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.

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.

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.

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.

Hyperchloremia Is Associated With Acute Kidney Injury in Patients With Subarachnoid Hemorrhage.

OBJECTIVE: To assess the prevalence of acute kidney injury in patients with subarachnoid hemorrhage patients. DESIGN: Retrospective analysis of all subarachnoid hemorrhage admissions. SETTINGS: Neurocritical care unit. PATIENTS: All patients with a diagnosis of subarachnoid hemorrhage between 2009 and 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,267 patients included in this cohort, 16.7% developed acute kidney injury, as defined by Kidney Disease Improving Global Outcome criteria (changes in creatinine only). Compared to patients without acute kidney injury, patients with acute kidney injury had a higher prevalence of diabetes mellitus (21.2% vs 9.8%; p < 0.001) and hypertension (70.3% vs 50.5%; p < 0.001) and presented with higher admission creatinine concentrations (1.21 ± 0.09 vs 0.81 ± 0.01 mg/dL [mean ± SD], respectively; p < 0.001). Patients with acute kidney injury also had higher mean serum chloride and sodium concentrations during their ICU stay (113.4 ± 0.6 vs 107.1 ± 0.2 mmol/L and 143.3 ± 0.4 vs 138.8 ± 0.1 mmol/L, respectively; p < 0.001 for both), but similar chloride exposure. The mortality rate was also significantly higher in patients with acute kidney injury (28.3% vs 6.1% in the non-acute kidney injury group [p < 0.001]). Logistic regression analysis revealed that only male gender (odds ratio, 1.82; 95% CI, 1.28-2.59), hypertension (odds ratio, 1.64; 95% CI, 1.11-2.43), diabetes mellitus (odds ratio, 1.88; 95% CI, 1.19-2.99), abnormal baseline creatinine (odds ratio, 2.48; 95% CI, 1.59-3.88), and increase in mean serum chloride concentration (per 10 mmol/L; odds ratio, 7.39; 95% CI, 3.44-18.23), but not sodium, were associated with development of acute kidney injury. Kidney recovery was noted in 78.8% of the cases. Recovery reduced mortality compared to non-recovering subgroup (18.6% and 64.4%, respectively; p < 0.001). CONCLUSIONS: Critically ill patients with subarachnoid hemorrhage show a strong association between hyperchloremia and acute kidney injury as well as acute kidney injury and mortality.

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

DISCLAIMER: 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. PURPOSE: 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. SUMMARY: 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. CONCLUSION: This case illustrates the potential benefit of using dual IVT vasodilators to improve outcomes for pediatric patients with refractory cerebral vasospasm.

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.

An examination of aneurysm rerupture rates with epsilon aminocaproic acid.

BACKGROUND: Epsilon aminocaproic acid (EACA) has been used in the past to prevent cerebral aneurysm rerupture. Recent studies have indicated that short-term treatment with EACA can lower rebleeding rates without significantly increasing ischemic or thrombotic complications or permanent shunt rates. The goal of this study is to determine the efficacy of EACA in the prevention of aneurysm rerupture at a high volume subarachnoid hemorrhage center. METHODS: We conducted a retrospective study of 355 consecutive subarachnoid hemorrhage patients over a 2-year period under our current protocol for EACA use. Patients were divided by presentation time to our institution and whether the patient received EACA. The primary endpoints of the study were rebleeding rates, ischemic complications, thrombotic complications, vasospasm, shunt rates, and outcomes. RESULTS: Rerupture rates were reduced by half in the entire pool of patients on EACA after controlling for Hunt and Hess Scores and Fisher Scores. In patients who received early aneurysm treatment, this effect persisted but was non-statistically significant due to the small numbers of reruptures. In addition, there was no evidence to suggest that EACA increased ischemic or thrombotic complications, vasospasm, or VPS rates. In patients presenting earlier than 24 h to our institution, there was a non-significant trend toward worse outcomes after EACA use. This trend was reversed in patients arriving after 24 h. CONCLUSION: There is evidence to suggest that EACA is protective from aneurysm rerupture without significant ischemic or thrombotic complications when used for less than 72 h. However, if the aneurysm is treated, this effect is modest indicating that early aneurysm treatment remains the gold standard for rerupture prevention.

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.

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.

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.

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.

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.

Reversible brain death after cardiopulmonary arrest and induced hypothermia.

OBJECTIVE: To describe a patient with transient reversal of findings of brain death after cardiopulmonary arrest and attempted therapeutic hypothermia. DESIGN: Case report. SETTING: Intensive care unit of an academic tertiary care hospital. PATIENT: A 55-yr-old man presented with cardiac arrest preceded by respiratory arrest. Cardiopulmonary resuscitation was performed, spontaneous perfusion restored, and therapeutic hypothermia was attempted for neural protection. After rewarming to 36.5°C, neurologic examination showed no eye opening or response to pain, spontaneous myoclonic movements, sluggishly reactive pupils, absent corneal reflexes, and intact gag and spontaneous respirations. Over 24 hrs, remaining cranial nerve function was lost. The neurologic examination was consistent with brain death. Apnea test and repeat clinical examination after a duration of 6 hrs confirmed brain death. Death was pronounced and the family consented to organ donation. Twenty-four hrs after brain death pronouncement, on arrival to the operating room for organ procurement, the patient was found to have regained corneal reflexes, cough reflex, and spontaneous respirations. The care team faced the challenge of offering an adequate explanation to the patient's family and other healthcare professionals involved. INTERVENTIONS: Induced hypothermia and brain death determination. MEASUREMENTS AND MAIN RESULTS: This represents the first published report in an adult patient of reversal of a diagnosis of brain death made in full adherence to American Academy of Neurology guidelines. Although the reversal was transient and did not impact the patient's prognosis, it impacted his eligibility for organ donation and cast doubt about the ability to determine irreversibility of brain death findings in patients treated with hypothermia after cardiac arrest. CONCLUSIONS: We strongly recommend caution in the determination of brain death after cardiac arrest when induced hypothermia is used. Confirmatory testing should be considered and a minimum observation period after rewarming before brain death testing ensues should be established.

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.

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.

Use of intrathecal nicardipine for aneurysmal subarachnoid hemorrhage-induced cerebral vasospasm.

BACKGROUND: Cerebral vasospasm leading to delayed ischemia is a common and serious complication of aneurysmal subarachnoid hemorrhage that often results in increased morbidity and mortality. Treatments for cerebral vasospasm, including triple-H therapy (therapeutic hypervolemia, hypertension, and hemodilution), nimodipine, balloon angioplasty, and intra-arterial vasodilators have limitations in their efficacy and safety profiles. Nicardipine, a calcium channel blocker, is available for intravenous administration for blood pressure reduction. A recent study reported its efficacy in the treatment of cerebral vasospasm when given intrathecally (IT). We present our experiences with IT nicardipine for treatment of cerebral vasospasm. METHODS: IT nicardipine was administered to six patients with aneurysmal subarachnoid hemorrhage after prophylactic and aggressive therapeutic management for vasospasm failed. RESULTS: In these patients, IT nicardipine treatment was followed within 8 hours by a 43.1 +/- 31.0 cm/s decrease in middle cerebral arterial flow velocity, as measured by transcranial Doppler ultrasound. CONCLUSIONS: Based on these positive results, we believe that larger scale studies evaluating the safety and efficacy of IT nicardipine for the management of cerebral vasospasm are warranted.