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.

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.

Glasgow Coma Scale Score Fluctuations are Inversely Associated With a NIRS-based Index of Cerebral Autoregulation in Acutely Comatose Patients.

BACKGROUND: The Glasgow Coma Scale (GCS) is an essential coma scale in critical care for determining the neurological status of patients and for estimating their long-term prognosis. Similarly, cerebral autoregulation (CA) monitoring has shown to be an accurate technique for predicting clinical outcomes. However, little is known about the relationship between CA measurements and GCS scores among neurological critically ill patients. This study aimed to explore the association between noninvasive CA multimodal monitoring measurements and GCS scores. METHODS: Acutely comatose patients with a variety of neurological injuries admitted to a neurocritical care unit were monitored using near-infrared spectroscopy-based multimodal monitoring for up to 72 hours. Regional cerebral oxygen saturation (rScO2), cerebral oximetry index (COx), GCS, and GCS motor data were measured hourly. COx was calculated as a Pearson correlation coefficient between low-frequency changes in rScO2 and mean arterial pressure. Mixed random effects models with random intercept was used to determine the relationship between hourly near-infrared spectroscopy-based measurements and GCS or GCS motor scores. RESULTS: A total of 871 observations (h) were analyzed from 57 patients with a variety of neurological conditions. Mean age was 58.7±14.2 years and the male to female ratio was 1:1.3. After adjusting for hemoglobin and partial pressure of carbon dioxide in arterial blood, COx was inversely associated with GCS (ß=-1.12, 95% confidence interval [CI], -1.94 to -0.31, P=0.007) and GCS motor score (ß=-1.06, 95% CI, -2.10 to -0.04, P=0.04). In contrast rScO2 was not associated with GCS (ß=-0.002, 95% CI, -0.01 to 0.01, P=0.76) or GCS motor score (ß=-0.001, 95% CI, -0.01 to 0.01, P=0.84). CONCLUSIONS: This study showed that fluctuations in GCS scores are inversely associated with fluctuations in COx; as COx increases (impaired autoregulation), more severe neurological impairment is observed. However, the difference in COx between high and low GCS is small and warrants further studies investigating this association. CA multimodal monitoring with COx may have the potential to be used as a surrogate of neurological status when the neurological examination is not reliable (ie, sedation and paralytic drug administration).

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.

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.

Validation of Near-Infrared Spectroscopy for Monitoring Cerebral Autoregulation in Comatose Patients.

BACKGROUND: Transcranial Doppler (TCD) noninvasively measures cerebral blood flow (CBF) velocity and is a well-studied method to monitor cerebral autoregulation (CA). Near-infrared spectroscopy (NIRS) has emerged as a promising noninvasive method to determine CA continuously by using regional cerebral oxygen saturation (rSO2) as a surrogate for CBF. Little is known about its accuracy to determine CA in patients with intracranial lesions. The purpose of this study was to assess the accuracy of rSO2-based CA monitoring with TCD methods in comatose patients with acute neurological injury. METHODS: Thirty-three comatose patients were monitored at the bedside to measure CA using both TCD and NIRS. Patients were monitored daily for up to three days from coma onset. The cerebral oximetry index (COx) was calculated as the moving correlation between the slow waves of rSO2 and mean arterial pressure (MAP). The mean velocity index (Mx) was calculated as a similar coefficient between slow waves of TCD-measured CBF velocity and MAP. Optimal blood pressure was defined as the MAP with the lowest Mx and COx. Averaged Mx and COx as well as optimal MAP, based on both Mx and COx, were compared using Pearson's correlation. Bias analysis was performed between these same CA metrics. RESULTS: The median duration of monitoring was 60 min (interquartile range [IQR] 48-78). There was a moderate correlation between the averaged values of COx and Mx (R = 0.40, p = 0.005). Similarly, there was a strong correlation between optimal MAP calculated for COx and Mx (R = 0.87, p < 0.001). Bland-Altman analysis showed moderate agreement with bias (±standard deviation) of -0.107 (±0.191) for COx versus Mx and good agreement with bias of 1.90 (±7.94) for optimal MAP determined by COx versus Mx. CONCLUSIONS: Monitoring CA with NIRS-derived COx is correlated and had good agreement with previously validated TCD-based method. These results suggest that COx may be an acceptable substitute for Mx monitoring in patients with acute intracranial injury.