Refractory Cerebral Vasospasm Research Articles

Use of dual intraventricular vasodilators for refractory cerebral vasospasm in a pediatric patient with traumatic subarachnoid hemorrhage: A case report.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Subarachnoid hemorrhage (SAH) is a rare but life-threatening clinical event for pediatric patients. Cerebral vasospasm is a common complication of SAH that often leads to poor outcomes. This case report describes the use of dual intraventricular (IVT) vasodilators in a pediatric patient. An 11-year-old male presented with traumatic diffuse SAH and cranial vasospasm. Despite treatment with IVT nicardipine, intravenous (IV) milrinone by continuous infusion, enteral nimodipine, and intraarterial verapamil and milrinone given during digital subtraction angiography, transcranial Doppler (TCD) mean velocities continued to rise. IVT milrinone was then added to IVT nicardipine and IV milrinone. The combination of IVT nicardipine, IV milrinone, and rescue therapy with IVT milrinone was continued for a total of 7 days. TCD mean velocities decreased into the mild to moderate range within 2 days of the patient receiving this combined regimen and remained globally low thereafter. This case illustrates the potential benefit of using dual IVT vasodilators to improve outcomes for pediatric patients with refractory cerebral vasospasm.

Cerebral Hemodynamics and Levosimendan Use in Patients with Cerebral Vasospasm and Subarachnoid Hemorrhage: An Observational Perfusion CT-Based Imaging Study.

Delayed cerebral ischemia associated with cerebral vasospasm (CVS) in aneurysmal subarachnoid hemorrhage significantly affects patient prognosis. Levosimendan has emerged as a potential treatment, but clinical data are lacking. The aim of this study is to decipher levosimendan's effect on cerebral hemodynamics by automated quantitative measurements of brain computed tomography perfusion (CTP). We conducted a retrospective analysis of a database of a neurosurgical intensive care unit. All patients admitted from January 2018 to July 2022 for aneurysmal subarachnoid hemorrhage and treated with levosimendan for CVS who did not respond to other therapies were included. Quantitative measurements of time to maximum (Tmax), relative cerebral blood volume (rCBV), and relative cerebral blood flow (rCBF) were automatically compared with coregistered CTP before and after levosimendan administration in oligemic regions. Of 21 patients included, CTP analysis could be performed in 16. Levosimendan improved Tmax from 14.4s (interquartile range [IQR] 9.1-21) before treatment to 7.1s (IQR 5.5-8.1) after treatment (p < 0.001). rCBV (94% [IQR 79-103] before treatment and 89% [IQR 72-103] after treatment, p = 0.63) and rCBF (85% [IQR 77-90] before treatment and 87% [IQR 73-98] after treatment, p = 0.98) remained stable. The subgroup of six patients who did not develop cerebral infarction attributed to delayed cerebral ischemia showed an approximately 10% increase (rCBV 85% [IQR 79-99] before treatment vs. 95% [IQR 88-112] after treatment, p = 0.21; rCBF 81% [IQR 76-87] before treatment vs. 89% [IQR 84-99] after treatment, p = 0.4). In refractory CVS, levosimendan use was associated with a significant reduction in Tmax in oligemic regions. However, this value remained at an abnormal level, indicating the presence of a persistent CVS. Further analysis raised the hypothesis that levosimendan causes cerebral vasodilation, but other studies are needed because our design does not allow us to quantify the effect of levosimendan from that of the natural evolution of CVS.

