Abstract
Although metoclopramide has many adverse effects, Torsade de pointes
(TdP) is rare. We describe a fatal case of repeated ventricular
fibrillation following TdP, due to multiple administrations of
metoclopramide. Multiple administrations of metoclopramide over a short
time to a patient with risk factors of TdP should be reconsidered.
Introduction
Metoclopramide is a dopamine 2-receptor antagonist with antiemetic
activity that releases acetylcholine from postganglionic nerve endings
and prevents apomorphine-induced vomiting1.
Metoclopramide is an antiemetic agent for chemotherapy and
post-operative nausea and vomiting2,3. Although
metoclopramide has many adverse effects(1), torsade de pointes (TdP) was
not stated4. Some risk factors of TdP include advanced
age, female, congestive heart failure and myocardial infarction,
corrected QT (QTc) >500 ms, QT-prolonging drugs, impaired
hepatic drug metabolism, hypokalemia, hypomagnesemia, hypocalcemia,
diuretics causing hypokalemia and hypomagnesemia, and
bradycardia5. Recently, a meta-analysis finding
suggested metoclopramide increased cardiac event risk, including sudden
cardiac death6. However, few case reports associate
TdP with metoclopramide, and none report fatalities. We describe a fatal
case of repeated ventricular fibrillation (VF) following TdP, due to
multiple administrations of metoclopramide.
Case report
A 92-year-old woman was admitted for epigastric pain, nausea and
diarrhea that persisted for a week. Her medical history consisted of a
complete atrioventricular block on a pacemaker, atrial fibrillation,
ischemic cardiac disease and chronic kidney disease. She had been taken
enalapril, spironolactone, azosemide, carvedilol, apixaban, rabeprazole,
rosuvastatin, nicorandil and zolpidem. On admission, her body
temperature was 36.7 ℃, blood pressure 109/75 mmHg, heart rate 58 BPM,
and oxygen saturation 98% on room air. She had a slight percussion
tenderness on the right hypochondriac region. The laboratory data showed
leukocytes 20,600/μL, aspartate aminotransferase 27 U/L, alanine
aminotransferase 41 U/L, creatinine 2.07 mg/dL, potassium concentration
4.0 mmoL/L, magnesium concentration 1.8 mg/dL, and C-reactive protein
25.9 mg/dL. Her electrocardiogram showed pacemaker potential and QTc
interval of 453 ms (Figure A). Although her echocardiogram showed
diffuse hypo-kinesis with an ejection fraction of 30%, there was no
change compared to a week earlier. She received three drip infusions of
metoclopramide 10 mg for nausea after admission. Nine hours after
initial administration, ECG showed QTc prolongation of 551 m/s (Figure
B). Twenty hours from initial administration, she suddenly lost
consciousness with TdP (Figure C). Then, the laboratory data showed
creatine kinase-MB 7 U/L, troponin T 0.088 ng/dL, potassium
concentration 5.1 mmol/L, corrected calcium concentration 9.9 mg/dL, and
magnesium concentration 1.8 mg/dL. The venous blood gas analysis showed
pH 7.344, oxygen partial pressure 37.9 mmHg,
carbon dioxide partial pressure 40.3 mmHg,
bicarbonate level 21.5 mmol/L, lactate level 2.08 mmol/L. Contrast CT
revealed liver abscess and portal vein thrombosis. Despite
cardiopulmonary resuscitation with three defibrillations for every
instance of VF following TdP and administration of adrenalin and
amiodarone, VF returned, and she died. No antibiotics were
administrated. Escherichia coli from her blood culture was
positive on the fifth day from collection.
Discussion
Some reports suggested QT prolongation caused by
metoclopramide7-9. A recent study stated that
supratherapeutic doses of metoclopramide might lead to QT and action
potential prolongation by inhibiting the human Ether-a-go-go-related
gene and sodium channel, resulting in ventricular
arrhythmias8. Moreover, 80% of metoclopramide is
excreted in the urine, and impaired renal function prolongs the
half-life1. Therefore, we hypothesized that QT
prolongation due to metoclopramide was excessively expressed under
multiple doses on impaired renal dysfunction.
To our knowledge, there are only three survived cases of torsade de
pointes associated with metoclopramide. All cases experienced TdP caused
by metoclopramide plus other risk factors. The first case was a
92-year-old woman taking two different QT-prolonging
drugs10. The second case was an 86-year-old man
administered metoclopramide four times daily with heart and renal
failure11. The third case was a 50-year-old woman
using three different QT-prolonging drugs12. Although
our patient had been taking diuretics, her electrolytes were normal.
None of the patient’s other drugs interacted with metoclopramide, and
she was not taking any QT-prolonging drugs known to cause
TdP4. Therefore, three administrations of 10 mg
metoclopramide in addition to advanced age, female, ischemic cardiac
disease and chronic kidney disease might have contributed to repeated VF
following TdP. Multiple administrations of metoclopramide over a short
time to a patient with risk factors of TdP should be reconsidered.