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

Recruiting now · Not applicable

Conditions studied: Traumatic Brain Injury

In brief

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.

Key facts

Study ID: NCT06311604
Run by: University Hospital, Grenoble
People needed: 30
Starts: 2024-06-20
Expected to finish: 2027-03-20
Last updated by the study team: 2024-07-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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.

You may not qualify if…

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

Where it is running

University Hospital Grenoble — Grenoble, Choisir Une Région, France (enrolling)

Full record on ClinicalTrials.gov

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