RECRUITINGINTERVENTIONAL

Evaluation of the Safety of Inhaled Sedation With Isoflurane in Head Trauma Patients

Evaluation of the Safety of Inhaled Sedation With Isoflurane in Patients With Severe Traumatic Brain Injury

About This Trial

Intensive care management of patient with severe traumatic brain injury (TBI) includes deep and prolonged sedation with intravenous hypnotics (propofol, midazolam, ketamine) in combination with opioids to prevent and/or treat episodes of intracranial hypertension. However, some patients may develop tachyphylaxis with a gradual increase of administered intravenous hypnotics and opioids to maintain the same level of sedation. This situation leads to a failure in controlling intracranial pressure (ICP) and/or to the risk of adverse effects due to high-dose sedatives: haemodynamic instability, prolonged mechanical ventilation, neuromyopathy, delirium, withdrawal syndrome. Halogenated agents (Isoflurane, Sevoflurane) are a class of hypnotics routinely used in the operating room. However, doses used in surgical patients (\> 1 Minimal Alveolar Concentration, MAC) are not suitable in neuro-intensive care unit (ICU) patients at risk of intracranial hypertension because of the cerebral vasodilator effects of halogenated agents at this dosage, hence the risk of high ICP and compromised cerebral perfusion pressure. The use of halogenated agents has been recently possible in the ICU through dedicated medical devices (Sedaconda ACD, Mirus). Recommended dosage are lower in the ICU, i.e. 0.3-0.7 MAC, because of their association with intravenous hypnotics and the absence of surgical stimuli. Several clinical studies in general ICUs showed improved sedation quality, reduced duration of mechanical ventilation, faster arousal and shorter extubation time, and lower costs in halogenated group compared with control group receiving midazolam or propofol. At low doses, the effects on ICP and intracerebral haemodynamics of halogenated agents are minor according to the available literature. In addition, beneficial effects were found on cerebral ischaemic volume in animal models treated with halogenated agents. However, there is a need to explore the benefit-risk ratio of the use of halogenated agents in the severe TBI population. The investigator hypothesise that 0.7 MAC Isoflurane can be administered in this population without deleterious effect on ICP.

Who May Be Eligible (Plain English)

Who May Qualify: - Patient \> 18 years old - Hospitalized in surgical intensive care (CPR and RNC) for severe head trauma - On intravenous hypnotic therapy for at least 24 hours with at least 2 lines of IV hypnotics and requiring continued sedation for at least 24 hours, with a RASS of between -3 and -5 - Initial ICP \< 15 mmHg on introduction of isoflurane - Functional intracranial pressure sensor - Transcranial Doppler measurements performed within 24 hours - Written willing to sign a consent form from a legal representative/relative/trusted person. In the absence of a legal representative, the patient may be included under the emergency procedure. Who Should NOT Join This Trial: - Patients who have had a decompressive craniectomy - Patients with a personal or family history of malignant hyperthermia - Patients with a history of long QT syndrome - Patients taking MAOI-type antidepressants (iproniazid (MARSILID) and moclobemide (MOCLAMIDE)) - Patients with known hypersensitivity to isoflurane or other volatile halogenated anaesthetic agents - Patients who have experienced liver damage, jaundice, unexplained fever, or eosinophilia after administration of a halogenated anaesthetic. - Patients expected to die within the next 24 hours - Subject in a period of exclusion from another clinical trial, - Technical unavailability of the inhaler - Persons covered by articles L1121-5 to L1121-8 of the CSP (corresponding to all protected persons: pregnant women, women in childbirth, nursing mothers, persons deprived of their liberty by judicial or administrative decision, persons subject to a legal protection measure). - No European social security Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Patient \> 18 years old * Hospitalized in surgical intensive care (CPR and RNC) for severe head trauma * On intravenous hypnotic therapy for at least 24 hours with at least 2 lines of IV hypnotics and requiring continued sedation for at least 24 hours, with a RASS of between -3 and -5 * Initial ICP \< 15 mmHg on introduction of isoflurane * Functional intracranial pressure sensor * Transcranial Doppler measurements performed within 24 hours * Written informed consent from a legal representative/relative/trusted person. In the absence of a legal representative, the patient may be included under the emergency procedure. Exclusion Criteria: * Patients who have had a decompressive craniectomy * Patients with a personal or family history of malignant hyperthermia * Patients with a history of long QT syndrome * Patients taking MAOI-type antidepressants (iproniazid (MARSILID) and moclobemide (MOCLAMIDE)) * Patients with known hypersensitivity to isoflurane or other volatile halogenated anaesthetic agents * Patients who have experienced liver damage, jaundice, unexplained fever, or eosinophilia after administration of a halogenated anaesthetic. * Patients expected to die within the next 24 hours * Subject in a period of exclusion from another clinical trial, * Technical unavailability of the inhaler * Persons covered by articles L1121-5 to L1121-8 of the CSP (corresponding to all protected persons: pregnant women, women in childbirth, nursing mothers, persons deprived of their liberty by judicial or administrative decision, persons subject to a legal protection measure). * No European social security

Treatments Being Tested

DRUG

Isoflurane

Inclusions will have 4 phases according to gradual increased doses of isoflurane: Phase 1: Inclusion of 3 patients with 0.3 MAC isoflurane. In the absence of an increase of ICP \> 20% from baseline, inhaled sedation is maintained for 24 hours until the primary endpoint is assessed. If there one patient who does not tolerate this threshold, three additional patients will be included in this phase. A maximum of one treatment failure (see definition below) is tolerated in the phase 1 Phase 2: Inclusion of 3 additional patients with isoflurane dosage of 0.5 MAC under the same conditions as phase 1. Phase 3: Inclusion of 3 additional patients with isoflurane dosage of 0.7 MAC under the same conditions as phases 1 and 2. Phase 4: Inclusion of 12-15 additional patients will be included at the 0.7 MAC dose, to have 18 patients exposed to 0.7 MAC isoflurane.

Locations (1)

University Hospital Grenoble

Grenoble, Choisir Une Région, France