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.

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.

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.

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.

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.

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.

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.

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.

Determining the Upper and Lower Limits of Cerebral Autoregulation With Cerebral Oximetry Autoregulation Curves: A Case Series.

OBJECTIVE: Critical care guidelines recommend a single target value for mean arterial blood pressure in critically ill patients. However, growing evidence regarding cerebral autoregulation challenges this concept and supports individualizing mean arterial blood pressure targets to prevent brain and kidney hypo- or hyperperfusion. Regional cerebral oxygen saturation derived from near-infrared spectroscopy is an acceptable surrogate for cerebral blood flow and has been validated to measure cerebral autoregulation. This study suggests a novel mechanism to construct autoregulation curves based on near-infrared spectroscopy-measured cerebral oximetry. DESIGN: Case-series study. SETTING: Neurocritical care unit in a tertiary medical center. PATIENTS: Patients with acute neurologic injury and Glasgow coma scale score less than or equal to 8. MEASUREMENTS AND MAIN RESULTS: Autoregulation curves were plotted using the fractional-polynomial model in Stata after multimodal continuous monitoring of regional cerebral oxygen saturation and mean arterial blood pressure. Individualized autoregulation curves of seven patients exhibited varying upper and lower limits of autoregulation and provided useful clinical information on the autoregulation trend (curves moving to the right or left during the acute coma period). The median lower and upper limits of autoregulation were 86.5 mm Hg (interquartile range, 74-93.5) and 93.5 mm Hg (interquartile range, 83-99), respectively. CONCLUSIONS: This case-series study showed feasibility of delineating real trends of the cerebral autoregulation plateau and direct visualization of the cerebral autoregulation curve after at least 24 hours of recording without manipulation of mean arterial blood pressure by external stimuli. The integration of multimodal monitoring at the bedside with cerebral oximetry provides a noninvasive method to delineate daily individual cerebral autoregulation curves.

Effect of Body Temperature on Cerebral Autoregulation in Acutely Comatose Neurocritically Ill Patients.

OBJECTIVES: Impaired cerebral autoregulation following neurologic injury is a predictor of poor clinical outcome. We aimed to assess the relationship between body temperature and cerebral autoregulation in comatose patients. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Neurocritical care unit of the Johns Hopkins Hospital. PATIENTS: Eighty-five acutely comatose patients (Glasgow Coma Scale score of ≤ 8) admitted between 2013 and 2017. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Cerebral autoregulation was monitored using multimodal monitoring with near-infrared spectroscopy-derived cerebral oximetry index. Cerebral oximetry index was calculated as a Pearson correlation coefficient between low-frequency changes in regional cerebral oxygenation saturation and mean arterial pressure. Patients were initially analyzed together, then stratified by temperature pattern over the monitoring period: no change (< 1°C difference between highest and lowest temperatures; n = 11), increasing (≥ 1°C; n = 9), decreasing (≥ 1°C; n = 9), and fluctuating (≥ 1°C difference but no sustained direction of change; n = 56). Mixed random effects models with random intercept and multivariable logistic regression analysis were used to assess the association between hourly temperature and cerebral oximetry index, as well as between temperature and clinical outcomes. Cerebral oximetry index showed a positive linear relationship with temperature (ß = 0.04 ± 0.10; p = 0.29). In patients where a continual increase or decrease in temperature was seen during the monitoring period, every 1°C change in temperature resulted in a cerebral oximetry index change in the same direction by 0.04 ± 0.01 (p < 0.001) and 0.02 ± 0.01 (p = 0.12), respectively, after adjusting for PaCO2, hemoglobin, mean arterial pressure, vasopressor and sedation use, and temperature probe location. There was no significant difference in mortality or poor outcome (modified Rankin Scale score of 4-6) between temperature pattern groups at discharge, 3, or 6 months. CONCLUSIONS: In acute coma patients, increasing body temperature is associated with worsening cerebral autoregulation as measured by cerebral oximetry index. More studies are needed to clarify the impact of increasing temperature on cerebral autoregulation in patients with acute brain injury.

Acute Kidney Injury Following Acute Ischemic Stroke and Intracerebral Hemorrhage: A Meta-Analysis of Prevalence Rate and Mortality Risk.

BACKGROUND: The epidemiology of acute renal dysfunction after stroke is routinely overlooked following stroke events. Our aim in this meta-analysis is to report the prevalence of acute kidney injury (AKI) following acute stroke and its impact on mortality. METHODS: A systematic literature search was performed on PubMed, EMBASE and Google Scholar for observational studies examining the prevalence and mortality risk of stroke patients with AKI as a complication. The pooled prevalence rates and odds ratios for mortality risk were calculated using subgroup analyses between the stroke subtypes: acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). RESULTS: A total of 12 studies (4,532,181 AIS and 615,636 ICH) were included. The pooled prevalence rate of AKI after all stroke types was 11.6% (95% CI 10.6-12.7). Subgroup analyses revealed that the pooled prevalence rate of AKI after AIS was greater but not statistically significantly different than ICH (19.0%; 95% CI 8.2-29.7 vs. 12.9%; 95% CI 10.3-15.5, p = 0.5). AKI was found to be a significant risk factor of mortality in AIS (adjusted OR [aOR] 2.23; 95% CI 1.28-3.89; I2 = 98.8%), whereas this relationship did not reach statistical significance in ICH (aOR 1.20; 95% CI 0.68-2.12; I2 = 74.2%). CONCLUSIONS: This meta-analysis provides evidence that AKI is a common complication following both AIS and ICH and it is associated with increased mortality following AIS but not ICH. This highlights the need for early assessment of renal function in the acute phase of AIS, in particular, and avoidance of factors than may induce AKI in vulnerable patients.

Cerebral Blood Flow Autoregulation in Sepsis for the Intensivist: Why Its Monitoring May Be the Future of Individualized Care.

Cerebral blood flow (CBF) autoregulation maintains consistent blood flow across a range of blood pressures (BPs). Sepsis is a common cause of systemic hypotension and cerebral dysfunction. Guidelines for BP management in sepsis are based on historical concepts of CBF autoregulation that have now evolved with the availability of more precise technology for its measurement. In this article, we provide a narrative review of methods of monitoring CBF autoregulation, the cerebral effects of sepsis, and the current knowledge of CBF autoregulation in sepsis. Current guidelines for BP management in sepsis are based on a goal of maintaining mean arterial pressure (MAP) above the lower limit of CBF autoregulation. Bedside tools are now available to monitor CBF autoregulation continuously. These data reveal that individual BP goals determined from CBF autoregulation monitoring are more variable than previously expected. In patients undergoing cardiac surgery with cardiopulmonary bypass, for example, the lower limit of autoregulation varied between a MAP of 40 to 90 mm Hg. Studies of CBF autoregulation in sepsis suggest patients frequently manifest impaired CBF autoregulation, possibly a result of BP below the lower limit of autoregulation, particularly in early sepsis or with sepsis-associated encephalopathy. This suggests that the present consensus guidelines for BP management in sepsis may expose some patients to both cerebral hypoperfusion and cerebral hyperperfusion, potentially resulting in damage to brain parenchyma. The future use of novel techniques to study and clinically monitor CBF autoregulation could provide insight into the cerebral pathophysiology of sepsis and offer more precise treatments that may improve functional and cognitive outcomes for survivors of sepsis.

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

PURPOSE: Although evidence from observational studies in a variety of clinical settings supports the utility of cerebral oximetry as a predictor of outcomes, prospective clinical trials thus far have reported conflicting results. This systematic review and meta-analysis was designed to evaluate the influence of management associated with intraoperative cerebral oximetry on postoperative outcomes. The primary outcome was postoperative cognitive dysfunction (POCD), with secondary outcomes that included postoperative delirium, length of intensive care unit (ICU) stay, and hospital length of stay (LOS). SOURCE: After searching the PubMed, EMBASE, Cochrane Library, Scopus, and Google Scholar databases, all randomized controlled trials (RCTs) assessing the impact of intraoperative cerebral oximetry-guided management on clinical outcomes following surgery were identified. PRINCIPAL FINDINGS: Fifteen RCTs comprising 2,057 patients (1,018 in the intervention group and 1,039 in control group) were included. Intraoperative management guided by the use of cerebral oximetry was associated with a reduction in the incidence of POCD (risk ratio [RR] 0.54; 95% confidence interval [CI], 0.33 to 0.90; P = 0.02; I2 = 85%) and a significantly shorter length of ICU stay (standardized mean difference [SMD], -0.21 hr; 95% CI, -0.37 to -0.05; P = 0.009; I2 = 48%). In addition, overall hospital LOS (SMD, -0.06 days; 95% CI, -0.18 to 0.06; P = 0.29; I2 = 0%) and incidence of postoperative delirium (RR, 0.69; 95% CI, 0.36 to 1.32; P = 0.27; I2 = 0%) were not impacted by the use of intraoperative cerebral oximetry. CONCLUSIONS: Intraoperative cerebral oximetry appears to be associated with a reduction in POCD, although this result should be interpreted with caution given the significant heterogeneity in the studies examined. Further large (ideally multicentre) RCTs are needed to clarify whether POCD can be favourably impacted by the use of cerebral oximetry-guided management.

