Hypothermia after aneurysmal subarachnoid hemorrhage

Abstract

Aneurysmal subarachnoid hemorrhage (SAH) is a common and frequently devastating condition, accounting for 1 to 7% of all strokes with an incidence of 9.1 per 100,000 [1]. Major advances in SAH management over the past three decades have decreased case fatality by 0.8% per year, but it is still 40% and many survivors have long-term disabilities [2]. The most important and potentially treatable complication is development of delayed cerebral ischemia (DCI), which can progress to cerebral infarction associated with poor outcome. The pathogenesis of DCI is multifactorial and assumed to be initiated in the early phase of SAH [3]. The onset of SAH is characterized by a short-lasting and cerebral perfusion pressure (CPP)-dependent decrease in cerebral blood flow (CBF) leading to global cerebral ischemia [4]. Elevated intracranial pressure (ICP) and acute cerebral ischemia are the main factors for early disruption of the blood-brain barrier as well as impairment of autoregulation associated with brain edema and brain swelling. Important pathogenic mechanisms of CPP-independent hypoperfusion include acute vasoconstriction, cortical spreading ischemia, and activation of the inflammatory response. The release of oxyhemoglobin and endothelin-1 (ET-1) are the key factors for cortical spreading ischemia, reduced nitric oxide (NO) availability, and secondary cytotoxic edema formation. Cerebral vasospasm (CVS) is a delayed morphological narrowing of cerebral arteries, occurring 4 to 10 days after SAH. Although CVS have been associated with DCI, it is generally accepted that CVS is not solely responsible for DCI [5]. In fact, DCI may occur in the absence of CVS and vice versa and the distribution of CVS may fail to reliably predict the subsequent pattern of cerebral infarction [6]. Neuroprotective strategies to prevent DCI have been mainly focused on treatment of CVS, but despite extensive research, effective and/or causative prophylaxis and treatment are not available [7]. So far, oral nimodipine is the only drug that can reduce the incidence of DCI and poor outcome, but there is no beneficial effect on CVS [8]. Hypothermia (HT) treatment exerting numerous protective effects such as a decrease in cerebral metabolism [9], stabilization of the blood-brain barrier [10], reduction of cerebral edema [11], suppression of excitatory neurotransmitter concentrations [12] and inflammatory reactions [13] seems to be well suited as a neuroprotective strategy. In the following, the clinical application of HT after SAH is presented by reviewing the existing literature.