Stellate Ganglion Block and Intraarterial Spasmolysis in Patients with Cerebral Vasospasm: A Retrospective Cohort Study

BackgroundIn patients with symptomatic cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage who do not respond to medical therapy, urgent treatment escalation has been suggested to be beneficial for brain tissue at risk. In our routine clinical care setting, we implemented stellate ganglion block (SGB) as a rescue therapy with subsequent escalation to intraarterial spasmolysis (IAS) with milrinone for refractory CV.MethodsIn this retrospective analysis from 2012 to 2021, patients with CV following aneurysmal subarachnoid hemorrhage who received an SGB or IAS were identified. Patients were assessed through neurological examination and transcranial Doppler. Rescue therapy was performed in patients with mean cerebral blood flow velocity (CBFV) ≥ 120 cm/s and persistent neurological deterioration/intubation under induced hypertension. Patients were reassessed after therapy and the following day. The Glasgow Outcome Scale was assessed at discharge and 6-month follow-up.ResultsA total of 82 patients (mean age 50.16 years) with 184 areas treated with SGB and/or IAS met the inclusion criteria; 109 nonaffected areas were extracted as controls. The mean CBFV decrease in the middle cerebral artery on the following day was − 30.1 (± 45.2) cm/s with SGB and − 31.5 (± 45.2) cm/s with IAS. Mixed linear regression proved the significance of the treatment categories; other fixed effects (sex, age, aneurysm treatment modality [clipping or coiling], World Federation of Neurological Surgeons score, and Fisher score) were insignificant. In logistic regression, the presence of cerebral infarction on imaging before discharge from the intensive care unit (34/82) was significantly associated with unfavorable outcomes (Glasgow Outcome Scale ≤ 3) at follow-up.ConclusionsStellate ganglion block and IAS decreased CBFV the following 24 h in patients with CV. We suggest SGB alone for patients with mild symptomatic CV (CBFV < 180 cm/s), while subsequent escalation to IAS proved to be beneficial in patients with refractory CV and severe CBFV elevation (CBFV ≥ 180 cm/s).

Cervical Ganglion Sympathectomy to Treat Cerebral Vasospasm in Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is still a significant cause of death and disability after aneurysmal subarachnoid hemorrhage. Cerebral vasospasm represents one of the most reported mechanisms associated with DCI. The management of DCI-related vasospasm remains a significant challenge for clinicians; induced hypertension, intraarterial vasodilators, and/or intracranial vessel angioplasty-particularly in refractory or recurrent cases-are the most used therapies. Because an essential role in the pathophysiology of cerebral vasospasm has been attributed to the adrenergic sympathetic nerves, a "sympatholytic" intervention, consisting of a temporary interruption of the sympathetic pathways using local anesthetics, has been advocated to minimize the vascular narrowing and reverse the consequences of cerebral vasospasm on tissue perfusion. In this review, we have analyzed the existing literature on the block of the cervical ganglions, particularly the stellate ganglion, in managing refractory cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. These findings could help clinicians to understand the potential role of such intervention and to develop future interventional trials in this setting.

Analysis of Angiographic Treatment Response to Intra-Arterial Nimodipine Bolus Injection in Patients with Medically Refractory Cerebral Vasospasm After Spontaneous Subarachnoid Hemorrhage

Intra-arterial nimodipine (IAN) injections are performed in refractory delayed cerebral ischemia (DCI) related to cerebral vasospasm (CVS) after spontaneous subarachnoid hemorrhage (sSAH), but the clinical benefits are inconclusive and angiographic treatment failure is observed. We analyzed angiographic IAN response in a detailed vessel-specific manner and examined the impact of poor angiographic response on the further clinical course. Clinical data were retrospectively assessed in patients with spontaneous subarachnoid hemorrhage with symptomatic CVS receiving IAN bolus treatment. Clinical and angiographic predictors for poor angiographic response, DCI-related infarction, and unfavorable outcome were analyzed. Eighty-nine patients were included and 356 treated vessel segments, mainly located in the anterior circulation (93%), were analyzed. Angiographic response was good in 77% of the treated segments. Older age, poor World Federation of Neurosurgical Societies (WFNS) grade 4-5 and early onset of CVS were independently associated with poor angiographic response. The factors short-segment, distal, and bilateral CVS as well as treatment of multiple vessel segments, WFNS grade 4-5, and early onset of CVS were significantly associated with an increased risk of DCI-related infarction. Clinical outcome was significantly influenced by poor WFNS grade and early onset of CVS, whereas poor angiographic response was not related to DCI-related infarction or unfavorable outcome. The risk of angiographic treatment failure is significantly increased in older patients and those with poor WFNS grade as in cases of early-onset CVS. Although the extent of angiographic CVS significantly affected the development of DCI-related infarction, poor angiographic response had no impact on cerebral infarction and clinical outcome.

