Domestic swine model for the assessment of chemical warfare agent-anesthetic interactions: some effects of sulfur mustard.
A domestic swine model was developed to examine the interaction of chemical warfare agents with anesthetics and other drugs used during general anesthesia. Animals were fully instrumented, and clinically relevant physiological parameters were monitored throughout the experimental procedures. Exposure of animals under halothane anesthesia to the chemical warfare agent sulfur mustard (HD; 1 mg/kg intravenous) produced mild signs of systemic intoxication during the subsequent 5 hours. Induction doses of ketamine 1 hour after HD exposure resulted in periods of profound apnea, with continued respiratory distress for the next 2 hours. When animals were treated with HD 1 hour after the initiation of ketamine anesthesia, severe and persistent convulsion-like muscular activity was observed within 45 minutes of HD administration. This nonpurposeful activity was not ameliorated by diazepam but was dramatically reduced or eliminated by resumption of halothane anesthesia. Treatment of HD-intoxicated pigs with succinylcholine produced a prolonged apnea resulting in death. In these apparently mildly HD-intoxicated animals, the introduction of ketamine or succinylcholine can rapidly induce potentially life-threatening situations.
Conley
J
J
Kinchyle Enterprises, Inc., Medicine Hat, Alberta, Canada.
Hunter
K
K
Lundy
P
P
Hamilton
M
M
Sawyer
T W
TW
D000768:Anesthesia, General / Q000379:methods; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001049:Apnea / Q000139:chemically induced; D002618:Chemical Warfare; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D016903:Drug Monitoring; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008887:Military Medicine; D009151:Mustard Gas / Q000506:poisoning*; D009465:Neuromuscular Agents / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced; D013390:Succinylcholine / Q000494:pharmacology; D013552:Swine; D013997:Time Factors
D000777:Anesthetics; D009465:Neuromuscular Agents; D007649:Ketamine; D013390:Succinylcholine; D009151:Mustard Gas; D006221:Halothane