scholarly journals Milrinone for refractory cerebral vasospasm with delayed cerebral ischemia

2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yasser B. Abulhasan ◽  
Johanna Ortiz Jimenez ◽  
Jeanne Teitelbaum ◽  
Gabrielle Simoneau ◽  
Mark R. Angle
Keyword(s):  
Cerebral Ischemia ◽  
Functional Outcome ◽  
Cerebral Vasospasm ◽  
Standard Therapy ◽  
Therapy Group ◽  
Rescue Therapy ◽  
Delayed Cerebral Ischemia ◽  
World Federation ◽  
Study Cohort ◽  
Poor Grade

OBJECTIVEIntravenous (IV) milrinone is a promising option for the treatment of cerebral vasospasm with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, data remain limited on the efficacy of treating cases that are refractory to standard therapy with IV milrinone. The aim of this study was to determine predictors of refractory vasospasm/DCI despite treatment with IV milrinone, and to analyze the outcome of rescue therapy with intraarterial (IA) milrinone and/or mechanical angioplasty.METHODSThe authors conducted a retrospective cohort study of all patients with aSAH admitted between 2010 and 2016 to the Montreal Neurological Institute and Hospital. Patients were stratified into 3 groups: no DCI, standard therapy, and rescue therapy. The primary outcome was frequency of DCI-related cerebral infarction identified on neuroimaging before hospital discharge. Secondary outcomes included functional outcome reported as modified Rankin Scale (mRS) score, and segment reversal of refractory vasospasm.RESULTSThe cohort included 322 patients: 212 in the no DCI group, 89 in the standard therapy group, and 21 in the rescue therapy group. Approximately half (52%, 168/322) were admitted with poor-grade aSAH at treatment decision (World Federation of Neurosurgical Societies grade III–V). Among patients with DCI and imaging assessing severity of vasospasm, 62% (68/109) had moderate/severe radiological vasospasm on DCI presentation. Nineteen percent (21/110) of patients had refractory vasospasm/DCI and were treated with rescue therapy. Targeted rescue therapy with IA milrinone reversed 32% (29/91) of the refractory vasospastic vessels, and 76% (16/21) of those patients experienced significant improvement in their neurological status within 24 hours of initiating therapy. Moderate/severe radiological vasospasm independently predicted the need for rescue therapy (OR 27, 95% CI 8.01–112). Of patients with neuroimaging before discharge, 40% (112/277) had developed new cerebral infarcts, and only 21% (23/112) of these were vasospasm-related. Overall, 65% (204/314) of patients had a favorable functional outcome (mRS score 0–2) assessed at a median of 4 months (interquartile range 2–8 months) after aSAH, and there was no difference in functional outcome between the 3 groups (p = 0.512).CONCLUSIONSThe aggressive use of milrinone was safe and effective based on this retrospective study cohort and is a promising therapy for the treatment of vasospasm/DCI after aSAH.

scholarly journals Does intrathecal nicardipine for cerebral vasospasm following subarachnoid hemorrhage correlate with reduced delayed cerebral ischemia? A retrospective propensity score–based analysis

2021 ◽  
pp. 1-10
Author(s):  
Ofer Sadan ◽  
Hannah Waddel ◽  
Reneé Moore ◽  
Chen Feng ◽  
Yajun Mei ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Propensity Score ◽  
Functional Outcome ◽  
Cerebral Vasospasm ◽  
Delayed Cerebral Ischemia ◽  
University Hospital ◽  
World Federation ◽  
Ventriculoperitoneal Shunting ◽  
Fisher Grade

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.

