Induced hypothermia after cardiac arrest

Sammanfattning: This thesis is based on studies of the clinical use of induced hypothermia as an intervention to reduce mortality and neurological impairment after cardiac arrest. After the publication of two trials indicating benefit of induced hypothermia, we developed a registry to assess outcome, possible adverse events and conduct of induced hypothermia when this intervention was implemented in a clinical population of cardiac arrest patients. Approximately half of the patients admitted to intensive care after out-of-hospital cardiac arrest survive and few patients have severe residual neurological impairment. The timing of hypothermia (early versus late induction of hypothermia and achievement of target temperature) was not associated to outcome. Adverse events were common, but only sustained hyperglycaemia and anticonvulsants administered for seizures were associated with increased mortality. Bleeding and infections were more common for patients having invasive procedures performed, but these adverse events were not associated with increased mortality. In a study of biomarkers of brain damage, neuron specific enolase was superior to S-100B as a predictor of a poor outcome. In a systematic review with meta-analyses and trial sequential analyses we conclude that the accumulated evidence for induced hypothermia is associated with substantial risks of systematic errors and the quality of the evidence is low. Trial sequential analyses indicate that the required information size to establish firm conclusions is not yet reached. Thus, we still do not know if induced hypothermia is beneficial, neutral or harmful for cardiac arrest patients Accordingly, clinical equipoise exists with respect to induced hypothermia and we therefore propose a randomised trial with the design based on the findings in this thesis.