Low-Dose Intravenous Heparin Infusion After Aneurysmal Subarachnoid Hemorrhage is Associated With Decreased Risk of Delayed Neurological Deficit and Cerebral Infarction

Neurosurgery ◽  
2020 ◽  
Author(s):  
Matthew J Kole ◽  
Aaron P Wessell ◽  
Beatrice Ugiliweneza ◽  
Gregory J Cannarsa ◽  
Enzo Fortuny ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Infarction ◽  
Low Dose ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Neurological Deficits ◽  
Comparison Analysis ◽  
Cohort Comparison ◽  
Multivariable Logistic Regression ◽  
Intravenous Heparin

Abstract BACKGROUND Patients who survive aneurysmal subarachnoid hemorrhage (aSAH) are at risk for delayed neurological deficits (DND) and cerebral infarction. In this exploratory cohort comparison analysis, we compared in-hospital outcomes of aSAH patients administered a low-dose intravenous heparin (LDIVH) infusion (12 U/kg/h) vs those administered standard subcutaneous heparin (SQH) prophylaxis for deep vein thrombosis (DVT; 5000 U, 3 × daily). OBJECTIVE To assess the safety and efficacy of LDIVH in aSAH patients. METHODS We retrospectively analyzed 556 consecutive cases of aSAH patients whose aneurysm was secured by clipping or coiling at a single institution over a 10-yr period, including 233 administered the LDIVH protocol and 323 administered the SQH protocol. Radiological and outcome data were compared between the 2 cohorts using multivariable logistic regression and propensity score-based inverse probability of treatment weighting (IPTW). RESULTS The unadjusted rate of cerebral infarction in the LDIVH cohort was half that in SQH cohort (9 vs 18%; P = .004). Multivariable logistic regression showed that patients in the LDIVH cohort were significantly less likely than those in the SQH cohort to have DND (odds ratio (OR) 0.53 [95% CI: 0.33, 0.85]) or cerebral infarction (OR 0.40 [95% CI: 0.23, 0.71]). Analysis following IPTW showed similar results. Rates of hemorrhagic complications, heparin-induced thrombocytopenia and DVT were not different between cohorts. CONCLUSION This cohort comparison analysis suggests that LDIVH infusion may favorably influence the outcome of patients after aSAH. Prospective studies are required to further assess the benefit of LDIVH infusion in patients with aSAH.

Timing of clinical grade assessment and poor outcome in patients with aneurysmal subarachnoid hemorrhage

2012 ◽  
Vol 117 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Elias A. Giraldo ◽  
Jay N. Mandrekar ◽  
Mark N. Rubin ◽  
Stefan A. Dupont ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Infarction ◽  
Functional Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Intracerebral Hematoma ◽  
Poor Functional Outcome ◽  
Poor Outcome ◽  
Grade Assessment ◽  
Clinical Grading

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.

scholarly journals An Externally Validated Dynamic Nomogram for Predicting Unfavorable Prognosis in Patients With Aneurysmal Subarachnoid Hemorrhage

2021 ◽  
Vol 12 ◽  
Author(s):  
Ping Hu ◽  
Yang Xu ◽  
Yangfan Liu ◽  
Yuntao Li ◽  
Liguo Ye ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Prognostic Factors ◽  
Subarachnoid Hemorrhage ◽  
Validation Cohort ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
External Validation ◽  
Brier Score ◽  
Web Based ◽  
Training Cohort ◽  
Multivariable Logistic Regression

