Cerebral Oxygen Extraction Research Articles

Effect of dexmedetomidine on perioperative hemodynamics and organ protection in children with congenital heart disease: A randomized controlled trial.

Background:This study aimed to investigate the effects of dexmedetomidine (Dex) on hemodynamics and organ protection in congenital heart disease (CHD) children who underwent open-heart surgery under cryogenic cardiopulmonary bypass.Methods:Ninety children were randomly allocated to group C (0.9% saline 0.2 μg/kg/hour), group D1 (Dex 0.2 μg/kg/hour), and group D2 (Dex 0.4 μg/kg/hour) (n = 30 per group). All participants received fentanyl, propofol and 1% sevoflurane for anesthesia induction. Hemodynamic data were measured from T0 (before the induction) to T7 (30 minutes after extubation). The difference of arterial internal jugular vein bulbar oxygen difference and cerebral oxygen extraction ratio were calculated according to Fick formula. Enzyme-linked immunosorbent assay was performed to detect the serum myocardial, brain and kidney injury markers. The incidence of acute kidney injury (AKI) was calculated by serum creatinine level. Tracheal extubation time, postoperative pain score and emergence agitation score were also recorded.Results:Compared with group C, group D1, and D2 exhibited reduction in hemodynamic parameters, myocardial and brain injury indicators, and tracheal extubation time. There were no significant differences in blood urea nitrogen and neutrophil gelatinase-associated lipocalin or incidence of AKI among the 3 groups. Besides, the incidence of tachycardia, nausea, vomiting and moderate agitation, and the FLACC scale in group D1 and D2 were lower than those in group C. Moreover, Dex 0.4 g/kg/hour could further reduce the dosage of fentanyl and dopamine compared with Dex 0.2 g/kg/hour.Conclusions:Dex anesthesia can effectively maintain hemodynamic stability and diminish organ injuries in CHD children.

Cerebral oxygenation in preterm infants during maternal singing combined with skin-to-skin care.

Our aim was to investigate the effect of music therapy in combination with skin-to-skin care (SSC) on regional cerebral oxygenation (rSO2) measured with near-infrared spectroscopy (NIRS) in premature infants and to study physiological stability during the interventions. This was a prospective single-center observational cohort study conducted in a tertiary neonatal intensive care unit. The study consisted of four phases: (1) baseline measurements in an incubator for 30 min; (2) quiet SSC for 30 min (SSC-Pre); (3) SSC with live maternal singing accompanied by live guitar music for 20 min (SSC-Music); (4) final quiet SSC for another 30 min (SSC-Post). The primary outcome measure of mean rSO2 for the 31 preterm infants analyzed showed a significant increase from baseline during SSC-Music (76.87% vs 77.74%, p = 0.04) and SSC-Post (76.87% vs 78.0%, p = 0.03) phases. There were no significant changes observed in heart rate (HR), peripheral oxygen saturation (SpO2), and cerebral fractional tissue oxygen extraction (cFTOE). The coefficient of variation (CV) of rSO2 and SpO2 decreased during each intervention phase. Combining music therapy with SSC appears to be safe in preterm neonates. The impact of the small increase in rSO2 and reduced variability of SpO2 and rSO2 warrants further investigation. Music therapy combined with skin-to-skin care (SSC) is safe in clinically stable premature infants and could be encouraged as part of developmental care. This is the first report where near-infrared spectroscopy (NIRS) was used to detect the simultaneous effect of music therapy and SSC on cerebral rSO2 in preterm infants. Music therapy with SSC caused a modest increase in rSO2 and decreased the coefficient of variation of rSO2 and peripheral oxygen saturation (SpO2), which suggest short-term benefits for preterm infants.

Cerebral oxygen extraction fraction (OEF): Comparison of challenge-free gradient echo QSM+qBOLD (QQ) with 15O PET in healthy adults

We aimed to validate oxygen extraction fraction (OEF) estimations by quantitative susceptibility mapping plus quantitative blood oxygen-level dependence (QSM+qBOLD, or QQ) using 15O-PET. In ten healthy adult brains, PET and MRI were acquired simultaneously on a PET/MR scanner. PET was acquired using C[15O], O[15O], and H2[15O]. Image-derived arterial input functions and standard models of oxygen metabolism provided quantification of PET. MRI included T1-weighted imaging, time-of-flight angiography, and multi-echo gradient-echo imaging that was processed for QQ. Region of interest (ROI) analyses compared PET OEF and QQ OEF. In ROI analyses, the averaged OEF differences between PET and QQ were generally small and statistically insignificant. For whole brains, the average and standard deviation of OEF was 32.8 ± 6.7% for PET; OEF was 34.2 ± 2.6% for QQ. Bland-Altman plots quantified agreement between PET OEF and QQ OEF. The interval between the 95% limits of agreement was 16.9 ± 4.0% for whole brains. Our validation study suggests that respiratory challenge-free QQ-OEF mapping may be useful for non-invasive clinical assessment of regional OEF impairment.

