Does Targeted Temperature Management Improve Neurological Outcome in Extracorporeal Cardiopulmonary Resuscitation (ECPR)?

PURPOSE: Targeted temperature management (TTM) is a standard of care in patients after cardiac arrest for neuroprotection. Currently, the effectiveness and efficacy of TTM after extracorporeal cardiopulmonary resuscitation (ECPR) is unknown. We aimed to compare neurological and survival outcomes between TTM vs non-TTM in patients undergoing ECPR for refractory cardiac arrest. METHODS: We searched PubMed and 5 other databases for randomized controlled trials and observational studies reporting neurological outcomes or survival in adult patients undergoing ECPR with or without TTM. Good neurological outcome was defined as cerebral performance category <3. Two independent reviewers extracted the data. Random-effects meta-analyses were used to pool data. RESULTS: We included 35 studies (n = 2,643) with the median age of 56 years (interquartile range [IQR]: 52-59). The median time from collapse to ECMO cannulation was 58 minutes (IQR: 49-82) and the median ECMO duration was 3 days (IQR: 2.0-4.1). Of 2,643, 1,329 (50.3%) patients received TTM and 1,314 (49.7%) did not. There was no difference in the frequency of good neurological outcome at any time between TTM (29%, 95% confidence interval [CI]: 23%-36%) vs. without TTM (19%, 95% CI: 9%-31%) in patients with ECPR (P = 0.09). Similarly, there was no difference in overall survival between patients with TTM (30%, 95% CI: 22%-39%) vs. without TTM (24%, 95% CI: 14%-34%) (P = 0.31). A cumulative meta-analysis by publication year showed improved neurological and survival outcomes over time. CONCLUSIONS: Among ECPR patients, survival and neurological outcome were not different between those with TTM vs. without TTM. Our study suggests that neurological and survival outcome are improving over time as ECPR therapy is more widely used. Our results were limited by the heterogeneity of included studies and further research with granular temperature data is necessary to assess the benefit and risk of TTM in ECPR population.

Transcranial-Doppler-Measured Vasospasm Severity is Associated with Delayed Cerebral Infarction After Subarachnoid Hemorrhage.

BACKGROUND: Angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed cerebral ischemia (DCI)-related cerebral infarction (radiological DCI) and worsened neurological outcome. Transcranial Doppler (TCD) measurements of cerebral blood flow velocity are commonly used after aSAH to screen for vasospasm; however, their association with cerebral infarction is not well characterized. We sought to determine whether time-varying TCD-measured vasospasm severity is associated with cerebral infarction and investigate the performance characteristics of different time/severity cutoffs for predicting cerebral infarction. METHODS: We conducted a retrospective single-center cohort study of consecutive adult patients with aSAH with at least one TCD study between 2011 and 2020. The primary outcome was radiological DCI, defined as a cerebral infarction developing at least 2 days after any surgical or endovascular intervention without an alternative cause. Cox proportional hazards models were used to examine associations between time-varying vasospasm severity and radiological DCI. Optimal TCD-based time/severity thresholds for predicting radiological DCI were then determined. RESULTS: Of 262 patients with aSAH who underwent TCD studies, 27 (10%) developed radiological DCI. Patients with radiological DCI had higher modified Fisher scale scores and trended toward earlier onset of vasospasm. Adjusted for age, Hunt and Hess scores, and modified Fisher scale scores, the worst-vessel vasospasm severity was associated with radiological DCI (adjusted hazard ratio 1.7 [95% confidence interval 1.1-2.4]). Vasospasm severity within a specific vessel was associated with risk of delayed infarction in the territory supplied by that vessel. Optimal discrimination of patients with radiological DCI was achieved with thresholds of mild vasospasm on days 4-5 or moderate vasospasm on days 6-9, with negative predictive values greater than 90% and positive predictive values near 20%. CONCLUSIONS: TCD-measured vasospasm severity is associated with radiological DCI after aSAH. An early, mild TCD-based vasospasm severity threshold had a high negative predictive value, supporting its role as a screening tool to identify at-risk patients.

Volume replacement is associated with a diminished osmolar effect of mannitol in patients with acute brain injury.

