Brain injury: the pathophysiology of the first hours.'Talk and Die revisited'

In the 25 years since the 'Talk and Die' paper there have been substantial advances in the management of patients with severe closed head injury. This paper discusses developments in understanding of primary and secondary injury. Current management focuses on preventing secondary brain injury. That this has been successful is illustrated by a fall in mortality in recent decades. Evidence based guidelines have set standards of management but they do not take into account variations between individuals, between regions of the brain and variations with time from injury. Various monitoring techniques such as transcranial doppler, jugular venous oxygen saturation and ICP waveform analysis attempt to set individual therapeutic endpoints and to target therapy appropriately. Primary injury is no longer seen as a single irreversible event occurring at the time of impact, but rather as a process initiated by the impact and evolving over subsequent hours and days. Experimental studies have identified agents which reduce the evolution of brain injury and improve outcome. An experimental model of brain injury developed by the Adelaide He ad Injury Group identifies diffuse axonal injury as a target for therapeutic manipulation. Magnesium has been shown in other studies to improve outcome after diffuse brain injury. This has now been linked with upregulation of beta amyloid precursor prote in. Although this and several other experimental therapies have shown great promise, they have not so far produced benefit in large clinical studies. Avoiding secondary insults will remain the goal of management for the foreseeable future. Halting the evolution of the primary injury remains a highly sought after goal. Although elusive so far, it is likely to be the next major advance in clinical care.