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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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 : INASED Study

Conditions
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Prevention of Delirium

Intervention / Treatment
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* Drug: Propofol + analgesic drug
* Drug: Isoflurane + analgesic drug


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual sedation<br>Sedation according to a written, standardized Nurse management protocol using at least one sedative drug (propofol) and one analgesic drug. | Drug: Propofol + analgesic drug<br>* sedation according to a written, standardized Nurse management protocol using at least one sedative drug (propofol) and one analgesic drug. It uses the nurse driven analgesia protocol of each ward involved in the study. It uses a pain assessment score (BPS, VICOMORE, FLACC), local or regional anesthesia, non-opioïd adjuncts (acetaminophen, NSAIDs, nefopam), opioïds (per os opioïds, bolus of sufentanyl followed by continuous infusion if necessary, continuous infusion of remifentanyl<br>|
| Experimental: Inhaled sedation<br>Sedation by inhalation of halogenated gas (Isoflurane) delivered by the Anesthetic-Conserving Device (ACD) system ANACONDA ™ associated with the administration of an analgesic drug. | Drug: Isoflurane + analgesic drug<br>* sedation by inhalation of halogenated gas (Isoflurane) delivered by the Anesthetic-Conserving Device (ACD) system ANACONDA ™ associated with the administration of a analgesic drug. It uses the nurse driven analgesia protocol of each ward involved in the study. It uses a pain assessment score (BPS, VICOMORE, FLACC), local or regional anesthesia, non-opioïd adjuncts (acetaminophen, NSAIDs, nefopam), opioïds (per os opioïds, bolus of sufentanyl followed by continuous infusion if necessary, continuous infusion of remifentanyl.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of a delirium in intensive care | Occurrence of delirium in intensive care will be observed (yes / no) | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality in intensive care | Mortality in intensive care will be observed | Throuh exit from the intensive care unit, an average of 28 days | 
| Mortality at day 28 | Mortality at day 28 will be observed | 28 days | 
| Hospital cost per patient | 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. | Through study completion, an average of 1 year. | 
| Number of days with vasopressors or inotropic agents | Number of days with vasopressors or inotropic agents will be observed | Throuh exit from the intensive care unit, an average of 28 days | 
| Number of days with sedation | Number of days with sedation will be observed | Throuh exit from the intensive care unit, an average of 28 days | 
| Cumulative dose anesthetics drugs | Cumulative dose anesthetics drugs will be observed | Throuh exit from the intensive care unit, an average of 28 days | 
| Duration of anesthetics drugs | Duration of anesthetics drugs will be observed | Throuh exit from the intensive care unit, an average of 28 days | 
| Maximum dose of vasopressors or inotropic agents | Maximum dose of vasopressors or inotropic agents will be observed | Throuh exit from the intensive care unit, an average of 28 days | 
| Ventilation free days at 28 days following randomisation | Ventilation free days at 28 days following randomisation will be observed | 28 days | 
| Incidence of delirium | Incidence of delirium will be observed | 28 days | 
| Duration of delirium | Duration of delirium will be observed | 28 days | 
| Length of ICU stay | Length of ICU stay will be calculated | Throuh exit from the intensive care unit, an average of 28 days | 
| Requirement of patients physical restraints | Requirement of physical restraints, of patients with unplanned extubation, unplanned catheter, urinary probe or gastric probe removal will be observed | Throuh exit from the intensive care unit, an average of 28 days | 
| Self aggressive act | Self aggressive act will be observed | Throuh exit from the intensive care unit, an average of 28 days | 
| Hetero-aggressive act | Hetero-aggressive act will be observed | Throuh exit from the intensive care unit, an average of 28 days | 
| Evaluation of cognitive functions | 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 | Through study completion, an average of 1 year. |