Permissive Hyperthermia in Acute Brain Injury

Background Fever is common in patients with acute brain injury and is routinely suppressed despite limited evidence from randomized trials demonstrating benefit. Observational studies associate hyperthermia with worse outcomes, but it remains unclear whether fever is causative or reflects injury severity. Experimental and clinical data suggest that temperature reduction may adversely affect cerebral perfusion pressure and brain tissue oxygenation. This pilot study evaluates the feasibility and safety of permissive hyperthermia compared with standard normothermic care in neurocritical patients with severe acute brain injury.

Methods The investigators conduct a prospective, randomized, open-label pilot study in a neurointensive care unit. Twenty adult patients with severe acute brain injury requiring mechanical ventilation, sedation, and intracranial pressure monitoring are randomized 1:1 to permissive hyperthermia or standard care. In the intervention group, fever is tolerated up to 39.5°C, whereas the control group receives active temperature control from 37.5°C according to current practice. All patients are monitored using a multimodal intracranial system enabling continuous intracranial pressure and brain tissue oxygen tension measurement, cerebral microdialysis, and transcranial Doppler ultrasonography. Primary outcome is feasibility, defined by the need for temperature-lowering interventions due to refractory intracranial hypertension. Secondary outcomes include intracranial pressure, cerebral perfusion pressure, brain tissue oxygenation, cerebral metabolism, vasopressor requirements, length of stay, and functional status.

Results This is an ongoing pilot study. Recruitment feasibility, protocol adherence, and safety outcomes will be reported. Interim safety analysis is planned after inclusion of 10 patients.

Conclusions This pilot study will provide essential feasibility and safety data on permissive hyperthermia in severe acute brain injury. The results will inform the design of a future multicenter study.

Inclusion criteria

• Severe acute brain injury.
• Requirement for:

Mechanical ventilation Sedation Intracranial pressure (ICP) monitoring

Exclusion criteria

• Pregnancy
• Moribund patients or patients in whom withdrawal of active treatment is anticipated