A comparison of protocols for simulating hemorrhage in humans: step versus ramp lower body negative pressure.

Lower body negative pressure (LBNP) elicits central hypovolemia, and it has been used to simulate the cardiovascular and cerebrovascular responses to hemorrhage in humans. LBNP protocols commonly use progressive stepwise reductions in chamber pressure for specific time periods. However, continuous ramp LBNP protocols have also been utilized to simulate the continuous nature of most bleeding injuries. The aim of this study was to compare tolerance and hemodynamic responses between these two LBNP profiles. Healthy human subjects (N = 19; age, 27 ± 4 y; 7 female/12 male) completed a 1) step LBNP protocol (5-min steps) and 2) continuous ramp LBNP protocol (3 mmHg/min), both to presyncope. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), middle and posterior cerebral artery velocity (MCAv and PCAv), cerebral oxygen saturation (ScO2), and end-tidal CO2 (etCO2) were measured. LBNP tolerance, via the cumulative stress index (CSI, summation of chamber pressure × time at each pressure), and hemodynamic responses were compared between the two protocols. The CSI (step: 911 ± 97 mmHg/min vs. ramp: 823 ± 83 mmHg/min; P = 0.12) and the magnitude of central hypovolemia (%Δ SV, step: -54.6% ± 2.6% vs. ramp: -52.1% ± 2.8%; P = 0.32) were similar between protocols. Although there were no differences between protocols for the maximal %Δ HR (P = 0.88), the %Δ MAP during the step protocol was attenuated (P = 0.05), and the reductions in MCAv, PCAv, ScO2, and etCO2 were greater (P ≤ 0.08) when compared with the ramp protocol at presyncope. These results indicate that when comparing cardiovascular responses to LBNP across different laboratories, the specific pressure profile must be considered as a potential confounding factor.NEW & NOTEWORTHY Ramp lower body negative pressure (LBNP) protocols have been utilized to simulate the continuous nature of bleeding injuries. However, it unknown if tolerance or the physiological responses to ramp LBNP are similar to the more common stepwise LBNP protocol. We report similar tolerance between the two protocols, but the step protocol elicited a greater increase in cerebral oxygen extraction in the presence of reduced blood flow, presumably facilitating the matching of metabolic supply and demand.

Abstract 153: Non-invasive Measurement of Cerebral Tissue Oxygen Extraction Fraction is Correlated with Microdialysis Brain Injury Biomarkers During Extracorporeal Cardiopulmonary Resuscitation

Introduction: Extracorporeal membrane oxygenation (ECMO) assisted CPR (ECPR) can improve outcomes after prolonged or unsuccessful resuscitative efforts, but neurological injury remains common in survivors. The lack of routine neuromonitoring during ECPR and ECMO prohibits brain-targeted management to help improve neurological outcomes. In this study, we examine the association of non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) measurements of cerebral tissue oxygen extraction fraction (OEF), an indicator of metabolic stress, with invasively collected brain injury biomarkers to explore the utility of this monitoring modality during ECPR. Hypothesis: FD-DOS measurement of cerebral OEF is positively correlated with biomarkers of brain injury (lactate-pyruvate ratio, LPR; glycerol). Methods: Cerebral OEF was continuously monitored by FD-DOS in nine pediatric swine (8-11 kg) who underwent 30-60 minutes of manual CPR, were cannulated for ECMO, and remained on ECMO for 22-24 hours. Cerebral pyruvate, lactate, glycerol and glucose content were measured from cerebral microdialysate samples collected hourly. The correlation between OEF and microdialysis parameters were assessed using a linear mixed-effects model incorporating subject-specific random slope and intercept effects. Significance was determined at p<0.05. Results: Microdialysis parameters from 192 samples were compared against non-invasive OEF values. OEF was significantly correlated with LPR (p=0.001), and relative change in glycerol (p=0.005) and glucose (p=0.020) concentrations from baseline. Conclusions: Non-invasive FD-DOS neuromonitoring of OEF demonstrated significant correlations with invasive brain injury biomarkers; increasing OEF was associated with elevated LPR and glycerol, and diminished glucose. FD-DOS detection of critical neurometabolic stress at the bedside may facilitate brain-targeted ECMO management after cardiac arrest.

