Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

BACKGROUND: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. METHODS: This is a single-center prospective observational study. We measured COx, a surrogate measurement of cerebral blood flow measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure (MAP) and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT) and lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. RESULTS: Fifteen patients (median age 57 years [interquartile range 47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO (VA-ECMO), and four were on veno-venous ECMO (VV-ECMO). Mean COx was higher on postcannulation day 1 than on day 2 (0.2 vs. 0.09, p < 0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO patients (0.12 vs. 0.06, p = 0.04). Median MAPOPT for the entire cohort was highly variable, ranging from 55 to 110 mm Hg. Patients with mRS scores 0-3 (good outcome) at 3 and 6 months spent less time outside MAPOPT compared with patients with mRS scores 4-6 (poor outcome) (74% vs. 82%, p = 0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on postcannulation day 1 than on day 2 (18.2% vs. 3.3%, p < 0.01). CONCLUSIONS: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between postcannulation days 1 and 2. CA was more impaired in VA-ECMO patients than in VV-ECMO patients. Spending less time outside MAPOPT may be associated with achieving a good neurologic outcome.

Mechanistic Evaluation of Diffusion Weighted Hyperintense Lesions After Large Spontaneous Intracerebral Hemorrhage: A Subgroup Analysis of MISTIE III.

BACKGROUND: Ischemic lesions on diffusion weighted imaging (DWI) are common after acute spontaneous intracerebral hemorrhage (ICH) but are poorly understood for large ICH volumes (> 30 mL). We hypothesized that large blood pressure drops and effect modification by cerebral small vessel disease markers on magnetic resonance imaging (MRI) are associated with DWI lesions. METHODS: This was an exploratory analysis of participants in the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial with protocolized brain MRI scans within 7 days from ICH. Multivariable logistic regression analysis was performed to assess biologically relevant factors associated with DWI lesions, and relationships between DWI lesions and favorable ICH outcomes (modified Rankin Scale 0-3). RESULTS: Of 499 enrolled patients, 300 had MRI at median 7.5 days (interquartile range 7-8), and 178 (59%) had DWI lesions. The incidence of DWI lesions was higher in patients with systolic blood pressure (SBP) reduction ≥ 80 mm Hg in first 24 h (76%). In adjusted models, factors associated with DWI lesions were as follows: admission intraventricular hematoma volume (p = 0.03), decrease in SBP ≥ 80 mm Hg from admission to day 1 (p = 0.03), and moderate-to-severe white matter disease (p = 0.01). Patients with DWI lesions had higher odds of severe disability at 1 month (p = 0.04), 6 months (p = 0.036), and 12 months (p < 0.01). No evidence of effect modification by cerebral small vessel disease on blood pressure was found. CONCLUSIONS: In patients with large hypertensive ICH, white matter disease, intraventricular hemorrhage volume, and large reductions in SBP over the first 24 h were independently associated with DWI lesions. Further investigation of potential hemodynamic mechanisms of ischemic injury after large ICH is warranted.

Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

Background: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. Methods: This is a single-center prospective observational study. We measured Cox, a surrogate measurement of cerebral blood flow, measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT), lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. Results: Fifteen patients (median age=57 years [IQR=47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO and 4 on veno-venous. Mean COx was higher on post-cannulation day 1 than on day 2 (0.2 vs 0.09, p<0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO (0.12 vs 0.06, p=0.04). Median MAPOPT for entire cohort was highly variable, ranging 55-110 mmHg. Patients with mRS 0-3 (good outcome) at 3 and 6 months spent less time outside of MAPOPT compared to patients with mRS 4-6 (poor outcome) (74% vs 82%, p=0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on post-cannulation day 1 than on day 2 (18.2% vs 3.3%, p<0.01). Conclusions: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between post-cannulation days 1 and 2. CA was more impaired in VA-ECMO than VV-ECMO. Spending less time outside of MAPOPT may be associated with achieving a good neurologic outcome.

Reducing the incidence and mortality of traumatic brain injury in Latin America.