Evaluation of Intra-Arterial Nimodipine Therapy in Post-Subarachnoid Hemorrhage Refractory Cerebral Vasospasm

Background: Cerebral vasospasm is a major cause of morbidity and mortality in patients with subarachnoid hemorrhage. Vasospasm is managed with triple H and vasodilators but sometimes, patients do not respond. Intra-arterial vasodilator infusion has been shown to improve outcome in such patients. In this study, we try to evaluate the efficacy of intra-arterial nimodipine therapy in 43 patients of post-aneurysmal subarachnoid hemorrhage refractory cerebral vasospasm.

Early Fevers and Elevated Neutrophil-to-Lymphocyte Ratio are Associated with Repeat Endovascular Interventions for Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage.

Patients with aneurysmal subarachnoid hemorrhage (aSAH) may develop refractory arterial cerebral vasospasm requiring multiple endovascular interventions. The aim of our study is to evaluate variables associated with need for repeat endovascular treatments in refractory vasospasm and to identify differences in outcomes following one versus multiple treatments. We retrospectively reviewed patients treated for aSAH between 2017 and 2020 at two tertiary care centers. We included patients who underwent treatment (intraarterial infusion of vasodilatory agents or mechanical angioplasty) for radiographically diagnosed vasospasm in our analysis. Patients were divided into those who underwent single treatment versus those who underwent multiple endovascular treatments for vasospasm. Of the total 418 patients with aSAH, 151 (45.9%) underwent endovascular intervention for vasospasm. Of 151 patients, 95 (62.9%) underwent a single treatment and 56 (37.1%) underwent two or more treatments. Patients were more likely to undergo multiple endovascular treatments if they had a Hunt-Hess score > 2 (odds ratio [OR] 5.10 [95% confidence interval (CI) 1.82-15.84]; p = 0.003), a neutrophil-to-lymphocyte ratio > 8.0 (OR 3.19 [95% CI 1.40-7.62]; p = 0.028), and more than two fevers within the first 5days of admission (OR 7.03 [95% CI 2.68-20.94]; p < 0.001). Patients with multiple treatments had poorer outcomes, including increased length of stay, delayed cerebral ischemia, in-hospital complications, and higher modified Rankin scores at discharge. A Hunt-Hess score > 2, a neutrophil-to-lymphocyte ratio > 8.0, and early fevers may be predictive of need for multiple endovascular interventions in refractory cerebral vasospasm after aSAH. These patients have poorer functional outcomes at discharge and higher rates of in-hospital complications.

Continuous intra-arterial nimodipine infusion as rescue treatment of severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage

Severe refractory cerebral vasospasm (CV) is a major cause of disability and death in patients with aneurysmal subarachnoid hemorrhage (SAH). One rescue therapy in selected patients is intra-arterial nimodipine, either given as a single shot or as continuous infusion. To evaluate treatment efficacy, we analyzed outcome factors such as the incidence of craniectomy, ventriculo-peritonial (VP) shunting, and tracheotomy after intra-arterial nimodipine infusion. We retrospectively analyzed the rates of cerebral infarction, decompressive craniectomy, VP shunting, and tracheotomy in patients with severe CV after SAH. Three different patient groups were compared: group 1 had only been treated with oral nimodipine and hypervolemic hypertensive therapy (HHT) (2006–2010), group 2 with a single shot of intra-arterial nimodipine (SSN) in addition to oral conservative treatment (2006–2010), and group 3 with continuous intra-arterial nimodipine (CIAN) (2011–2017). The incidence of cerebral infarction was significantly lower in CIAN group (p = 0.005) than in conservative and SSN group. The indication for consecutive decompressive craniectomy was significantly lower in CIAN group in comparison with the conservative group (p = 0.018). The rates of VP shunting and tracheotomy were significantly higher in the CIAN group than in the conservative group (p = 0.028 for VP, and p = 0.003 for tracheotomy). The significantly lower rate of craniectomy in the CIAN group was most probably attributable to the significantly lower rate of CV-induced infarction. The higher rate of tracheotomy reflects more extensive sedation and the need of longer stays on the intensive care unit. Thus, the effect on long-term neurological outcome and quality of life has to be evaluated separately.