INTRODUCTION: Animal experiments recently demonstrated that replacing urinary loses with crystalloid diminishes the therapeutic effect of mannitol by reducing the increase in osmolality. We aimed to investigate whether this effect is similarly seen in in brain-injured patients by studying the association between total body fluid balance (TBB) and the osmolar response to mannitol. METHODS: We performed a retrospective cohort study of adult patients with acute brain injury between 2015 and 2021 who received ≥ 2 doses of mannitol within 8 hours and no intercurrent concentrated saline solution. We analyzed the association between the change in TBB (∆TBB) and change in osmolality (∆Osm) before and after mannitol in a linear model, both as univariate and after adjustment for common confounding factors. RESULTS: Of 6,145 patients who received mannitol, 155 patients met inclusion criteria (mean age 60 ± 17 years, 48% male, 83% white). The mean total mannitol dose was 2 ± 0.5 g/kg and the mean change in plasma osmolality was 7.9 ± 7.1 mOsm/kg. Each 1 L increase in ∆TBB was associated with a change of -1.1 mOsm/L in ∆Osm (95% CI [-2.2, -0.02], p = 0.045). The magnitude of association was similar to that of total mannitol dose and remained consistent in an adjusted model and after excluding outliers. CONCLUSIONS: In patients with acute brain injury, a positive TBB is associated with a diminished mannitol-induced increase in plasma osmolality. Future prospective studies are needed to confirm these findings and their influence on the therapeutic effect of mannitol.

Determination of Brain Death in Patients Undergoing Short-Term Mechanical Circulatory Support Devices.

OBJECTIVE: To describe apnoea test (AT) and ancillary study performance for brain death (BD) determination among patients undergoing short-term mechanical circulatory support (MCS) devices, including extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP). METHODS: We retrospectively analysed data regarding use of AT and ancillary study in consecutive adult patients who were diagnosed with BD while on MCS devices (including ECMO and IABP) over a 10-year period. RESULTS: Out of 140 patients, eight were on MCS devices at the time of BD (four ECMO, two ECMO and IABP, two IABP). The most common aetiology of BD was hypoxic ischaemic brain injury (6/8, 75%). In four patients (50%), the AT was not attempted because of haemodynamic instability and ECMO; in the remaining four (50%), both AT and ancillary studies were used. In three patients on ECMO, AT was performed by reducing the ECMO sweep flow rate to a range 0.5-2.7 L/min in order to achieve hypercarbia. One patient underwent AT while on IABP which was complicated by hypotension. All patients underwent ancillary tests, most commonly transcranial Doppler ultrasonography (TCD) (7/8, 88%); among those, cerebral circulatory arrest was confirmed in six of seven patients (86%), all of whom had left ventricular ejection fracture (LVEF) ≥20% and/or were supported with IABP. CONCLUSIONS: There are multiple uncertainties regarding BD diagnosis while on MCS, prompting the need for ancillary studies in most patients. Our study shows that TCD can be used to support BD diagnosis in patients on ECMO who have sufficient cardiac contractility and/or IABP to produce pulsatile flow. TCD use in ECMO patients low LVEF needs further study.

Outcomes, Time-Trends, and Factors Associated With Ancillary Study Use for the Determination of Brain Death.

OBJECTIVES: Brain death determination often requires ancillary studies when clinical determination cannot be fully or safely completed. We aimed to analyze the results of ancillary studies, the factors associated with ancillary study performance, and the changes over time in number of studies performed at an academic health system. DESIGN: Retrospective cohort. SETTING: Multihospital academic health system. PATIENTS: Consecutive adult patients declared brain dead between 2010 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 140 brain death patients, ancillary studies were performed in 84 (60%). The false negative rate of all ancillary studies was 4% (5% of transcranial Doppler ultrasounds, 4% of nuclear studies, 0% of electroencephalograms, and 17% of CT angiography). In univariate analysis, ancillary study use was associated with female sex (odds ratio, 2.4; 95% CI, 1.21-5.01; p = 0.013) and the etiology of brain death being hypoxic-ischemic brain injury (odds ratio, 2.9; 95% CI, 1.43-5.88; p = 0.003), nontraumatic intracranial hemorrhage (odds ratio, 0.45; 95% CI, 0.21-0.96; p = 0.039), or traumatic brain injury (odds ratio, 0.22; 95% CI, 0.04-0.8; p = 0.031). In multivariable analysis, female sex (odds ratio, 5.7; 95% CI, 2.56-15.86; p = 0.004), the etiology of brain death being hypoxic-ischemic brain injury (odds ratio, 3.2; 95% CI, 1.3-8.8; p = 0.015), and the neurologists performing brain death declaration (odds ratio, 0.08; 95% CI, 0.004-0.64; p = 0.034) were factors independently associated with use of ancillary studies. Over the study period, the total number of ancillary studies performed each year did not significantly change; however, the number of electroencephalograms significantly decreased with time (odds ratio per 1-yr increase, 0.67; 95% CI, 0.49-0.90; p = 0.014). CONCLUSIONS: A large number of ancillary studies were performed despite a clinical determination of brain death; patients with hypoxic-ischemic brain injury are more likely to undergo ancillary studies for brain death determination, and neurologists were less likely to use ancillary studies for brain death. Recently, the use of electroencephalograms for brain death determination has decreased, likely reflecting significant concerns regarding its validity and reliability.