Traumatic brain injury (TBI) represents a considerable portion of the global injury burden. The incidence of TBI will continue to increase in view of an increase in population density, an aging population, and the increased use of motor vehicles, motorcycles, and bicycles. The most common causes of TBI are falls and road traffic injuries. Deaths related to road traffic injury are three times higher in low-and middle-income countries (LMIC) than in high-income countries (HIC). The Latin American Caribbean region has the highest incidence of TBI worldwide, primarily caused by road traffic injuries. Data from HIC indicates that road traffic injuries can be successfully prevented through concerted efforts at the national level, with coordinated and multisector responses to the problem. Such actions require implementation of proven measures to address the safety of road users and the vehicles themselves, road infrastructure, and post-crash care. In this review, we focus on the epidemiology of TBI in Latin America and the implementation of solutions and preventive measures to decrease mortality and long-term disability.

Assessing risk factors associated with breakthrough early post-traumatic seizures in patients receiving phenytoin prophylaxis.

Objective: Post-traumatic seizure (PTS) is a well-known complication of traumatic brain injury (TBI). The objective of this study was to identify risk factors associated with breakthrough early PTS in TBI patients receiving phenytoin prophylaxis. Methods: This was a single-centered retrospective study including adult patients admitted to the intensive care unit (ICU), had a TBI, and started on phenytoin for seizure prophylaxis within 24 h of admission. The primary outcome was the incidence and factors associated with early PTS, defined as a confirmed seizure on a continuous electroencephalogram within 7 days of TBI. Secondary outcomes included the association between early post-traumatic seizures and ICU length of stay, hospital length of stay, and in-hospital mortality. Results: A total of 105 patients were included in the final analysis. Patients with early PTS were older (65 vs. 48 years old, p = 0.01), had a higher Marshall score (5 vs. 2, p = 0.01), were more likely to have a Marshall score > 2 (73 vs. 37%, p = 0.01), and had more neurosurgeries for hematoma evacuation (57 vs. 19%, p = 0.01). In patients with early PTS, 57% had a level at the time of seizure, and of those, 87.5% had a therapeutic level (>10 mcg/mL). Patients with early PTS had a longer ICU length of stay (14.7 vs. 5.9 days, p = 0.04) and a greater proportion of hospital mortality (21 vs. 2%, p = 0.02). Conclusion: Patients with higher age, Marshall score, and neurosurgical procedures for hematoma evacuation had higher incidences of breakthrough early PTS despite the use of phenytoin prophylaxis. The majority of patients with early PTS had therapeutic phenytoin levels at the time of seizure when a level was available; however, approximately half (43%) did not have a level.

Impact of Cerebral Autoregulation Monitoring in Cerebrovascular Disease: A Systematic Review.

Cerebral autoregulation (CA) prevents brain injury by maintaining a relatively constant cerebral blood flow despite fluctuations in cerebral perfusion pressure. This process is disrupted consequent to various neurologic pathologic processes, which may result in worsening neurologic outcomes. Herein, we aim to highlight evidence describing CA changes and the impact of CA monitoring in patients with cerebrovascular disease, including ischemic stroke, intracerebral hemorrhage (ICH), and aneurysmal subarachnoid hemorrhage (aSAH). The study was preformed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. English language publications were identified through a systematic literature conducted in Ovid Medline, PubMed, and Embase databases. The search spanned the dates of each database's inception through January 2021. We selected case-control studies, cohort observational studies, and randomized clinical trials for adult patients (≥ 18 years) who were monitored with continuous metrics using transcranial Doppler, near-infrared spectroscopy, and intracranial pressure monitors. Of 2799 records screened, 48 studies met the inclusion criteria. There were 23 studies on ischemic stroke, 18 studies on aSAH, 5 studies on ICH, and 2 studies on systemic hypertension. CA impairment was reported after ischemic stroke but generally improved after tissue plasminogen activator administration and successful mechanical thrombectomy. Persistent impairment in CA was associated with hemorrhagic transformation, malignant cerebral edema, and need for hemicraniectomy. Studies that investigated large ICHs described bilateral CA impairment up to 12 days from the ictus, especially in the presence of small vessel disease. In aSAH, impairment of CA was associated with angiographic vasospasm, delayed cerebral ischemia, and poor functional outcomes at 6 months. This systematic review highlights the available evidence for CA disruption during cerebrovascular diseases and its possible association with long-term neurological outcome. CA may be disrupted even before acute stroke in patients with untreated chronic hypertension. Monitoring CA may help in establishing individualized management targets in patients with cerebrovascular disease.

Coronavirus Disease 2019 Policy Restricting Family Presence May Have Delayed End-of-Life Decisions for Critically Ill Patients.

