Moving Correlation Coefficient Research Articles

Abstract 51: Impact of Cerebral Autoregulation on the Relationship Between Blood Pressure Variability and Functional Outcome Following Endovascular Thrombectomy

Background: Both increased blood pressure (BP) variability and impaired autoregulation have been linked to worse outcome after endovascular thrombectomy (EVT). This study examined the combined effect of these variables on the risk of poor outcome in patients with large-vessel occlusion (LVO) stroke. Methods: Autoregulation was continuously measured for up to 24 hours after EVT and quantified as a moving correlation coefficient between arterial BP and the near-infrared spectroscopy-derived cerebral oxygen saturation. Systolic BP variability was assessed using the standard deviation of the mean. Values were averaged for the entire recording period and dichotomized at the lowest tertile for both variables. Functional outcome was assessed using the modified Rankin scale (mRS) at 90 days and dichotomized into good (mRS 0-2) and poor outcome (mRS 3-6). Results: We included 195 patients (mean age 70 + 16, 45% female, mean NIHSS 14, mean monitoring time 15 + 7 hours). After adjusting for age, NIHSS, ASPECTS, and TICI score, patients with low BP variability and intact autoregulation were significantly more likely to achieve a good outcome than those with high BP variability and impaired autoregulation (OR 3.7, 95% CI 1.2-12.1, p=0.028, Figure 1A). We found an interaction between BP variability and autoregulation (p=0.067). Patients with high BP variability showed a gradual decrease in the probability of a good outcome with worsening autoregulation. However, for patients with low BPV, autoregulation had minimal impact. (Figure 1B). No significant correlation was seen between autoregulatory function and BP variability (r=0.07, p=0.33). Conclusions: For LVO stroke patients with high BP variability after EVT, worse 90-day functional outcome may be exacerbated by impaired autoregulation. These results suggest that autoregulatory status should be considered in the management of BP after EVT to identify high-risk patients and develop individualized treatment strategies.

Cerebrovascular Pressure Reactivity Has a Strong and Independent Association With Outcome in Children With Severe Traumatic Brain Injury.

To examine cerebrovascular pressure reactivity index (PRx) in a large cohort of children with severe traumatic brain injury (sTBI) in association with physiologic variables and outcome. Retrospective observational cohort study. Red Cross War Memorial Children's Hospital in Cape Town, South Africa. Pediatric (≤ 14 yr old) sTBI patients with intracranial pressure (ICP) monitoring (postresuscitation Glasgow Coma Score [Glasgow Coma Scale (GCS)] of ≤ 8). Data were analyzed from ICM+ files sampled at 100Hz. PRx (a mathematical indicator of pressure reactivity) was calculated as a moving correlation coefficient between ICP and mean arterial pressure (MAP) as previously described. Associations between PRx, age, GCS, ICP, MAP, and cerebral perfusion pressure (CPP) were examined with summary measures and correlation analysis using high-frequency data. Associations between PRx and mortality/outcome were examined with multivariable logistic regression analysis and the prognostic ability of PRx with receiver operating characteristic (ROCs) curves. The dataset included over 1.7 million minutes (28,634 hr) of MAP and ICP data in 196 children. The series mortality was 10.7% (21/196), and unfavorable outcome 29.6% (58/196). PRx had a moderate positive correlation with ICP ( r = 0.44; p < 0.001), a moderate negative correlation with CPP ( r = -0.43; p < 0.001), and a weak negative correlation with MAP ( r = -0.21; p = 0.004). PRx was consistently higher in patients with poor outcome and had a strong, independent association with mortality (ROC area under the curve = 0.91). A PRx threshold of 0.25 showed the best predictive ability for mortality. This is the largest cohort of children with PRx analysis of cerebrovascular reactivity to date. PRx had a strong association with outcome that was independent of ICP, CPP, GCS, and age. The data suggest that impaired autoregulation is an independent factor associated with poor outcome and may be useful in directing clinical care.

Optimal Cerebral Perfusion Pressure and Brain Tissue Oxygen in Aneurysmal Subarachnoid Hemorrhage.

