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Dopamine for renal protection

¹ Ludwigshafen, Germany
² Aschaffenburg, Germany

To the Editor:

We have read the comments of Bracco and Parlow¹ on the meta-analysis of Kellum and Decker² with interest. They have reviewed a seemingly important meta-analysis and provided interesting additional viewpoints on an important topic. Unfortunately, the paper by Kellum and Decker is a problematic basis for such detailed analyses. As we have shown in a letter to Critical Care Medicine,³ the meta-analysis of Kellum and Decker has minor flaws in data selection and presentation and several major flaws in data analysis that make its results questionable. There was no attempt by Kellum and Decker to reject our criticism, so we can assume that most of our points are valid.

The abstract of Kellum and Decker’s publication in the Canadian Journal of Anesthesia contains a table with the main outcome data, which states that "values have been re-calculated", although it is unclear why, how and by whom. This re-calculation includes two wrong numbers. For one, the risk of death is 12/258 = 4.65% in the dopamine group and 14/250 = 5.60% in the placebo group, giving a relative risk ratio of 0.83, not 0.86. Secondly, the risk for onset of renal failure is 38/253 = 15.0% with dopamine and 59/270 = 21.9% with placebo, resulting in a relative risk of 0.69, not 0.72.

Finally, although the re-calculated risk ratios are not significant at the usual 0.05 level, it should be mentioned that the trend for reduction of acute renal failure with dopamine is quite strong, with P < 0.06 in Fisher’s exact test. Consequently, we think that Bracco’s conclusion that "there are no data from prospective, well-controlled, randomized clinical trials that support the use of dopamine in critically ill patients..." is premature. Rather, we would conclude with Parlow that a "further large-scale investigation into effective means of prevention is warranted".

This should include a state-of-the-art meta-analysis that replaces the values of Kellum and Decker with reliable (and updated) data. Such a meta-analysis should preferably be conducted by a group who is not biased by its own prior publications on dopamine. Alternatively, it could be a joint effort of scientists who have published pro and contra dopamine in the past.

References

1 Bracco D, Parlow JL. Best evidence in anesthetic practice. Prevention: dopamine does not prevent death, acute renal failure, or need for dialysis. Can J Anesth 2002; 49: 417–9.[Free Full Text]

2 Kellum JA, Decker JM. Use of dopamine in acute renal failure: a meta-analysis. Crit Care Med 2001; 29: 1526–31.[Medline]

3 Maleck WH, Piper SN, Koetter KP. Use of dopamine in acute renal failure. Crit Care Med 2002; 30: 1934–6.[Medline]

REPLY

³ Hamilton, Ontario

I thank Dr. Maleck and his colleagues for their interest in the summary¹ on the meta-analysis of Kellum and Decker.² As the editor for the Best Evidence in Anesthetic Practice, my policy is to recalculate the effect estimates of a featured study if sufficient data has been published. This policy is consistent with that of secondary journals such as the ACP Journal Club.

Kellum and Decker identified 24 studies that reported at least one of their outcomes of interest; 18 were randomized controlled trials. The authors state that, "because a sufficient number of randomized trials were identified, the remainder of the analysis was restricted to these studies."² Cumulative risk ratios (RR) were calculated using the Mantel-Haenszel fixed effects model. The recalculated values featured in Best Evidence¹ are based on data published in Table II of the original report² using the same model and Meta-Analyst version 0.988 (© Joseph Lau, Boston, MA, USA). The RR of 0.83 and 0.69 for death and onset of renal failure suggested by Maleck et al. appear to be based on an equal effects model, which assumes identical within-study and between-study variances for all pooled studies.³ This is analogous to assuming that all the results are from one single study. Such an assumption is not valid for this meta-analysis.

Like all other types of studies, the validity of a systematic review can be threatened by various confounders and biases. However, Kellum and Decker’s meta-analysis provided the most up-to-date summary of the relevant literature at the time of its publication. Two recent studies have reported similar results.^4,5 An updated meta-analysis would be welcomed and eagerly appraised.

References

1 Bracco D, Parlow JL. Best evidence in anesthetic practice. Prevention: dopamine does not prevent death, acute renal failure, or need for dialysis. Can J Anesth 2002; 49: 417–9.

2 Kellum JA, Decker JM. Use of dopamine in acute renal failure: a meta-analysis. Crit Care Med 2001; 29: 1526–31.

3 Laird NM, Mosteller F. Some statistical methods for combining experimental results. Int J Technol Assess Health Care 1990; 6: 5–30.[Medline]

4 Marik PE, Iglesias J. Low-dose dopamine does not prevent acute renal failure in patients with septic shock and oliguria. NORASEPT II Study Investigators Am J Med 1999; 107: 387–90.

5 Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000; 356: 2139–43.[Medline]

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