Abstract P40: Declining Morbidity From Subarachnoid Hemorrhage in the Last 4 Decades: A Pooled Analysis of 13,343 Patients

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sean Neifert ◽  
Eric Oermann ◽  
J D Mocco ◽  
Michael M Todd ◽  
James Torner ◽  
...  

Introduction: Subarachnoid hemorrhage (SAH) mortality is decreasing, but data on functional outcomes over time is lacking. Methods: We created trends of good (Glasgow Outcomes Scale [GOS] of 4 or 5) and optimal (GOS of 5) functional outcomes and mortality (GOS of 1) using linear regression in 15 SAH trials and registries from 1982 to 2014. Models adjusted for age, sex, history of hypertension, World Federation of Neurological Surgeons grade, Fisher grade, aneurysm size, location, and repair modality, and whether data was from a clinical trial or registry. Analyses were repeated separately for the clinical trials and registries. Missing data were handled with multiple imputation. Results: Overall, 13,343 SAH patients were included. 9,524 (71%) patients had good functional outcome, while 1,608 (12%) died. There was a 0.6% adjusted improvement (95% confidence interval [CI]: 0.5% to 0.7%; p<0.001) per year in good functional outcome and a 0.1% adjusted reduction (95% CI: -0.2% to -0.08%; p<0.001) per year in mortality. For patients enrolled in clinical trials, there was no change good functional outcomes (0%; 95% CI: -0.2% to 0.1%; p=0.923) or mortality (0.0% change per year; 95% CI: -0.09% to 0.1%; p=0.676). Clinical registry patients experienced a 1.2% improvement (95% CI: 1.0% to 1.4%; p<0.001) in good functional outcome and a 0.3% reduction (95% CI: -0.4% to -0.1%; p<0.001) in mortality. Conclusions: SAH morbidity and mortality decreased from the 1980s to 2010s. This data can be helpful for researchers planning trials, clinicians discussing expected outcomes with patients and family members, and healthcare administrators planning resource utilization.

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sean Neifert ◽  
Alexander Schupper ◽  
Michael Martini ◽  
Emily Chapman ◽  
William Shuman ◽  
...  

Introduction: Despite their high prevalence, prospective data on medical complications after aneurysmal subarachnoid hemorrhage (aSAH) and their contribution to functional outcome are sparse. We review rates of such events and correlate them to functional outcomes in three prospective datasets of patients with aSAH. Methods: Patients from two clinical trials (NEWTON-2, CONSCIOUS-1) and one clinical registry (Subarachnoid Hemorrhage Outcomes Project) were included. A good functional outcome was defined as a Glasgow Outcomes Scale (GOS) score of 4 or 5. Seventeen medical complications were assessed and their association with functional outcomes was determined with multivariable logistic regression. The variance in outcome explained by medical complications was calculated using difference in Nagelkerke’s R-squared. Results: Among the 1,430 patients, the most common complications were fever (564, 39%), anemia (410, 29%), and pneumonia (341, 24%). Patients who suffered any complication (OR: 0.45; 95% CI: 0.36 to 0.57; p<0.001) were less likely to have a good functional outcome in unadjusted analyses. In multivariable analysis, complications independently associated with lower rates of good functional outcome were anemia (OR: 0.60; 95% CI: 0.44 to 0.80; p<0.001), cardiac arrest (OR: 0.14; 95% CI: 0.05 to 0.37; p<0.001), pneumonia (OR: 0.48; 95% CI: 0.35 to 0.66; p<0.001), pulmonary edema (OR: 0.67; 95% CI: 0.45 to 0.99; p=0.047), and acute kidney injury (OR: 0.34; 95% CI: 0.12 to 0.98; p=0.047). A panel of eleven medical complications explained 8% of the variation in functional outcomes. Conclusions: Medical complications contribute to functional outcomes after aSAH, but their individual contributions to outcomes are relatively small. This should be noted when considering trials directed at preventing or treating any one complication and raises the question of studying comprehensive neurointensive care packages in the future.


Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 242-243
Author(s):  
Christopher J Stapleton ◽  
Hannah Irvine ◽  
Zoe Wolcott ◽  
Aman B Patel ◽  
Jonathan Rosand ◽  
...  

