Correspondence

Overdose of Metoprolol Treated with Enoximone

N Engl J Med 1996; 335:1538-1539November 14, 1996

Article

To the Editor:

Severe poisoning with β-adrenergic–receptor blocking agents, which leads to decreased production of cellular cyclic AMP and impaired release of calcium from the sarcoplasmic reticulum, causes bradycardia and hypotension that can be refractory to treatment with catecholamines, calcium, and glucagon.1 We report on a patient with a life-threatening overdose of metoprolol, whose hemodynamic condition improved dramatically with the administration of enoximone, an inhibitor of phosphodiesterase III.

The patient was a 55-year-old woman who intentionally ingested metoprolol in a total dose of 10 g. She was found unconscious about one hour later, with a heart rate of 55 beats per minute and a systolic blood pressure of 50 mm Hg. Cardiopulmonary resuscitation was started, and high doses of epinephrine and atropine were given before a sufficiently stable blood pressure of 90/50 mm Hg could be established. Gastric lavage was performed, and the patient was transported to our institution.

The initial serum concentration of metoprolol was 23.2 mg per liter (therapeutic range, 0.1 to 0.6). An electrocardiogram showed a sinus rhythm at 65 beats per minute. However, the blood pressure was unstable, despite the administration of high doses of atropine, calcium, glucagon, and epinephrine. A Swan–Ganz catheter was inserted and revealed a severely depressed cardiac output (1.3 liters per minute) and a stroke volume of 19 ml. The calculated systemic vascular resistance was 4000 dyn · sec · cm-⁵.

After these measurements had been made, the patient received a bolus injection of 0.5 mg of enoximone per kilogram of body weight, which resulted in an immediate increase in the cardiac output to 2.0 liters per minute. Concomitantly, the stroke volume increased to 27 ml, and the systemic vascular resistance dropped to 2972 dyn · sec · cm-⁵. The patient then received a continuous infusion of 15 μg of enoximone per kilogram per minute. Two hours later, the cardiac output was 3.6 liters per minute, the stroke volume was 48 ml, and the systemic vascular resistance was 2058 dyn · sec · cm-⁵. During the following 48 hours, the patient's clinical condition markedly improved. All medication was discontinued, metoprolol was no longer detectable in the serum, and the patient was extubated without further complications.

Enoximone is a drug with positive inotropic and vasodilating effects that are mediated by the selective inhibition of phosphodiesterase III and the elevation of intracellular cyclic AMP.2 This action is therefore independent of the β-adrenergic system. Enoximone is used for the short-term treatment of congestive heart failure, particularly after surgery.3 This case extends the potential therapeutic value of enoximone to the treatment of severe poisoning with β-adrenergic–receptor blocking agents.

Marius M. Hoeper, M.D.
Klaus H.W. Boeker, M.D.
Medizinische Hochschule Hannover, 30623 Hannover, Germany

3 References

1. 1

   Lovejoy FH Jr, Linden CH. Acute poison and drug overdosage. In: Wilson JD, Braunwald E, Isselbacher KJ, eds. Harrison's principles of internal medicine. 12th ed. Vol. 2. New York: McGraw-Hill, 1991:2163-82.
   

2. 2

   Bethke T, Eschenhagen T, Klimkiewicz A, et al. Phosphodiesterase inhibition by enoximone in preparations from nonfailing and failing human hearts. Arzneimittelforschung 1992;42:437-445
   Web of Science | Medline

3. 3

   Crawford MH. Intravenous use of enoximone. Am J Cardiol 1987;60:42C-45C
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Christopher R DeWitt, Javier C Waksman. (2004) Pharmacology, Pathophysiology and Management of Calcium Channel Blocker and ??-Blocker Toxicity. Toxicological Reviews 23:4, 223-238
   CrossRef

2. 2

   Simon F Shakar, William T Abraham, Edward M Gilbert, Alastair D Robertson, Brian D Lowes, Lawrence S Zisman, Debra A Ferguson, Michael R Bristow. (1998) Combined Oral Positive Inotropic and Beta-Blocker Therapy for Treatment of Refractory Class IV Heart Failure. Journal of the American College of Cardiology 31:6, 1336-1340
   CrossRef

3. 3

   &NA;. (1996) Metoprolol overdose. Reactions Weekly &NA;:628, 9
   CrossRef