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      Frusemide Administration in Critically Ill Patients by Continuous Compared to Bolus Therapy

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          Background: Frusemide is frequently administered to critically ill patients in the intensive care unit (ICU). We investigated whether continuous frusemide infusion therapy was more effective than regular intermittent bolus doses at causing diuresis. Methods: 59 adult patients with fluid overload admitted to two tertiary multidisciplinary ICUs were randomised to either a continuous frusemide infusion or regular intermittent intravenous boluses of frusemide according to pre-defined algorithms aiming for a minimum hourly urine output. Results: There was no significant difference in diuretic response between the two groups during the first 24 h (5.3 liters in the bolus group vs. 5.4 liters in the infusion group). In the bolus group a significantly higher dose of frusemide was needed to achieve target diuresis (24.1 vs. 9.2 mg/h in the infusion group, p = 0.0002). Mean urine output per dose of frusemide was significantly higher in the infusion group (31.6 vs. 18 ml/mg in the bolus group, p = 0.014). At the end of the study, there were no differences in hospital mortality, number of patients requiring ventilatory support, change in serum creatinine or change in estimated glomerular filtration rate. Conclusions: Both intermittent boluses and continuous infusion of frusemide were successful in achieving algorithm-driven diuresis. However, continuous infusion therapy was more effective than intermittent boluses since the dose of frusemide required was significantly less.

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          Most cited references 18

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          Diuretics, mortality, and nonrecovery of renal function in acute renal failure.

          Acute renal failure is associated with high mortality and morbidity. Diuretic agents continue to be used in this setting despite a lack of evidence supporting their benefit. To determine whether the use of diuretics is associated with adverse or favorable outcomes in critically ill patients with acute renal failure. Cohort study conducted from October 1989 to September 1995. A total of 552 patients with acute renal failure in intensive care units at 4 academic medical centers affiliated with the University of California. Patients were categorized by the use of diuretics on the day of nephrology consultation and, in companion analyses, by diuretic use at any time during the first week following consultation. All-cause hospital mortality, nonrecovery of renal function, and the combined outcome of death or nonrecovery. Diuretics were used in 326 patients (59%) at the time of nephrology consultation. Patients treated with diuretics on or before the day of consultation were older and more likely to have a history of congestive heart failure, nephrotoxic (rather than ischemic or multifactorial) origin of acute renal failure, acute respiratory failure, and lower serum urea nitrogen concentrations. With adjustment for relevant covariates and propensity scores, diuretic use was associated with a significant increase in the risk of death or nonrecovery of renal function (odds ratio, 1.77; 95% confidence interval, 1.14-2.76). The risk was magnified (odds ratio, 3.12; 95% confidence interval, 1.73-5.62) when patients who died within the first week following consultation were excluded. The increased risk was borne largely by patients who were relatively unresponsive to diuretics. The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function. Although observational data prohibit causal inference, it is unlikely that diuretics afford any material benefit in this clinical setting. In the absence of compelling contradictory data from a randomized, blinded clinical trial, the widespread use of diuretics in critically ill patients with acute renal failure should be discouraged.
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            Meta-analysis of frusemide to prevent or treat acute renal failure.

            To investigate the potential beneficial and adverse effects of frusemide to prevent or treat acute renal failure in adults. Meta-analysis of randomised controlled trials. Cochrane controlled trials register (2005 issue 4), Embase, and Medline (1966 to 1 February 2006), without language restrictions. Two reviewers checked the quality of the studies and independently extracted data. Nine randomised controlled trials totalling 849 patients with or at risk of acute renal failure were included. Outcome measures not significantly different after frusemide treatment were in-hospital mortality (relative risk 1.11, 95% confidence interval 0.92 to 1.33), risk for requiring renal replacement therapy or dialysis (0.99, 0.80 to 1.22), number of dialysis sessions required (weight mean difference--0.48 sessions, -1.45 to 0.50), and proportion of patients with persistent oliguria (urine output < 500 ml/day: 0.54, 0.18 to 1.61). Stratifying studies that used frusemide to prevent or treat acute renal failure did not change the results on mortality (relative risk ratio 2.10, 95% confidence interval 0.67 to 6.63) and the risk for requiring dialysis (4.12, 0.46 to 37.2). Evidence suggested an increased risk of temporary deafness and tinnitus in patients treated with high doses of frusemide (relative risk 3.97, 95% confidence interval 1.00 to 15.78). Frusemide is not associated with any significant clinical benefits in the prevention and treatment of acute renal failure in adults. High doses may be associated with an increased risk of ototoxicity.
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              Diuretics and mortality in acute renal failure.

               ,  R Bellomo,  Miet Schetz (2004)
              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. Prospective, multiple-center, multinational epidemiologic study. Intensive care units from 54 centers and 23 countries. Patients were 1,743 consecutive patients who either were treated with renal replacement therapy or fulfilled predefined criteria for acute renal failure. 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. 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. 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.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                October 2007
                20 September 2007
                : 107
                : 2
                : c70-c76
                Program in Critical Care, University of Western Ontario, London Health Sciences Centre, London, Ont., Canada
                108641 Nephron Clin Pract 2007;107:c70–c76
                © 2007 S. Karger AG, Basel

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                Figures: 3, Tables: 2, References: 30, Pages: 1
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