Atrial Fibrillation and Ischemic Stroke: A Clinical Review.

Atrial fibrillation (AF) is an important risk factor for ischemic stroke resulting in a fivefold increased stroke risk and a twofold increased mortality. Our understanding of stroke mechanisms in AF has evolved since the concept of atrial cardiopathy was introduced as an underlying pathological change, with both AF and thromboembolism being common manifestations and outcomes. Despite the strong association with stroke, there is no evidence that screening for AF in asymptomatic patients improves clinical outcomes; however, there is strong evidence that patients with embolic stroke of undetermined source may require long-term monitoring to detect silent or paroxysmal AF. Stroke prevention in patients at risk, assessed by the CHA2DS2-VASc score, was traditionally achieved with warfarin; however, direct oral anticoagulants have solidified their role as safe and effective alternatives. Additionally, left atrial appendage exclusion has emerged as a viable option in patients intolerant of anticoagulation. When patients with AF have an acute stroke, the timing of initiation or resumption of anticoagulation for secondary stroke prevention has to be balanced against the risk of hemorrhagic conversion. Multiple randomized clinical trials are currently underway to determine the best timing for administration of anticoagulants following acute ischemic stroke.

Cerebral Hyperperfusion and Delayed Coma Recovery after Subdural Hematoma Evacuation.

Acute subdural hematoma is a devastating neurological injury with significant morbidity and mortality. In patients with large subdural hematoma resulting in compression of the underlying brain and lateral brain shift, severe neurological deficits and coma can occur. Emergent neurosurgical decompression is a life-saving intervention which improves mortality and neurological function. Persistent coma despite subdural hematoma evacuation is often the result of persistent midline shift, cerebral infarctions related to initial elevated intracranial pressure and herniation, nonconvulsive seizures, and other metabolic and infectious causes; however, a subset of patients remains comatose without a discernable etiology. In this report, we describe an elderly patient who remained comatose without a known cause for several weeks after subdural hematoma evacuation and was found to have delayed cerebral hyperperfusion on brain imaging. After several days, there was marked recovery of consciousness which occurred in a timeframe that matched improvement in brain imaging findings. Cerebral hyperperfusion following subdural hematoma evacuation requires further investigation, and should be considered as a cause of persistent but potentially recoverable coma.

Brain Injury and Neurologic Outcome in Patients Undergoing Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

