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      Association of Onset-to-Treatment Time With Discharge Destination, Mortality, and Complications Among Patients With Aneurysmal Subarachnoid Hemorrhage

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          Key Points

          Question

          What is the optimal time between symptom onset and treatment after aneurysmal subarachnoid hemorrhage (SAH) to maximize patient outcomes?

          Findings

          In this cohort study, more favorable patient outcomes (discharge home and survival at 12 months) were observed when treatment occurred within 12.5 hours after aneurysmal SAH symptom onset. Treatment delay did not affect neurologic complications after aneurysmal SAH.

          Meaning

          The findings of this study provide more information regarding the optimal timelines of surgical treatment for people with aSAH.

          Abstract

          Importance

          Rapid access to specialized care is recommended to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH), but understanding of the optimal onset-to-treatment time for aneurysmal SAH is limited.

          Objective

          To assess the optimal onset-to-treatment time for aneurysmal SAH that maximized patient outcomes after surgery.

          Design, Setting, and Participants

          This cohort study assessed 575 retrospectively identified cases of first-ever aneurysmal SAH occurring within the referral networks of 2 major tertiary Australian hospitals from January 1, 2010, to December 31, 2016. Individual factors, prehospital factors, and hospital factors were extracted from the digital medical records of eligible cases. Data analysis was performed from March 1, 2020, to August 31, 2021.

          Exposures

          Main exposure was onset-to-treatment time (time between symptom onset and aneurysm surgical treatment in hours) derived from medical records.

          Main Outcomes and Measures

          Clinical characteristics, complications, and discharge destination were extracted from medical records and 12-month survival obtained from data linkage. The associations of onset-to-treatment time (in hours) with (1) discharge destination of survivors (home vs rehabilitation), (2) 12-month survival, and (3) neurologic complications (rebleed, delayed cerebral ischemia, meningitis, seizure, hydrocephalus, and delayed cerebral injury) were investigated using natural cubic splines in multivariable Cox proportional hazards and logistic regression models.

          Results

          Of the 575 patients with aneurysmal SAH, 482 patients (mean [SD] age, 55.0 [14.5] years; 337 [69.9%] female) who received endovascular coiling or neurosurgical clipping were studied. A nonlinear association of treatment delay was found with the odds of being discharged home vs rehabilitation (effective df = 3.83 in the generalized additive model, χ 2 test P = .002 for the 4- df cubic spline), with a similar nonlinear association remaining significant after adjustment for sex, treatment modality, severity, Charlson Comorbidity Index, history of hypertension, and hospital transfer (likelihood ratio test: df = 3, deviance = 9.57, χ 2 test P = .02). Both unadjusted and adjusted cox regression models showed a nonlinear association between time to treatment and 12-month mortality with the lowest hazard of death with receipt of treatment at 12.5 hours after symptom onset, although the nonlinear term became nonsignificant upon adjustment. The odds of being discharged home were higher with treatment before 20 hours after onset, with the probability of being discharged home compared with rehabilitation or other hospital increased by approximately 10% when treatment was received within the first 12.5 hours after symptom onset and increased by an additional 5% from 12.5 to 20 hours. Time to treatment was not associated with any complications.

          Conclusions and Relevance

          This cohort study found evidence that more favorable outcomes (discharge home and survival at 12 months) were achieved when surgical treatment occurred at approximately 12.5 hours. These findings provide more clarity around optimal timelines of treatment with people with aneurysmal SAH; however, additional studies are needed to confirm the findings.

          Abstract

          This cohort study of patients with aneurysmal subarachnoid hemorrhage assesses the associations between onset-to-treatment time and postsurgical outcomes.

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          Most cited references16

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          Prediction of symptomatic vasospasm after subarachnoid hemorrhage: the modified fisher scale.

