Altered d ‐tubocurarine disposition during cardiopulmonary bypass surgery

Kinetics of the neuromuscular blocker d‐tubocurarine (dTc) were investigated in 13 adult patients undergoing surgery involving cardiopulmonary bypass (CPB). Approximately 1 hr before CPB surgery, each received dTc as an intravenous bolus of 0.6 mg/kg and a maintenance infusion of 3 µg/kg/min. dTc plasma concentration–time data before CPB did not differ from those reported in normal surgical patients. There was an abrupt discontinuity in the plasma concentration–time profile with the onset of CPB, and both total and free plasma concentrations increased 400% during the period of CPB. Although computer simulations suggest that these rises in dTc plasma concentrations can be attributed to contraction in central compartment volume, there also was decreased renal and total plasma clearance of dTc together with a prolonged elimination t½, which suggests that clearance processes of dTc are also altered as a result of CPB. A 27% rise in dTc free fraction in plasma during CPB could be attributed to hemodilution associated with the CPB procedure itself. Lower doses of dTc will need to be used in patients undergoing surgery that involves CPB unless the concentration‐effect relationship for dTc is so altered that higher concentrations are needed to elicit the same response as in normal patients. Clinical Pharmacology and Therapeutics (1984) 35, 686–694; doi: 10.1038/clpt.1984.96