Page 53 - 2022 Spring JSOM

an excellent choice in environments in which constant mon- through surgery to postoperative care. Even when using the
itoring can be difficult. Benzodiazepines, specifically midaz- original ketamine (called CI-581), researchers in 1964 ob-
olam, on the other hand, are well known for their sometimes served “frank emergence delirium was minimal. Most of our
profound respiratory depression, a phenomenon that has been subjects described strange experiences like a feeling of float-
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well documented for nearly forty years. As such, adminis- ing.” When reactions did occur, they were easily treated “by
tering midazolam to prevent a potential reaction to ketamine coma-producing drugs.” 46
negates the advantages of ketamine and makes its administra-
tion less safe. Several papers have been published on the frequency of re-
actions to ketamine, but the results are unreliable given the
A plethora of data exists regarding the risk of apnea when broad and inconsistent definition of emergence reaction. The
benzodiazepines are co-administered with ketamine. In a case British military first published a review of battlefield ketamine
series of 266 pediatric patients who were randomized to ket- use in 1972. In 75 patients, without the addition of a ben-
amine versus ketamine and midazolam, the risk of oxygen zodiazepine, “side effects were neither common or serious.”
desaturation increased by 6% in the ketamine plus benzodiaze- Over half of the side effects noted in this study were vivid
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pine group, with no difference in emergence events. Similarly, dreams, with no serious reactions despite doses as large as
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in a case series of 210 procedural sedations with ketamine as 22mg/kg. A similar review of 70 cases of ketamine plus mid-
the primary agent, patients who received ketamine alone had azolam administration published in 2000 found that 7% of
no documented cases of apnea, while patients sedated with a patients reported emergence reactions despite co administra-
benzodiazepine had a documented apnea or hypoxia rate of tion of a benzodiazepine. Similar studies have demonstrated
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12%. While there was a 19.5% rate of emergence phenomena that while “dreaming” is a common consequence of ketamine
in the ketamine only group, the reaction was most commonly administration, these dreams are often described as pleasant
described as a “vivid dream that was not disturbing.” 43 or nondisturbing. 49
The same trends exist in military data. In 2014, a retrospective While much has changed over nearly 60 years of ketamine
case series of nine patients who received ketamine for combat use, fear of ketamine-specific emergence reactions remains.
wounds was published. Four of the nine patients were also A 2015 review of emergency department use of ketamine in
given midazolam. One of these four patients was given midaz- adults concluded that “historically, the reluctance to use ket-
olam with each dose of ketamine and had an episode of apnea amine in adults was because of an increased rate of emergence
that resolved with mild painful stimuli. No episodes of behav- reactions, but the severity of these reactions may have been
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ioral changes or emergence of clinical or tactical concern was overstated.” This fear is likely perpetuated by multiple stud-
documented despite some individuals receiving up to 450mg of ies that cite instances of emergence agitation that are of ques-
ketamine. During a prolonged evacuation scenario in Africa, tionable clinical significance. One such study was published in
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a patient who initially received oral transmucosal fentanyl ci- Annals of Emergency Medicine in 2011. This study assessed
trate (OTFC) then received midazolam prior to administration the occurrence of “recovery agitation,” a phenomenon that
of ketamine. While in flight, the patient was noted to have de- was incompletely defined, and the ability of midazolam to re-
1
creased respiratory effort and oxygen saturations, necessitat- duce its occurrence. Recovery agitation was noted to be either
ing the administration of flumazenil. No behavioral changes present or absent, which was addressed as a study limitation
or safety concerns after midazolam reversal were documented. as “minor transient restlessness or a single soft moan may
A second patient in this multiple-patient scenario was docu- have been thus coded as positive.” In this study, midazolam
mented as having “delirium” after 100mg of ketamine was de- reduced recovery agitation from 25% to 8%, with a number
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livered intramuscular (IM) but was also documented as being needed to treat of six. The supervising editor of this article
compliant with placement of two peripheral IV lines without discussed this further, noting that the number needed to treat
the need for further medication administration. 44 is likely higher given the subjective nature of evaluating emer-
gence agitation. 10
Conversely, a systematic review of ketamine use on the bat-
tlefield published in the Journal of Trauma and Acute Care Is Ketamine Safe Given to Patients
Surgery confirmed the safety and efficacy of ketamine when
used alone. Data from over 2000 causalities given ketamine With Preexisting Psychiatric Disease?
from 2000 to 2019 demonstrated that the majority of side ef- Yes. Although “known or suspected schizophrenia” is listed
fects described after ketamine administration were “extremity as one of only two absolute contraindications to ketamine
movements and incoherent speech.” Despite nearly 20% of in- use in the ACEP 2011 CPG, this is likely more opinion than
jured patients receiving ketamine towards the end of this study fact. More recent guidelines from this same body highlight
13
period, versus only 3.9% during the early portion, which is a ketamine’s “excellent safety profile”. A 2020 joint position
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significant increase due to updated guidance from the Com- statement from the American College of Emergency Physicians,
mittee of Tactical Combat Casualty Care in 2012, the inci- American College of Surgeons, and multiple EMS governing
dence of adverse events did not increase. 45 bodies states that “ketamine does not appear to increase the
incidence of psychosis” in patients with known schizophre-
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nia. It further highlights ketamine’s unique and impressive
Are Psychiatric Reactions to Ketamine safety profile in trauma patients in hemorrhagic shock or at
More Frequent and Severe in Adults?
significant risk of respiratory compromise.
No. Concerns about the severity and frequency of reactions
from ketamine are exaggerated. The authors have extensive A small case series of psychiatric patients from the psychiatry
experience with the administration of ketamine in numerous literature also highlights ketamine’s safety in this population.
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situations, at all dosing strategies, and from point of injury In this case series, the patients were so acutely agitated that,
Stopping Midazolam Coadministration With Ketamine | 51