Although early cooling after injury is considered to be beneficial, this is offset by the failure to show benefit from hypothermia in the absence of raised ICP. Enrolment to the Eurotherm3235Trial www.selleckchem.com/products/MG132.html will therefore be allowed for up to 72 hours following injury. This potential delay in cooling will be compensated for, to an extent, by inducing hypothermia with 20 to 30 mL/kg of refrigerated 0.9% saline given intravenously over the course of 30 minutes. No maximum duration of cooling is specified, and hypothermia will continue until ICP is no longer dependent on temperature reduction to remain below 20 mm Hg. Patients will then be slowly re-warmed at a rate of 0.25��C per hour (1��C/4 hours).Figure 2Stages of therapeutic management after traumatic brain injury.

These ‘stages’ have been developed for use in the Eurotherm3235Trial using evidence synthesis from the Brain Trauma Foundation [73] and the European Brain Injury Consortium [81]. CSF, cerebrospinal …The experience from previous hypothermia trials underscores the potential difficulties in using therapeutic hypothermia treatment for TBI. For this reason, and to reduce inter-centre variance, only centres experienced with the care of TBI patients and the use of hypothermia (after either cardiac arrest or TBI) will be initiated.ConclusionsMany potential neuro-protective pharmacological interventions have been tested and have failed to show benefit in TBI. Common reasons that have been cited include inadequate or low methodological quality preclinical studies and poor (and often underpowered) clinical study design.

Hypothermia has extensive preclinical data supporting clinical testing and generally meets the STAIR (Stroke Therapy Academic Industry Roundtable) recommendations [80]. The Eurotherm3235Trial will recruit 1,800 patients in 41 months and will be one of the largest TBI studies to date.AbbreviationsBBB: blood-brain barrier; CI: confidence interval; CNS: central nervous system; CT: computerised tomography; ICP: intracranial pressure; PKC: protein kinase C; RCT: randomised controlled trial; RR: relative risk; TBI: traumatic brain injury.Competing interestsHLS is a trial manager and PJDA is the chief investigator of the Eurotherm3235Trial http://www.eurotherm3235trial.eu.AcknowledgementsThis paper is a summary of the evidence that has supported the design of the Eurotherm3235Trial http://www.

eurotherm3235trial.eu, which is a large, multi-national, prospective, randomised controlled trial in patients with raised Cilengitide intracranial pressure after traumatic brain injury.
In a recent article for Critical Care, Bermejo-Martin and colleagues [1] describe Th1 and Th17 hypercytokinemia as an early signature host response to severe infection by the pandemic variant of the influenza virus (nvH1N1). The nvH1N1 infection is usually self-limiting in nature, but some patients develop severe symptoms requiring hospitalization [2].