OBJECTIVES: Extracorporeal cardiopulmonary resuscitation has shown survival benefit in select patients with refractory cardiac arrest but there is insufficient data on the frequency of different types of brain injury. We aimed to systematically review the prevalence, predictors of and survival from neurologic complications in patients who have undergone extracorporeal cardiopulmonary resuscitation. DATA SOURCES: MEDLINE (PubMed) and six other databases (EMBASE, Cochrane Library, CINAHL Plus, Web of Science, and Scopus) from inception to August 2019. STUDY SELECTION: Randomized controlled trials and observational studies in patients greater than 18 years old. DATA EXTRACTION: Two independent reviewers extracted the data. Study quality was assessed by the Cochrane Risk of Bias tool for randomized controlled trials, the Newcastle-Ottawa Scale for cohort and case-control studies, and the Murad tool for case series. Random-effects meta-analyses were used to pool data. DATA SYNTHESIS: The 78 studies included in our analysis encompassed 50,049 patients, of which 6,261 (12.5%) received extracorporeal cardiopulmonary resuscitation. Among extracorporeal cardiopulmonary resuscitation patients, the median age was 56 years (interquartile range, 52-59 yr), 3,933 were male (63%), 3,019 had out-of-hospital cardiac arrest (48%), and 2,289 had initial shockable heart rhythm (37%). The most common etiology of cardiac arrest was acute coronary syndrome (n = 1,657, 50% of reported). The median extracorporeal cardiopulmonary resuscitation duration was 3.2 days (interquartile range, 2.1-4.9 d). Overall, 27% (95% CI, 0.17-0.39%) had at least one neurologic complication, 23% (95% CI, 0.14-0.32%) hypoxic-ischemic brain injury, 6% (95% CI, 0.02-0.11%) ischemic stroke, 6% (95% CI, 0.01-0.16%) seizures, and 4% (95% CI, 0.01-0.1%) intracerebral hemorrhage. Seventeen percent (95% CI, 0.12-0.23%) developed brain death. The overall survival rate after extracorporeal cardiopulmonary resuscitation was 29% (95% CI, 0.26-0.33%) and good neurologic outcome was achieved in 24% (95% CI, 0.21-0.28%). CONCLUSIONS: One in four patients developed acute brain injury after extracorporeal cardiopulmonary resuscitation and the most common type was hypoxic-ischemic brain injury. One in four extracorporeal cardiopulmonary resuscitation patients achieved good neurologic outcome. Further research on assessing predictors of extracorporeal cardiopulmonary resuscitation-associated brain injury is necessary.

Brain Injury Is More Common in Venoarterial Extracorporeal Membrane Oxygenation Than Venovenous Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

OBJECTIVES: Despite the common occurrence of brain injury in patients undergoing extracorporeal membrane oxygenation, it is unclear which cannulation method carries a higher risk of brain injury. We compared the prevalence of brain injury between patients undergoing venoarterial and venovenous extracorporeal membrane oxygenation. DATA SOURCES: PubMed and six other databases from inception to April 2020. STUDY SELECTION: Observational studies and randomized clinical trials in adult patients undergoing venoarterial extracorporeal membrane oxygenation or venovenous extracorporeal membrane oxygenation reporting brain injury. DATA EXTRACTION: Two independent reviewers extracted the data from the studies. Random-effects meta-analyses were used to pool data. DATA SYNTHESIS: Seventy-three studies (n = 16,063) met inclusion criteria encompassing 8,211 patients (51.2%) undergoing venoarterial extracorporeal membrane oxygenation and 7,842 (48.8%) undergoing venovenous extracorporeal membrane oxygenation. Venoarterial extracorporeal membrane oxygenation patients had more overall brain injury compared with venovenous extracorporeal membrane oxygenation (19% vs 10%; p = 0.002). Venoarterial extracorporeal membrane oxygenation patients had more ischemic stroke (10% vs 1%; p < 0.001), hypoxic-ischemic brain injury (13% vs 1%; p < 0.001), and brain death (11% vs 1%; p = 0.001). In contrast, rates of intracerebral hemorrhage (6% vs 8%; p = 0.35) did not differ. Survival was lower in venoarterial extracorporeal membrane oxygenation (48%) than venovenous extracorporeal membrane oxygenation (64%) (p < 0.001). After excluding studies that included extracorporeal cardiopulmonary resuscitation, no significant difference was seen in the rate of overall acute brain injury between venoarterial extracorporeal membrane oxygenation and venovenous extracorporeal membrane oxygenation (13% vs 10%; p = 0.4). However, ischemic stroke (10% vs 1%; p < 0.001), hypoxic-ischemic brain injury (7% vs 1%; p = 0.02), and brain death (9% vs 1%; p = 0.005) remained more frequent in nonextracorporeal cardiopulmonary resuscitation venoarterial extracorporeal membrane oxygenation compared with venovenous extracorporeal membrane oxygenation. CONCLUSIONS: Brain injury was more common in venoarterial extracorporeal membrane oxygenation compared with venovenous extracorporeal membrane oxygenation. While ischemic brain injury was more common in venoarterial extracorporeal membrane oxygenation patients, the rates of intracranial hemorrhage were similar between venoarterial extracorporeal membrane oxygenation and venovenous extracorporeal membrane oxygenation. Further research on mechanism, timing, and effective monitoring of acute brain injury and its management is necessary.

