OPTPRESS — High vs Standard MAP Targets in Older Septic Shock

1. Publication

• Title: Efficacy of targeting high mean arterial pressure for older patients with septic shock (OPTPRESS): a multicentre, pragmatic, open-label, randomised controlled trial
• Acronym: OPTPRESS
• Year & Journal: Intensive Care Medicine, published May 13, 2025 (2025;51(5):883-892)
• Citation: Endo A, Yamakawa K, Tagami T, et al; OPTPRESS trial investigators. 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(5):883-892. doi:10.1007/s00134-025-07910-4

2. Context & Rationale

Background: The SEPSISPAM trial (Asfar et al., 2014) found no overall mortality benefit from a high (80-85mmHg) vs low (65-70mmHg) MAP target in septic shock, but suggested possible benefit in patients with chronic hypertension. Whether this applies to older patients in a population with a very high prevalence of chronic hypertension (Japan, where 66.9% of older individuals have chronic hypertension) — a previously underrepresented region in this research question — remained untested.

Research Question/Hypothesis: In older adults (≥65y) with septic shock, does targeting a high MAP (80-85 mmHg) improve 90-day mortality compared with standard care (65-70 mmHg), including in patients with chronic hypertension?

Why This Matters: Directly tests whether the hypertension-subgroup signal from SEPSISPAM generalizes to a population with a much higher baseline prevalence of chronic hypertension, in a region previously underrepresented in this research area.

3. Design & Methods

• Study Type: Multicenter, pragmatic, open-label, randomized controlled trial
• Setting & Centers: 29 hospitals, Japan; enrolled 2020-2023 (UMIN000041775, registered September 2020)
• Population:
• Inclusion: Adults ≥65y, clinically diagnosed septic shock, admitted to ICU
• Exclusions: Not detailed in available trial text
• Intervention: High-target MAP (80-85 mmHg), maintained for up to 72 hours or until vasopressor support no longer needed
• Comparator: Standard-target MAP (65-70 mmHg), same duration/discontinuation criteria
• Randomization: 1:1, 518 patients (258 high-target, 260 control)
• Blinding: Open-label
• Statistical Power & Follow-Up: Primary outcome: 90-day all-cause mortality. Secondary: organ support-free days (including renal-replacement-therapy-free days at 28 days), adverse events. Trial terminated early based on interim analysis suggesting harm from the high-target strategy.

4. Key Results

Stopped early for harm. 518 patients randomized (258 high-target, 260 control).

5. Internal Validity Assessment

• Randomization & Allocation: 1:1 randomization across 29 Japanese hospitals; specific concealment mechanics not detailed in available trial text.
• Protocol Adherence & Separation: Clear MAP target separation (80-85 vs 65-70 mmHg) by protocol design.
• Blinding & Detection Bias: Open-label (inherent to a hemodynamic-target trial); the primary endpoint (90-day mortality) is objective, limiting detection bias despite lack of blinding.
• Missing Data & Sensitivity Analyses: Early termination for harm based on a formal interim analysis — an appropriately conducted stopping decision protecting patient safety, though it means the trial did not reach its originally planned sample size.
• Overall Internal Validity Conclusion: Strong — the harm signal is large (10.7 percentage-point absolute mortality increase), consistent across the primary outcome and a key secondary outcome (RRT-free days), and prompted appropriate early termination via a properly conducted interim analysis — a genuinely credible, high-confidence harm finding rather than a chance result or underpowered non-finding.

6. External Validity Assessment

• Population Representativeness: Older (≥65y) Japanese septic shock population with very high chronic-hypertension prevalence (66.9%) — explicitly designed to test the SEPSISPAM hypertension-subgroup hypothesis in the population where it should most plausibly apply.
• Practice Context: Standard ICU MAP-titration capability, broadly generalizable methodology.
• Overall External Validity Conclusion: Good — specifically fills an evidence gap for a previously underrepresented region and population (older adults with very high hypertension prevalence), with results that should generalize to similar older, hypertension-prevalent septic shock populations globally.

7. Strengths & Limitations

Strengths:

• Directly and rigorously tests the SEPSISPAM hypertension-subgroup hypothesis in the population where it should most plausibly hold
• Large, consistent harm signal across primary and key secondary outcomes
• Appropriately stopped early for safety via formal interim analysis
• Fills a genuine evidence gap for an underrepresented (Japanese, high-hypertension-prevalence) population

Limitations:

• Early termination means the trial did not reach its full planned sample size
• Open-label design
• Single-country (Japan) trial, though this is also a strength given the specific population question being tested

8. Interpretation & Practice Impact

• Clinical Implications: Targeting a high MAP (80-85mmHg) in older septic shock patients significantly increases mortality compared with standard targets (65-70mmHg) — including in patients with chronic hypertension, directly refuting the hypothesis that hypertensive patients specifically benefit from higher pressure targets.
• Mechanistic Coherence: An accompanying commentary ("Hemodynamic targets in the initial resuscitation of older patients with sepsis: time for a reappraisal?") explicitly states that correcting blood pressure with the sole aim of achieving higher MAP targets, even among previously hypertensive patients, is likely harmful and should be avoided in clinical practice.
• Systems-Level Takeaway: Reinforces standard (65-70mmHg) MAP targets as the appropriate default even in older, hypertension-prevalent septic shock populations; future research should focus on perfusion-guided (rather than blood-pressure-number-guided) vasopressor strategies integrating macro- and microcirculatory assessment.

9. Controversies & Subsequent Evidence

• Editorial Commentary: An accompanying Intensive Care Medicine commentary explicitly reframes the clinical message: "Correcting it with the sole aim of achieving higher MAP targets, even among previously hypertensive patients, is likely harmful and should be avoided in clinical practice. Whether vasopressor test strategies targeting perfusion are beneficial should be the focus of future research."
• Guideline Integration: This directly contradicts the subgroup hypothesis generated by SEPSISPAM (Asfar et al., NEJM 2014), providing a rigorous, prospective, region-specific refutation — an important correction to prior subgroup-driven clinical practice patterns, particularly relevant globally given aging populations and high hypertension prevalence.

10. Summary & Executive Takeaway

Summary: OPTPRESS, stopped early for harm, randomized 518 older (≥65y) Japanese septic shock patients to high-target (80-85mmHg) or standard-target (65-70mmHg) MAP. 90-day mortality was significantly higher with the high-target strategy (39.3% vs 28.6%; risk difference 10.7 percentage points, 95% CI 2.6-18.9), with no benefit in any subpopulation including those with chronic hypertension.

Overall Takeaway: Targeting a high MAP in older septic shock patients causes harm, definitively refuting the hypothesis (from SEPSISPAM subgroup analysis) that chronically hypertensive patients specifically benefit from higher blood pressure targets — standard MAP targets (65-70mmHg) should remain the default even in older, hypertension-prevalent populations, with future research focused on perfusion-based rather than blood-pressure-number-based resuscitation strategies.

11. Bibliography

• Asfar P, Meziani F, Hamel JF, et al; SEPSISPAM Investigators. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370(17):1583-1593.
• Lamontagne F, Richards-Belle A, Thomas K, et al. Effect of reduced exposure to vasopressors on 90-day mortality in older critically ill patients with vasodilatory hypotension (65 trial). JAMA. 2020;323(10):938-949.
• Hemodynamic targets in the initial resuscitation of older patients with sepsis: time for a reappraisal? [commentary]. Intensive Care Med. 2025.