Delayed Surgical Closure of the Patent Ductus Arteriosus: Does the Brain Pay the Price?

OBJECTIVE: To investigate the relation between duration of hemodynamically significant patent ductus arteriosus (PDA), cerebral oxygenation, magnetic resonance imaging-determined brain growth, and 2-year neurodevelopmental outcome in a cohort of infants born preterm whose duct was closed surgically. STUDY DESIGN: Infants born preterm at <30 weeks of gestational age who underwent surgical ductal closure between 2008 and 2018 (n = 106) were included in this observational study. Near infrared spectroscopy-monitored cerebral oxygen saturation during and up to 24 hours after ductal closure and a Bayley III developmental test at the corrected age of 2 years is the institutional standard of care for this patient group. Infants also had magnetic resonance imaging at term-equivalent age. RESULTS: In total, 90 infants fulfilled the inclusion criteria (median [range]: 25.9 weeks [24.0-28.9]; 856 g [540-1350]. Days of a PDA ranged from 1 to 41. Multivariable linear regression analysis showed that duration of a PDA negatively influenced cerebellar growth and motor and cognitive outcome at 2 years of corrected age. CONCLUSIONS: Prolonged duration of a PDA in this surgical cohort is associated with reduced cerebellar growth and suboptimal neurodevelopmental outcome.

Brain injury and long-term outcome after neonatal surgery for non-cardiac congenital anomalies.

BACKGROUND: There is growing evidence that neonatal surgery for non-cardiac congenital anomalies (NCCAs) in the neonatal period adversely affects long-term neurodevelopmental outcome. However, less is known about acquired brain injury after surgery for NCCA and abnormal brain maturation leading to these impairments. METHODS: A systematic search was performed in PubMed, Embase, and The Cochrane Library on May 6, 2022 on brain injury and maturation abnormalities seen on magnetic resonance imaging (MRI) and its associations with neurodevelopment in neonates undergoing NCCA surgery the first month postpartum. Rayyan was used for article screening and ROBINS-I for risk of bias assessment. Data on the studies, infants, surgery, MRI, and outcome were extracted. RESULTS: Three eligible studies were included, reporting 197 infants. Brain injury was found in n = 120 (50%) patients after NCCA surgery. Sixty (30%) were diagnosed with white matter injury. Cortical folding was delayed in the majority of cases. Brain injury and delayed brain maturation was associated with a decrease in neurodevelopmental outcome at 2 years of age. CONCLUSIONS: Surgery for NCCA was associated with high risk of brain injury and delay in maturation leading to delay in neurocognitive and motor development. However, more research is recommended for strong conclusions in this group of patients. IMPACT: Brain injury was found in 50% of neonates who underwent NCCA surgery. NCCA surgery is associated with a delay in cortical folding. There is an important research gap regarding perioperative brain injury and NCCA surgery.

Neuromonitoring in neonatal critical care part I: neonatal encephalopathy and neonates with possible seizures.

The blooming of neonatal neurocritical care over the last decade reflects substantial advances in neuromonitoring and neuroprotection. The most commonly used brain monitoring tools in the neonatal intensive care unit (NICU) are amplitude integrated EEG (aEEG), full multichannel continuous EEG (cEEG), and near-infrared spectroscopy (NIRS). While some published guidelines address individual tools, there is no consensus on consistent, efficient, and beneficial use of these modalities in common NICU scenarios. This work reviews current evidence to assist decision making for best utilization of neuromonitoring modalities in neonates with encephalopathy or with possible seizures. Neuromonitoring approaches in extremely premature and critically ill neonates are discussed separately in the companion paper. IMPACT: Neuromonitoring techniques hold promise for improving neonatal care. For neonatal encephalopathy, aEEG can assist in screening for eligibility for therapeutic hypothermia, though should not be used to exclude otherwise eligible neonates. Continuous cEEG, aEEG and NIRS through rewarming can assist in prognostication. For neonates with possible seizures, cEEG is the gold standard for detection and diagnosis. If not available, aEEG as a screening tool is superior to clinical assessment alone. The use of seizure detection algorithms can help with timely seizures detection at the bedside.

Neuromonitoring in neonatal critical care part II: extremely premature infants and critically ill neonates.

