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

Regional University Hospital Center (CHRU)

Status and phase: Enrolling; Phase 3

Conditions: Prevention of Delirium

Treatments: Drug: Propofol + analgesic drug; Drug: Isoflurane + analgesic drug

Study type: Interventional

Funder types: Other

Identifiers

NCT04341350

INASED (29BRC19.0280)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 250 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

250 participants in 2 patient groups

Usual sedation

Active Comparator group

Description:

Sedation according to a written, standardized Nurse management protocol using at least one sedative drug (propofol) and one analgesic drug.

Treatment:

Drug: Propofol + analgesic drug

Inhaled sedation

Experimental group

Description:

Sedation by inhalation of halogenated gas (Isoflurane) delivered by the Anesthetic-Conserving Device (ACD) system ANACONDA ™ associated with the administration of an analgesic drug.

Treatment:

Drug: Isoflurane + analgesic drug