Poisoning By Intravenous Verapamil In Pediatric Case

A 17 month old child affected by Adams-Oliver Syndrome (AOS) was admitted to Children Hospital Complaining of lack of appetite and weight loss. The AOS has diagnosed based on the association of pulmonary hypertension, aplasia cutis congenita, teleangectasia and left foot fingers defects.The child was treated with 20 mg/die of Verapamil per mouth. The treatment was maintained after consultation with the pediatric cardiologist who examined the child at admission. Due to the drug being erroneously administered intra-venously, a sudden onset of hypotension followed by bradycardia anda cardiac arrest supervened. Intubation, O2 and external massage were required. An initial administration of adrenalin did not achieve any cardiopulmonary esponse. The heart activity was restored only after calcium infusion but a stable cardiovascular state was achieved when atropine was added. Mechanical ventilator support was required and calcium administration was continued. Despite the successful cardiopulmonary resuscitation, the prolonged cardiac arrest (20 min) resulted in extensive cerebral hypoxia. The child, after admission into the Intensive Care Unit, showed hypethermia (39,5 C°) and convulsions; he died two days thereafter. A post-mortem examination revealed the typical features of AOS. The body showed widening of the superficial veins of the abdomen and skull, dysplastic area in the occipital region of the head and aplasia of all fingers of the left foot. Cardiomegaly, right heart hypertrophy, dilatation of tricuspid valve ring were also recorded. Lungs were congested and showed a massive oedema; bilateral serous pleural effusions were present. There was brain swelling. Microscopic observation howed thickening of the lung vessel wall, organ congestion and pulmonary oedema. Prior to death, toxicological analyses were not performed therefore the Verapamil concentration in body fluids are unknown. Postmortem toxicological analyses showed Verapamil traces in the bile.Verapamil is a Calcium-antagonist. It blocks the inward flux of calcium ions into cells through “slow channels” from extracellular sites. Report verapamil overdosages are usually linked with oral assumption. After ingestion of therapeutic dosages, verapamil is rapidly and completely absorbed from the gastrointestinal tract, with extensive first-pass hepatic metabolism yielding generally low bioavailability. The volume of distribution is generally large and protein binding is high. Elimination is almost entirely by the liver. The effects of the Verapamil overdose consist in the enhancements of its pharmacologic activity. They include suppression of sinus node automaticity and inhibition of atrio-ventriculare conduction, vasodilatation and negative inotropic effects. More recently, the diabetogenic effects of verapamil overdose, an acute presentation of multifocal myoclonus and a non-cardiogenic pulmonary oedema with the same drug-induced etiology have been described. In slow releasing formulations a wide interval of time elapses between the administration and the onset of symptoms which generally allows to manage successfully overdosage. Due to the lack of a specific antidote, the management of verapamil toxicity is mainly supportive. After an early, effective gastrointestinal decontamination, including the use of oral activaded charcoal, calcium is indicated to reserve bradycardia and hypotension; inotropic support is also required. There are alternative and adjuvant drugs such ad amrinone, insulin-glucose, 4-aminoperydine and calcium entry promoters Management of fluid/electrolyte, acid/base and ventilation abnormalities is required to treat large ingestions of verapamil. Overdose with slow-release veapamil require prolonged treatment with calcium salts. Most of patients recover without deficits. In this case, however, 20 mg of verapamil were administered intravenously. The ensuing cardiac arrest was reversed by resuscitation and by administration of calcium and atropine but the prolonged cerebral hypoxia lead ultimately to death. As expected, no specific findings were obtained by the autopsy and post-mortem toxicology. The temporal association of bradycardia, hypotension and cardiac arrest with the witnessed intravenous injection of verapamil is consistent with a diagnosis of verapamil poisoning. The Ca-antagonist overdose was further confirmed by the restoration of cardiac activity after calcium infusion