Cerebrospinal Fluid Pharmacokinetics of Nicardipine Following Intrathecal Administration in Subarachnoid Hemorrhage Patients.

Subarachnoid hemorrhage (SAH) is a devastating type of stroke, leading to high mortality and morbidity rates. Cerebral vasospasm and delayed cerebral ischemia (DCI) are common complications following SAH that contribute significantly to the poor outcomes observed in these patients. Intrathecal (IT) nicardipine delivered via an existing external ventricular drain is an off-label intervention that has been shown to be correlated with reduced DCI and improved patient outcomes. The current study aims to characterize the population pharmacokinetic (popPK) properties of intermittent IT nicardipine. Following informed consent, serial cerebrospinal fluid (CSF) samples were obtained from 16 SAH patients (50.4 ± 9.3 years old; 13 females) treated with IT nicardipine every 6 h (q6h, n = 8) or every 8 h (q8h, n = 8) for an average of 72 ± 21 doses. High-performance liquid chromatography was used to quantify CSF concentration from each sample. Our popPK analysis showed that the CSF pharmacokinetics of IT nicardipine in the cohort was adequately described by a two-compartment model with a lag time. Model parameter estimates were reliable (relative standard error <50%). Intracranial pressure influenced both the total clearance and the central volume of nicardipine (i.e., negative correlation, P <-.001). Calculated PK parameters were similar between q6h and q8h dosing regimens. Despite a small cohort of SAH patients, we successfully developed a popPK model to describe the nicardipine disposition kinetics in the CSF following IT administration. These findings may help inform future clinical trials designed to examine the optimal dosing of IT nicardipine.

Pharmacologic Venous Thromboembolism Prophylaxis in Patients with Nontraumatic Subarachnoid Hemorrhage Requiring an External Ventricular Drain.

BACKGROUND: Optimal pharmacologic thromboprophylaxis dosing is not well described in patients with subarachnoid hemorrhage (SAH) with an external ventricular drain (EVD). Our patients with SAH with an EVD who receive prophylactic enoxaparin are routinely monitored using timed anti-Xa levels. Our primary study goal was to determine the frequency of venous thromboembolism (VTE) and secondary intracranial hemorrhage (ICH) for this population of patients who received pharmacologic prophylaxis with enoxaparin or unfractionated heparin (UFH). METHODS: A retrospective chart review was performed for all patients with SAH admitted to the neurocritical care unit at Emory University Hospital between 2012 and 2017. All patients with SAH who required an EVD were included. RESULTS: Of 1,351 patients screened, 868 required an EVD. Of these 868 patients, 627 received enoxaparin, 114 received UFH, and 127 did not receive pharmacologic prophylaxis. VTE occurred in 7.5% of patients in the enoxaparin group, 4.4% in the UFH group (p = 0.32), and 3.2% in the no VTE prophylaxis group (p = 0.08). Secondary ICH occurred in 3.83% of patients in the enoxaparin group, 3.51% in the UFH group (p = 1), and 3.94% in the no VTE prophylaxis group (p = 0.53). As steady-state anti-Xa levels increased from 0.1 units/mL to > 0.3 units/mL, there was a trend toward a lower incidence of VTE. However, no correlation was noted between rising anti-Xa levels and an increased incidence of secondary ICH. When compared, neither enoxaparin nor UFH use was associated with a significantly reduced incidence of VTE or an increased incidence of ICH. CONCLUSIONS: In this retrospective study of patients with nontraumatic SAH with an EVD who received enoxaparin or UFH VTE prophylaxis or no VTE prophylaxis, there was no statistically significant difference in the incidence of VTE or secondary ICH. For patients receiving prophylactic enoxaparin, achieving higher steady-state target anti-Xa levels may be associated with a lower incidence of VTE without increasing the risk of secondary ICH.

Comparison of diffuse correlation spectroscopy analytical models for measuring cerebral blood flow in adults.

