***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Background and Purpose — Early identification of patients at risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage ( SAH ) may mitigate its sequelae . One mechanism that may contribute to angiographic vasospasm is increased central sympathetic activity , which is also thought to cause electrocardiographic ( ECG ) changes after SAH . Here , we perform the first study to determine the association between ECG changes and angiographic vasospasm after SAH . Methods — Exploratory analysis was performed on 413 patients from CONSCIOUS-1 , a prospect i ve r and omized trial of clazosentan for the prevention of angiographic vasospasm .  ECGs  were obtained within 24 hours of aneurysm rupture and during the vasospasm risk period . Angiographic vasospasm was assessed using catheter angiography at baseline and 7 to 11 days after SAH . Multivariate logistic regression was used to identify significant associations . Results — The most prevalent finding on ECG both immediately following SAH and during the vasospasm risk period was QT prolongation ( 42 % and 25 % , respectively ) . A prolonged QT interval and tachycardia on the baseline ECG were associated with angiographic vasospasm ( OR , 1.86 ; 95 % CI , 1.00–3.45 ; and OR , 10.83 ; 95 % CI , 1.17–100.50 , respectively ) . QT prolongation on ECG during the vasospasm risk period was also associated with angiographic vasospasm ( OR , 3.53 ; 95 % CI , 1.67–7.39 ) . No ECG findings were associated with delayed ischemic neurological deficit , but tachycardia and ST changes were associated with worse clinical outcome . Conclusions — QT prolongation and tachycardia on ECG were independently associated with angiographic vasospasm after aneurysmal SAH on multivariate analysis . Clinical Trial Registration — URL : http:// clinical trials.gov . Unique Identifier : NCT00111085 BACKGROUND Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results . This r and omised controlled trial , done in 190 hospitals in 23 countries , was design ed to investigate the effects of perioperative beta blockers . METHODS We r and omly assigned 8351 patients with , or at risk of , atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate ( n=4174 ) or placebo ( n=4177 ) , by a computerised r and omisation phone service . Study treatment was started 2 - 4 h before surgery and continued for 30 days . Patients , health-care providers , data collectors , and outcome adjudicators were masked to treatment allocation . The primary endpoint was a composite of cardiovascular death , non-fatal myocardial infa rct ion , and non-fatal cardiac arrest . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00182039 . FINDINGS All 8351 patients were included in analyses ; 8331 ( 99.8 % ) patients completed the 30-day follow-up . Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint ( 244 [ 5.8 % ] patients in the metoprolol group vs 290 [ 6.9 % ] in the placebo group ; hazard ratio 0.84 , 95 % CI 0.70 - 0.99 ; p=0.0399 ) . Fewer patients in the metoprolol group than in the placebo group had a myocardial infa rct ion ( 176 [ 4.2 % ] vs 239 [ 5.7 % ] patients ; 0.73 , 0.60 - 0.89 ; p=0.0017 ) . However , there were more deaths in the metoprolol group than in the placebo group ( 129 [ 3.1 % ] vs 97 [ 2.3 % ] patients ; 1.33 , 1.03 - 1.74 ; p=0.0317 ) . More patients in the metoprolol group than in the placebo group had a stroke ( 41 [ 1.0 % ] vs 19 [ 0.5 % ] patients ; 2.17 , 1.26 - 3.74 ; p=0.0053 ) . INTERPRETATION Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm , and the importance and need for large r and omised trials in the perioperative setting . Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol A study was set up to assess the effect on the clinical course of subarachnoid haemorrhage ( SAH ) of giving propranolol 80 mg eight-hourly plus phentolamine 20 mg three-hourly by mouth for three weeks . Out of the 90 patients studied , 14 died . Two of the deaths occurred in an open pilot study of 10 patients , the remaining 12 deaths occurring in patients in a r and omised double-blind placebo-controlled study .  Postmortem examination was carried out on 12 of the patients , six of whom had been receiving placebo and six propranolol plus phentolamine .  Necrotic myocardial lesions were present in the hearts of all six patients ( age range 30 - 59 years ) who died while taking placebo ( all had had abnormal electrocardiograms ( ECGs ) . In contrast , no necrotic lesions were found in the hearts of the six patients ( age range 28 - 59 ) who died while receiving the drugs ( all had previously had normal ECGs ) . We conclude that the necrotic myocardial lesions were induced by catecholamines and that propranolol had a cardioprotective effect . While death from a further haemorrhage in cases of SAH is not affected by propranolol and phentolamine , propranolol may have a beneficial effect in other potentially lethal stresses Introduction Subarachnoid hemorrhage ( SAH ) is a devastating form of stroke . Causes and mechanisms of in-hospital death after SAH in the modern era of neurocritical care remain incompletely understood . Methods We studied 1200 consecutive SAH patients prospect ively enrolled in the Columbia University SAH Outcomes Project between July 1996 and January 2009 . Analysis was performed to identify predictors of in-hospital mortality . Results In-hospital mortality was 18 % ( 216/1200 ) : 3 % for Hunt-Hess grade 1 or 2 , 9 % for grade 3 , 24 % for grade 4 , and 71 % for grade 5 . The most common adjudicated primary causes of death or neurological devastation leading to withdrawal of support were direct effects of the primary hemorrhage ( 55 % ) , aneurysm rebleeding ( 17 % ) , and medical complications ( 15 % ) . Among those who died , brain death was declared in 42 % , 50 % were do-not-resuscitate at the time of cardiac death ( 86 % of whom had life support actively withdrawn ) , and 8 % died despite full support . Admission predictors of mortality were age , loss of consciousness at ictus , admission Glasgow Coma Scale score , large aneurysm size , Acute Physiology and Chronic Health Evaluation II ( APACHE II ) physiologic subscore , and Modified Fisher Scale score . Hospital complications that