Targeting a cerebral perfusion pressure optimal for cerebral autoregulation (CPPopt) has been gaining more attention to prevent secondary damage after acute neurological injury. Brain tissue oxygenation (PbtO2) can identify insufficient cerebral blood flow and secondary brain injury. Defining the relationship between CPPopt and PbtO2 after aneurysmal subarachnoid hemorrhage may result in (1) mechanistic insights into whether and how CPPopt-based strategies might be beneficial and (2) establishing support for the use of PbtO2 as an adjunctive monitor for adequate or optimal local perfusion. We performed a retrospective analysis of a prospectively collected 2-center dataset of patients with aneurysmal subarachnoid hemorrhage with or without later diagnosis of delayed cerebral ischemia (DCI). CPPopt was calculated as the cerebral perfusion pressure (CPP) value corresponding to the lowest pressure reactivity index (moving correlation coefficient of mean arterial and intracranial pressure). The relationship of (hourly) deltaCPP (CPP-CPPopt) and PbtO2 was investigated using natural spline regression analysis. Data after DCI diagnosis were excluded. Brain tissue hypoxia was defined as PbtO2 <20 mmHg. One hundred thirty-one patients were included with a median of 44.0 (interquartile range, 20.8-78.3) hourly CPPopt/PbtO2 datapoints. The regression plot revealed a nonlinear relationship between PbtO2 and deltaCPP (P<0.001) with PbtO2 decrease with deltaCPP <0 mmHg and stable PbtO2 with deltaCPP ≥0mmHg, although there was substantial individual variation. Brain tissue hypoxia (34.6% of all measurements) was more frequent with deltaCPP <0 mmHg. These dynamics were similar in patients with or without DCI. We found a nonlinear relationship between PbtO2 and deviation of patients' CPP from CPPopt in aneurysmal subarachnoid hemorrhage patients in the pre-DCI period. CPP values below calculated CPPopt were associated with lower PbtO2. Nevertheless, the nature of PbtO2 measurements is complex, and the variability is high. Combined multimodality monitoring with CPP/CPPopt and PbtO2 should be recommended to redefine individual pressure targets (CPP/CPPopt) and retain the option to detect local perfusion deficits during DCI (PbtO2), which cannot be fulfilled by both measurements interchangeably.

Clinical determinants of cerebrovascular reactivity in very preterm infants during the transitional period

Preterm infants are at enhanced risk of brain injury due to altered cerebral haemodynamics during postnatal transition. This observational study aimed to assess the clinical determinants of transitional cerebrovascular reactivity and its association with intraventricular haemorrhage (IVH). Preterm infants <32 weeks underwent continuous monitoring of cerebral oxygenation and heart rate over the first 72 h after birth. Serial cranial and cardiac ultrasound assessments were performed to evaluate the ductal status and to diagnose IVH onset. The moving correlation coefficient between cerebral oxygenation and heart rate (TOHRx) was calculated. Linear mixed-effect models were used to analyse the impact of relevant clinical variables on TOHRx. The association between TOHRx and IVH development was also assessed. Seventy-seven infants were included. A haemodynamically significant patent ductus arteriosus (hsPDA) (β = 0.044, 95% CI: 0.007-0.081) and ongoing dopamine treatment (β = 0.096, 95% CI: 0.032-0.159) were associated with increasing TOHRx, indicating impaired cerebrovascular reactivity. A significant association between TOHRx, mean arterial blood pressure (β = -0.004, 95% CI: -0.007, -0.001) and CRIB-II score (β = 0.007, 95% CI: 0.001-0.015) was also observed. TOHRx was significantly higher in infants developing high-grade IVH compared to those without IVH. Dopamine treatment, low blood pressure, hsPDA and high CRIB-II are associated with impaired cerebrovascular reactivity during postnatal transition, with potential implications on IVH development. The correlation coefficient between cerebral oxygenation and heart rate (TOHRx) provides a non-invasive estimation of cerebrovascular reactivity, whose failure has a potential pathogenic role in the development of IVH in preterm infants. This study shows that cerebrovascular reactivity during the transitional period improves over time and is affected by specific clinical and therapeutic factors, whose knowledge could support the development of individualized neuroprotective strategies in at-risk preterm infants. The evidence of increased TOHRx in infants developing high-grade compared to low-grade or no IVH during the transitional period further supports the role of impaired cerebrovascular reactivity in IVH pathophysiology.

Relationship of Pressure Reactivity Index and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage.