Significance: Although multilayer analytical models have been proposed to enhance brain sensitivity of diffuse correlation spectroscopy (DCS) measurements of cerebral blood flow, the traditional homogeneous model remains dominant in clinical applications. Rigorous in vivo comparison of these analytical models is lacking. Aim: We compare the performance of different analytical models to estimate a cerebral blood flow index (CBFi) with DCS in adults. Approach: Resting-state data were obtained on a cohort of 20 adult patients with subarachnoid hemorrhage. Data at 1 and 2.5 cm source-detector separations were analyzed with the homogenous, two-layer, and three-layer models to estimate scalp blood flow index and CBFi. The performance of each model was quantified via fitting convergence, fit stability, brain-to-scalp flow ratio (BSR), and correlation with transcranial Doppler ultrasound (TCD) measurements of cerebral blood flow velocity in the middle cerebral artery (MCA). Results: The homogeneous model has the highest pass rate (100%), lowest coefficient of variation (CV) at rest (median [IQR] at 1 Hz of 0.18 [0.13, 0.22]), and most significant correlation with MCA blood flow velocities (Rs=0.59, p=0.010) compared with both the two- and three-layer models. The multilayer model pass rate was significantly correlated with extracerebral layer thicknesses. Discarding datasets with non-physiological BSRs increased the correlation between DCS measured CBFi and TCD measured MCA velocities for all models. Conclusions: We found that the homogeneous model has the highest pass rate, lowest CV at rest, and most significant correlation with MCA blood flow velocities. Results from the multilayer models should be taken with caution because they suffer from lower pass rates and higher coefficients of variation at rest and can converge to non-physiological values for CBFi. Future work is needed to validate these models in vivo, and novel approaches are merited to improve the performance of the multimodel models.

Cerebrospinal Fluid Pharmacokinetics of Nicardipine Following Intrathecal Administration in Subarachnoid Hemorrhage Patients.

Subarachnoid hemorrhage (SAH) is a devastating type of stroke, leading to high mortality and morbidity rates. Cerebral vasospasm and delayed cerebral ischemia (DCI) are common complications following SAH and contribute significantly to the poor outcomes observed in these patients. Intrathecal (IT) nicardipine delivered via an existing external ventricular drain has been shown to be correlated with reduced DCI and improved patient outcomes. The current study aims to characterize population pharmacokinetic (popPK) properties of intermittent IT nicardipine. Following informed consent, serial cerebrospinal fluid (CSF) samples were obtained from 16 SAH patients (50.4 ± 9.3 years old; 12 females) treated with IT nicardipine every 6 hours (n=8) or every 8 hours (n=8), which were subject to high-performance liquid chromatography for measurement of its CSF concentration. Our popPK analysis showed that the CSF PK of IT nicardipine in the cohort was adequately described by a two-compartment model with a lag time, with reliable parameter estimates (relative standard error < 50%). The intracranial pressure influenced both the total clearance and the central volume. Calculated PK parameters were similar between q6h and q8h dosing regimens. Despite a small cohort of SAH patients, we successfully developed a popPK model to describe the nicardipine disposition kinetics in the CSF following IT administration. These findings may help inform future clinical trials designed to examine the optimal dosing of IT nicardipine.

Microvascular cerebral blood flow response to intrathecal nicardipine is associated with delayed cerebral ischemia.

One of the common complications of non-traumatic subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI). Intrathecal (IT) administration of nicardipine, a calcium channel blocker (CCB), upon detection of large-artery cerebral vasospasm holds promise as a treatment that reduces the incidence of DCI. In this observational study, we prospectively employed a non-invasive optical modality called diffuse correlation spectroscopy (DCS) to quantify the acute microvascular cerebral blood flow (CBF) response to IT nicardipine (up to 90 min) in 20 patients with medium-high grade non-traumatic SAH. On average, CBF increased significantly with time post-administration. However, the CBF response was heterogeneous across subjects. A latent class mixture model was able to classify 19 out of 20 patients into two distinct classes of CBF response: patients in Class 1 (n = 6) showed no significant change in CBF, while patients in Class 2 (n = 13) showed a pronounced increase in CBF in response to nicardipine. The incidence of DCI was 5 out of 6 in Class 1 and 1 out of 13 in Class 2 (p < 0.001). These results suggest that the acute (<90 min) DCS-measured CBF response to IT nicardipine is associated with intermediate-term (up to 3 weeks) development of DCI.