further increased the risk of dying in multivariable analysis included rebleeding , global cerebral edema , hypernatremia , clinical signs of brain stem herniation , hypotension of less than 90 mm Hg treated with pressors , pulmonary edema , myocardial ischemia , and hepatic failure . Delayed cerebral ischemia , defined as deterioration or infa rct ion from vasospasm , did not predict mortality . ConclusionS trategies directed toward minimizing early brain injury and aneurysm rebleeding , along with prevention and treatment of medical complication , hold the best promise for further reducing mortality after SAH Summary Over the last 15 years progressive interest has developed in the relationship between subarachnoid haemorrhage , sympathetie nervous system overactivity and the genesis of cerebral artery spasm . Following on from earlier work , vide infra , suggesting that adrenergic blockade might influence the course and prognosis of patients with subarachnoid haemorrhage , two double blind trials have recently been completed in Southampton . The first trial attempted to establish whether or not a single intracarotid injection of phenoxybenzamine improved the mortality and late morbidity of patients with subarachnoid haemorrhage . Results suggested that it did not . The second trial , comprising two groups of 50 patients each , attempted to assess the influence of prolonged treatment with propranolol on the course and prognosis of these subarachnoid haemorrhage patients . Early results suggest that , as with theα- blocker , the mortality and severe morbidity was not improved byβ-adrenergic blockade Introduction Sympathetic nervous system hyperactivity is common after subarachnoid hemorrhage ( SAH ) . We sought to determine whether uncontrolled prolonged heart rate elevation is a risk factor for adverse cardiopulmonary events and poor outcome after SAH . Methods We prospect ively studied 447 SAH patients between March 2006 and April 2012 . Prior studies define prolonged elevated heart rate ( PEHR ) as heart rate > 95 beats/min for > 12 h. Major adverse cardiopulmonary events were documented according to the predefined criteria . Global outcome at 3 months was assessed with the modified Rankin Scale ( mRS ) . Results 175 ( 39 % ) patients experienced PEHR . Nonwhite race/ethnicity , admission Hunt – Hess grade ≥4 , elevated APACHE-2 physiological subscore , and modified Fisher score were significant admission predictors of PEHR , whereas documented pre-hospital beta-blocker use was protective . After controlling for admission Hunt – Hess grade , Cox regression using time-lagged covariates revealed that PEHR onset in the previous 48 h was associated with an increased hazard for delayed cerebral ischemia , myocardial injury , and pulmonary edema . PEHR was associated with 3-month poor outcome ( mRS 4–6 ) after controlling for known predictors . Conclusions PEHR is associated with major adverse cardiopulmonary events and poor outcome after SAH . Further study is warranted to determine if early sympatholytic therapy targeted at sustained heart rate control can improve outcome after SAH Summary The effects of beta-blockade to prevent autonomic disorders after acute aneurysmal subarachnoid haemorrhage were prospect ively investigated . 11 patients were treated with the beta-1-selective beta-blocker metoprolol ( up to 200 mg/die intravenously ) . 14 patients received st and ard therapy as controls .  Pulse rate , blood pressure and dosage of the additional antihypertensive medication  as signs of sympathetic disturbance were registered . The main result was the normalizing of the pulse rate especially during the first two weeks in contrast to the control group . The patients in the beta-blocker group did not need further antihypertensive medication . This was mainly a result of the reduction in sympathetic activation . No severe side-effects were documented and the survival was better in the treated group . Thus , beta-blockade is able to prevent and reduce autonomic disorders , especially activation of the sympathetic tone , in subarachnoid haemorrhage . Metoprolol as a so called cardioselective beta-blocker seems to be one of the suitable agents and is considered superior to the non-selective agents Previous studies have shown that ECG changes following a subarachnoid haemorrhage are associated with increased catecholamine levels , necrotic myocardial lesions , and a poor prognosis . Furthermore , beta-blockade using propranolol reverses some of the ECG changes and prevents necrotic myocardial lesions . This study was established to assess the affects of adrenergic blockade on morbidity and mortality following subarachnoid haemorrhage . Patients were admitted to the r and omized double-blind between- patients study if they presented at the neurosurgical unit within 48 hours of a subarachnoid haemorrhage confirmed by lumbar puncture . Of 224 patients , the first 118 received an alpha-blocker , phentolamine 20 mg three-hourly , and either the beta-blocker propranolol 80 mg eight-hourly , or placebo . The last 106 patients received either propranolol or placebo . Treatment was continued for three weeks . Assessment at four weeks revealed significant improvements in the treated group for neurological deficit ( p = 0.003 ) and death ( p = 0.02 ) . More treated patients underwent operation and those that did had a better outcome ( p = 0.01 ) . Assessment at one year showed that although patients had improved in both groups , patients in the treated group had significantly fewer neurological deficits ( p = 0.003 ) . There were fewer deaths in the treated group but this difference was not significant ( p = 0.09 ) . Possible mechanisms for this protective effect of propranolol may include a reduction in plasma renin activity , a reduction in pulmonary oedema , prevention of myocardial infa rcts , and a reduction in cerebral oxygen requirements . It is concluded that early beta-blockade benefits patients with subarachnoid haemorrhage , in terms of fewer neurological deficits , for up to one 
    Output:
    
Statistically significant differences were not seen for other outcomes investigated .
In adult patients with aSAH  , beta-blocker therapy is associated with a mortality benefit .