Clinical and Functional Outcomes of Critically Ill Patients With COVID-19

Study Overview
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Brief Summary
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People affected by Severe Acute Respiratory Syndrome (SARS) by COVID-19 virus my require a long lasting invasive mechanical ventilation life support. To prevent damages to the lungs a number of protective lung ventilation measures are taken, one of them encounters the positive end expiratory pressure (PEEP) titration. Up to date, it is unclear the best method to titrate PEEP considering this unconventional syndrome compared to other etiologies. In addition to the long lasting advanced life support and bedridden condition, other factors may affect respiratory and peripheral muscle function of these patients. Therefore, the investigators intend to follow up these patients randomized to one of the three-arm experimental PEEP titration and after ICU discharge their status on clinical, laboratory and physical functions assessments.

Detailed Description
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Introduction: Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2) requires mechanical ventilatory (MV) life support. In this scenario, lung protective strategies have been recommended for avoiding ventilator induced lung injuries mainly by inappropriate positive end expiratory pressure (PEEP) titration. However, the best method of PEEP titration for these patients remains unclear, since its clinical and morphofunctional phenotype may differ from the conventional acute respiratory distress syndrome (ARDS) phenotype resulted from other etiologies. In addition, these patients' condition of long lasting MV dependency and bed restriction may lead to deterioration of respiratory and peripheral muscles functions. Objective: To compare the clinical and laboratory evolution and the respiratory and peripheral muscle functions in mechanically ventilated patients with COVID-19 submitted to PEEP titration by the following methods: ARDSNet protocol, driving pressure (DP) and electrical impedance tomography (EIT), as well as following them up after hospital discharge. Methods: This is a controlled, randomized, double blind clinical trial with 90 mechanically ventilated patients to be randomized in one of the 3 PEEP titration- related groups: ARDSNet protocol, Driving Pressure-DP (electing PEEP level by the lowest DP) and by the EIT (PEEP selected will be the closest level above the intercept point of cumulated collapse and overdistension percentage curves). Clinical, laboratory, oxygenation, ventilation, respiratory and regional mechanics data, as well as peripheral muscle outcomes (strength and functionality) will be monitored from intubation to extubation in the supine and prone position. The outcomes of respiratory and peripheral muscles functionality will be monitored for six months after hospital discharge. All ethical principles will be respected with either written Free and Consent Term by the patient or relatives at the intensive care phase or at the post ICU discharge phase. Data will be registered for posterior analysis, which considers the difference between groups with p <0.05. Expected results: Based on this study, it is expected to identify the Peep titration method associated to the greater beneficial and less deleterious effects in critically ill patients on MV. Also to address appropriate lung protective ventilation strategy for these patients and to detect respiratory and peripheral muscle disorders as early as possible in critically ill survivors.

Official Title
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Clinical, Respiratory, Peripheral, Muscle and Functionality Outcomes of Adult ICU Inpatients and Rehabilitation-center Outpatients With COVID-19

Conditions
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Acute Respiratory Distress Syndrome (ARDS)

Intervention / Treatment
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* Other: ARDSNet table
* Other: Driving Pressure
* Other: Electrical Impedance Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: mechanically ventilated patients due to acute respiratory failure associated to COVID-19 confirmed or suspected cases Exclusion Criteria: consent refusal by patient, family or doctor

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: three groups of treatments (A, B and C) are given so that one group receives only A while another group receives only B and the third group receives only C. All volunteers will be randomized to one of the three groups of treatment.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADRSNet protocol<br>ARDSnet protocol is the current, standard of care for ARDS. Its used by setting PEEP and the fraction of inspired oxygen (FiO2) to achieve the oxygenation goal (SpO2 ≥ 93% - accepting the range of 90-96%) | Other: ARDSNet table<br>* The setting of the lowest PEEP level and FiO2 match stated by the table to achieve a goal oxygenation.<br>|
| Experimental: Driving Pressure (DP)<br>setting PEEP after performing a modified alveolar recruitment maneuver followed by a decremental PEEP titration electing the level correspondent to the lowest driving pressure. | Other: Driving Pressure<br>* The setting of the lowest PEEP level by the lowest correspondent driving pressure, which is defined by the difference of plateau pressure, after a modified alveolar recruitment maneuver.<br>|
| Experimental: Electrical Impedance Tomography (EIT)<br>After performing a modified alveolar recruitment maneuver, the PEEP decremental titration guided by the EIT will be set at the level above the intersection of the curves representing relative alveolar overdistention and collapse. | Other: Electrical Impedance Tomography<br>* The setting of the PEEP level above the intersection of the curves representing relative alveolar overdistention and collapse, after a modified alveolar recruitment maneuver.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Murray Score (LIS) | Scoring system for lung injury including hypoxemia, respiratory system compliance, chest radiographic findings and level of PEEP. The minimum value is zero and the maximum value is sixteen. The higher the score the worse outcome. | 4 hours | 
| Potential lung recruitment measured during electrical impedance tomography | to quantify lung ventilation distribution | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of days in intensive care unit (ICU days) | to quantify the number of days spent in a critical care unit | Through study completion, an average of 1 year | 
| Work of breathing (WOB) measured during surface electromyography | measured in root-mean-squared electromyography signals | 4 hours | 
| Duration of mechanical ventilation (MV days) | to quantity the number of days with use of invasive mechanical ventilation in inpatients. | Through study completion, an average of 1 year | 
| ICU Mortality | to quantify number of living days between ICU admission and deceased status | Through study completion, an average of 1 year | 
| respiratory muscle strength | maximal static respiratory mouth pressures | Through study completion, an average of 1 year | 
| Forced vital capacity (FVC) measured during spirometry | measures obtained by spirometry in outpatients | Through study completion, an average of 1 year | 
| diaphragmatic mobility measured during ultrasonography | diaphragmatic excursion expressed in millimeters | Through study completion, an average of 1 year | 
| diaphragmatic thickening measured during ultrasonography | diaphragmatic thickening expressed in millimeters | Through study completion, an average of 1 year | 
| breathing pattern measured during airway flowmeter | a device to quantify airway flow | Through study completion, an average of 1 year | 
| peripheral muscle strength I | to be evaluated by Medical Research Council's scale. The minimum score is 0 and the maximum is 60. The higher the score, the better outcome. | Through study completion, an average of 1 year | 
| peripheral muscle strength II | to be evaluated by a handgrip dynamometers in outpatients | Through study completion, an average of 1 year | 
| peripheral muscle strength III | to be evaluated by a handheld dynamometer in outpatients | Through study completion, an average of 1 year | 
| six-minute walk test (6WT) | sub-maximal exercise test used to assess aerobic capacity and endurance in outpatients | Through study completion, an average of 1 year | 
| functional capacity (Perme scale) | The minimum score is 0 and the maximum is 32. The higher the score, the better outcome. | Through study completion, an average of 1 year | 
| daily activities performance | to be evaluated by Barthel Index in outpatients | Through study completion, an average of 1 year | 
| quality of life measured by Short Form Health survey 36 | score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | Through study completion, an average of 1 year |