title: Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients.
abstract: 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 x (1-0.00714 x (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.
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, ul. Marii Magdaleny 14, 61-861, Poznań, Poland. agnbienert@op.pl
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bienert
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kusza
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wawrzyniak
authors.forename: Edmund
authors.initials: E
authors.lastname: Grześkowiak
authors.forename: Zenon J
authors.initials: ZJ
authors.lastname: Kokot
authors.forename: Jan
authors.initials: J
authors.lastname: Matysiak
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grabowski
authors.forename: Anna
authors.initials: A
authors.lastname: Wolc
authors.forename: Paweł
authors.initials: P
authors.lastname: Wiczling
authors.forename: Miłosz
authors.initials: M
authors.lastname: Regulski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003422:Critical Care / Q000379:methods*; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010100:Oxygen / Q000097:blood; D015742:Propofol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D018686:Anesthetics, Intravenous; D010100:Oxygen; D015742:Propofol