Neonatal intensive care has expanded from cardiorespiratory care to a holistic approach emphasizing brain health. To best understand and monitor brain function and physiology in the neonatal intensive care unit (NICU), the most commonly used tools are amplitude-integrated EEG, full multichannel continuous EEG, and near-infrared spectroscopy. Each of these modalities has unique characteristics and functions. While some of these tools have been the subject of expert consensus statements or guidelines, there is no overarching agreement on the optimal approach to neuromonitoring in the NICU. This work reviews current evidence to assist decision making for the best utilization of these neuromonitoring tools to promote neuroprotective care in extremely premature infants and in critically ill neonates. Neuromonitoring approaches in neonatal encephalopathy and neonates with possible seizures are discussed separately in the companion paper. IMPACT: For extremely premature infants, NIRS monitoring has a potential role in individualized brain-oriented care, and selective use of aEEG and cEEG can assist in seizure detection and prognostication. For critically ill neonates, NIRS can monitor cerebral perfusion, oxygen delivery, and extraction associated with disease processes as well as respiratory and hypodynamic management. Selective use of aEEG and cEEG is important in those with a high risk of seizures and brain injury. Continuous multimodal monitoring as well as monitoring of sleep, sleep-wake cycling, and autonomic nervous system have a promising role in neonatal neurocritical care.

Normal regional tissue oxygen saturation in neonates: a systematic qualitative review.

BACKGROUND: The aim of this systematic qualitative review was to give an overview of reference ranges defined as normal values or centile charts of regional tissue oxygen saturation measured by near-infrared spectroscopy (NIRS) in term and preterm neonates. METHODS: A systematic search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was performed. Additional articles were identified by manual search of cited references. Only human studies in neonates were included. RESULTS: Nineteen studies were identified. Eight described regional tissue oxygen saturation during fetal-to-neonatal transition, six during the first 3 days after birth, four during the first 7 days after birth, and one during the first 8 weeks after birth. Nine described regional tissue oxygen saturation in term, nine in preterm neonates, and one in both. Eight studies published centile charts for cerebral regional tissue oxygen saturation, and only five included large cohorts of infants. Eleven studies described normal values for cerebral, muscle, renal, and abdominal regional tissue oxygen saturation, the majority with small sample sizes. Four studies of good methodological quality were identified describing centile charts of cerebral regional tissue oxygen saturation. CONCLUSIONS: In clinical settings, quality centile charts are available and should be the preferred method when using NIRS monitoring. IMPACT: Near-infrared spectroscopy (NIRS) enables a bed-side non-invasive continuous monitoring of tissue oxygenation. When using NIRS monitoring in a clinical setting, centile charts with good quality are available and should be preferred to normal values. High-quality reference ranges of regional tissue oxygenation in term and preterm born neonates are an important step toward routine clinical application of NIRS.

Brain Activity and Cerebral Oxygenation After Perinatal Arterial Ischemic Stroke Are Associated With Neurodevelopment.

Background and Purpose- In infants with perinatal arterial ischemic stroke (PAIS), early prognosis of neurodevelopmental outcome is important to adequately inform parents and caretakers. Early continuous neuromonitoring after PAIS may improve early prognosis. Our aim was to study early cerebral electrical activity and oxygenation measured by amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in term neonates with PAIS and relate these to the development of cerebral palsy and cognitive deficit. Methods- aEEG patterns and regional cerebral oxygen saturation (rScO2) levels of both hemispheres were studied for 120 hours from the first clinical symptoms of PAIS (ie, seizures) onward. Multivariable analyses were used to investigate the association between aEEG, near-infrared spectroscopy, clinical variables, and neurodevelopmental outcome. Results- In 52 patients with PAIS (gestational age, 40.4±1.4 weeks; birth weight, 3282±479 g), median time to a continuous background pattern was longer in the ipsilesional compared with the contralesional hemisphere (13.5 versus 10.0 hours; P<0.05). rScO2 decreased over time in both hemispheres but less in the ipsilesional one, resulting in a rScO2 asymmetry ratio of 4.5% (interquartile range, -4.3% to 5.9%; P<0.05) between hemispheres from day 3 after symptoms onward. Both time to normal background pattern and asymmetry in rScO2 were negatively affected by gestational age, size of the PAIS, use of antiepileptic drugs, and mechanical ventilation. After correction for size of the PAIS on magnetic resonance imaging, a slower recovery of background pattern on ipsilesional aEEG and increased rScO2 asymmetry between hemispheres was related with an increased risk for cognitive deficit (<-1 SD) at a median of 24.0 (interquartile range, 18.4-24.4) months of age. Conclusions- Recovery of background pattern on aEEG and cerebral oxygenation are both affected by PAIS and related to neurocognitive development. Both measurements may provide valuable early prognostic information. Additionally, monitoring cerebral activity and oxygenation may be useful in identifying infants eligible for early neuroprotective interventions and to detect early effects of these interventions.

