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

Clinical Question

• In patients renal dysfunction, does dopamine reduce the severity of acute kidney injury?

Design

• 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

Setting

• 23 Intensive Care Units – 22 in Australia and one in Hong Kong
• March 1996 to April 1999

Population

• 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

Intervention

• Dopamine infusion at 2 µg/kg/min
  • 163 assigned, and 161 analysed
  • Infused for a mean of 113 hours

Control

• 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

Outcome

• 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%

Authors’ Conclusions

• “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.”

Strengths

• Good methodology with adequate concealment and blinding
• Sensible inclusion criteria; good generalisability
• Multi-centre recruitment

Weaknesses

• 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)