Monitoring of cerebral blood flow autoregulation: physiologic basis, measurement, and clinical implications.

Cerebral blood flow (CBF) autoregulation is the physiologic process whereby blood supply to the brain is kept constant over a range of cerebral perfusion pressures ensuring a constant supply of metabolic substrate. Clinical methods for monitoring CBF autoregulation were first developed for neurocritically ill patients and have been extended to surgical patients. These methods are based on measuring the relationship between cerebral perfusion pressure and surrogates of CBF or cerebral blood volume (CBV) at low frequencies (<0.05 Hz) of autoregulation using time or frequency domain analyses. Initially intracranial pressure monitoring or transcranial Doppler assessment of CBF velocity was utilised relative to changes in cerebral perfusion pressure or mean arterial pressure. A more clinically practical approach utilising filtered signals from near infrared spectroscopy monitors as an estimate of CBF has been validated. In contrast to the traditional teaching that 50 mm Hg is the autoregulation threshold, these investigations have found wide interindividual variability of the lower limit of autoregulation ranging from 40 to 90 mm Hg in adults and 20-55 mm Hg in children. Observational data have linked impaired CBF autoregulation metrics to adverse outcomes in patients with traumatic brain injury, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, and in surgical patients. CBF autoregulation monitoring has been described in both cardiac and noncardiac surgery. Data from a single-centre randomised study in adults found that targeting arterial pressure during cardiopulmonary bypass to above the lower limit of autoregulation led to a reduction of postoperative delirium and improved memory 1 month after surgery compared with usual care. Together, the growing body of evidence suggests that monitoring CBF autoregulation provides prognostic information on eventual patient outcomes and offers potential for therapeutic intervention. For surgical patients, personalised blood pressure management based on CBF autoregulation data holds promise as a strategy to improve patient neurocognitive outcomes.

Cerebrovascular responses to a 90° tilt in healthy neonates.

BACKGROUND: Tilts can induce alterations in cerebral hemodynamics in healthy neonates, but prior studies have only examined systemic parameters or used small tilt angles (<90°). The healthy neonatal population, however, are commonly subjected to large tilt angles (≥90°). We sought to characterize the cerebrovascular response to a 90° tilt in healthy term neonates. METHODS: We performed a secondary descriptive analysis on 44 healthy term neonates. We measured cerebral oxygen saturation (rcSO2), oxygen saturation (SpO2), heart rate (HR), breathing rate (BR), and cerebral fractional tissue oxygen extraction (cFTOE) over three consecutive 90° tilts. These parameters were measured for 2-min while neonates were in a supine (0°) position and 2-min while tilted to a sitting (90°) position. We measured oscillometric mean blood pressure (MBP) at the start of each tilt. RESULTS: rcSO2 and BR decreased significantly in the sitting position, whereas cFTOE, SpO2, and MBP increased significantly in the sitting position. We detected a significant position-by-time interaction for all physiological parameters. CONCLUSION: A 90° tilt induces a decline in rcSO2 and an increase in cFTOE in healthy term neonates. Understanding the normal cerebrovascular response to a 90° tilt in healthy neonates will help clinicians to recognize abnormal responses in high-risk infant populations. IMPACT: Healthy term neonates (≤14 days old) had decreased cerebral oxygen saturation (~1.1%) and increased cerebral oxygen extraction (~0.01) following a 90° tilt. We detected a significant position-by-time interaction with all physiological parameters measured, suggesting the effect of position varied across consecutive tilts. No prior study has characterized the cerebral oxygen saturation response to a 90° tilt in healthy term neonates.

A pilot study: Comparing a novel noninvasive measure of cerebrovascular stability index with an invasive measure of cerebral autoregulation in neonates with congenital heart disease.

Infants with congenital heart disease (CHD) may have impaired cerebral autoregulation (CA) associated with cerebral fractional tissue oxygen extraction (FTOE). We conducted a pilot study in nine CHD neonates to validate a noninvasive CA measure, cerebrovascular stability index (CSI), by eliciting responses to postural tilts. We compared CSI to an invasive measure of CA and to FTOE collected during tilts (FTOESpot). FTOESpot correlated with CSI, as did the change in FTOE during tilts, but CSI's correlation with impaired CA did not reach significance. Larger trials are indicated to validate CSI, allowing for noninvasive CA measurements and measurements in outpatient settings.

