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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
1,180
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.
Sedation and analgesia will be administered according to the usual practices in each participating center.
Day-90 mortality
Time frame: Mortality at Day 90 after randomization
Mortality at Day 28
Time frame: at day 28
Hospital mortality
Time frame: at hospital discharge, up to day 90
1-yr mortality
Time frame: at 1 yr
Mechanical ventilation duration
Time frame: From onset of mechanical ventilation to day 28
Days alive with no mechanical ventilation
Time frame: From ICU admission up to day 28
Occurence of ventilator-associated pneumonia
Time frame: During mechanical ventilation duration, up to day 28
Use of non-invasive ventilation after extubation
Time frame: From extubation to ICU discharge up to day 28
Duration of ICU stay
Time frame: 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
Time frame: 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
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Hôpital Saint-Esprit
Agen, France
CHU d'Angers
Angers, France
Hopital Privé d'Antony
Antony, France
CH d'Argenteuil
Argenteuil, France
CH Germon et Gauthier
Beuvry, France
Hopital Avicenne
Bobigny, France
Hopital St-Andre
Bordeaux, France
Hopital Ambroise Pare
Boulogne-Billancourt, France
CHRU de la Cavale Blanche
Brest, France
Hopital Antoine Beclere
Clamart, France
...and 33 more locations
Time frame: 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
Time frame: At day 90 and 1 year
Time to weaning onset
Time frame: Time from mechancial ventilation initiation to first spontaneous breathing trial, up to day 28
Number of patients requiring tracheotomy
Time frame: During ICU stay, up to day 28
First sitting in chair
Time frame: During ICU stay, up to day 28