Critical Closing Pressure and PCO₂ Gap in Fluid Resuscitation for Septic Shock

This study is based on the following key hypotheses: PvaCO₂ (Venous-to-Arterial CO₂ Gap) Hypothesis: Changes in PvaCO₂ (ΔPvaCO₂) following fluid resuscitation correlate with changes in cardiac output (CO) and can serve as a reliable predictor of fluid responsiveness in septic shock patients. The relationship between PvaCO₂ and CO is influenced by metabolic factors (VCO₂), hemodynamic status, and the Haldane effect (oxygenation-dependent CO₂ binding to hemoglobin). Pcrit (Critical Closing Pressure) \& TPP (Tissue Perfusion Pressure) Hypothesis: Elevated Pcrit and reduced TPP (TPP = MAP - Pcrit) are associated with impaired microcirculatory flow and worse clinical outcomes (e.g., 28-day mortality, organ dysfunction). Restoring the "vascular waterfall" phenomenon (Pcrit \> mean systemic filling pressure) may improve macrocirculation-microcirculation coupling and tissue oxygenation. 2\. Study Design Overview 2.1 Study Type Prospective observational cohort with a retrospective validation arm using external databases (e.g., MIMIC-IV). Single-center study (Peking Union Medical College Hospital ICU). 2.2 Study Population Inclusion Criteria Adults (18-80 years) with septic shock (Sepsis-3 criteria + vasopressor-dependent hypotension + lactate \>2 mmol/L). Requires invasive hemodynamic monitoring (arterial line, central venous catheter). Undergoing fluid challenge (clinically indicated). Exclusion Criteria Pregnancy, non-septic shock (e.g., cardiogenic), mechanical circulatory support (ECMO/IABP). Severe COPD, intracardiac shunts, or conditions interfering with CO₂/VO₂ measurements. 2.3 Interventions \& Measurements Fluid Resuscitation Protocol 500 mL 4% gelatin infused over 15 min (pressure bag at 300 mmHg). Hemodynamic/metabolic data collected pre- and post-fluid challenge (within 10 min). Key Data Collected Hemodynamics: MAP, CVP, CO (PiCCO/ultrasound), Pcrit (derived from MAP-CO curve fitting). TPP = MAP - Pcrit. Metabolic Parameters: PvaCO₂, CvaCO₂, VCO₂, VO₂ (Es-COVX module). Lactate, ScvO₂, Hb, arterial/venous blood gases. Outcomes: Primary: 28-day mortality. Secondary: Lactate clearance, AKI incidence, ICU length of stay, vasopressor requirements.

NCT Number	NCT07043192
Lead Sponsor	Peking Union Medical College
Conditions	Septic Shock, Fluid Resuscitation, Tissue Perfusion Pressure, Carbon Dioxide Pressure
Enrollment	60 participants
Start Date	2025-04-18
Primary Completion	2026-02-01 (estimated)
Study Completion	2026-02-01 (estimated)
Updated on ClinicalTrials.gov	2025-07-03