Can pain under anesthesia be measured? Pain-related brain function using functional near-infrared spectroscopy during knee surgery.

Significance: Quantitative measurement of perisurgical brain function may provide insights into the processes contributing to acute and chronic postsurgical pain. Aim: We evaluate the hemodynamic changes in the prefrontal cortex (medial frontopolar cortex/mFPC and lateral prefrontal cortex) and the primary somatosensory cortex/S1 using functional near-infrared spectroscopy (fNIRS) in 18 patients (18.2±3.3 years, 11 females) undergoing knee arthroscopy. Approach: We examined the (a) hemodynamic response to surgery and (b) the relationship between surgery-modulated cortical connectivity (using beta-series correlation) and acute postoperative pain levels using Pearson's r correlation with 10,000 permutations. Results: We show a functional dissociation between mFPC and S1 in response to surgery, where mFPC deactivates, and S1 activates following a procedure. Furthermore, the connectivity between (a) left mFPC and right S1 (original r=-0.683, ppermutation=0.001), (b) right mFPC and right S1 (original r=-0.633, ppermutation=0.002), and (c) left mFPC and right S1 (original r=-0.695, ppermutation=0.0002) during surgery were negatively associated with acute postoperative pain levels. Conclusions: Our findings suggest that greater functional dissociation between mFPC and S1 is likely the result of inadequately controlled nociceptive barrage during surgery leading to more significant postoperative pain. It also supports the utility of fNIRS during the perioperative state for pain monitoring and patient risk assessment for chronic pain.

A Survey of the Congenital Cardiac Anesthesia Society on the Use and Clinical Application of Near- Infrared Tissue Oximetry in Pediatric Cardiac Surgery.

OBJECTIVE: To better understand the patterns of use and the perceived utility of tissue oximetry in pediatric cardiac surgery. DESIGN: A voluntary 32-question Research Electronic Data Capture survey instrument was sent twice via e-mail to the entire Congenital Cardiac Anesthesia Society (CCAS) membership (January 13, 2021 and March 9,2021). SETTING: International multi-institutional, universities, academic centers, and community hospitals. PARTICIPANTS: CCAS members. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: The survey was completed by 185 of 1,131 members (16.4% response rate). The majority of respondents (93.5%) reported use of tissue oximetry, with 97.1% reporting use for cardiac surgery with cardiopulmonary bypass, 76.3% for cardiac surgery without cardiopulmonary bypass, 34.7% in the cardiac catheterization laboratory, and 39.3% for major noncardiac surgeries. Only 14.5% reported that their institution had a formal near-infrared spectroscopy/tissue oximetry-based protocol. The most common sensor placement configuration was bilateral cerebral. More than 90% of respondents reported having made a clinical management change based on tissue oximetry values, although there was variability as to when respondents would intervene. The majority of respondents agreed or strongly agreed that tissue oximetry adds diagnostic value to standard intraoperative monitors, validates clinical observations, and aids in guiding patient management. Most, however, felt that tissue oximetry alone is not enough to inform management changes. CONCLUSIONS: Near-infrared spectroscopy-based tissue oximetry frequently used was by CCAS members, but with significant variations in clinical application.

Measuring "pain load" during general anesthesia.

Introduction: Functional near-infrared spectroscopy (fNIRS) allows for ongoing measures of brain functions during surgery. The ability to evaluate cumulative effects of painful/nociceptive events under general anesthesia remains a challenge. Through observing signal differences and setting boundaries for when observed events are known to produce pain/nociception, a program can trigger when the concentration of oxygenated hemoglobin goes beyond ±0.3 mM from 25 s after standardization. Method: fNIRS signals were retrieved from patients undergoing knee surgery for anterior cruciate ligament repair under general anesthesia. Continuous fNIRS measures were measured from the primary somatosensory cortex (S1), which is known to be involved in evaluation of nociception, and the medial polar frontal cortex (mPFC), which are both involved in higher cortical functions (viz. cognition and emotion). Results: A ±0.3 mM threshold for painful/nociceptive events was observed during surgical incisions at least twice, forming a basis for a potential near-real-time recording of pain/nociceptive events. Evidence through observed true positives in S1 and true negatives in mPFC are linked through statistically significant correlations and this threshold. Conclusion: Our results show that standardizing and observing concentrations over 25 s using the ±0.3 mM threshold can be an arbiter of the continuous number of incisions performed on a patient, contributing to a potential intraoperative pain load index that correlates with post-operative levels of pain and potential pain chronification.

