Sevoflurane pharmacokinetics: effect of cardiac output

Sevoflurane uptake (V-sevo) can be predicted by the square root of time model or the four-compartment model. However, V-sevo and the effect of cardiac output on anaesthetic uptake have not been quantified clinically. After obtaining IRE approval and informed consent, 34 adult patients received closed-circuit anaesthesia with sevoflurane for 1 h. The end-expired sevoflurane concentration was maintained at 2.6% by infusion of liquid sevoflurane into the breathing system. In a subgroup of 12 patients, cardiac output was measured every 5 min by thermodilution (CO group). The effect of patient characteristics (age, height, weight, body surface area) and cardiac output on V-sevo were determined, and V-sevo was compared with the theoretical models. In the CO group, measured cardiac output was used in the formulae of these models. A two-exponential curve described average V-sevo well: V-sevo (ml liquid) =0+1.62x(1-e(-2.3xt))+18.1x(1-e(-0.0089xt)), r(2) >0.999. There was no correlation between V-sevo and patient characteristics, except that V-sevo was greater in patients with a greater cardiac output (r(2)=0.36) and cardiac index (r(2)=0.35). The rate of sevoflurane uptake decreased less than predicted by the square root of time and four-compartment models, even when measured cardiac output was used in the formulae. These findings confirm that the square root of time and four-compartment models do not accurately predict anaesthetic uptake. In addition, uptake of sevoflurane cannot be predicted by patient characteristics but was higher in patients with a higher cardiac output.