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Acute and sustained effects of early administration of inhaled nitric oxide to children with acute respiratory distress syndrome*

Fioretto, José R. MD, PhD; de Moraes, Marcos A. MD; Bonatto, Rossano C. MD, PhD; Ricchetti, Sandra M. Q. MD; Carpi, Mário F. MD

Pediatric Critical Care Medicine: September 2004 - Volume 5 - Issue 5 - p 469-474
doi: 10.1097/01.PCC.0000137986.83738.D7
Clinical Investigations

Objective: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome.

Design: Observational study.

Setting: Pediatric intensive care unit at a university-affiliated hospital.

Patients: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs.

Interventions: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000.

Measurements and Main Results: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao2/Fio2 ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao2/Fio2 ratio was lower (CTG, 116.9 ± 34.5; iNOG, 62.5 ± 12.8, p < .0001) and oxygenation index higher (CTG, 15.2 [range, 7.2–32.2]; iNOG, 24.3 [range, 16.3–70.4], p < .0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio2 and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p < .001). There was no difference in intensive care stay (CTG, 10 days [range, 2–49]; iNOG, 12 [range, 6–26], p > .05) or duration of mechanical ventilation (TCG, 9 days [range, 2–47]; iNOG, 10 [range, 4–25], p > .05).

Conclusions: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.

From the Pediatric Intensive Care Unit, Department of Pediatrics, São Paulo State University-Unesp, Botucatu Medical School, São Paulo, Brazil.

*See also p. 496.

Supported, in part, by FAPESP, process number 2001/04971-3.

Address requests for reprints to: José Roberto Fioretto, MD, PhD, UNESP, Faculdade de Medicina de Botucatu, Departamento de Pediatria, 18.618–970, Botucatu, São Paulo, Brasil. E-mail:

©2004The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies