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13 of which received it via the IV route. No adverse events
were reported in this patient population, which may suggest
the safety of this route. These authors again reported on the
use of IV olanzapine in 4 acutely agitated patients in the ED
setting.16 They found no complications attributable to IV
olanzapine administration with cumulative doses ranging
from 10 to 30 mg in their patients over the course of their ED
stay.16 The same investigators conducted a trial in which IV
droperidol or olanzapine was used in conjunction with midazolam in the treatment of acutely agitated patients.13 In this
trial, 109 patients were randomized to the olanzapine arm and
those patients experienced similar adverse event profiles to
the droperidol and placebo arms; the investigators reported
that recorded events were readily and easily managed.13
Martel et al15 also reported the use of IV olanzapine for various indications in 713 patients in the ED setting; the investigators reported that hypoxia was commonly seen, but this
rarely resulted in serious airway compromise. However, these
investigations primarily used olanzapine as a sedative rather
than agent for the treatment of delirium.13-16 For this reason, it
is difficult to use this evidence to come to a conclusion regarding the efficacy of IV olanzapine as an agent for the treatment
of delirium. Haloperidol is not FDA-approved for IV administration but it is widely used by this route and now has
become an acceptable route of administration in the critically
ill patient. The "intramuscular" formulation of olanzapine has
a neutral pH and contains substances that can be given intravenously (lactose and tartrate).11 The case reported here highlights some of the difficulties that may be seen while providing
care to a critically ill patient and the need for innovative therapy choices when faced with these challenges. To our knowledge, this is the first reported case describing the use of IV
olanzapine in the ICU setting. The use of nonintravenous
olanzapine in delirious patients is well documented and has
shown safety and efficacy in this setting.7-10 Highly selective
binding for the D2 receptors makes olanzapine an attractive
option for patients in whom there is a concern for QT prolongation chosen due to its low binding affinity for the Ikr
channel.19 In addition, in a meta-analysis to validate the clinical utility of the ratio of the half-maximum inhibition concentration of the hERG channel (hERG IC50) to the peak serum
concentration of unbound drug (Cmax), Lehmann et al20
reported that olanzapine is the antipsychotic with the least
risk of drug-induced torsade de pointes. Although olanzapine
is only approved parenterally for IM use, evidence suggests
that IV use may be safe.13-16 It is worth noting that our patient
did experience bradycardia and hypotension, both of which
are reported side effects of IM olanzapine, with a temporal
relationship with administered doses of olanzapine.21 Of note,
the use of IV olanzapine has not had a significant association
with hypotension or bradycardia when compared with other
agents or placebo.13,15 However, our patient was also receiving other medications, dexmedetomidine, morphine, and
diazepam (IV), which might have contributed to the

Hospital Pharmacy 55(2)
bradycardia and hypotension. Other concerning side effects
such as extrapyramidal symptoms or respiratory depression
secondary to olanzapine use were not observed in this
case.11,12 Off-label routes of administration are not uncommon and have been safely and effectively used before; such
examples include the IV use of haloperidol, intravaginal use
of misoprostol, and the intravitreal use of various anti-infectives. One major limitation in the evidence as it applies to our
case is that experience with IV olanzapine has only been
reported in the ED setting, mostly being used for agitated
patients.
Recent updates by the Society of Critical Care Medicine
guidelines concerning the management of delirium in adult
patients in the ICU have been published.22 These guidelines
recommend against the routine use of antipsychotics in the
treatment of delirium owing to limited evidence of benefit and
potential risk of harm due to medication-related adverse
events.22 However, they do acknowledge there are certain circumstances including but not limited to agitated patients who
may harm themselves or others, who may benefit from the
short-term use of an antipsychotic.22 We feel that this patient,
due to the agitation displayed, likely would have warranted
therapy in conjunction with these updated guidelines, and consistent with their goal of sparing patients of undue adverse
events, IV olanzapine would likely be a treatment for consideration, possibly mitigating the potential risk of precipitating a
drug-induced arrhythmia. Despite the need for further investigation of the IV route of administration of olanzapine in critically ill patients, we think our experience adds to the literature
and enforces the comfortability and safety of this route of
olanzapine administration in critically ill agitated patients.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.

References
1. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines
for the management of pain, agitation, and delirium in adult
patients in the intensive care unit. Crit Care Med. 2013;41:263306.
2. Siddiqi N, House AO, Holmes JD. Occurrence and outcome of
delirium in medical in-patients: a systematic literature review.
Age Ageing. 2006;35:350-364.
3. McNicoll L, Pisani MA, Zhang Y, Ely EW, Siegel MD, Inouye
SK. Delirium in the intensive care unit: occurrence and clinical
course in older patients. J Am Geriatr Soc. 2003;51:591-598.
4. Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van
Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit
Care Med. 2009;180:1092-1097.

Hospital Pharmacy - April 2020

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