Clinical trials in head injury.
Secondary brain damage, following severe head injury is considered to be a major cause for bad outcome. Impressive reductions of the extent of brain damage in experimental studies have raised high expectations for cerebral neuroprotective treatment, in the clinic. Therefore multiple compounds were and are being evaluated in trials. In this review we discuss the pathomechanisms of traumatic brain damage, based upon their clinical importance. The role of hypothermia, mannitol, barbiturates, steroids, free radical scavengers, arachidonic acid inhibitors, calcium channel blockers, N-methyl-D-aspartate (NMDA) antagonists, and potassium channel blockers, will be discussed. The importance of a uniform strategic approach for evaluation of potentially interesting new compounds in clinical trials, to ameliorate outcome in patients with severe head injury, is proposed. To achieve this goal, two nonprofit organizations were founded: the European Brain Injury Consortium (EBIC) and the American Brain Injury Consortium (ABIC). Their aim lies in conducting better clinical trials, which incorporate lessons learned from previous trials, such that the succession of negative, or incomplete studies, as performed in previous years, will cease.
Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0631, USA.
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Bullock
D016718:Arachidonic Acid / Q000037:antagonists & inhibitors; D001463:Barbiturates / Q000627:therapeutic use; D001921:Brain / Q000098:blood supply*; D002545:Brain Ischemia / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006259:Craniocerebral Trauma / Q000150:complications* / Q000175:diagnosis; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods; D015601:Injury Severity Score; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D013256:Steroids / Q000627:therapeutic use
D001463:Barbiturates; D002121:Calcium Channel Blockers; D016166:Free Radical Scavengers; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D013256:Steroids; D016718:Arachidonic Acid; D016202:N-Methylaspartate