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Meta-Analysis: Low-Dose Dopamine Increases Urine Output but Does Not Prevent Renal Dysfunction or Death

Jan O. Friedrich, MD, DPhil; Neill Adhikari, MD, CM; Margaret S. Herridge, MD, MPH; and Joseph Beyene, PhD
[+] Article and Author Information

From St. Michael's Hospital, Sunnybrook and Women's College Health Sciences Centre, Toronto General Hospital, University Health Network, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.


Note: Drs. Friedrich and Adhikari contributed equally to this study and are co–first authors.

Acknowledgments: The authors thank Deborah Cook and Gordon Guyatt for constructive comments on the manuscript; Stephen Walter and Michael Newman for statistical advice; Elizabeth Uleryk for assistance with bibliographic searches; and Yumiko Imai and Ayse Yuce for assistance with translation of Japanese and Turkish papers, respectively. The authors also acknowledge all authors who provided additional clinical outcomes data, in particular, Rinaldo Bellomo, Lydia de Lasson, Susan Garwood, Michael Hiesmayr and Andrea Lassnigg, Haus Leusink, Larry McNicol and Stephanie Poustie, Jerome O'Hara and Jacek Cywinski, Swen Piper, Miguel Sánchez, Karl Schulze, Pilar Taurá, Lawrence Weisberg, and Edwin Woo for also kindly providing additional renal physiologic outcomes data.

Grant Support: Dr. Beyene is supported by the Research Institute of the Hospital for Sick Children.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Jan O. Friedrich, MD, DPhil, Departments of Critical Care and Medicine, St. Michael's Hospital, 30 Bond Street, Bond Wing 4-011, Toronto, Ontario M5B 1W8, Canada; e-mail, j.friedrich@utoronto.ca.

Current Author Addresses: Dr. Friedrich: Departments of Critical Care and Medicine, St. Michael's Hospital, 30 Bond Street, Bond Wing 4-011, Toronto, Ontario M5B 1W8, Canada.

Dr. Adhikari: Department of Critical Care Medicine, Sunnybrook and Women's College Health Sciences Centre, 2075 Bayview Avenue, Room B7.04a, Toronto, Ontario M4N 3M5, Canada.

Dr. Herridge: Department of Respiratory and Critical Care Medicine, Toronto General Hospital, University Health Network, 585 University Avenue, NCSB 11C-1180, Toronto, Ontario M5G 2N2, Canada.

Dr. Beyene: Population Health Sciences, Research Institute, Hospital for Sick Children, Department of Public Health Sciences, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.


Ann Intern Med. 2005;142(7):510-524. doi:10.7326/0003-4819-142-7-200504050-00010
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Background: Surveys have documented the continued popularity of low-dose dopamine to influence renal dysfunction even though few data support it and editorials and reviews have discouraged its use.

Purpose: To evaluate the effects of low-dose dopamine (≤5 µg/kg of body weight per minute) compared with placebo or no therapy in patients with or at risk for acute renal failure.

Data Sources: MEDLINE (1966–January 2005), EMBASE (1980–week 5, 2005), CANCERLIT (1975–2002), CINAHL (1982–January 2005), and CENTRAL (The Cochrane Library, fourth quarter, 2004); bibliographies of retrieved publications; and additional information from 50 trials.

Study Selection: Two reviewers independently selected parallel-group randomized and quasi-randomized, controlled trials of low-dose dopamine versus control.

Data Extraction: Study methods, clinical and renal physiologic outcomes, and adverse events (arrhythmias and myocardial, limb, and cutaneous ischemia) were extracted.

Data Synthesis: 61 trials that randomly assigned 3359 patients were identified. Meta-analyses using random-effects models showed no effect of low-dose dopamine on mortality (relative risk, 0.96 [95% CI, 0.78 to 1.19]), need for renal replacement therapy (relative risk, 0.93 [CI, 0.76 to 1.15]), or adverse events (relative risk, 1.13 [CI, 0.90 to 1.41]). Low-dose dopamine increased urine output by 24% (CI, 14% to 35%) on day 1. Improvements in serum creatinine level (4% relative decrease [CI, 1% to 7%]) and measured creatinine clearance (6% relative increase [CI, 1% to 11%]) on day 1 were clinically insignificant. There were no significant changes on days 2 and 3 of therapy.

Limitations: Statistically significant between-study heterogeneity in physiologic but not clinical outcomes was unexplained by prespecified hypotheses.

Conclusion: Low-dose dopamine offers transient improvements in renal physiology, but no good evidence shows that it offers important clinical benefits to patients with or at risk for acute renal failure.

Figures

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Figure 1.
Effect of low-dose dopamine on mortality.

Weight refers to the contribution of each study to the overall estimate of treatment effect. The pooled estimate is calculated by using a random-effects model. The summary relative risk is calculated on the natural logarithm scale. The weight of each study is calculated as the inverse of the variance of the natural logarithm of its relative risk. The size of the symbol denoting the point estimate does not represent the weighting of the study. See the Methods section for a discussion of the weighting. ANZICS = Australian and New Zealand Intensive Care Society; n/n = numbers of deaths/patients randomly assigned; RR = relative risk.

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Figure 2.
Effect of low-dose dopamine on need for renal replacement therapy.

Weight refers to the contribution of each study to the overall estimate of treatment effect. The pooled estimate is calculated by using a random-effects model. The summary relative risk is calculated on the natural logarithm scale. The weight of each study is calculated as the inverse of the variance of the natural logarithm of its relative risk. The size of the symbol denoting the point estimate does not represent the weighting of the study. See the Methods section for a discussion of the weighting. ANZICS = Australian and New Zealand Intensive Care Society; n/n = numbers of patients requiring renal replacement therapy/patients randomly assigned; RR = relative risk.

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Figure 3.
Effect of low-dose dopamine on day 1 urine output.

Weight refers to the contribution of each study to the overall estimate of treatment effect. Ratio of means is mean value in dopamine group divided by the mean value in control group. The pooled estimate is calculated by using a random-effects model.

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Appendix Figure.
Trials evaluated at each stage of the systematic review.
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