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

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.

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Low-dose intravenous heparin infusion in patients with aneurysmal subarachnoid hemorrhage: a preliminary assessment

Journal of Neurosurgery ◽

10.3171/2013.8.jns1337 ◽

2013 ◽

Vol 119 (6) ◽

pp. 1611-1619 ◽

Cited By ~ 36

Author(s):

J. Marc Simard ◽

E. Francois Aldrich ◽

David Schreibman ◽

Robert F. James ◽

Adam Polifka ◽

...

Keyword(s):

Low Dose ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Rescue Therapy ◽

Heparin Group ◽

Heparin Infusion ◽

Vein Thrombosis ◽

Intravenous Heparin ◽

Fisher Grade ◽

Grade 3 ◽

Deep Vein

Object Aneurysmal subarachnoid hemorrhage (aSAH) predisposes to delayed neurological deficits, including stroke and cognitive and neuropsychological abnormalities. Heparin is a pleiotropic drug that antagonizes many of the pathophysiological mechanisms implicated in secondary brain injury after aSAH. Methods The authors performed a retrospective analysis in 86 consecutive patients with Fisher Grade 3 aSAH due to rupture of a supratentorial aneurysm who presented within 36 hours and were treated by surgical clipping within 48 hours of their ictus. Forty-three patients were managed postoperatively with a low-dose intravenous heparin infusion (Maryland low-dose intravenous heparin infusion protocol: 8 U/kg/hr progressing over 36 hours to 10 U/kg/hr) beginning 12 hours after surgery and continuing until Day 14 after the ictus. Forty-three control patients received conventional subcutaneous heparin twice daily as deep vein thrombosis prophylaxis. Results Patients in the 2 groups were balanced in terms of baseline characteristics. In the heparin group, activated partial thromboplastin times were normal to mildly elevated; no clinically significant hemorrhages or instances of heparin-induced thrombocytopenia or deep vein thrombosis were encountered. In the control group, the incidence of clinical vasospasm requiring rescue therapy (induced hypertension, selective intraarterial verapamil, and angioplasty) was 20 (47%) of 43 patients, and 9 (21%) of 43 patients experienced a delayed infarct on CT scanning. In the heparin group, the incidence of clinical vasospasm requiring rescue therapy was 9% (4 of 43, p = 0.0002), and no patient suffered a delayed infarct (p = 0.003). Conclusions In patients with Fisher Grade 3 aSAH whose aneurysm is secured, postprocedure use of a low-dose intravenous heparin infusion may be safe and beneficial.

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Decrease of blood flow velocity in the middle cerebral artery after stellate ganglion block following aneurysmal subarachnoid hemorrhage: a potential vasospasm treatment?

Journal of Neurosurgery ◽

10.3171/2019.5.jns182890 ◽

2020 ◽

Vol 133 (3) ◽

pp. 773-779

Author(s):

Christopher Wendel ◽

Ricardo Scheibe ◽

Sören Wagner ◽

Wiebke Tangemann ◽

Hans Henkes ◽

...

Keyword(s):

Blood Flow ◽

Subarachnoid Hemorrhage ◽

Middle Cerebral Artery ◽

Flow Velocity ◽

Neurological Deficit ◽

Blood Flow Velocity ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Stellate Ganglion ◽

Stellate Ganglion Block ◽

Ganglion Block

OBJECTIVECerebral vasospasm (CV) is a delayed, sustained contraction of the cerebral arteries that tends to occur 3–14 days after aneurysmal subarachnoid hemorrhage (aSAH) from a ruptured aneurysm. Vasospasm potentially leads to delayed cerebral ischemia, and despite medical treatment, 1 of 3 patients suffer a persistent neurological deficit. Bedside transcranial Doppler (TCD) ultrasonography is used to indirectly detect CV through recognition of an increase in cerebral blood flow velocity (CBFV). The present study aimed to use TCD ultrasonography to monitor how CBFV changes on both the ipsi- and contralateral sides of the brain in the first 24 hours after patients have received a stellate ganglion block (SGB) to treat CV that persists despite maximum standard therapy.METHODSThe data were culled from records of patients treated between 2013 and 2017. Patients were included if an SGB was administered following aSAH, whose CBFV was ≥ 120 cm/sec and who had either a focal neurological deficit or reduced consciousness despite having received medical treatment and blood pressure management. The SGB was performed on the side where the highest CBFV had been recorded with 8–10 ml ropivacaine 0.2%. The patient’s CBFV was reassessed after 2 and 24 hours.RESULTSThirty-seven patients (male/female ratio 18:19), age 17–70 years (mean age 49.9 ± 11.1), who harbored 13 clipped and 22 coiled aneurysms (1 patient received both a coil and a clip, and 3 patients had 3 untreated aneurysms) had at least one SGB. Patients received up to 4 SGBs, and thus the study comprised a total of 76 SGBs.After the first SGB, CBFV decreased in 80.5% of patients after 2 hours, from a mean of 160.3 ± 28.2 cm/sec to 127.5 ± 34.3 cm/sec (p < 0.001), and it further decreased in 63.4% after 24 hours to 137.2 ± 38.2 cm/sec (p = 0.007). A similar significant effect was found for the subsequent SGB. Adding clonidine showed no significant effect on either the onset or the duration of the SGB. Contralateral middle cerebral artery (MCA) blood flow was not reduced by the SGB.CONCLUSIONSTo the authors’ knowledge, this is the largest study on the effects of administering an SGB to aSAH patients after aneurysm rupture. The data showed a significant reduction in ipsilateral CBFV (MCA 20.5%) after SGB, lasting in about two-thirds of cases for over 24 hours with no major complications resulting from the SGB.