Abstract INTRODUCTION The quantification of metabolites in plasma samples in patients with aneurysmal subarachnoid hemorrhage (aSAH) can highlight important alterations in critical metabolic pathways. As metabolites reflect changes associated with disease conditions, metabolite profiling (metabolomics) can identify candidate biomarkers for disease and potentially uncover pathways for intervention. METHODS We performed high throughput metabolite profiling across a broad spectrum of chemical classes (173 metabolites) on plasma samples taken from 119 patients with aSAH. Samples were drawn at 3 time points following ictus: 2–4, 7–10, and 12–14 days. Univariate and logistic regression analyses were performed to examine the relation of each metabolite with multiple outcome variables, including short- and long-term functional outcome (modified Rankin Scale, mRS). RESULTS >A good functional outcome (mRS 0–2) was found in 63.1% and 66.7% of patients at 30 and 90 days, respectively, following aSAH. Plasma concentrations of the endogenous cannabinoid anandamide during days 2–4 after aneurysmal SAH were decreased by 48.1% (P < 0.0001) and 57.6% (P <0.0001) in patients with mRS 0–2 at 30 and 90 days, respectively. A similar statistical result was noted with plasma anandamide concentrations averaged across all time periods. Logistic regression further demonstrated that anandamide remained an independent predictor of functional outcome (30 days: P = 0.04; 90 days: P = 0.03), even after adjusting for other factors that influence outcome, including age, World Federation of Neurological Surgeons grade (WFNS), Fisher grade, and symptomatic vasospasm. CONCLUSION Decreased plasma anandamide following aSAH predicts a good functional outcome at 30 and 90 days. While a role for anandamide in aneurysmal SAH has not been previously reported, elevated anandamide levels have been implicated in neuronal apoptosis and cerebral edema in the acutely injured brain. These data highlight the increasing capability of metabolomics techniques in profiling large-sized cohorts to illuminate novel markers of disease and potential metabolic regulators.


2021 ◽  
pp. 1-10
Author(s):  
Ofer Sadan ◽  
Hannah Waddel ◽  
Reneé Moore ◽  
Chen Feng ◽  
Yajun Mei ◽  
...  

OBJECTIVE Cerebral vasospasm and delayed cerebral ischemia (DCI) contribute to poor outcome following subarachnoid hemorrhage (SAH). With the paucity of effective treatments, the authors describe their experience with intrathecal (IT) nicardipine for this indication. METHODS Patients admitted to the Emory University Hospital neuroscience ICU between 2012 and 2017 with nontraumatic SAH, either aneurysmal or idiopathic, were included in the analysis. Using a propensity-score model, this patient cohort was compared to patients in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository who did not receive IT nicardipine. The primary outcome was DCI. Secondary outcomes were long-term functional outcome and adverse events. RESULTS The analysis included 1351 patients, 422 of whom were diagnosed with cerebral vasospasm and treated with IT nicardipine. When compared with patients with no vasospasm (n = 859), the treated group was significantly younger (mean age 51.1 ± 12.4 years vs 56.7 ± 14.1 years, p < 0.001), had a higher World Federation of Neurosurgical Societies score and modified Fisher grade, and were more likely to undergo clipping of the ruptured aneurysm as compared to endovascular treatment (30.3% vs 11.3%, p < 0.001). Treatment with IT nicardipine decreased the daily mean transcranial Doppler velocities in 77.3% of the treated patients. When compared to patients not receiving IT nicardipine, treatment was not associated with an increased rate of bacterial ventriculitis (3.1% vs 2.7%, p > 0.1), yet higher rates of ventriculoperitoneal shunting were noted (19.9% vs 8.8%, p < 0.01). In a propensity score comparison to the SAHIT database, the odds ratio (OR) to develop DCI with IT nicardipine treatment was 0.61 (95% confidence interval [CI] 0.44–0.84), and the OR to have a favorable functional outcome (modified Rankin Scale score ≤ 2) was 2.17 (95% CI 1.61–2.91). CONCLUSIONS IT nicardipine was associated with improved outcome and reduced DCI compared with propensity-matched controls. There was an increased need for permanent CSF diversion but no other safety issues. These data should be considered when selecting medications and treatments to study in future randomized controlled clinical trials for SAH.


