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Three Part Question

In [a critically ill patient] is [low dose (renal dose) dopamine effective] at [preventing renal failure]?

Clinical Scenario

You are asked to review a 75 year old patient who is 1 day post coronary arterial bypass surgery. He has passed 8ml of urine in the last hour and only 70ml in the last 6 hours. Of note he has had 40mg of Frusemide 1 hour ago. His pulse is 95 and he is in sinus rhythm, his blood pressure is 105/70 and his CVP is 5cm. He has no history of renal failure and he is on no reno-toxic drugs, althouogh he is on a small dose of noradrenaline. You note that it had been a difficult operation and there had been a long bypass time. You suggest an increase in the noradrenaline to increase his blood pressure and thus his renal perfusion pressure. The nurse suggests that you try a 'renal dose of dopamine' instead. You do not believe that dopamine is actually reno-protective and thus you elect to search for the evidence for or against this commonly held view.

Search Strategy

Medline 1966-07/2003 using OVID interface.
(no new papers identified on 10/2003 repeat search)
[dopamine.sh OR dopamine agents.sh OR dopamine.mp] AND [renal failure, acute.sh OR renal failure.mp OR kidney failure.mp] AND [maximally sensitive RCT filter] LIMIT to human AND English language.

Search Outcome

143 papers were found of which 24 were included in the meta-analysis reported below. Two further papers were found which were of relevance. One hundred and twelve abstracts were irrelevant and 3 were of insufficient quality for inclusion. The relevant papers are presented in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Bellomo R et al, 2000, Australia	328 critically ill adults with early renal dysfunction from 23 intensive care units 161 patients received continuous infusion of low dose dopamine (2mcg/kg/min) via a central line 163 patients received placebo infusion.	Double-blind PRCT (level 1b)	Peak creatinine ìmol/l	Dopamine 245, placebo 249	Of 467 patients screened for entry into the study only 328 were entered Large amount of diuretic used by physicians during the study: dopamine group mean dose 192mg but placebo group mean dose 268mg The dopamine group had a lower baseline urine output that almost reached significance (37ml/hr vs 50ml/hr, difference 13 (CI –1 to 27ml/hr)
			No. pts with creatinine conc>300	Dopamine 56, placebo 56
			No. pts requiring renal replacement therapy	Dopamine 35, placebo 40
			Urine output (mls/hr) After 24hrs	Dopamine 96ml/hr, placebo 92ml/hr
			Output after 48hrs	Dopamine 99ml/hr, placebo 109ml/hr
Kellum JA and Decker JM, 2001, USA	Medline search 1966 to Dec 1999 of papers reporting the effects on the kidney (drug effects) of low dose dopamine <5mcg/kg/ml 24 studies found (n=1019) of which 17 were RCTs (n=854)	Meta-analysis (level 1a)	Mortality in treatment and control group n= 508	Dopamine 4.7 %, placebo 5.6 % N/S	58 studies were found but data could only be extracted from 24 studies Power calculations showed that they could confidently exclude that Dopamine reduces renal failure by over 50%. But even this meta-analysis cannot detect more subtle differences
			Requirement for haemodialysis n=618	Dopamine 13.9 %, placebo 16.5 % N/S
			Acute renal failure n=508	Dopamine 15.3 %, placebo 19.5 % N/S
Marik PE and Iglesias J, 1999, USA	A sub-study of 395 oliguric patients with septic shock 3 groups identified: Group 1: 174 patients receiving dopamine at <3 µg/kg/min Group 2:127 patients receiving dopamine at >3 µg/kg/min Group 3: 94 patients receiving no dopamine	Non-randomised case-control study (level 4)	Development of acute renal failure	Group 1 29%. Group 2 31%. Group 3 29%, N/S	This is a sub-study of the NORASEPT II study that was a PRCT looking at monoclonal antibody to TNF in sepsis). This analysis is retrospective, non randomised, non-matched, and did not have prospective data collection regarding adverse events. Included here as it is a similar quality paper to those in the meta-analysis but this was not included by Kellum and Decker
			Requirement for dialysis or ultrafiltration	Group 1 13%. Group 2 14%. Group 3 13%, N/S
			28-day survival	Group 1 64%. Group 2 58%. Group 3 66%, N/S

Comment(s)

The meta-analysis by Kellum and Decker could demonstrate no benefit of low dose dopamine for the preservation of renal function. this was a well conducted meta-analysis, however, 53 relevant papers found, data could only be extracted from half. We also found two more recently published trials not included in this meta-analysis. These also presented negative results. The ANZICS trial found no reno-protective effect with dopamine, and the NORASEPT II study also found no reno-protective effect. The meta-analysis and the two RCTs presented here find that there is no reno-protective effect with dopamine. To ensure that there has not been a Type I error (finding no difference when in fact one does exist) the papers must be adequately powered. Kellum and Decker provide power calculations showing that they are very unlikely to have missed benefits to renal failure of over 50%. However even this meta-analysis is not able to exclude smaller effects than this. Our calculations show that to detect a 20% difference in acute renal failure (control event rate from this meta-analysis was 19.5%) with a power of 80%, one would need 4100 patients for a double blind RCT, or meta-analysis. thus, while it can firmly conclude that dopamine does not halve the rate of acute renal failure, it is currently unknown as to whether dopamine might have a smaller positive effect than this. In order to exclude 20% reduction in acute renal failure with dopamine, an RCT would have to recruit 4100 critically ill patients.

Editor Comment

The search strategy was repeated in October 2003. No new relevant papers identified.

Clinical Bottom Line

There is no evidence to support the use of low-dose dopamine to treat acute renal failure in critically ill patients.

Level of Evidence

Level 1 - Recent well-done systematic review was considered or a study of high quality is available.

References

1. Bellomo R, Chapman M, Finfer S, et al. Australia and New Zealand intensive care society (ANZICS) clinical trial group. Low-dose dopamine in patients with early renal dysfunction:a placebo-controlled randomised trial. Lancet 2000;356(9248):2139-43.
2. Kellum JA, Decker JM. Use Of Dopamine in Acute Renal Failure: A meta-analysis. Crit Care Med 2001;29(8):1526-1531.
3. Marik PE, Iglesias J. Low-dose Dopamine Does Not Prevent Acute Renal Failure in Patients with Septic Shock and Oliguria :The NORASEPT II Study Investigators. Am J Med 1999;107(4):387-390.