Correspondence
Treatment of Calcium-Channel–Blocker Intoxication with Insulin Infusion
N Engl J Med 2001; 344:1721-1722May 31, 2001
- Article
To the Editor:
Overdose of calcium-channel blockers remains an important cause of fatal poisoning.1 Conventional therapy, consisting of intravenous fluids, calcium, dopamine, dobutamine, norepinephrine, and glucagon, often fails to improve hemodynamic function in intoxicated patients.2 Recent recommendations for treatment of intoxication with calcium-channel blockers include induction of hyperinsulinemia and euglycemia as adjunctive therapy.3 We report two cases of overdose of calcium-channel blockers in which a striking benefit was achieved with hyperinsulinemia–euglycemia therapy.
A 34-year-old nondiabetic woman with hypertension and renal failure ingested 12 extended-release tablets containing 2.5 mg of amlodipine each. Hypotension and bradycardia developed. Because of her history of renal failure, the treating physicians did not administer calcium and instead provided intravenous fluids, vasopressors, and glucagon.
A 48-year-old nondiabetic man with hypertension, chronic obstructive pulmonary disease, congestive heart failure, and depression was witnessed ingesting an unknown amount of extended-release diltiazem. He became hemodynamically unstable in the emergency department and did not respond to calcium, intravenous fluids, and vasopressors.
When conventional therapy failed to improve the hemodynamic status of these patients, hyperinsulinemia–euglycemia therapy with a continuous infusion of insulin at a rate of 0.5 IU per kilogram of body weight per hour rapidly reversed cardiovascular collapse in both. Despite the high doses of insulin administered, the first patient required no supplemental glucose, whereas the second received 10 percent dextrose at 100 ml per hour to maintain an average serum glucose concentration of 140 mg per deciliter. The clinical courses of the two patients are outlined in Table 1Table 1
Clinical Courses of Two Patients Treated with Hyperinsulinemia–Euglycemia Therapy..The clinical features of toxicity from calcium-channel blockers arise from blockade of L-type calcium channels in myocardial cells, smooth-muscle cells, and beta cells.4 Antagonism of these channels produces bradycardia, conduction delay, peripheral vasodilation, hypoinsulinemia, hyperglycemia, metabolic acidosis, and shock. Hypoinsulinemia may be a critical factor in overdose of calcium-channel blockers.5 In an unstressed state, myocytes oxidize free fatty acids for metabolic energy.3,4 In a state of shock, such as that associated with overdose of calcium-channel blockers, myocytes use glucose for fuel.3,4 Hypoinsulinemia may prevent the uptake of glucose by myocytes, causing a loss of inotropy, decreased peripheral vascular resistance, and shock.3
The exact mechanism of action of hyperinsulinemia–euglycemia therapy is poorly defined. Hyperinsulinemia–euglycemia therapy improves inotropy and peripheral vascular resistance and reverses acidosis, possibly by improving the uptake of carbohydrates by myocytes and smooth-muscle cells.3,4 Although hypoglycemia may occur with this therapy, the ease with which serum glucose can be measured by bedside capillary testing minimizes the likelihood of this complication. As other case reports have suggested, hyperinsulinemia–euglycemia therapy is safe and effective for life-threatening overdose of calcium-channel blockers.3
5 ReferencesEdward W. Boyer, M.D., Ph.D.
Michael Shannon, M.D., M.P.H.
Children's Hospital, Boston, MA 021551
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