Measurements of maternal protein binding of bupivacaine throughout pregnancy

Pregnancy-related decreases in protein binding may contribute to altered ef fects of local anesthetics in the parturient. Previous studies have measure d protein binding of bupivacaine in term parturients; the current study def ines the ratio of bound-to-free bupivacaine throughout gestation at both th erapeutic and toxic systemic concentrations of bupivacaine. Venous samples were obtained from 81 women, including 70 parturients, ranging from 7 to 42 wk of gestation and 11 non-pregnant controls. The percent bound bupivacain e at a fixed concentration was determined for each sample at both therapeut ic (1 mu g/mL) and toxic (5 mu g/mL) concentrations using an ultrafiltratio n technique. Albumin and alpha-1-glycoprotein levels were also measured. Li near regression analysis showed a significant increase in concentration of free bupivacaine throughout gestation at the 5-mu g/mL concentration, corre sponding to a decrease demonstrated in both albumin and alpha-1-glycoprotei n levels. A similar correlation was not found at the 1-mu g/mL concentratio n. Although the relative magnitude of these changes is small, the relative change in free drug throughout gestation is large. Protein binding is only one of several mechanisms that may influence the susceptibility to local an esthetic toxicity in the parturient; however, its relative importance remai ns unclear. Implications: When venous samples taken from pregnant women wer e mixed with 5 mu g/ml bupivacaine and analyzed, an increase in the free fr action of drug was seen with increasing gestational age, corresponding to d ecreases in alpha-1-glycoprotein and albumin.