690 - Inhaled Nitric Oxide (iNO) Selectively Improves Gut Microcirculation in ELBW Neonates but not CNS or Renal NIRS After Packed Red Blood Cell (PRBC) Transfusion (Tx) for Extreme Anemia
Monday, April 28, 2025
7:00am – 9:15am HST
Publication Number: 690.5548
Edmund F.. LaGamma, New York Medical College, Valhalla, NY, United States; Kristina Ericksen, Brookdale Medical Center, Brooklyn, NY, United States; Clare Giblin BSN-NIC, Maria Fareri Children's Hospital at Westchester Medical Center, Valhalla, NY, United States; Marisa Larson, Maria Fareri Children's Hospital at Westchester Medical Center, Nanuet, NY, United States; Gabriel Rios, Maria Fareri Children's Hospital at Westchester Medical Center, White Plains, NY, United States
Professor of Pediatrics and Biochemistry & Molecular Biology New York Medical College Valhalla, New York, United States
Background: PRBC Tx is Related to Acute Gut Injury in severely anemic neonates (TRAGI; LaGamma, Guest Editor, Sem Perinatol 2012:36(4); NeoRev 16(7):e420, 2015). PRBCs are deficient in NO, have excess free Hgb & both scavenge endogenous NO causing vasoconstriction in dependent microvasculature such as intestinal villi. Repeated Tx’s deplete low neonatal hemopexin levels resulting in free heme that contributes to an inflammatory process. Administration of iNO may mitigate this by increasing the rate of nitrosylation of hemoglobin (Hgb) during RBC/Hgb’s first passage through the lung. We hypothesize that iNO during PRBC Tx may lessen the putative adverse peripheral vascular effects of NO scavenging. Objective: To evaluate the effect of iNO on NIRS before, during, & after PRBC Tx (15 ml/kg) for extreme anemia. Design/Methods: 50 ELBWs, > 2 weeks postnatal age, Hct < 28 on oral iron (2-4 mg/kg/d), full breast milk + 4 Prolacta™ feeding, on PPO2 & no PDA or acute medical problems, were masked & randomized to receive either iNO (20ppm) 1h before, during, and 2h following a PRBC Tx infused over 3h vs placebo. All infants were made NPO 1h before, during & 12h after Tx. Cerebral, flank, and splanchnic NIRS were used as metrics of tissue oxygenation & as an index of regional blood flow. Results: The groups did not differ in contributing perinatal variables (Table). Baseline NIRS signals (Figure) were all low relative to normal values consistent with increased VO2 extraction due to extreme anemia. Baseline HR, BP, and RR rates were similar & did not change significantly after Tx. In iNO vs placebo groups, while the average Hct increased significantly by 9 ± 1 & 11 ± 1 points after Tx, NIRS signals increased by 13 & 12% for CNS and 34 & 25% for the flank (p < 0.05) - remaining continuously elevated x 13h after the Tx ended. The gut increased significantly by 23 & 17% but remained transiently elevated before returning to baseline 10h after iNO exposure vs just 5h for placebo (Figure; arrows).
Conclusion(s): The unique splanchnic divergence in regional NIRS following discontinuation of iNO is consistent with the hypothesis of S-nitrosylHgb being the vehicle to achieve this and that the gut’s countercurrent villus circulation is responsive to iNO. The data suggests that in extremely anemic neonates with low baseline NIRS, iNO can selectively affect the splanchnic vasculature after Tx and thus, avert splanchnic microvascular ischemia. A randomized controlled trial is needed to determine whether iNO during PRBC Tx may indeed be beneficial in the prevention of TRAGI. Funded: unrestricted grant & iNO, Ikaria; NCT02851472; FDA IND 126254