Assessment of Cerebral Blood Flow and Oxygen Extraction in Pediatric Sickle Cell Disease with Non-Invasive Diffuse Optical Spectroscopies

Introduction: Cerebral infarcts and associated cognitive impairments are a devastating consequence of sickle cell disease (SCD). While the underlying mechanisms are poorly understood, infarctions are thought to arise from anemia-induced microvascular perfusion abnormalities and subsequent reduced cerebrovascular reserve that is insufficient to meet tissue metabolic demands. Thus, quantification of abnormalities in microvascular cerebral blood flow (CBF) and oxygen extraction (OEF) may be useful in identifying infarct risk and monitoring therapeutic efficacy. Unfortunately, current modalities that quantify microvascular hemodynamics (e.g., PET, MRI) are prohibitively expensive, have limited availability, and require anesthesia in children <6y, making them inappropriate as routine monitoring tools. Transcranial Doppler ultrasound (TCD) is currently the standard screening tool for overt stroke risk in pediatric SCD, but it only measures blood flow velocity in the large arteries, which is a poor surrogate for microvascular perfusion in sickle cell disease. Diffuse optical spectroscopies (specifically near-infrared frequency-domain spectroscopy, FDNIRS, and diffuse correlation spectroscopy, DCS) offer a low-cost, non-invasive alternative for bedside monitoring of tissue-level OEF and CBF. We previously demonstrated that FDNIRS/DCS are sensitive to elevations in resting-state OEF and CBF in children with sickle cell disease compared to healthy controls (Lee, Neurophotonics 2019), consistent with previous studies using MRI and PET. In this feasibility study, we demonstrate these optical techniques are sensitive to altered cerebral hemodynamics in sickle patients who are 1) undergoing chronic transfusion, and 2) experiencing vaso-occlusive pain episodes (VOE). Methods: To date, we have recruited 6 pediatric patients with sickle cell disease undergoing chronic transfusion (5 females and 1 male, 6 - 14 y, mean ± std hemoglobin change pre- to post-transfusion = 1 ± 0.8 g/dL) and 4 patients admitted to the Emergency department for VOE (2 females and 2 males, 8 - 18 y, mean±std hemoglobin on admission = 8.9 ± 1.6 g/dL). For the transfusion cohort, FDNIRS/DCS measurements were made immediately prior to the start of transfusion and again immediately upon completion. For the VOE cohort, FDNIRS/DCS measurements were made upon hospital admission. For all FDNIRS/DCS assessments, a custom sensor was manually held over right and left forehead to assess oxygen extraction fraction (OEF, %) and an index of microvascular cerebral blood flow (CBFi, cm2/s) (Lee, Neurophotonics 2019). Hemispheric results were averaged to yield a mean of each measured parameter. Total measurement time was less than 15 minutes. Results: In the cohort undergoing chronic transfusion, one patient data was excluded due to poor DCS signal quality. Of the remaining 5 patients, OEF and CBFi decreased after transfusion by a median of -6.4% and -30.0%, respectively (Fig 1A, B). The FDNIRS-measured OEF decrease is comparable to previous results with MRI (Guilliams, Blood 2017) that quantified both cortical OEF and CBF response to transfusion in a similarly aged cohort. However, the DCS-measured CBFi decrease is more prominent than previously reported (30% vs. 9%). The enhanced sensitivity of DCS to CBF in sickle cell disease was reported in our recent study and is likely attributed to the confounding influences of hematocrit on the DCS-measured CBFi (Sathialingam, Biomed Opt Exp 2020). In the cohort measured during VOE, one patient data was excluded due to poor FDNIRS data quality. Of the remaining 3 subjects, OEF was elevated compared to healthy controls and was on the upper range of values measured in a cohort of otherwise subjects with sickle cell disease who were without clinical complications and were measured as part of a separate study (Fig. 1C). Conclusion: These data demonstrate how FDNIRS/DCS may be used as a simple, low-cost tool for bedside assessment of cerebral hemodynamics in non-sedated sickle children that could be used to track brain health over time, particularly during periods thought to be prone to hemodynamic instability like transfusion or VOEs. Although ~20% of data was discarded in this dataset due to improper sensor positioning leading to poor signal quality, we have recently implemented real-time quality control feedback to ensure our data passes quality criteria. Disclosures Lam: Sanguina, Inc: Current equity holder in private company.

Potential Relationship between Cerebral Fractional Tissue Oxygen Extraction (FTOE) and the Use of Sedative Agents during the Perioperative Period in Neonates and Infants.

Fractional tissue oxygen extraction (FTOE) by means of cerebral near-infrared spectroscopy (NIRS) provides information about oxygen uptake in the brain. Experimental animal data suggest that sedative agents decrease cerebral oxygen demand. The aim of the present study was to investigate the association between the cerebral FTOE and the use of pre and intraoperative sedative agents in infants aged 1–90 days. Cerebral NIRS was continuously applied during open major non-cardiac surgery in 46 infants. The main outcomes were the mean intraoperative FTOE and the percentage (%) of time of intraoperative hyperoxiaFTOE relative to the total duration of anesthesia. HyperoxiaFTOE was defined as FTOE ≤ 0.1. Cumulative doses of sedative agents (benzodiazepines and morphine), given up to 24 h preoperatively, correlated with the mean intraoperative FTOE (Spearman’s rho = −0.298, p = 0.0440) and were predictive for the % of time of intraoperative hyperoxiaFTOE (β (95% CI) 47.12 (7.32; 86.92)) when adjusted for the patients’ age, type of surgery, preoperative hemoglobin, intraoperative sevoflurane and fentanyl dose, mean intraoperative arterial blood pressure, and end-tidal CO2 by multivariate 0.75 quantile regression. There was no association with 0.5 quantile regression. We observed the suggestive positive association of decreased fractional cerebral tissue oxygen extraction and the use of sedative agents in neonates and infants undergoing surgery.