Low Cerebral Oxygenation in Preterm Infants Is Associated with Adverse Neurodevelopmental Outcome.

OBJECTIVE: To assess whether high and low levels of cerebral oxygenation (regional cerebral oxygenation [rScO2]) in infants born at <32 weeks of gestation were associated with adverse long-term outcome. STUDY DESIGN: Observational cohort study including preterm infants born at <32 weeks of gestation at the Wilhelmina Children's Hospital, The Netherlands, between April 2006 and April 2013. The rScO2 was continuously monitored for 72 hours after birth using near-infrared spectroscopy. Outcome was assessed at 15 and 24 months of corrected age by certified investigators. An unfavorable composite outcome was defined as an outcome score below -1 SD or death. Various rScO2 thresholds were explored. RESULTS: In total, 734 infants were eligible for analysis, 60 of whom died. Associations with an unfavorable cognitive outcome in multivariable analysis were comparable for time spent with a rScO2 below 55% and -1.5 SD (according to published reference values), with an OR of 1.4 (CI 1.1-1.7) for 20% of time below either threshold. Results at 15 months were comparable with results at 24 months. Results were not statistically significant for thresholds defining high values of rScO2. The composite motor outcome was not significantly related to either low or high values or rScO2. CONCLUSIONS: Low, but not high, rScO2 was associated with an unfavorable cognitive outcome. This suggests the use of a threshold of rScO2 <55% for future clinical studies when using adult near-infrared sensors (rScO2 <65% for neonatal sensors, approximately).

No neurodevelopmental benefit of cerebral oximetry in the first randomised trial (SafeBoosC II) in preterm infants during the first days of life.

AIM: Cerebral hypoxia has been associated with neurodevelopmental impairment. We studied whether reducing cerebral hypoxia in extremely preterm infants during the first 72 hours of life affected neurological outcomes at two years of corrected age. METHODS: In 2012-2013, the phase II randomised Safeguarding the Brains of our smallest Children trial compared visible cerebral near-infrared spectroscopy (NIRS) monitoring in an intervention group and blinded NIRS monitoring in a control group. Cerebral hypoxia was significantly reduced in the intervention group. We followed up 115 survivors from eight European centres at two years of corrected age, by conducting a medical examination and assessing their neurodevelopment with the Bayley Scales of Infant and Toddler Development, Second or Third Edition, and the parental Ages and Stages Questionnaire (ASQ). RESULTS: There were no differences between the intervention (n = 65) and control (n = 50) groups with regard to the mean mental developmental index (89.6 ± 19.5 versus 88.4 ± 14.7, p = 0.77), ASQ score (215 ± 58 versus 213 ± 58, p = 0.88) and the number of children with moderate-to-severe neurodevelopmental impairment (10 versus six, p = 0.58). CONCLUSION: Cerebral NIRS monitoring was not associated with long-term benefits or harm with regard to neurodevelopmental outcome at two years of corrected age.

Mortality in Robin sequence: identification of risk factors.