Intra-arterial nimodipine for severe cerebral vasospasm after aneurysmal subarachnoid haemorrhage - neurological and radiological outcome.

ObjectivesCerebral vasospasm is a known complication to aneurysmal subarachnoid haemorrhage, which can lead to severe morbidity. Intra-arterial vasodilation therapy is widely used as a last resort treatment in patients with symptomatic refractory cerebral vasospasm but there is limited data about the outcome. The purpose of this study is to evaluate the neurological and radiological outcome in patients treated with intra-arterial nimodipine in relation to cerebral infarction, procedure-related complications and clinical outcome.MethodsPatients with refractory cerebral vasospasm treated with intra-arterial nimodipine during 2009–2020 at Sahlgrenska University Hospital were retrospectively reviewed. Neurological outcome (modified Rankin Scale) at 30 days and 6 months, development of cerebral infarction after intra-arterial nimodipine treatment and procedure-related complications were studied.ResultsForty-eight patients were treated with intra-arterial nimodipine. A good outcome (modified Rankin Scale 0–2) was seen in 25% (n = 12) of the patients after 30 days and in 47% (n = 22) of the patients after six months. Infarction related to the vasospastic vessel after treatment with intra-arterial nimodipine was seen in 60% (n = 29) of the patients. A total of 124 procedures with intra-arterial nimodipine were performed where complications were seen in 10 (21%) patients in 10 (8%) procedures. Four (8%) patients died within 30 days.ConclusionsA majority of patients developed an ischaemic cerebral infarction in spite of intra-arterial nimodipine treatment. However, a good clinical recovery was seen in almost half of the patients after 6 months. Minor complications occurred in one out of five patients.

Stellate ganglion block combined with intra-arterial treatment: a "one-stop shop" for cerebral vasospasm after aneurysmal subarachnoid hemorrhage-a pilot study.

Delayed cerebral ischemia (DCI) is a frequent cause of morbidity and mortality in patients with cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (aSAH). Refractory CV remains challenging to treat and often leads to permanent deficits and death despite aggressive therapy. We hereby report the feasibility and safety of stellate ganglion block (SGB) performed with a vascular roadmap-guided technique to minimize the risk of accidental vascular puncture and may be coupled to a diagnostic or therapeutic cerebral angiography. In addition to a detailed description of the technique, we performed a retrospective analysis of a series of consecutive patients with refractory CV after aSAH that were treated with adjuvant roadmap-guided SGB. Clinical outcomes at discharge are reported. Nineteen SGB procedures were performed in 10 patients, after failure of traditional hemodynamic and endovascular treatments. Each patient received 1 to 3 SGB, usually interspaced by 24 h. In 4 patients, an indwelling microcatheter for continuous infusion was inserted. First SGB occurred on average 7.3 days after aSAH. SGB was coupled to intra-arterial nimodipine infusion or balloon angioplasty in 9 patients. SGB was technically successful in all patients. There were no technical or clinical complications. Adjuvant SGB may be coupled to endovascular therapy to treat refractory cerebral vasopasm within the same session. To guide needle placement, using a roadmap of the supra-aortic arteries may decrease the risk of complications. More prospective data is needed to evaluate the therapeutic efficacy, durability, and safety of SGB compared with the established standard of care.

