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Comparison of an Inhaled Sedation Strategy to an Intravenous Sedation Strategy in Intensive Care Unit Patients Treated With Invasive Mechanical Ventilation

Phase 3
Recruiting
Conditions
Prevention of Delirium
Interventions
Registration Number
NCT04341350
Lead Sponsor
University Hospital, Brest
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
250
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Inhaled sedationIsoflurane + analgesic drugSedation by inhalation of halogenated gas (Isoflurane) delivered by the Anesthetic-Conserving Device (ACD) system ANACONDA ™ associated with the administration of an analgesic drug.
Usual sedationPropofol + analgesic drugSedation according to a written, standardized Nurse management protocol using at least one sedative drug (propofol) and one analgesic drug.
Primary Outcome Measures
NameTimeMethod
Occurrence of a delirium in intensive care28 days

Occurrence of delirium in intensive care will be observed (yes / no)

Secondary Outcome Measures
NameTimeMethod
Incidence of delirium28 days

Incidence of delirium will be observed

Mortality in intensive careThrouh exit from the intensive care unit, an average of 28 days

Mortality in intensive care will be observed

Mortality at day 2828 days

Mortality at day 28 will be observed

Hospital cost per patientThrough study completion, an average of 1 year.

The average cost of hospitalization for each patient will be calculated taking into account their length of hospital stay, examinations carried out and medical treatment taken.

Number of days with vasopressors or inotropic agentsThrouh exit from the intensive care unit, an average of 28 days

Number of days with vasopressors or inotropic agents will be observed

Duration of delirium28 days

Duration of delirium will be observed

Requirement of patients physical restraintsThrouh exit from the intensive care unit, an average of 28 days

Requirement of physical restraints, of patients with unplanned extubation, unplanned catheter, urinary probe or gastric probe removal will be observed

Duration of anesthetics drugsThrouh exit from the intensive care unit, an average of 28 days

Duration of anesthetics drugs will be observed

Length of ICU stayThrouh exit from the intensive care unit, an average of 28 days

Length of ICU stay will be calculated

Hetero-aggressive actThrouh exit from the intensive care unit, an average of 28 days

Hetero-aggressive act will be observed

Number of days with sedationThrouh exit from the intensive care unit, an average of 28 days

Number of days with sedation will be observed

Cumulative dose anesthetics drugsThrouh exit from the intensive care unit, an average of 28 days

Cumulative dose anesthetics drugs will be observed

Maximum dose of vasopressors or inotropic agentsThrouh exit from the intensive care unit, an average of 28 days

Maximum dose of vasopressors or inotropic agents will be observed

Ventilation free days at 28 days following randomisation28 days

Ventilation free days at 28 days following randomisation will be observed

Self aggressive actThrouh exit from the intensive care unit, an average of 28 days

Self aggressive act will be observed

Evaluation of cognitive functionsThrough study completion, an average of 1 year.

Cognitive function will be evaluated at discharge, 3- and 12 months using two kinds of score :

* Cantab test, combining 6 cognitive evaluations with an iPad during a 45-60 minutes medical consultation

* PCLS (Posttraumatic stress disorder Checklist Scale), HADS (Hospital Anxiety and Depression scale), SF36 (medical outcome study short form 36), IADL (instrumental activities of daily living) practised by a clinical research associate

Trial Locations

Locations (12)

CH Melun

🇫🇷

Melun, France

CHU de Brest

🇫🇷

Brest, France

CH Bourges

🇫🇷

Bourges, France

CHU Poitiers

🇫🇷

Poitiers, France

CHU Rennes

🇫🇷

Rennes, France

CH Corbeil Essonnes

🇫🇷

Corbeil-Essonnes, France

CH Le Mans

🇫🇷

Le Mans, France

GHBS Lorient

🇫🇷

Lorient, France

CHU Montpellier

🇫🇷

Montpellier, France

CH Morlaix

🇫🇷

Morlaix, France

CHU Tours - Réanimation Chirurgicale

🇫🇷

Tours, France

CHU Tours

🇫🇷

Tours, France

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