PHARMACOKINETICS OF DOXACURIUM DURING NORMOTHERMIC AND HYPOTHERMIC CARDIOPULMONARY BYPASS-SURGERY

Purpose: To compare the pharmacokinetic behaviour oi doxacurium in pat ients undergoing normothermic or hypothermic cardiopulmonary bypass (C PB) for coronary artery bypass graft surgery. Methods: Twenty patients in two equal groups were studied. Anaesthesia was induced with sufent anil and midazolam after a standard premedication. Doxacurium was admi nistered at 3 x ED95 (80 mu g.kg(-1)), and anaesthesia was maintained with 0.5 mu g.kg(-1) hr(-1) sufentanil, 0.05 mg.kg(-1) midazolam and i soflurane 0.5-1 %.Systemic temperature for patients in the normothermi c and hypothermic groups was maintained at 33-36C and 26-30C respectiv ely. Timed blood and urine samples were collected and pharmacokinetic parameters were estimated using a non-compartmental approach. Results: For the normothermic and hypothermic groups, terminal elimination hal f-life (t(1/2)beta) was 100.1 +/- 28 and 183.8 +/- 60 min (P < 0.05) r espectively, elimination half-life during the CPB phase (T-1/2 CPB) 11 4.5 +/- 10 and 183.8 +/- 60 min (P < 0.05), mean residence rime 108.8 +/- 25 and 164.8 +/- 34 min (P < 0.05) and apparent volume of distribu tion at steady state 0.20 +/- 0.03 and 0.26 +/- 0.04 L.kg(-1) (P < 0.0 5). Compared with the hypothermic group, the normothermic group had a higher rate of renal clearance (1.40 +/- 0.4 vs 0.93 +/- 0.3 ml.min(-1 ).kg(-1); P < 0.05) and a higher value for renal clearance as a percen tage of the total clearance (76.2 +/- 10 vs 58.3 +/- 20%). Conclusion: The elimination rate of doxacurium during normothermic CPB is raster than that in hypothermic CPB.