title: Loop diuretics in the management of acute renal failure: a systematic review and meta-analysis.
abstract: BACKGROUND
  Loop diuretics are commonly used in critically ill patients with acute renal failure (ARF), but their effect on clinical outcome remains uncertain. We systematically reviewed the literature comparing loop diuretics with control in the management of ARF.
  
  
  METHODS
  Studies were identified by search of MEDLINE, EMBASE, and the Cochrane Controlled Clinical Trials Register, and review of proceedings from selected scientific meetings and clinical trial registries, and bibliographies of retrieved citations. We selected randomised controlled trials (RCTs) comparing loop diuretics with control in patients with ARF. Data were extracted in duplicate by two independent reviewers on study characteristics, quality and outcomes. Primary outcomes were mortality, need for renal replacement therapy (RRT) and renal recovery. Secondary outcomes were change to urine output, serum potassium level and acid-base status, duration of ARF or RRT, length of hospital stay and toxicity.
  
  
  RESULTS
  Of 62 studies reviewed, five RCTs, enrolling 555 patients, were eligible and analysed. These trials enrolled a mix of patients, but only two included critically ill patients. Overall trial quality was low. There was no statistical difference in mortality (odds ratio [OR], 1.28; 95% CI, 0.89-1.84; P=0.18) or renal recovery (OR, 0.88; 95% CI, 0.59-1.31; P=0.5) with use of loop diuretics compared with control. However, loop diuretics were associated with a shorter duration of RRT (weighted mean difference, ?1.4 days; 95% CI, ?0.2 to ?2.3 days; P=0.02), shorter time to spontaneous decline in serum creatinine level (weighted mean difference, ?2.1 days; 95% CI, ?0.4 to ?3.7 days; P=0.01) and a greater increase in urine output from baseline (OR, 2.6; 95% CI, 1.4-4.9; P=0.004). Insufficient data were available on acid-base status, hospital length of stay or health costs. Four studies reported toxicity, most commonly transient tinnitus and deafness.
  
  
  CONCLUSIONS
  Loop diuretics were not associated with improved mortality or rate of independence from RRT, but were associated with shorter duration of RRT and increased urine output. However, these findings have limited relevance to critically ill patients. The relative paucity of high-quality data assessing the value of loop diuretics in ARF for the critically ill suggests a need for a suitably powered randomised trial.
authors.affiliation: Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia. sean.bagshaw@austin.org.au
authors.forename: Sean M
authors.initials: SM
authors.lastname: Bagshaw
authors.forename: Anthony
authors.initials: A
authors.lastname: Delaney
authors.forename: Michael
authors.initials: M
authors.lastname: Haase
authors.forename: William A
authors.initials: WA
authors.lastname: Ghali
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
mesh_terms: D000136:Acid-Base Equilibrium; D058186:Acute Kidney Injury / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000652:urine; D003404:Creatinine / Q000097:blood; D016638:Critical Illness; D003627:Data Interpretation, Statistical; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011188:Potassium / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D017582:Renal Replacement Therapy; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D000077786:Torsemide; D016896:Treatment Outcome
chemical_list: D049994:Sodium Potassium Chloride Symporter Inhibitors; D013449:Sulfonamides; D005665:Furosemide; D003404:Creatinine; D011188:Potassium; D000077786:Torsemide