Patients with aneurysmal subarachnoid hemorrhage (SAH) continue to have poor functional outcome due to the occurrence of delayed cerebral ischemia (DCI). Although vasospasm represents the primary therapeutic target for mitigating DCI, DCI occurs through multifocal etiologies that involve impaired cerebral autoregulation. Worse pressure reactivity index (PRx) values, which consists of a moving correlation coefficient between intracranial pressures and mean arterial pressures, have been shown to be associated with DCI in non-randomized clinical trials. We discuss two patients that presented with high-grade SAH and comatose exams. Patient one was a 34-year-old male diagnosed with SAH from a ruptured right middle cerebral artery aneurysm. He had intact PRx values (Mean: -0.07 during hospital days 9-19), while having severe, refractory vasospasm. At the conclusion of his hospitalization, he was functionally independent, had negligible DCI, and was successfully discharged home. Patient two was a 78-year-old female diagnosed with SAH from a ruptured anterior communicating artery aneurysm. She had an improving PRx ranging from -0.1 to 0.1 early in her hospitalization. However, upon developing severe vasospasm, her PRx increased to 0.6 (overall PRx from hospital days 4-16 was 0.3), and she suffered from extensive DCI in bilateral middle cerebral and anterior cerebral artery distributions that ultimately resulted in malignant cerebral edema and brain death. Cerebral autoregulation as measured by PRx may represent a viable target for neuroprognostication by evaluating DCI risk in patients with SAH who develop severe or refractory vasospasm. Further studies evaluating the role of cerebral autoregulation, PRx, and its pathophysiological role in DCI are warranted.

Impacts of human activity on Bayin River runoff as revealed by tree rings in Qaidam Basin, China

Evaluating the impacts of human activity on river runoff has important implications for regional water resource management. Here, we used seven tree-ring width chronologies to establish a regional mean tree-ring width chronology from the northern mountain of Delingha, Qaidam Basin. We conducted the correlation, moving correlation and regression analysis of regional mean tree-ring width chronology with runoff data from Bayin River gauge station. Then, we stimulated the June runoff of Bayin River from 1956 to 2002. The results showed that the highest correlation coefficient was found for June runoff (r=0.63, P<0.01), and their moving correlation coefficient decreased after 1986. Based on the stable relationship between tree-ring width chronology and the June runoff during 1956-1986, we built the reconstruction function, which was explained 50.8% of observed runoff. The stimulated runoff during 1987 to 2002 was significantly higher than the observed runoff (3.01 m3·s-1, P<0.001). These results indicated that human activity from the upper river had significant impacts on Bayin River runoff. Human activity should be considered as an important factor to protect security of sustainable water resource utilization for future water resource development and utilization in Bayin River region.

Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial

BackgroundImpaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury.MethodsA post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TOx) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TOx > 0 indicating impaired reactivity and TOx > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TOx was analysed in the 0–12, 12–24, 24–48 h time-periods and integrated over 0–48 h. The primary outcome was the association between TOx and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3–5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury.ResultsIn 108 patients with sufficient data to calculate TOx, 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TOx for 0–48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [− 1.17 to 2.94] vs. − 2.71 95% CI [− 4.16 to − 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p < 0.05). NfL concentrations were higher in patients with impaired CVR compared to those with intact CVR (43 IQR [15–650] vs 20 IQR [13–199] pg/ml, p = 0.042).ConclusionImpaired CVR over 48 h was more common in patients with chronic hypertension and associated with poor outcome. Decreased upper MAP bound and a narrower MAP range for maintained CVR were associated with poor outcome and more severe brain injury assessed with NfL.Trial registration ClinicalTrials.gov, NCT02698917.

Association of transcranial Doppler blood flow velocity slow waves with delayed cerebral ischemia in patients suffering from subarachnoid hemorrhage: a retrospective study

