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BACKGROUND: Association between clinical effect and serum concentration of amiodarone (AMI) and its active metabolite desethylamidarone (DEA) in patients after surgical ablation (SA) of atrial fibrillation (AF) has not yet been studied. AIMS: We wanted to find a correlation between AMI and DEA serum concentration and maintaining sinus rhythm (SR) after SA of AF. METHODS: Sixty eight patients with AF who had undergone surgical ablation between 2014 and 2017 were included in a single-centre, prospective, observational study. Maintaining of SR was evaluated by standard 12-lead ECG and 24-hour Holter ECG monitoring at months 1, 3, 6 and 12 following surgery. Therapeutic monitoring of AMI and DEA concentrations was done to optimize therapy and adverse effects were followed up. RESULTS: We have noticed a high success rate in maintaining of SR (overall 83%). The median of serum concentration of AMI was 0.81 mg/L (range 0.16-2.35 mg/L) and DEA 0.70 mg/l (range 0.19-2.63 mg/L). No significant differences were found in the serum concentratration of AMI, DEA or DEA/AMI concentratration ratios between patients with SR and persistent supraventricular tachyarrhythmia except on the second outpatient visit. We observed significant correlation between serum concentration of DEA and thyroid-stimulating hormone elevation. CONCLUSION: We confirmed the efficacy of AMI and DEA at the measured serum concentrations. However, analysis of these concentrations alone cannot replace assessment of the clinical response for treatment. Establishment of individual AMI (and DEA) concentrations at which the optimal therapeutic response is achieved seems to be advantageous. Therapeutic monitoring of AMI and DEA is helpful in personalised pharmacotherapy after SA of AF.
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INTRODUCTION: The ß1 adrenergic receptor blocker metoprolol is often prescribed together with the antiarrhythmic drug propafenone. Both are metabolized by cytochrome P450 2D6 and propafenone is also an inhibitor of this enzyme. We present a pediatric case showing metoprolol and propafenone intoxication in combination. CASE: A 14-year-old girl was admitted to a local emergency department after ingestion of metoprolol (probably 1g) and propafenone (probably 1.5-3g) in a suicide attempt. She developed cardiogenic shock with cardiac arrest and was fully resuscitated. Veno-arterial femorofemoral extracorporeal membrane oxygenation was started immediately. High serum levels of both drugs were detected approximately 10h after ingestion (2630ng/mL metoprolol and 2500ng/mL propafenone). Other serial samples for the monitoring of the levels of metoprolol and its metabolite alfa-hydroxymetoprolol were obtained between days 2 and 4 after admission. The metoprolol/alfa-hydroxymetoprolol ratio on the 2nd day was 36.1, indicative of a poor metabolizer phenotype. The elimination half-life of metoprolol was prolonged to 13.2h and the clearance decreased by about 70%. The patient condition gradually worsened, brain edema and intracerebral hemorrhage occurred, and on the 6th day, the patient died. CONCLUSION: We document a pediatric case report of death due to a mixed drug overdose of metoprolol and propafenone, along with data regarding serum metoprolol, alfa-hydroxymetoprolol, and propafenone levels.