Neurosurgery ◽  
2015 ◽  
Vol 78 (4) ◽  
pp. 487-491 ◽  
Author(s):  
Rabih G. Tawk ◽  
Sanjeet S. Grewal ◽  
Michael G. Heckman ◽  
Bhupendra Rawal ◽  
David A. Miller ◽  
...  

Abstract BACKGROUND: The value of neuron-specific enolase (NSE) in predicting clinical outcomes has been investigated in a variety of neurological disorders. OBJECTIVE: To investigate the associations of serum NSE with severity of bleeding and functional outcomes in patients with subarachnoid hemorrhage (SAH). METHODS: We retrospectively reviewed the records of patients with SAH from June 2008 to June 2012. The severity of SAH bleeding at admission was measured radiographically with the Fisher scale and clinically with the Glasgow Coma Scale, Hunt and Hess grade, and World Federation of Neurologic Surgeons scale. Outcomes were assessed with the modified Rankin Scale at discharge. RESULTS: We identified 309 patients with nontraumatic SAH, and 71 had NSE testing. Median age was 54 years (range, 23-87 years), and 44% were male. In multivariable analysis, increased NSE was associated with a poorer Hunt and Hess grade (P = .003), World Federation of Neurologic Surgeons scale score (P &lt; .001), and Glasgow Coma Scale score (P = .003) and worse outcomes (modified Rankin Scale at discharge; P = .001). There was no significant association between NSE level and Fisher grade (P = .81) in multivariable analysis. CONCLUSION: We found a significant association between higher NSE levels and poorer clinical presentations and worse outcomes. Although it is still early for any relevant clinical conclusions, our results suggest that NSE holds promise as a tool for screening patients at increased risk of poor outcomes after SAH.


2020 ◽  
Vol 133 (6) ◽  
pp. 1842-1849 ◽  
Author(s):  
Christopher J. Stapleton ◽  
Animesh Acharjee ◽  
Hannah J. Irvine ◽  
Zoe C. Wolcott ◽  
Aman B. Patel ◽  
...  

OBJECTIVEMetabolite profiling (or metabolomics) can identify candidate biomarkers for disease and potentially uncover new pathways for intervention. The goal of this study was to identify potential biomarkers of functional outcome after subarachnoid hemorrhage (SAH).METHODSThe authors performed high-throughput metabolite profiling across a broad spectrum of chemical classes (163 metabolites) on plasma samples taken from 191 patients with SAH who presented to Massachusetts General Hospital between May 2011 and October 2016. Samples were drawn at 3 time points following ictus: 0–5, 6–10, and 11–14 days. Elastic net (EN) and LASSO (least absolute shrinkage and selection operator) machine learning analyses were performed to identify metabolites associated with 90-day functional outcomes as assessed by the modified Rankin Scale (mRS). Additional univariate and multivariate analyses were then conducted to further examine the relationship between metabolites and clinical variables and 90-day functional outcomes.RESULTSOne hundred thirty-seven (71.7%) patients with aneurysmal SAH met the criteria for inclusion. A good functional outcome (mRS score 0–2) at 90 days was found in 79 (57.7%) patients. Patients with good outcomes were younger (p = 0.002), had lower admission Hunt and Hess grades (p < 0.0001) and modified Fisher grades (p < 0.0001), and did not develop hydrocephalus (p < 0.0001) or delayed cerebral ischemia (DCI) (p = 0.049). EN and LASSO machine learning methods identified taurine as the leading metabolite associated with 90-day functional outcome (p < 0.0001). Plasma concentrations of the amino acid taurine from samples collected between days 0 and 5 after aneurysmal SAH were 21.9% (p = 0.002) higher in patients with good versus poor outcomes. Logistic regression demonstrated that taurine remained a significant predictor of functional outcome (p = 0.013; OR 3.41, 95% CI 1.28–11.4), after adjusting for age, Hunt and Hess grade, modified Fisher grade, hydrocephalus, and DCI.CONCLUSIONSElevated plasma taurine levels following aneurysmal SAH predict a good 90-day functional outcome. While experimental evidence in animals suggests that this effect may be mediated through downregulation of pro-inflammatory cytokines, additional studies are required to validate this hypothesis in humans.


