Unfavorable Outcome After Good Grade Aneurysmal Subarachnoid Hemorrhage: Exploratory Analysis

Object In a previous randomized controlled trial, the authors demonstrated that acute erythropoietin (EPO) therapy reduced severe vasospasm and delayed ischemic deficits (DIDs) following aneurysmal subarachnoid hemorrhage. In this study, the authors aimed to investigate the potential interaction of neurovascular protection by EPO with age, sepsis, and concurrent statin therapy. Methods The clinical events of 80 adults older than 18 years and with < 72 hours of aneurysmal subarachnoid hemorrhage, who were randomized to receive 30,000 U of intravenous EPO-β or placebo every 48 hours for a total of 3 doses, were analyzed by stratification according to age (< or ≥ 60 years), sepsis, or concomitant statin therapy. End points in the trial included cerebral vasospasm and impaired autoregulation on transcranial Doppler ultrasonography, DIDs, and unfavorable outcome at discharge and at 6 months measured with the modified Rankin Scale and Glasgow Outcome Scale. Analyses were performed using the t-test and/or ANOVA for repeated measurements. Results Younger patients (< 60 years old) or those without sepsis obtained benefits from EPO by a reduction in vasospasm, impaired autoregulation, and unfavorable outcome at discharge. Compared with nonseptic patients taking EPO, those with sepsis taking EPO had a lower absolute reticulocyte count (nonsepsis vs sepsis, 143.5 vs. 105.8 × 109/L on Day 6; p = 0.01), suggesting sepsis impaired both hematopoiesis and neurovascular protection by EPO. In the EPO group, none of the statin users suffered DIDs (p = 0.078), implying statins may potentiate neuroprotection by EPO. Conclusions Erythropoietin-related neurovascular protection appears to be attenuated by old age and sepsis and enhanced by statins, an important finding for designing Phase III trials.

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Fatty Acid-Binding Protein 3 and CXC-Chemokine Ligand 16 are Associated with Unfavorable Outcome in Aneurysmal Subarachnoid Hemorrhage

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2021.106068 ◽

2021 ◽

Vol 30 (11) ◽

pp. 106068

Author(s):

Daniel Schranz ◽

Tihamer Molnar ◽

Szabina Erdo-Bonyar ◽

Diana Simon ◽

Tímea Berki ◽

...

Keyword(s):

Fatty Acid ◽

Subarachnoid Hemorrhage ◽

Fatty Acid Binding Protein ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Binding Protein ◽

Unfavorable Outcome ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Cxc Chemokine ◽

Chemokine Ligand

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Abstract TMP105: Endovascular Treatment of Severe and Refractory Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage Improves Outcome: A Systematic Review and Meta-analysis of Different Treatment Options Evaluated Since 2006 for Cerebral Vasospasm

Stroke ◽

10.1161/str.47.suppl_1.tmp105 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Gregoire Boulouis ◽

Marc-Antoine Labeyrie ◽

Jean Raymond ◽

Christine Rodriguez-Regent ◽

Anne-Claire Lukaszewicz ◽

...

Keyword(s):

Systematic Review ◽

Subarachnoid Hemorrhage ◽

Clinical Outcome ◽

Endovascular Treatment ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Meta Analysis ◽