OBJECTIVES: To determine if a restrictive visitor policy inadvertently lengthened the decision-making process for dying inpatients without coronavirus disease 2019. DESIGN: Regression discontinuity and time-to-event analysis. SETTING: Two large academic hospitals in a unified health system. PATIENTS OR SUBJECTS: Adult decedents who received greater than or equal to 1 day of ICU care during their terminal admission over a 12-month period. INTERVENTIONS: Implementation of a visit restriction policy. MEASUREMENTS AND MAIN RESULTS: We identified 940 adult decedents without coronavirus disease 2019 during the study period. For these patients, ICU length of stay was 0.8 days longer following policy implementation, although this effect was not statistically significant (95% CI, -2.3 to 3.8; p = 0.63). After excluding patients admitted before the policy but who died after implementation, we observed that ICU length of stay was 2.9 days longer post-policy (95% CI, 0.27-5.6; p = 0.03). A time-to-event analysis revealed that admission after policy implementation was associated with a significantly longer time to first do not resuscitate/do not intubate/comfort care order (adjusted hazard ratio, 2.2; 95% CI, 1.6-3.1; p < 0.0001). CONCLUSIONS: Policies restricting family presence may lead to longer ICU stays and delay decisions to limit treatment prior to death. Further policy evaluation and programs enabling access to family-centered care and palliative care during the ongoing coronavirus disease 2019 pandemic are imperative.

Diffusion-Weighted Imaging Lesions After Intracerebral Hemorrhage and Risk of Stroke: A MISTIE III and ATACH-2 Analysis.

BACKGROUND AND PURPOSE: Punctate ischemic lesions noted on diffusion-weighted imaging (DWI) are associated with poor functional outcomes after intracerebral hemorrhage (ICH). Whether these lesions increase long-term risk of stroke is poorly understood. METHODS: We pooled individual patient data from the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) and the MISTIE III trial (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3). We included subjects with a magnetic resonance imaging scan. The exposure was a DWI lesion. The primary outcome was any stroke, defined as a composite of ischemic stroke or recurrent ICH, whereas secondary outcomes were incident ischemic stroke and recurrent ICH. Using multivariate Cox regression analysis, we evaluated the risk of stroke. RESULTS: Of 505 patients with ICH with magnetic resonance imaging, 466 were included. DWI lesions were noted in 214 (45.9%) subjects, and 34 incident strokes (20 ischemic stroke and 14 recurrent ICH) were observed during a median follow-up of 324 days (interquartile range, 91-374). Presence of a DWI lesion was associated with a 6.9% (95% CI, 2.2-11.6) absolute increase in risk of all stroke (hazard ratio, 2.6 [95% CI, 1.2-5.7]). Covariate adjustment with Cox regression models also demonstrated this increased risk. In the secondary analyses, there was an increased risk of ischemic stroke (hazard ratio, 3.5 [95% CI, 1.1-11.0]) but not recurrent ICH (hazard ratio, 1.7 [95% CI, 0.6-5.1]). CONCLUSIONS: In a heterogeneous cohort of patients with ICH, presence of a DWI lesion was associated with a 2.5-fold heightened risk of stroke among ICH survivors. This elevated risk persisted for ischemic stroke but not for recurrent ICH.

Lateral Brain Displacement and Cerebral Autoregulation in Acutely Comatose Patients.

OBJECTIVES: Lateral displacement and impaired cerebral autoregulation are associated with worse outcomes following acute brain injury, but their effect on long-term clinical outcomes remains unclear. We assessed the relationship between lateral displacement, disturbances to cerebral autoregulation, and clinical outcomes in acutely comatose patients. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Neurocritical care unit of the Johns Hopkins Hospital. PATIENTS: Acutely comatose patients (Glasgow Coma Score ≤ 8). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebral oximetry index, derived from near-infrared spectroscopy multimodal monitoring, was used to evaluate cerebral autoregulation. Associations between lateral brain displacement, global cerebral autoregulation, and interhemispheric cerebral autoregulation asymmetry were assessed using mixed random effects models with random intercept. Patients were grouped by functional outcome, determined by the modified Rankin Scale. Associations between outcome group, lateral displacement, and cerebral oximetry index were assessed using multivariate linear regression. Increasing lateral brain displacement was associated with worsening global cerebral autoregulation (p = 0.01 septum; p = 0.05 pineal) and cerebral autoregulation asymmetry (both p < 0.001). Maximum lateral displacement during the first 3 days of coma was significantly different between functional outcome groups at hospital discharge (p = 0.019 pineal; p = 0.008 septum), 3 months (p = 0.026; p = 0.007), 6 months (p = 0.018; p = 0.010), and 12 months (p = 0.022; p = 0.012). Global cerebral oximetry index was associated with functional outcomes at 3 months (p = 0.019) and 6 months (p = 0.013). CONCLUSIONS: During the first 3 days of acute coma, increasing lateral brain displacement is associated with worsening global cerebral autoregulation and cerebral autoregulation asymmetry, and poor long-term clinical outcomes in acutely comatose patients. The impact of acute interventions on outcome needs to be explored.

