Hemodynamic Effects of Norepinephrine Reduction on Critical Closing Pressure in Distributive Shock

Changes in Critical Closing Pressure and Derived Hemodynamic Parameters Following Norepinephrine Dose Reduction in Distributive Shock Patients: a Prospective Observational Study

This study prospectively observes changes in critical closing pressure (Pcc) and derived hemodynamic parameters in mechanically ventilated distributive shock patients when clinically indicated norepinephrine dose reduction is performed by the attending physician. Pcc is measured before and 30 minutes after dose reduction using a stepwise inspiratory hold maneuver via PiCCO monitoring.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Distributive Shock; Hemodynamic Assessment
• Intervention / Treatment: Other: Not applicable- observational study

Detailed Description

In distributive shock patients receiving norepinephrine with MAP maintained in the 75-85 mmHg range, attending physicians may reduce norepinephrine dose based on clinical judgment. This study observes hemodynamic changes associated with such reductions without any investigator-initiated intervention. Critical closing pressure (Pcc) and derived parameters including tissue perfusion pressure (TPP), mean systemic filling pressure analogue (Pmsf), and vascular waterfall (VW) are measured at baseline and 30 minutes after dose reduction, provided MAP variability is less than 5 mmHg. Pcc is derived from linear regression of simultaneously measured cardiac output (CO) and mean arterial pressure (MAP) during stepwise inspiratory hold maneuvers. Steady-state CO and MAP values are recorded during the final 3 seconds of 12-second inspiratory holds at plateau pressures of 5, 15, 25, and 35 cmH2O. The x-intercept of the CO-MAP regression line is taken as Pcc.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Bin Du, Dr; Phone Number: 86+15136289398; Email: sunyaliii@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Bin Du; Phone Number: 86-15136289398; Email: sunyaliii@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult distributive shock patients receiving invasive mechanical ventilation and norepinephrine treatment

Description

Inclusion Criteria:

1. Adult distributive shock patients aged ≥18 years;
2. Receiving norepinephrine infusion with MAP in the 75-85 mmHg range;
3. PiCCO catheter in situ;
4. Under mechanical ventilation;
5. Clinically indicated norepinephrine dose reduction per attending physician judgment.

Exclusion Criteria:

1. Significant cardiac arrhythmia affecting CO measurement reliability;
2. Contraindication to airway plateau pressure maneuver;
3. Active titration of other vasoactive agents within 30 minutes prior to measurement;
4. Hemodynamic instability making it impossible to reduce norepinephrine dose.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Distributive shock patients undergoing norepinephrine dose reduction; Mechanically ventilated distributive shock patients in whom the attending physician clinically indicated norepinephrine dose reduction, with MAP transitioning from the 75-85 mmHg range to the 65-75 mmHg range.	Other: Not applicable- observational study; Observation of hemodynamic parameters before and after clinically indicated norepinephrine dose reduction. No investigator-initiated intervention was performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in critical closing pressure (Pcc, Unit: mmHg) before and after norepinephrine dose reduction	Pcc is derived from linear regression of simultaneously measured cardiac output against mean arterial pressure during stepwise inspiratory hold maneuvers via PiCCO monitoring. The x-intercept of the regression line (at zero flow) represents Pcc. Measurement is performed at baseline and 30 minutes after norepinephrine dose reduction.	Baseline and 30 minutes after norepinephrine dose reduction
Change in tissue perfusion pressure (TPP, unit: mmHg) before and after norepinephrine dose reduction	TPP is calculated as the difference between mean arterial pressure (MAP) and critical closing pressure (Pcc): TPP = MAP minus Pcc, unit: mmHg	Baseline and 30 minutes after norepinephrine dose reduction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean systemic filling pressure analogue (Pmsf, unit: mmHg) before and after norepinephrine dose reduction	Pmsf is estimated as the x-intercept of the linear regression of cardiac output against central venous pressure (CVP), representing the venous pressure at zero flow.	Baseline and 30 minutes after norepinephrine dose reduction
Change in Vascular waterfall (VW, unit: mmHg) before and after norepinephrine dose reduction	Vascular waterfall (VW) is calculated as Pcc minus Pmsf.	Baseline and 30 minutes after norepinephrine dose reduction
Change in capillary refill time (CRT, unit: seconds）	Capillary refill time is assessed by applying pressure to the fingertip for 5 seconds and measuring the time for color to return after release.	Baseline and 30 minutes after norepinephrine dose reduction

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 12, 2026
• First Posted (Actual): June 17, 2026

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Critical closing pressure; Tissue perfusion pressure; Vascular waterfall; Norepinephrine dose; Distributive shock
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Critical Illness
• Other Study ID Numbers: pumch-micu202606

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No