HemodynamIc eFfects of Lung Collapse and overdIstension During ARDS (HI-FIVE)

HemodynamIc eFfects of Lung Collapse and overdIstension in Patients With Moderate-to-seVEre Acute Respiratory Distress Syndrome: the HI-FIVE Physiologic Study

The management ARDS relies on ventilatory strategies aimed at limiting ventilator-induced lung injury (VILI). The setting of PEEP is still subject of debate, as randomized clinical trials comparing standardized higher versus lower PEEP strategies failed to demonstrate a clear survival advantage. Only few studies explored the hemodynamic effects of various PEEP levels depending on lung recruitability. Furthermore, the role of PEEP-mediated lung collapse and overdistention on patients' hemodynamics has yet to be elucidated. In this physiologic study, the association between EIT-measured lung collapse and overdistention and cardiac function will be explored, accounting for the individual potential for lung recruitment, partitioned respiratory mechanics and cardiac preload responsiveness. Three PEEP levels will be tested in a randomized, crossover fashion: PEEP corresponding to the crossing point between lung collapse and overdistention, PEEP associated with low lung collapse, PEEP associated with low lung overdistention.

Study Overview

• Status: Not yet recruiting
• Conditions: ARDS; AHRF
• Intervention / Treatment: Other: Change in PEEP

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Domenico Luca Grieco, MD; Phone Number: +393397681623; Email: dlgrieco@outlook.it

Study Locations

• Italy
  • Rome
    • Rome, Rome, Italy, 00168
      • Fondazione Policlinico Universitario A.Gemelli IRCCS
      • Sub-Investigator: Filippo Bongiovanni, MD
      • Contact: Domenico Luca Grieco, MD; Phone Number: +393397681623; Email: dlgrieco@outlook.it
      • Principal Investigator: Massimo Antonelli, MD
      • Sub-Investigator: Tommaso Rosà, MD
      • Sub-Investigator: Antonio Maria Dell'Anna, MD
      • Sub-Investigator: Simone Carelli, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• acute respiratory failure with onset < 1 week from a predisposing risk factor, such as pneumonia, non-pulmonary infection, trauma, transfusion, aspiration, or shock;
• bilateral opacities on chest radiography and computed tomography or bilateral B lines and/or consolidations on lung ultrasound not fully explained by effusions, atelectasis, or nodules/masses;
• pulmonary edema not exclusively or primarily attributable to cardiogenic pulmonary edema/fluid overload, and hypoxemia/gas exchange abnormalities not primarily attributable to atelectasis;
• PaO2/FiO2 ratio ≤ 200 during invasive controlled mechanical ventilation;

Exclusion Criteria:

• age <18 years;
• pregnancy;
• signs of barotrauma or documented pneumothorax;
• severe tachycardia (HR > 120 bpm) and severe lacticaemia (lac > 4 mmol/L)
• pre-existing decompensated heart failure (NYHA class 3-4 and/or documented left ventricular ejection fraction < 35%);
• contraindications to EIT placing (open chest wounds, presence of cardiac pacemaker);
• intubation as a result of an acute exacerbation of chronic pulmonary disease;
• contraindications to esophageal balloon placement (high bleeding risk, esophageal varices).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lung collapse and overdistention crossing point PEEP	Other: Change in PEEP; Patients will undergo a decremental PEEP trial to determine the crossing-point PEEP. Secondly, three PEEP levels (low collapse PEEP, low overdistention PEEP and crossing point between lung collapse and overdistention PEEP) will be compared in a randomized order with 30-minute steps
Experimental: Low lung collapse PEEP	Other: Change in PEEP; Patients will undergo a decremental PEEP trial to determine the crossing-point PEEP. Secondly, three PEEP levels (low collapse PEEP, low overdistention PEEP and crossing point between lung collapse and overdistention PEEP) will be compared in a randomized order with 30-minute steps
Experimental: Low lung overdistention PEEP	Other: Change in PEEP; Patients will undergo a decremental PEEP trial to determine the crossing-point PEEP. Secondly, three PEEP levels (low collapse PEEP, low overdistention PEEP and crossing point between lung collapse and overdistention PEEP) will be compared in a randomized order with 30-minute steps