Management and Long-Term Outcomes of Patients With Infectious Intracranial Aneurysms.

BACKGROUND: Infectious intracranial aneurysms (IIAs) are rare complications of infective endocarditis (IE). Data on management and long-term outcomes remain limited. OBJECTIVE: To retrospectively study long-term outcomes of IIAs in patients treated medically or surgically. METHODS: Adult cases of IE and/or IIAs admitted to Emory or Grady Healthcare Systems between May 2015 and May 2020 were reviewed for demographic, clinical, and radiographic variables for up to 2 years. Primary outcome measure was 2-year survival. RESULTS: Among 1714 cases of IE, intracerebral hemorrhage occurred in 322 patients and IIAs in 17 patients. The presence of IIAs in IE was associated with higher odds of disposition to hospice/death (odds ratio = 6.9). Including non-IE patients, 24 patients had 38 IIAs mainly involving the distal middle cerebral artery and 16 were ruptured on admission. IIAs were predominantly treated with antibiotics as the primary approach. Open microsurgery was the primary approach for 5 aneurysms and was used as salvage in 7 IIAs. Endovascular management was the primary approach for 2 IIAs and used as salvage for 5 IIAs with antibiotic failure. Medical management had high rate of treatment failure (15/31) which predominantly occurred within 2 weeks of onset. The 2-year survival in this cohort was 70% (17/24). CONCLUSION: IIAs are rare complications of IE with a poor prognosis. Patients treated with antibiotics have higher risk of treatment failure requiring salvage surgical or endovascular intervention. Medical treatment failure occurred mostly within 2 weeks of onset and had a negative prognostic value emphasizing the need for close follow-up and early surgical or endovascular management.

Surge Capacity in the COVID-19 Era: a Natural Experiment of Neurocritical Care in General Critical Care.

BACKGROUND: COVID-19 surges led to significant challenges in ensuring critical care capacity. In response, some centers leveraged neurocritical care (NCC) capacity as part of the surge response, with neurointensivists providing general critical care for patients with COVID-19 without neurologic illness. The relative outcomes of NCC critical care management of patients with COVID-19 remain unclear and may help guide further surge planning and provide broader insights into general critical care provided in NCC units. METHODS: We performed an observational cohort study of all patients requiring critical care for COVID-19 across four hospitals within the Emory Healthcare system during the first three surges. Patients were categorized on the basis of admission to intensive care units (ICUs) staffed by general intensivists or neurointensivists. Patients with primary neurological diagnoses were excluded. Baseline demographics, clinical complications, and outcomes were compared between groups using univariable and propensity score matching statistics. RESULTS: A total of 1141 patients with a primary diagnosis of COVID-19 required ICU admission. ICUs were staffed by general intensivists (n = 1071) or neurointensivists (n = 70). Baseline demographics and presentation characteristics were similar between groups, except for patients admitted to neurointensivist-staffed ICUs being younger (59 vs. 65, p = 0.027) and having a higher PaO2/FiO2 ratio (153 vs. 120, p = 0.002). After propensity score matching, there was no correlation between ICU staffing and the use of mechanical ventilation, renal replacement therapy, and vasopressors. The rates of in-hospital mortality and hospice disposition were similar in neurointensivist-staffed COVID-19 units (odds ratio 0.9, 95% confidence interval 0.31-2.64, p = 0.842). CONCLUSIONS: COVID-19 surges precipitated a natural experiment in which neurology-trained neurointensivists provided critical care in a comparable context to general intensivists treating the same disease. Neurology-trained neurointensivists delivered comparable outcomes to those of general ICUs during COVID-19 surges. These results further support the role of NCC in meeting general critical care needs of neurocritically ill patients and as a viable surge resource in general critical care.

Delayed Presentations and Worse Outcomes After Aneurysmal Subarachnoid Hemorrhage in the Early COVID-19 Era.

