Length of hospital stay in aneurysmal subarachnoid hemorrhage patients without vasospasm on angiography: potential for a fast-track discharge cohort

BackgroundPatients with aneurysmal subarachnoid hemorrhage (aSAH) frequently suffer from vasospasm. We analyzed the association between absence of early angiographic vasospasm and early discharge.MethodsAll aSAH patients treated from August 1, 2007, to July 31, 2019, at a single tertiary center were reviewed. Patients undergoing diagnostic digital subtraction angiography (DSA) on post-aSAH days 5 to 7 were analyzed; cohorts with and without angiographic vasospasm (angiographic reports by attending neurovascular surgeons) were compared. Primary outcome was hospital length of stay; secondary outcomes were intensive care unit length of stay, 30 day return to the emergency department (ED), and poor neurologic outcome, defined as a modified Rankin Scale (mRS) score >2.ResultsA total of 298 patients underwent DSA on post-aSAH day 5, 6, or 7. Most patients (n=188, 63%) had angiographic vasospasm; 110 patients (37%) did not. Patients without vasospasm had a significantly lower mean length of hospital stay than vasospasm patients (18.0±7.1 days vs 22.4±8.6 days; p<0.001). The two cohorts did not differ significantly in the proportion of patients with mRS scores >2 at last follow-up or those returning to the ED before 30 days. After adjustment for Hunt and Hess scores, Fisher grade, admission Glasgow Coma Scale score, and age, logistic regression analysis showed that the absence of vasospasm on post-aSAH days 5–7 predicted discharge on or before hospital day 14 (OR 3.4, 95% CI 1.8 to 6.4, p<0.001).ConclusionLack of angiographic vasospasm 5 to 7 days after aSAH is associated with shorter hospitalization, with no increase in 30 day ED visits or poor neurologic outcome.

Vasospasm severity is associated with cerebral infarction after subarachnoid hemorrhage

BackgroundThe 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.

The role of Transcranial Doppler in the detection of vasospasm after subarachnoid hemorrhage: updates and new parameters

Introduction: Transcranial Doppler (DTC) is useful in the evaluation of vasospasm after subarachnoid hemorrhage (SAH). Thus, it is important to know the accuracy and impact of this tool in the management of patients. Objective: Analyze the use of DTC in the detection of vasospasm after subarachnoid hemorrhage and its clinical relevance. Design and Setting: This is a literature review, produced in Bahiana School of Medicine and Public Health, Bahia, Brazil. Methods: The evaluated studies were obtained in PubMed, published since 2010. The studies did not correspond with the purpose of this review were excluded. Results: 26 of the 515 articles found, were select. Clinical studies that sought to demonstrate the accuracy of TCD in the detection of vasospasm and prediction of Delayed Cerebral Ischemia show high sensitivity and negative predictive value.There are studies that measure the accuracy of DTC in detecting angiographic vasospasm with high specificity. New parameters are emerging for the detection of vasospasm, even early. However, there are studies that demonstrate that the use of TCD does not favor the clinical outcomes of patients after SAH. Conclusion: TCD has moderate-high accuracy and can help in the detection and management of patients with vasospasm. Nonetheless, there are studies that refute the relevance of TCD in HSA. Furthermore, there is a lack of concrete evidence, with larger studies, for the widespread use of this tool with greater reliability and precision.

Complete relief of vasospasm – Effect of nicardipine coating during direct clipping for the patient with symptomatic vasospasm of subarachnoid hemorrhage

Background: Some patients come to the hospital presenting with ischemic neurological deficits due to postsubarachnoid hemorrhage (SAH) cerebral vasospasm. In such a situation, neurosurgeons tend to avoid direct clipping, since mechanical irritation to the vessels could worsen the vasospasm and exacerbate ischemic symptoms. The optimal timing of direct clipping in patients with evidence of vasospasm is undetermined. Herein, we present the case of a patient who underwent direct clipping in the presence of severe symptomatic and post-SAH angiographic vasospasm. During surgery, we coated the severely spastic artery with nicardipine. Case Description: A 49-year-old woman was admitted to our hospital with the diagnosis of ruptured intracranial aneurysm and severe vasospasm. On the admission day, we performed direct clipping together with direct application of nicardipine to the spastic artery. Postoperative immediate cerebral angiography showed complete disappearance of the vasospasm. Conclusion: Direct clipping should not be contraindicated during the vasospasm period in patients with a ruptured aneurysm, and direct application of nicardipine on the spastic artery would completely relieve vasospasm.

