Pharmacokinetics of vecuronium during acute isovolaemic haemodilution

To evaluate the effect of acute isovolaemic haemodilution on the pharmacokinetics of vecuronium, we studied 13 patients undergoing haemodilution during surgery and 13 control patients. General anaesthesia was induced with thiopentone 4-6 mg kg-1 and fentanyl 2-4 micrograms kg-1, and maintained with enflurane and 60% nitrous oxide in oxygen. The haemodilution patients underwent major elective plastic surgery with an anticipated surgical loss of more than 600 ml. Haemodilution was achieved by drainage of venous blood and i.v. infusion of lactated Ringer's solution and 6% dextran, during which the packed cell volume and haemoglobin concentration decreased from 45% to 28.1% and from 14.7 g dl-1 to 9.1 g dl-1, respectively. After administration of a bolus of vecuronium 100 micrograms kg-1, an improved fluorimetric assay was used to measure the plasma concentrations of vecuronium for 5 h. The results showed that the disposition kinetics of vecuronium were best described mathematically by a three-compartment open model in the two groups. The mean volume of the central compartment and volume of distribution at steady state were 42.3 (SD 11.8) ml kg-1 and 168.4 (31.5) ml kg-1, respectively, in control patients, and significantly greater (55.2 (13.4) ml kg-1 and 225.9 (53.3) ml kg-1) in the haemodilution patients (P < 0.05). The elimination half-life was 50.3 (11.5) min in control patients and significantly greater (68.2 (15.1) min) in the haemodilution patients (P < 0.05). The half-lives of fast distribution and distribution, mean residual time, area under the plasma concentration curve and plasma clearance were unchanged in patients who underwent haemodilution compared with the control group.