Intact Cerebral Autoregulation Research Articles

Impact of intravenous antihypertensive therapy on cerebral blood flow and neurocognition: a systematic review and meta-analysis.

Intravenous antihypertensivedrugs are commonly used in acute care settings, yet their impact on cerebral blood flow (CBF) remains uncertain. A systematic review and meta-analysis of 50 studies evaluated the effects of commonly used i.v. antihypertensive agents on CBF in normotensive, hypertensive, and intracranial pathology populations. Meta-analyses used standardised mean differences (SMD), stratified by population type, consciousness state, antihypertensive agent, and CBF measurement method. Intravenous antihypertensivedrug therapy significantly reduced CBF in normotensive individuals without intracranial pathology (SMD-0.31, 95% confidence interval-0.51 to-0.11), primarily driven by nitroprusside and nitroglycerin in awake subjects (SMD-0.80, 95% confidence interval-1.15 to-0.46), with a median CBF decrease of 14% (interquartile range 13-16%) and a median mean arterial pressure reduction of 17% (interquartile range 9-22%). Other antihypertensives showed no significant effects on CBF in normotensive individuals, nor were changes observed in hypertensive patients or those with intracranial pathology when the median mean arterial pressure reduction was ∼20%. No correlation was found between mean arterial pressure reduction and CBF change, supporting intact cerebral autoregulation. Historical data revealed neurocognitive changes when CBF fell to ∼30 ml 100 g-1 min-1, associated with a 58% mean arterial pressure reduction and a 38% CBF reduction. Most i.v. antihypertensive agents do not significantly affect CBF in clinical dose ranges; however, nitroprusside and nitroglycerin can reduce CBF under specific clinical conditions. The certainty of evidence remains low. Neurocognitive changes appear to depend on the magnitude of blood pressure and CBF reductions. PROSPERO (CRD42024511954).

Dynamic cerebral autoregulation is preserved during orthostasis and intrathoracic pressure regulation in healthy subjects: A pilot study.

Resistance breathing may restore cardiac output (CO) and cerebral blood flow (CBF) during hypovolemia. We assessed CBF and cerebral autoregulation (CA) during tilt, resistance breathing, and paced breathing in 10 healthy subjects. Blood velocities in the internal carotid artery (ICA), middle cerebral arteries (MCA, four subjects), and aorta were measured by Doppler ultrasound in 30° and 60° semi-recumbent positions. ICA blood flow and CO were calculated. Arterial blood pressure (ABP, Finometer), and end-tidal CO2 (ETCO2) were recorded. ICA blood flow response was assessed by mixed-models regression analysis. The synchronization index (SI) for the variable pairs ABP-ICA blood velocity, ABP-MCA velocities in 0.005-0.08 Hz frequency interval was calculated as a measure of CA. Passive tilting from 30° to 60° resulted in 12% decrease in CO (p = 0.001); ICA blood flow tended to fall (p = 0.04); Resistance breathing restored CO and ICA blood flow despite a 10% ETCO2 drop. ETCO2 and CO contributed to ICA blood flow variance (adjusted R2: 0.9, p < 0.0001). The median SI was low (<0.2) indicating intact CA, confirmed by surrogate date testing. The peak SI was transiently elevated during resistance breathing in the 60° position. Resistance breathing may transiently reduce CA efficiency. Paced breathing did not restore CO or ICA blood flow.

The role of intracranial pressure variability as a predictor of intracranial hypertension and mortality in critically ill patients.

Intracranial pressure (ICP) monitoring is a widely utilized and essential tool for tracking neurosurgical patients, but there are limitations to the use of a solely ICP-based paradigm for guiding management. It has been suggested that ICP variability (ICPV), in addition to mean ICP, may be a useful predictor of neurological outcomes, as it represents an indirect measure of intact cerebral pressure autoregulation. However, the current literature regarding the applicability of ICPV shows conflicting associations between ICPV and mortality. Thus, the authors aimed to investigate the effect of ICPV on intracranial hypertensive episodes and mortality using the eICU Collaborative Research Database version 2.0. The authors extracted from the eICU database 1,815,676 ICP readings from 868 patients with neurosurgical conditions. ICPV was computed using two methods: the rolling standard deviation (RSD) and the absolute deviation from the rolling mean (DRM). An episode of intracranial hypertension was defined as at least 25 minutes of ICP > 22 mm Hg in any 30-minute window. The effects of mean ICPV on intracranial hypertension and mortality were computed using multivariate logistic regression. A recurrent neural network with long short-term memory was used for time-series predictions of ICP and ICPV to prognosticate future episodes of intracranial hypertension. A higher mean ICPV was significantly associated with intracranial hypertension using both ICPV definitions (RSD: aOR 2.82, 95% CI 2.07-3.90, p < 0.001; DRM: aOR 3.93, 95% CI 2.77-5.69, p < 0.001). ICPV was significantly associated with mortality in patients with intracranial hypertension (RSD: aOR 1.28, 95% CI 1.04-1.61, p = 0.026, DRM: aOR 1.39, 95% CI 1.10-1.79, p = 0.007). In the machine learning models, both definitions of ICPV achieved similarly good results, with the best F1 score of 0.685 ± 0.026 and an area under the curve of 0.980 ± 0.003 achieved with the DRM definition over 20 minutes. ICPV may be useful as an adjunct for the prognostication of intracranial hypertensive episodes and mortality in neurosurgical critical care as part of neuromonitoring. Further research on predicting future intracranial hypertensive episodes with ICPV may help clinicians react expediently to ICP changes in patients.

