Pharmacokinetics of Doxacurium During Normothermic and Hypothermic Cardiopulmonary Bypass Surgery

Purpose: To compare the pharmacokinetic behaviour of doxacurium in patients undergoing normothermic or hypothermic cardiopulmonary bypass (CPB) for coronary artery bypass graft surgery.

Methods: Twenty patients in two equal groups were studied. Anaesthesia was induced with sufentanil and midazolam after a standard premedication. Doxacurium was administered at 3 x ED95 (80 micrograms.kg-1), and anaesthesia was maintained with 0.5 microgram.kg-1 hr-1 sufentanil, 0.05 mg.kg-1 midazolam and isoflurane 0.5-1%. Systemic temperature for patients in the normothermic and hypothermic groups was maintained at 33-36 C and 26-30 C respectively. 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 half-life (t1/2 beta) was 100.1 +/- 28 and 183.8 +/- 60 min (P < 0.05) respectively, elimination half-life during the CPB phase (T1/2 CPB) 114.5 +/- 10 and 183.8 +/- 60 min (P < 0.05), mean residence time 108.8 +/- 25 and 164.8 +/- 34 min (P < 0.05) and apparent volume of distribution at steady state 0.20 +/- 0.03 and 0.26 +/- 0.04 L.kg-1 (P < 0.05). 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 percentage of the total clearance (76.2 +/- 10 vs 58.3 +/- 20%).

Conclusion: The elimination rate of doxacurium during normothermic CPB is faster than that in hypothermic CPB.