Preventing pediatric chronic postsurgical pain: Time for increased rigor.

Chronic postsurgical pain (CPSP) results from a cascade of events in the peripheral and central nervous systems following surgery. Several clinical predictors, including the prior pain state, premorbid psychological state (e.g., anxiety, catastrophizing), intraoperative surgical load (establishment of peripheral and central sensitization), and acute postoperative pain management, may contribute to the patient's risk of developing CPSP. However, research on the neurobiological and biobehavioral mechanisms contributing to pediatric CPSP and effective preemptive/treatment strategies are still lacking. Here we evaluate the perisurgical process by identifying key problems and propose potential solutions for the pre-, intra-, and postoperative pain states to both prevent and manage the transition of acute to chronic pain. We propose an eight-step process involving preemptive and preventative analgesia, behavioral interventions, and the use of biomarkers (brain-based, inflammatory, or genetic) to facilitate timely evaluation and treatment of premorbid psychological factors, ongoing surgical pain, and postoperative pain to provide an overall improved outcome. By achieving this, we can begin to establish personalized precision medicine for children and adolescents presenting to surgery and subsequent treatment selection.

La douleur chronique post-chirurgicale (DCPC) résulte d'une cascade d'événements dans les systèmes nerveux central et périphérique suite à une intervention chirurgicale. Plusieurs prédicteurs cliniques, y compris l'état douloureux antérieur, l'état psychologique prémorbide (p. ex., anxiété, catastrophisme), la charge chirurgicale peropératoire (établissement d'une sensibilisation périphérique et centrale) et la prise en charge de la douleur postopératoire aiguë, peuvent contribuer au risque du patient de développer une DCPC. Cependant, la recherche sur les mécanismes neurobiologiques et biocomportementaux contribuant à la DCPC pédiatrique et sur les stratégies de prévention et de traitement efficaces font encore défaut. Nous évaluons ici le processus périchirurgical en cernant les problémes clés et en proposant des solutions potentielles pour les états douloureux pré, per et postopératoires afin de prévenir et de prendre en charge la transition de la douleur aiguë à la douleur chronique. Nous proposons un processus en huit étapes impliquant l'analgésie préemptive et préventive, les interventions comportementales et l'utilisation de biomarqueurs (cérébraux, inflammatoires ou génétiques) pour faciliter l'évaluation et le traitement opportuns des facteurs psychologiques prémorbides, de la douleur chirurgicale persistante et de la douleur postopératoire afin d'améliorer le résultat global. En y parvenant, nous pouvons commencer à établir une médecine de précision personnalisée pour les enfants et les adolescents qui subissent une intervention chirurgicale et à la sélection du traitement qui s'ensuit.

Brain-based measures of nociception during general anesthesia with remifentanil: A randomized controlled trial.

BACKGROUND: Catheter radiofrequency (RF) ablation for cardiac arrhythmias is a painful procedure. Prior work using functional near-infrared spectroscopy (fNIRS) in patients under general anesthesia has indicated that ablation results in activity in pain-related cortical regions, presumably due to inadequate blockade of afferent nociceptors originating within the cardiac system. Having an objective brain-based measure for nociception and analgesia may in the future allow for enhanced analgesic control during surgical procedures. Hence, the primary aim of this study is to demonstrate that the administration of remifentanil, an opioid widely used during surgery, can attenuate the fNIRS cortical responses to cardiac ablation. METHODS AND FINDINGS: We investigated the effects of continuous remifentanil on cortical hemodynamics during cardiac ablation under anesthesia. In a randomized, double-blinded, placebo (PL)-controlled trial, we examined 32 pediatric patients (mean age of 15.8 years,16 females) undergoing catheter ablation for cardiac arrhythmias at the Cardiology Department of Boston Children's Hospital from October 2016 to March 2020; 9 received 0.9% NaCl, 12 received low-dose (LD) remifentanil (0.25 mcg/kg/min), and 11 received high-dose (HD) remifentanil (0.5 mcg/kg/min). The hemodynamic changes of primary somatosensory and prefrontal cortices were recorded during surgery using a continuous wave fNIRS system. The primary outcome measures were the changes in oxyhemoglobin concentration (NadirHbO, i.e., lowest oxyhemoglobin concentration and PeakHbO, i.e., peak change and area under the curve) of medial frontopolar cortex (mFPC), lateral prefrontal cortex (lPFC) and primary somatosensory cortex (S1) to ablation in PL versus remifentanil groups. Secondary measures included the fNIRS response to an auditory control condition. The data analysis was performed on an intention-to-treat (ITT) basis. Remifentanil group (dosage subgroups combined) was compared with PL, and a post hoc analysis was performed to identify dose effects. There were no adverse events. The groups were comparable in age, sex, and number of ablations. Results comparing remifentanil versus PL show that PL group exhibit greater NadirHbO in inferior mFPC (mean difference (MD) = 1.229, 95% confidence interval [CI] = 0.334, 2.124, p < 0.001) and superior mFPC (MD = 1.206, 95% CI = 0.303, 2.109, p = 0.001) and greater PeakHbO in inferior mFPC (MD = -1.138, 95% CI = -2.062, -0.214, p = 0.002) and superior mFPC (MD = -0.999, 95% CI = -1.961, -0.036, p = 0.008) in response to ablation. S1 activation from ablation was greatest in PL, then LD, and HD groups, but failed to reach significance, whereas lPFC activation to ablation was similar in all groups. Ablation versus auditory stimuli resulted in higher PeakHbO in inferior mFPC (MD = 0.053, 95% CI = 0.004, 0.101, p = 0.004) and superior mFPC (MD = 0.052, 95% CI = 0.013, 0.091, p < 0.001) and higher NadirHbO in posterior superior S1 (Pos. SS1; MD = -0.342, 95% CI = -0.680, -0.004, p = 0.007) during ablation of all patients. Remifentanil group had smaller NadirHbO in inferior mFPC (MD = 0.098, 95% CI = 0.009, 0.130, p = 0.003) and superior mFPC (MD = 0.096, 95% CI = 0.008, 0.116, p = 0.003) and smaller PeakHbO in superior mFPC (MD = -0.092, 95% CI = -0.680, -0.004, p = 0.007) during both the stimuli. Study limitations were small sample size, motion from surgery, indirect measure of nociception, and shallow penetration depth of fNIRS only allowing access to superficial cortical layers. CONCLUSIONS: We observed cortical activity related to nociception during cardiac ablation under general anesthesia with remifentanil. It highlights the potential of fNIRS to provide an objective pain measure in unconscious patients, where cortical-based measures may be more accurate than current evaluation methods. Future research may expand on this application to produce a real-time indication of pain that will aid clinicians in providing immediate and adequate pain treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02703090.

fNIRS brain measures of ongoing nociception during surgical incisions under anesthesia.

