Critical Closing and Tissue Perfusion Pressures in Sepsis—Implications for Risk Stratification: A Retrospective Cohort Study

Background: Optimal target of mean arterial pressure (MAP) remains controversial in sepsis management. Critical closing pressure (Pcc), the arterial pressure at which blood flow ceases, is the key determinant of vascular waterfall phenomenon. Tissue perfusion pressure (TPP), the difference between MAP and Pcc, represents the driving pressure for arterial blood flow. We evaluated the prognostic value of Pcc and TPP for improving risk stratification in sepsis. Methods: This retrospective cohort study included adult patients with sepsis in 18 hospitals between August 2013 to October 2022 from two independent datasets (the SEPSIS-EDT registry and the critical care database of PUMCH). Pcc was estimated via linear regression of hourly MAP against product of heart rate and pulse pressure, while TPP was calculated as MAP minus Pcc. Patients were categorized into four groups based on the optimal thresholds for mean Pcc and TPP within 24 hours of sepsis diagnosis: Low TPP-Low Pcc, Low TPP-High Pcc, High TPP-Low Pcc, and High TPP-High Pcc. Clinical outcomes included mortality rates and development of acute kidney injury (AKI) within two and seven days of sepsis diagnosis. External validation was performed using MIMIC-IV cohort. Results: A total of 6,769 patients (mean age 61; 61.0% men) were included. ICU mortality was highest in the Low TPP–Low Pcc group and lowest in the High TPP–High Pcc group (35.1% vs. 20.1%; risk difference: 15.0%, 95% confidence interval: 10.2–19.8%). Similar patterns were observed for other outcomes. After adjustment for MAP, increased Pcc with concomitant reduced TPP showed a significant U-shaped association with both mortality and AKI development ( P < 0.001). The findings were consistent in the MIMIC-IV cohort. Conclusion: While MAP remains central to sepsis management, Pcc and TPP provide complementary prognostic information. Incorporating these parameters into clinical assessment may improve risk stratification and optimize blood pressure management.