Peripheral Perfusion Index-guided Fluid Resuscitation for Preventing Acute Skin Failure in Elderly Critically Ill Patients (PPI-PROTECT)

Effect of Peripheral Perfusion Index-guided Fluid Resuscitation on the Prevention of Acute Skin Failure in Elderly Critically Ill Patients: A Prospective, Randomized, Controlled Trial

This prospective, randomized, controlled trial aimed to evaluate whether fluid resuscitation guided by the Peripheral Perfusion Index (PPI) could reduce the incidence of Acute Skin Failure (ASF) in elderly critically ill patients. A total of 216 patients aged ≥65 years with sepsis or other types of shock requiring early aggressive fluid resuscitation were enrolled and randomly assigned in a 1:1 ratio to either the PPI-guided resuscitation group or the conventional resuscitation group. The intervention group targeted maintaining PPI ≥1.4 in addition to conventional hemodynamic goals, while the control group followed standard resuscitation protocols. The primary outcome was the incidence of ASF within 7 days of ICU admission, diagnosed according to NPUAP/EPUAP (2014) criteria. Secondary outcomes included time to ASF occurrence, lactate clearance, cumulative fluid balance, organ function, and long-term prognosis.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock; Acute Skin Failure
• Intervention / Treatment: Other: Peripheral Perfusion Index-guided Fluid Resuscitation Protocol; Other: Conventional Goal-Directed Fluid Resuscitation

• Study Type: Interventional
• Enrollment (Estimated): 216
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ying Wang; Phone Number: +86 13485139816; Email: wenquxingdiyi@163.com

Study Locations

• China
  • Jiangsu
    • Nantong, Jiangsu, China, 226000
      • Recruiting
      • Nantong First People's Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 65 years.
2. Diagnosis of sepsis (according to Sepsis-3 criteria) or other types of shock requiring early and aggressive fluid resuscitation.
3. APACHE II score ≥ 15 at ICU admission.
4. Expected ICU length of stay ≥ 72 hours.
5. Written informed consent obtained from the patient or their legally authorized representative.

Exclusion Criteria:

1. Pre-existing stage III or higher pressure injury or skin necrosis at the time of enrollment.
2. Severe dermatological disease or peripheral vascular disease that could interfere with the assessment of skin or peripheral perfusion.
3. Inability to perform continuous finger pulse oximetry monitoring (e.g., due to bilateral finger injury, amputation, or severe peripheral edema).
4. Contraindications to liberal fluid resuscitation (e.g., acute cardiogenic pulmonary edema, severe heart failure with fluid overload).
5. Expected survival < 24 hours due to terminal illness or irreversible condition. Concurrent participation in another interventional clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: eripheral Perfusion Index-guided Fluid Resuscitation Protocol	Other: Peripheral Perfusion Index-guided Fluid Resuscitation Protocol; In addition to achieving conventional macro-hemodynamic goals (mean arterial pressure ≥65 mmHg, etc.), a resuscitation protocol targeting a Peripheral Perfusion Index (PPI) value ≥1.4 is implemented. PPI is continuously monitored via a finger pulse oximeter. If PPI remains below 1.4 for >30 minutes, a fluid responsiveness assessment (e.g., passive leg raising test) is performed. Fluid boluses (balanced crystalloid) are administered only if the patient is fluid-responsive. Otherwise, vasoactive agents are optimized.
Active Comparator: Conventional Fluid Resuscitation Group	Other: Conventional Goal-Directed Fluid Resuscitation; Fluid resuscitation is performed according to the Surviving Sepsis Campaign International Guidelines. Resuscitation targets include: mean arterial pressure ≥65 mmHg, central venous pressure 8-12 mmHg, urine output ≥0.5 mL·kg-¹·h-¹, and normalization/decreasing trend of serum lactate. The type, rate, and volume of fluid administration are determined by the treating physician based on these standard macro-hemodynamic and perfusion parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Acute Skin Failure（per the NPUAP/EPUAP 2014 Guidelines）	Proportion of patients who develop new-onset Acute Skin Failure (ASF) within 7 days after ICU admission. ASF is diagnosed and staged according to the NPUAP/EPUAP (2014) criteria.	From ICU admission up to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Acute Skin Failure (ASF) Onset	Number of days from ICU admission to the first diagnosis of ASF (assessed in patients who develop ASF)	From ICU admission up to 7 days
Maximum Stage of Acute Skin Failure	The most severe stage of ASF (according to NPUAP/EPUAP 2014 criteria) observed within 7 days after ICU admission	From ICU admission up to 7 days
Lactate Clearance Rate at 6 Hours	Percentage decrease in serum lactate concentration from baseline to 6 hours after initiation of resuscitation	Baseline and 6 hours after resuscitation initiation
Lactate Clearance Rate at 24 Hours	Percentage decrease in serum lactate concentration from baseline to 24 hours after initiation of resuscitation	Baseline and 24 hours after resuscitation initiation
Cumulative Fluid Balance at 72 Hours	Net fluid balance (total fluid intake minus total output) calculated over the first 72 hours of ICU stay	From ICU admission up to 72 hours
Incidence of Acute Kidney Injury	Proportion of patients who develop AKI according to KDIGO criteria within 7 days after ICU admission	From ICU admission up to 7 days
Duration of Mechanical Ventilation	Total number of days requiring invasive mechanical ventilation during ICU stay	From ICU admission until ICU discharge, up to 90 days
Length of ICU Stay	Total number of days from ICU admission to ICU discharge	From ICU admission until ICU discharge, up to 90 days
28-Day All-Cause Mortality	Proportion of patients who die from any cause within 28 days after ICU admission	From ICU admission up to 28 days
90-Day All-Cause Mortality	Proportion of patients who die from any cause within 90 days after ICU admission	From ICU admission up to 90 days
Barthel Index at Hospital Discharge	Score of the Barthel Index (a measure of activities of daily living) assessed at the time of hospital discharge in surviving patients. Range: 0-100, higher scores indicate greater independence	At hospital discharge, up to 90 days after ICU admission
Total Hospitalization Costs	Total direct medical costs incurred during the index hospitalization, expressed in local currency	From hospital admission to hospital discharge, up to 90 days
30-Day Unplanned Readmission Rate	Proportion of patients who have an unplanned readmission to any hospital within 30 days after hospital discharge	30 days after hospital discharge
Incidence of Resuscitation-Related Serious Adverse Events	Proportion of patients who experience serious adverse events related to fluid resuscitation (e.g., new-onset cardiogenic pulmonary edema, arrhythmia requiring intervention) during the ICU stay	From ICU admission until ICU discharge, up to 90 days

Collaborators and Investigators

• Sponsor: Ying Wang
• Collaborators: Nantong First People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 16, 2026
• First Submitted That Met QC Criteria: January 16, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Sepsis; Shock, Septic
• Other Study ID Numbers: HAYY - 2025 - LW - 045

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The investigators may have further research, and the investigators may not consider releasing the research data until the results are announced

Drug and device information, study documents

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