Lower Limit Of Autoregulation Research Articles

Abstract WP152: Association Between Cerebrospinal Fluid Interleukin-6 Levels and Cerebral Autoregulation After Aneurysmal Subarachnoid Hemorrhage

Introduction: Elevated levels of Interleukin-6 (IL-6) levels in cerebrospinal fluid (CSF) have been correlated with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, the role of neuroinflammation in SAH pathophysiology remains incompletely understood. In a pig stroke model, IL-6 antagonist prevented hypotension-induced pial artery impairment, suggesting a role in post-stroke vascular derangement. This research assesses serial CSF IL-6 levels' relationship with cerebral autoregulation in aSAH patients. Methods: We prospectively enrolled aSAH patients at Yale-New Haven Hospital. Autoregulatory function was measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation response to changes in mean arterial pressure (MAP). The resulting autoregulatory index was used to trend the MAP range at which autoregulation was most preserved. Percent time that MAP exceeded the upper limit of autoregulation or decreased below the lower limit of autoregulation was calculated for each patient. IL-6 levels were assessed through serial CSF samples and correlated with hemodynamic parameters. Results: We calculated limits of autoregulation for twenty-two patients (mean age 60 ± 9 years, mean Hunt Hess score 3.4 ± 1.2, mean modified Fisher score 3.7 ± 0.58, average monitoring time 10.1 ± 7.3 hours). Optimal MAP and limits were calculated an average of 74% ± 20% of monitoring time. Our study provides preliminary support for a potential association between IL-6 levels and percent time that MAP was within limits of autoregulation (b = -0.31, p=0.009, Fig. 1A). Additionally, there was a significant correlation between IL-6 levels and the extent to which MAP deviated from computed optimal MAP (r= 0.636, p=0.009, Fig. 1B). Conclusions: IL-6 may contribute to impaired autoregulation post aSAH. Further studies are needed to validate findings and refine MAP management for improved outcomes in aSAH patients.

Cerebral autoregulation derived blood pressure targets in elective neurosurgery.

Poor postoperative outcomes may be associated with cerebral ischaemia or hyperaemia, caused by episodes of arterial blood pressure (ABP) being outside the range of cerebral autoregulation (CA). Monitoring CA using COx (correlation between slow changes in mean ABP and regional cerebral O2 saturation-rSO2) could allow to individualise the management of ABP to preserve CA. We aimed to explore a continuous automated assessment of ABPOPT (ABP where CA is best preserved) and ABP at the lower limit of autoregulation (LLA) in elective neurosurgery patients. Retrospective analysis of prospectively collected data of 85 patients [median age 60 (IQR 51-68)] undergoing elective neurosurgery. ABPBASELINE was the mean of 3 pre-operative non-invasive measurements. ABP and rSO2 waveforms were processed to estimate COx-derived ABPOPT and LLA trend-lines. We assessed: availability (number of patients where ABPOPT/LLA were available); time required to achieve first values; differences between ABPOPT/LLA and ABP. ABPOPT and LLA availability was 86 and 89%. Median (IQR) time to achieve the first value was 97 (80-155) and 93 (78-122) min for ABPOPT and LLA respectively. Median ABPOPT [75 (69-84)] was lower than ABPBASELINE [90 (84-95)] (p < 0.001, Mann-U test). Patients spent 72 (56-86) % of recorded time with ABP above or below ABPOPT ± 5mmHg. ABPOPT and ABP time trends and variability were not related to each other within patients. 37.6% of patients had at least 1 hypotensive insult (ABP < LLA) during the monitoring time. It seems possible to assess individualised automated ABP targets during elective neurosurgery.

Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study.

The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation. Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP. Individualized limits of autoregulation were computed in 55 patients (mean age 38years, mean monitoring time 92h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14mm Hg to 79 ± 17mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6mm Hg to 21.9 ± 5.6mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60min after compared with before an intervention (11% vs. 23%, p = 0.05). Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes.

Cerebral autoregulation monitoring using the cerebral oximetry index after neonatal cardiac surgery: A single-center retrospective cohort study

ObjectiveTo investigate whether cerebral autoregulation is impaired after neonatal cardiac surgery and whether changes in autoregulation metrics are associated with different congenital heart defects or the incidence of postoperative neurologic events. MethodsThis is a retrospective observational study of neonates undergoing monitoring during the first 72 hours after cardiac surgery. Archived data were processed to calculate the cerebral oximetry index (COx) and derived metrics. Acute neurologic events were identified by an electronic medical record review. The Skillings-Mack test and the Wilcoxon signed-rank test were used to analyze the evolution of autoregulation metrics over time; the Mann-Whitney U test was used for comparison between groups. ResultsWe included 28 neonates, 7 (25%) with hypoplastic left heart syndrome and 21 (75%) with transposition of the great arteries. Overall, the median percentage of time spent with impaired autoregulation, defined as percentage of time with a COx >0.3, was 31.6% (interquartile range, 21.1%-38.3%). No differences in autoregulation metrics between different cardiac defects subgroups were observed. Seven patients (25%) experienced a postoperative acute neurologic event. Compared to the neonates without an acute neurologic event, those with an acute neurologic event had a higher COx (0.16 vs 0.07; P = .035), a higher percentage of time with a COx >0.3 (39.4% vs 29.2%; P = .017), and a higher percentage of time with a mean arterial pressure below the lower limit of autoregulation (13.3% vs 6.9%; P = .048). ConclusionsCOx monitoring after cardiac surgery allowed for the detection of impaired cerebral autoregulation, which was more frequent in neonates with postoperative acute neurologic events.

Additional predictors of the lower limit of cerebral autoregulation during cardiac surgery.

The lower limit of autoregulation (LLA) of cerebral blood flow was previously shown to vary directly with the Ambulatory Arterial Stiffness Index (AASI) redefined as 1-regression slope of DBP-versus-SBP readings invasively measured from the radial artery before the bypass. We aimed expanding the predictive capacity of the LLA with AASI by combining it with additional predictors and provide new indications whether mean arterial pressure (MAP) is above/below the LLA. In 181 patients undergoing cardiac surgery, mean (SD) age 71 (8) years), we identified from the demographic, preoperative and intraoperative characteristics independent and statistically significant 'single predictors' of the LLA (including AASI). This was achieved using multivariate linear regression with a backward-elimination technique. The single predictors combined with 1-AASI generated new multiplicative and additive composite predictors of the LLA. Indicators for the MAP-to-LLA difference (DIF) were determined using DIF-versus-predictor plots. The odds ratio (OR) for the DIF sign (Outcome = 1 for DIF≤0) and predictor-minus-median sign (Exposure = 1 for Predictor ≤ Median) were calculated using logistic regression. BMI, 1-AASI and systolic coefficient of variation were identified single predictors that correlated similarly with the LLA ( r = -0.26 to -0.27, P < 0.001). The multiplicative and additive composite predictors displayed higher correlation with LLA ( r = -0.41 and r = -0.43, respectively, P < 0.001) and improved LLA estimation. The adjusted OR for the composite predictors was nearly twice that of the single predictors. The novel composite predictors may enhance the LLA estimation and the ability to maintain MAP in the cerebral autoregulatory range during cardiac surgery.

Abstract 9: Autoregulation-based Blood Pressure Targets After Endovascular Thrombectomy

Background: Optimal level blood pressure (BP) targets in acute stroke remain elusive. Tailored hemodynamic management after endovascular thrombectomy (EVT) may reduce the risk of reperfusion injury and promote penumbral recovery. Our study aimed to evaluate the relationship between personalized autoregulation-based BP targets, secondary brain injury, and functional outcomes. Methods: We prospectively enrolled 200 patients with acute ischemic stroke who underwent EVT. Autoregulatory function was continuously measured for &gt;=24 hours using simultaneous recordings of near-infrared spectroscopy and mean arterial pressure (MAP). The resulting autoregulatory index was used to calculate and trend the BP range at which autoregulation was most preserved. Percent time and “dose” that MAP exceeded the upper limit or dropped below the lower limit of autoregulation (ULA, LLA) were calculated for each patient. Hemodynamic parameters were correlated with short-term clinical endpoints (symptomatic ICH), biomarkers of secondary brain injury (net water uptake, hemorrhagic transformation (HT), infarct progression), and 90-day functional outcomes. Results: Personalized BP targets were successfully computed in 195 patients (mean age 70 ± 16, 45% female, mean NIHSS 14, mean monitoring time 31 ± 28 hours). Time above the ULA was associated with worse functional outcomes at 90-days after adjusting for age, sex, NIHSS, ASPECTS and TICI (adjusted OR per 10% increase 1.4, 95% CI 1.1-1.6, P=0.004). The burden of hyperperfusion was significantly greater among patients with HT (median 2.7 vs. 3.2 mmHg*min, p=0.01) and sICH (median 2.8 vs. 4.8 mmHg*min, p=0.05) than in those without it. Furthermore, time spent above the ULA was significantly correlated with net water uptake at 72 hours (r=0.37, p=0.03). Among patients with unsuccessful reperfusion, there was a non-significant correlation between time below the LLA and infarct progression (r=0.35, p=0.064). Conclusions: In the largest study conducted to date, deviations from personalized BP targets were associated with an increased risk of secondary brain injury and worse functional outcomes. Autoregulation-oriented BP management represents a promising strategy for maximizing recovery after ischemic stroke.

Pro-Con Debate: The Clinical (Ir)relevance of the Lower Limit of Cerebral Autoregulation for Anesthesiologists.

In this Pro-Con commentary article, we discuss whether the lower limit of cerebral autoregulation is clinically relevant for anesthesiologists. The central question regarding this issue is whether mean arterial blood pressure below the lower limit of autoregulation is detrimental for the brain. The Pro side argues that continuous monitoring of cerebral autoregulation has revealed an association between going below the lower limit and mortality in the critically ill patient. Conversely, the Con side argues that cerebral autoregulation is only one of various defense mechanisms of the brain that protect against cerebral hypoperfusion, and that cerebral autoregulation may be more important to protect against intracranial hypertension.

Cerebral Autoregulation in Healthy Term Newborns: Brief Report

Cerebral autoregulation is a homeostatic process that maintains cerebral blood flow (CBF) across a range of mean arterial pressures (MAPs). Cerebral autoregulation can be impaired in pathologic systemic and neurological conditions and can lead to cerebral hypoperfusion or cerebral hyperperfusion from low and high MAPs, respectively. 1 Obrist W.D. Gennarelli T.A. Segawa H. Dolinskas C.A. Langfitt T.W. Relation of cerebral blood flow to neurological status and outcome in head-injured patients. J Neurosurg. 1979; 51: 292-300 Crossref PubMed Scopus (116) Google Scholar Little is known about the maturation of cerebral autoregulation after birth or whether there are sex differences in CBF at birth. One study of 16 term neonates without congenital heart disease tested autoregulation using cerebral oximeter monitoring with tilt testing and reported that cerebral autoregulation was intact between three and 10 days. 2 Tran N.N. Kumar S.R. Hodge F.S. Macey P.M. Cerebral autoregulation in neonates with and without congenital heart disease. Am J Crit Care. 2018; 27: 410-416https://doi.org/10.4037/ajcc2018672 Crossref PubMed Scopus (11) Google Scholar Sex differences in CBF have been observed in older ages. Similar to healthy adolescents aged 10 to 16 years and healthy adults, prepubertal girls between four and eight years have higher middle cerebral and basilar artery flow velocities than age-matched boys. 3 Vavilala M.S. Kincaid M.S. Muangman S.L. Suz P. Rozet I. Lam A.M. Gender differences in cerebral blood flow velocity and autoregulation between the anterior and posterior circulations in healthy children. Pediatr Res. 2005; 58: 574-578 Crossref PubMed Scopus (92) Google Scholar ,4 Tontisirin N. Muangman S.L. Suz P. et al. Early childhood gender differences in anterior and posterior cerebral blood flow velocity and autoregulation. Pediatrics. 2007; 119: e610-e615 Crossref PubMed Scopus (62) Google Scholar Studies report that both healthy boys and girls aged between four and 16 years have intact cerebral autoregulation and children aged two to six years have a lower limit of autoregulation (LLA) similar to adolescents and adults. 3 Vavilala M.S. Kincaid M.S. Muangman S.L. Suz P. Rozet I. Lam A.M. Gender differences in cerebral blood flow velocity and autoregulation between the anterior and posterior circulations in healthy children. Pediatr Res. 2005; 58: 574-578 Crossref PubMed Scopus (92) Google Scholar , 4 Tontisirin N. Muangman S.L. Suz P. et al. Early childhood gender differences in anterior and posterior cerebral blood flow velocity and autoregulation. Pediatrics. 2007; 119: e610-e615 Crossref PubMed Scopus (62) Google Scholar , 5 Vavilala M.S. Lee L.A. Lam A.M. The lower limit of cerebral autoregulation in children during sevoflurane anesthesia. J Neurosurg Anesthesiol. 2003; 15: 307-312 Crossref PubMed Scopus (78) Google Scholar This finding means that infants and young children have less cerebral autoregulatory reserve (difference between MAP and LLA) than older children. 5 Vavilala M.S. Lee L.A. Lam A.M. The lower limit of cerebral autoregulation in children during sevoflurane anesthesia. J Neurosurg Anesthesiol. 2003; 15: 307-312 Crossref PubMed Scopus (78) Google Scholar However, girls aged four to 16 years have higher normative autoregulatory indices of the basilar artery compared with age-matched boys and healthy boys aged four to 16 years have higher normative autoregulatory indices of the middle cerebral artery (MCA) compared with healthy girls; the reasons for these differences are not well understood. 3 Vavilala M.S. Kincaid M.S. Muangman S.L. Suz P. Rozet I. Lam A.M. Gender differences in cerebral blood flow velocity and autoregulation between the anterior and posterior circulations in healthy children. Pediatr Res. 2005; 58: 574-578 Crossref PubMed Scopus (92) Google Scholar ,4 Tontisirin N. Muangman S.L. Suz P. et al. Early childhood gender differences in anterior and posterior cerebral blood flow velocity and autoregulation. Pediatrics. 2007; 119: e610-e615 Crossref PubMed Scopus (62) Google Scholar In clinical practice, hypotension is commonly defined in relation to gestational age (GA), and hypotension is common in critically ill neonates. 6 Dilli D. Soylu H. Tekin N. Neonatal hemodynamics and management of hypotension in newborns. Turk Pediatri Ars. 2018; 53: S65-S75 Crossref PubMed Scopus (10) Google Scholar Obtaining normative data for female and male newborns is a requisite for further understanding CBF and cerebral autoregulation and optimizing cerebral perfusion in critically ill neonates. We explored CBF velocity and cerebral autoregulation of the anterior cerebral circulation among healthy term newborns.

