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

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

Universidade Federal de Pernambuco, Coordination for the Improvement of Higher Education Personnel, Brazilian National Council for Scientific and Technological Development (CNPq), Pernambuco Research Foundation (FACEPE)

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.

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.

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.

trial participants, data collectors and outcome assessors or committees will remain blinded to the patient assigned group of treatment.

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%)

setting PEEP after performing a modified alveolar recruitment maneuver followed by a decremental PEEP titration electing the level correspondent to the lowest driving pressure.

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.

The setting of the lowest PEEP level and FiO2 match stated by the table to achieve a goal oxygenation.

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.

The setting of the PEEP level above the intersection of the curves representing relative alveolar overdistention and collapse, after a modified alveolar recruitment maneuver.

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.

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.

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

participant characteristics (age, gender) clinical measurements (blood pressure, heart rate) medical history clinical laboratory results images (X-rays) adverse events (hemodynamic and respiratory instability, interruptions) details of randomisation and treatment received

individual participant data (IPD) access will be granted by the PI after request review for approval via email. It will be shared with researchers and general public of interest on the subject for descriptive analyses related to our sample medical and clinical characteristics. A committee of researchers will be in charge of discussing the request before approving the access.

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