Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial
Bellomo et al. Lancet 2000; 356:2139-2143. doi:10.1016/S0140-6736(00)03495-4
- In patients renal dysfunction, does dopamine reduce the severity of acute kidney injury?
- Randomised, placebo-controlled trial
- Block randomised with stratification by centre, with adequate concealment
- Allocation blinded to patient, nurses, physicians and investigators
- Aimed to recruit 230 patients to provide 80% power to detect a 20% decrease in peak serum creatinine, with alpha = 0.05. This assumed a normal distribution of peak serum creatinine, with a mean of 250 µmol/l and standard deviation of 150 µmol/l in the control arm.
- 20% chance of false negative
- 5% chance of false positive
- 23 Intensive Care Units – 22 in Australia and one in Hong Kong
- March 1996 to April 1999
- Inclusion: 2 or more features of systemic inflammatory response syndrome (SIRS); and central venous catheter in situ; and at least one indicator of early renal dysfunction
- < 0.5 ml/kg/hr over 4 hours or longer
- Creatinine > 150 µmol/l if no premorbid kidney disease
- Rise in serum creating of > 80 µmol/l in less than 24 hours in absence of CK > 5000 IU/ml or myoglobinurea
- Exclusion: under 18 years of age; acute renal failure within last 3 months; renal transplant patients; use of dopamine during current hospital stay; baseline serum creatinine > 300 µmol/l
- 467 patients screened of which 328 patients randomised
- Mean APACHE II = 18 and SAPS II = 40.5
- Shock present in 60%
- Ventilated in 86%
- Mean baseline creatinine 182 µmol/l and urea 14.4 mmol/l
- Dopamine infusion at 2 µg/kg/min
- 163 assigned, and 161 analysed
- Infused for a mean of 113 hours
- Same infusion rate of identically prepared placebo fluid infusion (specific fluid composition not described)
- 165 assigned, and 163 analysed
- Infused for a mean of 125 hours
- Both the intervention and control were continued until any of the following: renal replacement therapy (RRT); death; related serious adverse event; SIRS and renal dysfunction resolved for at least 24 hours; discharge from ICU.
- Primary outcome: peak serum creatinine concentration (as a clinically appropriate surrogate for glomerular filtration rate) showed no statistically significant difference between the groups
- dopamine 245 µmol/l (SD=144) vs 249 µmol/l (147); difference 4 µmol/l (-28 to 36); p=0.8.
- Secondary outcome: there were no differences in any measures
- duration of mechanical ventilation: dopamine 10 vs placebo 11 days (p=0.63)
- duration of ICU stay: 13 vs 14 days (p=0.67)
- duration of hospital stay: 29 vs 33 days (p=0.29)
- incidence of arrhythmias: 33% vs 33%
- survival to ICU discharge: 67% vs 64%
- survival to hospital discharge: 57% vs 60%
- stopped due to related serious incident: 4% vs 4%
- “These findings support the view that low-dose dopamine does not confer a clinically significant degree of renal protection in critically ill patients, with SIRS, at risk of renal failure.”
- Good methodology with adequate concealment and blinding
- Sensible inclusion criteria; good generalisability
- Multi-centre recruitment
- Is peak serum creatinine an important outcome measure? Does it matter how high it goes, or does it matter how the renal dysfunction upsets patients pathophysiologically?
- Concurrent administration of other renal-active drugs, such as furosemide (n=90 in each group)
The Bottom Line
- There is no place for dopamine to prevent renal dysfunction from getting worse in patients with SIRS.
- [article] Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial.
- [Editorial] Renal-dose dopamine: will the message now get through? by Galley
- [Further reading] Dopamine by Life in the Fast Lane