The concurrent administration of
dantrolene and
verapamil has the theoretical advantage of being more efficacious than
dantrolene alone in the treatment of
malignant hyperthermia. However, the combination has been reported to cause fatal
hyperkalemia in pigs. The present study evaluated the serum concentrations of
cations, serum osmolarity, and cardiovascular responses in 20 mongrel dogs after
dantrolene with and without the concurrent administration of
verapamil. The dogs were randomly classified into four groups of five dogs each: group 1 received neither
dantrolene nor
verapamil; group 2 received three successive intravenous doses of
dantrolene (1, 3, and 6 mg/kg) at 30-minute intervals; group 3 received
verapamil 0.1 mg/kg IV bolus, followed by a continuous infusion of 5 micrograms.kg-1.hr-1; and group 4 received
verapamil as in group 3, followed by
dantrolene as in group 2. Measurements were made at 15-minute intervals for 2 1/2 hours. Progressive and similar statistically significant increases in mean serum
potassium occurred after 105 minutes in dogs given
dantrolene (group 2, mean peak serum
potassium levels 5.4 +/- 0.5 mmol/L) and after 90 minutes in dogs given
verapamil-
dantrolene (group 4, 5.2 +/- 1.6 mmol/L). A statistically significant decrease in serum
sodium levels was also found in groups 2 and 4. One dog in group 4 developed intermittent second-degree
heart block after the final dose of
dantrolene. Serum
calcium levels (ionized and total) tended to decrease in groups 2 and 4. There were no statistically significant differences in osmolarities, cardiac outputs, or mean arterial blood pressures among groups. In summary, significant elevations of serum
potassium were observed in this dog model given
dantrolene with and without
verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)