The Influence of Hemorrhagic Shock on the Electroencephalographic and Immobilizing Effects of Propofol in a Swine Model

Abstract

Hemorrhagic shock increases the hypnotic effect of propofol, but the influence of hemorrhagic shock on the immobilizing effect of propofol is not fully defined. Twenty-four swine (30.3 +/- 3.6 kg) were anesthetized by inhalation of isoflurane and randomly assigned to either a control (n = 12) or a hemorrhagic shock (n = 12) group. Animals in the shock group were bled to a mean arterial blood pressure of 50 mm Hg and maintained at this level for 60 min. After isoflurane inhalation was stopped, propofol was infused at 50 mg x kg(-1) x h(-1) until no movement was observed after application of a dewclaw clamp every 2 min. Arterial samples for measurement of the propofol concentration were collected just before each use of the dewclaw clamp and the Bispectral Index (BIS) was also recorded. Analysis of the pharmacodynamics was performed using a sigmoidal inhibitory maximal effect model for BIS versus effect-site concentration and a logistic regression analysis for the probability of movement versus effect-site concentration. The propofol doses needed to reach a 50% decrease from baseline BIS, and no movement after noxious stimuli were reduced by hemorrhagic shock by 54% and 38%, respectively. Hemorrhagic shock decreased the effect-site concentration that produced 50% of the maximal BIS effect from 11.6 +/- 3.8 to 9.1 +/- 1.7 microg/mL and that producing a 50% probability of movement from 26.8 +/- 1.0 to 20.6 +/- 1.0 microg/mL. The results show that hemorrhagic shock increases both the hypnotic and immobilizing effects of propofol due to pharmacokinetic and pharmacodynamic alterations, with the changes in pharmacodynamics occurring to a similar extent for both effects.