Excess cerebral oxygen delivery follows return of spontaneous circulation in near-term asphyxiated lambs

Hypoxic-ischaemia renders the neonatal brain susceptible to early secondary injury from oxidative stress and impaired autoregulation. We aimed to describe cerebral oxygen kinetics and haemodynamics immediately following return of spontaneous circulation (ROSC) and evaluate non-invasive parameters to facilitate bedside monitoring. Near-term sheep fetuses [139 ± 2 (SD) days gestation, n = 16] were instrumented to measure carotid artery (CA) flow, pressure, right brachial arterial and jugular venous saturation (SaO2 and SvO2, respectively). Cerebral oxygenation (crSO2) was measured using near-infrared spectroscopy (NIRS). Following induction of severe asphyxia, lambs received cardiopulmonary resuscitation using 100% oxygen until ROSC, with oxygen subsequently weaned according to saturation nomograms as per current guidelines. We found that oxygen consumption did not rise following ROSC, but oxygen delivery was markedly elevated until 15 min after ROSC. CrSO2 and heart rate each correlated with oxygen delivery. SaO2 remained > 90% and was less useful for identifying trends in oxygen delivery. CrSO2 correlated inversely with cerebral fractional oxygen extraction. In conclusion, ROSC from perinatal asphyxia is characterised by excess oxygen delivery that is driven by rapid increases in cerebrovascular pressure, flow, and oxygen saturation, and may be monitored non-invasively. Further work to describe and limit injury mediated by oxygen toxicity following ROSC is warranted.

Can Use of Cerebral Oxygenation Predict Developmental Outcomes in Preterm Infants With NEC?

* Abbreviations: NEC — : necrotizing enterocolitis NIRS — : near-infrared spectroscopy In this issue of Pediatrics, Howarth et al1 report on a completed longitudinal study of 46 preterm infants born at <30 weeks’ gestational age in which they recorded cerebral oxygenation using near-infrared spectroscopy (NIRS) for 1 hour per week until hospital discharge or transfer. The 6 infants who developed necrotizing enterocolitis (NEC) had consistently lower levels of cerebral oxygenation (mean −6.6%) and small increases in cerebral fractional tissue oxygen extraction (mean 0.08) throughout the study. Using multilevel mixed-effects linear models nested within each infant, the authors adjusted for a large number of confounding variables, including patent ductus arteriosus, sex, ethnicity, volume of enteral feeding, hemoglobin, and gestational age. Although the small number of infants who developed NEC limited the study, the study provides preliminary evidence that lowered cerebral oxygenation may underpin the worse neurodevelopmental outcomes that have been reported in preterm infants with NEC.2–4 Worldwide, >15 million infants are born preterm (<37 weeks’ gestation) each year, and these rates are increasing. Improvements in the care of these infants have dramatically improved survival. However, contrary to expectations, recent data, in which outcomes in … Address correspondence to Rosemary S.C. Horne, PhD, DSc, Department of Paediatrics, Level 5, Monash Children’s Hospital, 246 Clayton Rd, Melbourne, VIC 3168, Australia. E-mail: rosemary.horne{at}monash.edu

Changes in cerebral tissue oxygenation and fractional oxygen extraction with gestational age and postnatal maturation in preterm infants.

This study examined the correlation of cerebral tissue oxygen saturation (SctO2) and cerebral tissue fractional oxygen extraction (cFTOE) with gestational age (GA) and postnatal age over the first 28 days of life. Preterm infants with birth weight (BW) <1500 g were monitored with near-infrared spectroscopy (NIRS) during the first 28 days of life. SctO2 and cFTOE measurements were analyzed using a linear mixed model. A total of 70 preterm infants were included. Mean SctO2 decreased with increasing GA; SctO2 was 76.4% and 74.6% in the first 24 h for infants 24 and 28-week GA, respectively. For infants born at 24 and 28 it decreased to 52.9% and 58.4% at 28 days of life, respectively. cFTOE increased with increasing GA and postnatal age. There is an inverse relationship between SctO2 and gestational age and postnatal age but a direct relationship between cFTOE with GA and postnatal age.

Cerebral oxygen extraction fraction: Comparison of dual-gas challenge calibrated BOLD with CBF and challenge-free gradient echo QSM+qBOLD.

