PHARMACOKINETICS OF VECURONIUM DURING ACUTE ISOVOLAEMIC HEMODILUTION

To evaluate the effect of acute isovolaemic haemodilution on the pharm acokinetics of vecuronium, we studied 13 patients undergoing haemodilu tion during surgery and 13 control patients. General anaesthesia was i nduced with thiopentone 4-6 mg kg(-1) and fentanyl 2-4 mu g kg(-1) and maintained with enflurane and 60% nitrous oxide in oxygen. The haemod ilution patients underwent major elective plastic surgery with an anti cipated surgical loss of more than 600 ml. Haemodilution was achieved by drainage of venous blood and i.v. infusion of lactated Ringer's sol ution and 6% dextran, during which the packed cell volume and haemoglo bin concentration decreased from 45% to 28.1% and from 14.7 g dl(-1) t o 9.1 g dl(-1), respectively. After administration of a bolus of vecur onium 100 mu g kg(-1), an improved fluorimetric assay was used to meas ure the plasma concentrations of vecuronium for 5 h. The results showe d that the disposition kinetics of vecuronium were best described math ematically by a three-compartment open model in the two groups. The me an volume of the central compartment and volume of distribution at ste ady state were 42.3 (SD 11.8) ml kg(-1) and 168.4 (31.5) ml kg(-1), re spectively, 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 pat ients and significantly greater (68.2 (15.1) min) in the haemodilution patients (P<0.05). The half-lives of fast distribution and distributi on, mean residual time, area under the plasma concentration curve and plasma clearance were unchanged in patients who underwent haemodilutio n compared with the control group.