Abstract P555: Safety and Efficacy of Daily Intra-Arterial Endovascular Therapy for Medically Refractory Cerebral Vasospasm Following Subarachnoid Hemorrhage

Introduction: Delayed cerebral ischemia (DCI) and cerebral infarction due to medically refractory vasospasm in aneurysmal SAH (aSAH) is a major cause of death and disability. The guidelines for endovascular therapy (EVT) for medically refractory vasospasm are not well established, especially regarding duration and frequency of therapy. Methods: Single center retrospective chart review was performed. We included patients with aSAH who had medically refractory vasospasm and underwent EVT. Demographics, clinical characteristics, imaging data, procedural details and outcomes were collected. Results: From 2016 to 2019, 303 subarachnoid hemorrhage (SAH) patients were identified. 133 (43.9%) were aSAH, of which 120 (90.2%) had DCI. Forty-one (34.1%) patients met our inclusion criteria. Median age was 56 years [Interquartile range (IQR) 46, 63] and 33 (80.5%) patients were female. We divided the EVT arm into two groups, group 1 underwent &lt; 3 consecutive days of EVT comprising of 11 patients (26.8%) and group 2 underwent ≥3 consecutive days of EVT comprising of 30 patients (73.2%). Median Hunt and Hess score and Fisher grade were 1.5 (IQR 1,3) and 3.5 (IQR 2,4)in group 1 and 3 (IQR 2,4) and 4 (3,4) in group 2, (p =0.08) and (p =0.5) respectively . Median number of days of EVT was 4(IQR 2,6.5) for the entire cohort. Median days of EVT in group 1 was 2 (IQR 1,2) and for group 2 was 5 (IQR 3,7, p=0.24). Cerebral infarction was seen in 5/11 (45.4%) patients in group 1 and 16/30 (53.3%) patients in group 2 (p = 0.73). Median modified Rankin scale (mRS) at discharge in both groups was 4 (p=0.55, r=0.1). Good clinical outcome at discharge (mRS 0-2) was seen in 4/11 (36.3%) patients in group 1 and 5/30 (16.7%) patients in group 2 (p=0.22). Procedure related complications were seen in 3/11 (27.2%) patients in group 1 and 3/30 (10%) patients in group 2 (p=0.32) whereas mortality rate was 1/11(9.1%) and 8/30 (26.6%) (p=0.4)respectively. No mortality was associated with the procedure. Conclusion: Daily endovascular therapy in medically refractory vasospasm is safe but not efficacious in reducing the rates of cerebral infarctions.

In Reply to the Letter to the Editor Regarding “Intra-arterial Dantrolene for Refractory Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage”

In Reply to the Letter to the Editor Regarding “Intra-arterial Dantrolene for Refractory Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage”

Novel Treatment of Cerebral Vasospasm Using Solitaire Stent Retriever−Assisted Angioplasty: Case Series

Endovascular procedures such as intraarterial (IA) vasodilator injection and balloon angioplasty are used to treat medically refractory cerebral vasospasm. The effects of IA therapy may be short lived and thus require multiple treatments. Balloon angioplasty also has limitations including transient occlusion of the spastic blood vessel, possible endothelial injury, and limited access to proximal vessels. We aim to demonstrate a novel technique using a stent retriever for the management of medically refractory vasospasm, especially in distal vessels. Compared with balloon angioplasty, stent retrievers provide a passive, self-limiting expansion of blood vessels. Other benefits over balloon angioplasty include 1) ability to simultaneously inject IA vasodilators, 2) limited contact and damage to vessel wall, 3) nonocclusive expansion, and 4) technical ease. Fourteen blood vessels from 6 patients with symptomatic vasospasm after subarachnoid hemorrhage were identified. We injected 5 mg of IA vasodilator medication into the vasospastic segments without radiographic improvement in vessel diameter and blood flow. The stent retriever was deployed for 2-5 minutes in each vasospastic segment. Distal anterior and posterior circulation segments were easily accessible with the stent retriever system. It resulted in improved vessel diameter and blood flow with subsequent improvement in neurologic examination. All patients demonstrated radiographic resolution of vasospasm. No procedural-related complications were noted. We demonstrate the safety and efficacy of a novel technique for the treatment of medically refractory cerebral vasospasm using stent retriever angioplasty in distal vessels. Stent angioplasty can be used as an additional tool in the management of subarachnoid hemorrhage-induced cerebral vasospasm.