Comparison of different metrics of cerebral autoregulation in association with major morbidity and mortality after cardiac surgery

BackgroundCardiac surgery studies have established the clinical relevance of personalised arterial blood pressure management based on cerebral autoregulation. However, variabilities exist in autoregulation evaluation. We compared the association of several cerebral autoregulation metrics, calculated using different methods, with outcomes after cardiac surgery. MethodsAutoregulation was measured during cardiac surgery in 240 patients. Mean flow index and cerebral oximetry index were calculated as Pearson's correlations between mean arterial pressure (MAP) and transcranial Doppler blood flow velocity or near-infrared spectroscopy signals. The lower limit of autoregulation and optimal mean arterial pressure were identified using mean flow index and cerebral oximetry index. Regression models were used to examine associations of area under curve and duration of mean arterial pressure below thresholds with stroke, acute kidney injury (AKI), and major morbidity and mortality. ResultsBoth mean flow index and cerebral oximetry index identified the cerebral lower limit of autoregulation below which MAP was associated with a higher incidence of AKI and major morbidity and mortality. Based on magnitude and significance of the estimates in adjusted models, the area under curve of MAP < lower limit of autoregulation had the strongest association with AKI and major morbidity and mortality. The odds ratio for area under the curve of MAP < lower limit of autoregulation was 1.05 (95% confidence interval, 1.01–1.09), meaning every 1 mm Hg h increase of area under the curve was associated with an average increase in the odds of AKI by 5%. ConclusionsFor cardiac surgery patients, area under curve of MAP < lower limit of autoregulation using mean flow index or cerebral oximetry index had the strongest association with AKI and major morbidity and mortality. Trials are necessary to evaluate this target for MAP management.

Abstract 89: Nimodipine-induced Blood Pressure Reductions Below Personalized Limits Of Autoregulation Are Associated With Worse Outcomes After Subarachnoid Hemorrhage

Background: Impairment of cerebral autoregulation after subarachnoid hemorrhage (SAH) makes patients vulnerable to changes in blood pressure (BP). While oral nimodipine is recommended for improving neurological outcomes, its administration is frequently associated with reductions in BP. In this observational study, we examined the effect of nimodipine-induced BP reductions below personalized limits of autoregulation on outcome after aneurysmal SAH. Methods: Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure (MAP). The resulting autoregulatory index was used for trending the BP range at which autoregulation was most preserved. Cerebral hypoperfusion was defined as episodes with at least 30 minutes of MAP reductions below the lower limit of autoregulation (LLA) following nimodipine administration (Fig. 1). Functional outcome was measured with the modified Rankin Scale at 90 days. Results: We identified 593 occurrences of nimodipine administration with simultaneous recording of continuous physiologic data for 60 minutes before and after the intervention among 26 SAH patients (mean age 57 + 14, 21 F). Following nimodipine administration, the mean MAP decreased from 103 to 98 mmHg (p&lt;0.001), and the time with MAP below the LLA increased from 9.5 to 21.7% (p&lt;0.001). Moreover, the proportion of episodes with cerebral hypoperfusion was associated with worse 90-day outcomes after adjusting for age and SAH severity (OR for 10% increase 1.5, 95% CI 1.2-2.2, P=0.038). Conclusions: Nimodipine-induced BP reductions below the LLA may increase the risk of secondary brain injury and poor functional outcomes. A more personalized treatment approach accounting for cerebral autoregulation status could help identify vulnerable patients and maximize the benefit from current clinical interventions.

Cerebral Autoregulation during Orthostatic Challenge in Congenital Central Hypoventilation Syndrome.

