HIMALAIA (Hypertension Induction in the Management of AneurysmaL subArachnoid Haemorrhage with Secondary IschaemiA): A Randomized Single-Blind Controlled Trial of Induced Hypertension vs. no Induced Hypertension in the Treatment of Delayed Cerebral Ischemia after Subarachnoid Hemorrhage

Background: Tranexamic acid (TA) administration in aneurysmal subarachnoid hemorrhage (SAH) within the first 24 hours may reduce the incidence of early aneurysmal rebleeding. However, this is also the potential for an increased risk of delayed cerebral ischemia if TA is administered for more than 72 hours following the initial aneurysmal rupture. Methods: In the ultra-early tranexamic acid after subarachnoid hemorrhage randomized controlled trial by Post et al., patients were randomized to receive TA within the first 24 hours, or until start of aneurysm treatment. These results were compared to a matched control group. Results: Ultra-early administration (≤24 h) of TA reduced the incidence of rebleeding, and did not alter the incidence of delayed cerebral ischemia and/or extracranial thrombosis. Further, no significant differences were noted between the TA group and control arm in the incidence of good (modified Rankin scores 0-3) clinical outcomes at 6 months. Conclusion: Ultra-early administration of TA (≤24 h) resulted in a lower rate of recurrent hemorrhage, without increasing the incidence of delayed cerebral ischemia in SAH patients.

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Literature Review of Aneurysmal Subarachnoid Hemorrhage from Incidence to Treatment Options

Acta Chirurgica Latviensis ◽

10.2478/chilat-2020-0017 ◽

2020 ◽

Vol 18 (1) ◽

pp. 70-78

Author(s):

Ieva Buce-Satoba ◽

Daina Rozkalne ◽

Jevgenijs Stepanovs ◽

Biruta Mamaja ◽

Gaida Krumina ◽

...

Keyword(s):

Risk Factors ◽

Cerebral Ischemia ◽

Literature Review ◽

Glasgow Coma Scale ◽

Subarachnoid Haemorrhage ◽

Cerebral Vasospasm ◽

Treatment Options ◽

Delayed Cerebral Ischemia ◽

Late Complications ◽

Aneurysmal Subarachnoid Haemorrhage

SummaryIntroductionAneurysmal subarachnoid haemorrhage (SAH) is associated with high mortality and morbidity. Rebleeding, cerebral vasospasm (VS) with delayed cerebral ischemia (DCI) are major complications after SAH associated with poor neurological outcome.Aim of the studyTo summarize the existing research data on the SAH from incidence, risk factors and clinical presentation to diagnostic, monitoring and treatment options after SAH.Materials and MethodsLiterature review was carried out to identify factors associated with SAH using specific keywords (aneurysmal subarachnoid haemorrhage, rebleeding, cerebral vasospasm, delayed cerebral ischemia) in the PUBMED database. In the time period from 2000 to 2019, 34 full articles were reviewed.ResultsAccording to the literature, the key risk factors for cerebral aneurysms and the SAH are hypertension, smoking, chronic alcohol abuse, family history of intracranial aneurysms in first-degree relatives and female sex. The key risk factor for early complication - rebleeding after SAH - is hypertension. The factors responsible for late complications - cerebral VS and DCI after SAH - are initially lower Glasgow coma scale and higher grades of Fisher scale, where grade IV and III predict cerebral VS in 31–37%. Furthermore, hyperglycaemic state, hyponatremia, hypotension and cerebral hypoperfusion, increased level of Troponin correlate with the incidence of cerebral VS and DCI. Although the golden standard to detect cerebral VS is digital subtraction angiography, CT angiography has become a routine examination. Transcranial doppler sonography is recommended and regional cerebral oximetry also seems to be promising. To avoid rebleeding for wide-necked, gigantic aneurysms or when SAH is combined with intraparenchymal hematoma, surgical clipping is preferred. For posterior circulation aneurisms, poor grade SAH and patients with age >70 years superior is endovascular treatment. To avoid late complications, the pharmacological method is used with Nimodipine.ConclusionsSAH is still associated with poor clinical outcome due to the development of early and late complications. The highest risk patients are those with low Glasgow coma scale and high grades of Fisher scale. Timely performed obliteration methods of the ruptured aneurysm are crucial and Nimodipine is the main agent to prevent cerebral VS and DCI.

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Effects of Induced Hypertension on Cerebral Perfusion in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Stroke ◽

10.1161/strokeaha.115.010537 ◽

2015 ◽

Vol 46 (11) ◽

pp. 3277-3281 ◽

Cited By ~ 34

Author(s):

Celine S. Gathier ◽

Jan Willem Dankbaar ◽

Mathieu van der Jagt ◽

Bon H. Verweij ◽

Annemarie W. Oldenbeuving ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Cerebral Perfusion ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Induced Hypertension

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Comparison of Initial Vasopressors Used for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage

Cerebrovascular Diseases ◽

10.1159/000458536 ◽

2017 ◽

Vol 43 (5-6) ◽

pp. 266-271 ◽

Cited By ~ 9

Author(s):

Bhaskar Roy ◽

Louise D. McCullough ◽

Rajat Dhar ◽

James Grady ◽

Yu-Bo Wang ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Adverse Effects ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Response To Therapy ◽

