Use of vasopressin in a canine model of severe verapamil poisoning: a preliminary descriptive study.
OBJECTIVE
The purpose of this preliminary study was to evaluate the effect of arginine vasopressin (AVP) administration in a model of shock induced by calcium channel antagonist overdose and to determine endogenous serum AVP concentrations in calcium channel antagonist-induced shock.


METHODS
This was a controlled, randomized laboratory investigation based on a previously described canine model of verapamil toxicity. After induction of verapamil toxicity, animals in both the control and the experimental groups (n = 6 each) received a continuous infusion of verapamil. Experimental animals received an escalating dose of AVP, while control animals received an equal volume of 0.9% saline infusion. The hemodynamic end point was return of mean arterial pressure (MAP) to within 20% of baseline. Surviving animals were killed after 60 minutes.


RESULTS
In the treatment group, administration of low-dose AVP (4 mU/kg/min) resulted in further declines in cardiac index and heart rate. No significant change was noted in MAP with low-dose AVP. A slight increase in MAP was noted with both escalating doses of AVP and equivalent volumes of normal saline. By the end of the 60-minute antidote/saline phase, the MAPs of the saline control group and the AVP experimental group were similar. The primary hemodynamic end point was not achieved in either the AVP or the saline control arm. Mean baseline serum AVP concentration in control animals was 5.8 pg/mL, increasing to 225 pg/mL during the toxicity phase.


CONCLUSIONS
In an animal model of verapamil-induced shock, endogenous AVP levels increased nearly 40-fold compared with baseline levels. Escalating doses of exogenous AVP worsened cardiac index and failed to return MAP to within 20% of baseline.
Sztajnkrycer
Matthew D
MD
Department of Emergency Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. sztajnkrycer.matthew@mayo.edu
Bond
G Randall
GR
Johnson
Susan B
SB
Weaver
Amy L
AL
D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000506:poisoning*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose; D006339:Heart Rate / Q000187:drug effects; D011041:Poisoning / Q000188:drug therapy; D012769:Shock / Q000139:chemically induced* / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000097:blood / Q000627:therapeutic use*; D014700:Verapamil / Q000506:poisoning*
D002121:Calcium Channel Blockers; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D014700:Verapamil