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Merck

The spectrum of acute heart failure after venlafaxine overdose.

Clinical toxicology (Philadelphia, Pa.) (2013-01-11)
M Batista, T Dugernier, M Simon, V Haufroid, A Capron, S Fonseca, F Bonbled, P Hantson
ABSTRACT

Venlafaxine is a bicyclic antidepressant that may be associated with severe cardiotoxicity following large overdose. The purpose of this short case series is to present different patterns of venlafaxine-related cardiotoxicity and to discuss the potential mechanisms. Between January 2010 and July 2011, four patients were admitted to an ICU with acute left ventricular failure following large venlafaxine overdoses. The age of the four female patients ranged from 35 to 65 years. None of them had no history of cardiovascular disease. The amount of venlafaxine ingested by history ranged from 3150 to 13500 mg (extended-release preparation in two cases). The peak serum venlafaxine concentration was between 2153.3 and 9950 ng/ml. Three patients died and one recovered rapidly. The initial ECG revealed only mild abnormalities in two cases. In two patients, at least one ECG recording demonstrated a widening of QRS interval. In three patients, echocardiography disclosed a left ejection fraction of 15%-18%. Two patients presented a severe serotonin syndrome, with major rhabdomyolysis. Seizures were noted in two cases, including one patient with status epilepticus. Three patients were mechanically ventilated. The causes of death were refractory hypoxemia, malignant arrhythmias, and cardiogenic shock, respectively. Severe and diffuse left ventricular dysfunction may be observed after large venlafaxine overdoses and this is not always associated with severe cardiac conduction function abnormalities. The mechanisms underlying venlafaxine-related cardiac failure with preserved normal cardiac conduction are discussed. A possible explanation may be a catecholamine-induced myocardial damage in relationship with the inhibition of norepinephrine (and dopamine) reuptake.

MATERIALS
Product Number
Brand
Product Description

Venlafaxine for system suitability, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Venlafaxine hydrochloride, ≥98% (HPLC), powder
Supelco
Venlafaxine hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
Venlafaxine hydrochloride, European Pharmacopoeia (EP) Reference Standard