OPTPRESS: High vs. Standard MAP in Older Patients with Septic Shock (2025)

“Among older patients with septic shock, high-target MAP significantly increased mortality compared with standard care.” — The OPTPRESS trial investigators

1. Publication Details

  • Trial Title: Efficacy of targeting high mean arterial pressure for older patients with septic shock (OPTPRESS): a multicentre, pragmatic, open-label, randomised controlled trial
  • Citation: Endo A, Yamakawa K, Tagami T, et al. Efficacy of targeting high mean arterial pressure for older patients with septic shock (OPTPRESS): a multicentre, pragmatic, open-label, randomised controlled trial. Intensive Care Med (2025) 51:883-892.
  • Published: May 13, 2025, in Intensive Care Medicine
  • Author: Akira Endo, MD
  • Funding: Japan Society for the Promotion of Science KAKENHI

2. Keywords

  • Septic Shock, Geriatrics, Mean Arterial Pressure (MAP), Vasopressors, Critical Care, Japan

3. The Clinical Question

  • In patients aged 65 years or older with septic shock (Population), does targeting a high mean arterial pressure of 80–85 mmHg (Intervention) compared to a standard mean arterial pressure of 65–70 mmHg (Comparison) reduce 90-day all-cause mortality (Outcome)?

4. Background and Rationale

  • Existing Knowledge: The optimal blood pressure target in septic shock is debatable. While a target MAP of >65 mmHg is common, some evidence suggests older patients with chronic hypertension might benefit from higher targets to maintain organ perfusion. However, other studies have suggested lower targets may be preferable in older populations.
  • Knowledge Gap: The effect of a high-target MAP had not been specifically studied in a very elderly population (≥65 years) in a region like Japan, where the prevalence of chronic hypertension is high. It was also unclear if a protocol using early vasopressin to spare catecholamines would alter the risk-benefit balance of a high MAP strategy.
  • Proposed Hypothesis: The investigators aimed to evaluate the effects of a high-target MAP strategy in older patients with septic shock.

5. Study Design and Methods

  • Design: Multicentre, pragmatic, open-label, randomised controlled trial.
  • Setting: 29 hospitals in Japan.
  • Trial Period: July 1, 2021, to December 12, 2023.
  • Population:
    • Inclusion Criteria: Patients aged ≥65 years clinically diagnosed with septic shock (Sepsis-3 criteria) and admitted to an ICU.
    • Exclusion Criteria: Patients on vasopressors for ≥3 hours prior to screening, uncontrolled bleeding, or other conditions requiring stricter blood pressure control.
  • Intervention: High-target group: Norepinephrine (with early concomitant vasopressin if norepinephrine dose ≥0.1 µg/kg/min) titrated to maintain a MAP of 80–85 mmHg.
  • Control: Control group: Norepinephrine (with early vasopressin as above) titrated to maintain a MAP of 65–70 mmHg.
  • Management Common to Both Groups: The assigned MAP target was maintained for 72 hours or until vasopressors were no longer needed.
  • Outcomes:
    • Primary Outcome: All-cause mortality at 90 days.
    • Secondary Outcomes: 28-day mortality, organ support-free days at 28 days, and safety endpoints (e.g., arrhythmia, ischemic events).

6. Key Results

  • Enrollment and Baseline: 518 patients were randomized, with 516 included in the final analysis (257 in the high-target group, 259 in the control group). The median age was 78 years, and over 50% had a history of chronic hypertension.
  • Trial Status: The trial was terminated early by the Safety Monitoring Committee after a planned interim analysis suggested harm in the high-target group.
  • Primary Outcome: 90-day mortality was significantly higher in the high-target group. Death occurred in 101 of 257 patients (39.3%) in the high-target group versus 74 of 259 patients (28.6%) in the control group (Risk Difference = 10.7%; 95% CI, 2.6 to 18.9).
  • Secondary Outcomes: The high-target group had significantly fewer renal replacement therapy-free days, ventilator-free days, and catecholamine-free days at 28 days.
  • Adverse Events: All major safety outcomes (arrhythmia, ischemic events, hemorrhagic events) occurred more frequently in the high-target group, although these differences were not individually statistically significant.