To compare cortical gray matter oxygen extraction fraction (OEF) estimated from 2 MRI methods: (1) the quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level dependent imaging (qBOLD) (QSM+qBOLD or QQ), and (2) the dual-gas calibrated-BOLD (DGCB) in healthy subjects; and to investigate the validity of iso-cerebral metabolic rate of oxygen consumption assumption during hypercapnia using QQ. In 10 healthy subjects, 3 tesla MRI including a multi-echo gradient echo sequence at baseline and hypercapnia for QQ, as well as an EPI dual-echo pseudo-continuous arterial spin labeling for DGCB, were performed under a hypercapnic and a hyperoxic condition. OEFs from QQ and DGCB were compared using region of interest analysis and paired t test. For QQ, cerebral metabolic rate of oxygen consumption = cerebral blood flow*OEF*arterial oxygen content was generated for both baseline and hypercapnia, which were compared. Average OEF in cortical gray matter across 10 subjects from QQ versus DGCB was 35.5 ± 6.7% versus 38.0 ± 9.1% (P = .49) at baseline and 20.7 ± 4.4% versus 28.4 ± 7.6% (P = .02) in hypercapnia: OEF in cortical gray matter was significantly reduced as measured in QQ (P < .01) and in DGCB (P < .01). Cerebral metabolic rate of oxygen consumption (in μmol O2 /min/100 g) was 168.2 ± 54.1 at baseline from DGCB and was 153.1 ± 33.8 at baseline and 126.4 ± 34.2 (P < .01) in hypercapnia from QQ. The differences in OEF obtained from QQ and DGCB are small and nonsignificant at baseline but are statistically significant during hypercapnia. In addition, QQ shows a cerebral metabolic rate of oxygen consumption decrease (17.4%) during hypercapnia.

Correlation of brain flow variables and metabolic crisis: a prospective study in patients with severe traumatic brain injury.

Current treatment guidelines for patients with severe TBI (sTBI) are aimed at preventing secondary brain injury targeting specific endpoints of intracranial physiology to avoid the development of metabolic crisis. We sought to identify factors contributing to development of metabolic crisis in the setting of a Multi-modality Monitoring and Goal-Directed Therapy (MM&GDTP) approach to patients with severe TBI. Prospective monitoring of sTBI patients was performed, with retrospective data analysis. MM&GDTP was targeted to intracranial pressure (ICP) ≤ 20mmHg, cerebral perfusion pressure (CPP) ≥ 60mmHg, brain tissue oxygen pressure (PbtO2) ≥ 20mmHg, and cerebral oxygen extraction measured by bi-frontal Near infrared Spectroscopy (NIRS) > 55%. Brain flow abnormality was defined by one of the following combinations: CPP < 60mmHg with NIRS < 55% (Type 1), CPP < 60mmHg with PbtO2 < 20mmHg (Type 2), or PbtO2 < 20mmHg with NIRS < 55% (Type 3). Cerebral micro-dialysate was analyzed hourly for glucose, lactate, pyruvate, glutamate, glycerol, and lactate/pyruvate ratio (LPR). Statistical analysis was performed with student t-test, chi-square and Pearson's tests as applicable. A total of 109,474 consecutive minutes of recorded multimodality monitoring was available for analysis. There was a significant difference in the number of minutes of brain flow abnormalities between survivors and non-survivors: 0.8% (875) versus 7.49% (8,199), respectively (p < 0.05). The duration of Type 1-3 flow abnormality per patient was higher in non-survivors (5.7 ± 2.5h) compared to survivors (0.7 ± 0.6h) as well as the duration of metabolic crisis, namely, 5.2 ± 2.2 versus 0.6 ± 1.0h per patient. The occurrence of severe metabolic crisis was associated with a Type 2 flow abnormality (CPP < 60mmHg and PbtO2 < 20mmHg), r = 0.97, p < 0.001, but not with Type 1 and 3. Metabolic crisis can occur despite a MM&GDTP approach aimed at optimizing cerebral blood flow. Severe metabolic crisis is associated to failure to maintain CPP and PbtO2 above 60 and 20mmHg, respectively. The occurrence of severe metabolic crisis portends a poor prognosis in patients with sTBI.

Fetal Inflammatory Response Syndrome and Cerebral Oxygenation During Immediate Postnatal Transition in Preterm Neonates.