Relationship between cerebral oxygenation, cardiac output, and blood pressure during transitional period in extremely low gestational age neonates.

To describe the relationship between cerebral oxygenation, cardiac output, arterial blood pressure (BP), and cerebral blood flow velocity in extremely low gestational age neonates (ELGANs) during transition. This study comprises secondary analyses from a prospective observational study conducted at a tertiary Neonatal Intensive Care Unit. Recruited ELGANs underwent cerebral saturation (CrSO2) monitoring and serial echocardiography during 72 h from birth. Correlative analyses of CrSO2 and cerebral fractional tissue oxygen extraction (CFTOE) with left (LVO) and right ventricular output (RVO), superior vena cava (SVC) flow, middle cerebral artery blood flow mean velocity (MCA.MV), systolic (SBP), diastolic (DBP), and mean (MBP) BP were conducted. Fifty ELGANs with median (range) gestational age of 25.9 (23.1-27.9) weeks were recruited. Echocardiography was performed sequentially at a median (range) age 5.0 (3.8-6.6), 17.3 (15.4-19.4), 31.0 (27.0-34.1), and 53.7 (49.3-58.3) hours. RVO, LVO, CrSO2, and SBP increased over time but no changes in MBP, DBP, CFTOE, MCA.MV or SVC flow were noted. A weak correlation was identified between CrSO2 and SBP (r2 = 0.11, p = 0.047) and MBP (r2 = 0.12, p = 0.04) at 17.3 (15.4-19.4) hours. No correlation of either CrSO2 or CFTOE with any measures of blood flow was identified. There is a weak correlation between measures of cardiac output, BP, and MCA.MV with both CrSO2 and CFTOE in ELGANs during transition. Whether this finding suggests intact cerebral autoregulation requires prospective evaluation in a cohort of sick ELGANs.

Critical Care Experience With Clinical Cerebral Autoregulation Testing in Adults With Traumatic Brain Injury.

To describe the setting, feasibility, and safety of static cerebral autoregulation testing in critically injured adults with traumatic brain injury (TBI). Methods: We reviewed static autoregulation testing using transcranial Doppler (TCD) ultrasound in patients > 18 years with TBI ICD codes between January 1, 2014, and December 31, 2021. Adverse events during testing were defined as systemic hypertension (systolic blood pressure (SBP>180 mmHg), bradycardia (HR<40 bpm), and high ICP (>30 mmHg). Impaired and absent cerebral autoregulation was defined as an autoregulatory index (ARI) <0.4 and ARI 0, respectively. We characterized prescribed changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targets by autoregulation testing results. Results: A total of 135 patients, median age 31 (interquartile range (IQR) 24, 43) years, 71.9% male, admission Glasgow coma scale (GCS) score 3 (IQR 3, 5.5), and 70.9% with subdural hematoma from severe (GCS 3-8; 133 (98.5%)) and moderate (GCS 9-12; 2 (1.5%)) TBI, underwent 309 attempted testing. All patients were mechanically ventilated and had ICP monitoring; 246 (80%) had brain tissue oxygen monitoring, and 68 (22%) had an external ventricular drain. The median number of autoregulation tests was two (range 1-3) tests/patient, and the median admission to the first test time was two days (IQR 1, 3). Of 55 (17.8%) tests not completed, systemic hypertension (32, 10.4%), intracranial hypertension (10, 3.2%), and bradycardia (3, 0.9%) were transient. Fifty-three (51%) of the first (n=104) autoregulation tests showed impaired/absent cerebral autoregulation. Impaired/absent autoregulation results at the first test were associated with repeat cerebral autoregulation testing (RR 2.25, 95% CI [1.40-3.60], p=0.0007) than intact cerebral autoregulation results. Pre-testing cerebral hemodynamic targets were maintained (n=131; 86.8%) when cerebral autoregulation was impaired (n=151; RR 1.49, 95% CI [1.25-1.77], p<0.0001). However, 15 (9.9%) test results led to higher ICP targets (from 20 mmHg to 25 mmHg), 5 (3.3%) results led to an increase in CPP target (from 60 mmHg to 70 mmHg), and five out of 131 (3.8%) patients underwent decompressive craniectomy and placement of an external ventricular drain. Intact cerebral autoregulation results (n=43/103, 41.7%) were associated with a change in ICP targets from 20 mmHg to 25 mmHg (RR 3.15, 95% CI [1.97-5.03], p<0.0001). Conclusions: Static cerebral autoregulation testing was feasible, safe, and useful in individualizing the care of patients with moderate-severe TBI receiving multimodal neuromonitoring. Testing results guided future testing, cerebral hemodynamic targets, and procedural decisions. Impaired cerebral autoregulation was very common.

Insights into Neonatal Cerebral Autoregulation by Blood Pressure Monitoring and Cerebral Tissue Oxygenation: A Qualitative Systematic Review.

The aim of this qualitative systematic review was to identify publications on blood pressure monitoring in combination with cerebral tissue oxygenation monitoring during the first week after birth focusing on cerebral autoregulation. A systematic search was performed on PubMed. The following search terms were used: infants/newborn/neonates, blood pressure/systolic/diastolic/mean/MAP/SAP/DAP, near-infrared spectroscopy, oxygenation/saturation/oxygen, and brain/cerebral. Additional studies were identified by a manual search of references in the retrieved studies and reviews. Only human studies were included. Thirty-one studies focused on preterm neonates, while five included preterm and term neonates. In stable term neonates, intact cerebral autoregulation was shown by combining cerebral tissue oxygenation and blood pressure during immediate transition, while impaired autoregulation was observed in preterm neonates with respiratory support. Within the first 24 h, stable preterm neonates had reduced cerebral tissue oxygenation with intact cerebral autoregulation, while sick neonates showed a higher prevalence of impaired autoregulation. Further cardio-circulatory treatment had a limited effect on cerebral autoregulation. Impaired autoregulation, with dependency on blood pressure and cerebral tissue oxygenation, increased the risk of intraventricular hemorrhage and abnormal neurodevelopmental outcomes. Integrating blood pressure monitoring with cerebral tissue oxygenation measurements has the potential to improve treatment decisions and optimizes neurodevelopmental outcomes in high-risk neonates.

Correlation between heart rate variability and cerebral autoregulation in septic patients.

Heart rate variability (HRV) may provide an estimation of the autonomous nervous system (ANS) integrity in critically ill patients. Disturbances of cerebral autoregulation (CAR) may share common pathways of ANS dysfunction. To explore whether changes in HRV and CAR index correlate in critically ill septic patients. Prospectively collected data on septic adult (> 18years) patients admitted into a mixed Intensive Care between February 2016 and August 2019 with a recorded transcranial doppler CAR assessment. CAR was assessed calculating the Pearson's correlation coefficient (i.e. mean flow index, Mxa) between the left middle cerebral artery flow velocity (FV), insonated with a 2-MHz probe, and invasive blood pressure (BP) signal, both recorded simultaneously through a Doppler Box (DWL, Germany). MATLAB software was used for CAR assessment using a validated script; a Mxa >0.3 was considered as impaired CAR. HRV was assessed during the same time period using a specific software (Kubios HRV 3.2.0) and analyzed in both time-domain and frequency domain methods. Correlation between HRV-derived variables and Mxa were assessed using the Spearman's coefficient. A total of 141 septic patients was studied; median Mxa was 0.35 [0.13-0.60], with 77 (54.6%) patients having an impaired CAR. Mxa had a significant although weak correlation with HRV time domain (SDNN, r=0.17, p=0.04; RMSSD, r=0.18, p=0.03; NN50, r=0.23, p=0.006; pNN50, r=0.23, p=0.007), frequency domain (FFT-HF, r=0.21; p=0.01; AR-HF, r=0.19; p=0.02), and non-linear domain (SD1, r=0.18, p=0.03) parameters. Impaired CAR patients had also all of these HRV-derived parameters higher than those with intact CAR. In this exploratory study, a potential association of ANS dysfunction and impaired CAR during sepsis was observed.

Cardiovascular and cerebrovascular responses to urodynamics testing after spinal cord injury: The influence of autonomic injury.

Autonomic dysfunction is a prominent concern following spinal cord injury (SCI). In particular, autonomic dysreflexia (AD; paroxysmal hypertension and concurrent bradycardia in response to sensory stimuli below the level of injury) is common in autonomically-complete injuries at or above T6. AD is currently defined as a >20 mmHg increase in systolic arterial pressure (SAP) from baseline, without heart rate (HR) criteria. Urodynamics testing (UDS) is performed routinely after SCI to monitor urological sequelae, often provoking AD. We, therefore, aimed to assess the cardiovascular and cerebrovascular responses to UDS and their association with autonomic injury in individuals with chronic (>1 year) SCI. Following blood draw (plasma norepinephrine [NE]), continuous SAP, HR, and middle cerebral artery blood flow velocity (MCAv) were recorded at baseline (10-minute supine), during standard clinical UDS, and recovery (10-minute supine) (n = 22, age 41.1 ± 2 years, 15 male). Low frequency variability in systolic arterial pressure (LF SAP; a marker of sympathetic modulation of blood pressure) and cerebral resistance were determined. High-level injury (≥T6) with blunted/absent LF SAP (<1.0 mmHg2) and/or low plasma NE (<0.56 nmol•L−1) indicated autonomically-complete injury. Known electrocardiographic markers of atrial (p-wave duration variability) and ventricular arrhythmia (T-peak–T-end variability) were evaluated at baseline and during UDS. Nine participants were determined as autonomically-complete, yet 20 participants had increased SAP >20 mmHg during UDS. Qualitative autonomic assessment did not discriminate autonomic injury. Maximum SAP was higher in autonomically-complete injuries (207.1 ± 2.3 mmHg) than autonomically-incomplete injuries (165.9 ± 5.3 mmHg) during UDS (p < 0.001). HR during UDS was reduced compared to baseline (p = 0.056) and recovery (p = 0.048) only in autonomically-complete lesions. MCAv was not different between groups or phases (all p > 0.05). Cerebrovascular resistance index was increased during UDS in autonomically-complete injuries compared to baseline (p < 0.001) and recovery (p < 0.001) reflecting intact cerebral autoregulation. Risk for both atrial and ventricular arrhythmia increased during UDS compared to baseline (p < 0.05), particularly in autonomically-complete injuries (p < 0.05). UDS is recommended yearly in chronic SCI but is associated with profound AD and an increased risk of arrhythmia, highlighting the need for continued monitoring during UDS. Our data also highlight the need for HR criteria in the definition of AD and the need for quantitative consideration of autonomic function after SCI.

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.

Midlife aerobic exercise and dynamic cerebral autoregulation: associations with baroreflex sensitivity and central arterial stiffness.

Midlife aerobic exercise may significantly impact age-related changes in the cerebro- and cardiovascular regulations. This study investigated the associations of midlife aerobic exercise with dynamic cerebral autoregulation (dCA), cardiovagal baroreflex sensitivity (BRS), and central arterial stiffness. Twenty middle-aged athletes (MA) who had aerobic training for >10 yr were compared with 20 young (YS) and 20 middle-aged sedentary (MS) adults. Beat-to-beat cerebral blood flow velocity, blood pressure (BP), and heart rate were measured at rest and during forced BP oscillations induced by repeated sit-stand maneuvers at 0.05 Hz. Transfer function analysis was used to calculate dCA and BRS parameters. Carotid distensibility was measured by ultrasonography. MA had the highest peak oxygen uptake (V̇o2peak) among all groups. During forced BP oscillations, MS showed lower BRS gain than YS, but this age-related reduction was absent in MA. Conversely, dCA was similar among all groups. At rest, BRS and dCA gains at low frequency (∼0.1 Hz) were higher in the MA than in MS and YS groups. Carotid distensibility was similar between MA and YS groups, but it was lower in the MS. Across all subjects, V̇o2peak was positively associated with BRS gains at rest and during forced BP oscillations (r = 0.257∼0.382, P = 0.003∼0.050) and carotid distensibility (r = 0.428∼0.490, P = 0.001). Furthermore, dCA gain at rest and carotid distensibility were positively correlated with BRS gain at rest in YS and MA groups (all P < 0.05). These findings suggest that midlife aerobic exercise improves central arterial elasticity and BRS, which may contribute to cerebral blood flow (CBF) regulation through dCA.NEW & NOTEWORTHY Middle-aged athletes (MA) showed intact dynamic cerebral autoregulation (dCA) during sit-stand maneuvers when compared with young (YS) and middle-aged sedentary (MS) adults. Conversely, MA showed the significant attenuation of age-related carotid distensibility and baroreflex sensitivity (BRS) impairments. In MA and YS groups, BRS was positively associated with dCA gain at rest and carotid distensibility. Our findings suggest that midlife aerobic exercise improves BRS by reducing central arterial stiffness, which contributes to CBF regulation through dCA.

Human Adaptations to Multiday Saturation on NASA NEEMO.

Human adaptation to extreme environments has been explored for over a century to understand human psychology, integrated physiology, comparative pathologies, and exploratory potential. It has been demonstrated that these environments can provide multiple external stimuli and stressors, which are sufficient to disrupt internal homeostasis and induce adaptation processes. Multiday hyperbaric and/or saturated (HBS) environments represent the most understudied of environmental extremes due to inherent experimental, analytical, technical, temporal, and safety limitations. National Aeronautic Space Agency (NASA) Extreme Environment Mission Operation (NEEMO) is a space-flight analog mission conducted within Florida International University’s Aquarius Undersea Research Laboratory (AURL), the only existing operational and habitable undersea saturated environment. To investigate human objective and subjective adaptations to multiday HBS, we evaluated aquanauts living at saturation for 9–10 days via NASA NEEMO 22 and 23, across psychologic, cardiac, respiratory, autonomic, thermic, hemodynamic, sleep, and body composition parameters. We found that aquanauts exposed to saturation over 9–10 days experienced intrapersonal physical and mental burden, sustained good mood and work satisfaction, decreased heart and respiratory rates, increased parasympathetic and reduced sympathetic modulation, lower cerebral blood flow velocity, intact cerebral autoregulation and maintenance of baroreflex functionality, as well as losses in systemic bodyweight and adipose tissue. Together, these findings illustrate novel insights into human adaptation across multiple body systems in response to multiday hyperbaric saturation.

Delay of cerebral autoregulation in traumatic brain injury patients

IntroductionAdequate cerebral perfusion prevents secondary insult after traumatic brain injury (TBI). Cerebral autoregulation (CAR) keeps cerebral blood flow (CBF) constant when arterial blood pressure (ABP) changes. Aim of the study was to evaluate the existence of delayed CAR in TBI patients and its possible association with outcome. MethodsWe retrospectively analysed TBI patients. Flow velocity (FV) in middle cerebral artery, invasive intra-cranial pressure (ICP) and ABP were recorded. Cerebral perfusion pressure (CPP) was calculated as ABP - ICP. Mean flow index (Mx) > 0.3 defined altered CAR. Samples from patients with altered CAR were further analysed: FV signal was shifted backward relative to CPP; Mx was calculated after each shift (MxD). Mx > 0.3 plus MxD ≤ 0.3 defined delayed CAR. Favourable outcome (FO) at 6 months was defined as Glasgow Outcome Scale 4−5. Results154 patients were included. GCS was 6 [4–9], ICP was 14 [9–20] mmHg. Data on 6 months outcome were available for 131 patients: 104/131 patients (79 %) were alive; GOS was 4 [3–5]; 70/131 (53 %) had FO. Mx was 0.07 [−0.19 to 0.28] overall. Mx was lower in patients with FO compared others (0.00 [−0.21 to 0.20] vs 0.17 [−0.12 to 0.37], p = 0.02). 118 (77 %) patients had intact CAR and 36 (23 %) patients had altered CAR; 23 patients - 15 % of the general cohort and 64 % of patients with altered CAR - had delayed CAR. Delay in the autoregulatory response was 2 [1–4] seconds. 80/98 (82 %) of patients with intact CAR survived, compared to 16/21 (76 %) with delayed and 8/12 (67 %) with altered CAR (p = 0.20). 80/98 (58 %) patients with intact, 10/21 (48 %) patients with delayed and 3/12 (25 %) patients with altered CAR had FO (p = 0.03). ConclusionA subgroup of TBI patients with delayed CAR was identified. Delayed CAR was associated with better neurological outcome than altered CAR.

Influence of cerebral hyperthermia on intracranial pressure and autoregulation of cerebral circulation in patients with acute brain injury

To study the effect of hyperthermia on intracranial pressure (ICP) and cerebral autoregulation (Prx). There were 8 patients with acute brain injury, signs of brain edema and intracranial hypertension. Cerebral autoregulation was assessed by using of PRx. ICP, CPP, BP, PRx were measured before and during hyperthermia. We have analyzed 33 episodes of cerebral hyperthermia over 38.30 C. Statistica 10.0 (StatSoft) was used for statistical analysis. Only ICP was significantly increased by 6 [3; 11] mm Hg (p<0.01). In patients with initially normal ICP, hyperthermia resulted increase of ICP in 48% of cases (median 24 [22; 28] mm Hg). In patients with baseline intracranial hypertension, progression of hypertension was noted in 100% cases (median 31 [27; 32] mm Hg) (p<0.01). Hyperthermia resulted intracranial hypertension regardless brain autoregulation status. Cerebral hyperthermia in patients with initially normal ICP results intracranial hypertension in 48% of cases. In case of elevated ICP, further progression of intracranial hypertension occurs in 100% of cases. Cerebral hyperthermia is followed by ICP elevation in both intact and impaired cerebral autoregulation.

