Sulfoconjugation and renal excretion contribute to the interpatient variation of exogenous catecholamine clearance in critically ill children

Objective: To delineate the contributions of sulfoconjugation, renal excretion, and patient age to the wide interpatient variability in exogenous dobutamine and dopamine plasma clearance. Design: Simultaneous plasma free and sulfoconjugated dobutamine and/or dopamine, respective urine free catecholamine, and serum creatinine were determined on stable critically ill children receiving unchanged continuous infusions of dobutamine and/or dopamine for at least 1 hr. Free dobutamine and dopamine clearance rates were calculated. Setting: Pediatric and neonatal intensive care units in university settings. Patients: Forty-seven stable critically ill neonates and children. Interventions: Continuous infusions of dobutamine and/or dopamine: nine patients received dopamine only, 27 patients received dobutamine only, and 11 patients received both simultaneously. Measurements and Main Results: Fractions of plasma dobutamine and dopamine sulfoconjugated were 0.73 +/- 0.05 and 0.76 +/- 0.05, respectively. Free plasma dobutamine and dopamine clear ances were 102 +/- 15 mL/kg/min and 250 +/- .38 mL/kg/min, respectively. Linear regression analyses demonstrated relationships of the fraction of plasma dobutamine and dopamine sulfoconjugated to the respective free plasma clearances (r(2) = .30, p<.01, end r(2) = 0.29, p < .01, respectively), and, more impressively, to the natural logarithm of the respective free plasma clearances (r(2) = 0.58, p < .001, and r(2) = 0.39, p < .01). Patients with serum creatinine concentrations >2 mg/dL had lower free plasma dobutamine and dopamine clearance rates than those patients with serum creatinine of <2 mg/dL (6 +/- 1 vs. 107 +/- 15 mL/kg/min for dobutamine and 40 +/- 38 vs. 270 +/- 39 mL/kg/min for dopamine, respectively, p < .05 for both by Mann-Whitney U test). No relationship was noted between free catecholamine clearance and age. Conclusion: Sulfoconjugation and renal excretion are important determinants of the wide interpatient variability in plasma free dobutamine and dopamine clearance rates.