title: Feasibility of hypothermia beyond 3 weeks in severe ischemic stroke: an open pilot study using γ-hydroxybutyrate.
abstract: OBJECTIVE
  Hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of very prolonged moderate hypothermia for severe acute ischemic stroke.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  This study shows the feasibility of very prolonged hypothermia beyond 3 weeks using GHB sedation in severe hemispheric infarcts.
authors.affiliation: Département de Neurologie, Hôpital Gui de Chauliac, 80 avenue Augustin Fliche, 34295 Montpellier Cedex 5, France. i-mourand@chu-montpellier.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mourand
authors.forename: Edmond
authors.initials: E
authors.lastname: Escuret
authors.forename: Chérif
authors.initials: C
authors.lastname: Héroum
authors.forename: Olivier
authors.initials: O
authors.lastname: Jonquet
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Picot
authors.forename: Grégoire
authors.initials: G
authors.lastname: Mercier
authors.forename: Didier
authors.initials: D
authors.lastname: Milhaud
mesh_terms: D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015331:Cohort Studies; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods / Q000639:trends*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012720:Severity of Illness Index; D012978:Sodium Oxybate / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D013997:Time Factors
chemical_list: D012978:Sodium Oxybate