Significance: Functional near-infrared spectroscopy (fNIRS) has evaluated pain in awake and anesthetized states. Aim: We evaluated fNIRS signals under general anesthesia in patients undergoing knee surgery for anterior cruciate ligament repair. Approach: Patients were split into groups: those with regional nerve block (NB) and those without (non-NB). Continuous fNIRS measures came from three regions: the primary somatosensory cortex (S1), known to be involved in evaluation of nociception, the lateral prefrontal cortex (BA9), and the polar frontal cortex (BA10), both involved in higher cortical functions (such as cognition and emotion). Results: Our results show three significant differences in fNIRS signals to incision procedures between groups: (1) NB compared with non-NB was associated with a greater net positive hemodynamic response to pain procedures in S1; (2) dynamic correlation between the prefrontal cortex (PreFC) and S1 within 1 min of painful procedures are anticorrelated in NB while positively correlated in non-NB; and (3) hemodynamic measures of activation were similar at two separate time points during surgery (i.e., first and last incisions) in PreFC and S1 but showed significant differences in their overlap. Comparing pain levels immediately after surgery and during discharge from postoperative care revealed no significant differences in the pain levels between NB and non-NB. Conclusion: Our data suggest multiple pain events that occur during surgery using devised algorithms could potentially give a measure of "pain load." This may allow for evaluation of central sensitization (i.e., a heightened state of the nervous system where noxious and non-noxious stimuli is perceived as painful) to postoperative pain levels and the resulting analgesic consumption. This evaluation could potentially predict postsurgical chronic neuropathic pain.

Rhythmic Change of Cortical Hemodynamic Signals Associated with Ongoing Nociception in Awake and Anesthetized Individuals: An Exploratory Functional Near Infrared Spectroscopy Study.

BACKGROUND: Patients undergoing surgical procedures are vulnerable to repetitive evoked or ongoing nociceptive barrage. Using functional near infrared spectroscopy, the authors aimed to evaluate the cortical hemodynamic signal power changes during ongoing nociception in healthy awake volunteers and in surgical patients under general anesthesia. The authors hypothesized that ongoing nociception to heat or surgical trauma would induce reductions in the power of cortical low-frequency hemodynamic oscillations in a similar manner as previously reported using functional magnetic resonance imaging for ongoing pain. METHODS: Cortical hemodynamic signals during noxious stimuli from the fontopolar cortex were evaluated in two groups: group 1, a healthy/conscious group (n = 15, all males) where ongoing noxious and innocuous heat stimulus was induced by a contact thermode to the dorsum of left hand; and group 2, a patient/unconscious group (n = 13, 3 males) receiving general anesthesia undergoing knee surgery. The fractional power of low-frequency hemodynamic signals was compared across stimulation conditions in the healthy awake group, and between patients who received standard anesthesia and those who received standard anesthesia with additional regional nerve block. RESULTS: A reduction of the total fractional power in both groups-specifically, a decrease in the slow-5 frequency band (0.01 to 0.027 Hz) of oxygenated hemoglobin concentration changes over the frontopolar cortex-was observed during ongoing noxious stimuli in the healthy awake group (paired t test, P = 0.017; effect size, 0.70), and during invasive procedures in the surgery group (paired t test, P = 0.003; effect size, 2.16). The reduction was partially reversed in patients who received a regional nerve block that likely diminished afferent nociceptive activity (two-sample t test, P = 0.002; effect size, 2.34). CONCLUSIONS: These results suggest common power changes in slow-wave cortical hemodynamic oscillations during ongoing nociceptive processing in conscious and unconscious states. The observed signal may potentially promote future development of a surrogate signal to assess ongoing nociception under general anesthesia.

Cerebral Emboli Monitoring Using Transcranial Doppler Ultrasonography in Adults and Children: A Review of the Current Technology and Clinical Applications in the Perioperative and Intensive Care Setting.

Transcranial Doppler (TCD) ultrasonography is the only noninvasive bedside technology for the detection and monitoring of cerebral embolism. TCD may identify patients at risk of acute and chronic neurologic injury from gaseous or solid emboli. Importantly, a window of opportunity for intervention-to eliminate the source of the emboli and thereby prevent subsequent development of a clinical or subclinical stroke-may be identified using TCD. In this review, we discuss the application of TCD sonography in the perioperative and intensive care setting in adults and children known to be at increased risk of cerebral embolism. The major challenge for evaluation of emboli, especially in children, is the need to establish the ground truth and define true emboli identified by TCD. This requires the development and validation of a predictive TCD emboli monitoring technique so that appropriately designed clinical studies intended to identify specific modifiable factors and develop potential strategies to reduce pathologic cerebral embolic burden can be performed.

