioral disturbances and unpleas- cardiovascular and respiratory depressant effects are poten-
ant reactions. These myths have led to protocolled midazolam tially disastrous in the acutely traumatized patient. Because
co-administration. Properties of midazolam and other benzo- of all of the above, midazolam should be administered at the
diazepines have the potential to cause significant morbidity discretion of the treating provider when truly needed, and not
and potential mortality. Because of this risk, benzodiazepines in a protocolled fashion.
should only be administered when the treating provider deter-
mines that the patient’s symptoms warrant it. We also present There are two very important lessons for medical personnel that
evidence that agitation and altered mental status (AMS) en- use ketamine in chaotic and austere situations. First, the em-
countered with ketamine occurs during titration of lower pain piric administration of midazolam with ketamine is not neces-
control regimens and is much less likely to occur with higher sary and potentially dangerous. Second, sub- dissociative doses
doses. As such, in most prehospital situations, the treatment of ketamine may cause behavioral/psychiatric sequelae – most
for this “incomplete dissociation” is more ketamine, not the of which are not clinically important. It is the authors’ hope
addition of a potentially dangerous benzodiazepine. that the evidence presented here will serve as a framework to
remove co-administration of midazolam with ketamine from
Keywords: ketamine; emergence; midazolam; Versed; dissociation protocolized treatment algorithms.

What Is an “Emergence Reaction,”
Introduction and When Does It Occur?
Over the past two decades, ketamine has been used with in- This term is poorly defined. Classic emergence reactions oc-
creasing frequency on the battlefield. Its favorable cardiovas- cur as anesthesia is wearing off, but unwanted reactions can
cular profile, wide margin of safety, and lack of respiratory occur at any time. For the purposes of this paper, we will
depressant side effects make it the drug of choice for battle- use the terms “psychiatric/behavioral sequelae.” Psychiatric/
field analgesia and anesthesia. However, significant concern behavioral sequelae may occur at any time after administra-
remains about ketamine’s potential to cause “emergence reac- tion of any medication that provides sedation, analgesia, and/
tions.” These undesired psychiatric and behavioral side effects or anesthesia, and is not specific to ketamine.
have resulted in prehospital and battlefield protocols, requir-
ing co-administration of midazolam with ketamine. For prehospital providers, psychiatric or behavioral reactions
to medications are of particular concern. In resource-limited
Concerns over reactions to ketamine are perpetuated in environments, an agitated patient is hard to monitor. Agitation
many courses of instruction. These reactions are not unique in an ambulance or aircraft puts both the patient and crew at
to ketamine and can occur at any time, not just as ketamine increased risk of crashing. A loud or agitated patient also has
is wearing off. We will review the literature associated with the potential to betray tactical position. For the purposes of
“emergence reactions,” introduce the concept of “incomplete ketamine administration, we will define behavioral sequelae as
dissociation,” and discuss why midazolam should be only be any behavior that the treating medic perceives as (1) making
given in select situations. care more difficult or (2) putting the patient, medic, or trans-
port team at risk.
Not only is the term “emergence reaction” poorly defined,
but these behavioral sequelae can occur prior to complete Emergence reactions have been described with terms that
dissociation with ketamine. Unfortunately, there is a paucity include unpleasant, giddy, disconnected, floating, agitation,
*Correspondence to hughhiller@gmail.com
1 CPT Hugh Hiller is an emergency medicine physician at Carl R. Darnall Army Medical Center, Fort Hood, TX, where he serves as the director
of Operational Medicine for the Emergency Medicine Residency Program. CAPT Brendon Drew is the chair of the Joint Trauma System Com-
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mittee on Tactical Combat Casualty Care and serves as the I Marine Expeditionary Force Surgeon and the Navy Emergency Medicine Specialty
Leader. MAJ Andrew Fisher is a general surgery resident physician at the University of New Mexico School of Medicine, Albuquerque, NM,
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and previously served on active duty as a physician assistant within USASOC. MAJ Matthew Cuthrell is a physician assistant at Womack Army
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Medical Center at Fort Bragg, NC. CDR James Spradling is a certified registered nurse anesthetist at Naval Hospital Camp Lejeune, Jackson-
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ville, NC, and an associate clinical instructor for the Duke University School of Nursing, Durham, NC.
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