Introduction: Fetal inflammatory response syndrome (FIRS), defined as elevated umbilical cord blood interleukin-6 (IL-6) values > 11 pg/ml, is associated with an increased risk of neonatal morbidity and mortality. The primary aim of the present study was to evaluate a potential influence of FIRS on cerebral oxygen saturation (crSO2) and fractional tissue oxygen extraction (cFTOE) during immediate postnatal transition in preterm neonates. The secondary aim was to analyze the potential influence of FIRS on cerebral injury and mortality.Methods: Secondary outcome parameters of prospective observational studies were analyzed. Preterm neonates with measured IL-6 values from umbilical cord blood and cerebral near-infrared spectroscopy (NIRS) measurements during immediate transition after birth were included. Preterm neonates with FIRS (FIRS group) were matched 1:1 for gestational age (± 1 week) to preterm neonates without FIRS (non-FIRS group). crSO2, cFTOE, arterial oxygen saturation (SpO2), heart rate (HR), and fraction of inspired oxygen (FiO2) were compared between both groups. In addition, cerebral injury and mortality were compared between both groups.Results: A total of 46 preterm neonates were included. Twenty-three neonates in the FIRS group [median gestational age 32.1 (IQR 30.3–33.0) weeks; median IL-6 19.7 (IQR 12.2–37.0) pg/ml] were compared to 23 neonates in the non-FIRS group [gestational age: 32.0 (30.4–33.1) weeks; IL-6: 5.4 (3.0–6.7) pg/ml]. cFTOE showed significantly lower values within the first 4 min and a trend toward lower values in minute 5 after birth in the FIRS group. There were no significant differences in crSO2 within the first 15 min after birth between the two groups. SpO2 was significantly lower in minutes 5 and 6 and HR was significantly lower in minutes 2 and 4 after birth in the FIRS group compared to the non-FIRS group. Survival without cerebral injury was similar in both groups.Conclusion: In preterm neonates with FIRS the crSO2 was similar despite significantly lower cFTOE values during the first minutes after birth. This observation may be a result of compromised oxygen consumption and delivery in the first minutes after birth in neonates with FIRS.

Cerebral and Renal Oxygenation in Infants Undergoing Laparoscopic Gastrostomy Tube Placement

The aim of this study was to evaluate the effects of a carbon dioxide pneumoperitoneum on cerebral and renal oxygenation and oxygen extraction, in a cohort of infants from the neonatal intensive care unit, undergoing laparoscopic gastrostomy. After institutional review board approval, between February 2018 and June 2019, infants 0-3mo corrected age, undergoing laparoscopic gastrostomy tube placement, were included. Strict exclusion criteria created a homogeneous cohort. Cerebral and renal tissue oxygen saturation (rSO2) by near-infrared spectroscopy, skin surface oxygen saturation (SpO2), by pulse oximetry, and amplitude-integrated electroencephalography were measured. Monitoring was divided into preoperative, intraoperative and postoperative time periods. Cerebral and renal fractional tissue oxygen extraction was calculated using arterial (SpO2) and tissue oxygen saturation (rSO2): (SpO2-rSO2SpO2)X100. Data were averaged into one-minute epochs and significant changes from baseline during the intraoperative and postoperative periods were detected using one-way analysis of variance with repeated measures. This pilot study examined sixteen infants, born at a median gestational age of 34.2wk (range: 23.0-40.6) with a median corrected age of 42.9wk (range: 40.0-46.3) at operation. None had seizure activity or altered sleep-wake cycles. No statistically significant variations in cerebral and renal tissue oxygenation and extraction were observed. Pulse oximetry did demonstrate significant variation from baseline on analysis of variance, but post hoc analysis did not identify any one specific time point at which this difference was significant. During a short infant laparoscopic procedure, no significant alteration in cerebral or renal oxygenation or oxygen extraction was observed. No seizure activity or changes in infant sleep-wake cycles occurred.

Cerebral Oxygenation and Autoregulation in Very Preterm Infants Developing IVH During the Transitional Period: A Pilot Study.

Background: The transitional period, defined as the first 72 h after preterm birth, is often characterized by a significant hemodynamic instability, which represents an important risk factor for such neurological complications of prematurity as intraventricular hemorrhage (IVH). The impairment of cerebral autoregulation plays a key role in the pathogenesis of IVH, whose incidence is highest during the transitional period. This pilot study aimed to evaluate whether patterns of cerebral autoregulation and oxygenation differ in relation to IVH development in very preterm infants during the transitional period.Methods: Infants <32 weeks' gestation were enrolled within 12 h from birth. A simultaneous monitoring of cerebral oxygenation (CrSO2) by near-infrared spectroscopy and of heart rate and peripheral oxygen saturation by pulse oximetry was performed over the first 72 h. Cerebral fractional oxygen extraction (cFTOE) and tissue oxygenation-heart rate reactivity index (TOHRx), which represents a marker of cerebrovascular reactivity, were calculated. Daily cranial and cardiac ultrasound scans were performed, in order to assess the hemodynamic status and to detect a possible IVH onset. CrSO2 and cFTOE, clustered on 6-hour epochs, were compared between infants who developed IVH during the study period and those who did not. A between-group comparison of TOHRx before and after IVH detection was also performed.Results: Twenty preterm infants with a median gestational age of 27 weeks (interquartile range, IQR: 25-30 weeks) and median birth weight of 895 g (IQR: 822-1208 g) were enrolled. Of these, 8 developed IVH. The median age at IVH detection was 40 h (IQR: 30-48 h). Pre-IVH TOHRx was significantly higher compared to matched control periods (p <0.001). CrSO2 was significantly lower from 12 to 30 h and from 42 h onwards in cases compared to controls; however, a temporary CrSO2 rise preceded IVH detection. Similarly, cFTOE was significantly higher in IVH infants from 12 to 30 h and from 48 to 72 h, with a transient decrease between the two periods.Conclusions: In preterm infants during the transitional period, the development of IVH is preceded by transient changes in cerebral oxygenation and oxygen extraction which, in turn, may underlie an early impairment of cerebral autoregulation. Larger studies are needed to confirm these preliminary findings.

