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Mancano et al
(200 mg/kg over 4 consecutive days) 12 grams administered
over 4 days, hydration therapy with 2 L of IV normal saline
per day, intravenous rabbit antithymocyte globulins (2.5 mg/
kg/d over 3 consecutive days). In addition to conditioning
therapy, harvested CD34+ cells were thawed and reinfused
after being washed twice, to remove the maximal amount of
DMSO possible.
Within 12 hours after ASCT, progressive acute pulmonary
edema developed and intravenous diuretics were administered
for management. Ten hours later, signs of worsening acute pulmonary edema appeared, with the patient complaining of anterior chest pain and difficulty breathing, and confirmed on chest
radiograph and ECG. On examination, the patient had decreasing BP of 90/45 mm Hg, a heart rate of 130 bpm, bilateral
crackles, and an O2 saturation of 89% on room air. Laboratory
findings showed Troponin Ic of 9.59 μg/L (normal range,
≤0.04 μg/L) and B-type Natriuretic Peptide (BNP) of 7136
ng/L (normal range, ≤100 ng/L), and LVEF was <10% on
echocardiogram. Clinicians suspected cyclophosphamideinduced cardiotoxicity, and the patient was transferred to the
intensive care unit. Shortly thereafter, the patient suffered cardiac arrest, and despite supportive therapy involving dobutamine and heparin, the patient showed no improvement in her
cardiovascular condition. A thrombus formed in the left side of
her heart, extending into the pulmonary vein; concurrently, an
intracranial hemorrhage formed, posing a contraindication to
the intensive anticoagulation needed to treat the clot in her
heart. The patient died within 24 hours. On autopsy, the heart
exhibited signs of hemorrhagic pericarditis, thrombus formation, extending to the pulmonary veins and the inferior vena
cava. The authors3 noted these findings supported cyclophosphamide-induced cardiotoxicity as the likely cause of death.
The authors state that this case represents the first report of
histologically proven cyclophosphamide-related cardiotoxicity in a patient receiving ASCT for an autoimmune
disease. Reports of cyclophosphamide-mediated cardiotoxicity in the literature are almost exclusively related to the drug's
use in cancer patients, when used concomitantly with other
cardiotoxic medications. Although the authors intended to
take utmost precautions and completed an extremely comprehensive examination of the patient's cardiovascular health,
this toxicity still manifested, suggesting the seeming unpredictability of this reaction. Fortunately, the authors posit that
acute cyclophosphamide-induced cardiotoxicity is very rare;
nonetheless, further research is certainly warranted.

Acute Anterograde Amnestic
Syndrome Induced by Fentanyl
The authors4 evaluated a total of 14 patients that had an acute
anterograde amnestic syndrome in Massachusetts between
2012 and 2016, and noted 13 tested positive for opioids on a
toxicological screen or had a history of opioid use, but none
of them underwent testing for synthetic opioids such as fentanyl. Anterograde amnesia is a loss of the ability to create

new memories after the event that caused amnesia, leading to
a partial or complete inability to recall the recent past, while
long-term memories from before the event remain intact.
The acute anterograde amnestic syndrome described in these
patient cases lasted for months or longer and was characterized by a hyperintense signal involving both hippocampi on
magnetic resonance imaging diffusion-weighted sequences.
There were also variably observed deficits in other cognitive
domains such as orientation and attention.
In 2017, there was a patient with a history of heroin use
that experienced this amnestic syndrome after overdosing in
Maryland, who was later transferred to a tertiary care center
in West Virginia, and tested positive for the fentanyl metabolite norfentanyl and cocaine. In addition, there were 4 patients
with a history of heroin use (ages ranging 28 to 37 years) who
presented with the same amnestic syndrome in Massachusetts
who all tested positive for fentanyl and norfentanyl (3 confirmed by urine fentanyl level 1.8 to >200 ng/mL
and 1 confirmed by serum fentanyl level 1.87 ng/mL.
The authors suggest that interpretation of the cause of the
amnestic syndrome is limited because another unidentified
drug, adulterant, or contaminant that was not tested for may
be the cause of the amnestic syndrome. However, the authors
feel that the confirmed presence of fentanyl in the 4 patients,
and the fact that in 2 of the 4 patients fentanyl was the only
drug detected strengthens the association of fentanyl and this
syndrome, and the authors feel that this syndrome is being
observed in patients now because of the increasing presence
of fentanyl in illicit drugs. The authors end by suggesting an
expanded toxicologic screening for fentanyl and its analogues in patients with a history of substance use who present with this amnestic syndrome.

Ivermectin-Induced Toxic Epidermal
Necrolysis
A 45-year-old man presented with worsening rash involving
his entire body 3 days after taking 15 mg of ivermectin,
which was ordered in the ED for suspected body lice. On
examination, the patient had oral blisters, conjunctivitis, and
a generalized erythematous maculopapular rash involving
his entire body with denudation of the skin on his back. The
patient tested negative for HIV, hepatitis A, B, and C, urine
toxicology screen, autoimmune screen, and rapid plasma
regain. Skin biopsy and further pathological examination
showed acute vacuolar interface dermatitis with many
cytoids and epidermal necrosis consistent with toxic epidermal necrolysis (TEN). The patient received supportive care
and made an unremarkable recovery with no long-term
sequelae. Based on the Naranjo algorithm, the patient scored
7 out of 10 which supports the assessment that this was a
drug-related adverse event.
The authors5 note that TEN is a rare, severe, cutaneous
adverse reaction that can be fatal. The average mortality rate
of TEN is 25% to 35% but can be higher in elderly patients

Hospital Pharmacy - July/August 2019

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