Asymmetric cerebral edema presenting with severe neurologic impairment and seizures after cardiac and thoracic interventions.

INTRODUCTION: A syndrome of focal neurologic deficits with characteristic imaging features, acute encephalopathy, and seizures after cardiac and thoracic interventions has been previously briefly reported in the literature. In a retrospective observational study, we aim to identify the prevalence and characteristics of this syndrome, in addition to discussing the possible underlying pathophysiology. METHODS: In a retrospective study, we reviewed records of consecutive adult patients (≥18 years old) who underwent cardiac and thoracic procedures at a single institution between September 2014 to September 2019 and found to have evidence of focal cerebral edema following their procedure. We included and reported clinical course of patients who developed post-operative neurologic dysfunction and underwent magnetic resonance imaging (MRI) showing (1) asymmetric cerebral edema with (2) cortical diffusion restriction and (3) T2 cortical or subcortical hyperintensity and (4) no proximal vascular occlusion. RESULTS: Three out of 107 patients (2.8%) met our inclusion criteria. These represented one male and two females with age at presentation of 63, 81 and 69, respectively. All patients developed severe neurologic impairment on the same day following their procedure (sternotomy with valve or bypass surgery in 2 patients; esophageal dilatation procedure in 1 patient). All patients underwent MRI of the brain and vessel imaging qualifying our inclusion criteria. Two patients improved neurologically prior to discharge, and one patient expired after family elected to withdraw care. CONCLUSION: We present a series of cases with a rare syndrome after cardiac and thoracic interventions. Although the exact mechanism of this syndrome remains unclear, we believe it to be related to relative cerebral hyperperfusion and cerebral dysautoregulation following anesthesia and thoracic manipulation. Future studies should focus on understanding the true prevalence and pathophysiology of this syndrome.

Cerebral Microhemorrhage and Purpuric Rash in COVID-19: The Case for a Secondary Microangiopathy.

INTRODUCTION: Since the emergence of Coronavirus Disease 19 (COVID-19) pandemic, multiple neurologic complications in infected patients have been reported. Despite these reports, the mechanism of COVID-19 nervous system injury is not well understood. We report the case of a COVID-19 patient with diffuse microhemorrhages on brain MRI, positive anticardiolipin antibodies, and purpuric rash with biopsy showing a thrombotic vasculopathy, all features suggestive of secondary microangiopathy. CASE REPORT: A 69-year-old male with history of hypertension, chronic kidney disease, and hypothyroidism presented with one week of dyspnea, cough, diarrhea, and fevers. Chest x-ray demonstrated bibasilar consolidations and nasopharyngeal reverse transcriptase polymerase chain reaction confirmed SARS-CoV-2 infection. He had subsequent respiratory decline requiring intubation the day after admission. He developed a truncal morbilliform rash and diffuse purpura, a biopsy of which showed small dermal blood vessels with intraluminal microthrombi consistent with thrombotic vasculopathy. He was found to have elevated aCL IgM and IgG and equivocal lupus anticoagulant study. Brain MRI obtained for persistent encephalopathy showed innumerable areas of susceptibility weighted imaging changes throughout the bilateral juxtacortical white matter, corpus callosum, basal ganglia, and brainstem, as well as multiple small areas of FLAIR hyperintensities, consistent with microhemorrhage DISCUSSION: While there have been several reported cases of neurologic manifestations of COVID-19, the pathophysiology may not be related to neurotropism of the virus itself. The new development of antiphospholipid antibodies and thrombotic vasculopathy in dermal blood vessels in this patient suggest a secondary microangiopathy potentially related to a virally-induced inflammatory state.

Cerebral Microembolization in Left Ventricular Assist Device Associated Ischemic Events.

