The influence of hemorrhagic shock on etomidate: a pharmacokinetic and pharmacodynamic analysis.

UNLABELLED: We studied the influence of hemorrhagic shock on the pharmacology of etomidate in swine. Sixteen swine were randomly assigned to control and shock groups. The shock group was bled to a mean arterial blood pressure of 50 mm Hg and held there until 30 mL/kg blood was removed. Etomidate 300 micro g x kg(-1) x min(-1) was infused for 10 min to both groups. Fifteen arterial samples were collected until 180 min after the infusion began to determine drug concentration. Pharmacokinetic variables for each group were estimated by using a three-compartment model. The bispectral index scale was used as a measure of drug effect. The pharmacodynamics were characterized by using a sigmoid inhibitory maximal effect model. The raw data revealed a 25% increase in the plasma etomidate concentration at the end of the 10-min infusion which resolved after termination of the infusion in the shock group. The pharmacokinetic analysis revealed subtle changes in the variable estimates between groups. The etomidate infusion produced a similar Bispectral Index Scale change in both groups. These results demonstrated that, unlike the influence of hemorrhagic shock on other sedative hypnotics and opioids, moderate hemorrhagic shock produced minimal changes in the pharmacokinetics and no change in the pharmacodynamics of etomidate.

IMPLICATIONS: Hemorrhagic shock produced minimal changes in the pharmacokinetics and no change in the pharmacodynamics of etomidate in swine. These results suggest that, unlike other sedative hypnotics and opioids, minimal adjustment in the dose of etomidate is required to achieve the same drug effect during hemorrhagic shock.