Hospital Pharmacy - July/August 2018 - 221

Mancano
necessary to maintain cardiovascular circulation. The patient
also had an elevated troponin of 16.5 µg/L (normal range, ≤0.1
µg/L). In light of the elevated troponin, the patient underwent
a coronary angiography, which revealed unremarkable coronary arteries; however, the patient did have impaired systolic
left ventricular function. Within a few hours, bradyarrhythmias with subsequent asystole emerged requiring an external
pacemaker and frequent mechanical resuscitation. In addition,
the patient developed a fever, anuria, hyperkalemia, and metabolic acidosis. Sadly, the patient expired 8 hours after his second surgery. He had received a propofol infusion for a total of
132 hours at an average dose of 4.6 mg/kg/h.
Postmortem tissue samples had been obtained of the
patient's heart muscle from the ventricles, skeletal muscle,
and liver. Autopsy results revealed massive steatosis of the
liver and biventricular cardiac thickening. Also detected
were microvesicular fatty degeneration of the hepatocytes,
myocardial edema, and disseminated necrosis of heart muscle cells. Histological analysis of the skeletal muscle indicated the patient had rhabdomyolysis. The mitochondria of
skeletal muscle samples revealed a disintegration of the outer
membrane and a loss of cristae. Prior to the patient's death,
blood samples were drawn and analyzed for acylcarnitines.
Concentrations of several short-chain acylcarnitines showed
considerable increases in comparison with a healthy individual: C2-carnitine, 16.712 µmol/L vs 1.036 µmol/L;
C4-carnitine, 7.125 µmol/L vs 0.059 µmol/L, and C5-carnitine
4.957 µmol/L vs 0.073 µmol/L.
Prior research has hypothesized that the impairment of
mitochondrial fatty acid oxidation is the probable main cause
of PRIS. Vollmer et al2 conducted electron microscopic analysis of the patient's heart muscle tissue which showed prominent electron dense structures clearly associated with the
mitochondria. These electron dense structures might be composed of accumulated free fatty acids that did not pass the
mitochondrial membrane caused by propofol. Their analysis
gives evidence that mitochondria of cardiac muscle seem to
be the centrally affected structure in PRIS and may explain
the dramatic and self-accelerating process with initial
arrhythmias rapidly leading into progressive cardiac decompensation. The authors call for the development of suitable
diagnostic and predictive tools for the detection and prevention of PRIS.

Ivermectin-Induced Stevens-Johnson
Syndrome3
A 38-year-old man received a 12 mg oral dose of ivermectin
as part of a nationwide campaign against worm parasitic disease in the Republic of Cameroon. The next day, the patient
noted that he had blisters on his lips, which later extended to
involve his oral mucosa. These symptoms were also associated with pain while chewing and soreness of his entire oral
mucosa, which impaired his ability to eat. The patient also
developed a rash on his face. The rash was scaly and extended

221
toward the patient's hairline. The next day, the patient noted
that his eyes became reddish, itchy, painful, and began to
discharge a clear fluid. At this time, the patient decided to
seek medical attention for his condition.
A medication history revealed that the patient had not
ingested any other drug besides ivermectin. He did remember receiving a dose of ivermectin 1 year earlier during a
similar disease campaign but he did not experience any
adverse effects. The patient reported he was human immunodeficiency virus (HIV) negative based on an HIV test conducted 6 months earlier but he did not have any documentation.
However, he reported his wife is HIV positive and was currently receiving highly active antiretroviral therapy. The
patient reported he did not have any chronic diseases and
denied having any food or drug allergies. Physical exam
revealed desquamating hyperpigmented rashes on his face
with whitish plaques. The rashes were on the nasal bridge
and extended to the malar area, sparing the nostrils. There
were black eschars and erythematous erosions on the lips
with sores and blisters in the oral mucosa. His eyes were erythematous, tearing, and had sticky secretions that made his
eyelids difficult to separate.
The patient was suspected of having Stevens-Johnson syndrome (SJS). He was tested for HIV and a first-line HIV test
was positive. In addition, a repeat first-line HIV test and a second-line HIV test confirmed his HIV positive status. A subsequent CD4 count was 568 cells/mm3 (normal range, 500-1400
cells/mm3). Baseline laboratory tests were unremarkable as they
demonstrated a normal complete blood count, liver enzymes,
and kidney function. The patient was treated with an intramuscular dose of dexamethasone 4 mg followed by 15 days of a
prednisone taper starting at 20 mg of prednisone twice daily. He
was also given oral antihistamines, ciprofloxacin eye drops, and
oral hygiene. Within 1 week, the patient's symptoms improved
and most lesions had resolved within 3 weeks.
The authors point out that the antimicrobials that are commonly associated with causing SJS include sulfonamides and
aminopenicillins. Those less frequently associated with SJS
are cephalosporins, fluoroquinolones, vancomycin, and antituberculosis medications. Additional antimicrobials such as
fluconazole and streptomycin have also been associated with
causing SJS. This patient had previously ingested ivermectin
at the same dose 1 year earlier with no reaction. However,
after his current dose of ivermectin, he experienced SJS. This
may suggest that this case of SJS caused by ivermectin may
be idiosyncratic because it seems to be dose-independent. An
interesting fact is that 1 year earlier when the patient received
his first dose of ivermectin, the patient was confirmed HIV
negative. However, he developed SJS during the current
ingestion of ivermectin when he confirmed to be HIV positive. The authors conclude that there may be a link between
HIV infection and ivermectin-induced SJS, as underlying
diseases especially those that impair immunity may have a
role in the development of SJS and HIV-seropositive patients
have a higher incidence of SJS.

Table of Contents for the Digital Edition of Hospital Pharmacy - July/August 2018