Factors affecting the maternal-fetal distribution of pethidine and bupivacaine in the rabbit

Twenty pregnant New Zealand white rabbits (mean body weight 4.6 kg) within 3 days of term were anaesthetized and given an intravenous infusion of bupivacaine 1.25 mg/ml with pethidine 1.25 mg/ml at a rate of 12 ml/h for 20 min, 6 ml/h for 60 min and 3 ml/h thereafter. In 10 of the does the solution also contained adrenaline 1.25 microg/ml. Up to 8 fetuses were removed at 15 min intervals from the start of the infusion and umbilical vein pH was measured, together with bupivacaine and pethidine concentrations, in fetal plasma, fetal brain and maternal plasma sampled synchronously. Mean umbilical vein pH fell with time with no significant difference between the groups. Maternal plasma concentrations of both drugs did not alter significantly during the experiment. Maternal clearance of bupivacaine was 85.6 ml/min and of pethidine was 249 ml/min. Despite the three-fold higher maternal plasma concentrations of bupivacaine, concentrations of pethidine in fetal plasma and brain were consistently higher than those of bupivacaine. Fetal plasma pethidine concentrations rose 0.276 microg x ml(-1)h(-1) and bupivacaine concentrations rose 0.184 microg x ml(-1)h(-1). The mean (+/-SD) maximum fetal: maternal plasma ratio for bupivacaine was 0.361+/-0.127 and for pethidine 1.78+/-0.81. The fetal brain:plasma ratio of pethidine was consistently higher than that of bupivacaine and did not change significantly with time, whereas that of bupivacaine fell significantly (P<0.05). Concentrations of bupivacaine and pethidine in fetal and maternal brain were consistently higher with adrenaline, although adrenaline had no significant effect on the concentrations in this or any compartment.