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

Cerebrovascular Diseases ◽

10.1159/000445509 ◽

2016 ◽

Vol 42 (1-2) ◽

pp. 97-105 ◽

Cited By ~ 22

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.

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Vasospasm severity is associated with cerebral infarction after subarachnoid hemorrhage

10.1101/2021.04.20.21255798 ◽

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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Abstract 194: Cognitive Outcome in Acute Simvastatin Treatment for Aneurysmal Subarachnoid Hemorrhage

Stroke ◽

10.1161/str.47.suppl_1.194 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

George Wong ◽

Keyword(s):

Cognitive Impairment ◽

Subarachnoid Hemorrhage ◽

Cerebral Infarction ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Primary Outcome Measure ◽

Cognitive Outcomes ◽

Cognitive Outcome ◽

Secondary Outcome ◽

Modified Rankin Scale ◽

Simvastatin Treatment

Objectives: Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid haemorrhage (SAH). Recently, acute simvastatin treatment was not shown to be beneficial in neurological outcome using modified Rankin Scale. Cognitive function is another important dimension of outcome assessment and yet had not been investigated in statin studies for aneurysmal subarachnoid hemorrhage. We therefore explored whether acute simvastatin treatment would improve cognitive outcomes. Methods: The study recruited SAH patients with acute simvastatin treatment enrolled in a randomized controlled double-blinded clinical trial (ClinicalTrials.gov Identifier: NCT01038193). A control cohort of SAH patients without simvastatin treatment was identified with propensity score matching of age and admission grade. Primary outcome measure was Montreal Cognitive Assessment (MoCA). Secondary outcome measures were delayed ischaemic deficit (DID), delayed cerebral infarction, modified Rankin Scale (mRS), and Mini-Mental State Examination( MMSE). Results: Fifty-one SAH patients with acute simvastatin treatment and 51 SAH patients without simvastatin treatment were recruited for analysis. At 3 months, there were no differences in MoCA scores (MoCA: 21+/-6 vs. 21+/-5, p=0.772). MoCA-assessed cognitive impairment (MoCA<26) was not different (75% vs. 80%, OR 0.7, 95%CI 0.3 to 1.8, p=0.477). There were also no differences in DID, delayed cerebral infarction, favorable mRS outcome, and MMSE scores, and MMSE-assessed cognitive impairment between both groups. Conclusions: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage.

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Dose-Dependent Inhibitory Effects of Cilostazol on Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage

Translational Stroke Research ◽

10.1007/s12975-018-0650-y ◽

2018 ◽

Vol 10 (4) ◽

pp. 381-388 ◽

Cited By ~ 8

Author(s):

Hidenori Suzuki ◽

Yoshinari Nakatsuka ◽

Ryuta Yasuda ◽

Masato Shiba ◽

Yoichi Miura ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Infarction ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Inhibitory Effects ◽

Dose Dependent

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Hyperglycemia, excess weight, and history of hypertension as risk factors for poor outcome and cerebral infarction after aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/jns.2005.102.6.0998 ◽

2005 ◽

Vol 102 (6) ◽

pp. 998-1003 ◽

Cited By ~ 92

Author(s):

Seppo Juvela ◽

Jari Siironen ◽

Johanna Kuhmonen

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Infarction ◽

Patient Outcomes ◽

Plasma Glucose ◽

Clinical Condition ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Content Type ◽

