Influence of hemorrhagic shock on remifentanil : A pharmacokinetic and pharmacodynamic analysis

Hemorrhagic shock is known to alter significantly the pharmacokinetics of fentanyl, an opioid that requires delivery to the liver for metabolism. The authors hypothesized that the pharmacokinetics and pharmacodynamics of remifentanil, an esterase metabolized opioid that does not require delivery to a metabolic organ, would be altered less by hemorrhagic shock that those of fentanyl. Sixteen pigs were assigned randomly to control and shock groups. The shock group was bled using an isobaric hemorrhage model. Remifentanil 10 microg x kg(-1) x min(-1) was infused for 10 min to both groups. Arterial samples were collected for remifentanil concentration assay. Pharmacokinetic parameters were estimated using a three-compartment model. The electroencephalogram spectral edge was used as a measure of drug effect. The pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model. Remifentanil blood levels were higher in the shocked group. The central clearance was slower and the central compartment was smaller in shocked animals. No difference between groups was observed in the magnitude or time course of the remifentanil-induced decrease in spectral edge. Hemorrhagic shock altered the pharmacokinetics of remifentanil, suggesting that less remifentanil would be required to maintain a target plasma concentration. However, because of its rapid metabolism, the impact of hemorrhagic shock on the concentration decline of remifentanil after termination of the infusion was minimal. Hemorrhagic shock did not alter the pharmacodynamics of remifentanil.