INTRODUCTION: The significance of microembolic signals (MES) detected by transcranial Doppler ultrasound emboli monitoring (TCD-e) in patients supported with left ventricular assist devices (LVAD) remains unclear. We aimed to investigate the relationship between cerebral microembolization detected by TCD-e and acute ischemic events in LVAD patients. METHODS: We reviewed consecutive patients with acute ischemic stroke or transient ischemic attack (TIA) in a prospectively collected database of LVAD patients. TCD-e exams consisted of monitoring the middle cerebral arteries for microembolic signals (MES) over 30 minutes. RESULTS: Of 515 persons with LVAD, 41 TCD-e studies were performed in 35 patients with acute ischemic stroke or transient ischemic attack (TIA) in a median of 1 day (Interquartile range [IQR]: 0-2) after the event. MES were present in 15 (44%) TCD-e studies with a median MES count of 4 (IQR: 2-15.5). Bloodstream infections were more common in patients with MES (38% versus 8%, P = .039). There were trends for lower international normalized ratio (1.39 versus 1.69, P = .214), lower activated partial thromboplastin (33.2 versus 36.6, P = .577), higher lactate dehydrogenase (531 versus 409, P = .323) and a higher frequency of pump thrombosis (13% versus 8%, P = .637) in patients with MES compared with those without MES. CONCLUSIONS: LVAD patients with acute ischemic stroke or TIA have a high prevalence of MES on TCD-e, which may serve as a marker for a prothrombotic state. Further study of MES in LVAD patients is warranted.

MRI Presentation of Infectious Intracranial Aneurysms in Infective Endocarditis.

BACKGROUND: The radiographic appearance of infectious intracranial aneurysms (IIAs) of infective endocarditis (IE) on magnetic resonance imaging (MRI) of brain is varied. We aimed to describe the IIA-specific MRI features in a series of patients with IIAs. METHODS: Records of patients with active IE who had digital subtraction angiography (DSA) at a tertiary medical center from January 2011 to December 2016 were reviewed. MRIs performed prior to IIA treatment were reviewed for findings on susceptibility-weighted imaging (SWI), diffusion-weighted imaging, and T1 with and without contrast. RESULTS: Of the 732 patients with IE, 53 (7%) had IIAs. Of these, 28 patients had an evaluable pre-treatment MRI, in whom 33 IIAs were imaged. MRI to DSA median time was 1 day (interquartile range = 1-5). On MRI, 12 (36%) IIAs had SWI lesion with contrast enhancement, 7 (21%) had cerebral microbleeds, 3 (11%) had sulcal SWI lesion, 2 (6%) IIAs had abscesses, 3 (9%) had intraparenchymal hemorrhage, 3 (9%) had subarachnoid hemorrhage, and 6 (18%) had ischemic stroke at the anatomical locations of IIAs. Four IIAs (12%) had no correlating MRI findings, though those patients had MRI without contrast. CONCLUSION: The MRI features such as SWI lesion and contrast enhancement were the commonest MRI presentations associated with the presence of IIA.

Transcranial Doppler cerebrovascular reactivity: Thresholds for clinical significance in cerebrovascular disease.

BACKGROUND AND PURPOSE: Thresholds for abnormal transcranial Doppler cerebrovascular reactivity (CVR) studies are poorly understood, especially for patients with cerebrovascular disease. Using a real-world cohort with cerebral arterial stenosis, we sought to describe a clinically significant threshold for carbon dioxide reactivity (CO2R) and vasomotor range (VMR). METHODS: CVR studies were performed during conditions of breathing room air normally, breathing 8% carbon dioxide air mixture, and hyperventilation. The mean and standard deviation (SD) of CO2R and VMR were calculated for the unaffected side in patients with unilateral stenosis; a deviation of 2 SDs below the mean was chosen as the threshold for abnormal. Receiver operating characteristic (ROC) curves for both sides for patients with unilateral and bilateral stenosis were evaluated for sensitivity (Sn) and specificity (Sp). RESULTS: A total of 133 consecutive CVR studies were performed on 62 patients with stenosis with mean±SD age 55±16 years. Comorbidities included hypertension (60%), diabetes (15%), stroke (40%), and smoking (35%). In patients with unilateral stenosis, mean±SD CO2R for the unaffected side was 1.86±0.53%, defining abnormal CO2R as <0.80%. Mean±SD CO2R for the affected side was 1.27±0.90%. The CO2R threshold predicted abnormal acetazolamide single-photon emission computed tomography (SPECT) (Sn = .73, Sp = .79), CT/MRI perfusion abnormality (Sn = .42, Sp = .77), infarction on MRI (Sn = .45, Sp = .76), and pressure-dependent exam (Sn = .50, Sp = .76). For the unaffected side, mean±SD VMR was 39.5±15.8%, defining abnormal VMR as <7.9%. For the affected side, mean±SD VMR was 26.5±17.8%. The VMR threshold predicted abnormal acetazolamide SPECT (Sn = .46, Sp = .94), infarction on MRI (Sn = .27, Sp = .94), and pressure-dependent exam (Sn = .31, Sp = .90). CONCLUSIONS: In patients with multiple vascular risk factors, a reasonable threshold for clinically significant abnormal CO2R is <0.80% and VMR is <7.9%. Noninvasive CVR may aid in diagnosing and risk stratifying patients with stenosis.

