Abstract 121: A Pre-Clinical Randomized Blinded Trial of Inhaled Nitric Oxide During Pediatric Cardiopulmonary Resuscitation

Introduction: Inhaled nitric oxide (iNO) may result in higher systemic BP during CPR and may have a neuroprotective role post-arrest, but its effects on cerebral perfusion pressure (CePP), cerebral blood flow (CBF), and mitochondrial function when administered during CPR are unknown. Hypotheses: We hypothesized that administration of iNO during CPR would lead to higher CePP, higher CBF, and less brain injury as measured by cerebral mitochondrial function, neuronal apoptosis, and microglial activation. Methods: In 1-month-old swine (n=20), lipopolysaccharide was intravenously infused to induce a shock state, followed by induction of VF and treatment with hemodynamic-directed CPR (HD-CPR). Animals were randomized to blinded treatment with either: 1) HD-CPR with iNO (beginning 1 minute into CPR), or 2) HD-CPR without iNO. Defibrillation attempts began at 10 minutes with a maximum CPR duration of 20 minutes. Among animals surviving 1-hour post-arrest, cerebral tissue underwent high-resolution respirometry to evaluate the mitochondrial electron transport system and quantification of neuronal apoptosis and microglial activation. Chi-square test, Fisher’s exact test, Student’s t-test, Wilcoxon rank-sum test, and a generalized estimating equation regression model compared the two groups. Results: During CPR, the iNO group had higher mean aortic pressure (41.6±2.0 vs. 36.0±1.4 mmHg; p=0.005); diastolic BP (32.4±2.4 vs. 27.1±1.7 mmHg; p=0.03); CePP (25.0±2.6 vs. 19.1±1.8 mmHg; p=0.02); and CBF relative to pre-CPR baseline (243.2±54.1 vs. 115.5±37.2%; p=0.02). Among the 8/10 survivors in each group, the iNO group had higher mitochondrial Complex I oxidative phosphorylation in the cerebral cortex (3.60 [3.56, 3.99] vs. 3.23 [2.44, 3.46] pmol O 2 /s*mg; p=0.01) and hippocampus (4.79 [4.35, 5.18] vs. 3.17 [2.75, 4.58] pmol O 2 /s*mg; p=0.02). There were no other differences in mitochondrial respiration or brain injury between groups. Conclusions: Blinded treatment with iNO during CPR in a model of pediatric shock-associated cardiac arrest resulted in superior CePP, CBF, and cerebral mitochondrial Complex I respiration. These data suggest that iNO treatment during CPR may lead to improved neurologic outcomes from pediatric cardiac arrest.