A rigorously conducted multicenter RCT of low-dose dopamine in patients with early renal dysfunction was published in December 200012
). This trial randomized 328 patients who met the criteria for systemic inflammatory response syndrome and acute renal dysfunction to infusions of dopamine at 2 μg/kg/min or placebo. Renal dysfunction was defined as follows: urine output averaging < 0.5 mL/kg/h for > 4 h; serum creatinine concentration, > 150 μmol/L (1.7 mg/dL) in the absence of premorbid renal dysfunction; a rise in serum creatinine concentration of > 80 μmol/L (0.9 mg/dL) in < 24 h in the absence of a creatine kinase level of > 5,000 IU/L; or myoglobin in the urine. The criteria for stopping infusion included death, progression to renal replacement therapy, improvement in systemic inflammatory response syndrome and renal function, or discharge from the ICU. After randomization, dopamine was infused for a mean duration of 4.7 days and placebo was infused for a mean of 5.2 days. The primary end point was the peak serum creatinine level reached during the trial, and the secondary end points were duration of mechanical ventilation, duration of ICU stay, duration of hospital stay, duration of cardiac arrhythmias, duration of survival to hospital discharge, and time to renal recovery. The trial was powered to detect a 20% decrease in serum creatinine level, but after two interim analyses the size of the trial was increased to > 300 patients to increase the statistical power. This trial found no difference between the dopamine and placebo groups in peak serum creatinine concentration during treatment (dopamine group, 245 ± 144 μmol/L [2.8 ± 1.6 mg/dL]; control group, 249 ± 147 μmol/L [2.8 ± 1.7 mg/dL]; p = 0.93), in the increase from baseline to the highest value during treatment (dopamine group, 62 ± 107 μmol/L [0.7 ± 1.2 mg/dL]; control group, 66 ± 108 μmol/L [0.75 ± 1.2 mg/dL]; p = 0.82), or in the numbers of patients whose serum creatinine concentrations exceeded 300 μmol/L or 3.4 mg/dL (dopamine group, 56 patients; control group, 56 patients; p = 0.92), or the number of patients who required renal replacement therapy (dopamine group, 35 patients; control group, 40 patients; p = 0.55). Durations of ICU stay (dopamine group, 13 ± 14 days; control group, 14 ± 15 days; p = 0.67) and durations of hospital stay (dopamine group, 29 ± 27 days; control group, 33 ± 39 days; p = 0.29) were also similar. There were 69 deaths in the dopamine group and 66 deaths in the placebo group. The authors concluded, “Administration of low-dose dopamine by continuous IV infusion to critically ill patients at risk of renal failure does not confer clinically significant protection from renal dysfunction.” The three following questions remain: How does this RCT compare to previous, underpowered studies? How did this therapy become so widely used? Why does low-dose dopamine not work in critically ill patients?