Comparison of intensive versus conventional insulin therapy in traumatic brain injury: a meta-analysis of randomized controlled trials.

OBJECTIVE: To compare intensive insulin therapy (IIT) and conventional insulin therapy (CIT) on clinical outcomes of patients with traumatic brain injury (TBI). METHODS: MEDLINE, EMBASE, Google Scholar, ISI Web of Science, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing IIT to CIT in patients with TBI. Study-level characteristics, intensive care unit (ICU) events, and long-term functional outcomes were extracted from the articles. Meta-analysis was performed with random-effect models. RESULTS: Seven RCTs comprising 1070 patients were included. Although IIT was associated with better neurologic outcome (GOS > 3) (RR=0.87, 95% CI=0.78-0.97; P=0.01; I2=0%), sensitivity analysis revealed that one study influenced this overall estimate (RR=0.90, 95% CI=0.80-1.01, P=0.07; I2=0%). IIT was strongly associated with higher risk of hypoglycaemia (RR=5.79, 95% CI=3.27-10.26, P<0.01; I2=38%). IIT and CIT did not differ in terms of early or late mortality (RR=0.96, 95% CI=0.79-1.17, P=0.7; I2=0%), infection rate (RR=0.82, 95% CI=0.59-1.14, P=0.23; I2=68%), or ICU length of stay (SMD= -0.14, 95% CI=-0.35 to 0.07, P=0.18; I2=45%0.) Conclusions: IIT did not improve long-term neurologic outcome, mortality, or infection rate and was associated with increased risk of hypoglycaemia. Additional well-designed RCTs with defined TBI subgroups should be performed to generate more powerful conclusions.

Influence of Bleeding Pattern on Ischemic Lesions After Spontaneous Hypertensive Intracerebral Hemorrhage with Intraventricular Hemorrhage.

BACKGROUND: Concomitant acute ischemic lesions are detected in up to a quarter of patients with spontaneous intracerebral hemorrhage (ICH). Influence of bleeding pattern and intraventricular hemorrhage (IVH) on risk of ischemic lesions has not been investigated. METHODS: Retrospective study of all 500 patients enrolled in the CLEAR III randomized controlled trial of thrombolytic removal of obstructive IVH using external ventricular drainage. The primary outcome measure was radiologically confirmed ischemic lesions, as reported by the Safety Event Committee and confirmed by two neurologists. We assessed predictors of ischemic lesions including analysis of bleeding patterns (ICH, IVH and subarachnoid hemorrhage) on computed tomography scans (CT). Secondary outcomes were blinded assessment of mortality and modified Rankin scale (mRS) at 30 and 180 days. RESULTS: Ischemic lesions occurred in 23 (4.6%) during first 30 days after ICH. Independent risk factors associated with ischemic lesions in logistic regression models adjusted for confounders were higher IVH volume (p = 0.004) and persistent subarachnoid hemorrhage on CT scan (p = 0.03). Patients with initial IVH volume ≥ 15 ml had five times the odds of concomitant ischemic lesions compared to IVH volume < 15 ml. Patients with ischemic lesions had significantly higher odds of death at 1 and 6 months (but not poor outcome; mRS 4-6) compared to patients without concurrent ischemic lesions. CONCLUSIONS: Occurrence of ischemic lesions in the acute phase of IVH is not uncommon and is significantly associated with increased early and late mortality. Extra-parenchymal blood (larger IVH and visible subarachnoid hemorrhage) is a strong predictor for development of concomitant ischemic lesions after ICH.

Cerebrovascular Events After Continuous-Flow Left Ventricular Assist Devices.

BACKGROUND: Cerebrovascular events (CVE) are among the most common and serious complications after implantation of continuous-flow left ventricular assist devices (CF-LVAD). We studied the incidence, subtypes, anatomical distribution, and pre- and post-implantation risk factors of CVEs as well as the effect of CVEs on outcomes after CF-LVAD implantation at our institution. METHODS: Retrospective analysis of clinical and neuroimaging data of 372 patients with CF-LVAD between May 2005 and December 2013 using standard statistical methods. RESULTS: CVEs occurred in 71 patients (19%), consisting of 35 ischemic (49%), 26 hemorrhagic (37%), and 10 ischemic+hemorrhagic (14%) events. History of coronary artery disease and female gender was associated with higher odds of ischemic CVE (OR 2.84 and 2.5, respectively), and diabetes mellitus was associated with higher odds of hemorrhagic CVE (OR 3.12). While we found a higher rate of ischemic CVEs in patients not taking any antithrombotic medications, no difference was found between patients with ischemic and hemorrhagic CVEs. Occurrence of CVEs was associated with increased mortality (HR 1.62). Heart transplantation was associated with improved survival (HR 0.02). In patients without heart transplantation, occurrence of CVE was associated with decreased survival. CONCLUSIONS: LVADs are associated with high rates of CVE, increased mortality, and lower rates of heart transplantation. Further investigations to identify the optimal primary and secondary stroke prevention measures in post-LVAD patients are warranted.