Discharge Disposition ◽

Induced Hypertension ◽

Baseline Characteristics ◽

The Impact

Background: The main reason for morbidity after aneurysmal subarachnoid hemorrhage (aSAH) is delayed cerebral ischemia (DCI). The mainstay of medical therapy for treating DCI is induced hypertension with vasopressors to restore cerebral perfusion. Both phenylephrine (PE) and norepinephrine (NE) are commonly used for induced hypertension, but the impact of the initial choice of vasopressor on the efficacy, adverse effects, or outcome after hemodynamic therapy for DCI is unknown. Methods: Sixty-three patients with aSAH between January 2012 and October 2014, who developed DCI (defined as new focal deficit or decline in Glasgow Coma Score) and in which PE (n = 45) or NE (n = 18) treatment was initiated were evaluated in this retrospective study. Baseline characteristics, adverse effects, the need to change or add vasopressors, the response to therapy, the need for endovascular therapy, new infarct development, discharge disposition, and 3 months modified Rankin score were all compared between pressor groups. Results: Baseline characteristics (e.g., Hunt Hess and Fisher grades) were similar. There were no differences in the overall rate of complications including arrhythmia, pulmonary edema, or kidney injury. However, those initiated on PE were more likely to be changed to an alternate vasopressor (64 vs. 33%, p = 0.016), mostly for bradycardia or failure to reach therapeutic targets. Patients initially treated with PE were less likely to respond neurologically (71 vs. 94%, p = 0.01) or to be discharged to home or acute rehabilitation facilities (73 vs. 94%, p = 0.02) and were more likely to have a delayed infarct on imaging (62 vs. 33%, p = 0.04). Conclusions: Our study suggests that patients with DCI after aSAH initiated on PE are more likely to require treatment change to another vasopressor and are at greater risk for poor clinical outcomes compared to patients started on NE. Larger comparative studies are warranted.

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A phase II randomized controlled trial of tiopronin for aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/2019.4.jns19478 ◽

2020 ◽

Vol 133 (2) ◽

pp. 351-359

Author(s):

Natasha Ironside ◽

Brandon Christophe ◽

Samuel Bruce ◽

Amanda M. Carpenter ◽

Trae Robison ◽

...

Keyword(s):

Clinical Trial ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Phase Ii ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Controlled Trial ◽

Delayed Cerebral Ischemia ◽

Study Drug ◽

Double Blind ◽

Clinical Trial Registration

OBJECTIVEDelayed cerebral ischemia (DCI) is a significant contributor to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). The neurotoxin 3-aminopropanal (3-AP) is upregulated in cerebral ischemia. This phase II clinical trial evaluated the efficacy of tiopronin in reducing CSF 3-AP levels in patients with aSAH.METHODSIn this prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial, 60 patients were assigned to receive tiopronin or placebo in a 1:1 ratio. Treatment was commenced within 96 hours after aSAH onset, administered at a dose of 3 g daily, and continued until 14 days after aSAH or hospital discharge, whichever occurred earlier. The primary efficacy outcome was the CSF 3-AP level at 7 ± 1 days after aSAH.RESULTSOf the 60 enrolled patients, 29 (97%) and 27 (93%) in the tiopronin and placebo arms, respectively, received more than one dose of the study drug or placebo. At post-aSAH day 7 ± 1, CSF samples were available in 41% (n = 12/29) and 48% (n = 13/27) of patients in the tiopronin and placebo arms, respectively. No difference in CSF 3-AP levels at post-aSAH day 7 ± 1 was observed between the study arms (11 ± 12 nmol/mL vs 13 ± 18 nmol/mL; p = 0.766). Prespecified adverse events led to early treatment cessation for 4 patients in the tiopronin arm and 2 in the placebo arm.CONCLUSIONSThe power of this study was affected by missing data. Therefore, the authors could not establish or refute an effect of tiopronin on CSF 3-AP levels. Additional observational studies investigating the role of 3-AP as a biomarker for DCI may be warranted prior to its use as a molecular target in future clinical trials.Clinical trial registration no.: NCT01095731 (ClinicalTrials.gov)

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Placing intracerebral probes to optimise detection of delayed cerebral ischemia and allow for the prediction of patient outcome in aneurysmal subarachnoid haemorrhage

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16675880 ◽

2016 ◽

Vol 37 (8) ◽

pp. 2820-2832 ◽

Cited By ~ 6

Author(s):

Yannick Tholance ◽

Gleicy K Barcelos ◽

Armand Perret-Liaudet ◽

Edris Omar ◽

Romain Carrillon ◽

...

Keyword(s):

Patient Outcome ◽

Cerebral Ischemia ◽

Subarachnoid Haemorrhage ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Delayed Cerebral Ischemia ◽

Detection Sensitivity ◽

Cerebral Microdialysis ◽

Anterior Communicating Artery ◽

Aneurysmal Subarachnoid Haemorrhage

Cerebral microdialysis could be useful to detect delayed cerebral ischemia in aneurysmal subarachnoid haemorrhage patients. The optimal location of the probes, however, remains controversial. Here, we determined the vascular territories with the highest infarct risk in relation to aneurysm location to define probe implantation guidelines. These guidelines were retrospectively validated by studying the likelihood of probe to fall in a secondary infarct area, and by analysing their influence to predict patient outcome. The vascular territories with highest risk of infarction were the anterior cerebral arteries for anterior communicating artery aneurysms and the ipsilateral middle cerebral artery for internal carotid artery, posterior communicating artery and middle cerebral artery aneurysms. When cerebral microdialysis probes had been implanted in these territories, 79% were located within an infarcted area versus 54% when they were implanted in other territories. Delayed cerebral ischemia was detected only when the probe was located within a brain area later affected by secondary infarction, which could justify the use of implantation guidelines. Moreover, individual patient outcomes could be predicted when probes were placed in the brain territories as suggested by this study. Thus, a precise probe placement algorithm can improve delayed cerebral ischemia detection sensitivity and allow for a better prediction concerning patient outcome.

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