Near-infrared Spectroscopy-derived Cerebral Autoregulation Indices Independently Predict Clinical Outcome in Acutely Ill Comatose Patients.

OBJECTIVE: Outcome prediction in comatose patients with acute brain injury remains challenging. Regional cerebral oxygenation (rSO2) derived from near-infrared spectroscopy (NIRS) is a surrogate for cerebral blood flow and can be used to calculate cerebral autoregulation (CA) continuously at the bedside from the derived cerebral oximetry index (COx). We hypothesized that COx derived thresholds for CA are associated with outcomes in patients with acute coma from neurological injury. METHODS: A prospective cohort study was conducted in 88 acutely comatose adults with heterogenous brain injury diagnoses who were continuously monitored with COx for up to 3 consecutive days. Multivariable logistic regression was performed to investigate association between averaged COx and short (in-hospital and 3 mo) and long-term (6 mo) outcomes. RESULTS: Six month mortality rate was 62%. Median COx in nonsurvivors at hospital discharge was 0.082 [interquartile range, IQR: 0.045 to 0.160] compared with 0.042 [IQR: -0.005 to 0.110] in survivors (P=0.012). At 6 months, median COx was 0.075 [IQR: 0.27 to 0.158] in nonsurvivors compared with 0.029 [IQR: -0.015 to 0.077] in survivors (P=0.02). In the multivariable logistic regression model adjusted for confounders, average COx ≥0.05 was associated with both in-hospital mortality (adjusted odds ratio [OR]=2.9, 95% confidence interval [CI]=1.15-7.33, P=0.02), mortality at 6 months (adjusted OR=4.4, 95% CI=1.41-13.7, P=0.01), and severe disability (modified Rankin Score ≥4) at 6 months (adjusted OR=4.4, 95% CI=1.07-17.8, P=0.04). Area under the receiver operating characteristic curve for predicting mortality and severe disability at 6 months were 0.783 and 0.825, respectively. CONCLUSIONS: Averaged COx ≥0.05 is independently associated with short and long-term mortality and long-term severe disability in acutely comatose adults with neurological injury. We propose that COx ≥0.05 represents an accurate threshold to predict long-term functional outcome in acutely comatose adults.

Correction to: Intraoperative cerebral oximetry-based management for optimizing perioperative outcomes: a meta-analysis of randomized controlled trials.

In the article entitled "Intraoperative cerebral oximetry-based management for optimizing perioperative outcomes: a meta-analysis of randomized controlled trials" Can J Anesth 2018; 65: 529-42, we wish to clarify the following items.

Optimizing Mean Arterial Pressure in Acutely Comatose Patients Using Cerebral Autoregulation Multimodal Monitoring With Near-Infrared Spectroscopy.

