Abstract:
Endo et al. conducted the OPTPRESS trial, a multicenter randomized controlled trial in Japan, evaluating whether a higher mean arterial pressure (MAP) target (80–85 mmHg) reduces mortality in older patients (≥65 years) with septic shock compared to standard targets (65–70 mmHg). The trial was terminated early due to increased mortality and adverse events in the high-target MAP group, highlighting significant risks associated with higher MAP strategies.
Key Insights:
- Study Design and Participants: This pragmatic, multicenter, open-label trial involved 518 older Japanese patients (≥65 years old) admitted with septic shock, randomized to high-target MAP (80–85 mmHg) or control (65–70 mmHg) groups.
- Primary Outcome (90-Day Mortality): The high-target MAP group showed significantly higher 90-day mortality (39.3%) compared to the control group (28.6%), indicating a risk difference of 10.7%.
- Secondary Outcomes: Patients in the high-target MAP group experienced significantly fewer renal replacement therapy-free days and higher mortality rates from sepsis at both 28 and 90 days, reinforcing the negative impact of targeting higher MAPs.
- Adverse Events: Higher MAP targets correlated with increased adverse events, including arrhythmias, ischemic events, thromboembolism, and hemorrhagic complications requiring transfusion.
- Protocol and Intervention: To minimize catecholamine-related adverse effects, a unique protocol involving early vasopressin use alongside norepinephrine was employed; however, this strategy did not mitigate the increased risks observed.
- Influence of Chronic Hypertension: Despite a high prevalence (66.9%) of chronic hypertension among participants, subgroup analyses revealed no clinical benefit in hypertensive patients from the higher MAP target strategy.
- Physiological Considerations: The increased mortality and adverse outcomes in the high-MAP group may reflect harmful effects due to excessive vasopressor use, including vasoconstriction-mediated organ ischemia and immunosuppressive effects associated with high-dose norepinephrine.
- Generalizability and Relevance: Although previous Western trials suggested limited benefits from higher MAP targets, this Japanese trial provided crucial evidence from a population previously underrepresented, enhancing the global applicability of findings.
- Clinical Implications: The trial strongly advises caution against excessive vasopressor use to achieve higher MAP targets in older septic shock patients, recommending adherence to standard lower MAP targets unless future evidence suggests otherwise.
- Limitations: Potential biases included the open-label design, variable adherence to MAP targets, fixed-block randomization possibly affecting allocation concealment, and challenges in accurate baseline assessment of chronic hypertension in emergency settings.
Conclusion:
Targeting a higher MAP of 80–85 mmHg significantly increased mortality and adverse events among older septic shock patients compared to standard management strategies, emphasizing the importance of caution in vasopressor dosing and maintaining standard MAP targets.
Watch the following video on “MAP targets in the critically ill (sepsis, ICP, IAH)” by Critical Care Summit
Discussion Questions:
- Should current guidelines explicitly recommend against higher MAP targets in all older septic shock patients, or are there specific contexts in which they may be beneficial?
- How can clinicians balance individualized hemodynamic management strategies with standardized protocol-driven care in emergency septic shock scenarios?
- What further research is needed to clarify the mechanisms underlying the increased mortality associated with higher MAP targets?
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