NIRS measures in pain and analgesia: Fundamentals, features, and function.

Current pain assessment techniques based only on clinical evaluation and self-reports are not objective and may lead to inadequate treatment. Having a functional biomarker will add to the clinical fidelity, diagnosis, and perhaps improve treatment efficacy in patients. While many approaches have been deployed in pain biomarker discovery, functional near-infrared spectroscopy (fNIRS) is a technology that allows for non-invasive measurement of cortical hemodynamics. The utility of fNIRS is especially attractive given its ability to detect specific changes in the somatosensory and high-order cortices as well as its ability to measure (1) brain function similar to functional magnetic resonance imaging, (2) graded responses to noxious and innocuous stimuli, (3) analgesia, and (4) nociception under anesthesia. In this review, we evaluate the utility of fNIRS in nociception/pain with particular focus on its sensitivity and specificity, methodological advantages and limitations, and the current and potential applications in various pain conditions. Everything considered, fNIRS technology could enhance our ability to evaluate evoked and persistent pain across different age groups and clinical populations.

Sensitivity of a Next-Generation NIRS Device to Detect Low Mixed Venous Oxyhemoglobin Saturations in the Single Ventricle Population.

Regional cerebral oxygenation index (rSO2) based on near-infrared spectroscopy (NIRS) is frequently used to detect low venous oxyhemoglobin saturation (ScvO2). We compared the performance of 2 generations of NIRS devices. Clinically obtained, time-matched cerebral rSO2 and ScvO2 values were compared in infants monitored with the FORE-SIGHT (n = 73) or FORE-SIGHT ELITE (n = 47) by linear regression and Bland-Altman analyses. In both devices, cerebral rSO2 correlated poorly with measured ScvO2 (FORE-SIGHT partial correlation 0.50 [95% confidence interval {CI}, 0.40-0.58]; FORE-SIGHT ELITE partial correlation 0.47 [0.39-0.55]) and mean bias was +8 (standard deviation [SD] 13.2) for FORE-SIGHT and +14 (SD 12.5) for FORE-SIGHT ELITE. When ScvO2 was <30%, rSO2 was <40 in 8% of FORE-SIGHT ELITE readings. Future NIRS should be validated in more hypoxic cohorts.

A Time-Frequency Approach for Cerebral Embolic Load Monitoring.

OBJECTIVE: To enable reliable cerebral embolic load monitoring from high-intensity transient signals (HITS) recorded with single-channel transcranial Doppler (TCD) ultrasound. METHODS: We propose a HITS detection and characterization method using a weighted-frequency Fourier linear combiner that estimates baseline Doppler signal power. An adaptive threshold is determined by examining the Doppler signal power variance about the baseline estimate, and HITS are extracted if their Doppler power exceeds this threshold. As signatures from multiple emboli may be superimposed, we analyze the detected HITS in the time-frequency (TF) domain to segment the signals into individual emboli. A logistic regression classification approach is employed to classify HITS into emboli or artifacts. Data were collected using a commercial TCD device with emboli-detection capabilities from 12 children undergoing mechanical circulatory support or cardiac catheterization. A subset of 696 HITS were reviewed, annotated, and split into training and testing sets for developing and evaluating the HITS classification algorithm. RESULTS: The classifier yielded 98% and 96% sensitivity for 100% specificity on training and testing data, respectively. The TF approach decomposed 38% of candidate embolic signals into two or more embolic events that ultimately account for 69% of the overall embolic counts. Our processing pipeline resulted in highly accurate emboli identification and produced emboli counts that were lower (by a median of 64%) compared to the commercial ultrasound system's estimates. SIGNIFICANCE: Using only single-channel, single-frequency Doppler ultrasound, the proposed method enables sensitive detection and segmentation of embolic signatures. Our approach paves the way toward accurate real-time cerebral emboli monitoring.