OBJECTIVES: This study investigated whether comatose patients with greater duration and magnitude of clinically observed mean arterial pressure outside optimal mean arterial blood pressure have worse outcomes than those with mean arterial blood pressure closer to optimal mean arterial blood pressure calculated by bedside multimodal cerebral autoregulation monitoring using near-infrared spectroscopy. DESIGN: Prospective observational study. SETTING: Neurocritical Care Unit of the Johns Hopkins Hospital. SUBJECTS: Acutely comatose patients secondary to brain injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cerebral oximetry index was continuously monitored with near-infrared spectroscopy for up to 3 days. Optimal mean arterial blood pressure was defined as that mean arterial blood pressure at the lowest cerebral oximetry index (nadir index) for each 24-hour period of monitoring. Kaplan-Meier analysis and proportional hazard regression models were used to determine if survival at 3 months was associated with a shorter duration of mean arterial blood pressure outside optimal mean arterial blood pressure and the absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure. A total 91 comatose patients were enrolled in the study. The most common etiology was intracerebral hemorrhage. Optimal mean arterial blood pressure could be calculated in 89 patients (97%), and the median optimal mean arterial blood pressure was 89.7 mm Hg (84.6-100 mm Hg). In multivariate proportional hazard analysis, duration outside optimal mean arterial blood pressure of greater than 80% of monitoring time (adjusted hazard ratio, 2.13; 95% CI, 1.04-4.41; p = 0.04) and absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure of more than 10 mm Hg (adjusted hazard ratio, 2.44; 95% CI, 1.21-4.92; p = 0.013) were independently associated with mortality at 3 months, after adjusting for brain herniation, admission Glasgow Coma Scale, duration on vasopressors and midline shift at septum. CONCLUSIONS: Comatose neurocritically ill adults with an absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure greater than 10 mm Hg and duration outside optimal mean arterial blood pressure greater than 80% had increased mortality at 3 months. Noninvasive near-infrared spectroscopy-based bedside calculation of optimal mean arterial blood pressure is feasible and might be a promising tool for cerebral autoregulation oriented-therapy in neurocritical care patients.

Influence of Intracerebral Hemorrhage Location on Outcomes in Patients With Severe Intraventricular Hemorrhage.

Background and Purpose- We investigated the prognostic significance of spontaneous intracerebral hemorrhage location in presence of severe intraventricular hemorrhage. Methods- We analyzed diagnostic computed tomography scans from 467/500 (excluding primary intraventricular hemorrhage) subjects from the CLEAR (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) III trial. We measured intracerebral hemorrhage engagement with specific anatomic regions, and estimated association of each region with blinded assessment of dichotomized poor stroke outcomes: mortality, modified Rankin Scale score of 4 to 6, National Institutes of Health Stroke Scale score of >4, stroke impact scale score of <60, Barthel Index <86, and EuroQol visual analogue scale score of <50 and <70 at days 30 and 180, respectively, using logistic regression models. Results- Frequency of anatomic region involvement consisted of thalamus (332 lesions, 71.1% of subjects), caudate (219, 46.9%), posterior limb internal capsule (188, 40.3%), globus pallidus/putamen (127, 27.2%), anterior limb internal capsule (108, 23.1%), and lobar (29, 6.2%). Thalamic location was independently associated with mortality (days 30 and 180) and with poor outcomes on most stroke scales at day 180 on adjusted analysis. Posterior limb internal capsule and globus pallidus/putamen involvement was associated with increased odds of worse disability at days 30 and 180. Anterior limb internal capsule and caudate locations were associated with decreased mortality on days 30 and 180. Anterior limb internal capsule lesions were associated with decreased long-term morbidity. Conclusions- Acute intracerebral hemorrhage lesion topography provides important insights into anatomic correlates of mortality and functional outcomes even in severe intraventricular hemorrhage causing obstructive hydrocephalus. Models accounting for intracerebral hemorrhage location in addition to volumes may improve outcome prediction and permit stratification of benefit from aggressive acute interventions. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00784134.

Impact of antiepileptic drugs for seizure prophylaxis on short and long-term functional outcomes in patients with acute intracerebral hemorrhage: A meta-analysis and systematic review.

PURPOSE: The purpose of this analysis is to assess the effect of antiepileptics (AEDs) on seizure prevention and short and long term functional outcomes in patients with acute intracerebral hemorrhage. METHOD: The meta-analysis was conducted using the PRISMA guidelines. A literature search was performed of the PubMed, the Cochrane Library, and EMBASE databases. Search terms included "Anticonvulsants", "Intracerebral Hemorrhage", and related subject headings. Articles were screened and included if they were full-text and in English. Articles that did not perform multivariate regression were not included. Overall effect size was evaluated with forest plots and publication bias was assessed with the Begg's and Egger's tests. RESULTS: A total of 3912 articles were identified during the initial review. After screening, 54 articles remained for full review and 6 articles were included in the final analysis. No significant association between the use of AEDs after ICH and functional outcome (OR 1.53 [95%CI: 0.81-2.88] P = 0.18, I2 = 81.7%). Only one study evaluated the effect AEDs had in preventing post-ICH seizures. CONCLUSIONS: The use of prophylactic AEDs was not associated with improved short and long outcomes after acute ICH. This analysis supports the 2015 AHA/ASA recommendation against prophylactic AEDs (class III; level of evidence b).