2020 ◽  
Author(s):  
Ofer Sadan ◽  
Hannah Waddel ◽  
Reneé Moore ◽  
Chen Feng ◽  
Yajun Mei ◽  
...  

AbstractObjectivesCerebral vasospasm and delayed cerebral ischemia (DCI) contribute to poor outcome following subarachnoid hemorrhage (SAH). With the paucity of effective treatments, we describe our experience with intrathecal (IT) nicardipine for this indication.MethodsPatients admitted to Emory University Hospital Neuroscience ICU between 2012-2017 with non-traumatic SAH, either aneurysmal or idiopathic, were included in the analysis. This patient cohort was compared using a propensity-score model to patients in the SAH international trialist (SAHIT) repository who did not receive intrathecal nicardipine. The primary outcome was DCI. Secondary outcomes were long-term functional outcome and adverse events.ResultsThe analysis included 1,351 patients, 422 of whom were diagnosed with cerebral vasospasm and treated with IT nicardipine. When compared with patients with no vasospasm (n=859) the treated group was younger (51.1±12.4 vs. 56.7±14.1, p<0.01), had a higher World Federation of Neurological Surgeons score (WFNS), modified Fisher grade, and more likely to undergo clipping of the ruptured aneurysm as compared to endovascular treatment (30.3% vs. 11.3%, p<0.01). Treatment with IT nicardipine decreased daily mean transcranial Doppler velocities in 77.3% of the treated patients. When compared to patients not receiving IT nicardipine, treatment was not associated with an increase rate of bacterial ventriculitis (3.1% compared with 2.7%, p>0.1) yet higher rates of ventriculoperitoneal shunting were noted (19.9% vs. 8.8%, p<0.01). In a propensity score comparison to the SAHIT database, the odds ratio to develop DCI with IT nicardipine treatment was 0.61 with 95% CI[0.44-0.84], and to have a favorable functional outcome (mRS≤2) was 2.17[1.61-2.91].ConclusionsIT nicardipine was associated with improved outcome and reduced DCI compared with propensity matched controls. There was an increased need for permanent CSF diversion but no other safety issues. This data should be considered when selecting medications and treatments to study in future randomized controlled clinical trial for SAH.


2011 ◽  
Vol 114 (4) ◽  
pp. 1045-1053 ◽  
Author(s):  
Kelly B. Mahaney ◽  
Michael M. Todd ◽  
James C. Torner

ObjectThe past 30 years have seen a shift in the timing of surgery for aneurysmal subarachnoid hemorrhage (SAH). Earlier practices of delayed surgery that were intended to avoid less favorable surgical conditions have been replaced by a trend toward early surgery to minimize the risks associated with rebleeding and vasospasm. Yet, a consensus as to the optimal timing of surgery has not been reached. The authors hypothesized that earlier surgery, performed using contemporary neurosurgical and neuroanesthesia techniques, would be associated with better outcomes when using contemporary management practices, and sought to define the optimal time interval between SAH and surgery.MethodsData collected as part of the Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) were analyzed to investigate the relationship between timing of surgery and outcome at 3 months post-SAH. The IHAST enrolled 1001 patients in 30 neurosurgical centers between February 2000 and April 2003. All patients had a radiographically confirmed SAH, were World Federation of Neurosurgical Societies Grades I–III at the time of surgery, and underwent surgical clipping of the presumed culprit aneurysm within 14 days of the date of hemorrhage. Patients were seen at 90-day follow-up visits. The primary outcome variable was a Glasgow Outcome Scale score of 1 (good outcome). Intergroup differences in baseline, intraoperative, and postoperative variables were compared using the Fisher exact tests. Variables reported as means were compared with ANOVA. Multiple logistic regression was used for multivariate analysis, adjusting for covariates. A p value of less than 0.05 was considered to be significant.ResultsPatients who underwent surgery on Days 1 or 2 (early) or Days 7–14 (late) (Day 0 = date of SAH) fared better than patients who underwent surgery on Days 3–6 (intermediate). Specifically, the worst outcomes were observed in patients who underwent surgery on Days 3 and 4. Patients who had hydrocephalus or Fisher Grade 3 or 4 on admission head CT scans had better outcomes with early surgery than with intermediate or late surgery.ConclusionsEarly surgery, in good-grade patients within 48 hours of SAH, is associated with better outcomes than surgery performed in the 3- to 6-day posthemorrhage interval. Surgical treatment for aneurysmal SAH may be more hazardous during the 3- to 6-day interval, but this should be weighed against the risk of rebleeding.