BackgroundCerebral vasospasm (VS) and delayed cerebral ischemia (DCI) constitute major complications following subarachnoid hemorrhage (SAH). A few studies have examined the relationship between different indices of cerebrovascular dynamics with the occurrence of VS. However, their potential association with the development of DCI remains elusive. In this study, we investigated the pattern of changes of different transcranial Doppler (TCD)-derived indices of cerebrovascular dynamics during vasospasm in patients suffering from subarachnoid hemorrhage, dichotomized by the presence of delayed cerebral ischemia.MethodsA retrospective analysis was performed using recordings from 32 SAH patients, diagnosed with VS. Patients were divided in two groups, depending on development of DCI. Magnitude of slow waves (SWs) of cerebral blood flow velocity (CBFV) was measured. Cerebral autoregulation was estimated using the moving correlation coefficient Mxa. Cerebral arterial time constant (tau) was expressed as the product of resistance and compliance. Complexity of CBFV was estimated through measurement of sample entropy (SampEn).ResultsIn the whole population (N = 32), magnitude of SWs of ipsilateral to VS side CBFV was higher during vasospasm (4.15 ± 1.55 vs before: 2.86 ± 1.21 cm/s, p < 0.001). Ipsilateral SWs of CBFV before VS had higher magnitude in DCI group (N = 19, p < 0.001) and were strongly predictive of DCI, with area under the curve (AUC) = 0.745 (p = 0.02). Vasospasm caused a non-significant shortening of ipsilateral values of tau and increase in SampEn in all patients related to pre-VS measurements, as well as an insignificant increase of Mxa in DCI related to non-DCI group (N = 13).ConclusionsIn patients suffering from subarachnoid hemorrhage, TCD-detected VS was associated with higher ipsilateral CBFV SWs, related to pre-VS measurements. Higher CBFV SWs before VS were significantly predictive of delayed cerebral ischemia.

The association between early impairment in cerebral autoregulation and outcome in a pediatric swine model of cardiac arrest

AimsEvaluate cerebral autoregulation (CAR) by intracranial pressure reactivity index (PRx) and cerebral blood flow reactivity index (CBFx) during the first four hours following return of spontaneous circulation (ROSC) in a porcine model of pediatric cardiac arrest. Determine whether impaired CAR is associated with neurologic outcome. MethodsFour-week-old swine underwent seven minutes of asphyxia followed by ventricular fibrillation induction and hemodynamic-directed CPR. Those achieving ROSC had arterial blood pressure, intracranial pressure (ICP), and microvascular cerebral blood flow (CBF) monitored for 4h. Animals were assigned an 8-h post-ROSC swine cerebral performance category score (1=normal; 2–4=abnormal neurologic function). In this secondary analytic study, we calculated PRx and CBFx using a continuous, moving correlation coefficient between mean arterial pressure (MAP) and ICP, and between MAP and CBF, respectively. Burden of impaired CAR was the area under the PRx or CBFx curve using a threshold of 0.3 and normalized as percentage of monitoring duration. ResultsAmong 23 animals, median PRx was 0.14 [0.06,0.25] and CBFx was 0.36 [0.05,0.44]. Median burden of impaired CAR was 21% [18,27] with PRx and 30% [17,40] with CBFx. Neurologically abnormal animals (n=10) did not differ from normal animals (n=13) in post-ROSC MAP (63 vs. 61mmHg, p=0.74), ICP (15 vs. 14mmHg, p=0.78) or CBF (274 vs. 397 Perfusion Units, p=0.12). CBFx burden was greater among abnormal than normal animals (45% vs. 24%, p=0.001), but PRx burden was not (25% vs. 20%, p=0.38). ConclusionCAR is impaired early after ROSC. A greater burden of CAR impairment measured by CBFx was associated with abnormal neurologic outcome.CHOP Institutional Animal Care and Use Committee protocol 19-001327.

Comparing the effect of positioning on cerebral autoregulation during radical prostatectomy: a prospective observational study

PurposeSurgery in the prolonged extreme Trendelenburg position may lead to elevated intracranial pressure and compromise cerebral hemodynamic regulation. We hypothesized that robot-assisted radical prostatectomy with head-down tilt causes impairment of cerebral autoregulation compared with open retropubic radical prostatectomy in the supine position.MethodsPatients scheduled for elective radical prostatectomy were included at a tertiary care prostate cancer clinic. Continuous monitoring of the cerebral autoregulation was performed using the correlation method. Based on measurements of cerebral oxygenation with near-infrared spectroscopy and invasive mean arterial blood pressure (MAP), a moving correlation coefficient was calculated to obtain the cerebral oxygenation index as an indicator of cerebral autoregulation. Cerebral autoregulation was measured continuously from induction until recovery from anesthesia.ResultsThere was no significant difference in cerebral autoregulation between robot-assisted and open retropubic radical prostatectomy during induction (p = 0.089), intraoperatively (p = 0.162), and during recovery from anesthesia (p = 0.620). Age (B = 0.311 [95% CI 0.039; 0.583], p = 0.025) and a higher difference between baseline MAP and intraoperative MAP (B = 0.200 [95% CI 0.073; 0.327], p = 0.002) were associated with impaired cerebral autoregulation, whereas surgical technique was not (B = 3.339 [95% CI 1.275; 7.952], p = 0.155).ConclusionCompared with open radical prostatectomy in the supine position, robot-assisted surgery in the extreme Trendelenburg position with capnoperitoneum did not lead to an impairment of cerebral autoregulation during the perioperative period in our study population.Trial registration number: DRKS00010014, date of registration: 21.03.2016, retrospectively registered.

