Lisanne J. Stolwijk

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.

Effect of general anesthesia on neonatal aEEG—A cohort study of patients with non-cardiac congenital anomalies

Introduction The aim of the current study was to determine the effect of general anesthesia on neonatal brain activity using amplitude-integrated EEG (aEEG). Methods A prospective cohort study of neonates (January 2013-December 2015), who underwent major neonatal surgery for non-cardiac congenital anomalies. Anesthesia was administered at the discretion of the anesthetist. aEEG monitoring was started six hours preoperatively until 24 hours after surgery. Analysis of classes of aEEG background patterns, ranging from continuous normal voltage to flat trace in six classes, and quantitative EEG-measures, using spontaneous activity transients (SATs) and interSATintervals (ISI), was performed. Results In total, 111 neonates were included (36 preterm/75 full-term), age at time of surgery was (median (range) 2 (0–32) days. During anesthesia depression of brain activity was seen, with background patterns ranging from flat trace to discontinuous normal voltage. In most patients brain activity was two background pattern classes lower during anesthesia. After cessation of anesthesia, recovery to preoperative brain activity occurred within 24 hours in 86% of the preterm and 96% of the term infants. Gestational age and the dose of sevoflurane were significantly associated with SAT-rate (F(2,68) = 9.288, p < 0.001) and ISI- durations during surgery (F(3,71) = 12.96, p < 0.001). Background pattern and quantitative EEG-values were not associated with brain lesions (χ2(4) = 2.086, ns). Conclusion aEEG shows a variable reduction of brain activity in response to anesthesia in neonates with noncardiac congenital anomalies, with fast recovery after cessation of anesthesia. This reduction is related to gestational age and the dose of sevoflurane. The aEEG offers the opportunity to monitor the depth of anesthesia in the neonate.

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 Childrens 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−1, 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.

PO-0475 The Effect Of Co2-insufflation On Cerebral Oxygenation In Thoracoscopic Repair Of Esophageal Atresia In Neonates

Aim of the study Infants undergoing neonatal surgery for thoracoscopic esophageal atresia repair are at high risk of adverse neurodevelopmental outcomes. Increasing concerns have been raised about the incidence of perioperative brain injury, this is suggested to be due to haemodynamic instability and hypoxia perioperatively. We evaluated the effects of CO2-insufflation on regional cerebral oxygen saturation (rScO2) during thoracoscopic esophageal atresia repair. Methods Observational study of 20 neonates undergoing thoracoscopic esophageal atresia repair. During surgery mean blood pressure (MABP), FiO2, arterial saturation and the cerebral oxygen saturation (rScO2) were continuously monitored. Four periods of 10 min were selected: (T=0) during anaesthesia, (T=1 and T=2) during CO2-insufflation and (T=3) after desufflation. Main results Complete registration was obtained in 14 neonates (median GA 36.9 [30.6–41.9], birth weight 2358 g [1395–4490]) and were included. After CO2-insufflation the FiO2 increased from 41% to 58%, whilst the saturation decreased from 96.3% to 92.5%(p < 0.05). The arterial pCO2 (mmHg) changed from 47 ± 6.9 to 56 ± 13(p < 0.05) after CO2-insufflation and remained stable at the end of insufflation and after desufflation. The rScO2 did not change after CO2-insufflation or desufflation. Conclusion Intrathoracic CO2-insufflation causes a decrease in arterial saturation and an increase in arterial pCO2. However, more importantly these changes did not result in significant fluctuations in cerebral oxygenation throughout the procedure. The insufflation of CO2 with 5 mmHg during thoracoscopy seems to be safe in neonates, since the cerebral oxygenation was preserved during the procedure.

Early human brain development: insights into macroscale connectome wiring

BackgroundEarly brain development is closely dictated by distinct neurobiological principles. Here, we aimed to map early trajectories of structural brain wiring in the neonatal brain.MethodsWe investigated structural connectome development in 44 newborns, including 23 preterm infants and 21 full-term neonates scanned between 29 and 45 postmenstrual weeks. Diffusion-weighted imaging data were combined with cortical segmentations derived from T2 data to construct neonatal connectome maps.ResultsProjection fibers interconnecting primary cortices and deep gray matter structures were noted to mature faster than connections between higher-order association cortices (fractional anisotropy (FA) F = 58.9, p < 0.001, radial diffusivity (RD) F = 28.8, p < 0.001). Neonatal FA-values resembled adult FA-values more than RD, while RD approximated the adult brain faster (F = 358.4, p < 0.001). Maturational trajectories of RD in neonatal white matter pathways revealed substantial overlap with what is known about the sequence of subcortical white matter myelination from histopathological mappings as recorded by early neuroanatomists (mean RD 68 regions r = 0.45, p = 0.008).ConclusionEmploying postnatal neuroimaging we reveal that early maturational trajectories of white matter pathways display discriminative developmental features of the neonatal brain network. These findings provide valuable insight into the early stages of structural connectome development.

Predictive Role of F2-Isoprostanes as Biomarkers for Brain Damage after Neonatal Surgery

Objective Neonates have a high risk of oxidative stress during anesthetic procedures. The predictive role of oxidative stress biomarkers on the occurrence of brain injury in the perioperative period has not been reported before. Methods A prospective cohort study of patients requiring major surgery in the neonatal period was conducted. Biomarker levels of nonprotein-bound iron (NPBI) in plasma and F2-isoprostane in plasma and urine before and after surgical intervention were determined. Brain injury was assessed using postoperative MRI. Results In total, 61 neonates were included, median gestational age at 39 weeks (range 31–42) and weight at 3000 grams (1400–4400). Mild to moderate brain lesions were found in 66%. Logistic regression analysis showed a significant difference between plasma NPBI in patients with nonparenchymal injury versus no brain injury: 1.34 umol/L was identified as correlation threshold for nonparenchymal injury (sensitivity 67%, specificity 91%). In the multivariable analysis, correcting for GA, no other significant relation was found with the oxidative stress biomarkers and risk factors. Conclusion Oxidative stress seems to occur during anaesthesia in this cohort of neonates. Plasma nonprotein-bound iron showed to be associated with nonparenchymal injury after surgery, with values of 1.34 umol/L or higher. Risk factors should be elucidated in a more homogeneous patient group.