Comparison for the Effect of Neuromuscular Blocking Agents Versus Sedation Alone on Severe ARDS Patients Due to COVID-19

Study Overview
=================
Brief Summary
-----------------
Many questions about management of COVID-19 are still not answered. So, we recruit this study aiming to evaluate improvement of oxygenation in COVID-19 patients with severe ARDS, to improve morbidity and mortality of ICU covid patients, to participate in understanding of real hidden pathophysiology of COVID-19.

Official Title
-----------------
Comparison for the Effect of Neuromuscular Blocking Agents Versus Sedation Alone on Severe ARDS Patients Due to COVID-19

Conditions
-----------------
COVID-19 Acute Respiratory Distress Syndrome, Sedation Complication, ICU Acquired Weakness

Intervention / Treatment
-----------------
* Drug: muscle relaxation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Severe ARDS: PaO2/FiO2 <200, resistant hypoxemia and tachypnoea (RR > 40 breath/minute) Not relieved by high frequency nasal canula or CPAP. Need for invasive mechanical ventilation (uncooperative) Exclusion Criteria: Patient relatives' refusal Not mechanically ventilated. Combination of female, corticosteroids administration and vecuronium muscle relaxant. Neuromuscular diseases (especially demyelinating diseases).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control group(group A)<br>Only sedation for mechanically ventilated COVID patients | |
| Experimental: Muscle relaxant group(group B)<br>They will receive muscle relaxation treatment for at least 48 hours. Cisatracurium will be given. Short term infusions up to 24 hours will be given in a dose rate of 2-3 mic/Kg/min followed by intervallic shots of 2-5 mg. | Drug: muscle relaxation<br>* They will receive muscle relaxation treatment for at least 48 hours. Cisatracurium will be given. Short term infusions up to 24 hours will be given in a dose rate of 2-3 mic/Kg/min followed by intervallic shots of 2-5 mg.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PaO2/FiO2 | ratio of arterial oxygen pressure in millilitre mercury to fraction of inspired oxygen at same time within the arterial blood gas | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lung mechanics | measurement of peak and plateau pressures in cm H2O, airway resistance in cm H2O. s/mL, static and dynamic compliance in Litre/cm H2O and positive end expiratory pressure in cm H2O from ventilator settings | 48 hours | 
| SOFA score | Fulfilment of modified SOFA (Sepsis Organ Failure Assessment) score sheet | 48 hours | 
| Measurement of tissue perfusion | Measurement of tissue perfusion by serum lactate in mmol/L and jugular venous oxygen saturation % from a sample withdrawn from CVP | 48 hours | 
| Monitoring of Alveolar - Arterial Oxygen difference | An arterial canula is to be introduced and a quantity of 0.5 ml of blood samples are obtained from radial artery and arterial blood gas analysis are performed after anti-coagulation by heparin. Alveolar-arterial oxygen tension difference: [P(A-a) DO2] = [(Pa-PH2O) × FiO2%-PaCO2-PaO2] [(760-47) × FiO2%-PaCO2-PaO2] [713 × FiO2%-PaCO2-PaO2] | 48 hours | 
| 28 days survival | 28 days survival | after 28 days | 
| Recording risk factors | Recording risk factors as diabetes, renal failure, immunosuppression, smoking, COPD and obesity | 28 days | 
| Recording complications | Recording complications as VAP, HAP, neuromuscular weakness | 28 days |