AHRF, ARDS
Conditions
Keywords
ARDS, AHRF, acute respiratory distress syndrome, PEEP, collapse, overdistention, hemodynamics, heart-lung interactions, mechanical ventilation, randomized crossover trial
Brief summary
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.
Interventions
OTHERChange 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
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Randomized crossover trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Impact of lung collapse on cardiac output | Assesment performed at the end of each of the three 30 minute steps | Evaluation of the relative contribution of lung collapse (arbitrary units) on patients' cardiac output at different PEEP levels (L/min) |
| Impact of lung collapse on pulmonary vascular resistance | Assesment performed at the end of each of the three 30 minute steps | Evaluation of the relative contribution of lung collapse (arbitrary units) on pulmonary vascular resistance (dyn·s/cm\^5) at different PEEP levels |
| Impact of lung overdistention on cardiac output | Assesment performed at the end of each of the three 30 minute steps | Evaluation of the relative contribution of lung overdistention (arbitrary units) on patients' cardiac output at different PEEP levels (L/min) |
| Impact of lung overdistention on pulmonary vascular resistance | Assesment performed at the end of each of the three 30 minute steps | Evaluation of the relative contribution of lung overdistention (arbitrary units) on pulmonary vascular resistance (dyn·s/cm\^5) at different PEEP levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between potential for lung recruitment and PEEP-induced changes in cardiac output | Assessment at the end of each of the three 30 minute steps | 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) |
| Correlation between potential for lung recruitment and PEEP-induced changes in pulmonary vascular resistance | Assesment performed at the end of each of the three 30 minute steps | 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) |
| PEEP-induced effects on cardiac output in cardiac preload responsive vs. nonresponsive patients | Assesment performed at the end of each of the three 30 minute steps | 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 %) |
| PEEP-induced effects on pulmonary vascular resistance in cardiac preload responsive vs. nonresponsive patients | Assesment performed at the end of each of the three 30 minute steps | 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 %) |
| Relationship between transpulmonary pressures and central venous pressure variations | At the end of each of the three 30 minute steps | The relationship between transpulmonary pressure variations (cmH2O) and central venous pressure variations (cmH2O) between PEEP levels will be assessed through Pearson correlations |
| Lung hysteresis | At the end of each of the three 30 minute steps | 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 |
| Lung aeration distribution | At the end of each of the three 30 minute steps | 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) |
| Relationship between PEEP-induced changes in lung volume and PEEP-induced changes in pulmonary vascular resistance | Assesment performed at the end of each of the three 30 minute steps | 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) |
| Relationship between PEEP-induced changes in lung volume and PEEP-induced changes in cardiac output | Assesment performed at the end of each of the three 30 minute steps | The effects of PEEP cardiac output (L/min) will be correlated through Pearson correlations with the individual PEEP-induced changes in lung volume (mL) |
Countries
Italy
Contacts
CONTACTDomenico Luca Grieco, MD
PRINCIPAL_INVESTIGATORDomenico Luca Grieco, MD
Fondazione Policlinico Universitario A. Gemelli, IRCCS
Outcome results
None listed