555 - Optimal Maternal PaCO₂ and SpO₂ for Fetal Resuscitation in a Novel Model of Maternal Hypoxemia and Critical Illness

Publication Number: 3536.555

Jocelyn Livezey, University of California, Davis, School of Medicine, Davis, CA, United States; Xiaohan Li, University of California, Davis, School of Medicine, Davis, CA, United States; Deepika Sankaran, University of California Davis Children's Hospital, Sacramento, CA, United States; Evan M. Giusto, UC Davis Health, Sacramento, CA, United States; Sylvia Bowditch, University of California Davis Children's Hospital, Sacramento, CA, United States; Payam Vali, University of California, Davis, School of Medicine, sacramento, CA, United States; Evan Maher, University of California, Davis, School of Medicine, Woodland, CA, United States; Rebecca Valdez, University of California Davis Children's Hospital, Sacramento, CA, United States; Victoria Hammitt, UC Davis Stem Cell Research, Davis, CA, United States; Amy Lesneski, UC Davis, Davis, CA, United States; Nicholas Burke, University of California Davis Children's Hospital, Davis, CA, United States; Herman L. Hedriana, University of California Davis Children's Hospital, Sacramento, CA, United States; Kent E. Pinkerton, University of California, Davis, Davis, CA, United States; Satyan Lakshminrusimha, UC Davis, Sacramento, CA, United States; Michelle J. Lim, University of California, Davis, School of Medicine, Sacramento, CA, United States

Background: Management of respiratory failure during pregnancy is challenging because optimal maternal PaCO₂ and SpO₂ targets that best support fetal resuscitation and brain oxygen delivery (DO₂) remain undefined. Pregnancy increases ventilatory drive, causing mild respiratory alkalosis and elevated SpO₂, while close maternal-fetal PaCO₂ coupling makes the fetus vulnerable to hypercapnia and acidosis, reducing oxygen affinity and potentially compromising DO₂. In severe maternal respiratory failure, however, targeting the high SpO₂ and low PaCO₂ may increase the risk of ventilator-induced lung injury, highlighting the uncertainty of optimal maternal oxygen and CO₂ targets in critical illness.

Objective: To investigate the relationship between maternal PaCO₂ and fetal DO₂ in a novel ovine model of maternal acute respiratory distress syndrome (ARDS).

Design/Methods: Lung injury was induced in pregnant ewes at preterm gestation (132-135 days; term ~147 days) using a validated model of ARDS, with combined acid and small gastric particle (CASP), following surgical instrumentation of the maternal ewe and fetus. Maternal ewes were randomized to either high oxygen targets (SpO₂ > 95%), consistent with current maternal-fetal medicine (MFM) guidelines, or low oxygen targets (SpO₂ 88-95%), aligned with non-pregnant ARDS management recommendations. Serial maternal and fetal blood gases and hemodynamic parameters were monitored from baseline (pre-injury) through 4 hours post-induction of acute lung injury (ALI). A total of 17 pregnant ewes were included, with data analysis comparing baseline and 4 hours post ALI.

Results: We evaluated physiologic factors affecting maternal-fetal DO₂ following ALI (Figure 1). Maternal and fetal mean arterial pressure, carotid blood flow, and brain DO₂ were unchanged post-ALI, although maternal pH showed a mild decrease from baseline. Maternal and fetal PCO₂ were moderately correlated after ALI (r = 0.33, p < 0.001, Figure 2). Stratification by maternal PCO₂ revealed a significant decline in fetal brain DO₂ in ewes ventilated to hypocarbic levels (30-37 mmHg) compared with normocarbia (38-45 mmHg) or hypercarbia (46-60 mmHg). The greatest reduction occurred in ewes with both hypocarbia and low maternal oxygen targets (Figure 3).

Conclusion(s): Targeting physiologic normative PCO₂ in pregnancy with maternal ARDS may impair fetal brain oxygen delivery, especially under conservative oxygen targets. Permissive hypercarbia combined with high maternal oxygen saturation, aligned with MFM guidelines, may better preserve fetal brain DO₂ and support fetal resuscitation in severe maternal respiratory failure.

Baseline vs Post Acute Lung Injury Physiological Parameters
Physiological parameters are presented as mean ± standard deviation, stratified by subject (Maternal vs Fetal) and time (Baseline vs 4 Hr Post Acute Lung Injury). Groups were compared by paired t-test.

Fetal PaCO2 vs Maternal PaCO2 Post ALI Onset
Fetal PaCO2 and maternal PaCO2 are moderately correlated post-acute lung injury (evaluated at hours 1-4 post-ALI). Correlation coefficient (r) was determined by Pearson method. ALI; Acute Lung Injury.

Change in Fetal Brain Oxygen Delivery Post Maternal Lung Injury Onset Stratified by Maternal PaCO2 Subgroups
Fetal brain oxygen delivery is grouped by (A) PaCO2 targets and (B) PaCO2 and maternal oxygen targets. Maternal oxygen targets are further stratified by high O2 (as recommended by current maternal-fetal medicine societies) vs low O2 targets (as recommended by non-pregnant ARDS guidelines). Fetal Brain Oxygen delivery was calculated with the following equation: Q(ca) x systemic arterial oxygen content (CaO2). Qca=flow/kg through the carotid artery and CaO2 was measured by (1.34*Hb*SaO2) + (0.003*PaO2) mL/dL. Percent change from baseline was calculated as ((Post ALI values- Baseline)/ Baseline)*100, where the Post-ALI values represents fetal brain oxygen delivery after ALI injury. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 by primary ANOVA analysis with post-hoc pairwise comparisons. ALI; Acute Lung Injury.