Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Mechanical Ventilation - Effects on Physical Function

Study Overview
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Brief Summary
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Critically ill, ventilator-treated patients rapidly loose much of their muscle mass and strength. This can attribute to prolonged admission, prolonged mechanical ventilation, increased mortality and might have a negative impact on the physical function, degree of independence and quality of life. The pathophysiological background for the loss of muscle mass as well as possible effective treatment is still not well established. In the NONSEDA-trial we randomise critically ill patients to non-sedation or sedation with a daily wake-up trial during mechanical ventilation in the intensive care unit (ICU). It has never been assessed whether non-sedation reduces the loss of muscle mass and strength. Aim: To assess the effects of non-sedation versus sedation with a daily wake-up trial on physical function after discharge from ICU. Hypothesis: that non-sedation during ventilator-treatment will improve the physical function after ICU-discharge, compared with standard treatment of sedation with a daily wake-up.

Official Title
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Substudy of Non-Seda Trial (NCT01967680): Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Mechanical Ventilation - Effects on Physical Function. An Investigator-initiated, Randomised, Clinical, Parallel-group, Multinational, Superiority Trial

Conditions
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Critically Ill, Muscular Atrophy

Intervention / Treatment
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* Other: Non-sedation
* Other: Sedation, control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Endotracheally intubated Expected time on ventilator > 24 hours Age ≥ 18 years Informed consent Exclusion Criteria: Severe head trauma where therapeutic coma is indicated Therapeutic hypothermia where therapeutic coma is indicated Status epilepticus where therapeutic coma is indicated Patient has participated in the study before Patient is transferred from another ICU with length of stay > 48 hours Patient is comatose at admission PaO2/FiO2 ≤ 9, if sedation is necessary for oxygenation

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-sedation<br>The experimental group will not receive sedatives. Patients are thoroughly and repeatedly informed by the staff of where they are, what have happened, and what type of treatment they are going to receive. Participants will be awake and have a natural sleep rhythm. In case these patients develop and outward delirium, it is necessary to have a nurse or other caregiver at the bedside in order to calm the patient. Patients with delirium will be treated with haloperidol. | Other: Non-sedation<br> <br> |
| Active Comparator: Sedation with daily wake-up<br>The control group will be sedated to Ramsay score 3-4. The first 48 hours the patients will be sedated with propofol, after 48 hours midazolam will be used. During daytime, the patient will be awakened as the intravenous infusion of sedatives will be discontinued. The patient will be considered to be awake when he/she can perform at least three of the following four tasks: Open the eyes to verbal commands. Follow the examiner's instructions with the eyes. Squeeze hands on request. Stick out the tongue on request. After a successful wake-up, the infusion of sedative will be resumed, starting on half of the pre-wake-up dose and adjusted to Ramsey score 3-4. | Other: Sedation, control<br> <br> * Other names: Standard treatment, continuous iv-sedation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical function | Co-primary outcome of: patient-reported quality of life, as measured by SF-36v2, physical component and degree of independence in activities of daily living, as measured by Barthel Index. Since this is a co-primary outcome, the type I error probability associated with the test of the null hypothesis should be less than 0,025. | 3 months after ICU-discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 minute walk | Walking distance in the 6 minute walk test at 3 months follow-up | 3 months after ICU-discharge | 
| Handgrip | Handgrip-strength at 3 month follow-up | 3 months after ICU-discharge | 
| Thigh muscle size | Muscle size, measured as cross section area of the rectus femoris muscle at 3 months follow-up | 3 months after ICU-discharge | 
| Biomechanical data | Muscle strength, measured using biomechanical measurements - Maximal voluntary contraction (MVC), rate of force developement (RFD) and endurance at 25% of MVC at 3 months follow-up | 3 months after ICU-discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-sedation