Determining Thresholds for Three Indices of Autoregulation to Identify the Lower Limit of Autoregulation During Cardiac Surgery.

Monitoring cerebral autoregulation may help identify the lower limit of autoregulation in individual patients. Mean arterial blood pressure below lower limit of autoregulation appears to be a risk factor for postoperative acute kidney injury. Cerebral autoregulation can be monitored in real time using correlation approaches. However, the precise thresholds for different cerebral autoregulation indexes that identify the lower limit of autoregulation are unknown. We identified thresholds for intact autoregulation in patients during cardiopulmonary bypass surgery and examined the relevance of these thresholds to postoperative acute kidney injury. A single-center retrospective analysis. Tertiary academic medical center. Data from 59 patients was used to determine precise cerebral autoregulation thresholds for identification of the lower limit of autoregulation. These thresholds were validated in a larger cohort of 226 patients. Invasive mean arterial blood pressure, cerebral blood flow velocities, regional cortical oxygen saturation, and total hemoglobin were recorded simultaneously. Three cerebral autoregulation indices were calculated, including mean flow index, cerebral oximetry index, and hemoglobin volume index. Cerebral autoregulation curves for the three indices were plotted, and thresholds for each index were used to generate threshold- and index-specific lower limit of autoregulations. A reference lower limit of autoregulation could be identified in 59 patients by plotting cerebral blood flow velocity against mean arterial blood pressure to generate gold-standard Lassen curves. The lower limit of autoregulations defined at each threshold were compared with the gold-standard lower limit of autoregulation determined from Lassen curves. The results identified the following thresholds: mean flow index (0.45), cerebral oximetry index (0.35), and hemoglobin volume index (0.3). We then calculated the product of magnitude and duration of mean arterial blood pressure less than lower limit of autoregulation in a larger cohort of 226 patients. When using the lower limit of autoregulations identified by the optimal thresholds above, mean arterial blood pressure less than lower limit of autoregulation was greater in patients with acute kidney injury than in those without acute kidney injury. This study identified thresholds of intact and impaired cerebral autoregulation for three indices and showed that mean arterial blood pressure below lower limit of autoregulation is a risk factor for acute kidney injury after cardiac surgery.

Cerebral Hemodynamics Are Not Affected by the Size of the Patent Ductus Arteriosus

Introduction: Although patent ductus arteriosus (PDA) has been implicated to play a role in the development of cerebral ischemia and intraventricular hemorrhage (IVH) through a cerebral steal phenomenon, there is conflicting data on the impact of PDA size on cerebral blood flow (CBF). Cerebral autoregulation is the brain’s innate protective mechanism to maintain constant CBF despite changes in blood pressure, and it is unclear if it is influenced by PDA hemodynamics. Objective: To delineate the relationship between PDA size and CBF velocity (CBFv) in premature infants. Methods: 113 premature infants born at 23–29 weeks’ gestation had echocardiograms performed during the first week after birth to evaluate for PDA. The infants were divided into 3 groups according to PDA size: none-to-small, moderate, or large. All infants had continuous recordings of umbilical artery blood pressure (ABP) and CBFv during the first week after birth. Critical closing pressure (CrCP) was calculated from ABP and CBFv tracings. Diastolic closing margin (DCM), defined as diastolic blood pressure minus CrCP, was calculated as a marker for the risk of developing IVH. Results: Infants with a large PDA (n = 16) had the lowest ABP across all phases of the cardiac cycle (systole [p = 0.003], mean [p = 0.005], and diastole [p = 0.012]) compared to infants with a moderate (n = 19) or none-to-small PDA (n = 78). Despite blood pressure being different, systolic, mean, and diastolic CBFv were not different across groups. Cerebral autoregulation, as measured during systole, was intact regardless of the PDA size. CrCP and DCM were also not different across groups. Conclusions: In this cohort, CBFv and cerebral autoregulation during systole were not influenced by PDA size. Intact cerebral autoregulation may play a role in maintaining CBFv regardless of PDA size and differences in ABP.

Association Between the Cerebral Autoregulation Index (Pressure Reactivity), Patient's Clinical Outcome, and Quality of ABP(t) and ICP(t) Signals for CA Monitoring.

