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

NCT07043192 | Active Not Recruiting

• 1 other identifier: K8248
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Septic Shock; Fluid Resuscitation; Tissue Perfusion Pressure; Carbon Dioxide Pressure

Keywords

septic shock; fluid resuscitation; tissue perfusion pressure; carbon dioxide pressure

Outcome Measures

Primary Outcomes (1)

• Cardiac output

  Change in cardiac output (CO) after fluid resuscitation

  From enrollment to the end of treatment at 2 days

Secondary Outcomes (1)

• Lactate clearance

  From enrollment to the end of treatment at 1 weeks

Study Arms (2)

fluid responsiveness positive

The determination of an increase of ≥10% in cardiac output before and after expansion.

fluid responsiveness negetive

The determination of an increase of \<10% in cardiac output before and after expansion.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Septic shock patients

You may qualify if:

• Age 18-80 years.
• Diagnosis of septic shock per Sepsis-3 criteria.
• Requirement for invasive hemodynamic monitoring (arterial and central venous catheters).
• Clinical indication for fluid challenge (e.g., hypotension, signs of hypoperfusion).

You may not qualify if:

• Pregnancy or lactation.
• Other types of shock (e.g., cardiogenic, obstructive).
• Mechanical circulatory support (e.g., ECMO, IABP).
• Severe respiratory or cardiovascular contraindications.

Sponsors & Collaborators

• Peking Union Medical College: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, China

Location

MeSH Terms

Conditions

Shock, Septic

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 20, 2025
• First Posted: June 29, 2025
• Study Start: April 18, 2025
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: July 3, 2025

Record last verified: 2025-06

Locations

CN (1)