Allometric or lean body mass scaling of propofol pharmacokinetics: towards simplifying parameter sets for target-controlled infusions.
Uncertainty exists as to the most suitable pharmacokinetic parameter sets for propofol target-controlled infusions (TCI). The pharmacokinetic parameter sets currently employed are clearly not universally applicable, particularly when patient attributes differ from those of the subjects who participated in the original research from which the models were derived. Increasing evidence indicates that the pharmacokinetic parameters of propofol can be scaled allometrically as well as in direct proportion to lean body mass (LBM). Appraisal of hitherto published studies suggests that an allometrically scaled pharmacokinetic parameter set may be applicable to a wide range of patients ranging from children to obese adults. On the other hand, there is evidence that propofol pharmacokinetic parameters, scaled linearly to LBM, provide improved dosing in normal and obese adults. The 'Schnider' pharmacokinetic parameter set that has been programmed into commercially available TCI pumps cannot be employed at present for morbidly obese patients (body mass index >40 kg/m2), because of anomalous behaviour of the equation used to calculate LBM, resulting in administration of excessive amounts of propofol. Simulations of TCI using improved equations to calculate LBM indicate that the Schnider model delivers similar amounts of propofol to morbidly obese patients as do the allometrically scaled pharmacokinetic parameter sets. These hypotheses deserve further investigation. To facilitate further investigation, researchers are encouraged to make their data freely available to the WorldSIVA Open TCI Initiative (http://opentci.org).
Department of Anesthesiology and Critical Care, Stellenbosch University, South Africa. jfc@sun.ac.za
Johan Francois
JF
Coetzee
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D049628:Body Size; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000295:instrumentation; D054796:Drug Dosage Calculations; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D016014:Linear Models; D008875:Middle Aged; D008954:Models, Biological; D009767:Obesity, Morbid / Q000378:metabolism / Q000503:physiopathology; D015742:Propofol / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D055815:Young Adult
D018686:Anesthetics, Intravenous; D015742:Propofol