Abstract 65: Intrathecal Nicardipine for Cerebral Vasospasm Post Subarachnoid Hemorrhage - A Single Center Experience

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ofer Sadan ◽  
Chen Feng ◽  
David T Pearce ◽  
Jacqueline Kraft ◽  
Cederic Pimentel ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Functional Outcome ◽  
Effective Treatment ◽  
Cerebral Vasospasm ◽  
Delayed Cerebral Ischemia ◽  
Low Grade ◽  
Single Center ◽  
Duration Of Treatment ◽  
Single Center Experience

Introduction: Cerebral vasospasm leading to delayed cerebral ischemia (DCI) is one of the most significant factors impacting functional outcome in patients diagnosed with non-traumatic subarachnoid hemorrhage (SAH). Effective treatment in this setting is lacking. We now report a single center retrospective cohort experience with intrathecal (IT) Nicardipine for this indication. Methods: All patients discharged between 2013-2017 diagnosed with non-traumatic SAH, either aneurysmal or idiopathic, were included in the analysis. Demographics, risk factors, clinical courses, radiological DCI, and functional outcomes were analyzed. Results: 1,085 patients were admitted with aneurysmal (n=796) or idiopathic (n=289) SAH. The mean age was 54.5±14.1 and 67.7% were women. Low grade hemorrhage (WFNS 1) was found in 42.4%, medium (WFNS 2-3) in 26.9%, and high grade (WFNS 4-5) in 30.7%. Cerebral vasospasm was diagnosed in 36.6% of the patients, and 85.4% of those received IT Nicardipine (n=339). Only 8.4% of all patients required angiography to treat vasospasm. TCD data was available for 159 patients who received IT Nicardipine. Treatment reduced mean velocities in all arteries within one day by 15.4% on average (p<0.01). This reduction was sustained for the duration of treatment. Nineteen patients (1.8%) suffered from bacterial ventriculitis, and no statistically significant correlation was noted between IT treatment and infection (OR 1.06 95%CI[0.42-2.7]). The incidence of radiological DCI, identified by blinded assement of imaging, was 9.4% and clinical DCI was 5.7%. In this cohort, 65.5% had a favorable functional outcome (mRS≤2) at 90 days. Conclusions: In a retrospective analysis, off-label IT Nicardipine is a safe and potentially effective treatment for cerebral vasospasm and prevention of the subsequent cerebral ischemia. Being the largest of its kind, this cohort could serve as a baseline for future clinical trial designs assessing IT Nicardipine safety and efficacy in a prospective, controlled fashion.

scholarly journals Evidence-based cerebral vasospasm management

2006 ◽  
Vol 21 (3) ◽  
pp. 1-10 ◽  
Author(s):  
George W. Weyer ◽  
Colum P. Nolan ◽  
R. Loch Macdonald
Keyword(s):  
Clinical Trials ◽  
Cerebral Ischemia ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Rescue Therapy ◽  
Delayed Cerebral Ischemia ◽  
Antiplatelet Agents ◽  
Fibrinolytic Therapy ◽  
Endothelin Antagonists ◽  
Steroid Drugs

✓Cerebral vasospasm and delayed cerebral ischemia remain common complications of aneurysmal subarachnoid hemorrhage (SAH), and yet therapies for cerebral vasospasm are limited. Despite a large number of clinical trials, only calcium antagonists have strong evidence supporting their effectiveness. The purpose of this work was to perform a systematic review of the literature on the treatment of cerebral vasospasm. A literature search for randomized controlled trials of therapies used for prevention or treatment of cerebral vasospasm and/or delayed cerebral ischemia was conducted, and 41 articles meeting the review criteria were found. Study characteristics and primary results of these articles are reviewed. Key indicators of quality were poor when averaged across all studies, but have improved greatly over time. The only proven therapy for vasospasm is nimodipine. Tirilazad is not effective, and studies of hemodynamic maneuvers, magnesium, statin medications, endothelin antagonists, steroid drugs, anticoagulant/antiplatelet agents, and intrathecal fibrinolytic drugs have yielded inconclusive results. The following conclusions were made: nimodipine is indicated after SAH and tirilazad is not effective. More study of hemodynamic maneuvers, the effectiveness of other calcium channel antagonists such as nicardipine delivered by other routes (for example intrathecally), magnesium, statin drugs, endothelin antagonists, and intrathecal fibrinolytic therapy is warranted. There is less enthusiasm for the study of steroid drugs and anticoagulant/antiplatelet agents because they entail more risks and investigations so far have shown little evidence of efficacy. The study of rescue therapy such as balloon angioplasty and intraarterial vasodilating agents will be difficult. The quality of clinical trials should be improved.