Comparative Study of Novel Noninvasive Cerebral Autoregulation Volumetric Reactivity Indices Reflected by Ultrasonic Speed and Attenuation as Dynamic Measurements in the Human Brain

This is a comparative study of two novel noninvasive cerebrovascular autoregulation (CA) monitoring methods based on intracranial blood volume (IBV) changes in the human brain. We investigated the clinical applicability of the new volumetric reactivity index (VRx2), reflected by intracranial ultrasonic attenuation dynamics for noninvasive CA monitoring. The CA was determined noninvasively on 43 healthy participants by calculating the volumetric reactivity index (VRx1 from time-of-flight of ultrasound, VRx2 from attenuation of ultrasound). The VRx was calculated as a moving correlation coefficient between the arterial blood pressure and noninvasively measured IBV slow waves. Linear regression between VRx1 and VRx2 (averaged per participants) showed a significant correlation (r = 0.731, p < 0.0001, 95% confidence interval [0.501–0.895]) in data filtered by bandpass filtering. On the other hand, FIR filtering demonstrated a slightly better correlation (r = 0.769, p < 0.0001, 95% confidence interval [0.611–0.909]). The standard deviation of the difference by bandpass filtering was 0.1647 and bias −0.3444; and by FIR filtering 0.1382 and bias −0.3669. This comparative study showed a significant coincidence of the VRx2 index compared to that of VRx1. Hence, VRx2 could be used as an alternative, cost-effective noninvasive cerebrovascular autoregulation index in the same way as VRx1 values are used.

Advanced automatic detection of fetal body movements from multichannel magnetocardiographic signals

Objective: Both heart rate (HR) monitoring and detection and description of fetal movements provide essential information of the integrity of in utero development and fetal wellbeing. Our previously described method to identify movements from multichannel magnetocardiographic (MCG) recordings lacks of reliability in some cases. This work is aimed at the improvement of fetal movement detection by means of an advanced signal processing and validation strategy. Approach: The previously proposed methodology of fetal body movement detection from MCG recordings using single space angle (SSA), min–max amplitude (MMA) and a measure of the overall signal strength across (RSS) was extended by moving correlation coefficient (MCC). The methodology was developed with respect to the discrimination between active and quiet sleep, validated by testing its coupling with HR accelerations in a total of 137 recordings lasting 30 min from 98 fetuses aged 34–38 weeks of gestation (WGA) of normal pregnancy. Main results: The developed algorithm improves the reliable automatic detection of fetal body movements independent of the fetal sleep states and their changes in the individual MCG recordings. In the fetuses aged 34–38 WGA 94% of 15 × 15 HR accelerations were coupled with detected movements. The visual inspection of the movement graphs of 30 fetuses aged 20–32 WGA supports the transferability of the movement detector to this age. In four subjects MCG-based movement detection and maternal report on percepted fetal movements were consistent. Significance: The presented methodology allows the parallel automatic acquisition of precise fetal heart rate variability (HRV) indices based on subsequent beat intervals and of fetal body movements from MCG recordings during late 2nd and 3rd trimester. Potential advantages of parallel monitoring of fetal HRV and movements using MCG compared to established ultrasound technology should be investigated in subsequent studies with respect to the identification of fetuses at risk.

