Acute renal failure: high dose loop diuretics increased urine output and seizures.

Clinical bottom line (level 1b)

  1. In patients with renal failure treated with dopamine and mannitol, high dose loop diuretics increased urine flow (NNT = 4 at 21 days) , but patients were more likely to have seizures (NNT = 6 at 21 days) .
  2. The effect on dialysis and mortality was unclear.
  3. The time to dialysis was longer (~2 days), but the duration of dialysis was similar.
Shilliday et al: Nephrology Dialysis Transplantation 1997; 12: 2592-2596
Expires July 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: renal unit of university hospital, UK

92 patients (aged mean 59 years, 55% male) acute renal failure, defined by a rise in creatinine to >180 µ mol/l

Excluded if
  • aged <18 years
  • prerenal or postrenal failure
  • ultrasonographic evidence of obstruction
  • loop or osmotic diuretic in previous 12 hours
  • high dose loop diuretic (>100 mg furosemide or equivalent) in previous 48 hours
  • administration of an investigational substance within 30 days
  • women using inadequate contraception, or who were pregnant or lactating


    • Note:
  • Mean APACHE II score among patients was 19, hourly urine volume was 25 ml/h and creatinine was 73- µ mol/l.


    • Control Group: (n = 30, 30 analysed): placebo
    Experimental Group: (n = 62, 62 analysed): furosemide (n=32) or torsemide (n=30), 3 mg/kg as an i.v. infusion over one hour, every six hours for up to three days. The dose was progressively reduced if the creatinine began to fall.
    All patients had dopamine i.v. 2 µ g/kg/min; mannitol 100 ml of 20% solution over an hour every 6 hours for a maximum of 3 days. Dopamine and the study drug were continued if the patient became dialysis dependent or failed to recover renal function. All patients had bladder catheterisation, central venous or pulmonary artery catheter monitoring and arterial blood gases or pulse oximetry.
    100% followed for 21 days

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    no increase in urine flow 21 days 23
    (76.7%)    		 30
    (48.4%)    		 37%
    (13% to 54%)    		 28.3%
    (8.69% to 47.9%)    		 4
    (2 to 12)
    no renal recovery 21 days 23
    (76.7%)    		 48
    (77.4%)    		 -1%
    (-28% to 20%)    		 -0.75%
    (-19.1% to 17.6%)    		 -133
    (NNT = 6 to infinity;
    NNH = 5 to infinity)
    dialysis 21 days 12
    (40.0%)    		 21
    (33.9%)    		 15%
    (-48% to 52%)    		 6.13%
    (-15.0% to 27.3%)    		 16
    (NNT = 4 to infinity;
    NNH = 7 to infinity)
    death 21 days 15
    (50.0%)    		 42
    (67.7%)    		 -35%
    (-101% to 9%)    		 -17.7%
    (-39.1% to 3.60%)    		 -6
    (NNT = 28 to infinity;
    NNH = 3 to infinity)
    seizure 21 days 1
    (3.33%)    		 12
    (19.4%)    		 -481%
    (-4160% to 21%)    		 -16.0%
    (-27.8% to -4.28%)    		 -6
    (-23 to -4)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    time to dialysis (days) 2.8
    (1.2)     		5.5
    (5.0)     		2.7
    (0.85 to 4.5)
    duration of dialysis (days) 13.2
    (10.7)     		13.4
    (13.7)     		0.20
    (-5.5 to 5.9)

  • Furosemide and torsemide were considered together.

    • Comments

    1. All patients were initially treated with mannitol with planned treatment for 72 hours. However, only 22% received treatment for this length of time. Reasons for stopping mannitol included hyperosmolality in 16% and pulmonary oedema in 1%.
    2. The authors claimed this was an adequately powered study without giving details of their sample size calculation; however, with 30 per group, they would have 80% power to detect only very large difference in mortality or dialysis (e.g. 50% survival in controls and 80% in experimentals). Much smaller differences than this would be clinically important, so this study cannot be regarded as conclusively negative for these outcomes.
    3. This study suffers from numerous flaws including: an overly liberal definition of oliguria, no defined criteria for the initiation of dialysis, and a small size making it unlikely to have the necessary power to answer the questions asked.

    Citation

    1. Shilliday IR, Quinn KJ, Allison MEM: Loop diuretics in the management of acute renal failure; a prospective, double-blind, placebo-controlled, randomized study. Nephrology Dialysis Transplantation 1997; 12: 2592-2596
    Search Terms: acute renal failure [MeSH] and oliguri* [text word] OR oliguria [MeSH]
    Contributor: Catherine Clase, Chris Ball and Clare Wotton, April 2000
    Reviewer: Harold Szerlip

    Clinical Question.
    Patient acute renal failure
    Intervention or Exposure furosemide or torsemide
    Comparison placebo
    Outcome urine flow, renal recovery, dialysis, death