Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgery.
OBJECTIVE
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%).


CONCLUSIONS
The elimination rate of doxacurium during normothermic CPB is faster than that in hypothermic CPB.
Asokumar
B
B
Department of Anaesthesia, Toronto Hospital, University of Toronto, Ontario, Canada.
Cheng
D
D
Chung
F
F
Peniston
C
C
Sandler
A
A
Varin
F
F
D000368:Aged; D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D001831:Body Temperature; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D005260:Female; D006207:Half-Life; D006801:Humans; D007036:Hypothermia, Induced; D007530:Isoflurane / Q000008:administration & dosage; D007546:Isoquinolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007668:Kidney / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008874:Midazolam / Q000008:administration & dosage; D008875:Middle Aged; D019148:Neuromuscular Blockade; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011229:Preanesthetic Medication; D017409:Sufentanil / Q000008:administration & dosage; D013997:Time Factors
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D017409:Sufentanil; D007530:Isoflurane; C049429:doxacurium; D008874:Midazolam