Route Of Administration ◽

Unfavorable Outcome ◽

Q Value

Introduction: To report clinical outcome of aneurysmal subarachnoid hemorrhage (aSAH) patients exposed to cerebral vasospasm (CVS) targeted treatments in a systematic review and meta-analysis and compare the efficacy of endovascular and non-endovascular treatments in severe / refractory vasospasm patients. Methods: The literature was searched using PubMed, EMBASE, and The Cochrane Library database. Eligibility criteria were (1) Rated clinical outcome; (2) at least 10 patients; (3) aSAH; (4) study published in English or French (January 2006 - October 2014); and (5) methodological quality score > 10, according to STROBE criteria. Endpoint included unfavorable outcome rate, defined as mRS 3-6, GOS 1-3 or GOSE 1-4 at latest follow-up. Analyses included stratification per route of administration (oral, i.v., intra-arterial or cisternoventricular) and per study inclusion criteria (severe, CVS, refractory CVS or high risk for CVS). Univariate and multivariate subgroup analyses were performed to identify interventions associated with a better outcome. Results: Sixty-two studies, including 26 randomized controlled trials, were included (8976 patients). Overall 2490 patients had unfavorable outcome including death (random-effect weighted average: 33.7%, 99%CI, 28.1-39.7%; Q-value: 806.0, I 2 =92.7%). Clinical outcome was significantly better in severe or refractory patients for whom, on top of best medical treatment, endovascular intervention was performed (RR=0.76, IC95% [0.66-0.89], p <0.00001) whereas other route of administration didn’t show significant differences. RR of unfavorable outcome was significantly lower, vs control groups, in patients treated with Cilostazol (RR=0.46 (IC99% [0.25-0.85], P = 0.001, Q value 1.5, I 2 = 0). Conclusion: In case of CVS following aSAH, endovascular treatment in severe / refractory vasospasm patients. including intra-arterial injection of pharmacological agents or balloon angioplasty, improves outcome as compared to other route of administration.

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Elevated Baseline C-Reactive Protein as a Predictor of Outcome After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽

10.1227/neu.0000000000000963 ◽

2015 ◽

Vol 77 (5) ◽

pp. 786-793 ◽

Cited By ~ 22

Author(s):

◽

Carole L. Turner ◽

Karol Budohoski ◽

Christopher Smith ◽

Peter J. Hutchinson ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

White Blood Cells ◽

Cerebral Injury ◽

World Federation ◽

C Reactive Protein ◽

Reactive Protein ◽

Poor Outcome ◽

Fisher Grade ◽

Good Grade

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.

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Safety and Clinical Outcome of Good-Grade Aneurysmal Subarachnoid Hemorrhage in Non-Intensive Care Units

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2020.105123 ◽

2020 ◽

Vol 29 (10) ◽

pp. 105123

Author(s):

Clare Angeli G. Enriquez ◽

Jose Danilo B. Diestro ◽

Abdelsimar T. Omar ◽

Romergryko G. Geocadin ◽

Gerardo D. Legaspi

Keyword(s):

Intensive Care ◽

Subarachnoid Hemorrhage ◽

Clinical Outcome ◽

Intensive Care Units ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Good Grade

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Correlation Among Systemic Inflammatory Parameter, Occurrence of Delayed Neurological Deficits, and Outcome After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽

10.1227/neu.0b013e31828048ce ◽

2012 ◽

Vol 72 (3) ◽

pp. 367-375 ◽

Cited By ~ 48

Author(s):

Carl Muroi ◽

Michael Hugelshofer ◽

Martin Seule ◽

Ilhan Tastan ◽

Masayuki Fujioka ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Confidence Interval ◽

Early Phase ◽

Odds Ratio ◽

Time Course ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Unfavorable Outcome ◽

Neurological Deficits ◽

Inflammatory Parameters ◽

Leukocyte Counts

Abstract BACKGROUND: The role and impact of systemic inflammatory response after aneurysmal subarachnoid hemorrhage remain to be elucidated. OBJECTIVE: To assess the time course and correlation of systemic inflammatory parameters with outcome and the occurrence of delayed ischemic neurological deficits (DINDs) after subarachnoid hemorrhage. METHODS: Besides the baseline characteristics, daily interleukin-6 (IL-6), procalcitonin, C-reactive protein levels, and leukocyte counts were prospectively measured until day 14 after subarachnoid hemorrhage. Occurrence of infectious complications and application of therapeutic hypothermia were assessed as confounding factors. The primary end point was outcome after 3 months, assessed by Glasgow Outcome Scale; the secondary end point was the occurrence of DINDs. RESULTS: During a 3-year period, a total of 138 patients were included. All inflammatory parameters measured were higher in patients with unfavorable outcome (Glasgow Outcome Scale score, 1-3). After adjustment for confounding factors, elevated IL-6 and leukocyte counts remained significant risk factors for unfavorable outcome. The odds ratio for log IL-6 was 4.07 (95% confidence interval, 1.18 to 14.03; P = .03) and for leukocyte counts was 1.24 (95% confidence interval, 1.06-1.46, P = .008). The analysis of the time course established that IL-6 was the only significantly elevated parameter in the early phase in patients with unfavorable outcome. Higher IL-6 levels in the early phase (days 3-7) were associated with the occurrence of DINDs. The adjusted odds ratio for log IL-6 was 4.03 (95% confidence interval, 1.21-13.40; P = .02). CONCLUSION: Higher IL-6 levels are associated with worse clinical outcome and the occurrence of DINDs. Because IL-6 levels were significantly elevated in the early phase, they might be a useful parameter to monitor.

