651 - Hidden Brain Hypoxia: Two-Thirds of Cerebral Desaturation Events Occur Despite Normal Pulse Oximetry

Publication Number: 2634.651

Zachary A. Vesoulis, Washington University School of Medicine, St. Louis, MO, United States; May Yee Szeto, Stanford University School of Medicine, Palo Alto, CA, United States; Callie Marshall, Washington University in St. Louis School of Medicine, SAINT LOUIS, MO, United States; Andrew Hopper, Loma Linda University Children's Hospital, Loma Linda, CA, United States; Nicole Kraus, Loma Linda University Children's Hospital, Loma linda, CA, United States; Santina Zanelli, University of Virginia, Charlottesville, VA, United States; Karen Fairchild, University of Virginia School of Medicine, Charlottesville, VA, United States; Lina Chalak, Childrens Health Dallas UT Southwestern, DALLAS, TX, United States; Valerie Y.. Chock, Stanford University School of Medicine, Palo Alto, CA, United States

Background: Pulse oximetry-based oxygen saturation guidelines are intended to limit the hypoxia burden of extremely preterm infants who are at high risk for brain injury. We hypothesized that cerebral near-infrared spectroscopy (NIRS) would reveal cerebral hypoxia events undetected by conventional pulse oximetry (SpO2) and would correlate with brain injury.

Objective: To quantify the number and frequency of cerebral hypoxia events, to determine the fraction of the events which are clinically silent, to assess the relationship with brain injury.

Design/Methods: The multicenter BOx-II clinical trial (NCT05171881) utilized high-resolution physiologic data from extremely preterm neonates ( < 28 weeks' gestation). Infants underwent continuous cerebral NIRS (rSO2) and SpO2 monitoring for 72h, starting within 6h of birth. Cerebral hypoxia was defined as rSO2 < 63% (INVOS) or < 67% (ForeSight Elite). Prolonged desaturation events were defined as ≥10 min below threshold. Events were classified as "silent" when occurring while SpO2 remained ≥90%.

Results: Eighty-one infants were analyzed with median duration of 75.4h (IQR 68.2-83.1). The median gestational age was 25.4 weeks and median birth weight was 812g. Any IVH occurred in 32.7%, severe IVH in 6.1%, and death in 18.4%. The cerebral hypoxia burden was substantially lower than the SpO2 hypoxia burden (1.2% vs. 9.1%). A total of 229 prolonged cerebral desaturation events occurred in 35 patients; most of these (64%) were silent, occurring while SpO2 remained ≥90%.

The median event lasted 16.8 min, with some events extending beyond 4 hours. During events, average rSO2 nadir was 50.7±10.7%, decreasing to 9% in severe cases. Most events occurred early in postnatal life, with median time of first event at 10.4h after birth.

Clinical outcomes demonstrated concerning trends associated with cerebral desaturation events. Infants experiencing at least one prolonged cerebral desaturation event showed higher rates of any IVH compared to those without events (53.3% vs 23.5%, p=0.053) and increased composite adverse outcomes including IVH or death (60.0% vs 32.4%, p=0.114).

Conclusion(s): Nearly two-thirds of prolonged cerebral hypoxic events-exceeding 130 cumulative hours across the cohort-occurred while pulse oximetry appeared reassuring, indicating that SpO2 monitoring alone provides inadequate prediction of cerebral oxygenation status. Standard monitoring systematically fails to detect these threats to the developing brain. Concomitant monitoring using NIRS and pulse oximetry is recommended while awaiting future trials to reduce cerebral hypoxia burden through targeted interventions.

Figure 1. Distribution of oximetry values and hypoxia burdens
Histograms representing the distribution of SpO2 and rSO2 measurements (A), cerebral vs. systemic hypoxia burden in (B), and occult cerebral hypoxia burden (C).

Figure 2. Distribution of Prolonged Cerebral Desaturation Events per Patient
Slightly more than half (57%) had no recorded prolonged cerebral hypoxia episodes (>=10 minutes). The distribution of event counts varied widely.

Figure 3. Example cerebral desaturation event plot
Caption: A 3-hour time trace of SpO2 and rSO2 for a single patient. Note the nearly 45-minute episode of cerebral hypoxia (highlighted in yellow) reaching a nadir of 52%.