Letter to the Editor Regarding “Intraarterial Dantrolene for Refractory Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage”: Is Malignant Hyperthermia a Model for Showing Dantrolene Efficacy in Limiting Brain Damage?

A 71-year-old woman presented to our institution with a 2-week history of concentric bilateral left accentuated visual field loss. Examination of her eyes including funduscopy was normal. A gadolinium-enhanced magnetic resonance tomography showed contrast enhancement of the optic pathway in the T1-weighted sequence that included both optic nerves, the optic chiasm, and the left optic tract. Differential diagnoses of this kind of lesion extending along the optic nerves include neurosarcoidosis, lymphoma, and glioma. The patient was treated with high-dose corticosteroids under the suspicion of neurosarcoidosis. During that time her vision deteriorated, resulting in amaurosis on her left eye and marginal peripheral vision on the right. A biopsy of the left optic nerve revealed a pilocytic astrocytoma, which to some extent contrasted the observed clinical course. After discussing the treatment options including radiotherapy and chemotherapy, the patient opted for supportive care and died 3 months later.

Incidence of Arterial Hypotension in Patients Receiving Peroral or Continuous Intra-arterial Nimodipine After Aneurysmal or Perimesencephalic Subarachnoid Hemorrhage.

Oral nimodipine is used for prophylaxis and treatment of delayed cerebral ischemia in patients with aneurysmal or perimesencephalic subarachnoid hemorrhage (SAH). In cases of serious refractory cerebral vasospasm, a continuous intra-arterial (IA) infusion of nimodipine (CIAN) may be required to avoid cerebral ischemia. Nimodipine can cause arterial hypotension requiring either a dosage reduction or its discontinuation. Aim of the present study was to examine the effect of different nimodipine formulations on arterial blood pressure in aneurysmal or perimesencephalic SAH patients and to measure the plasma levels after both, peroral administration as tablet or solution and IA infusion. In a prospective setting, over a 1-year observation period, data on the course of arterial blood pressure and nimodipine dosage were collected for 38 patients undergoing treatment for aneurysmal or perimesencephalic SAH in an intensive care unit. In addition, plasma concentrations of nimodipine were measured by liquid chromatography-tandem mass spectrometry. The intended full dose of 60mg of nimodipine given orally every 4h could only be administered on 57.2% of the examined days. Ninety-seven episodes of relevant arterial hypotension probably caused by the administration of nimodipine were observed within the first 14days of treatment. Drops in blood pressure occurred about three times as often after administration of nimodipine as oral solution than as tablet. However, there were no differences in nimodipine plasma levels between the two formulations. In patients suffering from higher-grade SAH, arterial hypotension and consequent dosage reduction or discontinuation of nimodipine were more frequent than in patients with lower-grade SAH. Plasma concentrations of nimodipine during CIAN did not exceed those achieved by oral administration. Dosage reduction or discontinuation of oral nimodipine is often necessary in patients with higher-grade SAH. Oral nimodipine solutions cause drops in blood pressure more frequently than tablets. Intra-arterial infusion rates of less than 1mg/h result in venous plasma concentrations of nimodipine similar to those observed after oral application of 60mg every 4 h.

