SOAP II: Dopamine vs Norepinephrine in Shock (2010)

“Although there was no significant difference in the rate of death between the dopamine and norepinephrine groups in the entire cohort, dopamine was associated with a higher rate of death at 28 days among patients with cardiogenic shock.”

— The SOAP II Investigators

1. Publication Details

  • Trial Title: Comparison of Dopamine and Norepinephrine in the Treatment of Shock.
  • Citation: De Backer D, Biston P, Devriendt J, et al; for the SOAP II Investigators. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362(9):779-789. doi:10.1056/NEJMoa0907118.
  • Published: March 4, 2010, in The New England Journal of Medicine.
  • Author: Daniel De Backer, M.D., Ph.D.
  • Funding: European Society of Intensive Care Medicine (ESICM).

2. Keywords

Shock, Septic Shock, Cardiogenic Shock, Vasopressors, Dopamine, Norepinephrine, Catecholamines, Arrhythmia.

3. The Clinical Question

In adult patients with shock (Population), does the use of dopamine as the first-line vasopressor (Intervention) compared to norepinephrine (Comparison) affect the 28-day mortality rate (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Dopamine and norepinephrine were the most commonly used vasopressors to restore blood pressure in patients with shock. While both are effective at raising blood pressure, dopamine has more pronounced beta-adrenergic effects, which could increase heart rate and the risk of arrhythmias. Norepinephrine is a more potent alpha-adrenergic agonist.
  • Knowledge Gap: Despite widespread use of both agents, there was no large-scale, head-to-head randomized trial to determine which vasopressor was superior in terms of survival and safety for the undifferentiated patient in shock.
  • Proposed Hypothesis: The authors hypothesized that there would be no significant difference in 28-day mortality between dopamine and norepinephrine for the treatment of shock.

5. Study Design and Methods

  • Design: A prospective, multicenter, randomized, double-blind trial.
  • Setting: Eight intensive care units (ICUs) in Belgium, Austria, and Spain.
  • Trial Period: Enrollment from December 2003 to October 2007.
  • Population:
    • Inclusion Criteria: Adult patients (≥18 years) with shock, defined as hypotension (systolic BP <100 mmHg or MAP <70 mmHg) with signs of tissue hypoperfusion, despite adequate fluid resuscitation.
    • Exclusion Criteria: Patients with severe bradycardia, those already on high-dose vasopressors, or those for whom a specific vasopressor was deemed essential.
  • Intervention: Dopamine infusion, titrated from 5 up to a maximum of 50 µg/kg/min to achieve a target MAP of ≥70 mmHg.
  • Control: Norepinephrine infusion, titrated from 0.02 up to a maximum of 0.19 µg/kg/min to achieve a target MAP of ≥70 mmHg.
  • Management Common to Both Groups: If the maximum dose of the study drug was insufficient, open-label norepinephrine was added. All other aspects of care were at the discretion of the treating physicians.
  • Power and Sample Size: The trial was powered to detect a 10% absolute difference in 28-day mortality, requiring 1600 patients.
  • Outcomes:
    • Primary Outcome: All-cause mortality at 28 days.
    • Secondary Outcomes: 6- and 12-month mortality, ICU and hospital length of stay, organ-failure-free days, and incidence of adverse events (especially arrhythmias).

6. Key Results

  • Enrollment and Baseline: 1679 patients were randomized (858 to dopamine, 821 to norepinephrine). The groups were well-matched. The most common type of shock was septic shock (~62%), followed by cardiogenic (~16%) and hypovolemic (~16%).
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: There was no significant difference in 28-day mortality between the dopamine and norepinephrine groups (52.5% vs 48.5%; P=0.10).
  • Secondary Outcomes: There were no significant differences in 6- or 12-month mortality, length of stay, or organ-failure-free days. However, significantly more arrhythmic events occurred in the dopamine group (24.1% vs 12.4%; P<0.001).
  • Adverse Events: Dopamine was associated with a much higher rate of arrhythmias, particularly atrial fibrillation.

