Comparative Efficacy of Low-Dose Versus High-Dose Inhaled Nitric Oxide in Extreme Preterm Infants with Hypoxic Respiratory Failure: A Retrospective Cohort Study
Keywords:
persistent pulmonary hypertension of the newborn (PPHN), inhaled nitric oxide, preterm infantsAbstract
Background: Inhaled nitric oxide (iNO) is widely used in preterm infants for various respiratory
indications. However, the optimal dosing for extreme preterm infants with hypo
xic respiratory failure remains unclear. This study investigates the effects of different iNO
dosages on oxygenation and associated clinical outcomes in this vulnerable population.
Methods: We conducted a retrospective cohort study of preterm infants (<37 weeks gestation)
admitted to the WWRC NICU between January 1, 2015, and April 30, 2021. Infants were
categorized into high-dose (20 ppm) and low-dose (10 ppm) iNO groups. The primary outcome
was oxygenation improvement, measured by arterial PaO2, oxygen saturation, and oxygen
index (OI). Secondary outcomes included mortality, bronchopulmonary dysplasia (BPD),
retinopathy of prematurity (ROP), periventricular leukomalacia (PVL), and intraventricular
hemorrhage (IVH).
Results: A total of 150 extreme preterm infants were included, with 75 in each dosage group.
The 10 ppm group demonstrated greater improvements in PaO2 (18.2 mmHg vs. 12.5 mmHg,
p<0.01), O2 saturation (15% vs. 10%, p<0.05), and OI reduction (6.8 vs. 4.2, p<0.05).
Additionally, the incidence of BPD was lower in the 10 ppm group (28% vs. 38%, p<0.05).
Mortality and rates of ROP,PVL, and IVH were not significantly different between groups.
Conclusion: Inhaled nitric oxide at 10 ppm appears more effective and safer than 20 ppm for
treating hypoxic respiratory failure in extreme preterm infants. Lower doses may optimize
clinical outcomes in this population
References
1- Stritzke A, Bhandari V, Lodha A. Use of inhaled nitric oxide in preterm infants: Is there
sufficient evidence? Indian J Pediatr. 2021;88(2):1-5. doi:10.1007/s12098-020-03493-6
2- Tousoulis D, Kampoli AM, Tentolouris C, Papageorgiou N, Stefanadis C. The role of nitric
oxide on endothelial function. Curr Vasc Pharmacol. 2012;10(1):4-18.
doi:10.2174/157016112798829760
3- Ahluwalia J, Tooley J, Cheema I, et al. A dose-response study of inhaled nitric oxide in
hypoxic respiratory failure in preterm infants. Early Hum Dev. 2006;82(7):477-83.
doi:10.1016/j.earlhumdev.2005.12.003
4- Barrington KJ, Finer N, Pennaforte T. Inhaled nitric oxide for respiratory failure in preterm
infants. Cochrane Database Syst Rev. 2017;1(1) ,
doi:10.1002/14651858.CD000509.pub5
5- Askie LM, Ballard RA, Cutter GR, et al. Inhaled nitric oxide in preterm infants: an
individual-patient data meta-analysis of randomized trials. Pediatrics. 2011;128(4):729-
739. doi:10.1542/peds.2010-2722
6- Shiraishi J, Kusuda S, Cho K, et al. Standardization of nitric oxide inhalation in extremely
preterm infants in Japan. Pediatr Int. 2019;61(2):152-157. doi:10.1111/ped.13781
7- Jiang Q, Gao X, Liu C, et al. Early inhaled nitric oxide in preterm infants <34 weeks with
evolving bronchopulmonary dysplasia. J Perinatol. 2016;36(10):883-889.
doi:10.1038/jp.2016.112
8- Ballard RA, Truog WE, Cnaan A, et al. Inhaled nitric oxide in preterm infants undergoing
mechanical ventilation. N Engl J Med. 2006;355(4):343-353.
doi:10.1056/NEJMoa060442
9- Schreiber MD, Gin-Mestan K, Marks JD, Huo D, Lee G, Srisuparp P. Inhaled nitric oxide
in premature infants with the respiratory distress syndrome. Pediatrics.
2003;112(6):1414-1419. doi:10.1542/peds.112.6.1414
10- Kinsella JP, Cutter GR, Walsh WF, et al. Early inhaled nitric oxide therapy in premature
newborns with respiratory failure. Pediatrics. 2006;117(1):216-224.
doi:10.1542/peds.2005-0533
11- Mercier JC, Hummler H, Durrmeyer X, et al. Inhaled nitric oxide versus placebo in
isolated hypoxic respiratory failure of the neonate: a multicenter randomized controlled
trial. J Pediatr. 2010;157(5):676-682.e1. doi:10.1016/j.jpeds.2010.05.007
12- Subhedar NV, Elbourne D, Davies PA. Prolonged low-dose inhaled nitric oxide in
preterm infants: a pilot study. Cochrane Database Syst Rev. 2007;(1).
doi:10.1002/14651858.CD000509.pub4
13- Donohue PK, Gilmore MM, Cristofalo EA, et al. Inhaled nitric oxide in preterm infants: a
systematic review. Am J Respir Crit Care Med. 2011;184(5):573-579.
doi:10.1164/rccm.201101-0067C
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