Poor Outcome ◽

History Of ◽

Fine Print

Object. Stress-induced hyperglycemia has been shown to be associated with poor outcome after aneurysmal subarachnoid hemorrhage (SAH). The authors prospectively tested whether hyperglycemia, independent of other factors, affects patient outcomes and the occurrence of cerebral infarction after SAH. Methods. Previous diseases, health habits, medications, clinical condition, and neuroimaging variables were recorded for 175 patients with SAH who were admitted to the hospital within 48 hours after bleeding. The plasma level of glucose was measured at admission and the fasting value of glucose was measured in the morning after aneurysm occlusion. Factors found to be independently predictive of patient outcomes at 3 months after SAH onset and the appearance of cerebral infarction were tested by performing multiple logistic regression. Plasma glucose values at admission were found to be associated with patient age, body mass index (BMI), history of hypertension, clinical condition, amount of subarachnoid or intraventricular blood, shunt-dependent hydrocephalus, outcome variables, and the appearance of cerebral infarction. When considered independently of age, clinical condition, or amount of subarachnoid, intraventricular, or intracerebral blood, the plasma glucose values at admission predicted poor outcome (per millimole/liter the odds ratio [OR] was 1.24 with a 95% confidence interval [CI] of 1.02–1.51). After an adjustment was made for the amount of subarachnoid blood, the clinical condition, and the duration of temporary artery occlusion during surgery, the BMI was found to be a significant predictor (per kilogram/square meter the OR was 1.15 with a 95% CI of 1.02–1.29) for the finding of cerebral infarction on the follow-up computerized tomography scan. Hypertension (OR 3.11, 95% CI 1.11–8.73)—but not plasma glucose (OR 1.06, 95% CI 0.87–1.29)—also predicted the occurrence of infarction when tested instead of the BMI. Conclusions. Independent of the severity of bleeding, hyperglycemia at admission seems to impair outcome, and excess weight and hypertension appear to elevate the risk of cerebral infarction after SAH.

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Decompressive craniectomy in patients with cerebral infarction due to malignant vasospasm after aneurysmal subarachnoid hemorrhage

Journal of Neurosciences in Rural Practice ◽

10.4103/0976-3147.102598 ◽

2012 ◽

Vol 03 (03) ◽

pp. 251-255 ◽

Cited By ~ 8

Author(s):

Saffet Tuzgen ◽

Baris Kucukyuruk ◽

Seckin Aydin ◽

Fatma Ozlen ◽

Osman Kizilkilic ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Infarction ◽

Decompressive Craniectomy ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Clinical Results ◽

Cerebral Infarct ◽

World Federation ◽

Life Saving

ABSTRACT Aim: The authors present their experience and the clinical results in decompressive craniectomy (DC) in patients with vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Materials and Methods: Between 2002 and 2010, six patients underwent DC due to cerebral infarct and edema secondary to vasospasm after aneurysmal SAH. Four patients were male, and two were female. The age of patients ranged between 33 and 60 (mean: 47,6 ± 11,4). The follow up period ranged between 12 to 104 months (mean: 47,6 ± 36,6). The SAH grading according World Federation of Neurosurgeons (WFNS) score ranged between 3 to 5. Results: Last documented modified Rankin Score (mRS) ranged between 2 to 6. One patient died in the following year after decompression due to pneumonia and sepsis. Two patients had moderate disability (mRS of 4) and three patients continue their life with minimal deficit and no major dependency (mRS score 2 and 3). Conclusion: DC can be a life-saving procedure which provides a better outcome in patients with cerebral infarction secondary to vasospasm and SAH. However, the small number of the patients in this study is the main limitation of the accuracy of the results, and more studies with larger numbers are required to evaluate the efficiency of DC in this group of patients.

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High-Dose Nadroparin Following Endovascular Aneurysm Treatment Benefits Outcome After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽

10.1093/neuros/nyx381 ◽

2017 ◽

Vol 83 (2) ◽

pp. 281-287 ◽

Cited By ~ 1

Author(s):

Rene Post ◽

IJsbrand A.J Zijlstra ◽

Rene van den Berg ◽

Bert A Coert ◽

Dagmar Verbaan ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Dose Group ◽

Low Dose ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Controlled Trial ◽

Delayed Cerebral Ischemia ◽

Neurological Status ◽

High Dose ◽

Aneurysm Treatment ◽

Significant Difference

Abstract BACKGROUND Delayed cerebral ischemia (DCI) is one of the major causes of delayed morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE To evaluate the effect of high-dose nadroparin treatment following endovascular aneurysm treatment on the occurrence of DCI and clinical outcome. METHODS Medical records of 158 adult patients with an aSAH were retrospectively analyzed. Those patients treated endovascularly for their ruptured aneurysm were included in this study. They received either high-dose (twice daily 5700 AxaIE) or low-dose (once daily 2850 AxaIE) nadroparin treatment after occlusion of the aneurysm. Medical charts were reviewed and imaging was scored by 2 independent neuroradiologists. Data with respect to in-hospital complications, peri-procedural complications, discharge location, and mortality were collected. RESULTS Ninety-three patients had received high-dose nadroparin, and 65 patients prophylactic low-dose nadroparin. There was no significant difference in clinical DCI occurrence between patients treated with high-dose (34%) and low-dose (31%) nadroparin. More patients were discharged to home in patients who received high-dose nadroparin (40%) compared to low-dose (17%; odds ratio [OR] 3.13, 95% confidence interval [95% CI]: 1.36-7.24). Furthermore, mortality was lower in the high-dose group (5%) compared to the low-dose group (23%; OR 0.19, 95% CI: 0.07-0.55), also after adjusting for neurological status on admission (OR 0.21, 95% CI: 0.07-0.63). CONCLUSION Patients who were treated with high-dose nadroparin after endovascular treatment for aneurysmal SAH were more often discharged to home and showed lower mortality. High-dose nadroparin did not, however, show a decrease in the occurrence of clinical DCI after aSAH. A randomized controlled trial seems warranted.

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