Inhaled Nitric Oxide and Prevention of Pulmonary Hypertension After Congenital Heart Surgery: A Randomized Double-Blind Study - Inhaled Nitric Oxide and Prevention of Pulmonary Hypertension


Inhaled Nitric Oxide and Prevention of Pulmonary Hypertension After Congenital Heart Surgery: A Randomized Double-Blind Study.


Infants with large atrioventricular or ventricular septal defects and high pulmonary flow or pressure are at high risk for pulmonary hypertensive crises (PHTC) early after surgical correction. The authors evaluated the effect of routine continuous low-dose inhaled nitric oxide (NO) on the number of early post-operative pulmonary hypertensive crises, time to eligibility for extubation, length of stay in the intensive care unit and lung injury score on chest x-ray.

Study Design

Study Design:

Patients Enrolled: 124

Drug/Procedures Used:

Double-blind, randomized study of 124 infants, median age 3 months, who received continuous inhaled NO (10 ppm) or placebo after corrective cardiac surgery. PHTC (pulmonary/systemic artery pressure ratio >0.75 without hemodynamic compromise or pulmonary/systemic artery pressure >0.5 with drop in systolic blood pressure >20% or O2 saturation <90%) were treated with an aggressive stepwise, standardized protocol including sedation, hyperoxia, hyperventilation, vasopressors and epoprostenol. Recurrent or refractory PHTC were treated with rescue open-label NO.

Principal Findings:

Fewer PHTC occurred in infants receiving NO than those receiving placebo (4 vs. 7 PHTC, p < 0.001), and pulmonary vascular resistance while on study gas was lower. Time to eligibility for extubation was shorter in the NO group (80 vs. 112 hours, p = 0.01), but the actual time to extubation was not different, owing to other factors including removal of transthoracic lines and staffing levels. The number of infants requiring rescue NO (two receiving NO vs. five on placebo), the length of ICU stay, lung injury score and number of deaths were not different.

Continuous low-dose inhaled NO decreases the number of PHTC and shortens the time to eligibility to extubation in high risk infants after corrective surgery for congenital cardiac defects.


Although the number of PHTC was reduced by NO, there were no differences in hard clinical end points such as length of intubation or ICU stay. This is most likely due to the standardized aggressive protocol used for treating PHTC. Routine application of this standardized protocol may be less expensive than routine prophylactic use of inhaled NO and should be studied.


Miller OI, Tang SF, Keech A, Pigott NB, Beller E, Celermajer DS. Lancet 2000;356:1464-9.

Clinical Topics: Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Pulmonary Hypertension and Venous Thromboembolism, Cardiac Surgery and CHD and Pediatrics, Cardiac Surgery and Heart Failure, Congenital Heart Disease, CHD and Pediatrics and Interventions, CHD and Pediatrics and Prevention, Lipid Metabolism, Pulmonary Hypertension, Interventions and Structural Heart Disease

Keywords: Infant, Intensive Care Units, Epoprostenol, X-Rays, Blood Pressure, Nitric Oxide, Length of Stay, Hyperventilation, Intubation, Nitrates, Hypertension, Pulmonary, Hyperoxia, Heart Septal Defects, Ventricular, Vascular Resistance, Cardiac Surgical Procedures

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