Ventilatory and Orthostatic Challenges Reveal Biomarkers for Neurocognition in Children and Young Adults With Congenital Central Hypoventilation Syndrome.

BACKGROUND: Children and young adults with congenital central hypoventilation syndrome (CCHS) are at risk of cognitive deficits. They experience autonomic dysfunction and chemoreceptor insensitivity measured during ventilatory and orthostatic challenges, but relationships between these features are undefined. RESEARCH QUESTION: Can a biomarker be identified from physiologic responses to ventilatory and orthostatic challenges that is related to neurocognitive outcomes in CCHS? STUDY DESIGN AND METHODS: This retrospective study included 25 children and young adults with CCHS tested over an inpatient stay. Relationships between physiologic measurements during hypercarbic and hypoxic ventilatory challenges, hypoxic ventilatory challenges, and orthostatic challenges and neurocognitive outcomes (by Wechsler intelligence indexes) were examined. Independent variable inclusion was determined by significant associations in Pearson's analyses. Multivariate linear regressions were used to assess relationships between measured physiologic responses to challenges and neurocognitive scores. RESULTS: Significant relationships were identified between areas of fluid intelligence and measures of oxygen saturation (SpO2) and heart rate (HR) during challenges. Specifically, perceptual reasoning was related to HR (adjusted regression [ß] coefficient, -0.68; 95% CI, 1.24 to -0.12; P = .02) during orthostasis. Working memory was related to change in HR (ß, -1.33; 95% CI, -2.61 to -0.05; P = .042) during the hypoxic ventilatory challenge. Processing speed was related to HR (ß, -1.19; 95% CI, -1.93 to -0.46; P = .003) during orthostasis, to baseline SpO2 (hypercarbic and hypoxic ß, 8.57 [95% CI, 1.63-15.51]; hypoxic ß, 8.37 [95% CI, 3.65-13.11]; P = .002 for both) during the ventilatory challenges, and to intrachallenge SpO2 (ß, 5.89; 95% CI, 0.71-11.07; P = .028) during the hypoxic ventilatory challenge. INTERPRETATION: In children and young adults with CCHS, SpO2 and HR-or change in HR-at rest and as a response to hypoxia and orthostasis are related to cognitive outcomes in domains of known risk, particularly fluid reasoning. These findings can guide additional research on the usefulness of these as biomarkers in understanding the impact of daily physical stressors on neurodevelopment in this high-risk group.

Optical imaging and spectroscopy for the study of the human brain: status report.

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions.

Factor Analysis of the Einstein Neonatal Neurobehavioral Assessment Scale in Infants with Congenital Heart Disease and Healthy Controls.

Background: Administration of the Einstein Neonatal Neurobehavioral Assessment Scale (ENNAS) can be time-consuming, and items can be highly correlated. We aimed to determine: (1) its factor analytic structure; (2) the validity of the factor structure; and (3) the associations of physiologic measures with factor scores. Methods: A factor analysis reduced 21 ENNAS items into 5 factors in 57 congenital heart disease (CHD) and 35 healthy infants. Multiple linear regressions examined the association of factor scores with group, gestational age, and physiologic variables. Results: 5-factor solution: 1 (Orienting Reflex), 2 (Extensor Axial Tone), 3 (Primitive Reflexes), 4 (Flexor Tone), 5 (Reflexive Tone Around Extremity Joints). Moderate to strong evidence supported: face, discriminant, and construct validity of these factors, with Factor 2 having the strongest. Conclusions: Components of Factor 2 may provide similar information about neonatal development, thus reducing the time for and burden of administration for researchers and clinicians.

High-resolution perioperative cerebral blood flow autoregulation measurement: a practical and feasible approach for widespread clinical monitoring.