Cerebrovascular reactivity is not associated with therapeutic intensity in adult traumatic brain injury: a CENTER-TBI analysis

BackgroundImpaired cerebrovascular reactivity in adult traumatic brain injury (TBI) is known to be associated with poor outcome. However, there has yet to be an analysis of the association between the comprehensively assessed intracranial hypertension therapeutic intensity level (TIL) and cerebrovascular reactivity.MethodsUsing the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we derived pressure reactivity index (PRx) as the moving correlation coefficient between slow-wave in ICP and mean arterial pressure, updated every minute. Mean daily PRx, and daily % time above PRx of 0 were calculated for the first 7 days of injury and ICU stay. This data was linked with the daily TIL-Intermediate scores, including total and individual treatment sub-scores. Daily mean PRx variable values were compared for each TIL treatment score via mean, standard deviation, and the Mann U test (Bonferroni correction for multiple comparisons). General fixed effects and mixed effects models for total TIL versus PRx were created to display the relation between TIL and cerebrovascular reactivity.ResultsA total of 249 patients with 1230 ICU days of high frequency physiology matched with daily TIL, were assessed. Total TIL was unrelated to daily PRx. Most TIL sub-scores failed to display a significant relationship with the PRx variables. Mild hyperventilation (p < 0.0001), mild hypothermia (p = 0.0001), high levels of sedation for ICP control (p = 0.0001), and use vasopressors for CPP management (p < 0.0001) were found to be associated with only a modest decrease in mean daily PRx or % time with PRx above 0.ConclusionsCerebrovascular reactivity remains relatively independent of intracranial hypertension therapeutic intensity, suggesting inadequacy of current TBI therapies in modulating impaired autoregulation. These findings support the need for investigation into the molecular mechanisms involved, or individualized physiologic targets (ICP, CPP, or Co2) in order to treat dysautoregulation actively.

Intracranial pressure and compliance in hypoxic ischemic brain injury patients after cardiac arrest

IntroductionIn hypoxic ischemic brain injury (HIBI), increased intracranial pressure (ICP) can ensue from cerebral edema stemming from cytotoxic and vasogenic mechanisms. Downstream sequelae of restricted cerebral blood flow lead to neurologic braindeath. There is limited data characterizing the temporal trends and patterns of ICP and compliance in human HIBI patients. MethodsPatients underwent invasive ICP monitoring with a parenchymal probe (Camino) and were managed with a tier-based management algorithm for elevated ICP. Data pertaining to mean arterial pressure (MAP), ICP, brain tissue oxygenation (PbtO2), end tidal carbon dioxide (ETCO2), core body temperature and RAP (moving correlation coefficient between mean ICP and its mean pulse amplitude) as a measure of intracranial compliance were recorded in the ICM + software. Data pertaining to ICP lowering interventions was also collected. ResultsTen patients were included with a median age of 47 (range 20–71) and seven were male (7/10). The mean ICP was 14 mmHg (SD 11) and time of ICP> 20 mmHg was 22% (range 0–100). The mean MAP, ETCO2 and temperature were 89 mmHg (SD 13), 31 mmHg (SD 7), 35.7 °C (SD 0.9), respectively. The mean RAP was 0.58 (SD 0.34) and time of RAP > 0.4 was 78% (range 57–97). There were no significant relationships between ETCO2 and temperature with ICP. ConclusionsIn our cohort, HIBI was characterized by normal ICP but with limited intracranial compliance. However, significant in between patient heterogeneity exists with respect to temporal patterns of intracranial pressure — volume relationships in HIBI.Trial registration: clinicaltrials.gov (NCT03609333).

Late failure of cerebral autoregulation in hypoxic-ischemic encephalopathy is associated with brain injury: a pilot study

Background: Post-resuscitation reperfusion following hypoxic-ischemia (HIE) is associated with secondary brain injury in neonates. Objective: To quantify the association between perfusion exceeding autoregulatory limits and brain injury. Approach: Continuous mean arterial blood pressure (MABP) and cerebral near-infrared spectroscopy (NIRS) data were prospectively collected from infants with HIE. Cerebral oximetry index (COx) was calculated as a moving correlation coefficient between MABP and NIRS. Upper and lower limits of autoregulation were identified by transition from negative to positive correlation. The proportion of time MABP above (hyperperfusion) and below (hypoperfusion) autoregulatory limits was calculated during therapeutic hypothermia (days 1–3). Main results: Sixteen infants were included; injury was noted in 7/16. There was no significance in hyperperfusion burden between injured and uninjured infants during day one (7% versus 10%, p = 0.88) or two (4% versus 2%, p = 0.88), but there was a marked increase for injured infants on day three (54% versus 14%, p = 0.02). There was a corollary decrease in hypoperfusion for injured versus uninjured infants on day 3 (6% versus 24%, p = 0.05). Significance: HIE infants with brain injury have a late failure of cerebral autoregulation, manifested as a hyperperfusion burden, suggesting pathologic events are active on day 3 of hypothermia. This finding may help to identify infants which might need additional neuroprotection.

