Page 54 - 2022 Spring JSOM

without ketamine, intubation would have been required for in a randomized, double-blind, crossover trial of ketamine
the safety of crew and patient. Most had a primary diagno- 0.5mg/kg compared with midazolam 0.045mg/kg over 40 min-
sis of exacerbation of schizophrenia, were transported via utes to treat PTSD. Dissociative symptoms were observed but
air safely on ketamine, and were followed for 72 hours after not described in the results, however “no emergence of signifi-
admission to inpatient psychiatric units. None had worsening cant psychotic or manic symptoms was observed.” The patients
psychiatric symptoms upon awakening from ketamine disso- were followed for 7 days after medication administration and
ciation. A larger and more recent prehospital case series of 52 the authors concluded that a single dose of ketamine signifi-
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patients sedated with ketamine for excited delirium also found cantly reduced PTSD symptoms. In 2012, three experienced
ketamine to be safe and effective. 55 military certified registered nurse anesthetists with a combined
14 deployments to Iraq and Afghanistan voiced a strong pref-
Most recently, a retrospective cohort study was published in erence for ketamine total intravenous anesthesia (TIVA) with
2019 comparing IM ketamine to an IM benzodiazepine for military personnel who had or were at risk for PTSD/traumatic
prehospital agitation in patients with known psychiatric dis- brain injury (TBI) to reduce risk of emergence reactions. 63
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ease. The authors found that there was no difference in psy-
chosis, psychiatric evaluation, or admission to a behavioral Which Strategy for Midazolam Administration
health facility between the two groups. However, there was
however a difference in hospitalization, with patients given IM With Ketamine Is Recommended?
benzodiazepines requiring medical admission 63% of the time The “PRN strategy” should be used. Midazolam should only
versus only 3.8% of ketamine patients. This was due to signifi- be given if the patient is hemodynamically stable, no longer
cant airway compromise in the IM benzodiazepine group, with bleeding, and continued ketamine administration is no longer
no instances of airway compromise in patients given ketamine. required for the medical care of the patient. In a 2008 exten-
sive literature review, three strategies were presented. These
11
Interestingly, patients on psychiatric medications may actu- included “predissociation strategy” (sedative agent before ket-
ally have higher rates of emergence reactions when benzo- amine administration), “preemergence strategy” (sedative agent
diazepines are administered. One large study of 1359 adults shortly before emergence) and “PRN strategy.” We agree with
reported “preoperative medication by benzodiazepines is a the authors of this paper who recommended the PRN strategy
significant risk factor for emergence delirium in the PACU. due to decreased risk of respiratory depression and shorter re-
Use of benzodiazepines before surgery nearly doubled the risk covery time.11 Other recent literature supports the PRN strategy
of emergence delirium.” 36 as well. In a case series of 52 agitated patients controlled with
ketamine in the prehospital environment, half received midaz-
olam prior to hospital arrival for prevention of emergence. In
Does Ketamine Worsen this series, 12% of patients who received preemergence mid-
Posttraumatic Stress Disorder (PTSD)?
azolam experienced “significant” respiratory depression (one
No. Ketamine has been used safely in patients with both acute required bag-valve mask use and two required intubation). No
and chronic PTSD. Burned Servicemembers who underwent cases of respiratory depression were noted in the ketamine-only
surgery at the USAISR and received ketamine had lower PTSD group. Although a protocol violation, many medics often did
scores compared to those who did not receive ketamine. This not administer midazolam “due to the excellent sedation rou-
occurred despite patients in the ketamine group having total tinely achieved by ketamine alone.” The authors concluded
body surface area percentages, injury severity scores, total in- that “this suggests that further sedation with a benzodiazepine
tensive care unit days, and number of operative interventions could potentially be delayed until hospital arrival.” 55
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twice that of the no-ketamine group. The results of a larger
follow-up study from the same institution again demonstrated The PRN strategy is effective and prehospital medics have
no increase in PTSD symptoms in the patients who received demonstrated an ability to execute this strategy safely. In a case
ketamine. A recent retrospective study from France of pa- series discussing the British protocol, simultaneous adminis-
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tients who received ketamine on the battlefield demonstrated tration of midazolam and ketamine is specifically avoided due
that ketamine does not increase the risk of development of to the risk of respiratory compromise. Midazolam is admin-
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PTSD in this patient population. 59 Furthermore, ketamine istered only when “aggression or agitation” was noted during
has even been used in patients with PTSD and known prior recovery from ketamine. In a report of 32 patients who re-
emergence reactions to general anesthesia. Two patients with ceived prehospital ketamine in Britain, no cases of respiratory
PTSD and a history of emergence reactions were anesthetized compromise were documented in the 12 patients who received
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with different regimens in an attempt to avoid recurrence of midazolam following this protocol. In 2013, the Journal of
emergence agitation. The adult given midazolam and propofol Special Operations Medicine published a review of the use of
had “severe emergence delirium” and the elderly female given ketamine to facilitate evacuation in trauma patients. Midaz-
ketamine and had no side effects. 60 olam was only given with ketamine during transport if the
provider judged its administration to be safe. Specifically, “the
Not only is ketamine safe in this patient population, but there dose of midazolam was at the request of the emergency de-
is an increasing popularity in the psychiatry community re- partment at the primary Role III hospital to help mitigate the
garding the potential benefits of ketamine in patients with se- possible emergence phenomenon the patient may experience
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vere, refractory PTSD. PTSD has been linked to 3,4-methyl if extubated.” In this series, the medics transporting the pa-
enedioxymethamphetamine (MDMA) receptor overactivity tients demonstrated a higher comfort level with ketamine than
making ketamine, a medication that works directly to inhibit the emergency physicians receiving the patients.
MDMA receptors, a logical choice. Early human studies
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show this theory to be promising. In one study, patients with Israeli protocols during prolonged transport promote a similar
“moderate to severe PTSD symptom levels” were enrolled strategy. In one case series from Israel, 11 severely injured and

52 | JSOM Volume 21, Edition 4 / Winter 2021