BACKGROUND: The early phase of the COVID-19 pandemic led to significant healthcare avoidance, perhaps explaining some of the excess reported deaths that exceeded known infections. The impact of the early COVID-19 era on aneurysmal subarachnoid hemorrhage (aSAH) care remains unclear. OBJECTIVE: To determine the impact of the early phase of the COVID-19 pandemic on latency to presentation, neurological complications, and clinical outcomes after aSAH. METHODS: We performed a retrospective cohort study from March 2, 2012, to June 30, 2021, of all patients with aSAH admitted to our center. The early COVID-19 era was defined as March 2, 2020, through June 30, 2020. The pre-COVID-19 era was defined as the same interval in 2012 to 2019. RESULTS: Among 499 patients with aSAH, 37 presented in the early COVID-19 era. Compared with the pre-COVID-19 era patients, patients presenting during this early phase of the pandemic were more likely to delay presentation after ictus (median, interquartile range; 1 [0-4] vs 0 [0-1] days, respectively, P < .001). Radiographic-delayed cerebral ischemia (29.7% vs 10.2%, P < .001) was more common in the early COVID-19 era. In adjusted analyses, presentation in the early COVID-19 era was independently associated with increased inhospital death or hospice disposition (adjusted odds ratio 3.29 [1.02-10.65], P = .046). Both latency and adverse outcomes returned to baseline in 2021. CONCLUSION: aSAH in the early COVID-19 era was associated with delayed presentation, neurological complications, and worse outcomes at our center. These data highlight how healthcare avoidance may have increased morbidity and mortality in non-COVID-19-related neurosurgical disease.

Prognostic Value of the Neurological Pupil Index in Patients With Acute Subarachnoid Hemorrhage.

BACKGROUND: The Neurological Pupil index (NPi) provides a quantitative assessment of pupil reactivity and may have prognostic value in patients with subarachnoid hemorrhage (SAH). We aimed to explore associations between the NPi and clinical outcomes in patients with SAH. METHODS: A retrospective analysis of 79 consecutive patients with acute SAH. Age, sex, Acute Physiology and Chronic Health Evaluation-II score, and respiratory failure and NPi in each eye were recorded at admission. The primary outcomes included death and poor clinical outcome (defined as inpatient death, care withdrawal, or discharge Glasgow Outcome Score <4). Groups were compared using the Fisher exact test, and predictive models developed with fast-and-frugal trees (FFTs). RESULTS: A total of 53 patients were included: 21 (40%) had poor clinical outcomes and 2 (4%) died. Univariate analysis found that only APACHE-II score (P < 0.001) and respiratory failure (P = 0.04) were significantly associated with poor clinical outcomes. NPi was lower among patients with poor clinical outcomes (mean 4.3 in the right eye and 4.2 in the left eye) vs those without (mean 4.5 in the right eye and 4.5 in the left eye), but neither was significant. However, the most accurate FFTs for death and poor clinical outcome included NPi after accounting for age in the death FFT and APACHE-II score in the poor outcome FFT (sensitivity [sn] = 100%, specificity [sp] = 94%, and accuracy (ac) = 94% in a model for death; sn = 100%, sp = 50%, and ac = 70%) in a model for poor clinical outcome. CONCLUSIONS: Our study supports the NPi as a useful prognostic marker for poor outcomes in acute SAH after accounting for age and APACHE-II score.

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

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.

Bridging thrombolysis in atrial fibrillation stroke is associated with increased hemorrhagic complications without improved outcomes.

