248 - Improved oxygenation and right ventricular function in preterm infants with acute pulmonary hypertension following inhaled nitric oxide: case series

Publication Number: 4244.248

Stephanie M. Boyd, The University of Sydney and The Children's Hospital at Westmead, Balmain, New South Wales, Australia; Adrianne R. Bischoff, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; Patrick McNamara, University of Iowa, Iowa city, IA, United States

Background: Randomized controlled trial (RCT) meta-analyses of inhaled nitric oxide (iNO) in preterm infants with hypoxemic respiratory failure have not identified benefit. The enrolled population, however, includes a heterogeneous group of varying etiology and hemodynamic phenotype. We hypothesized that the subgroup with targeted neonatal echocardiography (TNE) confirmed resistance-mediated acute pulmonary hypertension (PH) may benefit from iNO.

Objective: Assess clinical and TNE response to iNO in preterm infants with resistance-driven PH.

Design/Methods: Retrospective cohort study of preterm infants 30 weeks' gestational age (GA) (August 2019 - September 2022) with resistance-mediated PH, defined as: PH with pulmonary vascular resistance index (PVRi)[pulmonary artery acceleration time (PAAT)/right ventricular (RV) ejection time (RVET)] 4, left ventricular (LV) output < 200 mL/kg/min and absence of isolated LV dysfunction [LV ejection fraction < 55% with normal RV function]) on TNE < 72 hrs of age who underwent pre- and post-iNO TNE evaluation. Clinical and TNE outcomes included: oxygenation index (OI), acid-base status, indices of PH [systolic eccentricity index, patent ductus arteriosus (PDA) shunting, PVRi, PAAT, tricuspid regurgitant jet velocity], RV function [tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (FAC), RV systolic excursion velocity (RVs')]. Paired t-tests for parametric and Wilcoxon signed-rank tests for non-parametric data were performed.

Results: Twelve infants born at 25.7 (23.9, 27.3) weeks' GA with birthweight 884 ± 36g, were included. Post-iNO TNE was at 24.1 (19.3, 24.7) hours. Four infants had iNO ceased prior to 24 hours due to interval improvement. A reduction in FiO2, [1.0 (0.56, 1.0) vs. 0.29 (0.23, 0.37), p=0.01] was observed post-iNO [Figure 1], along with improvements in OI (p=0.03), pH (p=0.04), lactate (p=0.02) and respiratory severity score (p=0.02). Improvements in PAAT (p=0.001), FAC (p=0.01) and right and left ventricular outputs [p < 0.05, Figure 2, Table 1] were noted. Post-iNO, an improvement in transductal pressure gradient was noted with more PDA shunts bidirectional or left-to-right.

Conclusion(s): iNO use is associated with improved oxygenation, PVR and RV performance in preterm infants with resistance-mediated PH. Careful TNE monitoring of ductal physiology is warranted. Future RCTs of iNO in preterm infants should only enrol patients with TNE confirmed resistance-mediated PH.

Figure 1: Changes in clinical parameters prior to and following inhaled nitric oxide (iNO): A. Fractional inspired oxygen concentration (FiO2); B. Oxygenation index (OI); C. pH; D. Respiratory severity score (RSS) [mean airway pressure x FiO2]


Figure 2: Changes in echocardiography indices prior and following iNO: A. Pulmonary artery acceleration time (PAAT)(msec); B. Right ventricular fractional area change (RV FAC)(%); C. Right ventricular output (RVO)(mL/kg/min); D. Left ventricular output (LVO)(mL/kg/min)


Table 1: Clinical and echocardiography parameters prior to and following inhaled nitric oxide (iNO).
FiO2 = fraction of inspired oxygen; PDA = patent ductus arteriosus; LV = left ventricular; sEI = systolic eccentricity index; PAAT = pulmonary artery acceleration time; RVET = right ventricular ejection time; TAPSE = tricuspid annular plane systolic excursion; RV = right ventricular; FAC = fractional area change; s' = systolic excursion velocity; RVO.= right ventricular output; LV = left ventricular; EF = ejection fraction; LVO = left ventricular output;
Respiratory severity score is calculated by: mean airway pressure x FiO2
Systolic, diastolic and mean arterial pressure values were recorded from an umbilical arterial catheter
Values are number (percentage), mean (standard deviation) or median (interquartile range). Data analysed using paired t-tests for parametric data, Wilcoxon signed rank tests for continuous non-parametric data and McNemar tests for non-parametric categorical variables.