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

Background: Hemorrhagic shock is known to alter significantly the pharmacok inetics of fentanyl, an opioid that requires delivery to the Liver for meta bolism. The authors hypothesized that the pharmacokinetics and pharmacodyna mics of remifentanil, an esterase metabolized opioid that does not require delivery to a metabolic organ, would be altered less by hemorrhagic shock t hat those of fentanyl. Methods: Sixteen pigs were assigned randomly to control and shock groups. T he shock group was bled using an isobaric hemorrhage model. Remifentanil 10 mug.kg(-1).min(-1) was infused for 10 min to both groups. Aterial samples were collected for remifentanil concentration assay. Pharmacokinetic parame ters were estimated using a three-compartment model. The electroencephalogr am spectral edge was used as a measure of drug effect. The pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model. Results: Remifentanil blood levels were higher in the shocked group. The ce ntral clearance was slower and the central compartment was smaller Ln shock ed animals. No difference between groups was observed in the magnitude or t ime course of the remifentanil-induced decrease in spectral edge. Conclusions: 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 ter mination of the infusion was minimal, Hemorrhagic shock did not alter the p harmacodynamics of remifentanil.