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 × ED₉₅ (80μ·kg^?1), and anaesthesia was maintained with 0.5 μg·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 33–36C and 26–30C respectively. Timed blood and urine samples were collected and pharmacokinetic parameters were estimated using a non-compartmental approach.

Results

For the normothermic and hypothermie groups, terminal elimination half-life (t_1/2B) was 100.1 ± 28 and 183.8 ± 60 min (P < 0.05) respectively, elimination half-life during the CPB phase (T_1/2 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 hypothermie 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.