Abstract TP548: Stent Retrievers as a Novel Treatment Tool for Refractory Cerebral Vasospasm

Introduction: Cerebral vasospasm commonly contributes to morbidity in patients who survive aneurysmal subarachnoid hemorrhage. When vasospasm becomes refractory to medical management, endovascular treatment options include intraarterial (IA) vasodilator injections and/or balloon angioplasty. However, IA vasodilators often provide limited angiographic improvements and can cause secondary systemic hypotension. Limitations of balloon angioplasty include restricted use to proximal vessels, risk of rupture with balloon inflation, and temporary vessel occlusion. Methods: We report our initial experience on the use of stent retrievers for five cases of refractory vasospasm. After injecting IA nicardipine and noting minimal angiographic improvement, we deployed the stent retriever for two minutes before the stent was re-sheathed. Results: We show safe and successful angiographic resolution of vasospasm in all cases, with a representative angiography shown in Figure 1. Injection of the left vertebral artery shows vasospasm along the basilar (BA) and posterior cerebral arteries (PCA) (Fig 1A). Narrowing improves significantly after stent deployment in the left PCA and BA (Fig 1B). There were no procedural complications. Conclusion: Stent retrievers have several benefits over balloon angioplasty for treatment of vasospasm. Stent retrievers are non-occlusive, conform easily to the curvature of the vessel, and have a known, safe opening force that prevents vessel rupture. In contrast to balloon angioplasty, stent retrievers have limited surface interface with the lumen, theoretically resulting in less endothelial injury. Lastly, most endovascular surgeons have more technical experience with stent retrievers given its widespread use in mechanical thrombectomy. In summary, stent retrievers can be used as a facile, safe, and effective endovascular treatment and should be considered as one of the emerging therapies for refractory cerebral vasospasm.

Irritant-induced asthma to hypochlorite in mice due to impairment of the airway barrier

Dantrolene has a safe side-effect profile and a mechanism of action that makes it attractive as an option for treatment of cerebral vasospasm. The authors report 2 cases of refractory cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage that were successfully treated with intra-arterial (IA) dantrolene.Two patients, a 63-year-old woman and 36-year-old woman, developed severe vasospasm refractory to IA vasodilators after rupture of anterior communicating artery aneurysms. IA dantrolene was injected in doses of 15–30 mg in the affected distributions and mean arterial pressure, intracranial pressure, and heart rate were monitored. There was immediate improvement in lumen diameter of the affected vessels following dantrolene injection. No significant differences in mean arterial pressure or intracranial pressure before and after IA dantrolene were observed. Both patients demonstrated clinical improvement within 24 hours without any further deterioration during the rest of their admission. Follow-up angiography 48 hours after IA dantrolene treatment demonstrated continued resolution of cerebral vasospasm.This evidence suggests IA dantrolene as a safe and effective novel alternative for the treatment of cerebral vasospasm.

Higher dose intra-arterial milrinone and intra-arterial combined milrinone-nimodipine infusion as a rescue therapy for refractory cerebral vasospasm.

Background Cerebral vasospasm (CV) is a major cause of delayed morbidity and mortality in patients with subarachnoid hemorrhage (SAH). Various cerebral protectants have been tested in patients with aneurysmal SAH. We aimed to research the success rate of treatment of CV via intra-arterial milrinone injection and aggressive pharmacological therapy for refractory CV. Methods A total of 25 consecutive patients who received intra-arterial milrinone and nimodipine treatment for CV following SAH between 2014 and 2017 were included in the study. Patients who underwent surgical clipping were excluded. Refractory vasospasm was defined as patients with CV refractory to therapies requiring ≥3 endovascular interventions. Overall, six patients had refractory CV. Long-term neurological outcome was assessed 6-18 months after SAH using a modified Rankin score and Barthel index. Results The median modified Rankin scores were 1 (min: 0, max: 3) and Barthel index scores were 85 (min: 70, max: 100) From each vasospastic territory maximal 10-16 mg milrinone was given to patients; a maximum of 24 mg milrinone was given to each patient in a session and a maximum of 42 mg milrinone was given to a patient in a day. Both milrinone and nimodipine were given to three patients. There was a large vessel diameter increase after milrinone and nimodipine injections. No patient died due to CV; only one patient had motor dysfunction on the right lower extremity. Conclusion Higher doses of milrinone can be used effectively to control refractory CV. For exceptional patients with refractory CV, high dose intra-arterial nimodipine and milrinone infusion can be used as a rescue therapy.