Near-Infrared Spectroscopy in Pediatric Congenital Heart Disease.

Near-infrared spectroscopy (NIRS) is widely used to monitor tissue oxygenation in the pediatric cardiac surgical population. Clinicians who use NIRS must understand the underlying measurement principles in order to interpret and use this monitoring modality appropriately. The aims of this narrative review are to provide a brief overview of NIRS technology, discuss the normative and critical values of cerebral and somatic tissue oxygen saturation and the interpretation of these values, present the clinical studies (and their limitations) of NIRS as a perioperative monitoring modality in the pediatric congenital heart disease population, and introduce the emerging and future applications of NIRS.

Validation of a Second-Generation Near-Infrared Spectroscopy Monitor in Children With Congenital Heart Disease.

BACKGROUND: Cerebral oximetry using near-infrared spectroscopy is a noninvasive optical technology to detect cerebral hypoxia-ischemia and develop interventions to prevent and ameliorate hypoxic brain injury. Cerebral oximeters are calibrated and validated by comparison of the near-infrared spectroscopy-measured cerebral O2 saturation (SctO2) to a "field" or reference O2 saturation (REF CX) calculated as a weighted average from arterial and jugular bulb oxygen saturations. In this study, we calibrated and validated the second-generation, 5 wavelength, FORE-SIGHT Elite with the medium sensor (source-detector separation 12 and 40 mm) for measurement of SctO2 in children with congenital heart disease. METHODS: After institutional review board approval and written informed consent, 63 children older than 1 month and ≥2.5 kg scheduled for cardiac catheterization were enrolled. Self-adhesive FORE-SIGHT Elite medium sensors were placed on the right and left sides of the forehead. Blood samples for calculation of REF CX were drawn simultaneously from the aorta or femoral artery and the jugular bulb before (T1) and shortly after (T2) baseline hemodynamic measurements. FORE-SIGHT Elite SctO2 measurements were compared to the REF CX (REF CX = [0.3 SaO2] + [0.7 SjbO2]) using Deming regression, least squares linear regression, and Bland-Altman analysis. RESULTS: Sixty-one subjects (4.5 [standard deviation 4.4] years of age; 17 [standard deviation 13] kg, male 56%) completed the study protocol. Arterial oxygen saturation ranged from 64.7% to 99.1% (median 96.0%), jugular bulb venous oxygen saturation from 34.1% to 88.1% (median 68.2%), the REF CX from 43.8% to 91.4% (median 76.9%), and the SctO2 from 47.8% to 90.8% (median 76.3%). There was a high degree of correlation in SctO2 between the right and left sensors at a given time point (within subject between sensor correlation r = 0.91 and 95% confidence interval [CI], 0.85-0.94) or between T1 and T2 for the right and left sensors (replicates, within subject between time point correlation r = 0.95 and 95% CI, 0.92-0.96). By Deming regression, the estimated slope was 0.966 (95% CI, 0.786-1.147; P = .706 for testing against null hypothesis of slope = 1) with a y intercept of 2.776 (95% CI, -11.102 to 16.654; P = .689). The concordance correlation coefficient was 0.873 (95% CI, 0.798-0.922). Bland-Altman analysis for agreement between SctO2 and REF CX that accounted for repeated measures (both in times and sensors) found a bias of -0.30% (95% limits of agreement: -10.56% to 9.95%). CONCLUSIONS: This study calibrated and validated the FORE-SIGHT Elite tissue oximeter to accurately measure SctO2 in pediatric patients with the medium sensor.

Cerebral near-infrared spectroscopy insensitively detects low cerebral venous oxygen saturations after stage 1 palliation.

