The TEMA study (Targeting prEssure-Muscle-index to avoid ventilatory over-Assistance during pressure support ventilation) is a prospective, interventional crossover trial investigating the relationship between pressure support (PS) and tidal volume (Vt) in ICU patients with acute hypoxemic respiratory failure (AHRF) receiving pressure support ventilation (PSV). The study aims to assess whether the Pressure-Muscle Index (PMI)-a marker derived from the difference between plateau and peak inspiratory pressure-can help identify the optimal level of ventilatory assistance, preventing over-assistance and its associated complications such as diaphragm atrophy and patient self-inflicted lung injury (P-SILI). By exploring the sigmoidal relationship between PS and Vt, the study seeks to define a physiological threshold (PMI=0) that may serve as a personalized target for PSV titration.
The TEMA study is a prospective, interventional crossover trial designed to explore the physiological relationship between levels of pressure support (PS) and tidal volume (Vt) in mechanically ventilated ICU patients diagnosed with acute hypoxemic respiratory failure (AHRF). The goal is to identify a pressure support threshold beyond which over-assistance occurs, leading to excessive tidal volumes and suppression of respiratory muscle activity. The central hypothesis is that the PS-Vt curve follows a sigmoidal pattern: an initial plateau phase with stable Vt is followed by a steep, compliance-driven increase in Vt at higher PS levels. The Pressure-Muscle Index (PMI), calculated as the difference between plateau pressure (Pplat) and peak airway pressure (Ppeak) during an inspiratory occlusion, is used to define this inflection point (PMI=0), which marks the transition from physiologically appropriate to excessive assistance. Study Design: The study is conducted at the ICU of Santa Chiara Hospital (Trento, Italy) and includes seven levels of pressure support modulation-three above and three below the identified PMI=0 point. At each level, key physiological variables such as Vt, respiratory rate (RR), minute ventilation, PMI, and patient-ventilator asynchrony index are recorded. A second evaluation between days 4-6 post-enrollment is planned for patients who remain intubated, to assess whether the PS-Vt relationship evolves over time, reflecting changes in respiratory drive and mechanics during the ICU course. Technical Aspects: Measurements include respiratory system compliance, work of breathing (WOB), inspiratory effort, and occlusion-based indices. PS levels are applied in randomized order to minimize bias. Clinical PSV settings are reinstated between steps to avoid carryover effects and ensure patient safety. Analytical Approach: The primary outcome is to characterize the PS-Vt relationship and validate the use of PMI as a physiological marker of the optimal support threshold. Nonlinear regression models, including sigmoidal curve fitting, will be used to identify inflection points (c parameters) in the PS-Vt curve. A Monte Carlo simulation informed the sample size, targeting 36 patients to account for potential dropouts, ensuring \>90% power to detect a meaningful breakpoint. Multivariable models will adjust for potential confounders such as PaCO₂, sedation depth, BMI, and baseline compliance. Expected Impact: If successful, the TEMA study will provide a new physiologically grounded framework for tailoring pressure support in assisted ventilation. By validating PMI as a real-time bedside tool, the study may support a more personalized approach to weaning and ventilation management, potentially improving outcomes such as duration of ventilation, weaning success, and ICU stay.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Patients will undergo six randomized PS levels (+2, +4, +6 cmH₂O above and -2, -4, -6 cmH₂O below PSPMI=0).
Santa Chiara Hospital, Trento, Trentino-Alto Adige, Italy
Trento, Trento, Italy
RECRUITINGPressure Support-Tidal Volume (PS-Vt) Relationship
The primary aim is to determine whether the PS-Vt curve exhibits a flat region (where tidal volume remains stable) before transitioning into a steep, compliance-dependent increase at higher PS levels. This transition point, identified as PSPMI=0, is hypothesized to represent the threshold for over-assistance.
Time frame: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1)
Validation of Pressure-Muscle Index (PMI) as an Over-Assistance Marker
PMI will be tested as a real-time bedside indicator for detecting over-assistance in PSV. The study will assess whether PMI=0 reliably corresponds to the threshold of over-assistance, characterized by a minimal patient contribution to Vt and a linear increase in Vt proportional to PS.
Time frame: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1) and during follow-up assessment on Days 4-6 (if patient remains intubated)
Impact of Respiratory Mechanics on PS-Vt Relationship
Evaluation of how respiratory compliance (Crs) influence the PS-Vt curve. The study will investigate individual variations in ventilatory response to PS.
Time frame: During the interventional phase on Day 1 and during follow-up assessment on Days 4-6 (if patient remains intubated)
Rate of Ineffective Efforts During Over-Assistance
Quantification of ineffective respiratory efforts (i.e., inspiratory efforts not followed by ventilator-triggered breaths) during PS levels exceeding the identified PSPMI=0 threshold.
Time frame: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1) and during follow-up assessment on Days 4-6 (if patient remains intubated)
Effect of Over-Assistance on Ventilatory Asynchronies
Measurement of the asynchrony index (percentage of breaths with any form of patient-ventilator asynchrony) at different levels of pressure support, particularly above PSPMI=0.
Time frame: Up to 5 minutes after each PS level adjustment during the interventional phase (Day 1) and during follow-up assessment on Days 4-6 (if patient remains intubated)
Weaning failure
Defined as the inability to transition from PSV to unassisted breathing, requiring either reintubation, prolonged PSV dependence, or failure of a spontaneous breathing trial (SBT). The rate of weaning failure will be compared between patients receiving higher vs. lower levels of PSV support.
Time frame: Up to 100 months or until the of death from any cause, whichever came first.
Duration of mechanical ventilation
Total number of days on invasive mechanical ventilation (IMV), including both fully controlled and pressure-supported modes. The study will compare patients requiring different levels of PSV assistance.
Time frame: From date of randomization until the date of extubation or date of death from any cause, whichever came first, assessed up to 100 months
ICU length of stay (LOS)
Total duration (in days) of ICU admission, analyzing whether PSV settings influence prolonged ICU stays due to delayed weaning, respiratory complications, or ventilatory asynchronies
Time frame: Up to 100 months or until the of death from any cause, whichever came first.
Hospital length of stay (LOS)
Total number of days spent in the hospital from admission to discharge, evaluating whether PSV-related ventilatory strategies impact overall hospitalization duration and recovery time.
Time frame: Up to 100 months or until the of death from any cause, whichever came first.
Impact of Respiratory Mechanics on PS-Vt Relationship
Evaluation of how respiratory drive influence the PS-Vt curve. The study will investigate individual variations in ventilatory response to PS.
Time frame: From the randomization to 5 minutes.
Impact of Respiratory Mechanics on PS-Vt Relationship
Evaluation of how patient effort (Pmus) influence the PS-Vt curve. The study will investigate individual variations in ventilatory response to PS.
Time frame: From the randomization to 5 minutes.
Spontaneous breathing failure
Defined as the Number of Participants who fail transition from PCV to PSV.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.