OPTIMISE: Cardiac Output-Guided Hemodynamic Therapy in High-Risk Surgery (2014)

“Among high-risk patients undergoing major gastrointestinal surgery, a cardiac output–guided hemodynamic therapy algorithm, compared with usual care, did not significantly reduce a composite of complications and 30-day mortality.”

  • The OPTIMISE Study Group

1. Publication Details

  • Trial Title: Effect of a Perioperative, Cardiac Output–Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery: A Randomized Clinical Trial and Systematic Review
  • Citation: Pearse RM, Harrison DA, MacDonald N, et al. Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review. JAMA. 2014;311(21):2181-2190. DOI: 10.1001/jama.2014.5305
  • Published: June 4, 2014, in The Journal of the American Medical Association (JAMA)
  • Author: Rupert M. Pearse, M.D.
  • Funding: UK National Institute for Health Research.

2. Keywords

  • Perioperative Care, High-Risk Surgery, Goal-Directed Therapy, Hemodynamic Optimization, Cardiac Output, Dopexamine, Randomized Controlled Trial

3. The Clinical Question

  • In adult patients undergoing major high-risk gastrointestinal surgery (Population), does a perioperative, cardiac output-guided hemodynamic therapy algorithm using an inotrope (Intervention) compared to usual care (Comparison) reduce a composite of 30-day moderate or major complications and mortality (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Postoperative complications are common after major surgery and are associated with increased mortality. Goal-directed therapy (GDT), a strategy of using advanced hemodynamic monitoring to guide fluids and inotropes to achieve specific physiological targets (like optimizing cardiac output), was hypothesized to improve organ perfusion and reduce complications.
  • Knowledge Gap: While numerous small, single-center trials had suggested a benefit for perioperative GDT, the evidence was inconsistent, and the practice was not widely adopted. A large, multicenter trial was needed to provide a more definitive answer on the efficacy of this complex intervention.
  • Proposed Hypothesis: The authors hypothesized that a cardiac output-guided hemodynamic therapy algorithm would be superior to usual care in reducing the risk of postoperative complications and death.

5. Study Design and Methods

  • Design: A multicenter, pragmatic, randomized, controlled trial (used to test the effectiveness of interventions).
  • Setting: 17 National Health Service (NHS) hospitals in the United Kingdom.
  • Trial Period: Enrollment ran from September 2010 to March 2013.
  • Population:
    • Inclusion Criteria: Adult patients (≥50 years) undergoing major gastrointestinal surgery who were considered high-risk based on pre-defined criteria.
    • Exclusion Criteria: Included patient or clinician refusal and emergency surgery precluding consent.
  • Intervention: A cardiac output-guided therapy algorithm. Patients received 10-minute fluid challenges (250 ml colloid) to maximize stroke volume, followed by an infusion of a low-dose inotrope (dopexamine at 0.5 µg/kg/min) for 6 hours postoperatively.
  • Control: Usual care. All hemodynamic management decisions were at the discretion of the treating clinicians.
  • Management Common to Both Groups: All patients received standard anesthetic and surgical care.
  • Power and Sample Size: The authors calculated that a sample size of 734 patients would provide 80% power to detect an 8% absolute risk 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: A composite of moderate or major complications and all-cause mortality within 30 days of surgery.
    • Secondary Outcomes: Included the individual components of the primary outcome, length of hospital stay, and incidence of infection.

6. Key Results

  • Enrollment and Baseline: 734 patients were randomized (368 to the intervention group and 366 to usual care). 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 composite outcome. The primary outcome occurred in 134 of 368 patients (36.6%) in the intervention group and in 154 of 366 patients (42.5%) in the usual care group (p=0.13).
  • Secondary Outcomes: There were no significant differences between the groups in 30-day mortality or length of hospital stay. However, the incidence of postoperative infection was significantly lower in the intervention group (23% vs. 31%).
  • Adverse Events: The incidence of serious adverse events was similar in both groups.