Hypercapnia promotes microglial pyroptosis via inhibiting mitophagy in hypoxemic adult rats.

BackgroundHypoxemia is a typical symptom of acute respiratory distress syndrome. To avoid pulmonary morbidity, low tidal volume ventilation is often applied. The ventilation strategy will certainly cause hypercapnia. This study aimed to explore whether hypercapnia would promote microglial pyroptosis via inhibiting mitophagy in adult rats with hypoxemia.MethodsThe cerebral oxygen extraction ratio (CERO2) and partial pressure of brain tissue oxygen (PbtO2) in a rat model of hypercapnia/hypoxemia were assessed. The reactive oxygen species (ROS) production and the expression of LC3‐II/I, p62, caspase‐1, gasdermin D‐N domains (GSDMD‐N), IL‐1β, and IL‐18 in microglial cells were detected.ResultsHypercapnia decreased the PbtO2 levels of the hypoxic rats, which was further evidenced by the increased levels of CERO2. Expression levels of LC3‐II were reduced, while p62 expression was increased by hypercapnia in hypoxic microglia. Hypercapnia increased the production of ROS and the expression of caspase‐1, GSDMD‐N, IL‐1β, and IL‐18 in hypoxia‐activated microglia. Scavenging ROS inhibited microglial pyroptosis and expression of IL‐1β and IL‐18.ConclusionsThese results suggest that hypercapnia‐induced mitophagy inhibition may promote pyroptosis and enhance IL‐1β and IL‐18 release in hypoxia‐activated microglia.

Effect of Fentanyl Boluses on Cerebral Oxygenation and Hemodynamics in Preterm Infants: A Prospective Observational Study

Background: Fentanyl is a commonly used off-label medication for pain control and sedation in preterm infants. Yet, the effect of fentanyl on cerebral hemodynamics in preterm neonates remains unexplored. Objective: To evaluate the effect of a bolus dose of fentanyl on the regional cerebral oxygen saturation (RcSO₂), cerebral fractional tissue oxygen extraction (cFTOE) and left ventricular output (LVO) as compared with pre-administration baseline in preterm infants. Methods: This was a prospective observational study conducted in a level III Canadian NICU from September 2017 to February 2019. Preterm infants born <37 weeks of gestation and scheduled to receive a fentanyl bolus (1–2 μg/kg/dose) were eligible. Infants with major congenital anomalies, medically unstable and those who had received fentanyl in the previous 48 h were excluded. Outcomes: The primary outcome was the difference between RcSO₂ measured 5 min prior to and RcSO₂ measured at defined time points after administration of fentanyl. Results: Twenty-eight infants were enrolled during the study period (median gestational age 28 weeks; interquartile range [IQR] 25–29 weeks; median birth weight 1,035 g [IQR 830–1,292 g]; median age 4 days [IQR 3–7 days]). Mean (±standard deviation) baseline RcSO₂ was 73.6% (±11.8), cFTOE was 21.9 (±11.2) and LVO was 380 (±147) mL/kg/min prior to fentanyl infusion. One-way ANOVA showed no statistically significant difference between baseline and any of the post-fentanyl cerebral oxygenation, tissue oxygen extraction or cardiac output measures (p > 0.05). Conclusion: Administration of fentanyl bolus for procedural pain and sedation was not shown to significantly affect cerebral oxygenation, cerebral tissue oxygen extraction or cardiac output in stable preterm infants.

Brain Oxygen Extraction Is Differentially Altered by Alzheimer's and Vascular Diseases.

Alzheimer's disease and vascular cognitive impairment (VCI), as well as their concurrence, represent the most common types of cognitive dysfunction. Treatment strategies for these two conditions are quite different; however, there exists a considerable overlap in their clinical manifestations, and most biomarkers reveal similar abnormalities between these two conditions. To evaluate the potential of cerebral oxygen extraction fraction (OEF) as a biomarker for differential diagnosis of Alzheimer's disease and VCI. We hypothesized that in Alzheimer's disease OEF will be reduced (decreased oxygen consumption due to decreased neural activity), while in vascular diseases OEF will be elevated (increased oxygen extraction due to abnormally decreased blood flow). Prospective cross-sectional. Sixty-five subjects aged 52-89 years, including 33 mild cognitive impairment (MCI), 7 dementia, and 25 cognitively normal subjects. 3T T2 -relaxation-under-spin-tagging (TRUST) and fluid-attenuated inversion recovery imaging (FLAIR). OEF, consensus diagnoses of cognitive impairment, vascular risk factors (such as hypertension, hypercholesterolemia, diabetes, smoking, and obesity), cognitive assessments, and cerebrospinal fluid concentration of amyloid and tau were assessed. Multiple linear regression analyses of OEF with diagnostic category (normal, MCI, or dementia), vascular risks, cognitive performance, amyloid and tau pathology. When evaluating the entire group, OEF was found to be lower with more severe cognitive impairment (β = -2.70 ± 1.15, T = -2.34, P = 0.02), but was higher with greater vascular risk factors (β = 1.36 ± 0.55, T = 2.48, P = 0.02). Further investigation of the subgroup of participants with low vascular risks (N = 44) revealed that lower OEF was associated with worse cognitive performance (β = 0.04 ± 0.01, T = 3.27, P = 0.002) and greater amyloid burden (β = 92.12 ± 41.23, T = 2.23, P = 0.03). Among cognitively impaired individuals (N = 40), higher OEF was associated with greater vascular risk factors (β = 2.19 ± 0.71, T = 3.08, P = 0.004). These findings suggest that OEF is differentially affected by Alzheimer's disease and VCI pathology and may be useful in etiology-based diagnosis of cognitive impairment. 1 TECHNICAL EFFICACY: Stage 3 J. MAGN. RESON. IMAGING 2020;52:1829-1837.

