Feasibility of hypothermia beyond 3 weeks in severe ischemic stroke: an open pilot study using γ-hydroxybutyrate

Hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of very prolonged moderate hypothermia for severe acute ischemic stroke.

Moderate hypothermia was induced within 24h after a severe ischemic stroke involving the middle cerebral artery. Hypothermia, with cooling blankets, reduced body-core temperature to 32-33°C, and was prolonged for up to 22 days until cerebral edema had significantly decreased (assessed by serial cerebral computed tomography) before slow rewarming (<1.5°C/day). Patients were mechanically ventilated and sedated with gamma-hydroxybutyrate (GHB), a naturally occurring metabolite of gamma-aminobutyric acid (GABA), which acts on the GABA(B) receptors. Outcomes and side effects at 12 months were recorded.

Nineteen patients (mean age: 52.6 years, mean National Institute of Health Stroke Scale (NIHSS) score 21) were enrolled. Cooling was achieved in all patients. The mean time to reach target temperature was 11.4 ± 8.6h and the mean duration of rewarming was 4.0 ± 1.1 days. For the 10 survivors (53%), the mean duration of hypothermia and rewarming was 22.6 ± 4.9 days. Five patients underwent a hemicraniectomy. All patients presented with hypotension, bradycardia, and hematological side effects. Eight patients had pneumonia (42%). At 12 months, the mean NIHSS score was 8.3 ± 2.7, the Barthel Index was 67 ± 18, and the modified Rankin scale was 3.2 ± 0.9.

This study shows the feasibility of very prolonged hypothermia beyond 3 weeks using GHB sedation in severe hemispheric infarcts.