Does untreated post-cardiac-arrest fever counteract the benefit of therapeutic hypothermia?

The debate on the influence of body temperature on morality and neurologic outcome of arrested patients has taken on reat significance since the recommendation in 2005 to lower core ody temperature to 32–34 ◦C as soon as possible after return of pontaneous circulation (ROSC).1 Therapeutic hypothermia (TH) hould become common practice in emergency medical services nd departments, though recent reviews2 point out that the level f evidence is still low and experts call for high-level clinical trials.3 In animal models it has been shown that hypothermia attenutes all cascades leading to neurological cell death after ischaemic vents. These include depression of electrical activity, reducion of metabolism and inhibition of the release of amino acids uch as glutamate,4 which promotes Ca2+ influx into neurons5 nd contributes to induction of apoptosis and cell death. During eperfusion, hypothermia attenuates oxidative stress6 and lipid eroxidation,7 which are also responsible for the induction of apotosis. From the physiological perspective there is good reason to ssume that if lower temperatures protect, higher temperatures ay harm the human organism. However, results are ambiguous egarding the effect of fever on outcome of arrested patients. The uestion, already posed by Cronberg and Nielsen in this journal,8 emains fundamental: does post-cardiac-arrest fever only reflect he severity of ischaemia and therefore act as a harmless prognotic indicator or does it have the potential to deteriorate existing rgan dysfunction and thus require treatment? Only few investigations have focused on post-ischaemic effects f fever. Animal experiments have demonstrated that the induction f high core body temperatures (e.g. by heat exposure or adminstration of pyretics) is detrimental after an ischaemic insult. For nstance in dogs, even a minimal rise in temperature of 1–2 ◦C esulted in substantial alterations in post-ischaemic neurologic unction and cerebral histopathology.9 In a rat model of forebrain schaemia, hyperthermia delayed by 24 h more than doubled the umber of ischaemic neurons,10 triggered chronic neurodegenertion in the penumbra zone11 and caused immunohistochemical eurodegeneration similar to that seen in Alzheimer’s disease.12 ut the effect of treatment of post-ischaemic fever has only been eported in one study using a rodent model. In this experiment he group with spontaneous fever after transient ischaemia was reated with antipyretics or external cooling and compared to the ntreated group. Suppression of fever markedly diminished neuonal damage in the neocortex and hippocampus.13 Thus, from xperimental studies it seems there is increasing reason to support hat fever after an ischaemic event may not be only a surrogate