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Altered Cerebral Autoregulation and CO2 Reactivity after Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽

10.1227/00006123-198805000-00003 ◽

1988 ◽

Vol 22 (5) ◽

pp. 822-826 ◽

Cited By ~ 108

Author(s):

Paul D. Dernbach ◽

John R. Little ◽

Stephen C. Jones ◽

Zeyd Y. Ebrahim

Keyword(s):

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Early Operation ◽

Co2 Reactivity ◽

Aneurysm Clipping ◽

Arterial Blood ◽

Nearest Point ◽

Good Grade ◽

Grade Ii ◽

Pressure Autoregulation

Abstract Disruption of local cortical blood flow (CBF) autoregulation and CO2 reactivity, or vasoparalysis, has been documented in humans after aneurysmal subarachnoid hemorrhage (SAH). Generally, the degree of vasoparalysis is related to the patient's clinical grade. Using intraoperative measurement of local CBF, we evaluated pressure autoregulation and CO2 reactivity in patients after SAH. Fourteen patients with SAH and 10 patients with asymptomatic aneurysm underwent craniotomy for clipping of their aneurysms. During operation, local CBF was recorded with thermal conductivity probes placed on the middle frontal gyrus, 4 to 6 cm from the nearest point of retraction. Before retractor placement, CBF was measured with the PCO2 at 25 and 35 mm Hg and the mean arterial blood pressure (MABP) between 70 and 80 mm Hg. After aneurysm clipping, flows were again measured. With the PCO2 at 25 mm Hg, the MABP was raised from 65 to 85 mm Hg. The PCO2 was then allowed to rise to 35 mm Hg, after which the MABP was lowered from 85 to 65 mm Hg. Six patients underwent operation within the 1st week after SAH (Grade I, n = 3; Grade II, n = 3). The remainder (n = 8) were operated on 9 days to 3 months after SAH. After aneurysm clipping, significant CBF changes (P < 0.001) with PCO2 alteration occurred in control patients and those operated on more than 7 days after SAH. There was no significant change in CBF in patients operated on within 7 days after SAH. Changes in CBF reactivity to alteration of MABP were significantly larger in early operation patients than in other groups (P < 0.008). Pressure autoregulation and CO2 reactivity are significantly disturbed in good grade patients after early operation.

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Effects of decompressive craniectomy on functional outcomes and death in poor-grade aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

Journal of Neurosurgery ◽

10.3171/2016.9.jns161383 ◽

2017 ◽

Vol 127 (6) ◽

pp. 1315-1325 ◽

Cited By ~ 14

Author(s):

Naif M. Alotaibi ◽

Ghassan Awad Elkarim ◽

Nardin Samuel ◽

Oliver G. S. Ayling ◽

Daipayan Guha ◽

...

