Clinical trial NCT01617265: Study of a Strategy to Prevent Oversedation in Intensive Care Patients Under Mechanical Ventilation
Official title: Prevention of Oversedation in Intensive Care Patients Under Mechanical Ventilation : the AWARE Multicentric Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: ICU Patients Requiring Invasive Mechanical Ventilation
Keywords: intensive care
mechanical ventilation
sedatives
morphinics
oversedation
mortality
midazolam
propofol
pain
agitation
Lead sponsor: French Society for Intensive Care
Sponsor class: OTHER
Collaborators: name: University Hospital, Tours
First posted: 2012-06-12
Enrollment: 1180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Day-90 mortality
timeFrame: Mortality at Day 90 after randomization
Secondary outcomes:
measure: Mortality at Day 28
timeFrame: at day 28
measure: Hospital mortality
timeFrame: at hospital discharge, up to day 90
measure: 1-yr mortality
timeFrame: at 1 yr
measure: Mechanical ventilation duration
timeFrame: From onset of mechanical ventilation to day 28
measure: Days alive with no mechanical ventilation
timeFrame: From ICU admission up to day 28
measure: Occurence of ventilator-associated pneumonia
timeFrame: During mechanical ventilation duration, up to day 28
measure: Use of non-invasive ventilation after extubation
timeFrame: From extubation to ICU discharge up to day 28
measure: Duration of ICU stay
timeFrame: From ICU admission to ICU discharge or death in ICU, up to day 90
measure: ICU confusion
timeFrame: From Day 1 to 7, and at day 14, 21 and 28
measure: Proximal muscle weakness
timeFrame: from day 1 to 7, and at day 14, 21 and 28
measure: Functional, cognitive and psychological status
timeFrame: At day 90 and 1 year
measure: Time to weaning onset
timeFrame: Time from mechancial ventilation initiation to first spontaneous breathing trial, up to day 28
measure: Number of patients requiring tracheotomy
timeFrame: During ICU stay, up to day 28
measure: First sitting in chair
timeFrame: During ICU stay, up to day 28
Other outcomes:
Locations:
city: Agen
country: France
facility: Hôpital Saint-Esprit
city: Angers
country: France
facility: CHU d'Angers
city: Antony
country: France
facility: Hopital Privé d'Antony
city: Argenteuil
country: France
facility: CH d'Argenteuil
city: Beuvry
country: France
facility: CH Germon et Gauthier
city: Bobigny
country: France
facility: Hopital Avicenne
city: Bordeaux
country: France
facility: Hopital St-Andre
city: Boulogne Billancourt
country: France
facility: Hopital Ambroise Pare
city: Brest
country: France
facility: CHRU de la Cavale Blanche
city: Clamart
country: France
facility: Hopital Antoine Beclere
city: Corbeil-Essones
country: France
facility: CH Sud Francilien
city: Creteil
country: France
facility: CHU Henri Mondor
city: Garches
country: France
facility: Hopital Raymond Poincare
city: la Roche sur Yon
country: France
facility: CHD Les Oudairies
city: Le Chesnay
country: France
facility: CH de Versailles
city: Le Kremelin-Bicetre
country: France
facility: CHU Kremlin-Bicetre
city: Lille
country: France
facility: Hopital Roger Salengro
city: Lyon
country: France
facility: CH St-Joseph St-Luc
city: Lyon
country: France
facility: Groupe Hospitalier Edouard Herriot
city: Marseilles
country: France
facility: CHU Marseille Hopital Nord
city: Marseille
country: France
facility: Hopital de la Timone
city: Meaux
country: France
facility: CH de Meaux
city: Metz
country: France
facility: Hopital Notre-Dame de Bon Secours
city: Monaco
country: France
facility: CH Princesse Grace
city: Montfermeil
country: France
facility: GHIRM
city: Nantes
country: France
facility: Hopital Laennec
city: Nice
country: France
facility: Hopital l'Archet
city: Orléans
country: France
facility: CHR d'Orléans Hopital la Source
city: Paris
country: France
facility: Hopital St Louis
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Paris
country: France
facility: Hopital Tenon
city: Pau
country: France
facility: CH Francois Miterrand
city: Poissy
country: France
facility: CH Poissy
city: Pontoise
country: France
facility: CH de Pontoise
city: Pringy
country: France
facility: CH de la Région d'Annecy
city: Provins
country: France
facility: CH Leon Binet
city: St-Brieuc
country: France
facility: CH de St-Brieuc
city: St-Denis
country: France
facility: Hopital Delafontaine
city: St-Malo
country: France
facility: CH de St-Malo
city: St-Mande
country: France
facility: HIA Béjin
city: Tours
country: France
facility: CHRU Bretonneau
city: Valenciennes
country: France
facility: Hopital Jean Bernard
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: French Society of Intensive Care
name: Bernard DE JONGHE, MD
role: STUDY_CHAIR
References:
citation: Payen JF, Chanques G, Mantz J, Hercule C, Auriant I, Leguillou JL, Binhas M, Genty C, Rolland C, Bosson JL. Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology. 2007 Apr;106(4):687-95; quiz 891-2. doi: 10.1097/01.anes.0000264747.09017.da.
citation: Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G. The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest. 1998 Aug;114(2):541-8. doi: 10.1378/chest.114.2.541.
citation: Constantin JM, Chanques G, De Jonghe B, Sanchez P, Mantz J, Payen JF, Sztark F, Richebe P, Lagneau F, Capdevila X, Bazin JE, Lefrant JY. [Current use of sedation and analgesia: 218 resuscitations in France services practices survey]. Ann Fr Anesth Reanim. 2010 May;29(5):339-46. doi: 10.1016/j.annfar.2010.01.014. Epub 2010 Apr 13. French.
citation: Brook AD, Ahrens TS, Schaiff R, Prentice D, Sherman G, Shannon W, Kollef MH. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med. 1999 Dec;27(12):2609-15. doi: 10.1097/00003246-199912000-00001.
citation: De Jonghe B, Bastuji-Garin S, Fangio P, Lacherade JC, Jabot J, Appere-De-Vecchi C, Rocha N, Outin H. Sedation algorithm in critically ill patients without acute brain injury. Crit Care Med. 2005 Jan;33(1):120-7. doi: 10.1097/01.ccm.0000150268.04228.68.
citation: Quenot JP, Ladoire S, Devoucoux F, Doise JM, Cailliod R, Cunin N, Aube H, Blettery B, Charles PE. Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia. Crit Care Med. 2007 Sep;35(9):2031-6. doi: 10.1097/01.ccm.0000282733.83089.4d.
citation: Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000 May 18;342(20):1471-7. doi: 10.1056/NEJM200005183422002.
citation: Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010 Feb 6;375(9713):475-80. doi: 10.1016/S0140-6736(09)62072-9. Epub 2010 Jan 29.
citation: Treggiari MM, Romand JA, Yanez ND, Deem SA, Goldberg J, Hudson L, Heidegger CP, Weiss NS. Randomized trial of light versus deep sedation on mental health after critical illness. Crit Care Med. 2009 Sep;37(9):2527-34. doi: 10.1097/CCM.0b013e3181a5689f.
citation: Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753.
citation: SRLF Trial Group. Impact of oversedation prevention in ventilated critically ill patients: a randomized trial-the AWARE study. Ann Intensive Care. 2018 Sep 21;8(1):93. doi: 10.1186/s13613-018-0425-3.