title: Beta-blocker therapy and impact on outcome after aneurysmal subarachnoid hemorrhage: a cohort study.
abstract: OBJECTIVE Cerebral vasospasm (cVSP) is a frequent complication of aneurysmal subarachnoid hemorrhage (aSAH), with a significant impact on outcome. Beta blockers (BBs) may blunt the sympathetic effect and catecholamine surge associated with ruptured cerebral aneurysms and prevent cardiac dysfunction. The purpose of this study was to investigate the association between preadmission BB therapy and cVSP, cardiac dysfunction, and in-hospital mortality following aSAH. METHODS This was a retrospective cohort study of patients with aSAH who were treated at a tertiary high-volume neurovascular referral center. The exposure was defined as any preadmission BB therapy. The primary outcome was cVSP assessed by serial transcranial Doppler with any mean flow velocity ≥ 120 cm/sec and/or need for endovascular intervention for medically refractory cVSP. Secondary outcomes were cardiac dysfunction (defined as cardiac troponin-I elevation > 0.05 μg/L, low left ventricular ejection fraction [LVEF] < 40%, or LV wall motion abnormalities [LVWMA]) and in-hospital mortality. RESULTS The cohort consisted of 210 patients treated between February 2009 and September 2010 (55% were women), with a mean age of 53.4 ± 13 years and median Hunt and Hess Grade III (interquartile range III-IV). Only 13% (27/210) of patients were exposed to preadmission BB therapy. Compared with these patients, a higher percentage of patients not exposed to preadmission BBs had transcranial Doppler-mean flow velocity ≥ 120 cm/sec (59% vs 22%; p = 0.003). In multivariate analyses, lower Hunt and Hess grade (OR 3.9; p < 0.001) and preadmission BBs (OR 4.5; p = 0.002) were negatively associated with cVSP. In multivariate analysis, LVWMA (OR 2.7; p = 0.002) and low LVEF (OR 1.1; p = 0.05) were independent predictors of in-hospital mortality. Low LVEF (OR 3.9; p = 0.05) independently predicted medically refractory cVSP. The in-hospital mortality rate was higher in patients with LVWMA (47.4% vs 14.8%; p < 0.001). CONCLUSIONS The study data suggest that preadmission therapy with BBs is associated with lower incidence of cVSP after aSAH. LV dysfunction was associated with higher medically refractory cVSP and in-hospital mortality. BB therapy may be considered after aSAH as a cardioprotective and cVSP preventive therapy.
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Nohra
authors.initials: N
authors.lastname: Chalouhi
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Badih
authors.initials: B
authors.lastname: Daou
authors.affiliation: Medicine, and.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Okabe
authors.affiliation: Departments of 1 Neurosurgery.|Department of Neurosurgery, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Starke
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Richard
authors.initials: R
authors.lastname: Dalyai
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Cory D
authors.initials: CD
authors.lastname: Bovenzi
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Eliza Claire
authors.initials: EC
authors.lastname: Anderson
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Barros
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Adam
authors.initials: A
authors.lastname: Reese
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Pascal
authors.initials: P
authors.lastname: Jabbour
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Stavropoula
authors.initials: S
authors.lastname: Tjoumakaris
authors.affiliation: Departments of 1 Neurosurgery.
authors.forename: Robert
authors.initials: R
authors.lastname: Rosenwasser
authors.affiliation: Medicine, and.
authors.forename: Walter K
authors.initials: WK
authors.lastname: Kraft
authors.affiliation: Departments of 1 Neurosurgery.|Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania; and.
authors.forename: Fred
authors.initials: F
authors.lastname: Rincon
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D006331:Heart Diseases / Q000209:etiology; D017052:Hospital Mortality; D006801:Humans; D015994:Incidence; D002532:Intracranial Aneurysm / Q000150:complications*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000209:etiology; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists
keywords: AUC = area under the receiver operating characteristic curve; BB = beta blocker; DCI = delayed cerebral ischemia; HH = Hunt and Hess; LVEF = left ventricular ejection fraction; LVWMA = LV wall motion abnormalities; NSM = neurogenic stunned myocardium; TCD = transcranial Doppler; aSAH = aneurysmal subarachnoid hemorrhage; cTi = cardiac troponin-I; cVSP = cerebral vasospasm; delayed cerebral ischemia; mFV = mean flow velocity; stroke; transcranial Doppler; ultrasound; vascular disorders