Effect of nitric oxide in meconium aspiration syndrome after treatment with surfactant

Crit Care Med. 1997 Oct;25(10):1744-7. doi: 10.1097/00003246-199710000-00027.


Objective: To test the hypothesis that inhaled nitric oxide may be an effective therapeutic agent in meconium aspiration syndrome and may improve oxygenation after pretreatment with surfactant.

Design: Prospective, interventional study.

Setting: The animal research laboratory at The Children's National Medical Center.

Subjects: Eight newborn pigs, 1 to 2 wks of age, 4.1 +/- 0.4 kg, were used for the study.

Interventions: Animals were anesthetized, paralyzed, intubated, and mechanically ventilated. Catheters were placed in the femoral vein and artery, and in the pulmonary artery. After 1 hr of recovery, 10 mL/kg of 20% meconium in normal saline solution was insufflated into the lungs. Animals were ventilated to maintain arterial blood gases in a normal range (i.e., pH of 7.35 to 7.45, Paco2 of 40 to 45 torr [5.3 to 6.0 kPa], and Pao2 of 70 to 90 torr [9.3 to 12.0 kPa]). Ventilatory settings were increased, as needed, until the following maximum settings were reached: FIO2 of 1.0; peak inspiratory pressure of 40 cm H2O; and intermittent mandatory ventilation of 60 breaths/min. After 2 hrs of conventional ventilation or demonstration of clinically important lung disease by failure to maintain desired blood gases on the maximum ventilatory settings, 4 mL/kg of beractant was given intratracheally. After a short period of stabilization following surfactant therapy, inhaled nitric oxide was administered. Concentrations of 40, 20, and 10 parts per million were given. To assure that there was no additive effect of inhaled nitric oxide, each dose was given for 20 mins, followed by a 15-min normalization period at 0 parts per million.

Measurements and main results: Physiologic measurements, ventilatory settings, arterial blood gases, and methemoglobin were recorded at each study period. Measurements were taken after each exposure to inhaled nitric oxide and after its discontinuation. Arterial oxygen saturation and Pao2 were significantly lower after meconium aspiration when compared with baseline values. After treatment with surfactant, administration of inhaled nitric oxide improved oxygenation without a significant decrease in pulmonary arterial pressure.

Conclusions: In this model of meconium aspiration syndrome, short-term exposure to inhaled nitric oxide after treatment with surfactant improved oxygenation secondary to better distribution of inhaled nitric oxide. The increase in oxygenation may be secondary to an improved ventilation/perfusion mismatch, since the primary etiology of hypoxia in this model may be a combination of parenchymal lung disease and pulmonary hypertension.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Biological Products*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Drug Therapy, Combination
  • Humans
  • Infant, Newborn
  • Meconium Aspiration Syndrome / blood
  • Meconium Aspiration Syndrome / drug therapy*
  • Meconium Aspiration Syndrome / physiopathology
  • Nitric Oxide / administration & dosage*
  • Prospective Studies
  • Pulmonary Surfactants / administration & dosage*
  • Respiratory System Agents / administration & dosage*
  • Swine


  • Biological Products
  • Pulmonary Surfactants
  • Respiratory System Agents
  • Nitric Oxide
  • beractant