Current and Emerging Endovascular and Neurocritical Care Management Strategies in Large-Core Ischemic Stroke.

The volume of infarcted tissue in patients with ischemic stroke is consistently associated with increased morbidity and mortality. Initial studies of endovascular thrombectomy for large-vessel occlusion excluded patients with established large-core infarcts, even when large volumes of salvageable brain tissue were present, due to the high risk of hemorrhagic transformation and reperfusion injury. However, recent retrospective and prospective studies have shown improved outcomes with endovascular thrombectomy, and several clinical trials were recently published to evaluate the efficacy of endovascular management of patients presenting with large-core infarcts. With or without thrombectomy, patients with large-core infarcts remain at high risk of in-hospital complications such as hemorrhagic transformation, malignant cerebral edema, seizures, and others. Expert neurocritical care management is necessary to optimize blood pressure control, mitigate secondary brain injury, manage cerebral edema and elevated intracranial pressure, and implement various neuroprotective measures. Herein, we present an overview of the current and emerging evidence pertaining to endovascular treatment for large-core infarcts, recent advances in neurocritical care strategies, and their impact on optimizing patient outcomes.

Cannabis Use and Stroke: Does a Risk Exist?

AIMS: Cannabis use has been reported as a risk factor for stroke. We systematically review the prevalence and outcomes of stroke in people with cannabis use. METHODS: We searched MEDLINE and 6 other databases from inception to January 2020 for studies on the relationship between cannabis use and stroke. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations. Two independent reviewers extracted the data. Study quality was assessed by the Newcastle-Ottawa Scale for cohort and case-control studies. RESULTS: Seventeen studies involving 3,185,560 people with cannabis use were included. Descriptive statistics demonstrated 18,676 (median 1.1%, interquartile range [IQR] 0.3%-1.3%) experienced stroke compared with 0.8% of those without use (Odds Ratio 1.17, 95% CI 1.10-1.25). Among people with cannabis use, median age was 26.2 years (IQR 25.2-34.3 years) and mostly male (median 57.8%). Of stroke subtypes, ischemic stroke was most prevalent (median 1.2%, IQR 0.4%-1.9%), followed by undefined stroke subtype (median 1.2%, IQR 1.1%-1.2%) and hemorrhagic stroke (median 0.3%, IQR 0.1%-0.6%). The majority of people with cannabis use who experienced stroke survived (median: 85.1%, IQR 83%-87.5%) and 64.0% of people experienced a good neurologic outcome, defined as modified Rankin Scale of 0 to 3. Few studies included outcomes of vasospasm or seizure. CONCLUSIONS: In people with cannabis use, the prevalence of ischemic stroke and hemorrhagic stroke was 1.2% and 0.3%, respectively, higher than the prevalence of people without use (0.8% and 0.2%). There is insufficient information on timing, exposure, duration, and dose-responsive relationship.

The use of apnea test and brain death determination in patients on extracorporeal membrane oxygenation: A systematic review.