Although Robin sequence (RS) is a well-known phenomenon, it is still associated with considerable morbidity and even mortality. The purposes of this study were to gain greater insight into the mortality rate and identify risk factors associated with mortality in RS. We retrospectively reviewed all RS infants followed at the Wilhelmina Children's Hospital from 1995 to 2016. Outcome measurements were death and causes of death. The authors identified 103 consecutive RS infants with a median follow-up of 8.6 years (range 0.1-21.9 years). Ten of the 103 infants (10%) died at a median age of 0.8 years (range 0.1-5.9 years). Nine of these ten infants (90%) were diagnosed with an associated syndrome. Of these, seven infants died of respiratory insufficiency due to various causes (two related to upper airway obstruction). The other two syndromic RS infants died of arrhythmia due to hypernatremia and of West syndrome with status epilepticus. One isolated RS infant died of brain ischemia after MDO surgery. Cardiac anomalies were observed in 41% and neurological anomalies in 36%. The presence of a neurological anomaly was associated with a mortality rate of 40% versus 7% in infants with no neurological anomaly (p = 0.016), with an odds ratio of 8.3 (95% CI 1.4-49.0) for neurological anomaly versus no neurological anomaly. Mortality was 15% in infants with syndromic RS versus 2% in infants with isolated RS (p = 0.044). Mortality was not significantly associated with the presence of a cardiac anomaly, surgical treatment for severe respiratory distress in the neonatal period, or prematurity. CONCLUSION: RS represents a heterogeneous patient population and is associated with a high level of underlying syndromes. The present study reports a mortality rate of 10% significantly associated with syndromic RS and the presence of neurological anomalies. A multidisciplinary approach in all infants born with RS, including genetic testing and examination of neurological anomalies in a standardized way, is crucial to identify infants with underlying syndromes potentially associated with increased mortality. What is Known: • Reported mortality rates in Robin sequence vary from 2% to 26%. • Clinicians mainly focus on the morbidity of Robin sequence that includes respiratory complications due to upper airway obstruction in the period after birth. • Robin sequence represents a heterogeneous patient population and is associated with a high level of underlying syndromes. What is New: • The present study reports a mortality rate of 10% significantly associated with syndromic Robin sequence and the presence of neurological anomalies. • A multidisciplinary approach in all infants born with Robin sequence, including genetic evaluation and standardized workup for neurological anomalies, is crucial to identify infants with underlying syndromes potentially associated with increased mortality.

Carbon Dioxide Fluctuations Are Associated with Changes in Cerebral Oxygenation and Electrical Activity in Infants Born Preterm.

OBJECTIVES: To evaluate the effects of acute arterial carbon dioxide partial pressure changes on cerebral oxygenation and electrical activity in infants born preterm. STUDY DESIGN: This retrospective observational study included ventilated infants born preterm with acute fluctuations of continuous end-tidal CO2 (etCO2) as a surrogate marker for arterial carbon dioxide partial pressure, during the first 72 hours of life. Regional cerebral oxygen saturation and fractional tissue oxygen extraction were monitored with near-infrared spectroscopy. Brain activity was monitored with 2-channel electroencephalography. Spontaneous activity transients (SATs) rate (SATs/minute) and interval between SATs (in seconds) were calculated. Ten-minute periods were selected for analysis: before, during, and after etCO2 fluctuations of ≥5 mm Hg. RESULTS: Thirty-eight patients (mean ± SD gestational age of 29 ± 1.8 weeks) were included, with 60 episodes of etCO2 increase and 70 episodes of etCO2 decrease. During etCO2 increases, brain oxygenation increased (regional cerebral oxygen saturation increased, fractional tissue oxygen extraction decreased; P < .01) and electrical activity decreased (SATs/minute decreased, interval between SATs increased; P < .01). All measures recovered when etCO2 returned to baseline. During etCO2 decreases, brain oxygenation decreased (regional cerebral oxygen saturation decreased, fractional tissue oxygen extraction decreased; P < .01) and brain activity increased (SATs/minute increased, P < .05), also with recovery after return of etCO2 to baseline. CONCLUSION: An acute increase in etCO2 is associated with increased cerebral oxygenation and decreased brain activity, whereas an acute decrease is associated with decreased cerebral oxygenation and slightly increased brain activity. Combining continuous CO2 monitoring with near-infrared spectroscopy may enable the detection of otherwise undetected fluctuations in arterial carbon dioxide partial pressure that may be harmful to the neonatal brain.

Neonatal Surgery for Noncardiac Congenital Anomalies: Neonates at Risk of Brain Injury.

OBJECTIVE: To evaluate the incidence of brain injury after neonatal surgery for noncardiac congenital anomalies using magnetic resonance imaging (MRI). STUDY DESIGN: An MRI was obtained in 101 infants at 7 days [range: 1-115] after neonatal surgery for major noncardiac congenital anomalies. Brain injury was assessed using T1, T2, diffusion weighted imaging, and susceptibility-weighted imaging. RESULTS: Thirty-two preterm infants (<37 weeks of gestation) and 69 full-term infants were included. MRI abnormalities were found in 24 (75%) preterm and 40 (58%) full-term infants. Parenchymal lesions were noted in 23 preterm (72%) and 29 full-term infants (42%). These consisted of punctate white matter lesions (n = 45), punctate cerebellar lesions (n = 17), thalamic infarction (n = 5), and periventricular hemorrhagic infarction (n = 4). Nonparenchymal abnormalities were found in 9 (28%) preterm and 26 (38%) full-term infants. These included supra- and infratentorial subdural hemorrhages (n = 30), intraventricular hemorrhage grade II (n = 7), and asymptomatic sinovenous thrombosis (n = 1). A combination of parenchymal lesions was present in 21 infants. Of infants who had an MRI within 10 days after surgery, punctate white matter lesions were visible on diffusion weighted imaging in 22 (61%), suggestive of recent ischemic origin. Type of congenital anomaly and prematurity were most predictive of brain injury. CONCLUSIONS: Infants who have neonatal surgery for noncardiac congenital anomalies are at risk of brain injury, potentially accounting for the neurodevelopmental delay frequently observed in this population. Further research is warranted into potential mechanisms of brain injury and its timing of onset. Long-term neurodevelopmental follow-up is needed in this vulnerable population.

Brain Oxygenation During Thoracoscopic Repair of Long Gap Esophageal Atresia.

BACKGROUND: Elongation and repair of long gap esophageal atresia (LGEA) can be performed thoracoscopically, even directly after birth. The effect of thoracoscopic CO2-insufflation on cerebral oxygenation (rScO2) during the consecutive thoracoscopic procedures in repair of LGEA was evaluated. METHODS: Prospective case series of five infants, with in total 16 repetitive thoracoscopic procedures. A CO2-pneumothorax was installed with a pressure of maximum 5 mmHg and flow of 1 L/min. Parameters influencing rScO2 were monitored. For analysis 10 time periods of 10' during surgery and in the perioperative period were selected. RESULTS: Median gestational age was 35+3 [range 33+4 to 39+6] weeks; postnatal age at time of first procedure 4 [2-53] days and time of insufflation 127[22-425] min. Median rScO2 varied between 55 and 90%. Transient outliers in cerebral oxygenation were observed in three patients. In Patient 2 oxygenation values below 55% occurred during a low MABP and Hb < 6 mmol/L. The rScO2 increased after erythrocytes transfusion. Patient 5 also showed a rScO2 of 50% with a Hb <6 mmol/L during all procedures, except for a substantial increase during a high paCO2 of 60 mmHg. Patient 4 had a rScO2 > 85% during the first procedure with a concomitant high FiO2 > 45%. All parameters recovered during the surgical course. CONCLUSIONS: This prospective case series of NIRS during consecutive thoracoscopic repair of LGEA showed that cerebral oxygenation remained stable. Transient outliers in rScO2 occurred during changes in hemodynamic or respiratory parameters and normalized after interventions of the anesthesiologist. This study underlines the importance of perioperative neuromonitoring and the close collaboration between pediatric surgeon, anesthesiologist and neonatologist.

A survey of the dose of inhalational agents used to maintain anaesthesia in infants.

BACKGROUND: Various animal studies suggest that currently used anaesthetics are toxic to the developing brain. Many reviews advise that the total anaesthetic drug exposure should be reduced but the dose usually used in clinical practice has not been clearly elucidated. OBJECTIVES: To provide an overview of the dose ranges currently used in clinical practice during the maintenance phase of anaesthesia in infants undergoing anaesthesia for noncardiac surgery and diagnostic procedures. DESIGN: A two-centre mixed prospective (London) and retrospective (Utrecht) observational cohort study. SETTING: Two independent tertiary paediatric referral centres in March and November 2013; Great Ormond Street Hospital (GOSH), London, United Kingdom and Wilhelmina Children's Hospital, University Medical Center Utrecht (UMCU), The Netherlands. PATIENTS: A total of 76 infants were included in the analysis, 38 infants from each hospital. METHODS: Patients from GOSH were matched by procedure, age and weight with patients from the UMCU. The end-tidal concentrations of the inhalational agents were investigated from anaesthetic charts during the maintenance phase and corrected for the age-specific minimal alveolar concentration (MAC), expressed as a percentage from the MAC (%MAC). RESULTS: Three different types of inhalational anaesthetics were used: sevoflurane, desflurane, isoflurane. The mean %MAC was 0.85. No significant differences in %MAC were found between GOSH and the UMCU (P = 0.329); the mean %MAC in GOSH was 0.87 and in the UMCU was 0.82. There was a significant increase in the %MAC in relation to age (slope = 0.036 MAC month, P < 0.001). Of all patients, 75% had an end-tidal concentration lower than 1 MAC. There was no significant effect of the use of analgesia on the end-tidal concentration of inhalational anaesthetics (P = 0.366). CONCLUSION: The concentration of inhalational anaesthetics in %MAC increased with age and was lowest in neonates. Most young infants received inhalational anaesthetics at a concentration below 1 MAC, which accords with current guidance to minimise anaesthetic drug exposure but may have unintended consequences.

T2-prepared velocity selective labelling: A novel idea for full-brain mapping of oxygen saturation.

BACKGROUND AND AIM: Disturbances in cerebral oxygenation saturation (SO2) have been linked to adverse outcome in adults, children, and neonates. In intensive care, the cerebral SO2 is increasingly being monitored by Near-InfraRed Spectroscopy (NIRS). Unfortunately NIRS has a limited penetration depth. The "modified T2-prepared Blood Imaging of Oxygen Saturation" (T2-BIOS) MR sequence provides a step towards full brain SO2 measurement. MATERIALS AND METHODS: Tissue SO2, and venous SO2 (SvO2) were obtained simultaneously by T2-BIOS during a respiratory challenge in ten healthy volunteers. These two measures were compared to SO2 that was obtained by a single probe MR-compatible NIRS setup, and to cerebral blood flow and venous SO2 that were obtained by arterial spin labelling and T2-TRIR, respectively. RESULTS: SO2-T2-BIOS and SO2-NIRS had a mean bias of -4.0% (95% CI -21.3% to 13.3%). SvO2-T2-BIOS correlated with SO2-NIRS (R2=0.41, p=0.002) and SvO2-T2-TRIR (R2=0.87, p=0.002). In addition, SO2-NIRS correlated with SvO2-T2-TRIR (R2=0.85, p=0.003) Frontal cerebral blood flow correlated with SO2-T2-BIOS (R2=0.21, p=0.04), but was not significant in relation to SO2-NIRS. DISCUSSION/CONCLUSION: Full brain SO2 assessment by any technique may help validating NIRS and may prove useful in guiding the clinical management of patient populations with cerebral injury following hypoxic-ischaemic events. The agreement between NIRS and T2-BIOS provides confidence in measuring cerebral SO2 by either technique. As it stands now, the T2-BIOS represents a novel idea and future work will focus on improvements to make it a reliable tool for SO2 assessment.

Reference values of regional cerebral oxygen saturation during the first 3 days of life in preterm neonates.

BACKGROUND: Currently, reliable reference values of regional cerebral oxygen saturation (rScO2) for different gestational age (GA) groups are lacking, which hampers the implementation of near-infrared spectroscopy (NIRS) alongside monitoring arterial oxygen saturation (SaO2) and blood pressure in neonatal intensive care. The aim of this study was to provide reference values for rScO2 and cerebral fractional tissue oxygen extraction (cFTOE; (SaO2 - rScO2)/SaO2) for small adult and neonatal NIRS sensors. METHODS: In this study, 999 infants born preterm (GA <32 wk) were monitored with NIRS during the first 72 h of life. Mixed modeling was used to generate reference curves grouped per 2 wk of GA. In addition, the influence of a hemodynamically significant patent ductus arteriosus, gender, and birth weight were explored. RESULTS: Average rScO2 was ~65% at admission, increased with GA (1% per week) and followed a parabolic curve in relation to postnatal age with a peak at ~36 h. The cFTOE showed similar but inverse effects. On average, the neonatal sensor measured 10% higher than the adult sensor. CONCLUSION: rScO2 and cFTOE reference curves are provided for the first 72 h of life in preterm infants, which might support the broader implementation of NIRS in neonatal intensive care.

Brain injury in the international multicenter randomized SafeBoosC phase II feasibility trial: cranial ultrasound and magnetic resonance imaging assessments.

BACKGROUND: Abnormal cerebral perfusion during the first days of life in preterm infants is associated with higher grades of intraventricular hemorrhages and lower developmental score. In SafeBoosC II, we obtained a significant reduction of cerebral hypoxia by monitoring cerebral oxygenation in combination with a treatment guideline. Here, we describe (i) difference in brain injury between groups, (ii) feasibility of serial cranial ultrasound (cUS) and magnetic resonance imaging (MRI), (iii) local and central cUS assessment. METHODS: Hundred and sixty-six extremely preterm infants were included. cUS was scheduled for day 1, 4, 7, 14, and 35 and at term-equivalent age (TEA). cUS was assessed locally (unblinded) and centrally (blinded). MRI at TEA was assessed centrally (blinded). Brain injury classification: no, mild/moderate, or severe. RESULTS: Severe brain injury did not differ significantly between groups: cUS (experimental 10/80, control 18/77, P = 0.32) and MRI (5/46 vs. 3/38, P = 0.72). Kappa values for local and central readers were moderate-to-good for severe and poor-to-moderate for mild/moderate injuries. At TEA, cUS and MRI were assessed in 72 and 64%, respectively. CONCLUSION: There was no difference in severe brain injury between groups. Acquiring cUS and MRI according the standard operating procedures must be improved for future trials. Whether monitoring cerebral oxygenation during the first 72 h of life prevents brain injury should be evaluated in larger multicenter trials.

The SafeBoosC II randomized trial: treatment guided by near-infrared spectroscopy reduces cerebral hypoxia without changing early biomarkers of brain injury.

BACKGROUND: The SafeBoosC phase II multicentre randomized clinical trial investigated the benefits and harms of monitoring cerebral oxygenation by near-infrared spectroscopy (NIRS) combined with an evidence-based treatment guideline vs. no NIRS data and treatment as usual in the control group during the first 72 h of life. The trial demonstrated a significant reduction in the burden of cerebral hypoxia in the experimental group. We now report the blindly assessed and analyzed treatment effects on electroencephalographic (EEG) outcomes (burst rate and spectral edge frequency 95% (SEF95)) and blood biomarkers of brain injury (S100ß, brain fatty acid-binding protein, and neuroketal). METHODS: One hundred and sixty-six extremely preterm infants were randomized to either experimental or control group. EEG was recorded at 64 h of age and blood samples were collected at 6 and 64 h of age. RESULTS: One hundred and thirty-three EEGs were evaluated. The two groups did not differ regarding burst rates (experimental 7.2 vs. control 7.7 burst/min) or SEF95 (experimental 18.1 vs. control 18.0 Hz). The two groups did not differ regarding blood S100ß, brain fatty acid-binding protein, and neuroketal concentrations at 6 and 64 h (n = 123 participants). CONCLUSION: Treatment guided by NIRS reduced the cerebral burden of hypoxia without affecting EEG or the selected blood biomarkers.

Neonatal brain oxygenation during thoracoscopic correction of esophageal atresia.

BACKGROUND: Little is known about the effects of carbon dioxide (CO2) insufflation on cerebral oxygenation during thoracoscopy in neonates. Near-infrared spectroscopy can measure perioperative brain oxygenation [regional cerebral oxygen saturation (rScO2)]. AIMS: To evaluate the effects of CO2 insufflation on rScO2 during thoracoscopic esophageal atresia (EA) repair. METHODS: This is an observational study during thoracoscopic EA repair with 5 mmHg CO2 insufflation pressure. Mean arterial blood pressure (MABP), arterial oxygen saturation (SaO2), partial pressure of arterial carbon dioxide (paCO2), pH, and rScO2 were monitored in 15 neonates at seven time points: baseline (T0), after anesthesia induction (T1), after CO2-insufflation (T2), before CO2-exsufflation (T3), and postoperatively at 6 (T4), 12 (T5), and 24 h (T6). RESULTS: MABP remained stable. SaO2 decreased from T0 to T2 [97 ± 3-90 ± 6 % (p < 0.01)]. PaCO2 increased from T0 to T2 [41 ± 6-54 ± 15 mmHg (p < 0.01)]. pH decreased from T0 to T2 [7.33 ± 0.04-7.25 ± 0.11 (p < 0.05)]. All parameters recovered during the surgical course. Mean rScO2 was significantly higher at T1 compared to T2 [77 ± 10-73 ± 7 % (p < 0.05)]. Mean rScO2 levels never dropped below a safety threshold of 55 %. CONCLUSION: The impact of neonatal thoracoscopic repair of EA with insufflation of CO2 at 5 mmHg was studied. Intrathoracic CO2 insufflation caused a reversible decrease in SaO2 and pH and an increase in paCO2. The rScO2 was higher at anesthesia induction but remained stable and within normal limits during and after the CO2 pneumothorax, which suggest no hampering of cerebral oxygenation by the thoracoscopic intervention. Future studies will focus on the long-term effects of this surgery on the developing brain.