A growing body of evidence demonstrates that excursions of BP below or above the limits of cerebral blood flow autoregulation are associated with complications in patients with neurological injury or for those undergoing cardiac surgery. Moreover, recent evidence suggests that maintaining MAP above the lower limit of cerebral autoregulation during cardiopulmonary bypass reduces the frequency of postoperative delirium and is associated with improved memory 1 month after surgery. Continuous measurement of BP in relation to cerebral autoregulation limits using a virtual patient monitoring platform processing near-infrared spectroscopy digital signals offers the hope of bringing this application to the bedside.

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.

Perspective on Cerebral Autoregulation Monitoring in Neonatal Cardiac Surgery Requiring Cardiopulmonary Bypass.

The autoregulation of cerebral blood flow protects against brain injury from transient fluctuations in arterial blood pressure. Impaired autoregulation may contribute to hypoperfusion injury in neonates and infants. Monitoring cerebral autoregulation in neonatal cardiac surgery as a guide for arterial blood pressure management may reduce neurodevelopmental morbidity. Cerebral autoregulation monitoring has been validated in animal models and in an adult trial autoregulation monitoring during bypass improved postoperative delirium scores. The nuances of pediatric cardiac disease and congenital heart surgery make simply applying adult trial findings to this unique population inappropriate. Therefore, dedicated pediatric clinical trials of cerebral autoregulation monitoring are indicated.

Cerebral oxygen saturation and cerebrovascular instability in newborn infants with congenital heart disease compared to healthy controls.

OBJECTIVE: Infants with Congenital Heart Disease (CHD) are at risk for developmental delays, though the mechanisms of brain injury that impair development are unknown. Potential causes could include cerebral hypoxia and cerebrovascular instability. We hypothesized that we would detect significantly reduced cerebral oxygen saturation and greater cerebrovascular instability in CHD infants compared to the healthy controls. METHODS: We performed a secondary analysis on a sample of 43 term infants (28 CHD, 15 healthy controls) that assessed prospectively in temporal cross-section before or at 12 days of age. CHD infants were assessed prior to open-heart surgery. Cerebral oxygen saturation levels were estimated using Near-Infrared Spectroscopy, and cerebrovascular stability was assessed with the response of cerebral oxygen saturation after a postural change (supine to sitting). RESULTS: Cerebral oxygen saturation was 9 points lower in CHD than control infants in both postures (ß = -9.3; 95%CI = -17.68, -1.00; p = 0.028), even after controlling for differences in peripheral oxygen saturation. Cerebrovascular stability was significantly impaired in CHD compared to healthy infants (ß = -2.4; 95%CI = -4.12, -.61; p = 0.008), and in CHD infants with single ventricle compared with biventricular defects (ß = -1.5; 95%CI = -2.95, -0.05; p = 0.04). CONCLUSION: CHD infants had cerebral hypoxia and decreased cerebral oxygen saturation values following a postural change, suggesting cerebrovascular instability. Future longitudinal studies should assess the associations of cerebral hypoxia and cerebrovascular instability with long-term neurodevelopmental outcomes in CHD infants.

Critical Closing Pressure by Diffuse Correlation Spectroscopy in a Neonatal Piglet Model.

The critical closing pressure (CrCP) of the cerebral vasculature is the arterial blood pressure (ABP) at which cerebral blood flow (CBF) ceases. Because the ABP of preterm infants is low and close to the CrCP, there is often no CBF during diastole. Thus, estimation of CrCP may become clinically relevant in preterm neonates. Transcranial Doppler (TCD) ultrasound has been used to estimate CrCP in preterm infants. Diffuse correlation spectroscopy (DCS) is a continuous, noninvasive optical technique that measures microvascular CBF. Our objective was to compare and validate CrCP measured by DCS versus TCD ultrasound. Hemorrhagic shock was induced in 13 neonatal piglets, and CBF was measured continuously by both modalities. CrCP was calculated using a model of cerebrovascular impedance, and CrCP determined by the two modalities showed good correlation by linear regression, median r 2 = 0.8 (interquartile range (IQR) 0.71-0.87), and Bland-Altman analysis showed a median bias of -3.5 (IQR -4.6 to -0.28). This is the first comparison of CrCP determined by DCS versus TCD ultrasound in a neonatal piglet model of hemorrhagic shock. The difference in CrCP between the two modalities may be due to differences in vasomotor tone within the microvasculature of the cerebral arterioles versus the macrovasculature of a major cerebral artery.