          We developed a modification of the Fisher computed tomographic rating scale and compared it with the original Fisher scale to determine which scale best predicts symptomatic vasospasm after subarachnoid hemorrhage. We analyzed data from 1355 subarachnoid hemorrhage patients in the placebo arm of four randomized, double-blind, placebo-controlled studies of tirilazad. Modified Fisher computed tomographic grades were calculated on the basis of the presence of cisternal blood and intraventricular hemorrhage. Crude odds ratios (OR) reflecting the risk of developing symptomatic vasospasm were calculated for each scale level, and adjusted ORs expressing the incremental risk were calculated after controlling for known predictors of vasospasm. Of 1355 patients, 451 (33%) developed symptomatic vasospasm. For the modified Fisher scale, compared with Grade 0 to 1 patients, the crude OR for vasospasm was 1.6 (95% confidence interval [CI], 1.0-2.5) for Grade 2, 1.6 (95% CI, 1.1-2.2) for Grade 3, and 2.2 (95% CI, 1.6-3.1) for Grade 4. For the original Fisher scale, referenced to Grade 1, the OR for vasospasm was 1.3 (95% CI, 0.7-2.2) for Grade 2, 2.2 (95% CI, 1.4-3.5) for Grade 3, and 1.7 (95% CI, 1.0-3.0) for Grade 4. Early angiographic vasospasm, history of hypertension, neurological grade, and elevated admission mean arterial pressure were identified as risk factors for symptomatic vasospasm. After adjusting for these variables, the modified Fisher scale remained a significant predictor of vasospasm (adjusted OR, 1.28; 95% CI, 1.06-1.54), whereas the original Fisher scale was not. The modified Fisher scale, which accounts for thick cisternal and ventricular blood, predicts symptomatic vasospasm after subarachnoid hemorrhage more accurately than original Fisher scale.
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            The critical care management of poor-grade subarachnoid haemorrhage

            Aneurysmal subarachnoid haemorrhage is a neurological syndrome with complex systemic complications. The rupture of an intracranial aneurysm leads to the acute extravasation of arterial blood under high pressure into the subarachnoid space and often into the brain parenchyma and ventricles. The haemorrhage triggers a cascade of complex events, which ultimately can result in early brain injury, delayed cerebral ischaemia, and systemic complications. Although patients with poor-grade subarachnoid haemorrhage (World Federation of Neurosurgical Societies 4 and 5) are at higher risk of early brain injury, delayed cerebral ischaemia, and systemic complications, the early and aggressive treatment of this patient population has decreased overall mortality from more than 50 % to 35 % in the last four decades. These management strategies include (1) transfer to a high-volume centre, (2) neurological and systemic support in a dedicated neurological intensive care unit, (3) early aneurysm repair, (4) use of multimodal neuromonitoring, (5) control of intracranial pressure and the optimisation of cerebral oxygen delivery, (6) prevention and treatment of medical complications, and (7) prevention, monitoring, and aggressive treatment of delayed cerebral ischaemia. The aim of this article is to provide a summary of critical care management strategies applied to the subarachnoid haemorrhage population, especially for patients in poor neurological condition, on the basis of the modern concepts of early brain injury and delayed cerebral ischaemia.
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              Does treatment of ruptured intracranial aneurysms within 24 hours improve clinical outcome?

