Conivaptan was safe and effective in this small series of neurointensive care patients, including many patients who were hyponatremic despite traditional treatments to maintain normal sodium levels. Further studies are needed to clarify the role of conivaptan as an adjunctive and/or alternative therapy for hyponatremia in this patient population.

Background and Relevance: Atherosclerotic stenosis of the major intracranial arteries is an important cause of transient ischemic attack (TIA) or stroke. Of the 900,000 patients who suffer a TIA or stroke each year in the USA, intracranial stenosis is responsible for approximately 10%, i.e. 90,000 patients. There have been no prospective trials evaluating antithrombotic therapies for preventing recurrent vascular events in these patients. The main objective of this trial is to compare warfarin [International Normalized Ratio (INR) 2–3] with aspirin (1,300 mg/day) for preventing stroke (ischemic and hemorrhagic) and vascular death in patients presenting with TIA or stroke caused by stenosis of a major intracranial artery. Study Design: Prospective, randomized, double-blind, multicenter trial. The sample sizerequired will be 403 patients per group, based on stroke and vascular death rates of 33% per 3 years in the aspirin group vs. 22% per 3 years in the warfarin group, a p value of 0.05, power of 80%, a 24% rate of ‘withdrawal of therapy’, and a 1% rate of ‘lost to follow-up’. Conduct of Trial: Patients with TIA or nondisabling stroke caused by ≧50% stenosis of a major intracranial artery documented by catheter angiography are randomized to warfarin or aspirin. Patients are contacted monthly by phone and examined every 4 months until a common termination date. Mean follow-up in the study is expected to be 3 years. Conclusion: This study will determine whether warfarin or aspirin is superior for patients with symptomatic intracranial arterial stenosis. Furthermore, it will identify patients whose rate of ischemic stroke in the territory of the stenotic intracranial artery on best medical therapy is sufficiently high to justify a subsequent trial comparing intracranial angioplasty/stenting with best medical therapy in this subset of patients.

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

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.

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