Harm Diuretics and mortality in acute renal failure.
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Summary
Posted By:	Gordon S. Doig
E-Mail:	Gordon.Doig@EvidenceBased.net
Posted Date:	30 Jan 2006
Title:	Diuretics and mortality in acute renal failure.
Authors:	Uchino S, Doig GS, Bellomo R, et al
Reference:	Crit Care Med. 2004 Aug;32(8):1669-77.
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	OBJECTIVE: According to recent research, diuretics may increase mortality in acute renal failure patients. The administration of diuretics in such patients has been discouraged. Our objective was to determine the impact of diuretics on the mortality rate of critically ill patients with acute renal failure. DESIGN: Prospective, multiple-center, multinational epidemiologic study. SETTING: Intensive care units from 54 centers and 23 countries. PATIENTS: Patients were 1,743 consecutive patients who either were treated with renal replacement therapy or fulfilled predefined criteria for acute renal failure. INTERVENTIONS: Three distinct multivariate models were developed to assess the relationship between diuretic use and subsequent mortality: a) a propensity score adjusted multivariate model containing terms previously identified to be important predictors of outcome; b) a new propensity score adjusted multivariate model; and c) a multivariate model developed using standard methods, compensating for collinearity. MEASUREMENTS AND MAIN RESULTS: Approximately 70% of patients were treated with diuretics at study inclusion. Mean age was 68 and mean Simplified Acute Physiology Score II was 47. Severe sepsis/septic shock (43.8%), major surgery (39.1), low cardiac output (29.7), and hypovolemia (28.2%) were the most common conditions associated with the development of acute renal failure. Furosemide was the most common diuretic used (98.3%). Combination therapy was used in 98 patients only. In all three models, diuretic use was not associated with a significantly increased risk of mortality. CONCLUSIONS: Diuretics are commonly prescribed in critically ill patients with acute renal failure, and their use is not associated with higher mortality. There is full equipoise for a randomized controlled trial of diuretics in critically ill patients with renal dysfunction.
Are the Results Valid?
1. Were there clearly identified comparison groups that were similar with respect to important determinants of outcome, other than the one of interest?
	The two primary comparison groups were critically ill patients who fulfulled predefined criteria for acute renal failure who did or did not receive diuretics. Although these two groups differed with regards to key clinical characteristics, these differences were controlled using three different comprehensive multivariate approaches.
2. Were the outcomes and exposures measured in the same way in the groups being compared?
	Yes. All 54 study sites from 23 countries defined clinical chracteristics, exposure to diuretics and outcomes were measured the same way in both comparison groups.
3. Was follow-up sufficiently long and complete?
	Patients were followed until hospital discharge. Of 1,758 patients who met the eligibility criteria for this study, 15 had missing information regarding diuretic use and 12 patients had missing hospital discharge information. An extensive analysis of the potential impact of other missing values is presented.
4. Is the temporal relationship correct?
	Although it appears intuitive that diuretic use occurs before death, this relationship is not so simple. It is possible that diuretic use simply indicates the presence of worsening underlying cardiac and renal impairment, which could be the cause for the measured difference in outcome. There is no specific analysis to demonstrate definite temporal relationship between diuretic use and poor outcome.
5. Is there a dose response gradient?
	There was no specific analysis conducted to investigate a dose response relationship.
What are the Results?
1. How strong is the association between exposure and outcome?
	Three distinct multivariate models were developed to assess the relationship between diuretic use and subsequent mortality: a) a propensity score adjusted multivariate model containing terms previously identified to be important predictors of outcome; b) a new propensity score adjusted multivariate model; and c) a multivariate model developed using standard methods, compensating for collinearity. All three failed to find a significant relationship between diuretic use and mortality: a) Mehta's model: (OR 1.21, p=0.10) b) Mehta's method: (OR 1.21, p=0.18) c) Muliticollearity adjusted model: (OR 1.22, p=0.15).
2. How precise is the estimate of risk?
	95% Confidence Intervals: a) Mehta's model: OR 1.210 (0.96–1.5) b) Mehta's method: OR 1.217 (0.91–1.6) c) Muliticollearity adjusted model: OR 1.222 (0.92–1.6).
Will the Results Help Me In Caring For My Patients?
1. Are the results applicable to my practice?
	The extensive analysis conducted on this large multi-national data base failed to find any significant relationship between diuretic use in ARF and increased mortality. These results do not support discontinuing diuretic use in these patients.
2. What is the magnitude of the risk?
	The magnitude of risk obtained from all three analyses was not significant but was consistently a 1.2 increase in the relative odds of death (OR=1.2). If there is increased risk, given an overall mortality of 51.6%, converting an OR of 1.2 to an absolute mortality increase yields approximately 4.5%.
3. Should I attempt to stop the exposure?
	No.
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