Neuroprotective effect of therapeutic hypothermia versus standard care alone after convulsive status epilepticus: protocol of the multicentre randomised controlled trial HYBERNATUS.
Convulsive status epilepticus (CSE) is a major medical emergency associated with a 50 % morbidity rate. CSE guidelines have recommended prompt management for many years, but there is no evidence to date that they have significantly improved practices or outcomes. Developing neuroprotective strategies for use after CSE holds promise for diminishing morbidity and mortality rates. Hypothermia has been shown to afford neuroprotection in various health conditions. We therefore designed a trial to determine whether 90-day outcomes in mechanically ventilated patients with CSE requiring management in the intensive care unit (ICU) are improved by early therapeutic hypothermia (32-34 °C) for 24 h with propofol sedation. We are conducting a multicentre, open-label, parallel-group, randomised, controlled trial (HYBERNATUS) of potential neuroprotective effects of therapeutic hypothermia and routine propofol sedation started within 8 h after CSE onset in ICU patients requiring mechanical ventilation. Included patients are allocated to receive therapeutic hypothermia (32-34 °C) plus standard care or standard care alone. We plan to enrol 270 patients in 11 ICUs. An interim analysis is scheduled after the inclusion of 135 patients. The main study objective is to evaluate the effectiveness of therapeutic hypothermia (32-34 °C) for 24 h in diminishing 90-day morbidity and mortality (defined as a Glasgow Outcome Scale score <5). The HYBERNATUS trial is expected to a decreased proportion of patients with a Glasgow Outcome Scale score lower than 5 after CSE requiring ICU admission and mechanical ventilation. Trial registration Clinicaltrials.gov identifier NCT01359332 (registered on 23 May 2011).
Medical-Surgical Intensive Care Unit, Centre Hospitalier de Versailles - Site André Mignot, 177 rue de Versailles, 78150, Le Chesnay Cedex, France. slegriel@ch-versailles.fr.|INSERM U970 (Team 4), Paris Cardiovascular Research Center, Paris, France. slegriel@ch-versailles.fr.
Stephane
S
Legriel
Neurology and Stroke Department, Centre Hospitalier de Versailles - Site André Mignot, 177 rue de Versailles, 78150, Le Chesnay Cedex, France.
Fernando
F
Pico
Neurophysiology Department, Hôpital Lariboisière, AP-HP, 2 rue Ambroise Paré, 75010, Paris, France.
Yves-Roger
YR
Tran-Dinh
Medical Intensive Care Unit, Saint Louis University Hospital, AP-HP, Paris, France.
Virginie
V
Lemiale
Medical-Surgical Intensive Care Unit, Centre Hospitalier de Versailles - Site André Mignot, 177 rue de Versailles, 78150, Le Chesnay Cedex, France.
Jean-Pierre
JP
Bedos
SBIM Biostatistics and Medical information, Hôpital Saint-Louis, APHP, 1 avenue Claude Vellefaux, Paris, France.|Université Paris Diderot, Paris, France.|ECSTRA Team (Epidémiologie Clinique et Statistiques pour la Recherche en Santé), UMR 1153 INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Matthieu
M
Resche-Rigon
INSERM U970 (Team 4), Paris Cardiovascular Research Center, Paris, France.|Medical Intensive Care Unit, Cochin University Hospital, Hopitaux Universitaires-Paris Centre, AP-HP, Paris, France.|Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France.
Alain
A
Cariou
Intensive care unit; Outcome; Randomised controlled trial; Status epilepticus; Therapeutic hypothermia