Effects of Hypovolemia on Pharmacokinetics and Pharmacodynamics of Remifentanil in Pigs.Johnson et al.(page 322)
Building on their previous work with a porcine isobaric hemorrhagic shock model to investigate the influence of severe blood loss on the pharmacokinetics of fentanyl, Johnson et al. reported investigations using the same model while infusing remifentanil to shocked and control group pigs. A total of 16 pigs were assigned randomly to one of two groups: a control group and a shock group, in which animals were bled to a state of hemorrhagic shock. Remifentanil, 10 μg · kg−1 · min−1, was infused for 10 min in animals in both groups. Arterial samples were obtained for remifentanil concentration assays every 2 min during infusion and at designated intervals up to 65 min after the infusion was stopped. For pharmacokinetic analysis, the concentration-versus-time data for both groups was analyzed using several techniques. The electroencephalographic spectral edge was used as a measure of drug effect. Pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model.
As hypothesized, the remifentanil blood concentrations were higher in the shock group. In addition, central clearance was slower and the central compartment was smaller in the shock group. No difference between shock and control groups was observed in the magnitude or the time course of the remifentanil-induced decrease in spectral edge. The results indicate that less remifentanil would be needed to maintain a target plasma concentration during hemorrhagic shock. However, because of its rapid metabolism, the impact of hemorrhagic shock on the concentration decrease of remifentanil after termination of the infusion was minimal. The authors also noted several limitations of the study—in particular, the differences between the controlled hemorrhage over time used in their experiment and the dynamic process of hemorrhagic shock during trauma or surgery.