Predictors of Outcome With Cerebral Autoregulation Monitoring: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare cerebral autoregulation indices as predictors of patient outcome and their dependence on duration of monitoring. DATA SOURCES: Systematic literature search and meta-analysis using PubMed, EMBASE, and the Cochrane Library from January 1990 to October 2015. STUDY SELECTION: We chose articles that assessed the association between cerebral autoregulation indices and dichotomized or continuous outcomes reported as standardized mean differences or correlation coefficients (R), respectively. Animal and validation studies were excluded. DATA EXTRACTION: Two authors collected and assessed the data independently. The studies were grouped into two sets according to the type of analysis used to assess the relationship between cerebral autoregulation indices and predictors of outcome (standardized mean differences or R). DATA SYNTHESIS: Thirty-three studies compared cerebral autoregulation indices and patient outcomes using standardized mean differences, and 20 used Rs. The only data available for meta-analysis were from patients with traumatic brain injury or subarachnoid hemorrhage. Based on z score analysis, the best three cerebral autoregulation index predictors of mortality or Glasgow Outcome Scale for patients with traumatic brain injury were the pressure reactivity index, transcranial Doppler-derived mean velocity index based on cerebral perfusion pressure, and autoregulation reactivity index (z scores: 8.97, 6.01, 3.94, respectively). Mean velocity index based on arterial blood pressure did not reach statistical significance for predicting outcome measured as a continuous variable (p = 0.07) for patients with traumatic brain injury. For patients with subarachnoid hemorrhage, autoregulation reactivity index was the only cerebral autoregulation index that predicted patient outcome measured with the Glasgow Outcome Scale as a continuous outcome (R = 0.82; p = 0.001; z score, 3.39). We found a significant correlation between the duration of monitoring and predictive value for mortality (R = 0.78; p < 0.001). CONCLUSIONS: Three cerebral autoregulation indices, pressure reactivity index, mean velocity index based on cerebral perfusion pressure, and autoregulation reactivity index were the best outcome predictors for patients with traumatic brain injury. For patients with subarachnoid hemorrhage, autoregulation reactivity index was the only cerebral autoregulation index predictor of Glasgow Outcome Scale. Continuous assessment of cerebral autoregulation predicted outcome better than intermittent monitoring.

Cerebral Autoregulation-oriented Therapy at the Bedside: A Comprehensive Review.

This comprehensive review summarizes the evidence regarding use of cerebral autoregulation-directed therapy at the bedside and provides an evaluation of its impact on optimizing cerebral perfusion and associated functional outcomes. Multiple studies in adults and several in children have shown the feasibility of individualizing mean arterial blood pressure and cerebral perfusion pressure goals by using cerebral autoregulation monitoring to calculate optimal levels. Nine of these studies examined the association between cerebral perfusion pressure or mean arterial blood pressure being above or below their optimal levels and functional outcomes. Six of these nine studies (66%) showed that patients for whom median cerebral perfusion pressure or mean arterial blood pressure differed significantly from the optimum, defined by cerebral autoregulation monitoring, were more likely to have an unfavorable outcome. The evidence indicates that monitoring of continuous cerebral autoregulation at the bedside is feasible and has the potential to be used to direct blood pressure management in acutely ill patients.

Drug Interactions in Neurocritical Care.

Drug-drug interactions (DDIs) are common and avoidable complications that are associated with poor patient outcomes. Neurocritical care patients may be at particular risk for DDIs due to alterations in pharmacokinetic profiles and exposure to medications with a high DDI risk. This review describes the principles of DDI pharmacology, common and severe DDIs in Neurocritical care, and recommendations to minimize adverse outcomes. A review of published literature was performed using PubMed by searching for 'Drug Interaction' and several high DDI risk and common neurocritical care medications. Key medication classes included anticoagulants, antimicrobials, antiepileptics, antihypertensives, sedatives, and selective serotonin reuptake inhibitors. Additional literature was also reviewed to determine the risk in neurocritical care and potential therapeutic alternatives. Clinicians should be aware of interactions in this setting, the long-term complications, and therapeutic alternatives.