Neurocardiovascular coupling in congenital diaphragmatic hernia patients undergoing different types of surgical treatment

BACKGROUNDThe effect of peri-operative management on the neonatal brain is largely unknown. Triggers for perioperative brain injury might be revealed by studying changes in neonatal physiology peri-operatively.OBJECTIVETo study neonatal pathophysiology and cerebral blood flow regulation peri-operatively using the neuro-cardiovascular graph.DESIGNObservational, prospective cohort study on perioperative neuromonitoring. Neonates were included between July 2018 and April 2020.SETTINGMulticentre study in two high-volume tertiary university hospitals.PATIENTSNeonates with congenital diaphragmatic hernia were eligible if they received surgical treatment within the first 28 days of life. Exclusion criteria were major cardiac or chromosomal anomalies, or syndromes associated with altered cerebral perfusion or major neurodevelopmental impairment. The neonates were stratified into different groups by type of peri-operative management.INTERVENTIONEach patient was monitored using near-infrared spectroscopy and EEG in addition to the routine peri-operative monitoring. Neurocardiovascular graphs were computed off-line.MAIN OUTCOME MEASURESThe primary endpoint was the difference in neurocardiovascular graph connectivity in the groups over time.RESULTSThirty-six patients were included. The intraoperative graph connectivity decreased in all patients operated upon in the operation room (OR) with sevoflurane-based anaesthesia (P < 0.001) but remained stable in all patients operated upon in the neonatal intensive care unit (NICU) with midazolam-based anaesthesia. Thoracoscopic surgery in the OR was associated with the largest median connectivity reduction (0.33 to 0.12, P < 0.001) and a loss of baroreflex and neurovascular coupling. During open surgery in the OR, all regulation mechanisms remained intact. Open surgery in the NICU was associated with the highest neurovascular coupling values.CONCLUSIONNeurocardiovascular graphs provided more insight into the effect of the peri-operative management on the pathophysiology of neonates undergoing surgery. The neonate's clinical condition as well as the surgical and the anaesthesiological approach affected the neonatal physiology and CBF regulation mechanisms at different levels.TRIAL REGISTRATIONNL6972, URL: https://www.trialre-gister.nl/trial/6972

Cerebral Oxygenation and Activity During Surgical Repair of Neonates With Congenital Diaphragmatic Hernia: A Center Comparison Analysis

Background and aim: Neonatal brain monitoring is increasingly used due to reports of brain injury perioperatively. Little is known about the effect of sedatives (midazolam) and anesthetics (sevoflurane) on cerebral oxygenation (rScO2) and cerebral activity. This study aims to determine these effects in the perioperative period. Methods: This is an observational, prospective study in two tertiary pediatric surgical centers. All neonates with a congenital diaphragmatic hernia received perioperative cerebral oxygenation and activity measurements. Patients were stratified based on intraoperatively administrated medication: the sevoflurane group (continuous sevoflurane, bolus fentanyl, bolus rocuronium) and the midazolam group (continuous midazolam, continuous fentanyl, and continuous vecuronium). Results: Intraoperatively, rScO2 was higher in the sevoflurane compared to the midazolam group (84%, IQR 77–95 vs. 65%, IQR 59–76, p = < 0.001), fractional tissue oxygen extraction was lower (14%, IQR 5–21 vs. 31%, IQR 29–40, p = < 0.001), the duration of hypoxia was shorter (2%, IQR 0.4–9.6 vs. 38.6%, IQR 4.9–70, p = 0.023), and cerebral activity decreased more: slow delta: 2.16 vs. 4.35 μV2 (p = 0.0049), fast delta: 0.73 vs. 1.37 μV2 (p = < 0.001). In the first 30 min of the surgical procedure, a 3-fold increase in fast delta (10.48–31.22 μV2) and a 5-fold increase in gamma (1.42–7.58 μV2) were observed in the midazolam group. Conclusion: Sevoflurane-based anesthesia resulted in increased cerebral oxygenation and decreased cerebral activity, suggesting adequate anesthesia. Midazolam-based anesthesia in neonates with a more severe CDH led to alarmingly low rScO2 values, below hypoxia threshold, and increased values of EEG power during the first 30 min of surgery. This might indicate conscious experience of pain. Integrating population-pharmacokinetic models and multimodal neuromonitoring are needed for personalized pharmacotherapy in these vulnerable patients