Patient after Severe Head Injury

Background: The pharmacodynamic differences in time to onset and dissipation of effect of sufentanil, fentanyl, and alfentanil probably result from different rates of blood-brain equilibration. The authors investigated this hypothesis in humans. Methods: After simultaneous central venous bolus application of sufentanil (10 pg), fentanyl (100 pg), and alfentanil (1,000 pg), arterial and jugular bulb blood samples were drawn simultaneously at 20, 30, 45, 60, 7 5 , 90, 105, 120, 140, 160, 180, 210, 240, 300, 360, and 420 s from 19 patients during the postacute stage of head injury with normal htracranial pressure, cerebral perfusion pressure, and cerebral oxygen metabolism during normocapnia. Results: Peak brain concentration, indicated by equilibrium between arterial and jugular bulb opioid concentrations, was achieved for alfentanil at 45 s, for sufentanil at 5 min, and for fentanyl at 6 min. The corresponding median time intervals (fifth and ninety-lifth percentiles) to reach 50% of peak brain concentration were 15 (14-10, 25 (1838) and 35 (25-45) s, respectively. Uptake was highest 20 s after bolus and decreased continuously for fentanyl and sufentanil, whereas alfentanil uptake was biphasic. The ratio of the relative amounts of sufentanil, fentanyl, and alfentanil retained in the brain at peak brain concentration was 1 X : X 6 X : X 90. Conclusions: The differences in the time lag between changes in serum concentrations and drug effect after bolus application of nearly equipotent doses of sufentanil, fentanyl, and alfent a d originate from the different times required to reach bloodbrain equilibration, mainly depending on different levels and