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

Abstract

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 μV ² (p = 0.0049), fast delta: 0.73 vs. 1.37 μV ² (p = < 0.001). In the first 30 min of the surgical procedure, a 3-fold increase in fast delta (10.48-31.22 μV ²) and a 5-fold increase in gamma (1.42-7.58 μV ²) 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. Trial Registration: https://www.trialregister.nl/trial/6972, identifier: NL6972.

Keywords: cerebral activity; cerebral oxygenation; midazolam; neonates; sevoflurane; surgery.

Figure 1

Longitudinal overview of the perioperative changes in HR (A), MABP (B), SpO₂ (C), rSO₂ (D), FTOE (E), time in hypoxia (F), slow delta (G), fast delta (H), gamma (I) power.

Figure 2

Intraoperative cerebral activity; slow delta (A), fast delta (B), gamma (C) power. Blue, sevoflurane group; red, midazolam group; 0, start surgical procedure.

Figure 3

Correlation between the maximum sevoflurane concentration or maximum dosages of midazolam cerebral oxygenation (A,B) and cerebral activity: slow delta (C,D), fast delta (E,F), gamma (G,H) power. Blue, sevoflurane group; red, midazolam group; fat line, significant correlation.

Figure 4

Correlation between the cerebral activity and cerebral oxygenation and oxygen consumption preoperative (A,B), intraoperative (C,D), and postoperative (E,F). Blue, sevoflurane group; red, midazolam group; fat line, significant correlation.