BACKGROUND: Atrial fibrillation (AF) associated ischemic stroke is associated with worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Conversely, AF is not associated with hemorrhagic complications or functional outcomes in patients undergoing mechanical thrombectomy (MT). This differential effect of MT and IVT in AF associated stroke raises the question of whether bridging thrombolysis increases hemorrhagic complications in AF patients undergoing MT. METHODS: This international cohort study of 22 comprehensive stroke centers analyzed patients with large vessel occlusion (LVO) undergoing MT between June 1, 2015 and December 31, 2020. Patients were divided into four groups based on comorbid AF and IVT exposure. Baseline patient characteristics, complications, and outcomes were reported and compared. RESULTS: 6461 patients underwent MT for LVO. 2311 (35.8%) patients had comorbid AF. In non-AF patients, bridging therapy improved the odds of good 90 day functional outcomes (adjusted OR (aOR) 1.29, 95% CI 1.03 to 1.60, p=0.025) and did not increase hemorrhagic complications. In AF patients, bridging therapy led to significant increases in symptomatic intracranial hemorrhage and parenchymal hematoma type 2 (aOR 1.66, 1.07 to 2.57, p=0.024) without any benefit in 90 day functional outcomes. Similar findings were noted in a separate propensity score analysis. CONCLUSION: In this large thrombectomy registry, AF patients exposed to IVT before MT had increased hemorrhagic complications without improved functional outcomes, in contrast with non-AF patients. Prospective trials are warranted to assess whether AF patients represent a subgroup of LVO patients who may benefit from a direct to thrombectomy approach at thrombectomy capable centers.

Diffuse Angiogram-Negative Subarachnoid Hemorrhage is Associated with an Intermediate Clinical Course.

BACKGROUND: The cerebral angiography result is negative for an underlying vascular lesion in 15-20% of patients with nontraumatic subarachnoid hemorrhage (SAH). Patients with angiogram-negative SAH include those with perimesencephalic SAH and diffuse SAH. Consensus suggests that perimesencephalic SAH confers a more favorable prognosis than diffuse SAH. Limited data exist to contextualize the clinical course and prognosis of diffuse SAH in relation to aneurysmal SAH in terms of critical care complications, neurologic complications, and functional outcomes. Here we compare the clinical course and functional outcomes of patients with perimesencephalic SAH, diffuse SAH, and aneurysmal SAH to better characterize the prognostic implications of each SAH subtype. METHODS: We conducted a retrospective cohort study that included all patients with nontraumatic SAH admitted to a tertiary care referral center between January 1, 2012, and December 31, 2017. Bleed patterns were radiographically adjudicated, and patients were assigned to three groups: perimesencephalic SAH, diffuse SAH, and aneurysmal SAH. Patient demographics, complications, and clinical outcomes were reported and compared. RESULTS: Eighty-six patients with perimesencephalic SAH, 174 with diffuse SAH, and 998 with aneurysmal SAH presented during the study period. Patients with aneurysmal SAH were significantly more likely to be female, White, and active smokers. There were no significant differences between patients with diffuse SAH and perimesencephalic SAH patterns. Critical care complications were compared across all three groups, with significant between-group differences in hypotension and shock (3.5% vs. 16.1% vs. 38.4% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.01) and endotracheal intubation (0% vs. 26.4% vs. 48.8% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.01). Similar trends were noted with long-term supportive care with tracheostomy and gastrostomy tubes and length of stay. Cerebrospinal fluid diversion was increasingly required across bleed types (9.3% vs. 54.6% vs. 76.3% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively, p < 0.001). Vasospasm and delayed cerebral ischemia were comparable between perimesencephalic SAH and diffuse SAH but significantly lower than aneurysmal SAH. Patients with diffuse SAH had intermediate functional outcomes, with significant rates of nonhome discharge (23.0%) and poor functional status on discharge (26.4%), significantly higher than patients with perimesencephalic SAH and lower than patients with aneurysmal SAH. Diffuse SAH similarly conferred an intermediate rate of good functional outcomes at 1-6 months post discharge (92.3% vs. 78.6% vs. 47.3% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.016). CONCLUSIONS: We confirm the consensus data that perimesencephalic SAH is associated with a more benign clinical course but demonstrate that diffuse SAH confers an intermediate prognosis, more malignant than perimesencephalic SAH but not as morbid as aneurysmal SAH. These results highlight the significant morbidity associated with diffuse SAH and emphasize need for vigilance in the acute care of these patients. These patients will likely benefit from continued high-acuity observation and potential support to avert significant risk of morbidity and neurologic compromise.

