thiopental and Liver-Cirrhosis

Etomidate is the ester of a carboxylated imidazole. This lipophilic (octanol/water partition coefficient: 1000) and weak base (pKa = 4.5) is a potent short-acting hypnotic agent, which can be used for anaesthetic induction or maintenance. The plasma concentration curve fits an open three compartment pharmacokinetic model, with distribution half-lives of 2.6 and 20 min, and terminal elimination half-life of about 4-5 h. Hypnotic plasma concentrations (greater than 0.2 microgram.ml-1) are observed during the intermediate distribution phase (t1/2 approximately 20 min); they reflect the short lasting pharmacodynamic effect. The slow elimination phase is of importance for intravenous infusions lasting more than 2 h; it is recommended to decrease by half the maintenance dose (0.005 mg.kg-1.min-1) so as to prevent a cumulative effect. Etomidate is hydrolysed by hepatic esterases to the corresponding carboxylic acid, which is inactive. The pharmacokinetics of etomidate are altered in the elderly, with a decrease initial distribution volume and clearance (a decreased of 2 ml.min-1.kg-1 every decade) as well as in cirrhotic patients (a 100% increase in terminal half-life).

Topics: Adult; Age Factors; Aged; Etomidate; Humans; Liver Cirrhosis; Metabolic Clearance Rate; Methohexital; Middle Aged; Propofol; Thiopental; Tissue Distribution

The effect of cirrhosis on the pharmacokinetics and plasma protein binding of thiopental was studied in eight patients with cirrhosis, aged (mean +/- SD) 42 +/- 11 yr, and nine patients with normal hepatic and renal function, aged 48 +/- 12 yr, undergoing elective abdominal or orthopedic surgery. The total apparent volume of distribution at steady state was of 2.3 +/- 0.5 1 X kg-1 in the controls and of 3.5 +/- 1.9 1 X kg-1 in the patients with cirrhosis. Thiopental plasma clearance based upon total drug concentrations was 3.9 +/- 1.2 ml X min-1 X kg-1 in the normal group and did not differ significantly in the patients with cirrhosis: 4.4 +/- 2.2 ml X min-1 X kg-1. The elimination half-life was of 529 +/- 97 min in the controls and of 714 +/- 252 min in the patients with cirrhosis. The thiopental free fraction was 14.5 +/- 3.4% in the controls and was increased significantly to 25.2 +/- 3.9% in the patients with cirrhosis. Thiopental intrinsic clearance was decreased insignificantly (P = 0.06) from 28.3 +/- 9.0 ml X min-1 X kg-1 in the controls to 18.2 +/- 10.5 ml X min-1 X kg-1 in those with cirrhosis, suggesting that these patients may have a decreased capacity for thiopental metabolism. These results suggest that the risk of a prolonged effect following thiopental administration appears unlikely in patients with cirrhosis.

Topics: Adult; Aged; Blood Proteins; Female; Half-Life; Humans; Kinetics; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Metabolic Clearance Rate; Middle Aged; Protein Binding; Thiopental

Binding of thiopental to proteins in plasma from healthy, cirrhotic, and uremic subjects was studied using equilibrium dialysis. In plasma from healthy volunteers 28.0 plus or minus 0.9 per cent of thiopental was unbound. In plasma from patients with hepatic disease 53.0 plus or minus 2.1 per cent was unbound, while in patients with renal disease 55.7 plus or minus 1.5 per cent remained unbound. The decreased binding in uremia could not be explained completely by competitive displacement by nitrogenous end products or by hypoalbuminemia, although hypoalbuminemia may account for the decreased binding in cirrhotic patients.

Topics: Binding, Competitive; Blood Proteins; Blood Urea Nitrogen; Creatinine; Dialysis; Humans; In Vitro Techniques; Kidney Diseases; Liver Cirrhosis; Protein Binding; Renal Dialysis; Serum Albumin; Spectrophotometry; Thiopental; Uremia

The administration to albino rats of tannic acid as a retention enema (in doses of 0.2 g./kg. body weight and over) prolonged the duration of anesthesia induced by thiopental given immediately before, or 72 hours after, the tannic acid. This dose of tannic acid corresponds, on the basis of body weight, to a radiodiagnostic enema of 2 1. of 0.25% tannic acid in barium sulfate suspension given to a child weighing 25 kg. By excluding certain hypothermic effects of tannic acid, it was concluded that thiopental potentiation was probably due to impairment by the tannic acid of the liver's ability to detoxify the barbiturate. The results suggest that a drug which is detoxified in the liver should be administered three to five days after a tannic acid-barium sulfate radiodiagnostic enema only with considerable caution.

Topics: Anesthesia; Animals; Contrast Media; Liver Cirrhosis; Radiography; Rats; Tannins; Thiopental