Effects of propofol and of thiopentone anaesthesia on the regional kinetics of pethidine in the sheep.

We have examined the extraction ratios, net fluxes and clearances of pethidine by the liver, kidneys and hindquarters in sheep before, during and after continuous anaesthesia (70 min) with propofol or thiopentone. Before anaesthesia, the overall mean respective regional pethidine extraction ratios were 0.98 (SD 0.01), 0.20 (0.06) and 0.44 (0.13), the corresponding net fluxes were 47 (7), 5 (2) and 20 (10)% dose min-1 and the clearances 1.44 (0.22), 0.17 (0.07) and 0.80 (0.39) litre min-1. During propofol anaesthesia, arterial blood concentrations of pethidine approximately doubled (P less than 0.05), mean pethidine hepatic extraction ratio was unchanged, flux was increased to 145 (20)% and clearance decreased to 79 (10)% (P less than 0.05) of baseline values; mean pethidine renal extraction ratio, flux and clearance were 73 (34), 112 (43) and 69 (31)% of baseline values; mean hindquarter pethidine extraction ratio decreased to 65 (25)% (P less than 0.05) of baseline values. During thiopentone anaesthesia, arterial blood concentrations of pethidine approximately doubled (P less than 0.01), mean pethidine hepatic extraction ratio was 97 (2)% of baseline values and flux and clearance were unchanged, mean pethidine renal extraction ratios, flux and clearance decreased to 37 (21), 54 (18) and 27 (19)% (all P less than 0.05) of baseline values and mean pethidine hindquarter extraction ratio was 81 (20)% of baseline values. In spite of only modest changes in hepatic and renal blood flow during anaesthesia, blood concentrations of pethidine doubled and pethidine kinetics were disturbed for several hours after anaesthesia. Overall, however, the changes were of smaller magnitude and shorter duration than those that have been described for anaesthesia with the volatile anaesthetic agents.