Closing the Books on Low-Dose Dopamine in the ICU

Abstract & Commentary

David J. Pierson, MD, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, is Editor for Critical Care Alert

Synopsis: This extensive meta-analysis of available randomized, controlled trials shows that low-dose dopamine offers transient improvements in renal physiology but no good evidence that it offers important clinical benefits to patients with or at risk for renal failure.

Source: Friedrich JO, et al. Ann Intern Med. 2005;142:510-524.

In the absence of definitive systematic reviews, and in the presence of evidence for continued widespread administration of low-dose dopamine infusions to critically ill patients for the purpose of preventing renal failure, Friedrich and colleagues performed an exhaustive review of the literature on this subject. They searched MEDLINE, EMBASE, CINAHL, the Cochrane Library, and other sources, in an attempt to identify acceptable clinical trials to use in a meta-analysis. Included were parallel-group randomized and quasi-randomized controlled trials of low-dose dopamine versus control. Friedrich et al examined each trial’s methodology, outcomes, and adverse events.

After a comprehensive search, 61 trials, comprising data from 3359 randomized patients, were identified. Methodologic quality varied, but follow-up was largely complete. Meta-analyses using random-effects models showed that low-dose dopamine had a positive effect on urine output, increasing it by 24% (95% confidence interval [CI], 14%-35%) on the first day of infusion. Improvements in serum creatinine level (4% fall; with 95% CI, 1%-7%) and measured creatinine clearance (6% relative increase; 95% CI, 1%-11%) on day 1 were clinically insignificant. No significant effects on these variables could be detected on days 2 or 3 of therapy. Low-dose dopamine had no effect on mortality (relative risk, 0.96; 95% CI, 0.78%-1.19%), or on the need for dialysis or other renal replacement therapy (relative risk, 0.93; 95% CI, 0.76%-1.15%). There was also no evidence for an effect on adverse events (relative risk, 1.13; 95% CI, 0.90%-1.41%). Several statistical tests for heterogeneity, which would weaken the strength of the conclusion that the therapies were not different, failed to demonstrate it.

Comment by David J. Pierson, MD

For more than 40 years, the concept that low-dose (or renal-dose) intravenous dopamine infusions increase urine flow and protect the kidney from damage during acute illness has exerted a pervasive influence on clinical medicine, including patient management in the ICU. Recent surveys in several countries demonstrate that low-dose dopamine is still very widely used in critical care. No doubt this use is abetted by the bedside observation, corroborated by the present meta-analysis, that initiating low-dose dopamine therapy improves urine output, at least in many patients. However, Friedrich et al found that the improvements in urine output were short lived, and any salutary effects on serum creatinine levels or creatinine clearance were small and only temporary. And most importantly, this rigorous meta-analysis—the most extensive examination of this topic to date—failed to find any evidence for a detectable effect of low-dose dopamine on patient-relevant outcomes.

A widely used therapy has a solid theoretical rationale and produces short-term improvements in physiologic end points, but evidence that it helps patients in any meaningful way is lacking. Does that sound familiar? It reminds me of the current state of our knowledge about prone positioning in acute lung injury and the acute respiratory distress syndrome (ARDS).1 The same could be said for the administration of inhaled nitric oxide and its current spinoff, aerosolized prostacyclin. These interventions improve arterial PO2 in many if not most patients with severe ARDS. The clinical trials have consistently demonstrated this physiologic improvement, and yet those same trials have been unable to demonstrate improvements in survival or other outcomes that the patient would care about.

This rigorously performed meta-analysis should close the books, finally, on low-dose dopamine to prevent or ameliorate renal failure in critically ill patients. It does not seem to hurt-except for its cost in material and human resources-but it does not help. We should stop using it.

Reference

  1. Guerin C, et al. JAMA. 2004;292:2379-2387.