              The purpose of this study was to analyze whether treating ruptured intracranial aneurysms within 24 hours of subarachnoid hemorrhage improves clinical outcome. An 11-year database of consecutive ruptured intracranial aneurysms treated with endovascular coiling or craniotomy and clipping was analyzed. Outcome was measured by the modified Rankin Scale at 6 months. Our policy is to treat all cases within 24 hours of subarachnoid hemorrhage. Treatment delays are due to nonclinical logistical factors. Two hundred thirty cases were coiled or clipped within 24 hours of subarachnoid hemorrhage and 229 at >24 hours. No difference in age, gender, smoking, family history of subarachnoid hemorrhage, aneurysm size, or aneurysm location was found between the groups. Poor World Federation of Neurological Surgeons clinical grade patients were overrepresented in the ultra-early group. Increasing age and higher World Federation of Neurological Surgeons clinical grade were predictors of poor outcome. Eight point zero percent (16 of 199) of cases treated within 24 hours of SAH (ultra-early) were dependent or dead at 6 months compared with 14.4% (30 of 209) of those treated at >24 hours post-SAH (delayed; (χ2, P0.044) [corrected]. A total of 3.5% of cases coiled within 24 hours were dependent or dead at 6 months compared with 12.5% of cases coiled at 1 to 3 days, an 82% relative risk reduction and a 10.2% absolute risk reduction (χ2, P=0.040). These groups did not differ in age, World Federation of Neurological Surgeons clinical grade, aneurysm size, or aneurysm location. Treatment of ruptured aneurysms within 24 hours is associated with improved clinical outcomes compared with treatment at >24 hours. The benefit is more pronounced for coiling than clipping.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                21 January 2022
                January 2022
                21 January 2022
                : 5
                : 1
                : e2144039
                Affiliations
                [1 ]Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
                [2 ]NeuroInterventional Radiology, Monash Health, Melbourne, Victoria, Australia
                [3 ]School of Clinical Sciences Monash Health, Monash University, Melbourne, Victoria, Australia
                [4 ]School of Nursing, University of Tasmania, Hobart, Tasmania, Australia
                [5 ]Ambulance Victoria, Melbourne, Victoria, Australia
                [6 ]Department of Neurosurgery, Monash Health, Melbourne, Victoria, Australia
                [7 ]NeuroInterventional Radiology, Royal Hobart Hospital, Hobart, Tasmania, Australia
                [8 ]Department of Epidemiology, Michigan State University, East Lansing
                [9 ]Department of Neurosurgery, Royal Hobart Hospital, Hobart, Tasmania, Australia
                Author notes
                Article Information
                Accepted for Publication: November 7, 2021.
                Published: January 21, 2022. doi:10.1001/jamanetworkopen.2021.44039
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Buscot MJ et al. JAMA Network Open.
                Corresponding Author: Marie-Jeanne Buscot, PhD, Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool St, 7000 Hobart, Tasmania, Australia ( m.buscot@ 123456utas.edu.au ).
                Author Contributions: Dr Buscot had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Buscot, Chandra, Nichols, Stirling, Smith, Asadi, Reeves, Thani, Thrift, Gall.
                Acquisition, analysis, or interpretation of data: Buscot, Chandra, Maingard, Blizzard, Stirling, Smith, Lai, Asadi, Froelich, Thrift, Gall.
                Drafting of the manuscript: Buscot, Maingard, Nichols, Asadi, Gall.
                Critical revision of the manuscript for important intellectual content: All authors.
                Statistical analysis: Buscot, Blizzard, Reeves.
                Obtained funding: Chandra, Stirling, Thrift, Gall.
                Administrative, technical, or material support: Nichols, Smith, Froelich, Reeves, Gall.
                Supervision: Chandra, Maingard, Stirling, Lai, Asadi, Gall.
                Conflict of Interest Disclosures: Dr Chandra reported receiving grants from National Health and Medical Research Council of Australia Research during the conduct of the study. Dr Blizzard reported receiving grants from National Health and Medical Research Council of Australia during the conduct of the study. Dr Stirling reported receiving grants from National Health and Medical Research Council during the conduct of the study. Dr Thrift reported receiving grants from National Health and Medical Research Council of Australia during the conduct of the study and outside the submitted work and serving on the board of the Stroke Foundation (Australia). Dr Gall reported receiving grants from the National Health and Medical Research Council of Australia and the Heart Foundation during the conduct of the study and grants from the National Health and Medical Research Council of Australia, Minderoo Foundation, and Edwards Life Sciences outside the submitted work. No other disclosures were reported.
                Funding/Support: This study was funded by grant APP1143155 from the National Health and Medical Research Council. Dr Gall is funded by a National Heart Foundation of Australia Future Leader Fellowship
                Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Additional Contributions: Gemma Kitsos served as the project manager for data management and preparation. She received a salary to work on this project. Darius Tan, Kevin Zhou, Sue Mosely, and Sabah Rehman assisted with data collection and preparation. They were not compensated for their work. Ambulance Tasmania, Ambulance Victoria, the Australian Institute of Health and Welfare, the Centre for Victorian Data Linkage, the Tasmanian Data Linkage Unit, and data custodians assisted with data linkage and preparation and review of data. We acknowledge the patients with aneurysmal subarachnoid hemorrhage who were included in this study with a waiver of consent.
                Article
                zoi211218
                10.1001/jamanetworkopen.2021.44039
                8783267
                35061040
                3646ad0f-af8d-436c-8537-6783bf3ad497
                Copyright 2022 Buscot MJ et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 20 July 2021
                : 7 November 2021
                Categories
                Research
                Original Investigation
                Online Only
                Neurology

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