Successful Endovascular Therapy in COVID-19 Associated Pediatric Ischemic Stroke.

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.

Nicardipine Prolonged Release Implants for Prevention of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.

OBJECTIVES: A paucity of treatments to prevent delayed cerebral ischemia (DCI) has stymied recovery after aneurysmal subarachnoid hemorrhage (aSAH). Nicardipine has long been recognized as a potent cerebrovascular vasodilator with a history off-label use to prevent vasospasm and DCI. Multiple centers have developed nicardipine prolonged release implants (NPRI) that are directly applied during clip ligation to locally deliver nicardipine throughout the vasospasm window. Here we perform a systematic review and meta-analysis to assess whether NPRI confers protection against DCI and improves functional outcomes after aSAH. MATERIALS AND METHODS: A systematic search of PubMed, Ovid Embase, and Cochrane databases was performed for studies reporting the use of NPRI after aSAH published after January 1, 1980. We included all studies assessing the association of NPRI with DCI and or functional outcomes. Findings from studies with control arms were analyzed using a random effects model. A separate network meta-analysis was performed, including controlled NPRI studies, single-arm NPRI reports, and the control-arms of modern aSAH randomized clinical trials as additional comparators. RESULTS: The search identified 214 unique citations. Three studies with 284 patients met criteria for the random effects model. The pooled summary odds ratio for the association of NPRI and DCI was 0.21 (95% CI 0.09-0.49, p = 0.0002) with no difference in functional outcomes (OR 1.80, 95% CI 0.63 - 5.16, p = 0.28). 10 studies of 866 patients met criteria for the network meta-analysis. The pooled summary odds ratio for the association of NPRI and DCI was 0.30 (95% CI 0.13-0.89,p = 0.017) with a trend towards improved functional outcomes (OR 1.68, 0.63 - 4.13 95% CI, p = 0.101). CONCLUSIONS: In these meta-analyses, NPRI decreases the incidence of DCI with a non-significant trend towards improvement in functional outcomes. Randomized trials on the role of intrathecal calcium channel blockers are warranted to evaluate these observations in a prospective manner.

Aneurysmal Subarachnoid Hemorrhage: Trends, Outcomes, and Predictions From a 15-Year Perspective of a Single Neurocritical Care Unit.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with disproportionally high mortality and long-term neurological sequelae. Management of patients with aSAH has changed markedly over the years, leading to improvements in outcome. OBJECTIVE: To describe trends in aSAH care and outcome in a high-volume single center 15-yr cohort. METHODS: All new admissions diagnosed with subarachnoid hemorrhage (SAH) to our tertiary neuro-intensive care unit between 2002 and 2016 were reviewed. Trend analysis was performed to assess temporal changes and a step-wise regression analysis was done to identify factors associated with outcomes. RESULTS: Out of 3970 admissions of patients with SAH, 2475 patients proved to have a ruptured intracranial aneurysm. Over the years of the study, patient acuity increased by Hunt & Hess (H&H) grade and related complications. Endovascular therapies became more prevalent over the years, and were correlated with better outcome. Functional outcome overall improved, yet the main effect was noted in the low- and intermediate-grade patients. Several parameters were associated with poor functional outcome, including long-term mechanical ventilation (odds ratio 11.99, CI 95% [7.15-20.63]), acute kidney injury (3.55 [1.64-8.24]), pneumonia (2.89 [1.89-4.42]), hydrocephalus (1.80 [1.24-2.63]) diabetes mellitus (1.71 [1.04-2.84]), seizures (1.69 [1.07-2.70], H&H (1.67 [1.45-1.94]), and age (1.06 [1.05-1.07]), while endovascular approach to treat the aneurysm, compared with clip-ligation, had a positive effect (0.35 [0.25-0.48]). CONCLUSION: This large, single referral center, retrospective analysis reveals important trends in the treatment of aSAH. It also demonstrates that despite improvement in functional outcome over the years, systemic complications remain a significant risk factor for poor prognosis. The historic H&H determination of outcome is less valid with today's improved care.

Differential effect of mechanical thrombectomy and intravenous thrombolysis in atrial fibrillation associated stroke.

