thiopental and Hyperammonemia

Sodium thiopental in the comatogenic (but not soporogenic) dose caused hyperammoniemia in rats. Blood ammonium level increased 3-fold within 3 h and 5-fold within 18 h. Blood urea level increased by one-third within 18 h against the background of unchanged creatinine level and hematocrit. Urinary excretion of ammonium did not decrease, while its release with exhaled air increased, indicating intensification of ammonium formation in the body. Barbiturate coma did not change the slope of curves of dose-dependent increase of ammonium or urea levels in the blood of rats injected with ammonium acetate, which attested to the absence of appreciable disorders in the ammonium detoxifying function of the liver. Ammonium hyperproduction could be caused by gastrointestinal stasis verified by X-ray examination and confirmed by correlation between blood urea level and stool retention in narcotized rats.

Topics: Ammonia; Animals; Coma; Female; Gastrointestinal Motility; Hyperammonemia; Rats; Thiopental

Ammonia inhalation (0.84-1.07 mg/liter, 3 h) was accompanied by a 65% increase in ammonia concentration in mixed blood of intact rats. This treatment did not cause death of intact animals, but potentiated the lethal effect of sodium thiopental and inhibited external respiration and O2 consumption in animals. The resistance of rats to the lethal effect of barbiturate tended to decrease under conditions of experimental hyperammonemia induced by intraperitoneal injection of ammonium acetate in a nonlethal dose (6 mmol/kg). Our results indicate that potentiation of the toxic effect of barbiturates by atmospheric ammonia is related to its resorptive effects.

Topics: Acetates; Administration, Inhalation; Ammonia; Animals; Drug Synergism; Female; Hyperammonemia; Oxygen Consumption; Poisoning; Rats; Respiration; Thiopental

Fulminant hyperammonaemia as a threshold effect of coma-inducing dose of sodium thiopental has been revealed in rats. Blood ammonia content increased progressively after the introduction of 1.0 LD(50) (but not 0.8 LD(50)) of sodium thiopental three times in 3h and five times in 18h. The urinary ammonia excretion was not impaired while the volatilization of ammoniac from the body of ST-treated rats was higher, giving evidence of the augmentation of ammonia production. Blood urea increased by one third despite of insignificant alterations of haematocrit and blood creatinine. Ammonia hyperproduction in the digestive tract could result from gastrointestinal stasis, which has been verified by roentgenography and confirmed by correlation of hyperammonaemia with the stool retardation. In thiopental coma rats the slope of a dose-dependent increase of the blood ammonia and the blood urea after the intraperitoneal injection of ammonium acetate did not exceed that in intact animals. So the ammonia hyperproduction in the digestive tract could be the main contributing cause of fulminant hyperammonaemia in rats with thiopental coma and thus be involved into pathogenesis of the coma.

Topics: Acetates; Ammonia; Animals; Blood Urea Nitrogen; Coma; Defecation; Dose-Response Relationship, Drug; Gastrointestinal Contents; Gastrointestinal Tract; Hyperammonemia; Hypnotics and Sedatives; Injections, Intraperitoneal; Intestinal Obstruction; Rats; Thiopental; Time Factors