Background and Objectives: The aim of this study was to explore the association between the cerebral autoregulation (CA) index, the pressure reactivity index (PRx), the patient’s clinical outcome, and the quality of arterial blood pressure (ABP(t)) and intracranial blood pressure (ICP(t)) signals by comparing two filtering methods to derive the PRx. Materials and Methods: Data from 60 traumatic brain injury (TBI) patients were collected. Moving averaging and FIR (Finite Impulse Response) filtering were performed on the ABP(t) and ICP(t) signals, and the PRx was estimated from both filtered datasets. Sensitivity, specificity, and receiver-operating characteristic (ROC) curves with the area under the curves (AUCs) were determined using patient outcomes as a reference. The outcome chosen for comparison among the two filtering methods were mortality and survival. Results: The FIR filtering approach, compared with clinical outcome, had a sensitivity of 70%, a specificity of 81%, and a level of significance p = 0.001 with an area under the curve (AUC) of 0.78. The moving average filtering method compared with the clinical outcome had a sensitivity of 58%, a specificity of 72%, and a level of significance p = 0.054, with an area under the curve (AUC) of 0.66. Conclusions: The FIR (optimal) filtering approach was found to be more sensitive for discriminating between two clinical outcomes, namely intact (survival) and impaired (death) cerebral autoregulation for TBI treatment decision making.

UBC-Nepal expedition: dynamic cerebral autoregulation is attenuated in lowlanders upon ascent to 5050m.

We examined the effects of hypoxaemia on dynamic cerebral autoregulation (dCA) in lowlanders and Sherpa highlanders. We hypothesized that dCA in lowlanders would be reduced to a greater extent in the common carotid artery (CCA) compared to the internal carotid artery (ICA) during acute hypoxia at sea level and at high altitude, whereas Sherpa highlanders would have preserved dCA upon ascent to high altitude. dCA was calculated as the change in cerebrovascular conductance during transient hypotension induced via dualthigh-cuff release. Data were collected in 13 healthy lowlanders in normobaric normoxia and hypoxia (FIO2 = 0.11) at sea-level (344m), and the day after arrival at 3440m and 5050m. In addition, 10 healthy Sherpa highlanders were tested at Kathmandu (~ 1400m), and the day after arrival at 3440m and 5050m. The main findings were that: (1) in lowlanders, dCA in the CCA and ICA were both reduced by ~ 35% during normobaric hypoxia exposure at sea-level (P = 0.06 and P = 0.04, respectively); (2) CCA and ICA dCA were both similarly attenuated by ~ 40% at 5050m in lowlanders, but not 3440m, compared to sea-level (both P = 0.04); and (3) in Sherpa, high altitude had no impact on CCA dCA (P = 0.275), indicating intact cerebral autoregulation. Herein, we provide novel evidence that dCA, assessed via Duplex ultrasound, was attenuated in lowlanders with exposure to normobaric and hypobaric hypoxia, whereas it is potentially preserved in the Sherpa. The clinical implications of attenuated dCA in lowlanders, and the adaptive significance of this response in the Sherpa highlanders, remains to be elucidated.

Monitoring and Measurement of Intracranial Pressure in Pediatric Head Trauma.

Purpose of Review: Monitoring of intracranial pressure (ICP) is an important and integrated part of the treatment algorithm for children with severe traumatic brain injury (TBI). Guidelines often recommend ICP monitoring with a treatment threshold of 20 mmHg. This focused review discusses; (1) different ICP technologies and how ICP should be monitored in pediatric patients with severe TBI, (2) existing evidence behind guideline recommendations, and (3) how we could move forward to increase knowledge about normal ICP in children to support treatment decisions.Summary: Current reference values for normal ICP in adults lie between 7 and 15 mmHg. Recent studies conducted in “pseudonormal” adults, however, suggest a normal range below this level where ICP is highly dependent on body posture and decreases to negative values in sitting and standing position. Despite obvious physiological differences between children and adults, no age or body size related reference values exist for normal ICP in children. Recent guidelines for treatment of severe TBI in pediatric patients recommend ICP monitoring to guide treatment of intracranial hypertension. Decision on ICP monitoring modalities are based on local standards, the individual case, and the clinician's choice. The recommended treatment threshold is 20 mmHg for a duration of 5 min. Both prospective and retrospective observational studies applying different thresholds and treatment strategies for intracranial hypertension were included to support this recommendation. While some studies suggest improved outcome related to ICP monitoring (lower rate of mortality and severe disability), most studies identify high ICP as a marker of worse outcome. Only one study applied age-differentiated thresholds, but this study did not evaluate the effect of these different thresholds on outcome. The quality of evidence behind ICP monitoring and treatment thresholds in severe pediatric TBI is low and treatment can potentially be improved by knowledge about normal ICP from observational studies in healthy children and cohorts of pediatric “pseudonormal” patients expected to have normal ICP. Acceptable levels of ICP − and thus also treatment thresholds—probably vary with age, disease and whether the patient has intact cerebral autoregulation. Future treatment algorithms should reflect these differences and be more personalized and dynamic.

