Correspondence

Calcium Gluconate in Severe Verapamil Intoxication

N Engl J Med 1994; 330:718-720March 10, 1994

Article

To the Editor:

Intoxication with verapamil is a serious and often fatal condition, complicated by severe hypotension and cardiac-conduction abnormalities1-4. The current therapeutic approach involves intravenous atropine, catecholamines, ventilation, and the insertion of a pacemaker.

A 65-year-old woman treated with sustained-release verapamil for hypertension was admitted to our hospital in a coma (Glasgow coma score, 4). The blood pressure was 83/63 mm Hg, and the heart rate was 42 beats per minute (atrioventricular nodal rhythm with right bundle-branch block). The results of a routine drug screening were negative. Verapamil overdose was suspected, and gastric lavage was performed. The patient received endotracheal intubation, ventilation, a transvenous pacemaker, and catecholamines. Twenty-four hours later, her condition stabilized, and she was extubated. Eight hours later, the blood pressure dropped again to 42 mm Hg. Epinephrine, reintubation, ventilation, and cardiac pacing produced no improvement in hemodynamic variables (Figure 1Figure 1Heart Rate and Systolic and Diastolic Arterial Blood Pressure before and during the Intravenous Administration of Calcium Gluconate.). Then, calcium gluconate (20 ml of 10 percent calcium) was administered, resulting in a mean blood pressure of 80 mm Hg and sinus rhythm (Figure 1). The effects were transient, and repeated boluses (a total of 18 g of calcium) were required during the next 180 minutes. The serum calcium concentration increased from 2.76 to 3.04 mmol per liter. The patient's condition remained stable, and catecholamines were stopped. The plasma levels of verapamil and its metabolite, norverapamil, were excessively high5 (Figure 2Figure 2Plasma Concentrations of Verapamil and Its Main Metabolite, Norverapamil.).

The role of calcium gluconate in the treatment of intoxication with calcium-channel blockers is controversial. In animals, calcium chloride restores blood pressure, reverses conduction abnormalities, and prevents death after exposure to lethal doses of verapamil and propranolol1. In our patient standard therapy was effective only briefly; when the verapamil levels were highest, intravenous calcium gluconate was required. The different effects of calcium in this patient, as compared with those in other reports,2-4 are probably related to differences in dosages. In this patient, a total of 18 g was injected within a 3-hour period, whereas others gave small amounts (1 to 2 g)3,4 or larger doses over prolonged periods of time (24 g in 44 hours)2.

The late peak of serum verapamil concentrations could be due to the slow-release formulation and kinetics. After prolonged treatment, the bioavailability of verapamil increases and clearance decreases owing to the saturation of hepatic metabolism. The inhibitory effects of calcium-channel blockers on gastrointestinal smooth muscle also contributed to delayed resorption. Hypotension and shock with hypoperfusion of the liver, delayed metabolism, and reflow from peripheral tissues may also contribute to late and high peak values.

In summary, large quantities of calcium gluconate were safe and effective in this patient with severe intoxication with verapamil.

Thomas F. Luscher, M.D.
Georg Noll, M.D.
Inselspital, CH-3010 Bern, Switzerland

Til Sturmer, M.D.
Beat Huser, M.D.
Markus Wenk, Ph.D.
University Hospital, CH-4030 Basel, Switzerland

5 References

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Citing Articles (6)

Citing Articles

1. 1

   M. Sawatzki, O. Kummer, S. Krähenbühl, M. Siegemund. (2010) 35-jährige Patientin mit generalisiertem Krampfanfall und nicht-kardiogenem Lungenödem nach Intoxikation. Der Internist 51:4, 528-532
   CrossRef

2. 2

   S. Eliza Halcomb, Lewis S. Nelson. (2006) Case files of the medical toxicology fellowship training program at the New York City Poison Control Center: Hypotensive death — Therapeutic complication or suicide?. Journal of Medical Toxicology 2:2, 75-80
   CrossRef

3. 3

   Riccardo Gerloni, Roberto Copetti. (2004) Easily reversible hypoxemia and hypotension induced by nimodipine. European Journal of Emergency Medicine 11:5, 295-297
   CrossRef

4. 4

   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

5. 5

   Edward P. Krenzelok, Jerrold B. Leikin. (1996) Approach to the poisoned patient. Disease-a-Month 42:9, 514-607
   CrossRef

6. 6

   &NA;. (1994) Verapamil overdose. Reactions Weekly &NA;:493, 12
   CrossRef