scholarly journals Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage

Stroke ◽  
2021 ◽  
Vol 52 (1) ◽  
pp. 20-27
Author(s):  
Satoru Takeuchi ◽  
Kosuke Kumagai ◽  
Terushige Toyooka ◽  
Naoki Otani ◽  
Kojiro Wada ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Magnesium Sulfate ◽  
Cerebral Vasospasm ◽  
Barthel Index ◽  
Delayed Cerebral Ischemia ◽  
Neuron Specific Enolase ◽  
Control Group ◽  
Modified Rankin Scale ◽  
Poor Grade

Background and Purpose: Poor-grade subarachnoid hemorrhage still has a poor prognosis. This randomized controlled clinical trial evaluated intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy in patients with poor-grade subarachnoid hemorrhage. Methods: Thirty-seven patients with poor-grade subarachnoid hemorrhage were randomized to Mg+H 2 , Mg, and control groups. Mg and Mg+H 2 groups received intracisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days. Mg+H 2 group also received intravenous hydrogen-rich solution infusion for 14 days. Primary outcome measures were occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures were modified Rankin Scale and Karnofsky performance status at 3 and 12 months, Barthel index at 12 months, and serum and cerebrospinal fluid malondialdehyde and neuron-specific enolase. Results: Serum neuron-specific enolase levels were significantly lower in the Mg+H 2 group from days 3 to 14 than in the control group. Cerebrospinal fluid neuron-specific enolase levels were also significantly lower in the Mg+H 2 group from days 3 to 7 than in the control group. Incidences of cerebral vasospasm and delayed cerebral ischemia were significantly higher in the control group than in other groups. Modified Rankin Scale and Karnofsky performance status did not significantly differ between the three groups at 3 months. Modified Rankin Scale scores 0 to 2 were more common in the Mg and Mg+H 2 groups at 1 year. Barthel index was higher in the Mg+H 2 group than in the control group. Conclusions: Intracisternal magnesium sulfate infusion started immediately after surgery reduces the incidence of cerebral vasospasm and delayed cerebral ischemia and improves clinical outcomes without complications in patients with poor-grade subarachnoid hemorrhage. Intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy decreases serum malondialdehyde and neuron-specific enolase and improves Barthel index, indicating hydrogen has additional effects. Registration: URL: https://www.umin.ac.jp/ctr/index.htm . Unique identifier: UMIN000014696.

scholarly journals Intrathecal Nicardipine for Cerebral Vasospasm Post Subarachnoid Hemorrhage–a Retrospective Propensity-Based Analysis

2020 ◽  
Author(s):  
Ofer Sadan ◽  
Hannah Waddel ◽  
Reneé Moore ◽  
Chen Feng ◽  
Yajun Mei ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Propensity Score ◽  
Functional Outcome ◽  
Cerebral Vasospasm ◽  
Delayed Cerebral Ischemia ◽  
University Hospital ◽  
Controlled Clinical Trial ◽  
World Federation ◽  
Ventriculoperitoneal Shunting ◽  
Fisher Grade