367 Functional Outcome in Patients with Refractory Cerebral Vasospasm Treated with Repeat Instant Endovascular Interventions

Abstract INTRODUCTION For patients suffering from cerebral vasospasm refractory to medical and hemodynamic therapies, endovascular interventions often remain the last resort. Data from studies in large cohorts on the efficacy and safety of multiple immediate endovascular interventions are sparse. Our aim was to assess the functional outcome of multiple repeated instant endovascular interventions in patients with cerebral vasospasm refractory to medical, hemodynamic, and initial endovascular interventions. METHODS A single-center retrospective study of prospectively collected data on patients suffering from cerebral vasospasm refractory to therapies requiring at least 3 endovascular interventions during the course of treatment following aneurysmal subarachnoid hemorrhage. The primary endpoint was functional outcome at last follow-up (mRS &lt;3). The secondary endpoint was angiographic response to endovascular therapies and appearance of cerebral infarctions. RESULTS &gt;Over a 4-year period, 365 patients with aneurysmal subarachnoid hemorrhage were treated at our institution. Thirty-one (8.5%) met the inclusion criteria. In 52 (14%) patients, &lt;3 endovascular interventions were performed as rescue therapy for refractory cerebral vasospasm. At last follow-up, a good outcome was noted in 18 (58%) patients with 3 or more interventions compared to 31 (61%) of those with 1 or 2 interventions (P = 0.82). The initial Hunt and Hess score &lt;3 was a significant independent predictor of good outcome (OR 4.7, 95% CI, 1.2 18.5; P = 0.03), whereas infarcts in eloquent brain areas were significantly associated with a poor outcome (mRS 3 6; OR 13.5, 95% CI, 2.3 81.2; P = 0.004). CONCLUSION Repeated instant endovascular intervention is an aggressive but feasible last resort treatment strategy with a favorable outcome in two-thirds of patients with refractory cerebral vasospasm and in whom endovascular treatment has already been initiated.

Temperature variability in the day\u2013night cycle is associated with further intracranial pressure during therapeutic hypothermia

BackgroundTo assess whether circadian patterns of temperature correlate with further values of intracranial pressure (ICP) in severe brain injury treated with hypothermia.MethodsWe retrospectively analyzed temperature values in subarachnoid hemorrhage patients treated with hypothermia by endovascular cooling. The circadian patterns of temperature were correlated with the mean ICP across the following day (ICP24).ResultsWe analyzed data from 17 days of monitoring of three subarachnoid hemorrhage patients that underwent aneurysm coiling, sedation and hypothermia due to refractory intracranial hypertension and/or cerebral vasospasm. ICP24 ranged from 11.5 ± 3.1 to 24.2 ± 6.2 mmHg. The ratio between the coefficient of variation of temperature during the nocturnal period (18:00–6:00) and the preceding diurnal period (6:00–18:00) [temperature variability (TV)] ranged from 0.274 to 1.97. Regression analysis showed that TV correlated with ICP24 (Pearson correlation = −0.861, adjusted R square = 0.725, p < 0.001), and that ICP24 = 6 (4–TV) mmHg or, for 80% prediction interval, {text{ICP}}_{24} = 23.9 - 6.22,times,{text{TV }} pm 1.73,timessqrt {1.06 + (({text{TV}} - 1.1)^{2} /4.49)} mmHg. The results indicate that the occurrence of ICP24 higher than 20 mmHg is unlikely after a day with TV ≥1.0.ConclusionsTV correlates with further ICP during hypothermia regardless the strict range that temperature is maintained. Further studies with larger series could clarify whether intracranial hypertension in severe brain injury can be predicted by analysis of oscillation patterns of autonomic parameters across a period of 24 h or its harmonics.