Rebleeding drives poor outcome in aneurysmal subarachnoid hemorrhage independent of delayed cerebral ischemia: a propensity-score matched cohort study

2020 ◽  
Vol 133 (2) ◽  
pp. 360-368
Author(s):  
Victor M. Lu ◽  
Christopher S. Graffeo ◽  
Avital Perry ◽  
Lucas P. Carlstrom ◽  
Leonardo Rangel-Castilla ◽  
...  

OBJECTIVEDelayed cerebral ischemia (DCI) and aneurysm rebleeding contribute to morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH); however, the relationship between their impacts on overall functional outcome is incompletely understood.METHODSThe authors conducted a cohort study of all aSAH during the study period from 2001 to 2016. Primary end points were overall functional outcome and ischemic aSAH sequelae, defined as delayed cerebral ischemia (DCI), DCI with infarction, symptomatic vasospasm (SV), and global cerebral edema (GCE). Outcomes were compared between the rebleed and nonrebleed cohorts overall and after propensity-score matching (PSM) for risk factors and treatment modality. Univariate and multivariate ordered logistic regression analyses for functional outcomes were performed in the PSM cohort to identify predictors of poor outcome.RESULTSFour hundred fifty-five aSAH cases admitted within 24 hours of aneurysm rupture were included, of which 411 (90%) experienced initial aneurysm ruptures only, while 44 (10%) had clinically confirmed rebleeding. In the overall cohort, rebleeding was associated with significantly worse functional outcome, longer intensive care unit length of stay (LOS), and GCE (all p < 0.01); treatment modality, overall LOS, DCI, DCI with infarction, and SV were nonsignificant. In the PSM analysis of 43 matched rebleed and 43 matched nonrebleed cases, only poor functional outcome and GCE remained significantly associated with rebleeding (p < 0.01 and p = 0.02, respectively). Multivariate regression identified that both rebleeding (HR 21.5, p < 0.01) and DCI (HR 10.1, p = 0.01) independently predicted poor functional outcome.CONCLUSIONSRebleeding and DCI after aSAH are highly morbid and potentially deadly events after aSAH, which appear to have independent negative impacts on overall functional outcome. Early rebleeding did not significantly affect the risk of delayed ischemic complications.

Author(s):  
Claudia Ditz ◽  
Björn Machner ◽  
Hannes Schacht ◽  
Alexander Neumann ◽  
Peter Schramm ◽  
...  

AbstractPlatelet activation has been postulated to be involved in the pathogenesis of delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to investigate potentially beneficial effects of antiplatelet therapy (APT) on angiographic CVS, DCI-related infarction and functional outcome in endovascularly treated aSAH patients. Retrospective single-center analysis of aSAH patients treated by endovascular aneurysm obliteration. Based on the post-interventional medical regime, patients were assigned to either an APT group or a control group not receiving APT. A subgroup analysis separately investigated those APT patients with aspirin monotherapy (MAPT) and those receiving dual treatment (aspirin plus clopidogrel, DAPT). Clinical and radiological characteristics were compared between groups. Possible predictors for angiographic CVS, DCI-related infarction, and an unfavorable functional outcome (modified Rankin scale ≥ 3) were analyzed. Of 160 patients, 85 (53%) had received APT (n = 29 MAPT, n = 56 DAPT). APT was independently associated with a lower incidence of an unfavorable functional outcome (OR 0.40 [0.19–0.87], P = 0.021) after 3 months. APT did not reduce the incidence of angiographic CVS or DCI-related infarction. The pattern of angiographic CVS or DCI-related infarction as well as the rate of intracranial hemorrhage did not differ between groups. However, the lesion volume of DCI-related infarctions was significantly reduced in the DAPT subgroup (P = 0.011). Post-interventional APT in endovascularly treated aSAH patients is associated with better functional outcome at 3 months. The beneficial effect of APT might be mediated by reduction of the size of DCI-related infarctions.


2018 ◽  
Vol 128 (5) ◽  
pp. 1311-1317 ◽  
Author(s):  
Christoph J. Griessenauer ◽  
Robert M. Starke ◽  
Paul M. Foreman ◽  
Philipp Hendrix ◽  
Mark R. Harrigan ◽  
...  