Background: Aneurysmal subarachnoid hemorrhage (aSAH) leads to severe disability and functional dependence. However, no reliable method exists to predict the clinical prognosis after aSAH. Thus, this study aimed to develop a web-based dynamic nomogram to precisely evaluate the risk of poor outcomes in patients with aSAH.Methods: Clinical patient data were retrospectively analyzed at two medical centers. One center with 126 patients was used to develop the model. Least absolute shrinkage and selection operator (LASSO) analysis was used to select the optimal variables. Multivariable logistic regression was applied to identify independent prognostic factors and construct a nomogram based on the selected variables. The C-index and Hosmer–Lemeshow p-value and Brier score was used to reflect the discrimination and calibration capacities of the model. Receiver operating characteristic curve and calibration curve (1,000 bootstrap resamples) were generated for internal validation, while another center with 84 patients was used to validate the model externally. Decision curve analysis (DCA) and clinical impact curves (CICs) were used to evaluate the clinical usefulness of the nomogram.Results: Unfavorable prognosis was observed in 46 (37%) patients in the training cohort and 24 (29%) patients in the external validation cohort. The independent prognostic factors of the nomogram, including neutrophil-to-lymphocyte ratio (NLR) (p = 0.005), World Federation of Neurosurgical Societies (WFNS) grade (p = 0.002), and delayed cerebral ischemia (DCI) (p = 0.0003), were identified using LASSO and multivariable logistic regression. A dynamic nomogram (https://hu-ping.shinyapps.io/DynNomapp/) was developed. The nomogram model demonstrated excellent discrimination, with a bias-corrected C-index of 0.85, and calibration capacities (Hosmer–Lemeshow p-value, 0.412; Brier score, 0.12) in the training cohort. Application of the model to the external validation cohort yielded a C-index of 0.84 and a Brier score of 0.13. Both DCA and CIC showed a superior overall net benefit over the entire range of threshold probabilities.Conclusion: This study identified that NLR on admission, WFNS grade, and DCI independently predicted unfavorable prognosis in patients with aSAH. These factors were used to develop a web-based dynamic nomogram application to calculate the precise probability of a poor patient outcome. This tool will benefit personalized treatment and patient management and help neurosurgeons make better clinical decisions.

scholarly journals Ultra-early angiographic vasospasm associated with delayed cerebral ischemia and infarction following aneurysmal subarachnoid hemorrhage

2017 ◽  
Vol 126 (5) ◽  
pp. 1545-1551 ◽  
Author(s):  
Fawaz Al-Mufti ◽  
David Roh ◽  
Shouri Lahiri ◽  
Emma Meyers ◽  
Jens Witsch ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Functional Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Angiographic Vasospasm ◽  
Increased Risk ◽  
Address Data

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.

Association between weekend admissions and mortality after aneurysmal subarachnoid hemorrhage: the “weekend effect” revisited

2020 ◽  
Vol 132 (4) ◽  
pp. 1167-1173 ◽  
Author(s):  
Mirriam Mikhail ◽  
Oliver G. S. Ayling ◽  
Matthew E. Eagles ◽  
George M. Ibrahim ◽  
R. Loch Macdonald
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Neurological Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Weekend Effect ◽  
Medical Specialties ◽  
Poor Grade ◽  
Multivariable Logistic Regression ◽  
Wide Range

OBJECTIVEHigher mortality has been reported with weekend or after-hours patient admission across a wide range of surgical and medical specialties, a phenomenon termed the “weekend effect.” The authors evaluated whether weekend admission contributed to death and long-term neurological outcome in patients following aneurysmal subarachnoid hemorrhage.METHODSA post hoc analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) study was conducted. Univariable and stepwise multivariable logistic regression analyses were performed to assess the associations between weekend admission and mortality and long-term neurological outcome.RESULTSOf 413 subjects included in the CONSCIOUS-1 study, 140 patients had been admitted during the weekend. A significant interaction was identified between weekend admission and neurological grade on presentation, suggesting that the outcomes of patients who had initially presented with a poor grade were disproportionately influenced by the weekend admission. On stepwise multivariable logistic regression in the subgroup of patients who had presented with a poor neurological grade (29 of 100 patients), admission on the weekend was found to be independently associated with death (OR 6.59, 95% CI 1.62–26.88, p = 0.009). Weekend admission was not associated with long-term neurological outcome.CONCLUSIONSWeekend admission was an independent risk factor for death within 12 weeks following aneurysmal subarachnoid hemorrhage in patients presenting with a poor neurological grade. Further work is required to identify and mitigate any mediating factors.

Evidence for a conditioning effect of inhalational anesthetics on angiographic vasospasm after aneurysmal subarachnoid hemorrhage

2020 ◽  
Vol 133 (1) ◽  
pp. 152-158 ◽  
Author(s):  
Umeshkumar Athiraman ◽  
Diane Aum ◽  
Ananth K. Vellimana ◽  
Joshua W. Osbun ◽  
Rajat Dhar ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Multivariate Logistic Regression Analysis ◽  
Secondary Brain Injury ◽  
Large Artery ◽  
Inhalational Anesthetics ◽  
Angiographic Vasospasm ◽  
Inhalational Anesthetic

OBJECTIVEDelayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is characterized by large-artery vasospasm, distal autoregulatory dysfunction, cortical spreading depression, and microvessel thrombi. Large-artery vasospasm has been identified as an independent predictor of poor outcome in numerous studies. Recently, several animal studies have identified a strong protective role for inhalational anesthetics against secondary brain injury after SAH including DCI—a phenomenon referred to as anesthetic conditioning. The aim of the present study was to assess the potential role of inhalational anesthetics against cerebral vasospasm and DCI in patients suffering from an SAH.METHODSAfter IRB approval, data were collected retrospectively for all SAH patients admitted to the authors’ hospital between January 1, 2010, and December 31, 2013, who received general anesthesia with either inhalational anesthetics only (sevoflurane or desflurane) or combined inhalational (sevoflurane or desflurane) and intravenous (propofol) anesthetics during aneurysm treatment. The primary outcomes were development of angiographic vasospasm and development of DCI during hospitalization. Univariate and logistic regression analyses were performed to identify independent predictors of these endpoints.RESULTSThe cohort included 157 SAH patients whose mean age was 56 ± 14 (± SD). An inhalational anesthetic–only technique was employed in 119 patients (76%), while a combination of inhalational and intravenous anesthetics was employed in 34 patients (22%). As expected, patients in the inhalational anesthetic–only group were exposed to significantly more inhalational agent than patients in the combination anesthetic group (p < 0.05). Multivariate logistic regression analysis identified inhalational anesthetic–only technique (OR 0.35, 95% CI 0.14–0.89), Hunt and Hess grade (OR 1.51, 95% CI 1.03–2.22), and diabetes (OR 0.19, 95% CI 0.06–0.55) as significant predictors of angiographic vasospasm. In contradistinction, the inhalational anesthetic–only technique had no significant impact on the incidence of DCI or functional outcome at discharge, though greater exposure to desflurane (as measured by end-tidal concentration) was associated with a lower incidence of DCI.CONCLUSIONSThese data represent the first evidence in humans that inhalational anesthetics may exert a conditioning protective effect against angiographic vasospasm in SAH patients. Future studies will be needed to determine whether optimized inhalational anesthetic paradigms produce definitive protection against angiographic vasospasm; whether they protect against other events leading to secondary brain injury after SAH, including microvascular thrombi, autoregulatory dysfunction, blood-brain barrier breakdown, neuroinflammation, and neuronal cell death; and, if so, whether this protection ultimately improves patient outcome.

Effect of Cilostazol on Cerebral Vasospasm and Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized, Double-Blind, Placebo-Controlled Trial

2016 ◽  
Vol 42 (1-2) ◽  
pp. 97-105 ◽  
Author(s):  
Naoya Matsuda ◽  
Masato Naraoka ◽  
Hiroki Ohkuma ◽  
Norihito Shimamura ◽  
Katsuhiro Ito ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Infarction ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Control Group ◽  
Independent Factor ◽  
Double Blind ◽  
End Points ◽  
Double Blind Placebo ◽  
Poor Outcome

Background: Several clinical studies have indicated the efficacy of cilostazol, a selective inhibitor of phosphodiesterase 3, in preventing cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). They were not double-blinded trial resulting in disunited results on assessment of end points among the studies. The randomized, double-blind, placebo-controlled study was performed to assess the effectiveness of cilostazol on cerebral vasospasm. Methods: Patients with aneurysmal SAH admitted within 24 h after the ictus who met the following criteria were enrolled in this study: SAH on CT scan was diffuse thick, diffuse thin, or local thick, Hunt and Hess score was less than 4, administration of cilostazol or placebo could be started within 48 h of SAH. Patients were randomly allocated to placebo or cilostazol after repair of a ruptured saccular aneurysm by aneurysmal neck clipping or endovascular coiling, and the administration of cilostazol or placebo was continued up to 14 days after initiation of treatment. The primary end point was the occurrence of symptomatic vasospasm (sVS), and secondary end points were angiographic vasospasm (aVS) evaluated on digital subtraction angiography, vasospasm-related new cerebral infarction evaluated on CT scan or MRI, and clinical outcome at 3 months of SAH as assessed by Glasgow Outcome Scale, in which poor outcome was defined as severe disability, vegetative state, and death. All end points were evaluated with blinded assessment. Results: One hundred forty eight patients were randomly allocated to the cilostazol group (n = 74) or the control group (n = 74). The occurrence of sVS was significantly lower in the cilostazol group than in the control group (10.8 vs. 24.3%, p = 0.031), and multiple logistic analysis showed that cilostazol use was an independent factor reducing sVS (OR 0.293, 95% CI 0.099-0.568, p = 0.027). The incidence of aVS and vasospasm-related cerebral infarction were not significantly different between the groups. Poor outcome was significantly lower in the cilostazol group than in the control group (5.4 vs. 17.6%, p = 0.011), and multiple logistic analyses demonstrated that cilostazol use was an independent factor that reduced the incidence of poor outcome (OR 0.221, 95% CI 0.054-0.903, p = 0.035). Severe adverse events due to cilostazol administration did not occur during the study period. Conclusions: Cilostazol administration is effective in preventing sVS and improving outcomes without severe adverse events. A larger-scale study including more cases was necessary to confirm this efficacy of cilostazol.

