The Role of Venous-to-Arterial PCO₂ Gap and Critical Closing Pressure in Fluid Resuscitation Evaluation and Hemodynamic Evaluation in Patients With Sepsis Shock
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Cardiac output
研究概览
简要总结
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.
- 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.
详细描述
- Study Background Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with septic shock being a subset of sepsis. Septic shock is defined as persistent hypotension requiring vasopressors to maintain a mean arterial pressure (MAP) ≥65 mmHg and serum lactate >2 mmol/L despite adequate fluid resuscitation. The mortality rate associated with sepsis ranges from 13.1% to 35.5%, and its increasing incidence has led to significant healthcare resource utilization and economic burden. Early recognition and timely treatment are critical for patients with sepsis and septic shock.
Hemodynamics play a central role in sepsis resuscitation. The core issue in shock is inadequate cellular oxygen utilization, making the goal of shock therapy to increase oxygen delivery to meet demand and address systemic hypoperfusion. Carbon dioxide (CO₂), as a byproduct of cellular oxygen metabolism, has garnered attention.
The venous-to-arterial CO₂ gap (PvaCO₂) and critical closing pressure (Pcrit) are emerging as potential markers for evaluating fluid responsiveness and tissue perfusion. However, their clinical utility remains controversial due to conflicting results and the influence of factors such as hemoglobin, pH, and the Haldane effect. This study aims to explore the dynamic changes in PvaCO₂ and CvaCO₂ during fluid resuscitation and investigate the role of Pcrit and tissue perfusion pressure (TPP) in risk stratification and blood pressure management for septic shock patients. 2. Study Objectives To evaluate the predictive value of ΔPvaCO₂ (change in PvaCO₂) for fluid responsiveness in septic shock patients.
To assess the contributions of VCO₂, the Haldane effect, and cardiac output (CO) to changes in PvaCO₂ and CvaCO₂ during fluid resuscitation.
To investigate the role of Pcrit and TPP in risk stratification and their potential as additional targets for blood pressure management in sepsis. 3. Methods and Procedures Study Design: Prospective observational study in ICU patients with septic shock.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •Pregnancy or lactation.
- •Other types of shock (e.g., cardiogenic, obstructive).
- •Mechanical circulatory support (e.g., ECMO, IABP).
- •Severe respiratory or cardiovascular contraindications.
结局指标
主要结局
Cardiac output
时间窗: From enrollment to the end of treatment at 2 days
Change in cardiac output (CO) after fluid resuscitation
次要结局
- Lactate clearance(From enrollment to the end of treatment at 1 weeks)
研究者
Shitong Diao
Principal Investigator
Peking Union Medical College