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of lung collapse on cardiac output	Evaluation of the relative contribution of lung collapse (arbitrary units) on patients' cardiac output at different PEEP levels (L/min)	Assesment performed at the end of each of the three 30 minute steps
Impact of lung collapse on pulmonary vascular resistance	Evaluation of the relative contribution of lung collapse (arbitrary units) on pulmonary vascular resistance (dyn·s/cm^5) at different PEEP levels	Assesment performed at the end of each of the three 30 minute steps
Impact of lung overdistention on cardiac output	Evaluation of the relative contribution of lung overdistention (arbitrary units) on patients' cardiac output at different PEEP levels (L/min)	Assesment performed at the end of each of the three 30 minute steps
Impact of lung overdistention on pulmonary vascular resistance	Evaluation of the relative contribution of lung overdistention (arbitrary units) on pulmonary vascular resistance (dyn·s/cm^5) at different PEEP levels	Assesment performed at the end of each of the three 30 minute steps

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between potential for lung recruitment and PEEP-induced changes in cardiac output	The effects of PEEP on cardiac output (mL/min) will be correlated through Pearson correlations with the individual potential for lung recruitment, as determined by the recruitment-to-inflation ratio (R/I)	Assessment at the end of each of the three 30 minute steps
Correlation between potential for lung recruitment and PEEP-induced changes in pulmonary vascular resistance	The effects of PEEP on pulmonary vascular resistance (dyn·s/cm^5) will be correlated through Pearson correlations with the individual potential for lung recruitment, as determined by the recruitment-to-inflation ratio (R/I)	Assesment performed at the end of each of the three 30 minute steps
PEEP-induced effects on cardiac output in cardiac preload responsive vs. nonresponsive patients	The effects of PEEP on cardiac output (L/min) will be compared through subgroup comparisons (student t-test) in patients who are preload responsive and patients who are not (preload responsiveness assessed through pulse-pressure variation, expressed in %)	Assesment performed at the end of each of the three 30 minute steps
PEEP-induced effects on pulmonary vascular resistance in cardiac preload responsive vs. nonresponsive patients	The effects of PEEP on pulmonary vascular resistance (dyn·s/cm^5) will be compared through subgroup comparisons (student t-test) in patients who are preload responsive and patients who are not (preload resposnsiveness assessed through pulse-pressure variation, expressed in %)	Assesment performed at the end of each of the three 30 minute steps
Relationship between transpulmonary pressures and central venous pressure variations	The relationship between transpulmonary pressure variations (cmH2O) and central venous pressure variations (cmH2O) between PEEP levels will be assessed through Pearson correlations	At the end of each of the three 30 minute steps
Lung hysteresis	Lung hysteresis will be assessed at each of the tested PEEP levels and expressed as the area of the pressure-volume loop of the respiratory system obtained with a low-flow inflation/deflation maneuver from PEEP to a pressure of 30 cmH2O, in mL*cmH2O	At the end of each of the three 30 minute steps
Lung aeration distribution	Lung aeration distribution at each PEEP level tested will be assessed with electrical impedance tomography (EIT) and expressed as dorsal fraction of ventilation (% of total tidal volume)	At the end of each of the three 30 minute steps
Relationship between PEEP-induced changes in lung volume and PEEP-induced changes in pulmonary vascular resistance	The effects of PEEP on pulmonary vascular resistance (dyn·s/cm^5) will be correlated through Pearson correlations with the individual PEEP-induced changes in lung volume (mL)	Assesment performed at the end of each of the three 30 minute steps
Relationship between PEEP-induced changes in lung volume and PEEP-induced changes in cardiac output	The effects of PEEP cardiac output (L/min) will be correlated through Pearson correlations with the individual PEEP-induced changes in lung volume (mL)	Assesment performed at the end of each of the three 30 minute steps

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Domenico Luca Grieco, MD, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): February 28, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: January 7, 2026
• First Submitted That Met QC Criteria: February 14, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 14, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: mechanical ventilation; ARDS; hemodynamics; PEEP; acute respiratory distress syndrome; collapse; heart-lung interactions; AHRF; randomized crossover trial; overdistention
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Respiratory Tract Diseases; Neurobehavioral Manifestations; Lung Diseases; Respiration Disorders; Consciousness Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Respiratory Distress Syndrome; Unconsciousness; Therapeutics; Airway Management; Respiratory Therapy; Respiration, Artificial; Positive-Pressure Respiration
• Other Study ID Numbers: 7795

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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