Perioperative Assessment of Cerebral Oxygen Metabolism in Infants With Functionally Univentricular Hearts Undergoing the Bidirectional Cavopulmonary Connection.

The transition from single-ventricle lesions with surgically placed systemic-to-pulmonary artery shunt to the circulation following a bidirectional cavopulmonary connection results in higher pressure in the superior vena cava when compared with the preceding circulation. The aim of this study was to evaluate the impact of this transition on the perioperative cerebral oxygen metabolism. Prospective observational cohort study. Pediatric critical care unit of a tertiary referral center. Sixteen infants after bidirectional cavopulmonary connection. Cardiac surgery (bidirectional cavopulmonary connection). We measured regional cerebral oxygen saturation, amount of hemoglobin, blood flow velocity, and microperfusion immediately before, 12-24 hours, and 36-48 hours following bidirectional cavopulmonary connection. Based on these measurements, we calculated cerebral fractional tissue oxygen extraction and approximated cerebral metabolic rate of oxygen. Mean pressure in the superior vena cava increased significantly (8 vs 17 mm Hg; p < 0.001) following bidirectional cavopulmonary connection. Mean cerebral oxygen saturation increased from 49.0% (27.4-61.0) to 56.9% (39.5-64.0) (p = 0.008), whereas mean cerebral blood flow velocity decreased from 80.0 arbitrary units (61.9-93.0) to 67.3 arbitrary units (59.0-83.3) (p < 0.001). No change was found in the cerebral amount of hemoglobin and in the cerebral microperfusion. Mean cerebral fractional tissue oxygen extraction (0.48 [0.17-0.63] vs 0.30 [0.19-0.56]; p = 0.006) and approximated cerebral metabolic rate of oxygen (5.82 arbitrary units [2.70-8.78] vs 2.27 arbitrary units [1.19-7.35]; p < 0.001) decreased significantly. Establishment of bidirectional cavopulmonary connection is associated with postoperative improvement in cerebral oxygen metabolism. Cerebral amount of hemoglobin did not increase, although creation of the bidirectional cavopulmonary connection results in significant elevation in superior vena cava pressure. Improvement in cerebral oxygen metabolism was due to lower cerebral blood flow velocity and stable microperfusion, which may indicate intact cerebral autoregulation.

Dynamic Cerebral Autoregulation and Critical Closing Pressure in Experimental Human Endotoxemia and Sepsis Patients

Background: To investigate the influence of systemic inflammation on dynamic cerebral autoregulation and vascular tone during experimental human endotoxemia and sepsis. Methods: Healthy volunteers received 3 h continuous infusion of LPS (c-LPS, 4 ng/kg, n = 11, Clinicaltrials.gov NCT02922673) or a bolus of LPS (b-LPS, 2 ng/kg, n = 8, Clinicaltrials.gov NCT02675868) and 10 sepsis patients were studied. Mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) were monitored simultaneously. Cerebral autoregulation was analysed by transfer function analysis (TFA). Critical closing pressure (CrCP) was estimated as a measure of cerebral vascular tone. Results: c-LPS resulted in a more pronounced and prolonged plasma cytokine response compared with b-LPS. MAP decreased from 89 ± 3 to 75 ± 2 mmHg (p < 0.05) and from 91 ± 2 to 77 ± 3 mmHg (p < 0.001) in the c-LPS and b-LPS groups, respectively. MAP in sepsis patients was 65 ± 4 mmHg. TFA in both LPS groups showed no significant changes over time in coherence, gain and phase. Phase in sepsis patients was lower compared with both LPS groups (7 (2 to 33) [median (interquartile range)] in sepsis versus 57 (36 to 74) in the c-LPS (p = 0.02) and 53 (43 to 64) degrees in the b-LPS group (p = 0.01)). CrCP decreased from 49 ± 2 to 41 ± 2 mmHg (p = 0.16) in the c-LPS and from 50 ± 2 to 42 ± 2 mmHg in the b-LPS group (p < 0.01), and was 36 ± 2 mmHg in sepsis patients. Conclusions: Dynamic cerebral autoregulation is impaired in sepsis patients, but remains intact during experimental human endotoxemia. CrCP decreased during endotoxemia and was low in sepsis, reflecting decreased vascular tone. This indicates activation of a cerebrovascular adaptive process, also during experimental endotoxemia with intact cerebral autoregulation. Trial Registration: Clinicaltrials.gov NCT02922673 and Clinicaltrials.gov NCT02675868