Measurements of Maternal Protein Binding of Bupivacaine Throughout Pregnancy

Tsen, Lawrence C. MD*; Tarshis, Jordan MD‡; Denson, Donald D. PhD§; Osathanondh, Rapin MD†; Datta, Sanjay MD*; Bader, Angela M. MD*

doi: 10.1213/00000539-199910000-00027
Pediatric Anesthesia: Obstetric Anesthesia

Pregnancy-related decreases in protein binding may contribute to altered effects of local anesthetics in the parturient. Previous studies have measured protein binding of bupivacaine in term parturients; the current study defines the ratio of bound-to-free bupivacaine throughout gestation at both therapeutic 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 nonpregnant controls. The percent bound bupivacaine at a fixed concentration was determined for each sample at both therapeutic (1 μg/mL) and toxic (5 μg/mL) concentrations using an ultrafiltration technique. Albumin and α-1-glycoprotein levels were also measured. Linear regression analysis showed a significant increase in concentration of free bupivacaine throughout gestation at the 5-μg/mL concentration, corresponding to a decrease demonstrated in both albumin and α-1-glycoprotein levels. A similar correlation was not found at the 1-μg/mL concentration. 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 anesthetic toxicity in the parturient; however, its relative importance remains unclear.

Implications: When venous samples taken from pregnant women were mixed with 5 μg/ml bupivacaine and analyzed, an increase in the free fraction of drug was seen with increasing gestational age, corresponding to decreases in α-1-glycoprotein and albumin.

Departments of *Anesthesia, Perioperative, and Pain Medicine, and †Obstetrics and Gynecology, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts; ‡Department of Anesthesia, Sunnybrook Hospital, Toronto, Ontario, Canada; and §Department of Anesthesiology, Emory University, Atlanta, GA

June 22, 1999.

Address correspondence and reprint requests to Angela Bader, MD, 75 Francis St., Boston, MA 02115.

© 1999 International Anesthesia Research Society