Keyword(s):

Systematic Review ◽

Subarachnoid Hemorrhage ◽

Decompressive Craniectomy ◽

Glasgow Outcome Scale ◽

Functional Outcomes ◽

Event Rate ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Meta Analysis ◽

Unfavorable Outcome ◽

Poor Grade

OBJECTIVEPatients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) (World Federation of Neurosurgical Societies Grade IV or V) are often considered for decompressive craniectomy (DC) as a rescue therapy for refractory intracranial hypertension. The authors performed a systematic review and meta-analysis to assess the impact of DC on functional outcome and death in patients after poor-grade aSAH.METHODSA systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were identified through the Ovid Medline, Embase, Web of Science, and Cochrane Library databases from inception to October 2015. Only studies dedicated to patients with poor-grade aSAH were included. Primary outcomes were death and functional outcome assessed at any time period. Patients were grouped as having a favorable outcome (modified Rankin Scale [mRS] Scores 1–3, Glasgow Outcome Scale [GOS] Scores 4 and 5, extended Glasgow Outcome Scale [GOSE] Scores 5–8) or unfavorable outcome (mRS Scores 4–6, GOS Scores 1–3, GOSE Scores 1–4). Pooled estimates of event rates and odds ratios with 95% confidence intervals were calculated using the random-effects model.RESULTSFifteen studies encompassing 407 patients were included in the meta-analysis (all observational cohorts). The pooled event rate for poor outcome across all studies was 61.2% (95% CI 52%–69%) and for death was 27.8% (95% CI 21%–35%) at a median of 12 months after aSAH. Primary (or early) DC resulted in a lower overall event rate for unfavorable outcome than secondary (or delayed) DC (47.5% [95% CI 31%–64%] vs 74.4% [95% CI 43%–91%], respectively). Among studies with comparison groups, there was a trend toward a reduced mortality rate 1–3 months after discharge among patients who did not undergo DC (OR 0.58 [95% CI 0.27–1.25]; p = 0.168). However, this trend was not sustained at the 1-year follow-up (OR 1.09 [95% CI 0.55–2.13]; p = 0.79).CONCLUSIONSResults of this study summarize the best evidence available in the literature for DC in patients with poor-grade aSAH. DC is associated with high rates of unfavorable outcome and death. Because of the lack of robust control groups in a majority of the studies, the effect of DC on functional outcomes versus that of other interventions for refractory intracranial hypertension is still unknown. A randomized trial is needed.

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122 Significance of Fluctuations in Serum Sodium Levels Following Aneurysmal Subarachnoid Hemorrhage: An Exploratory Analysis

Neurosurgery ◽

10.1093/neuros/nyx417.122 ◽

2017 ◽

Vol 64 (CN_suppl_1) ◽

pp. 227-227

Author(s):

Matt E Eagles ◽

Michael K Tso ◽

R Loch Macdonald

Keyword(s):

Subarachnoid Hemorrhage ◽

Serum Sodium ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Statistical Significance ◽

Univariate Analysis ◽

Delayed Cerebral Ischemia ◽

Exploratory Analysis ◽

Base Line ◽

Poor Outcome ◽

Increased Risk

Abstract INTRODUCTION Changes in serum sodium levels are common following aneurysmal subarachnoid hemorrhage (aSAH), and may be linked to increased morbidity. In this exploratory analysis we assessed whether fluctuations in serum sodium levels after aSAH have an association with clinical outcomes and/or delayed cerebral ischemia (DCI). METHODS We performed a retrospective analysis of data from CONSCIOUS-1 (n = 413), a randomized controlled trial of clazosentan treatment in patients with aSAH. Patient serum sodium levels were checked daily during the hospital stay up to day 14. Mean-per-day fluctuations in serum sodium were calculated by summing the absolute deviation of serum sodium at day 2–14 from day 1 base-line divided by the total number of days with lab values. Logistic regression and LOWESS smoothing curves were used to determine association between serum sodium deviation and poor outcome at 3 months (defined as modified Rankin Scale, mRS> 2) or DCI. RESULTS >Mean-per-day deviation of serum sodium from baseline was associated with poor outcome on univariate analysis (P = 0.028), and maintained statistical significance after correcting for age and World Federation of Neurological Surgeons (WFNS) grade (P = 0.044). A LOWESS smoothing curve showed an increased risk of DCI for patients with greater deviations from their baseline sodium values. Multivariate regression, including WFNS and Fisher Scale grades, demonstrated absolute variation in sodium values to be associated with DCI (P = 0.045). CONCLUSION In this study, greater deviations in serum sodium values independently predicted poor outcome and the development of DCI.

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