Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double-blind study

Lancet. 2000 Oct 28;356(9240):1464-9. doi: 10.1016/S0140-6736(00)02869-5.

Abstract

Background: Pulmonary hypertensive crises (PHTC) are a major cause of morbidity and mortality after congenital heart surgery. Inhaled nitric oxide is frequently used as rescue therapy. We did a randomised double-blind study to investigate the role of routinely administered inhaled nitric oxide to prevent pulmonary hypertension in infants at high risk.

Methods: We enrolled 124 infants (64 male, 60 female; median age 3 months [IQR 1-5]), 76% with large ventricular or atrioventricular septal defects, who had high pulmonary flow, pressure, or both, and were undergoing corrective surgery for congenital heart disease. They were randomly assigned continuous low-dose inhaled nitric oxide (n=63) or placebo (n=61) from surgery until just before extubation. We measured the numbers of PHTC, time on study gas, and hours spent in intensive care. Analysis was done by intention to treat.

Findings: Compared with placebo, infants receiving inhaled nitric oxide had fewer PHTC (median four [IQR 0-12] vs seven [1-19]; relative risk, unadjusted 0.66, p<0.001, adjusted for dispersion 0.65, p=0.045) and shorter times until criteria for extubation were met (80 [38-121] vs 112 h [63-164], p=0.019). Time taken to wean infants off study gas was 35% longer in the nitric oxide group than in the placebo group (p=0.19), but the total time on the study gas was still 30 h shorter for the nitric oxide group (87 [43-125] vs 117 h [67-168], p=0.023). No important toxic effects arose.

Interpretation: In infants at high risk of pulmonary hypertension, routine use of inhaled nitric oxide after congenital heart surgery can lessen the risk of pulmonary hypertensive crises and shorten the postoperative course, with no toxic effects.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Double-Blind Method
  • Female
  • Heart Defects, Congenital / physiopathology
  • Heart Defects, Congenital / surgery*
  • Humans
  • Hypertension, Pulmonary / physiopathology
  • Hypertension, Pulmonary / prevention & control*
  • Infant
  • Infant, Newborn
  • Lung / blood supply
  • Male
  • Nitric Oxide / administration & dosage
  • Nitric Oxide / therapeutic use*
  • Treatment Outcome
  • Vascular Resistance / drug effects

Substances

  • Nitric Oxide