7. Medical Statistics

  • Analysis Principle: Intention-to-treat.
  • Statistical Tests Used: Fisher’s exact test for the primary outcome; logistic regression and survival analysis for secondary analyses.
  • Primary Outcome Analysis: Comparison of 90-day mortality rates.
  • Key Statistic(s) Reported: Risk Difference = 10.7% (95% CI, 2.6 to 18.9); P-value = 0.012; Hazard Ratio = 1.47 (95% CI, 1.08 to 2.01).
  • Interpretation of Key Statistic(s):
    • Hazard Ratio (HR):
      • Calculation: HR = 1.47
      • Clinical Meaning: The hazard of death at any given time within 90 days was 47% higher for patients in the high-target MAP group compared to the control group.
    • Confidence Interval (CI):
      • Calculation: 95% CI for HR, 1.08 to 2.01
      • Clinical Meaning: Since the 95% CI does not cross 1.0 and is entirely above it, the increased risk of death in the high-target group is statistically significant.
    • P-value:
      • Calculation: P=0.012 (for risk difference); P=0.007 (log-rank test for survival)
      • Clinical Meaning: The p-value is less than 0.05, indicating that the observed increase in mortality in the high-target group is highly unlikely to be due to chance.
  • Clinical Impact Measures:
    • Absolute Risk Reduction (ARR):
      • Calculation: ARR = 28.6% – 39.3% = -10.7% (an absolute risk increase).
      • Clinical Meaning: For every 100 older patients with septic shock treated with a high-MAP target, approximately 11 additional patients died.
    • Number Needed to Treat (NNT): The equivalent is the Number Needed to Harm (NNH).
      • Calculation: NNH = 1 / ARI = 1 / 0.107 ≈ 9.
      • Clinical Meaning: Approximately 9 older patients with septic shock would need to be treated with a high-MAP target for one additional patient to die.
  • Subgroup Analyses: No clinical benefit of the high-MAP strategy was observed in any subpopulation, including patients with known chronic hypertension.

8. Strengths of the Study

  • Study Design and Conduct: A well-conducted, multicenter, randomized controlled trial.
  • Clinical Relevance: Directly addresses an important clinical question in a specific, high-risk population (older adults) that is often underrepresented in trials.
  • Novel Protocol: The mandated early use of vasopressin to spare catecholamines was a novel aspect of the protocol.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The open-label design could have introduced bias, though the primary outcome of mortality is objective.
  • External Validity (Generalizability): The trial was conducted exclusively in Japan, so generalizability to other ethnic populations may be limited.
  • Other: The trial was stopped early for harm, which can sometimes overestimate the magnitude of the effect, but the direction of the finding is clear.

10. Conclusion of the Authors Among older patients with septic shock in Japan, management targeting a MAP of 80–85 mmHg did not reduce and instead significantly increased mortality compared with management targeting a MAP of 65–70 mmHg.

11. To Summarize

  • Impact on Current Practice: This trial provides strong evidence of harm for a routine strategy of targeting high blood pressure in older adults with septic shock.
  • Specific Recommendations:
    • Patient Selection: For patients aged 65 and older with septic shock, a high-MAP target should be avoided.
    • Actionable Intervention: A MAP target of 65-70 mmHg should be considered the standard of care for this population.
  • What This Trial Does NOT Mean: This trial does not preclude the possibility of individualized MAP targets for younger patients or for specific clinical scenarios guided by advanced hemodynamic monitoring.

12. Context and Related Studies

  • Building on Previous Evidence: This trial contradicts the hypothesis generated from a subgroup of the SEPSISPAM trial and provides a definitive answer against a high-MAP strategy in this specific elderly population, even when using a catecholamine-sparing protocol.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: Why this strategy was harmful remains a key question—whether it was due to excessive vasoconstriction, direct vasopressor toxicity, or other mechanisms.
  • Future Directions: Research should focus on personalized hemodynamic management that incorporates measures of organ perfusion beyond just blood pressure.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: A clear, focused, and highly relevant clinical question for a vulnerable population.
  • Methods: The randomized controlled trial design was appropriate and robust.
  • Results: The results are clear and show a statistically significant increase in harm with the intervention.
  • Conclusions and Applicability: The conclusion is strongly supported by the data. The findings are highly applicable to the management of septic shock in the growing population of older adults.

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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