Inspiratory Ratio: Predictor of Inspiratory Effort Response to High PEEP in Patients Recovering From ARDS

Study Overview
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Brief Summary
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Spontaneous Breathing (SB) can be potentially harmful in patient with Acute Respiratory Distress Syndrome (ARDS) during the transition phase of passive ventilation to partial ventilatory support. The application of high Positive End Expiratory Pressure (PEEP) during SB has shown to ameliorate the progression of lung injury by decreasing the TP and esophageal pressure (EP) swings and the stress / strain applied to the lung. The mechanisms proposed to be responsible for these effects are the activation of Hering Breuer reflex, the recruitment of previously collapsed tissue, the homogenization of lung and the improvement of respiratory system compliance and the impairment in the length - tension relationship of the diaphragm. If all the previously explained mechanisms have an effect on the control of inspiratory effort, a decrease in the intensity of effort is expected during an end-inspiratory occlusion in patients who will respond to high PEEP application. Based on this rationale, the investigators developed an index called Inspiratory Ratio (IR) to predict the response of patient's inspiratory effort to the application of high PEEP without need of esophageal manometry.

Detailed Description
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Spontaneous Breathing (SB) can be potentially harmful in patient with Acute Respiratory Distress Syndrome (ARDS) during the transition phase of passive ventilation to partial ventilatory support. A high respiratory drive and consequently, a strong inspiratory effort, may produce large transpulmonary pressure (TP) swings mainly in dependent lung regions closer to the diaphragm and cause alveolar rupture and inflammatory mediators release. The application of high Positive End Expiratory Pressure (PEEP) during SB has shown to ameliorate the progression of lung injury by decreasing the TP and esophageal pressure (EP) swings and the stress / strain applied to the lung. The mechanisms proposed to be responsible for these effects are the activation of Hering Breuer reflex caused by a greater stretch of the lung parenchyma at the end of inspiration; the recruitment of previously collapsed tissue, the homogenization of lung (fluid like behavior) and the improvement of respiratory system compliance (Crs); and the impairment in the length - tension relationship of the diaphragm which produces mechanical disadvantage to generate force due to a higher lung volume. However, it is uncertain which patient will respond adequately to the application of high PEEP and consequently will reduce the inspiratory effort. If all the previously explained mechanisms have an effect on the control of inspiratory effort, in patients who will respond to high PEEP application, a decrease in inspiratory effort is expected during an end-inspiratory occlusion. At end-inspiration lung parenchyma is more homogeneous, the lung volume is higher and the diaphragmic dome is flatter compared to the physiological condition end of expiration, where the lung volume is lower, the parenchyma is more heterogeneous and the diaphragmatic neuromechanical coupling is better. Based on this rationale, the investigators developed an index called Inspiratory Ratio (IR) to predict the response of patient's inspiratory effort to the application of high PEEP without having to measure esophageal pressure. The IR will be calculated using the following formula: (IPSexp - IPSinsp ) / (IPSexp) x 100 IPSexp = negative deflection in airway pressure expiratory pause; IPSinsp = negative deflection in airway pressure end inspiratory pause

Official Title
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Inspiratory Ratio: Predictor of Inspiratory Effort Response to High Positive End Expiratory Pressure in Patients Recovering From Acute Respiratory Distress Syndrome.

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Other: Positive end expiratory pressure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Need of invasive mechanical ventilation Patients who had fulfill ARDS criteria based on Berlin definition during any time of invasive mechanical ventilation. Patient ventilated in pressure support ventilation. Time of invasive ventilation expected to be longer than 24 hs after the day of enrollment. Exclusion Criteria: Neuromuscular diseases (e.g., amyotrophic lateral sclerosis, Duchenne Erb) previous diagnosis of chronic obstructed pulmonary disease not resolved pneumothorax bronchopleural fistula suspicion of central respiratory drive alteration (e.g., benzodiazepines intoxication).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Positive end expiratory pressure|Initially, the patients will be ventilated using pressure support ventilation with an inspiratory pressure adjusted to achieve 6 - 8 ml/kg of PBW with a minimal esophageal pressure swing of 5 cmH2O and a PEEP of 5 cmH2O. After 5 minutes, we will measure five IPSexp and five IPSinsp in random order and considering a resting period between each occlusion in order to avoid learning effect and disconfort. The IR will be calculated using the average of the measured IPSexp and the average of the IPSinsp. Besides, we will register the average of esophageal pressure and transpulmonary pressure swings continuously. The same procedure will be carried out with 10 and 15 cmH2O of PEEP. Inspiratory pressure will be kept constant throughout the protocol.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inspiratory ratio | Inspiratory ratio will be calculated using the formula (IPSexp - IPSinsp )/IPSexp x 100, being IPSexp = negative deflection in airway pressure during an end expiratory pause; IPSinsp = negative deflection in airway pressure during an end inspiratory pause. | 10 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Esophageal pressure swing | Esophageal pressure swing will be calculated as the difference between end expiration and end inspiration esophageal pressure during the las 30-60 seconds of each PEEP condition evaluated | 10 minutes | 
| Dynamic transpulmonary pressure swing | Dynamic transpulmonary pressure swing will be calculated as the difference between end expiration and end inspiration dynamic transpulmonary pressure during the las 30-60 seconds of each PEEP condition evaluated | 10 minutes |