A New Framework for the Assessment of Cerebral Hemodynamics Regulation in Neonates Using NIRS.

We present a new framework for the assessment of cerebral hemodynamics regulation (CHR) in neonates using near-infrared spectroscopy (NIRS). In premature infants, NIRS measurements have been used as surrogate variables for cerebral blood flow (CBF) in the assessment of cerebral autoregulation (CA). However, NIRS measurements only reflect changes in CBF under constant changes in arterial oxygen saturation (SaO2). This condition is unlikely to be met at the bedside in the NICU. Additionally, CA is just one of the different highly coupled mechanisms that regulate brain hemodynamics. Traditional methods for the assessment of CA do not take into account the multivariate nature of CHR, producing inconclusive results. In this study we propose a newly developed multivariate methodology for the assessment of CHR. This method is able to effectively decouple the influences of SaO2 from the NIRS measurements, and at the same time, produces scores indicating the strength of the coupling between the systemic variables and NIRS recordings. We explore the use of this method, and its derived scores, for the monitoring of CHR using data from premature infants who developed a grade III-IV intra-ventricular hemorrhage during the first 3 days of life.

The effects of CO2-insufflation with 5 and 10 mmHg during thoracoscopy on cerebral oxygenation and hemodynamics in piglets: an animal experimental study.

OBJECTIVE: To evaluate the effect of CO2-insufflation with 5 and 10 mmHg on cerebral oxygenation and hemodynamics in neonates. BACKGROUND: An increasing percentage of surgical interventions in neonates are performed by minimal invasive techniques. Recently, concerns have been raised regarding a decrease of cerebral oxygenation in neonates during thoracoscopy as a result of CO2-insufflation. METHODS: This was an animal experimental study. Piglets were anesthetized, intubated, ventilated, and surgically prepared for CO2-insufflation. Insufflation was done with 5 or 10 mmHg CO2 during 1 h. Arterial saturation (SaO2), heart rate (HR), mean arterial blood pressure (MABP), and cerebral oxygenation (rScO2) were monitored. CFTOE, an estimator of cerebral oxygen extraction ((SaO2 - rScO2)/SaO2)), was calculated. Arterial blood gases were drawn every 15': pre (T0), during (T1-T4) and after CO2-insufflation (T5). RESULTS: Ten piglets (4 kg) were randomized for 5 (P5) and 10 (P10) mmHg CO2-insufflation. Two P10 piglets needed resuscitation after insufflation, none P5. Linear mixed-effect modeling of paCO2, pH, and SaO2 showed that values were dependent on time and time squared (p < 0.001) but were not different between the 5 and 10 mmHg groups. Analysis demonstrated significant changes over time in heart rate and MABP between the 5 and 10 mmHg groups, with a significant higher heart rate and lower blood pressure in the 10 mmHg group (p < 0.001). For rScO2 and cFTOE, no group differences could be demonstrated, but a significant effect of time was found: rScO2 increased and cFTOE decreased (p < 0.001). CONCLUSIONS: Insufflation of CO2 during thoracoscopy with 10 mmHg caused more severe hemodynamic instability and seems to be related with a decrease of cerebral perfusion as represented by a higher oxygen extraction. CO2-insufflation of 5 mmHg for thoracoscopy seems to have no adverse effects on cerebral oxygenation.