Creatinine filtration kinetics in critically Ill neonates.

BACKGROUND: Creatinine values are unreliable within the first weeks of life; however, creatinine is used most commonly to assess kidney function. Controversy remains surrounding the time required for neonates to clear maternal creatinine. METHODS: Eligible infants had multiple creatinine lab values and were admitted to the neonatal intensive care unit (NICU). A mathematical model was fit to the lab data to estimate the filtration onset delay, creatinine filtration half-life, and steady-state creatinine concentration for each subject. Infants were grouped by gestational age (GA) [(1) 22-27, (2) >27-32, (3) >32-37, and (4) >37-42 weeks]. RESULTS: A total of 4808 neonates with a mean GA of 34.4 ± 5 weeks and birth weight of 2.34 ± 1.1 kg were enrolled. Median (95% confidence interval) filtration onset delay for Group 1 was 4.3 (3.71, 4.89) days and was significantly different than all other groups (p < 0.001). Creatinine filtration half-life of Groups 1, 2, and 3 were significantly different from each other (p < 0.001). There was no difference in steady-state creatinine concentration among the groups. CONCLUSIONS: We quantified the observed kidney behavior in a large NICU population as a function of day of life and GA using creatinine lab results. These results can be used to interpret individual creatinine labs for infants to detect those most at risk for acute kidney injury. IMPACT: One of the largest cohorts of premature infants to describe the evolution of kidney development and function over their entire hospitalization. New concept introduced of the kidney filtration onset delay, the time needed for the kidney to begin clearance of creatinine, and that it can be used as an early indicator of kidney function. The smallest premature infants from 22 to 27 weeks gestation took the longest time to begin and complete maternal creatinine clearance. Clinicians can easily compare the creatinine level of their patient to the normative curves to improve understanding of kidney function at the bedside.

Exploratory Assessment of the Relationship Between Hemoglobin Volume Phase Index, Magnetic Resonance Imaging, and Functional Outcome in Neonates with Hypoxic-Ischemic Encephalopathy.

BACKGROUND/OBJECTIVE: Near-infrared spectroscopy (NIRS)-based measures of cerebral autoregulation (CAR) can potentially identify neonates with hypoxic-ischemic encephalopathy (HIE) who are at greatest risk of irreversible brain injury. However, modest predictive abilities have precluded previously described metrics from entering clinical care. We previously validated a novel autoregulation metric in a piglet model of induced hypotension called the hemoglobin volume phase index (HVP). The objective of this study was to evaluate the clinical ability of the HVP to predict adverse outcomes neonates with HIE. METHODS: This is a prospective study of neonates with HIE who underwent therapeutic hypothermia (TH) at a level 4 neonatal intensive care unit (NICU). Continuous cerebral NIRS and mean arterial blood pressure (MAP) from indwelling arterial catheters were measured during TH and through rewarming. Multivariate autoregressive process was used to calculate the coherence between MAP and the sum total of the oxy- and deoxygenated Hb densities (HbT), a surrogate measure of cerebral blood volume (CBV). The HVP was calculated as the cosine-transformed phase shift at the frequency of maximal MAP-HbT coherence. Brain injury was assessed by neonatal magnetic resonance imaging (MRI), and developmental outcomes were assessed by the Bayley Scales of Infant Development (BSID-III) at 15-30 months. The ability of the HVP to predict (a) death or severe brain injury by MRI and (b) death or significant developmental delay was assessed using logistic regression analyses. RESULTS: In total, 50 neonates with moderate or severe HIE were monitored. Median HVP was higher, representing more dysfunctional autoregulation, in infants who had adverse outcomes. After adjusting for sex and encephalopathy grade at presentation, HVP at 21-24 and 24-27 h of life predicted death or brain injury by MRI (21-24 h: OR 8.8, p = 0.037; 24-27 h: OR 31, p = 0.011) and death or developmental delay at 15-30 months (21-24 h: OR 11.8, p = 0.05; 24-27 h: OR 15, p = 0.035). CONCLUSIONS: Based on this pilot study of neonates with HIE, HVP merits further study as an indicator of death or severe brain injury on neonatal MRI and neurodevelopmental delay in early childhood. Larger studies are warranted for further clinical validation of the HVP to evaluate cerebral autoregulation following HIE.

