Methylene blue used in the treatment of refractory vasoplegic shock resulting from severe quetiapine poisoning.

Abstract

Objective: Methylene blue (MetBlue) inhibits nitric oxide synthase and guanylate cyclase as well as scavenging endothelial nitric oxide, decreasing vasodilation and increasing responsiveness to vasopressors. It is reported to improve haemodynamics in vasoplegic shock from various causes including septicaemia1 and post-cardiac surgery2. Reports of use in overdose are limited.3 We describe the use of MetBlue to treat a case of refractory vasoplegic shock following quetiapine poisoning. Case report: A 41 year-old male presented following reported ingestion of 18 g extended-release quetiapine, 10 g controlledrelease carbamazepine, 240 mg fluoxetine, 35 g enteric-coated sodium valproate, 375 mg oxazepam. He was comatose, intubated on presentation. Progressive hypotension developed. Electrocardiogram (ECG) revealed sinus rhythm, rate 82 bpm, QRS 120 msec, QT-interval 536 msec. Echocardiogram revealed a hyperdynamic left ventricle, suggesting vasoplegic shock. The patient remained hypotensive despite intravenous fluid-boluses, escalating infusion of metaraminol, noradrenaline and vasopressin. Hypotension was made worse after a single-dose of intravenous adrenaline (100 micrograms) with systolic blood pressure falling to 50 mmHg. Arterial blood gas revealed worsening metabolic acidaemia and rising lactate (peak 13 mmol/L). At this point, MetBlue was administered as loading-dose of 1.5 mg/kg and continuous infusion (1.5 mg/kg/h for 12 hours, then 0.75 mg/kg/h for 12 hours). Rapid improvement in haemodynamic parameters and weaning of vasopressors resulted in the hour following the loading-dose. Serum quetiapine concentration was 18,600 ng/mL (30-160 ng/mL), collected at time of peak toxicity. Serum valproate concentration peaked at the same time and was 1221 micromol/L (300-700 micromol/L). Serum carbamazepine concentration was in the therapeutic range. Conclusion(s): Severe quetiapine poisoning produces hypotension primarily from alpha-adrenoreceptor antagonism. Worsening hypotension has been reported previously following adrenaline administration. MetBlue may have utility in the treatment of vasoplegic shock resulting from quetiapine poisoning refractory to standard vasopressor therapy.