ANZICS: Low-Dose Dopamine in Early Renal Dysfunction (2000)

“We have shown that, in critically ill patients at risk of acute renal failure, low-dose dopamine offers no benefit.”

  • Rinaldo Bellomo, on behalf of the ANZICS Trial Investigators

1. Publication Details

  • Trial Title: Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial
  • Citation: Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Lancet. 2000 Dec 23-30;356(9248):2139-43. DOI: 10.1016/s0140-6736(00)03495-4
  • Published: December 23, 2000, in The Lancet
  • Author: Rinaldo Bellomo, M.D.
  • Funding: Health Research Council of New Zealand and the Australian and New Zealand Intensive Care Society.

2. Keywords

  • Acute Kidney Injury (AKI), Dopamine, Renal Dose Dopamine, Critical Care, Randomized Controlled Trial

3. The Clinical Question

  • In critically ill adult patients with early renal dysfunction (Population), does an infusion of low-dose dopamine (Intervention) compared to placebo (Comparison) prevent the progression to severe acute renal failure (Outcome)?

4. Background and Rationale

  • Existing Knowledge: At the time, infusions of low-dose dopamine (so-called “renal-dose” dopamine) were widely used in ICUs around the world. The practice was based on physiological reasoning that dopamine could selectively dilate the renal arteries, thereby increasing blood flow to the kidneys and protecting them from injury.
  • Knowledge Gap: Despite its widespread use, there was no high-quality evidence from large, randomized controlled trials to support this practice. It was unknown if this physiological effect translated into any meaningful clinical benefit for patients.
  • Proposed Hypothesis: The authors hypothesized that low-dose dopamine would be superior to placebo in preventing the worsening of renal dysfunction in critically ill patients.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, double-blind, placebo-controlled trial (used to test the effectiveness of interventions).
  • Setting: 23 intensive care units (ICUs) in Australia and New Zealand.
  • Trial Period: Enrollment ran from March 1997 to March 1999.
  • Population:
    • Inclusion Criteria: Adult patients admitted to the ICU with at least two of the three following criteria for early renal dysfunction: oliguria (<30 mL/h for >2h), elevated creatinine (>1.7 mg/dL or 150 µmol/L), or the presence of at least two systemic inflammatory response syndrome (SIRS) criteria.
    • Exclusion Criteria: Included pre-existing end-stage renal disease, recent use of dopamine, and tachyarrhythmias.
  • Intervention: Patients received a continuous intravenous infusion of dopamine at 2-3 mcg/kg/min.
  • Control: Patients received a matching intravenous placebo (5% dextrose).
  • Management Common to Both Groups: All other aspects of patient care, including fluid management and other supportive therapies, were at the discretion of the treating clinicians.
  • Power and Sample Size: The authors calculated that a sample size of 320 patients would be required to have 80% power to detect a 25% relative reduction in the primary outcome. (Power is a study’s ability to find a real difference between treatments if one truly exists; 80% is the standard accepted level for clinical trials).
  • Outcomes:
    • Primary Outcome: The peak serum creatinine concentration during the study infusion.
    • Secondary Outcomes: Included the proportion of patients who required renal-replacement therapy (RRT), ICU and hospital mortality, and length of stay.

6. Key Results

  • Enrollment and Baseline: 328 patients were randomized (161 to dopamine and 167 to placebo). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: There was no significant difference in the primary outcome. The mean peak serum creatinine was 253 µmol/L in the dopamine group and 255 µmol/L in the placebo group (p=0.90).
  • Secondary Outcomes: There were no significant differences between the groups in the proportion of patients requiring RRT (20% in both groups), in ICU mortality (29% vs 27%), or in hospital mortality (42% vs 39%).
  • Adverse Events: Tachycardia was significantly more common in the dopamine group (24% vs 11%; p=0.004).

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a Student’s t-test. Proportions were compared with a chi-square test.
  • Primary Outcome Analysis: The primary outcome was a comparison of the mean peak serum creatinine between the two groups.
  • Key Statistic(s) Reported: The key statistics were the mean values for the primary outcome and the associated P-value.
  • Interpretation of Key Statistic(s):
    • P-value: The p-value of 0.90 is much higher than the 0.05 threshold, indicating that the very small difference in peak creatinine between the groups was not statistically significant and was due to chance (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures: As the trial was neutral, ARR and NNT are not applicable.
  • Subgroup Analyses: No significant differences were found in any of the pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The multicenter, randomized, double-blind, placebo-controlled design was a major strength and represented the highest level of evidence for this question at the time.
  • Generalizability: The inclusion of 23 diverse ICUs across two countries increases the external validity of the findings.
  • Statistical Power: The study was adequately powered for its primary outcome.
  • Patient-Centered Outcomes: While the primary outcome was a lab value, the study importantly tracked and reported on key patient-centered outcomes like the need for dialysis and mortality.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was well-conducted with a low risk of bias.
  • External Validity (Generalizability): The study population was broad, making the findings widely applicable to general ICU patients at risk of AKI.
  • Other: The primary outcome was a surrogate marker (serum creatinine) rather than a direct patient-centered outcome like need for RRT or mortality. However, the lack of benefit in these key secondary outcomes strongly supports the overall conclusion.

10. Conclusion of the Authors

  • In critically ill patients at risk of acute renal failure, low-dose dopamine does not confer any clinically significant renal protection.

11. To Summarize

  • Impact on Current Practice: This was a landmark, practice-changing trial. It provided the first high-quality evidence to definitively refute the long-standing and widespread practice of using “renal-dose” dopamine, leading to its de-adoption worldwide.
  • Specific Recommendations:
    • Patient Selection: For critically ill adult patients at risk of developing acute kidney injury.
    • Actionable Intervention: Do not administer low-dose dopamine with the expectation of preventing or treating AKI.
  • What This Trial Does NOT Mean: This trial does NOT mean that dopamine has no role in the ICU. Its findings are specific to the use of low-dose dopamine for renal protection and do not apply to its use as a vasopressor or inotrope at higher doses.
  • Implementation Caveats: The finding of increased tachycardia in the dopamine group highlights that even at low doses, the drug is not without side effects.

12. Context and Related Studies

  • Building on Previous Evidence: The ANZICS trial (2000) was designed to challenge a widespread practice that was based on physiological theory and weak observational data rather than robust evidence.
  • Influence on Subsequent Research: The definitive negative result of this trial was a major victory for evidence-based medicine and antimicrobial stewardship. It helped shift the focus of AKI research away from ineffective pharmacological interventions and towards supportive care strategies, such as optimizing hemodynamics and avoiding nephrotoxins.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: This trial definitively answered its primary question.
  • Future Directions: The results of this trial helped to close the book on “renal-dose” dopamine. Subsequent research in AKI has focused on other areas, such as the optimal timing of RRT initiation (e.g., AKIKI (2016) and STARRT-AKI (2020) trials).

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a very common and resource-intensive practice that lacked high-quality evidence.
  • Methods: The multicenter, randomized, double-blind, placebo-controlled design represents a high level of evidence and was appropriate for minimizing bias. The patient population was representative of general ICU patients at risk of AKI.
  • Results: The study reported a clear neutral finding for its primary outcome and, importantly, for all key patient-centered secondary outcomes. The finding of increased tachycardia in the dopamine group suggested potential harm without any benefit.
  • Conclusions and Applicability: The authors’ conclusion is strongly supported by the data. The high external validity of this pragmatic trial means its findings are broadly applicable to most ICUs. This trial is a classic example of a high-quality “negative” trial that was profoundly practice-changing by providing strong evidence to stop a common but ineffective therapy.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
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