Plasma concentrations of bupivacaine and two of its metabolites during continuous interscalene brachial plexus block. An interscalene brachial plexus block was performed via a catheter with 20-28 ml of 0.75% bupivacaine plus adrenaline for surgery of the shoulder region in 12 patients. Constant infusion of 0.25% bupivacaine 0.25 mg kg-1 h-1 was continued for 24 h. During surgery light general anaesthesia, without analgesics, was maintained. Plasma concentrations of total and unbound (free fraction) bupivacaine, desbutylbupivacaine (DBB), 4-hydroxybupivacaine (4-OHB) and alpha 1-acid glycoprotein (AAG) were measured at predetermined intervals during the continuous block. The greatest mean plasma concentrations of bupivacaine were measured at 30 min (1.63 (SD 0.55) micrograms ml-1) and 60 min (1.38 (0.48) micrograms ml-1). There was a small but statistically significant increase in the plasma concentration of bupivacaine between 12 and 24 h of infusion. The mean unbound concentration of bupivacaine in plasma decreased from 0.044 (0.015) microgram ml-1 (3.6 (1.1)% of total bupivacaine concentration) at 3 h to 0.023 (0.011) micrograms ml-1 (2.1 (1.0)%) at 24 h. The AAG concentration in plasma increased by 38% in 24 h. The metabolites DBB and 4-OHB were detectable in plasma from 30 min, with a gradual increase during infusion. At 24 h the mean concentrations of DBB and 4-OHB were 0.33 (0.22) micrograms ml-1 and 0.13 (0.04) micrograms ml-1, respectively. There were no toxic reactions during the blocks. 