ESTROGEN-INDUCED CHANGES IN PROTEIN-BINDING OF BUPIVACAINE DURING IN-VITRO FERTILIZATION

Background Patients having in vitro fertilization (IVF) procedures tha t use gonadotropin-releasing hormone agonist down-regulation undergo h ormonal manipulation of estrogen concentrations to induce oocyte matur ation. After achieving minimal estrogen concentrations (baseline), sti mulation increases estrogen concentrations to supraphysiologic levels, leading to egg retrieval. The isolated effect of estrogen on protein binding has not previously been reported. This study was conducted to measure the effect of estrogen concentrations on protein binding of tw o concentrations of bupivacaine, 1 mu g/ml and 5 mu g/ml, correspondin g, respectively, to systemic concentrations expected after administrat ion of epidural anesthesia and associated with bupivacaine toxicity. S erum proteins were measured to address the mechanism. Methods: Twenty- nine healthy women undergoing IVF procedures were: enrolled and venous samples were drawn at times of minimal and maximal estrogen concentra tions. The percentage of free bupivacaine was determined at fixed conc entrations of 1 and 5 mu g/ml. Serum albumin and alpha(1)-acid glycopr otein concentrations were measured at baseline and at retrieval In a g roup of 24 women. Results: The percentage of free bupivacaine increase d between times of minimal and maximal serum estrogen concentrations, corresponding to decreased protein binding. Concentrations of serum al bumin and alpha(1)-acid glycoprotein decreased between baseline and re trieval times. Conclusions: Patients undergoing IVF procedures demonst rate a decrease in protein binding of bupivacaine from baseline concen trations. These changes may be explained by a decrease in albumin and alpha(1)-acid glycoprotein. During anesthesia for egg retrieval, clini cians should consider the implications of increased free fraction of d rug, especially for highly protein-bound agents.