BACKGROUND: Measurement of cerebral venous oxyhemoglobin saturation (ScvO2) is considered a gold standard in assessing the adequacy of tissue oxygen delivery (DO2) after the stage 1 palliation (S1P), with SvO2 <30% often representing severely compromised DO2. Regional oxygenation index (rSO2) based on near-infrared resonance spectroscopy (NIRS) frequently is used to screen for compromised DO2, although its sensitivity to detect severe abnormalities in SvO2 is uncertain. METHODS: ScvO2 was measured by co-oximetry from the internal jugular vein as clinically indicated in 73 neonates after S1P. These values were compared with cerebral rSO2 (FORE-SIGHT; CASMED) via mixed effects model linear regression, Bland-Altman analysis, and sensitivity analysis. Because NIRS devices measure a composite of arterial and venous blood, we calculated an rSO2-based ScvO2 designed to remove arterial contamination from the rSO2 signal: rSO2-based ScvO2 = (rSO2 - arterial oxygen saturation × 0.3)/0.7. RESULTS: Among 520 time-matched pairs of ScvO2 and cerebral rSO2, the slope of the relationship between rSO2 and ScvO2 (after we adjusted for effects of hemoglobin) was 0.37 ± 0.04 with only modest correlation (r2 = 0.39), and mean bias of +8.26. When ScvO2 was <30%, cerebral rSO2 was <30 in less than 1%, <40 less than 1%, and <50 in 45.7% of data points; specificity of rSO2 in the same range is >99%. Correction of rSO2 for arterial contamination significantly decreased mean bias (+3.03) and improved the sensitivity of rSO2 to detect ScvO2 <30 to 6.5% for rSO2 <30, 29% for rSO2 <40, and 77.4% for rSO2 <50. CONCLUSIONS: Cerebral rSO2 in isolation should not be used to detect low ScvO2, because its sensitivity is low, although correction of rSO2 for arterial contamination may improve sensitivity. Cerebral rSO2 of 50 or greater should not be considered reassuring, though values below 30 are specific for low ScvO2.

Cerebral Oxygen Saturation in Children With Congenital Heart Disease and Chronic Hypoxemia.

BACKGROUND: Increased hemoglobin (Hb) concentration accompanying hypoxemia is a compensatory response to maintain tissue oxygen delivery. Near infrared spectroscopy (NIRS) is used clinically to detect abnormalities in the balance of cerebral tissue oxygen delivery and consumption, including in children with congenital heart disease (CHD). Although NIRS-measured cerebral tissue O2 saturation (ScO2) correlates with arterial oxygen saturation (SaO2), jugular bulb O2 saturation (SjbO2), and Hb, little data exist on the interplay between these factors and cerebral O2 extraction (COE). This study investigated the associations of ScO2 and ΔSaO2-ScO2 with SaO2 and Hb and verified the normal range of ScO2 in children with CHD. METHODS: Children undergoing cardiac catheterization for CHD were enrolled in a calibration and validation study of the FORE-SIGHT NIRS monitor. Two pairs of simultaneous arterial and jugular bulb samples were drawn for co-oximetry, calculation of a reference ScO2 (REF CX), and estimation of COE. Pearson correlation and linear regression were used to determine relationships between O2 saturation parameters and Hb. Data were also analyzed according to diagnostic group defined as acyanotic (SaO2 ≥ 90%) and cyanotic (SaO2 < 90%). RESULTS: Of 65 children studied, acceptable jugular bulb samples (SjbO2 absolute difference between samples ≤10%) were obtained in 57 (88%). The ΔSaO2-SjbO2, ΔSaO2-ScO2, and ΔSaO2-REF CX were positively correlated with SaO2 and negatively correlated with Hb (all P < .001). Although by diagnostic group ScO2 differed statistically (P = .002), values in the cyanotic patients were within the range considered normal (69% ± 6%). COE estimated by the difference between arterial and jugular bulb O2 content (ΔCaO2-CjbO2, mL O2/100 mL) was not different for cyanotic and acyanotic patients (P = .10), but estimates using ΔSaO2-SjbO2, ΔSaO2-ScO2, or ΔSaO2-ScO2/SaO2 were significantly different between the cyanotic and acyanotic children (P < .001). CONCLUSIONS: Children with adequately compensated chronic hypoxemia appear to have ScO2 values within the normal range. The ΔSaO2-ScO2 is inversely related to Hb, with the implication that in the presence of reduced Hb, particularly if coupled with a decreased cardiac output, the ScO2 can fall to values associated with brain injury in laboratory studies.

