Page 162 - JSOM Summer 2022

Overall, the data both in hospital and prehospital/operational Ahern et al. noted that 18 out of 500 patients receiving low
settings supports the current dosing strategy of low dose ket- dose ketamine (LDK) (3.5%) had psychomimetic or dysphoric
amine (LDK). Based upon a study finding that the weight of reactions, however, only 3 required a benzodiazepine. The
44
the average service member as of 2016 is 76.7 kg. and the authors of that study concluded that the “use of LDK as an
presumption of combat injury patterns requiring high doses of analgesic in a diverse ED patient population appears to be
92
analgesia, the CoTCCC recommends an initial ketamine dose safe and feasible for the treatment of many types of pain.”
of 20–30mg. The 30mg dose corresponds to 0.39mg/kg for Elsewhere, Sin’s review of four studies (n = 428) using LDK
a 76.7-kg patient (the upper limit of the 0.1–0.4mg/kg non- ranging from 0.2–0.3mg/kg found only one case of psycho-
93
dissociative dose range). While this amount slightly exceeds logical disturbances. Another study evaluating the service
0.4mg/kg for a 70-kg service member (corresponding to members’ ability to perform military tasks when given 50mg
0.42mg/kg), we believe this is a reasonable risk based upon IM ketamine demonstrated that patients were aware of their
the preponderance of service members requiring higher doses. impairment and performed tasks slower when compared to
94
LDK remains the ideal initial dosing strategy to minimize side morphine (10mg IM). The mid-range dosing of ketamine,
effects. Providers can redose and titrate this ketamine dose to 0.5–0.8mg/kg IV, is used by recreational users and for ket-
achieve the desired analgesic effect while maintaining safety. amine-assisted psychotherapy as it begins to produce euphoria
and hallucinations. When used in patients in pain, this dose
Intranasal (IN) Dosing Considerations range can produce disruptive hallucinations as the patient is
The intranasal (IN) route for administering medications is a not yet fully dissociated. At higher doses of 0.8–2mg/kg IV,
desirable method for several reasons including direct drug de- patients become dissociated from their environment gen-
livery to the central nervous system and bypassing the time and erally with preserved cardiac and respiratory status. This is
skill for IV placement. An ED study comparing IN ketamine most likely due to the disruption of the thalamocortical and
48
via atomization of a 50mg/mL solution dosed at 0.75mg/kg limbic systems. These effects last 20–30 minutes and vary
found similar pain control in migraine patients when com- by patient. While this dissociation may appear traumatic in
84
pared to standard protocols. Atomizers help achieve max- itself, a prehospital study using ketamine in severe agitation
85
imum efficacy in delivery. Atomizers are a small tool that noted there was no increased incidence of required psychiatric
can be added to the tip of a syringe and improve drug deliv- evaluations or admissions in the patients administered various
ery by creating smaller particles that absorb better, enhancing doses of prehospital ketamine. 95
systemic drug delivery and reducing leak and loss of medica-
tion. Notably, the patient must be cooperative patient and Emergence Phenomenon and
86
without dried blood or dirt in the nasal cavity for this method Incomplete Dissociation
of administration to work. IN dosing has to date proven to be The unpleasant sensations associated with incomplete disso-
difficult to sustain with limited effectiveness in the deployed ciation and emergence phenomenon are often confused and
setting. 31 poorly defined. Incomplete dissociation and emergence phe-
nomena are very similar in terms of signs and symptoms,
Dosing Considerations though incomplete dissociation tends to occur with the mid-
Ideally, casualties should receive one drug at the POI. This range dosing of ketamine (0.5–0.9mg/kg IV) while emergence
simplistic approach is optimal for better patient care and miti- reactions occur as a patient resurfaces after full dissociation.
gates the risk of polypharmacy and adverse events in a chaotic Descriptions of emergence phenomenon have included feelings
environment and prior to monitor placement. of unreality, “spaced out,” euphoria, disconnectedness, rest-
lessness, agitation, crying, inconsolability, hallucination, vivid
Ketamine has an excellent safety profile. However, as previ- dreaming, floating, and delirium. 93,96,97 A single double-blind
ously discussed, adverse events may increase with higher dose study comparing morphine to ketamine (0.5mg/kg) for pa-
and rate of administration. To mitigate any adverse events, the tients with long bone fractures demonstrated that ketamine
CoTCCC recommends that responders administer ketamine in was effective but also had an emergence phenomenon in 9.5%
more frequent smaller doses versus one larger dose. of the patients. 98

Ketamine Side Effects and Adverse Events There is no available data on the incidence of emergence phe-
The effects of ketamine are rate and dose dependent. 87,88 Rap- nomenon on the battlefield. Fisher et al. describe incomplete
idly pushing ketamine can induce unpleasant sensations, as dissociation in an operational setting but without emergence
well as impact the risk of apnea, nausea, vomiting, and diz- phenomenon issues, implying that true emergence phenome-
ziness. Nausea and vomiting are common side effects. While non is uncommon in this setting. Hence, the initial treatment
99
generally considered cardioprotective, IV ketamine has been of unpleasant sensations should be redosing of ketamine. If re-
reported to cause hypotension when pushed too rapidly or dosing ketamine is not possible or if responders suspect a true
when medication errors result in a large overdose of IV ket- emergence reaction, the CoTCCC recommends administering
amine. 90,91 Similarly, a recent observational analysis from the a benzodiazepine such as midazolam. However, it is of the
100
National Emergency Airway Registry (NEAR) found a greater utmost importance to emphasize that responders should not
risk of periintubation hypotension with ketamine as compared routinely administer benzodiazepines together with ketamine
to etomidate, though most of these patients received ketamine because of their respiratory depressant effect. A retrospective
in doses exceeding the low dose range. These observational study from Iraq reported that paramedics gave 5mg diazepam
21
50
findings require further study by randomized trial designs, but to 32% (n = 713) of the patients who received ketamine.
responders should understand the uncommon but nevertheless It appears that many of these doses were prophylactic and
possible outcome of ketamine administration reducing blood may have affected vital signs, however the authors do not
pressure, perhaps due to alleviation of catecholamine release report the changes in vitals for that cohort. Additionally, a
associated with pain. review of 35 studies with 8,282 pediatric patients found the

158 | JSOM Volume 22, Edition 2 / Summer 2022