Cooling after cardiac arrest—the longer the better?

Temperature plays a key role in the development of acute neurological injuries. Numerous animal experiments have convincingly demonstrated that temperature elevation (either spontaneous/infection related or induced by external warming) can significantly exacerbate all types of neurologic injury; in fact, the magnitude of fever-induced increase in injury is similar to the effects of severe hypoperfusion or severe hypoxia (1-4). This effect has been demonstrated in numerous animal models including rodents, cats, dogs, sheep, pigs, and primates, and in all types of neurologic injury (cardiac arrest, ischemic stroke, traumatic brain injury and haemorrhagic stroke). More than 40 observational studies have confirmed a link between temperature elevations and increased neurological damage and adverse outcome in various types of neurological injury (3-9). Some of these studies have shown that the effects of fever are dose-dependent, i.e., the greater the fever burden/time spent at high temperatures, the greater the extent of injury and likelihood of poor outcome (4-9). Such observations strongly suggest that the link is causal, i.e., fever is directly causing the additional injury. In these studies, the differences persist on multivariate analysis, and occur regardless of the presence of infection (i.e., are present both for infectious and non-infectious fever). Hyperthermia has also been linked to increased risk of complications such as haemorrhagic conversion in patients with ischemic stroke (6). Preliminary evidence suggests that controlling fever could improve neurological outcome (10), although there are as yet no conclusive data from randomized controlled trials (RCTs) proving this