Acute oxygenation response to inhaled nitric oxide when combined with high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome

Crit Care Med. 2003 Feb;31(2):383-9. doi: 10.1097/01.CCM.0000049953.86613.02.


Objective: To prospectively evaluate the oxygenation effect of inhaled nitric oxide (INO) delivered during high-frequency oscillatory ventilation in adult patients with the acute respiratory distress syndrome and oxygenation failure. DESIGN Prospective, clinical study.

Setting: Intensive care unit of a university teaching hospital.

Patients: A total of 23 adults (14 women, 9 men, 44.9 +/- 17.5 yrs, Acute Physiology and Chronic Health Evaluation II score of 28.6 +/- 7.1) with acute respiratory distress syndrome (lung injury score, 3.5 +/- 0.4) with Fio2 of > or = 0.6 and mean airway pressure of >or=28 cm H2O.

Interventions: INO was initiated at a dose of 5 ppm, and subsequently titrated according to a protocol, to determine the dose (5, 10, or 20 ppm) resulting in the greatest increase in Pao2/Fio2. Blood gas measurements were obtained 10-15 mins after initiation or any increase in INO dosage to assess the effect on Pao2/Fio2.

Measurements and main results: Arterial blood gases and ventilator settings were recorded at four time points: during conventional ventilation just before initiating high-frequency oscillatory ventilation, during high-frequency oscillatory ventilation just before initiating INO, after 30 mins on the optimal dose of INO, and 8-12 hrs after starting INO. Oxygenation index ([Fio2 x mean airway pressure x 100]/Pao2) and Pao2/Fio2 ratios were calculated at the same time intervals. At 30 mins after INO initiation, 83% of patients had a significant increase in blood oxygen tension, defined as > or = 20% increase in Pao2/Fio2. The mean change in Pao2/Fio2 at 30 mins was 38%. In these 19 patients, Pao2/Fio2 was highest at 20 ppm in four patients, at 10 ppm in eight patients, and at 5 ppm in seven patients. Compared with baseline measurements, Pao2/Fio2 improved significantly at both 30 mins (112 +/- 59 vs. 75 +/- 32, p=.01) and 8-12 hrs after INO initiation (146 +/- 52 vs. 75 +/- 32, p<.0001). In addition, oxygenation index was reduced at 8-12 hrs compared with baseline measurements (26 +/- 13 vs. 40 +/- 17, p=.08).

Conclusions: INO delivered at doses of 5 to 20 ppm during high-frequency oscillatory ventilation increases Pao2/Fio2 and may be a safe and effective rescue therapy for patients with severe oxygenation failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Female
  • High-Frequency Ventilation*
  • Humans
  • Male
  • Nitric Oxide / administration & dosage*
  • Oxygen / metabolism*
  • Prospective Studies
  • Respiratory Distress Syndrome / metabolism*
  • Respiratory Distress Syndrome / therapy*


  • Nitric Oxide
  • Oxygen