OBJECTIVEEndothelin-1, a potent vasoconstrictor, and its receptors may be involved in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH), clinical vasospasm, delayed cerebral ischemia (DCI), and functional outcome following aSAH. In the present study, common endothelin single nucleotide polymorphisms (SNPs) and their relation to aSAH were evaluated.METHODSBlood samples from all patients enrolled in the Cerebral Aneurysm Renin Angiotensin System (CARAS) study were used for genetic evaluation. The CARAS study prospectively enrolled patients with aSAH at 2 academic institutions in the US from 2012 to 2015. Common endothelin SNPs were detected using 5′ exonnuclease (TaqMan) genotyping assays. Analysis of associations between endothelin SNPs and aSAH and its clinical sequelae was performed.RESULTSSamples from 149 patients with aSAH and 50 controls were available for analysis. In multivariate logistic regression analysis, the TG (odds ratio [OR] 2.102, 95% confidence interval [CI] 1.048–4.218, p = 0.036) and TT genotypes (OR 7.884, 95% CI 1.003–61.995, p = 0.05) of the endothelin-1 T/G SNP (rs1800541) were significantly associated with aSAH. There was a dominant effect of the G allele (CG/GG genotypes; OR 4.617, 95% CI 1.311–16.262, p = 0.017) of the endothelin receptor A G/C SNP (rs5335) on clinical vasospasm. Endothelin SNPs were not associated with DCI or functional outcome.CONCLUSIONSCommon endothelin SNPs were found to be associated with presentation with aSAH and clinical vasospasm. Further studies are required to elucidate the relevant pathophysiology and its potential implications in the treatment of patients with aSAH.


2012 ◽  
Vol 117 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Elias A. Giraldo ◽  
Jay N. Mandrekar ◽  
Mark N. Rubin ◽  
Stefan A. Dupont ◽  
Yi Zhang ◽  
...  

Object Timing of clinical grading has not been fully studied in patients with aneurysmal subarachnoid hemorrhage (SAH). The primary objective of this study was to identify at which time point clinical assessment using the World Federation of Neurosurgical Societies (WFNS) grading scale and the Glasgow Coma Scale (GCS) is most predictive of poor functional outcome. Methods This study is a retrospective cohort study on the association between poor outcome and clinical grading determined at presentation, nadir, and postresuscitation. Poor functional outcome was defined as a Glasgow Outcome Scale score of 1–3 at 6 months after SAH. Results The authors identified 186 consecutive patients admitted to a teaching hospital between January 2002 and June 2008. The patients' mean age (± SD) was 56.9 ± 13.7 years, and 63% were women. Twenty-four percent had poor functional outcome (the mortality rate was 17%). On univariable logistic regression analyses, GCS score determined at presentation (OR 0.80, p < 0.0001), nadir (OR 0.73, p < 0.0001), and postresuscitation (OR 0.53, p < 0.0001); modified Fisher scale (OR 2.21, p = 0.0013); WFNS grade assessed at presentation (OR 1.92, p < 0.0001), nadir (OR 3.51, < 0.0001), and postresuscitation (OR 3.91, p < 0.0001); intracerebral hematoma on initial CT (OR 4.55, p < 0.0002); acute hydrocephalus (OR 2.29, p = 0.0375); and cerebral infarction (OR 4.84, p < 0.0001) were associated with poor outcome. On multivariable logistic regression analysis, only cerebral infarction (OR 5.80, p = 0.0013) and WFNS grade postresuscitation (OR 3.43, p < 0.0001) were associated with poor outcome. Receiver operating characteristic/area under the curve (AUC) analysis demonstrated that WFNS grade determined postresuscitation had a stronger association with poor outcome (AUC 0.90) than WFNS grade assessed upon admission or at nadir. Conclusions Timing of WFNS grade assessment affects its prognostic value. Outcome after aneurysmal SAH is best predicted by assessing WFNS grade after neurological resuscitation.


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.


2021 ◽  
Author(s):  
Kehua Chen ◽  
Guanghua Huang ◽  
Chengwei Cai ◽  
Chuangnan Yan ◽  
Fuguang Zhang ◽  
...  

Abstract Cystatin C (CysC) has been found to be associated with hemorrhagic and ischemic stroke in many studies. However, the association between CysC level and the risk of delayed cerebral ischemia after endovascular treatment of aneurysmal subarachnoid hemorrhage has been reported rarely. Our study was proposed to explore this association. Consecutive patients from June 2015 to February 2021 in this single-center retrospective study were selected. Univariate and multivariate analyses were used to identify potential prognostic risk factors for delayed cerebral ischemia, and the stability of the association was demonstrated by several statistical methods, such as subgroup analysis, interaction testing, generalized linear models, and propensity score matching. A total of 424 patients were included in the analysis. Cystatin C was independently associated with delayed cerebral ischemia. The independent effects of CysC on delayed cerebral ischemia were shown in generalized linear models with a logit link, and the results were relatively stable in crude, partial, and full models with ORs (95% CIs) for delayed cerebral ischemia. Subgroup analysis showed no significant subgroup differences in the effect of CysC on delayed cerebral ischemia. There was also no interaction effect between CysC and other confounders. Patients in the high CysC group had a higher risk of delayed cerebral ischemia than those in the low CysC group before and after propensity score matching. CysC level could be an independent predictor for the risk of delayed cerebral ischemia after endovascular treatment of aneurysmal subarachnoid hemorrhage.


2018 ◽  
Vol 128 (3) ◽  
pp. 717-722 ◽  
Author(s):  
Masaomi Koyanagi ◽  
Hitoshi Fukuda ◽  
Benjamin Lo ◽  
Minami Uezato ◽  
Yoshitaka Kurosaki ◽  
...  

OBJECTIVEDelayed cerebral ischemia (DCI) is an important complication after aneurysmal subarachnoid hemorrhage (aSAH). Although intrathecal milrinone injection via lumbar catheter to prevent DCI has been previously reported to be safe and feasible, its effectiveness remains unknown. The goal of this study was to evaluate whether intrathecal milrinone injection treatment after aSAH significantly reduced the incidence of DCI.METHODSThe prospectively maintained aSAH database was used to identify patients treated between January 2010 and December 2015. The cohort included 274 patients, with group assignment based on treatment with intrathecal milrinone injection or not. A propensity score model was generated for each patient group, incorporating relevant patient variables.RESULTSAfter propensity score matching, 99 patients treated with intrathecal milrinone injection and 99 without treatment were matched on the basis of similarities in their demographic and clinical characteristics. There were significantly fewer DCI events (4% vs 14%, p = 0.024) in patients treated with intrathecal milrinone injection compared with those treated without it. However, there were no significant differences between the 2 groups with respect to their 90-day functional outcomes (46% vs 36%, p = 0.31). The likelihood of chronic secondary hydrocephalus, meningitis, and congestive heart failure as complications of intrathecal milrinone injection therapy was also similar between the groups.CONCLUSIONSIn propensity score–matched groups, the intrathecal administration of milrinone via lumbar catheter showed significant reduction of DCI following aSAH, without an associated increase in complications.


2017 ◽  
Vol 126 (5) ◽  
pp. 1545-1551 ◽  
Author(s):  
Fawaz Al-Mufti ◽  
David Roh ◽  
Shouri Lahiri ◽  
Emma Meyers ◽  
Jens Witsch ◽  
...  

OBJECTIVEThe clinical significance of cerebral ultra-early angiographic vasospasm (UEAV), defined as cerebral arterial narrowing within the first 48 hours of aneurysmal subarachnoid hemorrhage (aSAH), remains poorly characterized. The authors sought to determine its frequency, predictors, and impact on functional outcome.METHODSThe authors prospectively studied UEAV in a cohort of 1286 consecutively admitted patients with aSAH between August 1996 and June 2013. Admission clinical, radiographic, and acute clinical course information was documented during patient hospitalization. Functional outcome was assessed at 3 months using the modified Rankin Scale. Logistic regression and Cox proportional hazards models were generated to assess predictors of UEAV and its relationship to delayed cerebral ischemia (DCI) and outcome. Multiple imputation methods were used to address data lost to follow-up.RESULTSThe cohort incidence rate of UEAV was 4.6%. Multivariable logistic regression analysis revealed that younger age, sentinel bleed, and poor admission clinical grade were significantly associated with UEAV. Patients with UEAV had a 2-fold increased risk of DCI (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.4–3.9, p = 0.002) and cerebral infarction (OR 2.0, 95% CI 1.0–3.9, p = 0.04), after adjusting for known predictors. Excluding patients who experienced sentinel bleeding did not change this effect. Patients with UEAV also had a significantly higher hazard for DCI in a multivariable model. UEAV was not found to be significantly associated with poor functional outcome (OR 0.8, 95% CI 0.4–1.6, p = 0.5).CONCLUSIONSUEAV may be less frequent than has been reported previously. Patients who exhibit UEAV are at higher risk for refractory DCI that results in cerebral infarction. These patients may benefit from earlier monitoring for signs of DCI and more aggressive treatment. Further study is needed to determine the long-term functional significance of UEAV.


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