Rationale: Congenital central hypoventilation syndrome (CCHS) is a rare autonomic disorder with altered regulation of breathing, heart rate (HR), and blood pressure (BP). Aberrant cerebral oxygenation in response to hypercapnia/hypoxia in CCHS raises the concern that altered cerebral autoregulation may contribute to CCHS-related, variably impaired neurodevelopment. Objectives: To evaluate cerebral autoregulation in response to orthostatic challenge in CCHS cases versus controls. Methods: CCHS and age- and sex-matched control subjects were studied with head-up tilt (HUT) testing to induce orthostatic stress. Fifty CCHS and 100 control HUT recordings were included. HR, BP, and cerebral oxygen saturation (regional oxygen saturation) were continuously monitored. The cerebral oximetry index (COx), a real-time measure of cerebral autoregulation based on these measures, was calculated. Measurements and Main Results: HUT resulted in a greater mean BP decrease from baseline in CCHS versus controls (11% vs. 6%; P < 0.05) and a diminished increase in HR in CCHS versus controls (11% vs. 18%; P < 0.01) in the 5 minutes after tilt-up. Despite a similar COx at baseline, orthostatic provocation within 5 minutes of tilt-up caused a 50% greater increase in COx (P < 0.01) and a 29% increase in minutes of impaired autoregulation (P < 0.02) in CCHS versus controls (4.0 vs. 3.1 min). Conclusions: Cerebral autoregulatory mechanisms appear to be intact in CCHS, but the greater hypotension observed in CCHS consequent to orthostatic provocation is associated with greater values of COx/impaired autoregulation when BP is below the lower limits of autoregulation. Effects of repeated orthostatic challenges in everyday living in CCHS necessitate further study to determine their influence on neurodevelopmental disease burden.

Association of Outcomes with Model-Based Indices of Cerebral Autoregulation After Pediatric Traumatic Brain Injury.

We investigated whether model-based indices of cerebral autoregulation (CA) are associated with outcomes after pediatric traumatic brain injury. This was a retrospective analysis of a prospective clinical database of 56 pediatric patients with traumatic brain injury undergoing intracranial pressure monitoring. CA indices were calculated, including pressure reactivity index (PRx), wavelet pressure reactivity index (wPRx), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Each CA index was used to compute optimal cerebral perfusion pressure (CPP). Time of CPP below lower limit of autoregulation (LLA) or above upper limit of autoregulation (ULA) were computed for each index. Demographic, physiologic, and neuroimaging data were collected. Primary outcome was determined using Pediatric Glasgow Outcome Scale Extended (GOSE-Peds) at 12months, with higher scores being suggestive of unfavorable outcome. Univariate and multiple linear regression with guided stepwise variable selection was used to find combinations of risk factors that can best explain the variability of GOSE-Peds scores, and the best fit model was applied to the age strata. We hypothesized that higher GOSE-Peds scores were associated with higher CA values and more time below LLA or above ULA for each index. At the univariate level, CPP, dose of intracranial hypertension, PRx, PAx, wPRx, RAC, percent time more than ULA derived for PAx, and percent time less than LLA derived for PRx, PAx, wPRx, and RAC were all associated with GOSE-Peds scores. The best subset model selection on all pediatric patients identified that when accounting for CPP, increased dose of intracranial hypertension and percent time less than LLA derived for wPRx were independently associated with higher GOSE-Peds scores. Age stratification of the best fit model identified that in children less than 2years of age or 8years of ageor more, percent time less than LLA derived for wPRx represented the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and dose of intracranial hypertension. For children 2years or younger to less than 8years of age, dose of intracranial hypertension was identified as the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and percent time less than LLA derived for wPRx. Increased dose of intracranial hypertension, PRx, wPRx, PAx, and RAC values and increased percentage time less than LLA based on PRx, wPRx, PAx, and RAC are associated with higher GOSE-Peds scores, suggestive of unfavorable outcome. Reducing intracranial hypertension and maintaining CPP more than LLA based on wPRx may improve outcomes and warrants prospective investigation.

The association of bispectral index values and metrics of cerebral perfusion during cardiopulmonary bypass

Study objectiveLow bispectral index (BIS) values have been associated with adverse postoperative outcomes. However, trials of optimizing BIS by titrating anesthetic administration have reported conflicting results. One potential explanation is that cerebral perfusion may also affect BIS, but the extent of this relationship is not clear. Therefore, we examined whether BIS would be associated with cerebral perfusion during cardiopulmonary bypass, when anesthetic concentration was constant. DesignObservational cohort study. SettingCardiac operating room. PatientsSeventy-nine patients with cardiopulmonary bypass surgery were included. MeasurementsContinuous BIS, mean arterial blood pressure (MAP), cerebral blood flow velocity (CBFV), and regional cerebral oxygen saturation (rSO2) were monitored, with analysis during a period of constant anesthetic. Mean flow index (Mx) was calculated as Pearson correlation between MAP and CBFV. The lower limit of autoregulation (LLA) was identified as the MAP value at which Mx increased >0.4 with decreasing blood pressure. Postoperative delirium was assessed using the 3D-Confusion Assessment Method. ResultsMean BIS was lower during periods of MAP < LLA compared with BIS when MAP>LLA (mean 49.35 ± 10.40 vs. 50.72 ± 10.04, p = 0.002, mean difference = 1.38 [standard error: 0.42]). There was a dose response effect, with the BIS proportionately decreasing as MAP decreased below LLA (β = 0.15, 95% CI for the average slope across all patients 0.07 to 0.23, p < 0.001). In contrast, BIS was relatively unchanged when MAP was above LLA (β = 0.03, 95% CI for the average slope across all patients −0.02 to 0.09, p = 0.22). Additionally, increasing CBFV and rSO2 were associated with increasing BIS. Patients with postoperative delirium had lower mean BIS and higher percentage of time duration with BIS <45 compared to patients without delirium. ConclusionsThere was an association of BIS and metrics of cerebral perfusion during a period of constant anesthetic administration, but the absolute magnitude of change in BIS as MAP decreased below the LLA was small.

