Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients

作者:Bienert Agnieszka*; Kusza Krzysztof; Wawrzyniak Katarzyna; Grzeskowiak Edmund; Kokot Zenon J; Matysiak Jan; Grabowski Tomasz; Wolc Anna; Wiczling Pawel; Regulski Milosz
来源:Journal of Pharmacokinetics and Pharmacodynamics, 2010, 37(3): 289-304.
DOI:10.1007/s10928-010-9161-5

摘要

This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were V (C) = 27.7 l, V (T) = 801 l, and CL (D) = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65 center dot(1 - 0.00714 center dot(SBP - 135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC (50) equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light-dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night-day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients.

  • 出版日期2010-6