Loop Diuretics for Chronic Renal Insufficiency: A Continuous Infusion Is More Efficacious Than Bolus Therapy

Abstract

To test the hypothesis that a continuous, low-dose infusion of a loop diuretic is more efficacious and better tolerated than conventional intermittent bolus therapy in patients with severe chronic renal insufficiency (CRI). Randomized, crossover clinical trial with subjects serving as their own controls. The General Clinical Research Center of Indiana University Hospital, Indianapolis, Indiana. Eight adult volunteers with severe stable CRI (mean creatinine clearance, 0.28 mL/s; range, 0.15 to 0.47 mL/s) were recruited from the outpatient nephrology clinics of Indiana University Medical Center. On admission, diuretic drugs were withdrawn and patients were equilibrated on an 80 mmol/d sodium, 60 mmol/d potassium metabolic diet. Patients were randomized to receive a 12-mg intravenous dose of bumetanide given either as two 6-mg bolus doses separated by 6 hours or as the same total dose administered as a 12-hour continuous infusion. When sodium balance was re-established, each patient was crossed over to the alternative study limb. All patients completed both phases of the study. Comparable amounts of bumetanide appeared in the urine during the study period (infusion, 912 +/- 428 micrograms; bolus, 944 +/- 421 micrograms; difference, 32 micrograms; 95% CI, -16 micrograms to 80 micrograms, P = 0.16). The continuous infusion resulted in significantly greater net sodium excretion (infusion, 236 +/- 77 mmol; bolus, 188 +/- 50 mmol; difference, 48 mmol; CI, 16 mmol to 80 mmol, P = 0.01). No patient had episodes of drug-induced myalgias during the continuous infusion compared with 3 of 8 patients with bolus therapy. In patients with severe CRI, a continuous intravenous infusion of bumetanide is more effective and less toxic than conventional intermittent bolus therapy. Continuous administration will probably be useful in patients with severe CRI who have not achieved an adequate natriuresis or who show evidence of drug toxicity with standard diuretic dosing regimens. A similar benefit may occur in selected diuretic-resistant patients with cardiac or hepatic disease, and studies in these patients seem warranted.