Impact of Arterial Carbon Dioxide and Oxygen Content on Cerebral Autoregulation Monitoring Among Children Supported by ECMO.

Cerebral autoregulation (CA) impairment is associated with neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Severe variations of arterial CO2 (PaCO2) and O2 (PaO2) tension after ECMO onset are common and associate with mortality and poor neurological outcome. The impact of gas exchange on CA among critically ill patients is poorly studied. Retrospective analysis of data collected prospectively from 30 children treated with veno-arterial or veno-venous ECMO in the PICU of Nantes University Hospital, France. A correlation coefficient between the variations of regional cerebral oxygen saturation (rSO2) and the variations of mean arterial blood pressure (MAP) was calculated as an index of CA (cerebral oxygenation reactivity index, COx). Cox-MAP plots were investigated allowing determining lower limit of autoregulation (LLA) and upper limit of autoregulation (ULA) limits of autoregulation. Age-based normal blood pressure was used to adjust the MAP, LLA, and ULA data from each patient and then reported as percentage (nMAP, nLLA, and nULA, respectively). RSO2, COx, nMAP, nLLA, and nULA values were averaged over one hour before each arterial blood gas (ABG) sample during ECMO run. Thirty children (median age 4.8months [Interquartile range (IQR) 0.7-39.1], median weight 5kg [IQR 4-15]) experiencing 31 ECMO runs were included in the study. Three hundred and ninety ABGs were analyzed. The highest values of COx were observed on day 1 (D1) of ECMO. The relationship between COx and PaCO2 was nonlinear, but COx values tended to be lower in case of hypercapnia compared to normocapnia. During the whole ECMO run, a weak but significant correlation between PaCO2 and nULA was observed (R = 0.432, p = 0.02). On D1 of ECMO, this correlation was stronger (R = 0.85, p = 0.03) and a positive correlation between nLLA and PaCO2 was also found (R = 0.726, p < 0.001). A very weak negative correlation between PaO2 and nULA was observed within the whole ECMO run and on D1 of ECMO (R = -0.07 p = 0.04 and R = -0.135 p = <0.001, respectively). The difference between nULA and nLLA representing the span of the autoregulation plateau was positively correlated with PaCO2 and negatively correlated with PaO2 (R = 0.224, p = 0.01 and R = -0.051, p = 0.004, respectively). We observed a complex relationship between PaCO2 and CA, influenced by the level of blood pressure. Hypercapnia seems to be globally protective in normotensive or hypertensive condition, while, in case of very low MAP, hypercapnia may disturb CA as it increases LLA. These data add additional arguments for very cautiously lower PaCO2, especially after ECMO start.

Quick Assessment of the Lower Limit of Autoregulation by Use of Transcranial Doppler Ultrasound During Cardiac Surgery.

Assessment of the individual safest minimal mean arterial pressure (MAP) during cardiac surgery remains empirical. The objective of this study was to evaluate the lower limit of autoregulation (LLA) within a short period (15min). After developing autoregulation software (OptiMAP) incorporated into transcranial Doppler ultrasound (Waki-Atys®, Lyon, France), we monitored the mean blood flow velocity (MV) and MAP. Thirty successive values of MV and MAP were automatically analysed to calculate the correlation (Mx) between the two parameters. We compared two methods of Mx sampling during a period of 15min: Mx10s=long averaging windows (one MAP/MV pair recorded every 10s), and Mx2s=short averaging windows (one MAP/MV pair recorded every 2s). The LLA value calculated from the whole recording (Mx10s) was used as the reference. Autoregulation was considered impaired at an Mx value >0.35. Five patients were included in the study. The surgery lasted for 138±32 min and cardiopulmonary bypass lasted for 72±33 min. MAP and MV were recorded for 117±24 min. MAP varied from 33±10 to 92±10mmHg. LLA calculated from the whole recording (Mx10s) was similar to LLA calculated from the 15-min recording (Mx2s): 70±2.5 versus 73±3.5mmHg. MAP remained below LLA during 48±12% of the recording. During the 15-min recording, Mx10s was not able to calculate the LLA value. In cases of haemodynamic instability, decreasing the Mx sampling window seems to accurately detect LLA.