7. Medical Statistics

  • Analysis Principle: An intention-to-treat analysis was performed.
  • Statistical Tests Used: The primary outcome was analyzed using a chi-square test.
  • Primary Outcome Analysis: The proportion of deaths at day 28 was compared between the two groups.
  • Key Statistic(s) Reported: Odds Ratio (OR) for death at 28 days with dopamine: 1.17 (95% CI, 0.97 to 1.42; P=0.10).
  • Interpretation of Key Statistic(s):
    • Odds Ratio (OR): An OR of 1.17 suggests a 17% higher odds of death with dopamine, but this result did not reach statistical significance.
    • Confidence Interval (CI): The 95% CI crosses 1.0, confirming the lack of a statistically significant difference in the overall population.
    • P-value: The p-value of 0.10 is above the 0.05 threshold.
  • Clinical Impact Measures: Not applicable for the primary outcome as no significant difference was shown.
  • Subgroup Analyses: In the pre-specified subgroup of patients with cardiogenic shock (n=280), dopamine use was associated with a significantly higher rate of death at 28 days compared to norepinephrine (OR 2.52; 95% CI, 1.17 to 5.43; P=0.03).

8. Strengths of the Study

  • Study Design and Conduct: This was the first large, multicenter, randomized, double-blind trial to provide a head-to-head comparison of the two most common vasopressors.
  • Generalizability: The inclusion of a broad, undifferentiated population of patients with various types of shock increases the external validity of the findings.
  • Important Subgroup Analysis: The pre-specified analysis of different shock subtypes was a key strength and revealed a critical safety signal.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was stopped for logistical reasons before reaching the planned sample size, which may have slightly underpowered it. A large number of patients received open-label norepinephrine in both groups.
  • External Validity (Generalizability): The maximum dose of norepinephrine allowed in the protocol (0.19 µg/kg/min) is lower than what is often used in contemporary practice.
  • Other: The primary outcome was neutral, with the key findings emerging from a subgroup analysis and secondary safety outcomes.

10. Conclusion of the Authors

“There was no significant difference in the rate of death at 28 days between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine. However, the use of dopamine was associated with a greater number of adverse events, including arrhythmias, and an increased risk of death in the subgroup of patients with cardiogenic shock.”

11. To Summarize

  • Impact on Current Practice: This was a landmark, practice-changing trial. Despite a neutral primary outcome, the clear signal of harm (increased arrhythmias overall and increased mortality in cardiogenic shock) led to a definitive shift in international guidelines. Norepinephrine was established as the first-choice vasopressor for most forms of shock, particularly septic shock, effectively ending the routine use of dopamine as a first-line agent.
  • Specific Recommendations:
    • Patient Selection: For the broad population of adult patients with shock requiring vasopressor support.
    • Actionable Intervention: Use norepinephrine as the first-line vasopressor agent.
    • Expected Benefit: No difference in mortality for the overall population, but a significantly lower risk of arrhythmias compared to dopamine. Avoidance of increased mortality in patients with cardiogenic shock.
  • What This Trial Does NOT Mean: This trial does not mean dopamine has no role in critical care. It may still be considered in highly selected patients with bradycardia and a low risk of tachyarrhythmias.
  • Implementation Caveats: Norepinephrine should be the readily available, first-choice vasopressor for undifferentiated shock.

12. Context and Related Studies

  • Building on Previous Evidence: This trial was designed to resolve decades of clinical equipoise and debate based on physiologic principles and smaller, non-definitive studies.
  • Influence on Subsequent Research: The SOAP II trial largely settled the “dopamine vs. norepinephrine” debate. Subsequent research in vasopressor therapy has focused on the role of second-line agents (like vasopressin, studied in the VASST trial) and on personalizing hemodynamic targets (studied in the SEPSISPAM trial).

13. Unresolved Questions & Future Directions

  • Unresolved Questions: Is there any specific subgroup of patients (beyond those with bradycardia) who might benefit from dopamine?
  • Future Directions: Research has moved on from this comparison to focus on other aspects of hemodynamic management in shock, such as the timing of vasopressor initiation and the use of other vasoactive agents.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The question was of fundamental importance, comparing two of the most commonly used drugs in critical care.
  • Methods: The randomized, double-blind, multicenter design was methodologically strong. The inclusion of a diverse shock population was a pragmatic approach.
  • Results: This is a classic example of a “negative” trial with practice-changing implications. While the primary outcome of mortality was not significantly different, the secondary outcome of arrhythmias and the subgroup finding of harm in cardiogenic shock were so compelling that they effectively answered the clinical question.
  • Conclusions and Applicability: The authors’ conclusion is a precise summary of the findings. The results are highly applicable and have been incorporated into practice guidelines worldwide, establishing norepinephrine as the standard of care and relegating dopamine to a second- or third-line agent in most situations.

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.

Scroll to Top