Treatment of Severe Combined Overdose of Calcium Antagonists and Converting Enzyme Inhibitors with Angiotensin II

Dr. J.L. Tovar, Servicio de Nefrologia, Hospital General Valle de Hebron, Po Valle de Hebron s/n, E-08035 Barcelona (Spain) Dear Sir, Angiotensin II has been proposed as an alternative treatment for refractory septic shock unresponsive to noradrenaline [1, 2], but there are other circumstances involving severe hypotension in which it may also prove useful; we are presenting a case in point. A 34-year-old previously healthy woman who took an overdose of 200 mg of enalapril maleate, 110 mg of ramipril, 300 mg of am-lodipine and 600 mg of nitrendipine by oral ingestion was admitted 4.5 h following inges-tion. When examined, no signs of neurological deficit were evident, systolic blood pressure was 50 mm Hg, heart rate 110 beats/ min and average urine output 10 ml/h. Significant serum biochemical data included: creatinine 120μmol/l (1.35 mg/dl), glucose 5.82 mmol/l (105 mg/dl), uric acid 374 μmol/l (6.5 mg/dl), sodium 140 mmol/l‚potas-sium 4.5 mmol/l, pH 7.39, pC02 38 mmol/l and total CC1⁄8 22.9 nmol/l. Treatment with intravenous calcium gluconate (1,000 mg), isotonic saline solution (2.08 ml/min), dopa-mine (4.9 μg/kg/min) and progressive doses of noradrenaline (up to a maximum of 60 μg/min) was administered. However, 3 h later, although the central venous pressure rose to 24 cm 7⁄8O, systolic blood pressure remained at the same level, diuresis did not improve and finally circulatory overload became apparent. Angiotensin II (Hypertensin®, Ciba) perfusion was then initiated at the rate of 5.0 μg/min and rapidly increased to 15μg/min. Almost immediately, systolic blood pressure rose to 100 mm Hg and both improvement of the diuresis output and disappearance of the cardiac failure signs were observed. The noradrenaline dose could then be reduced to 10 μg/min but the same angiotensin II dose has to be kept up for the next 24 h to preserve hemodynamic parameters. When angiotensin was discontinued, dopamine and noradrenaline had to be increased to 24 μg/kg/min and 33 μg/min respectively and then progressively reduced until totally phased out 72 h later. On the fourth day postadmission, the patient had totally recovered and was discharged from the intensive care unit. Creatinine clearance in the convalescent phase was 96 ml/min. Serum levels of enalapril and ramipril were 1.2 and 6.5 μg/ml respectively 10 h