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13,794 U/L (normal range, 10-30 U/L), alanine aminotransferase of 10,569 U/L (normal range, 10-40 U/L), international normalized ratio of 3.4 (normal range, 1-1.3), and
oliguric renal failure requiring continuous renal replacement
therapy (SrCr 3.08 mg/dL, normal, 0.5-1.1 mg/dL in adult
females). Plasma metanephrines were severely elevated,
with metanephrine of 543 nmol/L (normal, <0.9 nmol/L)
and normetanephrine at 443 nmol/L (normal, <0.5 nmol/L).
Elevated plasma metanephrines are the preferred diagnostic
biomarker for suspected pheochromocytoma, suggesting
pheochromocytoma as the likely diagnosis of the patient's
large adrenal mass. Pheochromocytoma was confirmed after
surgical removal of the mass on hospital day 27. No further
status of the patient's condition was provided post surgery.
The authors1 point out that metoclopramide-induced
hypertensive crisis in pheochromocytoma has been described
in the medical literature. This is caused by the catecholamine-releasing effect of metoclopramide in patients with
pheochromocytoma. Historically, D2 receptor antagonism
was thought to be responsible, but more recent evidence suggests that the 5-HT4 receptors also play an important role.
The authors report this case as an important reminder that
metoclopramide, a frequently used medication in the ED,
can trigger acute pheochromocytoma crisis.

Baclofen Dependence Following HighDose Therapy
Baclofen is a GABAB receptor agonist most commonly used
to treat muscle spasticity, but when used in high doses may
also be used in the treatment of treatment-resistant alcohol
dependence. Despite conflicting reports in the literature
regarding the effectiveness of baclofen for the treatment of
alcohol dependence, the French health authority approved its
use for this indication in March 2014.
A 63-year-old woman was hospitalized after suffering a
loss of consciousness. Upon admission, the patient reported
a dizziness, headache, disorientation to space and time, and
worsening vomiting episodes over the preceding 2 months.
For 6 months, the patient had been treated with gradually
increasing doses of baclofen for alcohol dependence to eventually reach a dose of 90 mg 3 times daily. The patient's
medical history was significant for anxiety, depression, and a
sleep disorder, managed with a regimen of escitalopram 10
mg daily, zopiclone 7.5 mg daily at bedtime, and oxazepam
12.5 mg daily; further, the patient also had uncontrolled
hypertension, for which she received no treatment. On
admission, vital signs and physical examination findings
were normal, except for an elevated BP of 200/130 mm Hg.
The patient had additional subjective complaints of widespread pain, dyspepsia, difficulty with visual accommodation, excessive tiredness, and insomnia. Neurological,
cardiovascular, and pulmonary findings were normal, apart
from an elevated BP. There was no alcohol in the patient's
blood, and the patient reported abstinence for 2 months.

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Baclofen was discontinued, given the likelihood of
baclofen toxicity at extremely high doses, and nicardipine
was administered intravenously to lower the BP. The patient
had been kept overnight for observation, when 4 days later,
she presented with severe anxiety, visual hallucinations, and
confusion. Clinicians ruled out alcohol withdrawal, given the
patient's prolonged abstinence from alcohol, and increased
oxazepam to 62.5 mg daily for symptomatic relief. After the
patient felt no relief of her symptoms, baclofen was reintroduced at a daily dose of 30 mg, prompting immediate relief
of the patient's anxiety and agitation. After a few days of
observation in the hospital, the patient was discharged on
baclofen 10 mg 3 times daily, escitalopram 10 mg daily,
oxazepam 12.5 daily, nicardipine if needed, and daily vitamin B1 and B6 supplementation.
The authors2 highlight the peculiarity of a withdrawal
syndrome that can only be managed with the exact agent that
was removed in the first place, rather than with benzodiazepines, which are often used to treat alcohol withdrawal
symptoms. Given that baclofen is a GABAB agonist, whereas
benzodiazepines, as a class, are GABAA agonists, the authors
suggest that these drugs would not alone be sufficient to treat
baclofen withdrawal syndrome. Last, it is important to note
the potential for dependence with baclofen, especially when
used at extremely high doses. It is reasonable to have a conversation between patient and clinician regarding these risks
before and throughout therapy.

Fatal Cardiotoxicity Following HighDose Cyclophosphamide
A 54-year-old woman with no significant medical history was
diagnosed with systemic sclerosis 2 years prior. Systemic sclerosis is an autoimmune connective tissue disease characterized
by fibrosis in skin and internal organs, damage to vasculature,
and autoantibody formation. Due to worsening skin fibrosis
and increasing pulmonary involvement, the patient was
referred for autologous hematopoietic stem cell transplantation (ASCT) with high-dose cyclophosphamide. Prior to transplantation, an extensive and comprehensive cardiopulmonary
examination was performed and found to be normal, including
physiologic, laboratory, radiological, and ECG.
Peripheral hematopoietic stem cells were mobilized with
cyclophosphamide (3 g/m2 total daily dose, given over 2 consecutive days) and filgrastim (10 µg/kg/d for 5 days). After
collection and cytapheresis, clinicians harvested 8.58 × 106
CD34+ cells/kg in one round, and froze the cells in DMSO
10% and albumin 4%. The patient was not experiencing
extreme toxicity or cardiovascular concerns.
The patient returned 1 month later for conditioning therapy
and to receive her ASCT, so cardiopulmonary markers were
examined. The patient had a normal left ventricular ejection
fraction (LVEF) of 63%, and troponins and other laboratory
findings were in the normal range. Conditioning therapy
involved administration of intravenous cyclophosphamide

Hospital Pharmacy - July/August 2019

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