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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.

Background and PurposeCerebral 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, p0.1) yet higher rates of VP shunting were noted (19.9% vs. 8.8%, pConclusionsIT 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.

Background Recent reports have demonstrated that among patients with subarachnoid hemorrhage (SAH) treated with hypertonic NaCl, resultant hyperchloremia has been associated with the development of acute kidney injury (AKI). We report a trial comparing the effect of two hypertonic solutions with different chloride contents on the resultant serum chloride concentrations in SAH patients, with a primary outcome aimed at limiting chloride elevation. Methods A low ChloridE hyperTonic solution for brain Edema (ACETatE) trial is a single-center, double-blinded, double-dummy, randomized pilot trial comparing bolus infusions of 23.4% NaCl and 16.4% NaCl/Na-acetate for the treatment of cerebral edema in patients with SAH. Randomization occurred when patients developed hyperchloremia (serum Cl− ≥ 109 mmol/L) and required hyperosmolar treatment. Results We enrolled 59 patients, of which 32 developed hyperchloremia and required hyperosmolar treatment. 15 patients were randomized to the 23.4% NaCl group, and 17 patients were randomized to the 16.4% NaCl/Na-acetate group. Although serum chloride levels increased similarly in both groups, the NaCl/Acetate group showed a significantly lower Cl− load at the end of the study period (978mEq vs. 2,464mEq, p < 0.01). Secondary outcome analysis revealed a reduced rate of AKI in the Na-acetate group (53.3% in the NaCl group vs. 11.8% in the Na-acetate group, p = 0.01). Both solutions had similar effects on ICP reduction, but NaCl/Acetate treatment had a more prominent effect on immediate post-infusion Na+ concentrations (increase of 2.2 ± 2.8 vs. 1.4 ± 2.6, (p < 0.01)). Proximal tubule renal biomarkers differed in concentration between the two groups. Conclusions Our pilot trial showed the feasibility and safety of replacing 23.4% NaCl infusions with 16.4% NaCl/Na-acetate infusions to treat cerebral edema in patients with SAH. The degree of hyperchloremia was similar in the two groups. 16.4% NaCl/Na-acetate infusions led to lower Cl− load and AKI rates than 23.4% NaCl infusions. Further multi-center studies are needed to corroborate these results. Trial registration clinicaltrials.gov # NCT03204955, registered on 6/28/2017

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 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.

Cerebrovascular diseases attributed to coronavirus disease 2019 (COVID-19) are uncommon but can result in devastating outcomes. Pediatric acute ischemic strokes are themselves rare and with very few large vessel occlusion related acute ischemic strokes attributed to COVID-19 described in the literature as of date. COVID-19 pandemic has contributed to acute stroke care delays across the world and with pediatric endovascular therapy still in its infancy, it poses a great challenge in facilitating good outcomes in children presenting with acute ischemic strokes in the setting of COVID-19. We present a pediatric patient who underwent endovascular therapy for an internal carotid artery occlusion related acute ischemic stroke in the setting of active COVID-19 and had an excellent outcome thanks to a streamlined stroke pathway involving the vascular neurology, neuro-interventional, neurocritical care, and anesthesiology teams.