OBJECTIVE: To review practices of brain death (BD) determination in patients on extracorporeal membrane oxygenation (ECMO). METHODS: A systematic search was applied to PubMed and 6 electronic databases from inception to May 22, 2019. Studies reporting methods of BD assessment in adult patients (>18 years old) while on ECMO were included, after which data regarding BD assessment were extracted. RESULTS: Twenty-two studies (n = 177 patients) met the inclusion criteria. Eighty-eight patients (50%) in 19 studies underwent the apnea test (AT); most commonly through decreasing the ECMO sweep flow in 14 studies (n = 42, 48%), followed by providing CO2 through the ventilator in 2 studies (n = 6, 7%), and providing CO2 through the ECMO oxygenator in 1 study (n = 1, 1%). The details of the AT were not reported in 2 studies (n = 39, 44%). In 19 patients (22%), the AT was nonconfirmatory due to hemodynamic instability, hypoxia, insufficient CO2 rise, or unreliability of the AT. A total of 157 ancillary tests were performed, including electroencephalogram (62%), computed tomography angiography (22%), transcranial Doppler ultrasound (6%), cerebral blood flow nuclear study (5%), cerebral angiography (4%), and other (1%). Forty-seven patients (53% of patients with AT) with confirmatory AT still underwent additional ancillary for BD confirmation. Only 21 patients (12% of all patients) were declared brain-dead using confirmatory ATs alone without ancillary testing. CONCLUSIONS: Performing AT for patients with ECMO was associated with high failure rate and hemodynamic complications. Our study highlights the variability in practice in regard to the AT and supports the use of ancillary tests to determine BD in patients on ECMO.

How Are We Monitoring Brain Injuries in Patients With Left Ventricular Assist Device? A Systematic Review of Literature.

Despite the common occurrence of brain injury in patients with left ventricular assist device (LVAD), optimal neuromonitoring methods are unknown. A systematic review of PubMed and six electronic databases from inception was conducted until June 5, 2019. Studies reporting methods of neuromonitoring while on LVAD were extracted. Of 5,190 records screened, 37 studies met the inclusion criteria. The neuromonitoring methods include Transcranial Doppler ultrasound for emboli monitoring (TCD-e) (n = 13) and cerebral autoregulation (n = 3), computed tomography and magnetic resonance imaging (n = 9), serum biomarkers (n = 7), carotid ultrasound (n = 3), and near-infrared spectroscopy (n = 2). Of 421 patients with TCD-e, thromboembolic events (TEs) were reported in 79 patients (20%) and microembolic signals (MES) were detected in 105 patients (27%). Ischemic stroke was more prevalent in patients with MES compared to patients without MES (43% vs.13%, p < 0.001). Carotid ultrasound for assessing carotid stenosis was unreliable after LVAD implantation. Elevated lactate dehydrogenase (LDH) levels were associated with TEs. Significant heterogeneity exists in timing, frequency, and types of neuromonitoring tools. TCD-e and serial LDH levels appeared to have potential for assessing the risk of ischemic stroke. Future prospective research incorporating protocolized TCD-e and LDH may assist in monitoring adverse events in patients with LVAD.

The effect of incorporating an arterial pH target during apnea test for brain death determination.

BACKGROUND: Persistent apnea despite an adequate rise in arterial pressure of CO2 is an essential component of the criteria for brain death (BD) determination. Current guidelines vary regarding the utility of arterial pH changes during the apnea test (AT). We aimed to study the effect of incorporating an arterial pH target < 7.30 during the AT (in addition to the existing PaCO2 threshold) on brain death declarations. METHODS: We performed retrospective analysis of consecutive adult patients who were diagnosed with BD and underwent AT at the Cleveland Clinic over the last 10 years. Data regarding baseline and post-AT blood gas analyses were collected and analyzed. RESULTS: Ninety-eight patients underwent AT in the study period, which was positive in 89 (91%) and inconclusive in 9 (9%) patients. The mean age was 50 years old (standard deviation [SD] 16) and 54 (55%) were female. The most common etiology BD was hypoxic ischemic brain injury (HIBI) due to cardiac arrest (42%). Compared to those with positive AT, patients with inconclusive AT had a higher post-AT pH (7.24 vs 7.17, p = 0.01), lower PaO2 (47 vs 145, p < 0.01), and a lower PaCO2 (55 vs 73, p = 0.01). Among patients with a positive AT using PaCO2 threshold alone, the frequency of patients with post-AT pH < 7.30 was 95% (83/87). CONCLUSION: Implementing a BD criteria requiring both arterial pH and PaCO2 thresholds reduced the total number of positive ATs; these inconclusive cases would have required longer duration of AT to reach both targets, repeated ATs, or ancillary studies to confirm BD. The impact of this on the overall number BD declarations requires further research.