NEWTON-2 Cisternal (Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage): A Phase 2, Multicenter, Randomized, Open-Label Safety Study of Intracisternal EG-1962 in Aneurysmal Subarachnoid Hemorrhage

ABSTRACT BACKGROUND A sustained release microparticle formulation of nimodipine (EG-1962) was developed for treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE To assess safety, tolerability, and pharmacokinetics of intracisternal EG-1962 in an open-label, randomized, phase 2 study of up to 12 subjects. METHODS Subjects were World Federation of Neurological Surgeons grades 1 to 2, modified Fisher grades 2 to 4, and underwent aneurysm clipping within 48 h of aSAH. EG-1962, containing 600 mg nimodipine, was administered into the basal cisterns. Outcome on the extended Glasgow Outcome Scale (eGOS), pharmacokinetics, delayed cerebral ischemia and infarction, rescue therapy, and safety were evaluated. RESULTS The study was halted when a phase 3 study of intraventricular EG-1962 stopped because that study was unlikely to meet its primary endpoint. Six subjects were randomized (5 EG-1962 and 1 oral nimodipine). After 90-d follow-up, favorable outcome on the eGOS occurred in 1 of 5 EG-1962 and in the single oral nimodipine patient. Four EG-1962 and the oral nimodipine subject had angiographic vasospasm. One EG-1962 subject had delayed cerebral ischemia, and all subjects with angiographic vasospasm received rescue therapy except 1 EG-1962 patient. One subject treated with EG-1962 developed right internal carotid and middle cerebral artery narrowing 5 mo after placement of EG-1962, leading to occlusion and cerebral infarction. Pharmacokinetics showed similar plasma concentrations of nimodipine in both groups. CONCLUSION Angiographic vasospasm and unfavorable clinical outcome still occurred after placement of EG-1962. Internal carotid artery narrowing and occlusion after placement of EG-1962 in the basal cisterns has not been reported.

Lessons from the CONSCIOUS-1 Study

After years of research on treatment of aneurysmal subarachnoid hemorrhage (aSAH), including randomized clinical trials, few treatments have been shown to be efficacious. Nevertheless, reductions in morbidity and mortality have occurred over the last decades. Reasons for the improved outcomes remain unclear. One randomized clinical trial that has been examined in detail with these questions in mind is Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1). This was a phase-2 trial testing the effect of clazosentan on angiographic vasospasm (aVSP) in patients with aSAH. Clazosentan decreased moderate to severe aVSP. There was no statistically significant effect on the extended Glasgow outcome score (GOS), although the study was not powered for this endpoint. Data from the approximately 400 patients in the study were detailed, rigorously collected and documented and were generously made available to one investigator. Post-hoc analyses were conducted which have expanded our knowledge of the management of aSAH. We review those analyses here.

Conditioning Effect of Inhalational Anesthetics on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

BACKGROUND Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) has been identified as an independent predictor of poor outcome in numerous studies. OBJECTIVE To investigate the potential protective role of inhalational anesthetics against angiographic vasospasm, DCI, and neurologic outcome in SAH patients. METHODS After Institutional Review Board approval, data were collected retrospectively for SAH patients who received general anesthesia for aneurysm repair between January 1st, 2010 and May 31st, 2018. Primary outcomes were angiographic vasospasm, DCI, and neurologic outcome as measured by modified Rankin scale at hospital discharge. Univariate and logistic regression analysis were performed to identify independent predictors of these outcomes. RESULTS The cohort included 390 SAH patients with an average age of 56 ± 15 (mean ± SD). Multivariate logistic regression analysis identified inhalational anesthetic only technique, Hunt-Hess grade, age, anterior circulation aneurysm and average intraoperative mean blood pressure as independent predictors of angiographic vasospasm. Inhalational anesthetic only technique and modified Fishers grade were identified as independent predictors of DCI. No impact on neurological outcome at time of discharge was noted. CONCLUSION Our data provide additional evidence that inhalational anesthetic conditioning in SAH patients affords protection against angiographic vasospasm and new evidence that it exerts a protective effect against DCI. When coupled with similar results from preclinical studies, our data suggest further investigation into the impact of inhalational anesthetic conditioning on SAH patients, including elucidating the most effective dosing regimen, defining the therapeutic window, determining whether a similar protective effect against early brain injury, and on long-term neurological outcome exists.