Benzodiazepine overdose associated atrioventricular block.

Sir,

Drug overdose is a medical emergency necessitating immediate attention, close observation and support of vital organ functions. The popularity, widespread and sometimes easy availability of benzodiazepines (BZD) has led to their frequent abuse in intentional drug poisoning. Cardiac dysrhythmias, although common in overdose situations are uncommon in BZD poisoning.

A 48-year-old male, a known case of adjustment disorder with depressive reaction, with history of suicidal poisoning 1 month back, presented to our emergency room with history of unknown drug poisoning with suicidal intent. At the time of presentation, the patient had a Glasgow coma scale (GCS) score of 11 (E3M4V4) with a bilaterally constricted pupils, which were reacting to light, a pulse rate of 100/min, which was regular and a blood pressure of 70/50 mmHg for which Dopamine infusion was started. Electrocardiogram (ECG) performed, showed first degree atrioventricular (AV) block, which progressed to second degree heart block (Mobitz type 1). Electrolytes analysis revealed hypokalemia and hypocalcemia, but the ECG changes persisted even after the correction of potassium and calcium.

Further treatment received by the patient included a gastric lavage with 2 L normal saline, activated charcoal and forced dieresis with sodium bicarbonate, normal saline and furosemide. After his GCS improved, he admitted of consuming 30 tablets of Diazepam 10 mg about 4 h ago. Relying on his confession, he was started on titrated doses of intravenous flumazenil up to a maximum of 2.5 mg, which resulted in ECG rhythm reverting back to normal sinus, gradual tapering of dopamine with normalization of blood pressure. The urine sample analysis by cassette test was positive for diazepam metabolites.

BZDs mainly acts through gamma amino butyric acid-chloride ionophore in the central nervous system. BZD receptors (particularly BZ-3) have also been found in the periphery including myocardium.[1] BZD receptor agonists can reduce the current through both transient (T, type I, dihydropyridine-insensitive) and long-acting (L, type II, dihydropyridine-sensitive) calcium channels. Thuillez et al.[2] reported a functional antagonism between BZD receptor antagonist and nicardipine, a calcium channel blocker. There are also structural similarities between BZD and diltiazem, another Ca2+ channel blocker. Thus, BZDs behave like weak calcium-channel blockers, overdose of which may have caused the AV blocks in our patient.

Nakajima et al.[3] studied the effect of diazepam on the AV nodal conductivity using a direct perfusion technique of the canine AV node artery in situ and found diazepam injected into the AV node artery in doses from 300 μg to 3 mg elicited first to third degree AV blocks of longer duration following gradual prolongation of PR interval. This response was not affected by bilateral vagotomy and sympathectomy or pre-treatment of the AV node with hexamethonium or atropine. Thus, diazepam seemed to suppress conductivity of the AV node by a direct action. These findings are also expected in humans as supported by case reports by Ziegenbein and Kropp[4] and Arroyo Plasencia et al.[5]

Flumazenil acts at the central BZD receptor to antagonize or reverse the behavioral, neurologic and electrophysiologic effects of BZD agonists and inverse agonists. Its role in reversal of alprazolam overdose induced first degree heart block with flumazenil has also been reported by Mullins.[6]

These cases serve to remind clinicians of this rare, but potentially serious complication associated with BZD exposure and use of flumazenil to revert it.