Clinical trial NCT04341350: Comparison of an Inhaled Sedation Strategy to an Intravenous Sedation Strategy in Intensive Care Unit Patients Treated With Invasive Mechanical Ventilation
Official title: Comparison of an Inhaled Sedation Strategy to an Intravenous Sedation Strategy in Intensive Care Unit Patients Treated With Invasive Mechanical Ventilation : INASED Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Prevention of Delirium
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
First posted: 2020-04-10
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study is to determine the impact on the frequency of occurrence of delirium of an early inhaled sedation strategy (from induction in rapid sequence if intubation in intensive care, or from admission if intubated in pre -hospital) by Isoflurane using an ANACONDA ™ type system, compared to a conventional intravenous sedation strategy.

Detailed description: Sedation-analgesia is used in most patients treated with mechanical ventilation (MV). The usual benzodiazepine and morphine sedation reduces pain and anxiety and allows tolerance of invasive procedures in intensive care. These molecules, used as part of the sedation titration protocol or the daily sedation stop protocol, have improved patient outcomes.

Although necessary, these drugs, by mechanisms still uncertain, would promote the occurrence of resuscitation delirium. Delirium itself responsible for worsening morbidity and mortality (increase in the duration of MV, increase in the length of hospital stay, discussed increase in mortality, long-term cognitive sequelae).

This finding favored the use of new drugs in the sedation strategies of patients on MV. Dexmedetomidine has for example reduced the number of days of delirium, the number of days of coma and even mortality in septic patients. Its large-scale use has however been questioned by a recent study.

Halogenated gases have been used for a long time in anesthesia. Their pharmacodynamics, their positive and adverse effects, their therapeutic margins are well known. Thanks to technical innovations they can be used on resuscitation respirators. Several studies on targeted populations have shown the feasibility and the benefits of this use, in particular, the absence of accumulation, the absence of tachyphylaxis, the broad therapeutic range, the small interindividual variation, the rapidity of efficacy and the speed of awakening. Safety in use for the staff in charge of the patient is established. In addition, their potential neuroprotective effect would make it an anesthetic of choice in the prevention of resuscitation delirium.

Eligibility criteria: Inclusion Criteria:

* Patient aged 18 and over
* Patient requiring mechanical ventilation for at least 24 hours
* The patient requires continuous and immediate sedation for more comfort, safety and to facilitate the administration of survival measures.
* Consent obtained from patient or relative

Exclusion Criteria:

Patient hospitalized for the following reasons for admission:

* Cardiac arrest
* State of refractory epilepticus
* Head trauma
* Stroke

  * Hearing, visual or aphasia disorders before inclusion making it impossible to take the CAM-ICU
  * Sedation started more than 24 hours ago
  * Impairment of cognitive functions and / or dementia
  * Contraindication to halogenated gases (personal or family history of malignant hyperthermia, acute or chronic neuromuscular disease, hepatocellular insufficiency with PT \<30%)
  * Severe acute respiratory distress syndrome (ARDS) (Berlin criteria: PaO2 / FiO2 \<100 after ventilatory optimisation))
  * PaCO2 at inclusion\> 50 mmHg after ventilatory optimisation
  * Patient for whom a procedure of "limitation of active therapies" is envisaged at inclusion
  * Patient under guardianship or curatorship
  * Minor patient
  * Pregnant or breastfeeding woman
  * Patient not affiliated to the social security scheme

Primary outcomes:
measure: Occurrence of a delirium in intensive care
timeFrame: 28 days
Secondary outcomes:
measure: Mortality in intensive care
timeFrame: Throuh exit from the intensive care unit, an average of 28 days
measure: Mortality at day 28
timeFrame: 28 days
measure: Hospital cost per patient
timeFrame: Through study completion, an average of 1 year.
measure: Number of days with vasopressors or inotropic agents
timeFrame: Throuh exit from the intensive care unit, an average of 28 days
measure: Number of days with sedation
timeFrame: Throuh exit from the intensive care unit, an average of 28 days
measure: Cumulative dose anesthetics drugs
timeFrame: Throuh exit from the intensive care unit, an average of 28 days
measure: Duration of anesthetics drugs
timeFrame: Throuh exit from the intensive care unit, an average of 28 days
measure: Maximum dose of vasopressors or inotropic agents
timeFrame: Throuh exit from the intensive care unit, an average of 28 days
measure: Ventilation free days at 28 days following randomisation
timeFrame: 28 days
measure: Incidence of delirium
timeFrame: 28 days
measure: Duration of delirium
timeFrame: 28 days
measure: Length of ICU stay
timeFrame: Throuh exit from the intensive care unit, an average of 28 days
measure: Requirement of patients physical restraints
timeFrame: Throuh exit from the intensive care unit, an average of 28 days
measure: Self aggressive act
timeFrame: Throuh exit from the intensive care unit, an average of 28 days
measure: Hetero-aggressive act
timeFrame: Throuh exit from the intensive care unit, an average of 28 days
measure: Evaluation of cognitive functions
timeFrame: Through study completion, an average of 1 year.
Other outcomes:
Locations:
city: Bourges
country: France
facility: CH Bourges
city: Brest
country: France
facility: CHU de Brest
city: Corbeil-Essonnes
country: France
facility: CH Corbeil Essonnes
city: Le Mans
country: France
facility: CH Le Mans
city: Lorient
country: France
facility: GHBS Lorient
city: Melun
country: France
facility: CH Melun
city: Montpellier
country: France
facility: CHU Montpellier
city: Morlaix
country: France
facility: CH Morlaix
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: CHU Rennes
city: Tours
country: France
facility: CHU Tours - Réanimation Chirurgicale
city: Tours
country: France
facility: CHU Tours
Study officials:
affiliation: CHRU Brest
name: Pierre Bailly, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bailly P, Egreteau PY, Ehrmann S, Thille AW, Guitton C, Grillet G, Reizine F, Huet O, Jaber S, Nowak E, L'her E. Inased (inhaled sedation in ICU) trial protocol: a multicentre randomised open-label trial. BMJ Open. 2021 Feb 19;11(2):e042284. doi: 10.1136/bmjopen-2020-042284.