Glucagon and phenylephrine combination vs glucagon alone in experimental verapamil overdose.
OBJECTIVE
To evaluate glucagon and phenylephrine in combination as a treatment for the hemodynamic effects of verapamil overdose.


METHODS
Pentobarbital-anesthetized and instrumented dogs were overdosed using a previously developed verapamil overdose model (15 mg/kg IV over 30 minutes). The animals were maintained and observed for 90 minutes or until death. Cardiac output (CO), heart rate (HR), and mean arterial pressure (MAP) were monitored. Following the 30-minute verapamil infusion (toxicity), the control animals received no treatment; the glucagon animals received a 5-mg glucagon bolus and a drip of 5 mg/90 minutes; and the glucagon/phenylephrine animals received the same glucagon therapy plus a phenylephrine drip titrated to 180 micrograms/min over 15 minutes. The groups were compared using analysis of variance: the experimental variables were group and time; the response variables were changes from toxicity for the hemodynamic parameters. Post-hoc comparisons were done with alpha set at 0.05.


RESULTS
A significant change in CO was seen in the glucagon group (delta = 2.6 L/min) and the glucagon/phenylephrine group (delta = 1.9 L/min) compared with the control group (delta = 0.8 L/min). The change in CO was significantly larger for the glucagon animals compared with the glucagon/phenylephrine animals. The change in MAP for the glucagon/phenylephrine group (delta = 24 mm Hg) was significant compared with the control group (delta = 14 mm Hg). The MAP change for the glucagon group (delta = 19 mm Hg) was not significantly different from that of either the control or the glucagon/phenylephrine group. The change in glucagon HR (delta = 6 beats/min) was significant compared with the control group (delta = -4 beats/min) and the glucagon/phenylephrine group (delta = -4 beats/min).


CONCLUSIONS
The glucagon/phenylephrine therapy improved MAP compared with the control, but reduced CO and HR compared with glucagon alone. Glucagon/phenylephrine therapy is not as effective as glucagon alone in reversing the hemodynamic effects of experimental verapamil overdose.
Stone
C K
CK
Department of Emergency Medicine, University of Kentucky Medical Center, Lexington 40536-0084, USA.
Thomas
S H
SH
Koury
S I
SI
Low
R B
RB
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000506:poisoning*; D004285:Dogs; D062787:Drug Overdose / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005069:Evaluation Studies as Topic; D005934:Glucagon / Q000008:administration & dosage / Q000627:therapeutic use*; D010656:Phenylephrine / Q000008:administration & dosage / Q000627:therapeutic use*; D018027:Receptors, Glucagon / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology / Q000506:poisoning*
D000316:Adrenergic alpha-Agonists; D000931:Antidotes; D002121:Calcium Channel Blockers; D018027:Receptors, Glucagon; D010656:Phenylephrine; D005934:Glucagon; D014700:Verapamil