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Lorenzo et al
Table 1. Medication Administrations and Concurrent QTc.
Day 1
(OSH)
QTc
Potential QT
prolonging
agents
administered

447
Ondansetron
4 mg (×1)

Day 4
451
None

Day 7

Day 8

Day 10

Day 13

442
Haloperidol
2 mg (×1)
Ziprasidone
10 mg (×1)

458
Ziprasidone
10 mg (×3)

485
Haloperidol
5 mg (×1)
Olanzapine
2.5 mg (×3)

475
Olanzapine
5 mg (×3)

Note. QTc = baseline-corrected QT interval.
OSH=Outside Hospital

transferred from an outside hospital to Upstate University
Hospital primarily for plasmapheresis. Past medical history
was significant for a left MCA stroke, arthritis, hypertension,
diverticulosis, benign prostatic hypertrophy, and renal calculus. The patient had a history of tobacco abuse with an estimated 81 pack-year history and had no reported history of
alcohol or recreational drug use. His records described use of
tamsulosin, terazosin, and ibuprofen for home medications.
On admission, the patient displayed signs of agitation and
required use of lorazepam for sedation.
Thrombocytopenia was present throughout the course of
the patient's care, despite repeated plasmapheresis sessions,
steroid use, and an infusion of rituximab in the setting of
presumed TTP, with a platelet nadir of 9000/µL and a peak of
54 000/µL over the patient's 11-day inpatient stay. Initially,
the patient had received IM injections of various medications, but once the platelet count fell below 20 000/µL, the
care team felt it was no longer safe to use this route of administration. The patient was not intubated during the stay; however, he refused the placement of a nasogastric tube and
enteral administration of medications was not feasible due to
difficulty in complying with care. During this time, the
patient continued to experience episodes of agitated delirium, consistently displaying altered consciousness, inattention, exaggerated responses to normal stimuli, and
psychomotor agitation. Based on hospital records, the patient
displayed an initial Intensive Care Delirium Screening
Checklist (ICDSC) score of 5 and Richmond Agitation and
Sedation Scale (RASS) score ranging from +3 (very agitated) to −3 (moderate sedation) throughout the stay.17,18
Intravenous treatment options to address agitation and delirium were sought out and the patient began receiving haloperidol 5 mg every 6 hours as needed, with the patient
receiving 2 doses before switching to IV olanzapine. Before
haloperidol administration, the patient had been treated with
combinations of IM ziprasidone and haloperidol with varying responses. The patient had also been receiving lorazepam
and diazepam as needed for agitation, and a continuous dexmedetomidine infusion for sedation.
A baseline-corrected QT interval (QTc) of 447 milliseconds was present on admission and did increase to 485 milliseconds during the patient's hospital stay and became a

concern in regard to medication management. The only medications being administered during these days with known
risks of QTc prolongation were haloperidol and ziprasidone.
Table 1 displays more extensive detail of medication administration in relation to the QTc.
Olanzapine 2.5 mg every 4 hours as needed was administered IV with variable response; the dose was then increased
to olanzapine 5 mg IV every 4 hours as needed. Dosing recommendations were guided largely by the dosing used in the
investigations by Chan et al13 and Martel et al,15 who reported
doses of largely 2.5 mg or 5 mg, with a small minority receiving higher doses. In total, the patient received 7 doses of 2.5
mg and 9 doses of 5 mg without significant incident. No further changes in the electrocardiogram (EKG) were noted,
and the therapy seemed, overall, to be safe and effective. Per
the medical record, the patient was reported to have been
more compliant with care and less agitated following the use
of olanzapine. The patient did become bradycardic following
olanzapine doses, and his blood pressures did seem to
decrease from the pressures that were normally seen during
his course of care, but they did not become low enough to
warrant the use of cardiovascular support (eg, vasopressors
or inotropes) or other interventions. The patient became
more ill secondary to worsening TTP despite receiving 10
days of plasmapheresis as well as high dose steroids, and
rituximab therapy. The family agreed to comfort measures
on day 11 of inpatient care and the patient expired.

Discussion
Intravenous administration of olanzapine is not an FDAapproved route of administration.12,13 Although FDA approval
is lacking, IV olanzapine is increasingly being recognized as
safe and effective route of administration.13-16 The literature
speaks almost exclusively to IV olanzapine use in the emergency department (ED) setting in agitated patients.13-16
Unfortunately, no pharmacokinetic investigations into the
distribution, metabolism, and elimination are available concerning this route, and its use in critically ill patients admitted
to the critical care unit is lacking. Chan et al14 were the first to
report a case series of patients requiring parenteral chemical
restraint in which 14 patients receiving parenteral olanzapine,

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