Optimal Mean Arterial Blood Pressure in Extremely Preterm Infants within the First 24 Hours of Life

To define levels of mean arterial blood pressure (MABP) where cerebrovascular reactivity is strongest (MABPOPT) during the early transitional circulation in extremely preterm infants and to investigate the association between deviations above and below MABPOPT with intraventricular hemorrhage (IVH) and mortality. A total of 44 infants born at a median gestational age 25 (23-27) weeks with indwelling arterial catheter were studied at a median 5.5 (3.1-12.6) hours within the first 24 hours of life. Cerebrovascular reactivity (tissue oxygenation heart rate reactivity index) was estimated by the moving correlation coefficient between heart rate and near-infrared spectroscopy tissue oxygenation index. MABPOPT was defined as the MABP where tissue oxygenation heart rate reactivity index reaches minimum value. Deviations below or above MABPOPT values were calculated along with MABPOPT values during retrospective data analysis. MABPOPT was detected in all infants. The mean (SD) MABPOPT was 31.3 (±4.7) mm Hg. MABPOPT increased with increasing gestational age, R = 0.424; P = .004. Deviations below MABPOPT were greater in the IVH group (mean 2.7 mm Hg; 95% CI 2.0-3.5) compared with no-IVH (mean 1.7 mm Hg; 1.1-2.2), P = .006. In infants who died, the deviation below MABPOPT was greater (mean 3.3; 95% CI 1.9-4.8) compared with those who survived (mean 1.9 mm Hg; 95% CI 1.4-2.3), P = .015. Defining optimal MABP based on the strength of cerebrovascular reactivity within the first 24 hours of life is feasible and can provide an individualized approach to the care of extremely preterm infants. Deviations below MABPOPT were significantly associated with IVH and death.

Noninvasive Monitoring of Dynamic Cerebrovascular Autoregulation and 'Optimal Blood Pressure' in Normal Adult Subjects.

Cerebrovascular autoregulation can be continuously monitored from slow fluctuations of arterial blood pressure (ABP) and regional cerebral oxygen saturation (rSO2). The purpose of this study was to evaluate the index of dynamic cerebrovascular autoregulation (TOx) and the associated 'optimal' ABP in normal adult healthy subjects. Twenty-eight healthy volunteers were studied. TOx was calculated as the moving correlation coefficient between spontaneous fluctuations of ABP and rSO2. ABP was measured with the Finometer photoplethysmograph. The ABP with optimal autoregulation (ABPOPT) was also determined as the ABP level with the lowest associated TOx (opt-TOx). Average rSO2 and TOx was 72.3 ± 2.9% and 0.05 ± 0.18, respectively. Two subjects had impaired autoregulation with a TOx > 0.3. The opt-TOx was - 0.1 ± 0.26. ABPOPT was 87.0 ± 16.7mmHg. The difference between ABP and ABPOPT was - 0.3 ± 7.5mmHg. In total, 44% of subjects had a deviation of ABP from ABPOPT exceeding 5mmHg. ABPOPT ranged from 57 to 117mmHg. TOx in healthy volunteers on average displays intact autoregulation and ABP close to ABPOPT. However, some subjects have possible autoregulatory dysfunction or a significant deviation of ABP from ABPOPT, which may confer a susceptibility to neurological injury.

Cerebral Autoregulation in the Prediction of Delayed Cerebral Ischemia and Clinical Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage Patients.

