Cardiovascular Management of Amisulpride Overdose

Abstract

A 61-year-old man presented to the emergency department following an intentional overdose of 32 g of amisulpride (therapeutic dose: 50-1,200 mg/day). On arrival, he was unconscious (Glasgow Coma Score 3), had poor respiratory effort, hypotension (blood pressure 90/40 mm Hg) and hypothermia (temperature 32.4°C). An ECG demonstrated sinus rhythm, a heart rate of 90 bpm, with intermittent selfresolving ventricular tachycardia and a prolonged QTc interval (corrected QT time, calculated with Bazett' s formula, of 431 msec). Laboratory results included: Na + 141 mmol/L, Cl -102 mmol/L, K + 3.9 mmol/L and an ionised Ca 2+ of 1.17 mmol/L. Blood gases showed a lactic acidosis with a pH of 7.05, base deficit of -15 mmol/L and a lactate of 12 mmol/L. The initial plasma amisulpride level was found to be 50 mg/L. Immediate treatment consisted of intubation, mechanical ventilation and fluid resuscitation. The patient required vasopressor therapy with noradrenaline at a rate of 0.25 µg/kg/min. Despite receiving 5 litres of Hartmann' s solution and maintaining a central venous pressure of around 12 cm H 2 O, his noradrenaline requirements increased to 0.56 µg/kg/min.He was transferred to the intensive care unit (ICU) where haemodynamic assessment using the LiDCO Rapid © technique demonstrated a low cardiac output. Considered together with lactic acidosis, this suggested low global tissue perfusion. This was treated with dobutamine, while continuous veno-venous haemofiltration (CVVHF) and a simultaneous sodium bicarbonate infusion were initiated to reduce the immediate cardiovascular effects of the low pH. CVVHF was maintained almost continuously, at a dose of 35 mL/kg/h. Accusol 35 (Baxter International Inc.) was used as the buffer solution.The plasma amisulpride level following haemofiltration was higher (59.5 mg/L) than the initial level, suggesting either a haemoconcentration effect or continued absorption.The lactic acidosis resolved over the initial 12 hours, but significant cardiovascular instability was a continuing feature over the next few days. There were four recorded episodes of torsades de pointes, one example of which is shown in Figure 1. One episode required a precordial thump, another direct current shock and others were self-resolving. These episodes resolved following further aggressive therapy, as suggested by TOXBASE, aimed at: • Maintenance of serum potassium, calcium, and magnesium levels at the high end of the normal range • Reduction of the QTc interval by increasing the heart rate above 100 bpm using an isoprenaline infusion. 1 After commencing the isoprenaline infusion, no further episodes of torsades de pointes occurred.The maximum QTc of 725 msec (Figure 2) was recorded at 50 hours post-overdose. It remained elevated at 451 msec in spite of therapy until 190 hours post-overdose.In view of the long-term ventilatory requirements, a tracheostomy was inserted on day eight. The patient was successfully decannulated on day 14 and made an uneventful and complete recovery.A 61-year-old man took an amisulprid...

Thorough QT study of the effect of intravenous amisulpride on QTc interval in Caucasian and Japanese healthy subjects

“…Overall, blood pressure variations were devoid of clinical significance and no arrhythmia was reported . The occurrence of torsade de pointes associated with amisulpride has been reported . However, all cases are related to extremely large acute overdoses of amisulpride, ranging from 4000–80 000 mg, leading to high plasma concentration of amisulpride.…”

“…The overall safety profile of amisulpride at its approved doses has been assessed in numerous clinical studies with no evidence of cardiac toxicity . However, very large overdoses of oral amisulpride have been associated with the development of torsade de pointes (TdP) and there is a solitary case report in the literature suggesting that TdP may have been caused by a low oral dose of 100 mg day −1 in a patient with a low body mass index .…”