Acute Hypoxemic Respiratory Failure (AHRF) is a condition in which injury to the lungs impairs the ability of the air sacs (alveoli) to ventilate and exchange oxygen. This impairment may be worsened in individuals with elevated body weight, particularly when fat tissue compresses the lungs and promotes alveolar collapse. The impact of body weight on lung function may be greater in individuals with upper-body fat distribution.

Two common interventions for AHRF-positive end-expiratory pressure (PEEP) and prone positioning-are used to improve lung ventilation. However, it is unclear whether these therapies are equally effective across different body weight categories and fat distributions.

This study will evaluate whether body weight and fat distribution affect patients' lung inflation responses to PEEP and prone positioning. Lung inflation will be assessed using electrical impedance tomography (EIT), a bedside imaging tool that maps lung ventilation, and esophageal manometry, which estimates lung compression through a thin catheter placed in the esophagus. Laboratory tests will also be used to measure markers of inflammation and AHRF severity and find correlations with fat distribution and responses to the tested treatments..

Patients with AHRF requiring mechanical ventilation will be enrolled across a range of body weights. Each participant will undergo combinations of two PEEP levels and two body positions (supine and prone) for 30 minutes each. At the end of the study procedures, clinical care will continue as determined by the treating team.

This study investigates the relationship between body habitus and the physiological response to ventilatory interventions in patients with Acute Hypoxemic Respiratory Failure (AHRF). The primary objectives are to determine:

1. Whether excess body weight affects the regional lung inflation response to PEEP and prone positioning;
2. Whether body fat distribution (e.g., central vs. peripheral) is associated with lung recruitment;
3. Whether inflation responses correlate with laboratory markers of systemic inflammation and AHRF severity.

Adult patients with AHRF requiring invasive mechanical ventilation will be screened daily in the intensive care units at Massachusetts General Hospital. The study team will coordinate with clinical staff and patient surrogates to obtain informed consent. Enrollment is limited to the period required to perform study-specific procedures. No follow-up visits or post-discharge interventions are planned.

After consent, participants will be equipped with two adhesive EIT electrode belts, placed bilaterally on the thorax, to measure regional ventilation. A pressure and flow sensor will be placed in the breathing circuit at the proximal end of the endotracheal tube. An esophageal balloon catheter will be inserted nasally into the distal esophagus (approximately 35-40 cm) to measure intrathoracic pressure (ITP) via esophageal manometry, recorded through an auxiliary module on the EIT device.

Once all monitoring devices are in place, patients will be evaluated for adequate sedation and ventilator synchrony. Baseline data will be recorded during ventilation at the clinician-selected PEEP level (PEEP_CLIN), including EIT, airway pressure, flow, and ITP signals over 20 consecutive breaths.

Subsequently, a PEEP titration trial will be conducted to identify an individualized PEEP value (PEEP_TIT) that minimizes both alveolar collapse and overdistension, using EIT-based criteria. The patient will then be ventilated at PEEP_TIT for 30 minutes, after which all measurements will be repeated.

Following supine data collection, patients will be transitioned to the prone position using standard clinical protocols, with participation from ICU staff (physicians, nurses, and respiratory therapists) in accordance with institutional practice. Continuous monitoring (including pulse oximetry and arterial blood pressure) will be maintained throughout the repositioning.

After achieving the prone position, a recruitment maneuver will be performed to standardize lung volume history. The EIT belts will then be reconnected, and the patient will be allowed to stabilize for 30 minutes at PEEP_CLIN before measurements are repeated. A second PEEP titration trial will be performed to determine PEEP_TIT in the prone position, followed by another 30-minute stabilization period and repeat data acquisition.

Arterial blood samples (2 mL each) will be obtained at each PEEP level in both positions (four total, 8 mL cumulative) for gas exchange analysis. An additional 10 mL sample will be collected during supine ventilation at PEEP_CLIN for biomarker analysis. Biomarkers of inflammation (e.g., IL-6, TNF-α, C-reactive protein) and adipose tissue-related factors (e.g., adiponectin, leptin, resistin) will be measured.

After study procedures, participants will be returned to the supine position unless otherwise indicated by the clinical team. All subsequent clinical decisions regarding ventilator management or patient positioning will be made by the attending care team.

This study seeks to generate mechanistic insights into how excess body weight and fat distribution affect the physiologic response to standard ventilatory interventions in AHRF, with the goal of informing more individualized approaches to respiratory support.

Inclusion Criteria:

• AHRF with PaO2/FiO2 <= 300 mmHg) intubated for less than 72 hours
• Presence of an arterial line for blood gas measurement and blood pressure monitoring
• 18 years or older

Exclusion Criteria:

• Suspected pregnancy, pregnancy or less than six weeks postpartum

• Younger than 18 years or older than 80 years.

• Subject enrolled in another interventional research study

• Presence of pneumothorax

• Usage of any devices with electric current generation such as pacemaker or internal cardiac defibrillator

• Preexisting chronic lung disease or pulmonary hypertension

• Acute cardiac failure causing pulmonary edema

• Past medical history of lung malignancy or pneumonectomy, or lung transplant

• Hemodynamic instability, defined as:

  • Persistent systolic blood pressure <90 mmHg and/or >180 mmHg despite the use of vasopressor or vasodilators, or
  • Requiring an increment in inotropic-vasopressors over the past two hours just before enrollment: more than 15 mcg/min for norepinephrine and dopamine, more than 10 mcg/min in epinephrine; and more than 50 mcg/ min for phenylephrine.

• Contraindications to placement in the prone position: complex abdominal surgical dressing, recent sternotomy, unstable spine or pelvic fractures, intracranial hypertension, serious facial injury

• Extracorporeal life support