Neurosurgery ◽  
2015 ◽  
Vol 77 (5) ◽  
pp. 786-793 ◽  
Author(s):  
◽  
Carole L. Turner ◽  
Karol Budohoski ◽  
Christopher Smith ◽  
Peter J. Hutchinson ◽  
...  

Abstract BACKGROUND: There remains a proportion of patients with unfavorable outcomes after aneurysmal subarachnoid hemorrhage, of particular relevance in those who present with a good clinical grade. A forewarning of those at risk provides an opportunity towards more intensive monitoring, investigation, and prophylactic treatment prior to the clinical manifestation of advancing cerebral injury. OBJECTIVE: To assess whether biochemical markers sampled in the first days after the initial hemorrhage can predict poor outcome. METHODS: All patients recruited to the multicenter Simvastatin in Aneurysmal Hemorrhage Trial (STASH) were included. Baseline biochemical profiles were taken between time of ictus and day 4 post ictus. The t-test compared outcomes, and a backwards stepwise binary logistic regression was used to determine the factors providing independent prediction of an unfavorable outcome. RESULTS: Baseline biochemical data were obtained in approximately 91% of cases from 803 patients. On admission, 73% of patients were good grade (World Federation of Neurological Surgeons grades 1 or 2); however, 84% had a Fisher grade 3 or 4 on computed tomographic scan. For patients presenting with good grade on admission, higher levels of C-reactive protein, glucose, and white blood cells and lower levels of hematocrit, albumin, and hemoglobin were associated with poor outcome at discharge. C-reactive protein was found to be an independent predictor of outcome for patients presenting in good grade. CONCLUSION: Early recording of C-reactive protein may prove useful in detecting those good grade patients who are at greater risk of clinical deterioration and poor outcome.


2016 ◽  
Vol 35 (02) ◽  
pp. 105-110
Author(s):  
Ariane Avellar ◽  
Gerival Vieira Junior ◽  
Lucas Albuquerque ◽  
Rodrigo Macedo ◽  
Marcos Dellaretti

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Andrew Silverman ◽  
Sreeja Kodali ◽  
Sumita Strander ◽  
Emily Gilmore ◽  
Alexandra Kimmel ◽  
...  

Abstract INTRODUCTION Effective blood pressure (BP) management after aneurysmal subarachnoid hemorrhage (aSAH) is critical for maintaining optimal cerebral perfusion and protecting the brain from further injury. How to best manage BP during the early stages of aSAH remains uncertain. In this study, we calculated individualized BP thresholds at which cerebral autoregulation was best preserved. We analyzed how deviating from these limits correlates with functional outcome. METHODS We prospectively enrolled 31 patients with aSAH. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy (NIRS)-derived tissue oxygenation – a surrogate for cerebral blood flow – as well as intracranial pressure (ICP) in response to changes in mean arterial pressure (MAP) using time-correlation analysis. The resulting autoregulatory indices were used to trend BP ranges at which autoregulation was most preserved. The percent time that MAP exceeded limits of autoregulation (LA) was calculated for each patient. Functional outcome was assessed using the modified Rankin Scale (mRS) at discharge and 90 d. Associations with outcome were analyzed using ordinal multivariate logistic regression. RESULTS Personalized LA were computed in all patients (age 57.5, 23F, mean WFNS 2, monitoring time 67.8 h). Optimal BP and LA were calculated on average for 89.5% of the total monitoring period. ICP- and NIRS-derived optimal pressures and LA strongly correlated with one another (P < .0001). Percent time that MAP deviated from LA significantly associated with worse functional outcome at discharge (NIRS P = .001, ICP P = .004) and 90 d (NIRS P = .002, ICP P = .003), adjusting separately for age, WFNS, vasospasm, or delayed cerebral ischemia. CONCLUSION Both invasive (ICP) and non-invasive (NIRS) determination of personalized BP thresholds for aSAH patients is feasible, and these 2 approaches revealed significant collinearity. Exceeding individualized autoregulatory thresholds may increase the risk of poor functional outcomes.


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