Study of a Strategy to Prevent Oversedation in Intensive Care Patients Under Mechanical Ventilation

Study Overview
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Brief Summary
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The purpose of the present study is to determine whether administration of sedation according to a strategy including a bundle of measures to prevent oversedation is associated with a reduction in mortality of intensive care unit patients requiring mechanical ventilation, compared to administration of sedation according to usual practices.

Detailed Description
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In intensive care unit (ICU) patients receiving mechanical ventilation (MV), potent hypnotics and morphinics are frequently administered to increase synchrony with the ventilator, control agitation and decrease discomfort and pain due to the tracheal tube, bed ridding, painful condition and diagnostic or therapeutic procedures. However, administration sedatives or morphinics is often excessive and may result in deep and prolonged alteration of consciousness, delayed weaning from MV and prolonged MV. and exposes the patient to a higher risk of ventilator-associated pneumonia, ICU delirium and neuromuscular weakness at awakening. The present randomized multicenter study will compare the day-90 mortality of a group of patients receiving conventional sedation to the mortality of a group of patients receiving sedation administered according to an algorithm aimed to prevent oversedation to the mortality. The algorithm is built on a graduate therapeutic response to increasingly intense symptoms of discomfort, pain, ventilator dyssynchrony and agitation, and includes the use of analgesics, non hypnotic benzodiazepines, neuroleptics, repeated intravenous (IV) boluses of hypnotics and short duration (6 hours) IV hypnotic infusions.

Official Title
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Prevention of Oversedation in Intensive Care Patients Under Mechanical Ventilation : the AWARE Multicentric Randomized Trial

Conditions
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ICU Patients Requiring Invasive Mechanical Ventilation

Intervention / Treatment
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* Procedure: Clinical Procedure to Prevent Oversedation
* Procedure: Usual sedation practice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 and older Admission to ICU with expected mechanical ventilation duration > 48 hrs Mechanical ventilation in ICU for less than 12 hours Information provided to the patient or proxy Exclusion Criteria: ICU Admission after cardiac arrest Acute or chronic neuromuscular disease Tracheotomy on ICU admission Acute cerebral injury with intracranial hypertension requiring continuous IV sedation with or without neuromuscular blockade Status epilepticus Treatment withdrawal decision Pregnancy, breast feeding Concurrent participation in another interventional study requiring a change in usual practice of sedation or mechanical ventilation

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prevention of oversedation group<br>In this arm sedation and analgesia will be administered according to a bundle of measures aimed at limiting oversedation, including repeated assessment of patients needs and graduate therapeutic response to control pain, discomfort, poor synchrony with the ventilator and agitation. The therapeutic options include non hypnotic anxiolytics, repeated intravenous (IV) hypnotics boluses, short-duration (6 hours) IV hypnotics infusion and round the clock IV hypnotics infusion. | Procedure: Clinical Procedure to Prevent Oversedation<br>* Sedation and analgesia will be administered according to a bundle of measures aimed at limiting oversedation, including repeated assessment of patients needs and graduate therapeutic response to control pain, discomfort, poor synchrony with the ventilator and agitation. The therapeutic options include non hypnotic anxiolytics, repeated IV hypnotics boluses, short-duration (6 hours) IV hypnotics infusion and round the clock IV hypnotics infusion.<br>|
| Active Comparator: Conventional sedation group<br>In this arm, sedation will be administered according to the usual practices in each participating center. | Procedure: Usual sedation practice<br>* Sedation and analgesia will be administered according to the usual practices in each participating center.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day-90 mortality |  | Mortality at Day 90 after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at Day 28 |  | at day 28 | 
| Hospital mortality |  | at hospital discharge, up to day 90 | 
| 1-yr mortality |  | at 1 yr | 
| Mechanical ventilation duration |  | From onset of mechanical ventilation to day 28 | 
| Days alive with no mechanical ventilation |  | From ICU admission up to day 28 | 
| Occurence of ventilator-associated pneumonia |  | During mechanical ventilation duration, up to day 28 | 
| Use of non-invasive ventilation after extubation |  | From extubation to ICU discharge up to day 28 | 
| Duration of ICU stay |  | From ICU admission to ICU discharge or death in ICU, up to day 90 | 
| ICU confusion | Number of patients alive, awaken, and free of ICU-delirium assessed on the CAM-ICU | From Day 1 to 7, and at day 14, 21 and 28 | 
| Proximal muscle weakness | Number of patients alive, awaken, cooperative and free of proximal muscle weakness | from day 1 to 7, and at day 14, 21 and 28 | 
| Functional, cognitive and psychological status | Functional status (measured on the Barthel scale), depression (measured on the Hospital Anxiety & Depression Scale), Posttraumatic stress disorder (measured on the Impact of Event Scale), Quality of Life (measured on the SF-36) and patient living location | At day 90 and 1 year | 
| Time to weaning onset |  | Time from mechancial ventilation initiation to first spontaneous breathing trial, up to day 28 | 
| Number of patients requiring tracheotomy |  | During ICU stay, up to day 28 | 
| First sitting in chair |  | During ICU stay, up to day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intensive care, mechanical ventilation, sedatives, morphinics, oversedation, mortality, midazolam, propofol, pain, agitation