BACKGROUND: Atrial fibrillation (AF) associated ischemic stroke has worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Limited data exist about the effect of AF on procedural and clinical outcomes after mechanical thrombectomy (MT). OBJECTIVE: To determine whether recanalization efficacy, procedural speed, and clinical outcomes differ in AF associated stroke treated with MT. METHODS: We performed a retrospective cohort study of the Stroke Thrombectomy and Aneurysm Registry (STAR) from January 2015 to December 2018 and identified 4169 patients who underwent MT for an anterior circulation stroke, 1517 (36.4 %) of whom had comorbid AF. Prospectively defined baseline characteristics, procedural outcomes, and clinical outcomes were reported and compared. RESULTS: AF predicted faster procedural times, fewer passes, and higher rates of first pass success on multivariate analysis (p<0.01). AF had no effect on intracranial hemorrhage (aOR 0.69, 95% CI 0.43 to 1.12) or 90-day functional outcomes (aOR 1.17, 95% CI 0.91 to 1.50) after MT, although patients with AF were less likely to receive IVT (46% vs 54%, p<0.0001). CONCLUSIONS: In patients treated with MT, comorbid AF is associated with faster procedural time, fewer passes, and increased rates of first pass success without increased risk of intracranial hemorrhage or worse functional outcomes. These results are in contrast to the increased hemorrhage rates and worse functional outcomes observed in AF associated stroke treated with supportive care and or IVT. These data suggest that MT negates the AF penalty in ischemic stroke.

Ocular Fundus Abnormalities in Acute Subarachnoid Hemorrhage: The FOTO-ICU Study.

BACKGROUND: Ocular fundus abnormalities, especially intraocular hemorrhage, may represent a clinically useful prognostic marker in patients with acute subarachnoid hemorrhage (SAH). OBJECTIVE: To evaluate associations between ocular fundus abnormalities and clinical outcomes in acute SAH. METHODS: Prospective evaluation of acute SAH patients with ocular fundus photography at bedside. Multivariable logistic models were used to evaluate associations between fundus abnormalities and poor outcome (inpatient death, care withdrawal, or discharge Glasgow Outcome Score <4) and intensive care unit (ICU) and hospital lengths-of-stay, controlling for APACHE II score, respiratory failure at ICU admission, Hunt & Hess score, aneurysmal etiology, age, and sex. RESULTS: Fundus abnormalities were present in 29/79 patients with acute SAH (35.4%), and 20/79 (25.3%) had intraocular hemorrhage. In univariate analyses, poor outcomes were more likely among patients with fundus abnormalities vs without (15/28 [53.6%] vs 15/51 [29.4%], P = .03); median length of ICU stay was longer in patients with intraocular hemorrhage than without (18 d [interquartile range (IQR) 12-25] vs 11 [IQR 7-17], P = .03). Logistic regression with fundus abnormality as predictor of interest showed that male sex (odds ratio [OR] 5.33 [95% CI 1.09-26.0], P = .045), higher APACHE II (OR, per 1-point increase, 1.35 [95% CI 1.08-1.78], P = .01), and aneurysmal etiology (OR 4.35 [95% CI 1.01-22.9], P = .048), but not fundus abnormalities (OR 1.56 [95% CI 0.43-5.65], P = .49) or intraocular hemorrhage (OR 1.28 [95% CI 0.26-5.59], P = .75) were associated with poor outcome. CONCLUSION: Although ocular fundus abnormalities are associated with disease severity in SAH, they do not add value to patients' acute management beyond other risk factors already in use.

The authors' response.

In response to comments raised, we acknowledge the shortcomings of our study. It is a small study. However, it is a pilot study, which is not meant to create generalizable data, rather to explore new potential directions. To this end, our conclusions were clearly supported by the results. We demonstrated that administration of 16.4% NaCl/Na-acetate solution was feasible, safe, and was associated with lower rates of AKI. We share the call that large RCTs are required to follow this pilot study and hope that our data will stimulate the ongoing discussion regarding the role of chloride in AKI mechanism.