Personalized Blood Pressure Management During Cardiac Surgery With Cerebral Autoregulation Monitoring: A Randomized Trial.

The purpose of this study was to determine if setting mean arterial pressure (MAP) targets during cardiopulmonary bypass (CPB) based on individualized cerebral autoregulation data reduces the frequency of neurological complications compared with usual care. Patients (n = 460) ≥ 55 years old at risk for neurological complications were randomized to have MAP targets during CPB to be above the lower limit of transcranial Doppler determined cerebral autoregulation versus usual institutional practices. The primary outcome was the frequency of the composite endpoint of clinical stroke, or new brain magnetic resonance imaging-detected ischemic injury, or cognitive decline 4-6 weeks after surgery from baseline. Secondary outcomes were components of the primary composite outcome and clinically detected delirium. Complete outcome data were available from 194 patients (stroke assessments, n = 460; magnetic resonance imaging data, n = 164; cognitive data n = 336). There was no difference between groups in the frequency of the composite neurological end-point or its components (P = 0.752). Compared with the usual care there was a 45% reduction in the frequency of clinically detected delirium in the autoregulation group (8.2% vs 14.9%, risk ratio = 0.55, 95% confidence interval = 0.32, 0.93, P = 0.035) and improved performance on test of memory 4-6 weeks after surgery from baseline (P = 0.019). Basing MAP during CPB on cerebral autoregulation monitoring did not reduce the frequency of the primary neurological outcome in high-risk patients compared with usual care but it was associated with a reduction in the frequency of delirium and better performance on tests of memory 4-6 weeks after surgery.

Continuous cerebral hemodynamic measurement during deep hypothermic circulatory arrest.

While survival of children with complex congenital heart defects has improved in recent years, roughly half suffer neurological deficits suspected to be related to cerebral ischemia. Here we report the first demonstration of optical diffuse correlation spectroscopy (DCS) for continuous and non-invasive monitoring of cerebral microvascular blood flow during complex human neonatal or cardiac surgery. Comparison between DCS and Doppler ultrasound flow measurements during deep hypothermia, circulatory arrest, and rewarming were in good agreement. Looking forward, DCS instrumentation, alone and with NIRS, could provide access to flow and metabolic biomarkers needed by clinicians to adjust neuroprotective therapy during surgery.

Acute hypercarbia increases the lower limit of cerebral blood flow autoregulation in a porcine model.

OBJECTIVES: In the present study, our objective was to determine if hypercarbia would alter cerebral blood flow (CBF) autoregulation and reduce the ability of cerebrovascular reactivity monitoring to identify the lower limit of cerebrovascular autoregulation (LLA). METHODS: Anaesthetised juvenile pigs were assigned between two groups: normocarbia (control group, n = 10) or hypercarbia [high carbon dioxide (CO2) group, n = 8]. Normocarbia subjects were maintained with an arterial CO2 of 40 Torr, while the hypercarbia subjects had an increase of inspired CO2 to achieve an arterial pCO2 of >80 Torr. Gradual hypotension was induced by continuous haemorrhage from a catheter in the femoral vein, and the LLA was determined by monitoring cortical laser Doppler flux (LDF). Vascular reactivity monitoring was performed using the pressure reactivity index (PRx) and haemoglobin volume index (HVx). RESULTS: There were no sustained differences in ICP between groups. Autoregulation was present in both groups, despite elevation in pCO2.The control group had an average LLA of 45 mmHg (95% CI: 43-47 mmHg) and the high CO2 group had a LLA of 75 mmHg (95% CI: 73-77 mmHg). The detected LLA for each subject correlated with the level of pCO2 (spearman R = 0.8243, P < 0.0001). Both the PRx and HVx accurately detected the LLA despite the presence of hypercarbia. DISCUSSION: Hypercarbia without acidosis increases the observed LLA independent of alterations in ICP. Elevations in CO2 can impair cerebrovascular autoregulation, but if there is a sufficient increase in blood pressure above the CO2 altered LLA, then autoregulation persists.