Effect of Intrauterine Growth Restriction on Cerebral Regional Oxygen Saturation in Preterm and Term Neonates during Immediate Postnatal Transition

Background: Intrauterine growth restriction (IUGR) is associated with adverse perinatal outcome. Affected fetuses commonly display typical blood flow redistribution towards the brain (“brain sparing”). Accordingly, increased cerebral oxygen saturation has been observed in IUGR neonates within the first days of life. Aim: The aim of our study was to assess cerebral oxygenation behavior during immediate neonatal transition in IUGR infants. Methods: This is a retrospective single-center observational cohort study. Cerebral regional oxygen saturation (crSO₂) was measured with near-infrared spectroscopy in neonates during the first 15 min after birth. Neonates with IUGR (IUGR group) were matched for gestational age (±1 week) and gender with neonates that were appropriate for gestational age (AGA). The AGA:IUGR matching ratio was 3:1. Arterial oxygen saturation (SpO₂), heart rate (HR), crSO₂, and cerebral fractional tissue oxygen extraction (cFTOE) were compared between the groups. Results: Between August 2010 and October 2017, 45 neonates with IUGR were identified and matched to 135 AGA neonates. Mean gestational age was 33.1 ± 3.0 weeks in the IUGR group and 33.5 ± 2.7 weeks in the AGA group. Mean birth weight was 1,559 ± 582 g in the IUGR group and 2,051 ± 679 g in the AGA group. There was a significant group difference in crSO₂ beginning at 5 min and continuing for the rest of the observation time with higher crSO₂ values in the IUGR group (main effect group: p = 0.011; interaction time × group: p = 0.039). In cFTOE, a significant difference could be observed at 5–9 and 11–13 min with lower rates of oxygen extraction in the IUGR group (main effect group: p = 0.025; interaction time × group: p = 0.463). Concerning SpO₂ and HR, there was no significant difference between the IUGR and the AGA neonates. Conclusion: Neonates of the IUGR group did show significantly higher crSO₂ values and significantly lower cFTOE values already during immediate neonatal transition compared to the AGA group.

Antenatal Magnesium Sulfate and Preeclampsia Differentially Affect Neonatal Cerebral Oxygenation

Introduction: Magnesium sulfate (MgSO₄) is frequently administered for maternal and fetal neuroprotection in preeclampsia (PE) and imminent preterm birth, respectively. Objective: To assess whether MgSO₄ affects neonatal cerebral oxygenation, blood flow, and cerebral autoregulation (CAR) during the first postnatal days independently from PE. Methods: 148 neonates <32 weeks gestational age were included. Cerebral fractional tissue oxygen extraction (cFTOE) was extracted from a daily 2-h period, during which peak systolic blood flow velocity (PSV) and resistance index (RI) of the pericallosal artery were obtained. The percent time of impaired CAR (correlation coefficient between mean arterial blood pressure and cerebral oxygen saturation >0.5) was determined. Linear mixed models were applied. Results: MgSO₄ exposure was recorded in 77 neonates. Twenty-nine neonates were born following PE. MgSO₄ independently lowered cFTOE (B: –0.026, 95% CI: –0.050 to 0.002, p < 0.05) but did not affect PSV and RI. PE was associated with a lower cFTOE (B: –0.041, 95% CI: –0.067 to –0.015, p < 0.05) and a tendency towards both lower PSV (B: –4.285, 95% CI: –9.067 to 0.497, p < 0.1) and more impaired CAR (B: 4.042, 95% CI: –0.028 to 8.112, p < 0.1), which seemed to be strongly mediated by fetal brain sparing. MgSO₄ did not alter CAR. Conclusions: In contrast to fetal brain sparing in PE, MgSO₄ seems to lower cFTOE by lowering cerebral oxygen demands in preterm neonates without affecting the cerebrovasculature.