Background and Purpose— Selective serotonin reuptake inhibitors (SSRIs) have a well-established association with bleeding complications and conflicting reports on outcome after stroke. We sought to evaluate whether pre–intracerebral hemorrhage (ICH) SSRI use increased ICH risk and post-ICH SSRI use improved ICH outcome. Methods— Through post hoc analysis of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage), SSRI use was categorized into no use, pre-ICH only, pre- and post-ICH use (termed “continuous”), and post-ICH only (termed “new”). Using multivariable modeling, associations were sought between pre-ICH SSRI use and ICH risk in the case-control set, and associations between post-ICH SSRI use and 3-month outcome were analyzed in the ICH case set. Exploratory analyses sought to assess influence of race/ethnicity in models. Results— The final study cohort consisted of 2287 ICH cases and 2895 controls. Pre-ICH SSRI use was not associated with ICH risk (odds ratio, 0.824 [95% CI, 0.632–1.074]) nor potentiation of ICH risk with anticoagulant or antiplatelet use. New post-ICH SSRI use was associated with unfavorable modified Rankin Scale score at 3 months after ICH (odds ratio, 1.673 [95% CI, 1.162–2.408]; P =0.006) in multivariable analyses. Additional propensity score analysis indicated a similar trend but did not reach statistical significance ( P =0.107). When stratified by race/ethnicity, multivariable modeling demonstrated reduced ICH risk with pre-ICH SSRI use in Hispanics (odds ratio, 0.513 [95% CI, 0.301–0.875]; P =0.014), but not non-Hispanic whites or blacks, and no associations between post-ICH SSRI use and 3-month outcome in any racial/ethnic group. Conclusions— In a large multiethnic cohort, pre-ICH SSRI use was not associated with increased ICH risk, but post-ICH SSRI use was associated with unfavorable 3-month neurological outcome after ICH. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01202864.

IntroductionCurrent guidelines recommend blood pressure (BP) lowering in patients after acute intracerebral haemorrhage (ICH) without guidance on initial choice of antihypertensive class. This study sought to determine if initial antihypertensive class differentially effects acute BP lowering in a large multiethnic ICH cohort.MethodsSubjects enrolled in the Ethnic/Racial Variations in ICH study between August 2010 and August 2017 with elevated admission BP and who received labetalol, nicardipine or hydralazine monotherapy as initial antihypertensive were analysed. Primary outcomes were systolic and diastolic BP changes from baseline to first BP measurement after initial antihypertensive treatment. Secondary outcomes included haematoma expansion (HE), hospital length of stay (LOS) and modified Rankin Score (mRS) up to 12 months after ICH. Exploratory outcomes assessed effects of race/ethnicity. Linear and logistic regression analyses, adjusted for relevant covariates, were performed to determine associations of antihypertensive class with outcomes.ResultsIn total, 1156 cases were used in analyses. Antihypertensive class was associated with diastolic BP change (p=0.003), but not systolic BP change (p=0.419). Initial dosing with nicardipine lowered acute diastolic BP than labetalol (least square mean difference (labetalol-nicardipine)=5.47 (2.37, 8.57), p<0.001). Initial antihypertensive class was also found to be associated with LOS (p=0.028), but not with HE (p=0.406), mortality (p=0.118), discharge disposition (p=0.083) or mRS score at discharge, 3, 6 and 12 months follow-up (p=0.262, 0.276, 0.152 and 0.36, respectively). Race/ethnicity variably affected multivariable models.ConclusionIn this large acute ICH cohort, initial antihypertensive class was associated with acute diastolic, but not systolic, BP-lowering suggesting differential effects of antihypertensive agents.Trial registration numberNCT01202864.

Background: Clopidogrel is a commonly prescribed antiplatelet drug in patients with stents and histories of arterial vascular disease. It generally has a favorable side effect profile with increasing bleeding risk as the main concern as an adverse event.Case Presentation: A 19-year-old previously healthy male presented to the neurological intensive care unit with a subarachnoid hemorrhage requiring a flow diverting stent to secure the aneurysm. The patient was stable for 2 weeks and had no changes to management or medication within 48 h of antiplatelet therapy. Within hours of first-time dosing of clopidogrel, the patient experienced a syncopal episode and dyspnea. He was difficult to arouse and using accessory muscles to breath with an otherwise benign exam. He was hypoxic with bibasilar crackles requiring bilevel positive airway pressure (BiPap). Imaging showed bilateral pulmonary edema and he was diagnosed with moderate acute respiratory distress syndrome (ARDS). Infectious, cardiogenic, and contrast-induced ARDS were ruled out. Upon cessation of clopidogrel, his pulmonary function and mental status improved.Conclusions: This is the first reported case of a young and immunocompetent patient's severe pulmonary edema leading to acute respiratory distress syndrome in association with first- time dosing of clopidogrel.

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons AttributionNonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Intracerebral hemorrhage (ICH) constitutes ~15% of strokes subtypes in the United States (US) and results in greater morbidity and mortality than ischemic stroke. 1-3 Despite priority reports by the National Institutes of Health and American Heart Association, 4,5 ICH remains the only stroke subtype without proven effective therapy. To date, ICH clinical trials have largely focused on hematoma reduction. Despite hematoma volume, robust secondary injury occurs through neuroinflammation, which manifests as cerebral edema after ICH. Prior reports have shown cerebral edema formation 6-8 and systemic inflammation 9-13 after ICH to be robust and inversely associated with neurological outcome. Strategies that target inflammation in the brain and body may carry high potential for improving ICH outcome. Based on preclinical work, one promising neurotherapeutic strategy may be gonadal hormone regulation. Despite this, results of prior clinical trials for progesterone in acute traumatic brain injury (TBI) and estrogen for ischemic stroke failed to show efficacy. However, treatment benefit in these trials may have been negated by (1) enrolling individuals with normal hormonal production or on oral replacement therapy and (2) lack of data on baseline levels or failure to understand hormonal physiology after the neurologic injury. Thus, effects of endogenous hormones on outcomes after ICH remain to be defined before embarking on an ICH clinical trial.The exact mechanisms underlying relationships between gonadal hormones, brain injury-associated stress response, neurological outcome, and mortality have not been wholly described. Data are needed on the impact of age, sex, and ethnicity on gonadal hormones in human ICH recovery. Brain recovery mechanisms are clearly tied to gonadal hormones physiology. For example, pleiotropic effects of gonadal hormones improve neurological recovery in up to 50% in preclinical central nervous system (CNS) injury studies. 14-17 Serum estradiol levels in humans are a robust marker of mortality both in men and women with TBI and subarachnoid hemorrhage, and the relationship changes with age. 18 Of course, age and ethnicity influence gonadal hormone regulation. [19][20][21] Finally, gonadal hormones are known to affect coagulation. [22][23][24] However, little of this has been evaluated after ICH. The first steps are (1) characterize gonadal hormone physiology after ICH and (2) define associations between hormone concentrations, pathophysiology, and recovery. These associations will lay the framework for defining if/how these hormones might contribute to neurop...