Multimodal Assessment of Cerebral Autoregulation and Autonomic Function After Pediatric Cerebral Arteriovenous Malformation Rupture.

Management after cerebral arteriovenous malformation (AVM) rupture aims toward preventing hemorrhagic expansion while maintaining cerebral perfusion to avoid secondary injury. We investigated associations of model-based indices of cerebral autoregulation (CA) and autonomic function (AF) with outcomes after pediatric cerebral AVM rupture. Multimodal neurologic monitoring data from the initial 3days after cerebral AVM rupture were retrospectively analyzed in children (< 18years). AF indices included standard deviation of heart rate (HRsd), root-mean-square of successive differences in heart rate (HRrmssd), low-high frequency ratio (LHF), and baroreflex sensitivity (BRS). CA indices include pressure reactivity index (PRx), wavelet pressure reactivity indices (wPRx and wPRx-thr), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Percent time of cerebral perfusion pressure (CPP) below lower limits of autoregulation (LLA) was also computed for each CA index. Primary outcomes were determined using Pediatric Glasgow Outcome Score Extended-Pediatrics (GOSE-PEDs) at 12months and acquired epilepsy. Association of biomarkers with outcomes was investigated using linear regression, Wilcoxon signed-rank, or Chi-square. Fourteen children were analyzed. Lower AF indices were associated with poor outcomes (BRS [p = 0.04], HRsd [p = 0.04], and HRrmssd [p = 0.00]; and acquired epilepsy (LHF [p = 0.027]). Higher CA indices were associated with poor outcomes (PRx [p = 0.00], wPRx [p = 0.00], and wPRx-thr [p = 0.01]), and acquired epilepsy (PRx [p = 0.02] and wPRx [p = 0.00]). Increased time below LLA was associated with poor outcome (percent time below LLA based on PRx [p = 0.00], PAx [p = 0.04], wPRx-thr [p = 0.03], and RAC [p = 0.01]; and acquired epilepsy (PRx [p = 0.00], PAx [p = 0.00], wPRx-thr [p = 0.03], and RAC [p = 0.01]). After pediatric cerebral AVM rupture, poor outcomes are associated with AF and CA when applying various neurophysiologic model-based indices. Prospective work is needed to assess these indices of CA and AF in clinical decision support.

Comparison of wavelet and correlation indices of cerebral autoregulation in a pediatric swine model of cardiac arrest

Existing cerebrovascular blood pressure autoregulation metrics have not been translated to clinical care for pediatric cardiac arrest, in part because signal noise causes high index time-variability. We tested whether a wavelet method that uses near-infrared spectroscopy (NIRS) or intracranial pressure (ICP) decreases index variability compared to that of commonly used correlation indices. We also compared whether the methods identify the optimal arterial blood pressure (ABPopt) and lower limit of autoregulation (LLA). 68 piglets were randomized to cardiac arrest or sham procedure with continuous monitoring of cerebral blood flow using laser Doppler, NIRS and ICP. The arterial blood pressure (ABP) was gradually reduced until it dropped to below the LLA. Several autoregulation indices were calculated using correlation and wavelet methods, including the pressure reactivity index (PRx and wPRx), cerebral oximetry index (COx and wCOx), and hemoglobin volume index (HVx and wHVx). Wavelet methodology had less index variability with smaller standard deviations. Both wavelet and correlation methods distinguished functional autoregulation (ABP above LLA) from dysfunctional autoregulation (ABP below the LLA). Both wavelet and correlation methods also identified ABPopt with high agreement. Thus, wavelet methodology using NIRS may offer an accurate vasoreactivity monitoring method with reduced signal noise after pediatric cardiac arrest.

Treatment targets based on autoregulation parameters in neurocritical care patients.

This review summarizes the physiological basis of autoregulation-oriented therapy in critically ill patients, with a particular emphasis on individual targets based on parameters that describe autoregulation of cerebral blood flow. The concepts of optimal cerebral perfusion (CPPopt) and arterial pressures (ABPopt), which both take advantage of continuous measures of cerebral autoregulation, recently have been introduced into clinical practice. It is hypothesized that if both pressures are used as individual targets and followed, the incidence and severity of dysautoregulation will diminish sufficiently to improve outcomes across the spectrum of acute neurological illnesses. These parameters have not been tested in randomized trials. However, a Phase II trial for CPPopt in Traumatic Brain Injury (COGITATE) is underway. Clinical series suggest that delirium following cardiac surgery may be reduced if blood pressure is actively regulated above the lower limit of autoregulation. In traumatic brain injury, using CPPopt as a single target allows monitoring of the upper and lower limits of autoregulation that provide a well tolerated 'corridor' for treatment. Pilot studies in which ABPopt is monitored in preterm newborns suggest fewer haemorrhagic events if blood pressure is closer to its optimal target. Brain imaging studies suggest worse tissue outcomes when blood pressure is below ABPopt. Targeted control of brain and systemic blood pressures to optimize cerebral autoregulation is of substantial interest to the neurocritical care and anaesthesia community, as this strategy may help to avoid secondary brain insults associated with ischemia or hyperaemia. The same strategy can be used outside the ICU (e.g. cardiac surgery, or in stroke patients after mechanical thrombectomy); this requires further research.