Pressure reactivity index and oxygen reactivity index are used to assess cerebral autoregulation after acute brain injury. The value of autoregulation indices in the prediction of delayed cerebral ischemia and outcome in patients with subarachnoid hemorrhage is still inconclusive. In this study, we aimed to focus on the predictive value of the first 72 hours commonly referred to as "early brain injury" in comparison to the overall monitoring period. Retrospective observational cohort study. Neurocritical care unit at a tertiary academic medical center. Forty-three consecutive poor-grade patients with nontraumatic subarachnoid hemorrhage admitted between 2012 and 2016 undergoing continuous high-frequency monitoring. High-frequency monitoring includes arterial blood pressure, intracranial pressure, and brain tissue oxygen tension. Pressure reactivity index and oxygen reactivity index were evaluated as moving correlation coefficient between mean arterial pressure/intracranial pressure and cerebral perfusion pressure/brain tissue oxygen tension, respectively. Median autoregulation monitoring time was 188 ± 91 hours per patient. Initial pressure reactivity index was 0.31 ± 0.02 and decreased significantly to 0.01 ± 0.01 (p < 0.001) 3 days after admission with a second peak 10 days after admission (0.18 ± 0.14; p = 0.001). Admission oxygen reactivity index was high, 0.25 ± 0.03, and decreased to a minimum of 0.11 ± 0.02 eight days after admission (p = 0.008). Patients with delayed cerebral ischemia had significantly higher overall mean pressure reactivity index values (p < 0.04), which were more pronounced during the first 72 hours, reflecting early brain injury (p < 0.02). High pressure reactivity index during the first 72 hours was associated with poor functional outcome (p < 0.001). No association between oxygen reactivity index and delayed cerebral ischemia or clinical outcome was observed (p = 0.8/0.78). High initial pressure reactivity index, presumably reflecting early brain injury, but not oxygen reactivity index, was associated with delayed cerebral ischemia and worse clinical outcome in poor-grade subarachnoid hemorrhage patients. Our data indicate that autoregulation indices should be interpreted cautiously when used in these patients and that timing is crucial when autoregulation indices are evaluated as predictor for delayed cerebral ischemia and outcome.

A Description of a New Continuous Physiological Index in Traumatic Brain Injury Using the Correlation between Pulse Amplitude of Intracranial Pressure and Cerebral Perfusion Pressure.

To describe a new continuous index of physiologic measurement in a traumatic brain injury (TBI) population, the moving correlation coefficient between intracranial pressure (ICP) pulse amplitude (AMP) and cerebral perfusion pressure (CPP), which we refer to as RAC. We use patient examples of sustained intracranial hypertension, systemic arterial hypotension, and plateau waves, as well as the retrospective analysis of 358 non-decompressive craniectomy (DC) TBI patients with high-frequency ICP and arterial blood pressure data, to explore the relationships of this new index, RAC, with AMP, ICP, CPP, RAP (correlation coefficient between AMP and ICP), pressure reactivity index (PRx), and pulse amplitude index (PAx). We compared the RAC-CPP relationship to that observed between CPP and both PRx and PAx. RAC displays temporal responsiveness to sustained increased ICP, arterial hypotension, and plateau waves, with positive values found during episodes of high ICP and low CPP. Analysis of AMP versus CPP and AMP versus ICP relationships in data from the entire non-DC cohort show lower breakpoints for AMP/CPP at CPP = 40 mm Hg and upper breakpoints for AMP/ICP at ICP = 50-60 mm Hg. RAC trends to positive values with increasing ICP, particularly with ICP values above the peak in AMP (ICP >50 mm Hg), though its interpretation requires concomitant interpretation of AMP, RAP, and PRx/PAx to determine contributions of compensatory reserve and cerebrovascular responsiveness to the changes observed in RAC. There is a parabolic relationship between RAC versus CPP, with trends toward positive RAC values near (and beyond) limits for low and high CPPs, suggesting that RAC may be used in the determination of optimum CPP. RAC appears to carry information regarding both cerebrovascular responsiveness and cerebral compensatory reserve. This contributes to RAC's uniqueness and complex interpretation. Further prospective, clinical studies of RAC in CPP optimum estimation and outcome prediction in TBI are required.

Moving correlations and chaos in the brain during closed eyes basal conditions

In this work we explored the use of linear and nonlinear, statistical approaches to studying basal EEG brain activity. To do this, we used the Moving Correlation Coefficient (MCC), and the Hurst exponent estimator to visualize short and long term EEG behavior during 2 minutes of EEG recording in closed eyes basal conditions. The EEG of 8 subjects served as data source for exploring the time series organization of the EEG in resting state. We found inter-subjects shared network patterns of high synchronic functional connectivity in frontal and right temporo-occipital regions. We also found a diversity of individual different networks of variable degree of synchronicity in the range of -0.5<R<0.5 (Spearman linear r). The nonlinear approach using Hurst exponent estimator for the chaos/order balance in the EEG time series, gave us averages values of H >0.5 for all channels. The short-term approximation to the chaos oscillation (M-Hurst) revealed several individual differences and a potential tool for subject’s characterization.