Shoulder surgery in the beach chair position is associated with diminished cerebral autoregulation but no differences in postoperative cognition or brain injury biomarker levels compared with supine positioning: the anesthesia patient safety foundation beach chair study.

BACKGROUND: Although controversial, failing to consider the gravitational effects of head elevation on cerebral perfusion is speculated to increase susceptibility to rare, but devastating, neurologic complications after shoulder surgery in the beach chair position (BCP). We hypothesized that patients in the BCP have diminished cerebral blood flow autoregulation than those who undergo surgery in the lateral decubitus position (LDP). A secondary aim was to examine whether there is a relationship between patient positioning during surgery and postoperative cognition or serum brain injury biomarker levels. METHODS: Patients undergoing shoulder surgery in the BCP (n = 109) or LDP (n = 109) had mean arterial blood pressure (MAP) and regional cerebral oxygen saturation (rScO2) monitored with near-infrared spectroscopy. A continuous, moving Pearson correlation coefficient was calculated between MAP and rScO2, generating the variable cerebral oximetry index (COx). When MAP is in the autoregulated range, COx approaches zero because there is no correlation between cerebral blood flow and arterial blood pressure. In contrast, when MAP is below the limit of autoregulation, COx is higher because there is a direct relationship between lower arterial blood pressure and lower cerebral blood flow. Thus, diminished autoregulation would be manifest as higher COx. Psychometric testing was performed before surgery and then 7 to 10 days and 4 to 6 weeks after surgery. A composite cognitive outcome was determined as the Z-score. Serum S100ß, neuron-specific enolase, and glial fibrillary acidic protein were measured at baseline, after surgery, and on postoperative day 1. RESULTS: After adjusting for age and history of hypertension, COx (P = 0.035) was higher and rScO2 lower (P < 0.0001) in the BCP group than in the LDP group. After adjusting for baseline composite cognitive outcome, there was no difference in Z-score 7 to 10 days (P = 0.530) or 4 to 6 weeks (P = 0.202) after surgery between the BCP and the LDP groups. There was no difference in serum biomarker levels between the 2 position groups CONCLUSIONS: : Compared with patients in the LDP, patients undergoing shoulder surgery in the BCP are more likely to have higher COx indicating diminished cerebral autoregulation and lower rScO2. There were no differences in the composite cognitive outcome between the BCP and the LDP groups after surgery after accounting for baseline Z-score.

Alteration in the lower limit of autoregulation with elevations in cephalic venous pressure.

OBJECTIVES: Recent studies suggest that elevated intracranial pressure (ICP), created by hydrocephalus, can alter the lower limit of cerebrovascular autoregulation (LLA). Our objective in the present study was to determine if ICP elevation from cerebral venous outflow obstruction would result in comparable alterations in the LLA. METHODS: Anesthetized juvenile pigs were assigned to one of two groups: naïve ICP (n  =  15) or high ICP (>20 mmHg; n  =  20). To elevate ICP through venous obstruction, a modified 5F esophageal balloon catheter was inserted via the right external jugular vein into the superior vena cava (SVC) and inflated to maintain an ICP of >20 mmHg. To calculate the LLA, gradual hypotension was induced by continuous hemorrhage from a catheter in the femoral vein. The LLA was determined by monitoring cortical laser Doppler flux (LDF). RESULTS: The naïve and high ICP groups had LLAs of 45 mmHg (95% CI: 41-49 mmHg) and 71 mmHg (95% CI: 66-77 mmHg) respectively by LDF. The LLA was significantly different between the two groups and correlated significantly with ICP. DISCUSSION: Elevated ICP from cephalic venous engorgement leads to an increase in the LLA. These findings suggest that pathologic processes resulting in cephalic venous outflow obstruction and intracranial venous congestion can acutely elevate ICP and may place the brain at risk for impaired cerebrovascular autoregulation.