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

Study Overview
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Brief Summary
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Through many years, the standard care has been to use continuous sedation of critically ill patients during mechanical ventilation. However, preliminary randomised clinical trials indicate that it is beneficial to reduce the sedation level in these patients. The NONSEDA trial is an investigator-initiated, randomised, clinical, parallel-group, multinational, superiority trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden, comparing no sedation with sedation and a daily wake-up trial during mechanical ventilation. This is a substudy of the NONSEDA trial, concerning 250 patients included at trialsite Kolding, Denmark. The aim of the substudy is to assess the effects of no sedation on delirium during admission and cognitive function after discharge from ICU. Our hypothesis is that critically ill patients who are not sedated during mechanical ventilation will have better cognitive function after discharge.

Official Title
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Substudy of the NONSEDA Trial (NCT01967680): Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Me-chanical Ventilation - Effects on Cognitive Function

Conditions
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Delirium, Cognition Disorders

Intervention / Treatment
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* Other: Non-sedation
* Other: Control: Sedation


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 Patient does not speak Danish, swedish or norwegian at a reasonable level

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>Non-sedation supplemented with pain management during mechanical ventilation. | Other: Non-sedation<br>* Patients are awake or have natural sleep during mechanical ventilation. Pain is treated with morphine iv.<br>|
| Active Comparator: Sedation<br>Current gold standard: Sedation with a daily wake-up trial. | Other: Control: Sedation<br>* Continuous iv-sedation (propofol first 48 hours, from then midazolam) to Ramsey 3-4 with a daily wake up attempt, where sedation is stopped until patient is awake.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive function | Cognitive t-score, in percentage, difference between the two groups. The t-score for each patient will be diagnosed by the neuropsycologist at a personal interview and use of following tests: Span of numbers Coding test Trailmaking A+B Rey auditory verbal learning test (immediate, recall) Rey-Ostherrieth complex figure test (immediate, recall, recognition) Word finding test (S-word, animals) Stroop test (congruent+incongruent) | 3 months after discharge from ICU | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attention/concentration | T-score in the two groups for the cognitive domaine attention/concentration | 3 months after discharge from ICU | 
| Learning/memory | t-score in the two groups for the cognitive domaine: learning/memory | 3 months after discharge from ICU | 
| Executive dysfunction | t-score in the two groups for the cognitive domaine: executive dysfunction | 3 months after discharge from ICU | 
| Mental pace | t-score in the two groups for the cognitive domaine: mental pace | 3 months after discharge from ICU | 
| Hypoactive delirium | Occurrence of hypoactive delirium (RASS ≤ 0, CAM-ICU positive) in each group related to cognitive function at follow up | 3 months after discharge from ICU | 
| Agitated delirium | Occurrence of agitated delirium (RASS ≥ +2, CAM-ICU positive) in each group related to cognitive function at follow up | 3 months after discharge from ICU | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiration, artificial, Critcal care