Pharmacokinetics of d-Tubocurarine in Patients with Thermal Injury

Abstract

d-Tubocurarine (dTc) requirements are increased following thermal injury. Significant increases in plasma binding only partially account for the altered requirement. To characterize the pharmacokinetic component of the increased requirement, the disposition of dTc was studied in eight patients with burns ranging from 15% to 80% of body surface area and compared with that in six nonburned surgical patients of comparable age and weight. Plasma levels of dTc were measured by radioimmunoassay at multiple times for 24 hours after a single bolus dose. Derived pharmacokinetic parameters were corrected for the predicted (not measured) fraction bound to plasma. The plasma disappearance curve of dTc was explained by linear sum of two or three exponential terms. The unbound central volume of distribution and renal excretion at 24 hours were significantly increased in burned patients (0.11 +/- 0.03 L/kg vs 0.057 +/- 0.015 L/kg, p less than 0.05, 57% +/- 7% vs 40% +/- 11%, p less than 0.05, respectively). On the other hand, comparable elimination half-lives (6.5 +/- 1.8 hr vs 6.2 +/- 1.3 hr, p greater than 0.05), unbound volume of distribution (0.86 +/- 0.2 L/kg vs 0.96 +/- 0.5 L/kg, p greater than 0.05), and intrinsic clearances (1.62 +/- 0.6 ml/kg/min vs 1.56 +/- 0.4 ml/kg/min, p greater than 0.05) were present in burned patients and control patients, respectively. Thus, altered kinetics contributes little to the increased doses required. Similar clearances and elimination half-lives in both groups suggest that loss of dTc through burned tissue is minimal.