The effects of obstructive jaundice on the pharmacodynamics of propofol: does the sensitivity of intravenous anesthetics change among icteric patients?
BACKGROUND
Some studies suggest that certain clinical symptoms of cholestasis, such as fatigue and pruritus, result from altered neurotransmission. Patients with obstructive jaundice also have labile blood pressure and heart rate. In the present study, the authors investigated whether obstructive jaundice affects a patient's sensitivity to hypnotics and the haemodynamic profile of propofol.


METHODS
Thirty-six ASA physical status I/II/III patients with serum total bilirubin (TBL) from 7.8 to 362.7 micromol/l scheduled for bile duct surgery were recruited. A computer-controlled propofol infusion programmed for effect site target was used to rapidly attain and maintain sequential increase of the compartment concentration (from 1 to 3 microg/ml). Each target-controlled concentration was maintained for about 12 min, and arterial blood samples were drawn for propofol concentration determination. The bispectral index (BIS) and mean arterial pressures (MAP) were used as indices of the propofol effect. The relation between the concentration and the effects was described by the Hill equation. The pharmacodynamic parameters were optimized using a nonlinear mixed-effect model.


RESULTS
TBL was not a significant covariate of EC(50) for the pharmacodynamic model. For BIS and MAP, the parameters of the pharmacodynamic model were E(max)=75.77%, EC(50)=2.34 microg/ml, and gamma=1.82, and E(max)=47.83%, EC(50)=1.49 microg/ml, and gamma=1.88, respectively.


CONCLUSIONS
We demonstrated that obstructive jaundice with serum TBL from 7.8 to 362.7 micromol/l had no effect on propofol pharmacodynamics observed by BIS and MAP.
Song
J C
JC
Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Changhai Road No. 225, Shanghai, China.
Zhang
M Z
MZ
Lu
Z J
ZJ
Yang
L Q
LQ
Song
J G
JG
Sun
Y M
YM
Yu
W F
WF
D000368:Aged; D000465:Algorithms; D001663:Bilirubin / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D041781:Jaundice, Obstructive / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015742:Propofol / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D016896:Treatment Outcome
D006993:Hypnotics and Sedatives; D001663:Bilirubin; D015742:Propofol