Non-invasive Assessment of Cerebral Blood Flow and Oxygen Metabolism in Neonates during Hypothermic Cardiopulmonary Bypass: Feasibility and Clinical Implications.

The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management.

Cerebral High-Intensity Transient Signals during Pediatric Cardiac Catheterization: A Pilot Study Using Transcranial Doppler Ultrasonography.

BACKGROUND AND PURPOSE: Cerebral emboli are one potential cause of acute brain injury in children with congenital heart disease (CHD) undergoing cardiac catheterization. In this pilot study using transcranial Doppler (TCD) ultrasonography, we sought to evaluate the incidence, burden, and circumstances of cerebral high-intensity transient signals (HITS), presumably representing emboli, during pediatric cardiac catheterization. METHODS: Emboli monitoring of the right middle cerebral artery was performed in five children. HITS, counted offline, were defined as unidirectional signals associated with audible "chirp" and sinusoidal correlation. HITS were grouped as single, >10 HITS ("cluster"), or HITS "with curtain effect" per 3-5 cardiac cycles. Cerebral blood flow velocity (CBFV) and pulsatility index (PI) were recorded after anesthetic induction (baseline). RESULTS: Total HITS in the cohort was 1,697 (790 single HITS, 606 HITS within clusters, and 301 HITS within curtains). HITS in clusters and curtains comprised 53% (907/1,697) of total HITS, and occurred in 44 clusters/curtains. Events associated with clusters/curtains included left ventricular angiography (39%; 17/44), right ventricular angiography (16%; 7/44), device placement (16%; 7/44), heparin bolus (9%; 4/44), pulmonary artery angiography (9%; 4/44), venous access (5%; 2/44), right atrial angiography (2%; 1/44), arterial access (2%; 1/44), and hemodynamic measurements (2%; 1/44). No patient had clinically detectable neurologic injury. CONCLUSIONS: HITS are common during pediatric cardiac catheterization, and associated with procedural factors. Whether curtains/clusters are worse than single, repetitive HITS is unknown. Larger studies are needed to determine whether HITS are a marker of risk of neurologic injury from emboli during pediatric cardiac catheterization.

Anesthesia, brain changes, and behavior: Insights from neural systems biology.

Long-term consequences of anesthetic exposure in humans are not well understood. It is possible that alterations in brain function occur beyond the initial anesthetic administration. Research in children and adults has reported cognitive and/or behavioral changes after surgery and general anesthesia that may be short lived in some patients, while in others, such changes may persist. The changes observed in humans are corroborated by a large body of evidence from animal studies that support a role for alterations in neuronal survival (neuroapoptosis) or structure (altered dendritic and glial morphology) and later behavioral deficits at older age after exposure to various anesthetic agents during fetal or early life. The potential of anesthetics to induce long-term alterations in brain function, particularly in vulnerable populations, warrants investigation. In this review, we critically evaluate the available preclinical and clinical data on the developing and aging brain, and in known vulnerable populations to provide insights into potential changes that may affect the general population of patients in a more, subtle manner. In addition this review summarizes underlying processes of how general anesthetics produce changes in the brain at the cellular and systems level and the current understanding underlying mechanisms of anesthetics agents on brain systems. Finally, we present how neuroimaging techniques currently emerge as promising approaches to evaluate and define changes in brain function resulting from anesthesia, both in the short and the long-term.