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 chi-square test.
  • Primary Outcome Analysis: The primary outcome was a comparison of the proportions of patients who met the composite endpoint between the two groups.
  • Key Statistic(s) Reported: Relative Risk (RR) for the primary outcome: 0.87 (95% CI, 0.72 to 1.05; P-value: 0.13).
  • Interpretation of Key Statistic(s):
    • Relative Risk (RR):
      • Formula: Conceptually, RR = (Risk in Intervention Group) / (Risk in Control Group).
      • Calculation: The paper reports the result as 0.87.
      • Clinical Meaning: An RR of 0.87 suggests a non-significant 13% lower relative risk of the primary outcome in the intervention group.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The 95% CI was 0.72 to 1.05.
      • Clinical Meaning: Since this range crosses the line of no effect (1.0), it confirms that the result is not statistically significant. The true effect could range from a 28% benefit to a 5% harm.
    • P-value: The p-value of 0.13 is higher than the 0.05 threshold, indicating the result is not statistically significant (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures: As the primary outcome was not met, 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, controlled design provided high-quality evidence.
  • Generalizability: The pragmatic design and inclusion of 17 diverse hospitals make the findings highly generalizable to real-world practice in similar healthcare systems.
  • Statistical Power: The study was adequately powered for its primary outcome.
  • Patient-Centered Outcomes: The primary outcome was a composite of important patient-centered outcomes.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was unblinded, which introduces a risk of performance bias.
  • External Validity (Generalizability): The “usual care” in the control group was of a very high standard, which may have made it more difficult for the intervention to show a superior benefit.
  • Other: The trial was technically “negative” for its primary outcome. The positive finding for the secondary outcome of infection should be interpreted with caution.

10. Conclusion of the Authors

  • The authors concluded that a perioperative, cardiac output–guided hemodynamic therapy algorithm did not significantly reduce the composite of 30-day moderate or major complications and mortality.

11. To Summarize

  • Impact on Current Practice: This was an important “negative” trial that failed to confirm the benefits of GDT seen in many previous, smaller studies. It has contributed to the ongoing debate about the true value of this complex and resource-intensive intervention.
  • Specific Recommendations:
    • Patient Selection: For high-risk adult patients undergoing major gastrointestinal surgery.
    • Actionable Intervention: The results do not support the routine implementation of this specific cardiac output-guided therapy algorithm.
  • What This Trial Does NOT Mean: This trial does NOT mean that hemodynamic optimization is not important. It only suggests that this specific, protocolized approach was not superior to high-quality usual care.
  • Implementation Caveats: The key takeaway is that in a system with already good outcomes, the incremental benefit of a complex GDT protocol may be small or non-existent.

12. Context and Related Studies

  • Building on Previous Evidence: The OPTIMISE trial (2014) was designed to be a larger, more definitive trial to confirm or refute the positive findings of numerous smaller, single-center studies on perioperative goal-directed therapy.
  • Influence on Subsequent Research: The neutral finding of this trial, along with other large negative trials like ARISE/ProCESS/ProMISe in sepsis, has led to a general shift in critical care research away from “one-size-fits-all” physiological protocols and towards more individualized approaches to hemodynamic management.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The key unresolved question is whether there are specific subgroups of high-risk surgical patients who might still benefit from a more intensive, goal-directed hemodynamic strategy.
  • Future Directions: Future research is focused on using more advanced and less invasive hemodynamic monitoring to guide a more personalized approach to perioperative fluid and vasopressor therapy.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a common and important clinical problem with a promising but unproven intervention.
  • Methods: The multicenter RCT design was appropriate and robust. The main methodological weakness is the open-label design. A key strength is that the control arm represented a very high standard of modern perioperative care, making the comparison a fair and relevant test.
  • Results: The study reported a clear neutral finding for its primary outcome, with a confidence interval that crossed the null value. The positive finding for the secondary outcome of infection is hypothesis-generating but should be interpreted with caution.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The high external validity of this pragmatic trial means its findings are broadly applicable. This is a classic example of a high-quality “negative” trial that challenges the findings of previous smaller studies and forces a re-evaluation of a complex intervention.

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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