MELBOURNE--Administration of low–dose dopamine does not prevent renal failure in critically ill patients at risk for this disorder, according to data from a randomized, placebo–controlled trial conducted by the Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group.[1] In this study, so–called “renal-dose” dopamine had no effect on peak serum creatinine concentrations or other markers of renal failure. It also did not alter the survival rate or the duration of intensive care unit and hospital stays.

“Low–dose dopamine, which has been and is frequently used to ‘protect’ the kidney during situations likely to induce renal stress, does not have a clinically significant beneficial effect on kidney function,” said study investigator Rinaldo Bellomo, MBBS, MD, in a recent interview with PULMONARY REVIEWS. He believes that the medical community should decrease use of low-dose dopamine in this context.

NO LARGE STUDIES

The rationale behind the use of low-dose dopamine in critically ill patients is that it has been shown to increase renal blood flow and to induce natriuresis and diuresis in healthy volunteers. Because the most common cause of acute renal failure is renal ischemia, many physicians have thought that low–dose dopamine would help preserve renal cellular oxygenation, glomerular filtration rate, and urine output. However, until the ANZICS study, no large controlled trials had been conducted to determine whether low–dose dopamine protects critically ill patients from renal failure.

The ANZICS researchers randomized 328 patients to a continuous intravenous infusion of low-dose dopamine (2 µg/kg/min) or placebo via a central venous catheter. The two treatment groups were matched for severity of illness and other baseline characteristics. All of the subjects met the following criteria:

• Had a central venous catheter in place.

• Had two or more of the pathophysiologic changes of the systemic inflammatory response syndrome.

• Had clinical evidence of early renal dysfunction (ie, urine output averaging less than 0.5 mL/kg each hour for four hours; serum creatinine concentration of more than 150 µmol/L [in the absence of premorbid renal dysfunction]; a rise in the serum creatinine concentration of more than 80 µmol/L in less than 24 hours [in the absence of a creatine kinase level above 5,000 IU/L], or myoglobin in the urine).

The researchers found no difference in the primary outcome studied–the peak serum creatinine concentration during treatment (245 µmol/L in the dopamine group and 249 µmol/L in the placebo group). In addition, no differences were detected between the two groups in terms of the following markers of renal failure: mean increase from baseline to the highest value for serum creatinine concentration during treatment (62 µmol/L vs 66 µmol/L); number of patients whose serum creatinine concentration was above 300 µmol/L during treatment (56 in both groups); and number of patients who required renal replacement therapy (35 vs 40).

NO SIGNIFICANT DIFFERENCES

The two groups also required similar durations of mechanical ventilation (10 vs 11 days), ICU stay (13 vs 14 days), and hospital stay (29 vs 33 days). Furthermore, there were no significant differences in the numbers of patients who survived to ICU discharge (108 vs 105 patients) and to hospital discharge (92 vs 97 patients).

In addition, cardiac arrhythmias occurred in a similar number of patients in both groups (53 vs 54 patients).

“The study had a 90% power to detect a small difference between the two groups. The groups were broadly representative of the kind of patients who develop renal dysfunction, and the intervention was early and prolonged,” said Dr. Bellomo, an Associate Professor of Medicine at the University of Melbourne as well as Director of Intensive Care Research at the Austin and Repatriation Medical Centre, in Heidelberg, Victoria, Australia. “On balance, we think that our study provides strong evidence that low–dose dopamine does not help maintain glomerular filtration rate in patients experiencing renal stress,” he added.

Furthermore, although low–dose dopamine is generally considered to be harmless, it can, in fact, be detrimental. In an editorial accompanying the ANZICS study, Helen F. Galley, PhD, noted, “Dopamine can suppress respiratory drive, increase cardiac output and myocardial oxygen consumption, and trigger myocardial ischemia and arrhythmias. The drug can also induce hypokalemia and hypophosphatemia, both potentially dangerous in the critically ill, and it may predispose to gut ischemia.” She added, “It is time to stop hedging: there is no justification for using ‘renal–dose’ dopamine in the critically ill.”

--Kristin Della Volpe

References
1. Australian and New Zealand Intensive Care Society Clinical Trials Group. Low–dose dopamine in patients with early renal dysfunction: a placebo–controlled randomised trial. Lancet. 2000;356:2139– 2143.

2. Galley HF. Renal–dose dopamine: will the message now get through? Lancet. 2000;356:2112– 2113.

Return to table of contents