AnaConDa-therapy in COVID-19 Patients

Study Overview
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Brief Summary
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COVID 19-pneumonia may evolve into respiratory insufficiency for which invasive mechanical ventilation is required. Recently, inhaled anesthetics have become available for sedation of critically ill patients. Based upon recent research, these anesthetics may provide advantages in improvement of P/F ratio in ARDS patients. However, up to now, its effects on COVID-19 pneumonia patients is unknown; therefore, this study was designed as a plan to investigate whether the use of inhaled sevoflurane leads to improvement of oxygenation compared to intravenous sedatives in mechanically ventilated COVID-19 patients

Detailed Description
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COVID-19 is an infectious disease caused by the virus SARS-CoV-2, which can lead to severe pneumonia with acute respiratory distress syndrome (ARDS)-like presentation. In this condition, the exchange of oxygen and carbon dioxide in the lungs is compromised because of an inflammatory response with capillary leak. This leads to deterioration of oxygenation with hypoxemia and a decrease in P/F (arterial oxygen tension/fraction of inspired oxygen) ratio, resulting in need for invasive mechanical ventilation. To accomplish this, the patient needs to be sedated. Classic, intravenous sedatives usually come with long half-lifes, which lead to prolonged need for mechanical ventilation, because of residual sedation. Next to short half-life, the inhalation anesthetic sevoflurane is supposed to have anti-inflammatory effects, which could improve oxygenation. This study is designed to investigate the hypothesis that sedation by use of sevoflurane leads to better oxygenation in COVID-19 patients, compared to intravenous sedatives. Secondarily, the effects of sevoflurane compared to intravenous sedatives on duration of admission and mechanical ventilation, on respiratory parameters and hemodynamics, inflammatory parameters, use of opioids, manner of waking up and prevalence of delirium, will be investigated. Study design: The study concerns a single center cohort study in the ICU of the Jeroen Bosch Hospital in The Netherlands. Inhaled anesthesia by sevoflurane is compared to intravenous sedation. Both are considered to be standard of care. Study population: Patients with respiratory insufficiency due to COVID-19 pneumonia, with need for invasive mechanical ventilation on the ICU in the Jeroen Bosch Hospital. Study parameters: Primary outcome is P/F ratio (arterial oxygen tension/fraction of inspired oxygen; PaO2/FiO2 ratio) on day 2 and day 5. Secondary outcomes are duration of ICU admission, number of ventilator-free days after 28 days (28VFD), inflammation parameters (CRP/PCT), quality of waking up, number of delirium free days after 28 days (28DFD) and need for vasopressors. Also patient characteristics like demographic information (age, sex, BMI, comorbidity), respiratory and hemodynamic values and use of other sedatives will be evaluated.

Official Title
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AnaConDa-therapy in COVID-19 Patients

Conditions
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COVID-19, SARS CoV-2

Intervention / Treatment
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* Drug: Sevoflurane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years More than 24 hours of invasive mechanical ventilation needed Positive test (e.g. Polymerase Chain Reaction (PCR)) for SARS-CoV-2 Exclusion Criteria: pulmonary history known allergy or hypersensitivity for halogenated anesthetics known or suspected predisposition for malignant hyperthermia suspected or proven intracranial hypertension severe liver dysfunction and/or icterus (serum bilirubin >42,8-51,3 μg per liter) neutropenia (<0.5X10^9 neutrophils per liter) chemotherapy in the month prior to ICU admission patients that are transported to other hospitals during admission

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sevoflurane<br>patients admitted because of respiratory insufficiency due to COVID-19 with need for invasive mechanical ventilation that are sedated by using sevoflurane | Drug: Sevoflurane<br>* sevoflurane inhalation<br>|
| Control<br>patients admitted because of respiratory insufficiency due to COVID-19 with need for invasive mechanical ventilation that are sedated by means of intravenous medication, such as propofol, midazolam, esketamine of fentanyl | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| P/F ratio | arterial oxygen tension divided by fraction of inspired oxygen | day 2 after intubation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration of ICU admission | number of days of admission | through ICU admission | 
| 28VFD | number of ventilator-free days after 28 days | 28 days after intubation | 
| 28DFD | number of delirium-free days after 28 days | 28 days after intubation | 
| need for vasopressors | cumulative dosage per day | duration of ICU stay | 
| 28DM | mortality after 28 days | 28 days after intubation | 
| P/F ratio day 5 | P/F ratio on day 5 after intubation | day 5 after intubation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sevoflurane, propofol, midazolam, COVID-19