What’s new in subarachnoid hemorrhage

- Delayed cerebral ischemia the absence of vasospasm and vice versa, and brain meta-analysis of seven randomized controlled trials of ischemia often involves more than one vascular territory. anti-platelet agents identified a trend towards improved Other mechanisms contributing to DCI include distal outcome but also a higher risk of intracranial haemorvascular dysautoregulation, micro-thrombi, direct neuro- rhagic complications [11]. toxic effects, inflammation and cortical spreading depolarizations (SDs) [4]. SDs are pathological events characterized by near-complete sustained depolarization of neurons and astrocytes that result in secondary injury Neuromonitoring related to mitochondrial damage, accumulation of intracellular calcium and excitotoxicity. SDs, which can only In addition to clinical neurological examination in conbe detected by electrocorticography, have been reported scious patients, serial transcranial Doppler (TCD) in up to 70 % of SAH patients. They are associated with ultrasonography supplemented by vascular and perfusionDCI and worse outcome, and management should focus imaging studies is the mainstay of monitoring for DCI. on controlling variables such as pyrexia, hypoxia, hypo- While such snapshots in time provide valuable informaglycemia and systemic hypotension which increase the tion, multimodal brain monitoring allows real-time incidence and duration of SDs [5]. bedside assessment of the efficacy of hemodynamic A combination of hypervolemia, hemodilution and augmentation to prevent or treat DCI. This is particularly hypertension (triple H therapy) has historically been the important when clinical neurological examination is mainstay of treatment to prevent and treat DCI, but the limited in sedated or poor-grade patients. focus of cardiovascular management after SAH is now on Increased ICP is common after SAH, particularly early a single Hhypertension [2]. Prophylactic hypervolemia after the ictus and in comatose patients [12]. The indiis not effective in increasing CBF or improving neuro- cations for ICP monitoring are often inter-related with the logical outcome, and there is some evidence of harm from need to treat obstructive hydrocephalus, so a ventricular overly aggressive filling [6]. Euvolemia is the target for catheter is the optimal ICP monitor, being both a diagboth prophylaxis and treatment of DCI, and hemodilution nostic and therapeutic modality. Intracranial hypertension has no place [2]. Induced hypertension can be effective in and lack of ICP response to medical therapy appear to be reversing DCI, and systemic blood pressure should be associated with DCI and poor clinical outcome after SAH, increased in a stepwise fashion guided by assessment of and ICP and CPP monitoring have a role in guiding neurological function, neuromonitoring or radiological therapy. Multimodal cerebral monitoring, including brain evidence of improved perfusion. The higher blood pres- tissue oxygen tension, TCD, cerebral microdialysis and sure should be maintained for 23 days and gradually electrophysiological monitoring in addition to ICP, allows weaned while monitoring for deterioration in clinical and individualized therapy with the aim of preventing or neuromonitoring variables [2]. There is preliminary evi- minimizing secondary ischemic injury [13]. Monitoring dence that early goal-directed hemodynamic therapy allows early detection of DCI and identifies end points for might reduce the risk of DCI and improve outcome after cardiovascular augmentation in its management. Changes SAH [7], but large, randomized controlled outcome in brain tissue oxygenation and biochemistry may identify studies are required before widespread adoption into impending or actual cerebral hypoxia/ischemia before clinical practice. changes in other monitoring modalities or clinical status, Several pharmacological agents which target the but it remains to be determined whether interventions diverse pathophysiology of DCI have been investigated, directed towards normalization of these variables affects but only nimodipine has been proven to improve outcome outcome. Data from small studies investigating the effi[1]. Despite the multiple beneficial effects of statins on cacy of multimodal neuromonitoring-guided treatment vascular function, a recent multicentre randomized phase after SAH have been encouraging, but outcome data are 3 trial found no benefit of simvastatin on short- or long- lacking [12]. Figure 1 shows a practical approach to term outcome after SAH [8]. In a recent meta-analysis, monitoring-guided management of DCI after SAH. intravenous magnesium administration was associated with a reduced incidence of DCI but not with beneficial effects on mortality or functional outcome [9]. Endothelin-A antagonists have been studied extensively after Seizures SAH because of the key role that endothelin plays in maintaining vascular tone. In randomized controlled tri- Using surface electroencephalography (EEG), seizures als, the endothelin-A antagonist clazosentan reduced are recorded in around 8 % of patients after SAH but angiographic vasospasm but had no significant effect on invasive EEG monitoring identifies seizure activity in outcome [10]. Attention has also focussed on agents almost 40 %. Continuous EEG monitoring is the only affecting the coagulation cascade because of the potential reliable way to detect subclinical seizures, and it may also role of microthrombosis in the pathogenesis of DCI. A predict DCI many hours in advance of clinical symptoms Fig. 1 Monitoring-guided management of delayed cerebral ischemia after subarachnoid haemorrhage. The figure shows a practical approach to monitoring-guided management of DCI after subarachnoid hemorrhage. The starting point is a frequent neurological evaluation and daily TCD, with clinically significant changes defined as new focal deficit or altered consciousness and TCD mean flow velocity [120 cm/s, increase [50 cm/s in 24 h, and/or a Lindegaard index (MCA/ICA blood flow velocity ratio) [6. If the neurological examination or TCD indicates a worsening state, a reasonable approach is to search for a potential reversible cause with a CT scan, CT angiography and perfusion CT. If angiographic vasospasm is present and CBF is reduced and/ or MTT increased, a trial of stepwise-induced hypertension is recommended. If this strategy reverses DCI, close monitoring with maintenance of the higher blood pressure for 23 days is recommended. If hypertension alone does not reverse DCI, advanced neuromonitoring and further imaging prior to interventional radiological treatment should be considered in salvageable patients. CBF cerebral blood flow, CT computerized tomography, DCI delayed cerebral ischemia, DSA digital subtraction angiography, ICA internal carotid artery, MCA middle cerebral artery, MTT mean transmit time, ptO2 brain tissue oxygen tension, rCBF regional cerebral blood flow, TCD transcranial Doppler ultrasonography, VS vaso (...truncated)