AbstractObjectivesCerebral vasospasm and delayed cerebral ischemia (DCI) contribute to poor outcome following subarachnoid hemorrhage (SAH). With the paucity of effective treatments, we describe our experience with intrathecal (IT) nicardipine for this indication.MethodsPatients admitted to Emory University Hospital Neuroscience ICU between 2012-2017 with non-traumatic SAH, either aneurysmal or idiopathic, were included in the analysis. This patient cohort was compared using a propensity-score model to patients in the SAH international trialist (SAHIT) repository who did not receive intrathecal nicardipine. The primary outcome was DCI. Secondary outcomes were long-term functional outcome and adverse events.ResultsThe analysis included 1,351 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 younger (51.1±12.4 vs. 56.7±14.1, p<0.01), had a higher World Federation of Neurological Surgeons score (WFNS), modified Fisher grade, and more likely to undergo clipping of the ruptured aneurysm as compared to endovascular treatment (30.3% vs. 11.3%, p<0.01). Treatment with IT nicardipine decreased 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 increase rate of bacterial ventriculitis (3.1% compared with 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 to develop DCI with IT nicardipine treatment was 0.61 with 95% CI[0.44-0.84], and to have a favorable functional outcome (mRS≤2) was 2.17[1.61-2.91].ConclusionsIT 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. This data should be considered when selecting medications and treatments to study in future randomized controlled clinical trial for SAH.

scholarly journals Is Hypothermia Helpful in Severe Subarachnoid Hemorrhage? An Exploratory Study on Macro Vascular Spasm, Delayed Cerebral Infarction and Functional Outcome after Prolonged Hypothermia

2015 ◽  
Vol 40 (5-6) ◽  
pp. 228-235 ◽  
Author(s):  
Joji B. Kuramatsu ◽  
Rainer Kollmar ◽  
Stefan T. Gerner ◽  
Dominik Madžar ◽  
Andrea Pisarčíková ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Functional Outcome ◽  
Delayed Cerebral Ischemia ◽  
Controlled Study ◽  
World Federation ◽  
Poor Grade ◽  
Novel Approach ◽  
Neuroprotective Therapy ◽  
Neuroprotective Treatment

Background: Therapeutic hypothermia (TH) is an established treatment after cardiac arrest and growing evidence supports its use as neuroprotective treatment in stroke. Only few and heterogeneous studies exist on the effect of hypothermia in subarachnoid hemorrhage (SAH). A novel approach of early and prolonged TH and its influence on key complications in poor-grade SAH, vasospasm and delayed cerebral ischemia (DCI) was evaluated. Methods: This observational matched controlled study included 36 poor-grade (Hunt and Hess Scale >3 and World Federation of Neurosurgical Societies Scale >3) SAH patients. Twelve patients received early TH (<48 h after ictus), mild (35°C), prolonged (7 ± 1 days) and were matched to 24 patients from the prospective SAH database. Vasospasm was diagnosed by angiography, macrovascular spasm serially evaluated by Doppler sonography and DCI was defined as new infarction on follow-up CT. Functional outcome was assessed at 6 months by modified Rankin Scale (mRS) and categorized as favorable (mRS score 0-2) versus unfavorable (mRS score 3-6) outcome. Results: Angiographic vasospasm was present in 71.0% of patients. TH neither influenced occurrence nor duration, but the degree of macrovascular spasm as well as peak spastic velocities were significantly reduced (p < 0.05). Frequency of DCI was 87.5% in non-TH vs. 50% in TH-treated patients, translating into a relative risk reduction of 43% and preventive risk ratio of 0.33 (95% CI 0.14-0.77, p = 0.036). Favorable functional outcome was twice as frequent in TH-treated patients 66.7 vs. 33.3% of non-TH (p = 0.06). Conclusion: Early and prolonged TH was associated with a reduced degree of macrovascular spasm and significantly decreased occurrence of DCI, possibly ameliorating functional outcome. TH may represent a promising neuroprotective therapy possibly targeting multiple pathways of DCI development, notably macrovascular spasm, which strongly warrants further evaluation of its clinical impact.

scholarly journals Effects of post-interventional antiplatelet therapy on angiographic vasospasm, delayed cerebral ischemia, and clinical outcome after aneurysmal subarachnoid hemorrhage: a single-center experience

2021 ◽  
Author(s):  
Claudia Ditz ◽  
Björn Machner ◽  
Hannes Schacht ◽  
Alexander Neumann ◽  
Peter Schramm ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Functional Outcome ◽  
Antiplatelet Therapy ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Control Group ◽  
Lesion Volume ◽  
Single Center ◽  
Single Center Experience

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.

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