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

Intensive care management of patients with severe neurological injury regularly involves deep and prolonged sedation with intravenous hypnotics (propofol, midazolam, ketamine) in combination with morphine, with the aim of preventing and/or treating episodes of intracranial hypertension (ICHT). However, the tachyphylaxis associated with intravenous hypnotics requires a continuous increase in the doses administered to maintain the same level of sedation, or even a combination of several pharmacological classes. This progressive tolerance to hypnotics may result in the failure of the sedation strategy for certain neuro-injured patients and/or expose them to the undesirable effects of high doses of intravenous hypnotics: haemodynamic instability, longer periods of mechanical ventilation, neuromyopathy, mental confusion and withdrawal syndrome.

Inhaled halogens are a class of hypnotics used daily in the operating theatre to maintain anaesthesia. At the doses used in anaesthesia (> 1 MAC - Minimal Alveolar Concentration), they are contraindicated in neuro-injured patients at risk of HTIC because of their cerebral vasodilatory effects, which can lead to an increase in intracranial pressure (ICP) and compromise cerebral perfusion. Halogens (Isoflurane, Sevoflurane) can be used in intensive care with appropriate medical devices (Isoconda, Mirus). They are used at more moderate doses (< 1 MAC) because they are combined with intravenous hypnotics and because there is no surgical stimulus. Several clinical studies in general intensive care have shown improved sedation quality, reduced duration of mechanical ventilation, quicker awakening and shorter time to tracheal extubation, and lower costs in the group treated with a halogenated agent compared with the control group receiving midazolam or propofol. At these low concentrations, the effects on ICP and intracerebral haemodynamics are much less marked, according to the studies published on this subject. In addition, beneficial effects on the volume of cerebral ischaemia have been shown in animal models treated with halogenated agents. However, there is a need for a precise study of the benefit-risk ratio of using halogenated agents in neurological patients.

The Anaesthesia and Intensive Care Unit at the CHUGA has been internationally recognised for many years in the management of sedation-analgesia in intensive care. In connection with this, the experience acquired by the CHUGA's neuro-resuscitation unit in brain monitoring will be used to explore in detail the effects of halogenated agents on intracerebral haemodynamics and intracranial pressure.

the investigator hypothesise that the administration of Isoflurane at 0.7 MAC can be used in this population without deleterious effect on ICP.

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