scholarly journals Efficacy and safety of 5 mg olanzapine for nausea and vomiting management in cancer patients receiving carboplatin: integrated study of three prospective multicenter phase II trials

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Senri Yamamoto ◽  
Hirotoshi Iihara ◽  
Ryuji Uozumi ◽  
Hitoshi Kawazoe ◽  
Kazuki Tanaka ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Cancer Patients ◽  
Phase Ii ◽  
Low Dose ◽  
Nausea And Vomiting ◽  
Efficacy And Safety ◽  
Multivariable Logistic Regression ◽  
Related Risk ◽  
Total Control

Abstract Background The efficacy of olanzapine as an antiemetic agent in cancer chemotherapy has been demonstrated. However, few high-quality reports are available on the evaluation of olanzapine’s efficacy and safety at a low dose of 5 mg among patients treated with carboplatin regimens. Therefore, in this study, we investigated the efficacy and safety of 5 mg olanzapine for managing nausea and vomiting in cancer patients receiving carboplatin regimens and identified patient-related risk factors for carboplatin regimen-induced nausea and vomiting treated with 5 mg olanzapine. Methods Data were pooled for 140 patients from three multicenter, prospective, single-arm, open-label phase II studies evaluating the efficacy and safety of olanzapine for managing nausea and vomiting induced by carboplatin-based chemotherapy. Multivariable logistic regression analyses were performed to determine the patient-related risk factors. Results Regarding the endpoints of carboplatin regimen-induced nausea and vomiting control, the complete response, complete control, and total control rates during the overall study period were 87.9, 86.4, and 72.9%, respectively. No treatment-related adverse events of grade 3 or higher were observed. The multivariable logistic regression models revealed that only younger age was significantly associated with an increased risk of non-total control. Surprisingly, there was no significant difference in CINV control between the patients treated with or without neurokinin-1 receptor antagonist. Conclusions The findings suggest that antiemetic regimens containing low-dose (5 mg) olanzapine could be effective and safe for patients receiving carboplatin-based chemotherapy.

scholarly journals Vasospasm severity is associated with cerebral infarction after subarachnoid hemorrhage

2021 ◽  
Author(s):  
Samuel B Snider ◽  
Ibrahim Migdady ◽  
Sarah L LaRose ◽  
Morgan E Mckeown ◽  
Robert W Regenhardt ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Infarction ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Time Varying ◽  
Single Center ◽  
Early Screening ◽  
Angiographic Vasospasm

AbstractBackgroundThe presence of angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed-cerebral ischemia (DCI)-related cerebral infarction and worsened neurological outcome. Transcranial doppler (TCD) measurements of cerebral blood velocity are commonly used after aSAH to screen for vasospasm. We sought to determine whether time-varying TCD measured vasospasm severity is associated with cerebral infarction and to investigate the performance characteristics of different time/severity cutoffs for predicting cerebral infarction.MethodsWe used a retrospective, single-center cohort of consecutive adult aSAH patients with angiographic vasospasm and at least one TCD study. Our primary outcome was DCI-related cerebral infarction, defined as an infarction developing at least 2 days after any surgical intervention without an alternative cause. Time-varying TCD vasospasm severity was defined ordinally (absent, mild, moderate, severe) by the most abnormal vessel on each post-admission hospital day. Cox proportional-hazards models were used to examine associations between time-varying vasospasm severity and infarction. The optimal TCD-based time/severity thresholds for predicting infarction were then identified using the Youden J statistic.ResultsOf 218 aSAH patients with angiographic vasospasm, 27 (12%) developed DCI-related infarction. As compared to those without infarction, patients with infarction had higher modified Fisher scale (mFS) scores, and an earlier onset of more-severe vasospasm. Adjusted for mFS, vasospasm severity was associated with infarction (aHR 1.9, 95% CI: 1.3-2.6). A threshold of at least mild vasospasm severity on hospital day 4 had a negative predictive value of 92% for the development of infarction, but a positive predictive value of 25%.ConclusionsIn aSAH, TCD-measured vasospasm severity is associated with DCI-related infarction. In a single-center dataset, a TCD-based threshold for predicting infarction had a high negative predictive value, supporting its role as an early screening tool to identify at-risk patients.

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