The effect of cardiopulmonary bypass on plasma protein binding of alfentanil.
The effect of cardiopulmonary bypass (CPB) on plasma concentration and protein binding of alfentanil was studied during continuous infusions in five cardiac surgical patients. Patients were given a loading infusion of 10 micrograms.min-1.kg-1 lean body mass (LBM) over 30 s followed by a fixed rate maintenance infusion of 1 microgram.min-1.kg-1 LBM for the duration of surgery. Prior to the commencement of CPB the total plasma alfentanil concentration was 177 micrograms.l-1. This fell to 92 micrograms.l-1 2 min after commencement of CPB and rose to 155 micrograms.l-1 at the end of CPB 2.01 h later. During the same period the unbound fraction of alfentanil rose from 0.16 to 0.35 two min after the start of CPB and fell gradually to 0.22 at the end of CPB. The unbound concentration prior to CPB was 29 micrograms.l-1 and was essentially unchanged by the onset of CPB, being 35 micrograms.l-1 at two min and then 31 micrograms.l-1 at the end of CPB. There was a good correlation between alfentanil bound/unbound concentration ratio and plasma albumin concentration (r = 0.57) and plasma alpha 1-acid glycoprotein concentration (r = 0.80), indicating that the decrease in binding during CPB was due primarily to haemodilution. In assessing the effects of CPB on plasma drug concentrations, it is therefore necessary to monitor unbound as well as total concentrations because the effects on these differ greatly.
Kumar
K
K
Victorian College of Pharmacy, Melbourne, Australia.
Crankshaw
D P
DP
Morgan
D J
DJ
Beemer
G H
GH
D000368:Aged; D015760:Alfentanil; D000700:Analgesics / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism; D002315:Cardiopulmonary Bypass; D005112:Extracorporeal Circulation; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011229:Preanesthetic Medication; D011485:Protein Binding; D013997:Time Factors; D014462:Ultrafiltration
D000700:Analgesics; D001798:Blood Proteins; D015760:Alfentanil; D005283:Fentanyl