Jasmina Jovic-Stosic

Severe propranolol and ethanol overdose with wide complex tachycardia treated with intravenous lipid emulsion: A case report

Background. Propranolol is a highly lipid-soluble beta-blocker. We describe a case of severe propranolol overdose, with atypical dysrhythmia – wide complex tachycardia – which was successfully treated with lipid emulsion. Case report. A 31-year-old woman ingested approximately 3.6 g of propranolol along with ethanol. Clinical manifestations of poisoning included coma, seizures, respiratory failure, hypoglycaemia, circulatory shock, and dysrhythmias. An ECG revealed nonspecific intraventricular conduction delay, followed by wide complex supraventricular tachycardia. Toxicological analysis of blood showed ethanol 2.42 g/L and propranolol 4.21 mg/L. The patient responded poorly to conventional therapy, so intravenous lipid emulsion was used. Apart from IV dopamine, the only treatment after the onset of wide complex tachycardia was 20% Intralipid. Transient improvement was noticed after the initial dose of 500 mL; during the infusion of further Intralipid, blood pressure returned to normal and sinus rhythm was re-established. Conclusion. We believe that lipid emulsion had a beneficial effect in the treatment of propranolol toxicity.

Determination of flumazenil in serum by liquid chromatography-mass spectrometry: Application to kinetics study in acute diazepam overdose.

BACKGOUND/AIM Flumazenil is benzodiazepine receptor antagonist. It has been studied for a various indications, including reversal of sedation after surgery or diagnostic procedures, awakening of comatose patients in benzodiazepine overdose, or for symptomatic treatment of hepatic encephalopathy. Some drugs, like theophylline, may prolong its elimination half-life. Considering the long half-life of diazepam and its metabolites, concomitant use of theophylline may reduce the need for repeated dosing of flumazenil in patients with acute diazepam poisoning. The aim of this study was to introduce a reliable and accurate method for determining the concentration of flumazenil after therapeutic application in patients with acute poisoning, and using that method to assess whether the kinetics of flumazenil change in the presence of aminophylline (combination of theophylline and ethylenediamine in a 2:1 ratio) applied as concomitant therapy. METHODS Blood samples from patients with acute diazepam poisoning that received flumazenil at the dose of 0.5 mg, or the same dose with 3 mg/kg of body weight of aminophylline, were collected 1, 3, 10, 30, 60, 120 and 240 min after its intravenous administration. Samples were prepared by solid-phase extraction on Oasis HLB cartridges with ethylacetate as extracting agens. Flumazenil was determined by liquid chromatography with mass spectrometry (LC-MS) in single ionmonitoring mode at m/z 304. Separation of flumazenil from matrix compound was performed on Lichrospher RP-8 column usingthe mixture of acidic acetonitrile and 20 mM of ammonium acetatein water (55 : 45) as a mobile phase. RESULTS The applied analitycal method showed excellent recovery (94.65%). The obtained extracts were much cleaner than the extracts obtained by the sameextractant in the process of liquid-liquid extraction. The limit ofdetection of the LC-MS method described in this paper was 0.5 ng/mL and the limit of quantitation was 1 ng/mL. In the patientstreated with both flumazenil and aminophylline, the eliminationconstant for flumazenil was significantly lower and the elimination half-life was longer (p < 0.05) in comparison with the same parameters in.the patients who received flumazenil alone. CONCLUSION The applied LC-MS method for the determination of flumazenil in serum samples of patients with acute diazepam poisoning is rapid, sensitive, precise and specific. Concomitant use with theophylline significantly prolonged elimination of flumazenil during the treatment of acute poisonings with diazepam.