Abstract 117: Fixed Compared to Autoregulation-oriented Blood Pressure Thresholds After Mechanical Thrombectomy for Ischemic Stroke

Background: Loss of cerebral autoregulation in the acute phase of ischemic stroke leaves patients vulnerable to blood pressure (BP) changes. Effective BP management after endovascular therapy (EVT) may protect the brain from hypo- or hyperperfusion. In this observational study, we compared personalized, autoregulation-guided BP management with two commonly used clinical approaches: (1) maintaining BP below a fixed, pre-determined value and (2) stratifying BP thresholds based on reperfusion status. Methods: We prospectively enrolled 90 patients undergoing EVT for stroke. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure (MAP). The resulting autoregulatory index was used to trend the BP range at which autoregulation was most preserved. Percent time that MAP exceeded the upper limit of autoregulation (ULA) or decreased below the lower limit of autoregulation (LLA) was calculated for each patient. Time above fixed SBP thresholds was computed in a similar fashion. Functional outcome was measured with the modified Rankin Scale (mRS) at 90 days. Results: Personalized limits of autoregulation (LA) were successfully computed in all 90 patients (mean age 72 + 16, 47% female, mean NIHSS 14, mean monitoring time 28 + 18 hours). Percent time with MAP above the ULA associated with worse 90-day outcomes (OR per 10% 1.84, 95% CI 1.3-2.7, P=0.002), and patients suffering from hemorrhagic transformation spent more time above the ULA (10.9% vs. 16.0%, P=0.042). While there appeared to be a non-significant trend towards worse outcome with increasing time above SBP thresholds of 140 mmHg and 160 mmHg, the effect sizes were smaller compared to the personalized approach. Conclusions: Non-invasive determination of personalized BP thresholds for stroke patients is feasible. Deviation from these limits may increase risk of further brain injury and poor functional outcome. This approach may present a better strategy compared to the classical approach of maintaining SBP below a pre-determined value, though a randomized trial is needed to determine the optimal approach for hemodynamic management.

Real-Time Intraoperative Determination and Reporting of Cerebral Autoregulation State Using Near-Infrared Spectroscopy.

BACKGROUND:Cerebral blood flow (CBF) is maintained over a range of blood pressures through cerebral autoregulation (CA). Blood pressure outside the range of CA, or impaired autoregulation, is associated with adverse patient outcomes. Regional oxygen saturation (rSo2) derived from near-infrared spectroscopy (NIRS) can be used as a surrogate CBF for determining CA, but existing methods require a long period of time to calculate CA metrics. We have developed a novel method to determine CA using cotrending of mean arterial pressure (MAP) with rSo2that aims to provide an indication of CA state within 1 minute. We sought to determine the performance of the cotrending method by comparing its CA metrics to data derived from transcranial Doppler (TCD) methods.METHODS:Retrospective data collected from 69 patients undergoing cardiac surgery with cardiopulmonary bypass were used to develop a reference lower limit of CA. TCD-MAP data were plotted to determine the reference lower limit of CA. The investigated method to evaluate CA state is based on the assessment of the instantaneous cotrending relationship between MAP and rSo2 signals. The lower limit of autoregulation (LLA) from the cotrending method was compared to the manual reference derived from TCD. Reliability of the cotrending method was assessed as uptime (defined as the percentage of time that the state of autoregulation could be measured) and time to first post.RESULTS:The proposed method demonstrated minimal mean bias (0.22 mmHg) when compared to the TCD reference. The corresponding limits of agreement were found to be 10.79 mmHg (95% confidence interval [CI], 10.09–11.49) and −10.35 mmHg (95% CI, −9.65 to −11.05). Mean uptime was 99.40% (95% CI, 99.34–99.46) and the mean time to first post was 63 seconds (95% CI, 58–71).CONCLUSIONS:The reported cotrending method rapidly provides metrics associated with CA state for patients undergoing cardiac surgery. A major strength of the proposed method is its near real-time feedback on patient CA state, thus allowing for prompt corrective action to be taken by the clinician.