Positive end-expiratory pressure and response to inhaled nitric oxide: changing nonresponders to responders

Inhaled nitric oxide (INO) has been shown to improve oxygenation in two thirds of patients with acute respiratory distress syndrome (ARDS). Failure to respond to INO is multifactorial. We hypothesized that the addition of positive end expiratory pressure (PEEP) might modify the response to INO in patients who had previously failed to respond to INO.

Patients with ARDS who failed to respond to INO at 1 ppm (PaO2 increase of < 20%) were selected. Each patient underwent a PEEP trial using an improvement in static lung compliance as the end point. One hour after the new PEEP level was reached, hemodynamic and blood gas values were obtained. INO was then reinstituted at 1 ppm, and hemodynamic and blood gas variables were obtained 1 hour later.

Six of nine patients demonstrated an increase in PaO2/FIO2 (161 +/- 27 to 186 +/- 29) with a mean increase in PEEP of 3.7 cm H2O. Each patient responding to PEEP further improved PaO2/FIO2 (186 +/- 29 to 223 +/- 36) with INO at 1 ppm. The three patients who failed to improve after the PEEP increase also failed to respond to a second trial of INO. There were no changes in cardiac output or systemic vascular resistance. Pulmonary artery pressures decreased slightly (39 +/- 5 vs 38 +/- 7 vs 35 +/- 9 mm Hg). Pulmonary vascular resistance decreased significantly after reintroduction of INO (298 +/- 131 vs 310 +/- 122 vs 249 +/- 105 dynes/sec/cm-5) in patients who responded positively.

The response of ARDS patients to INO can be improved if optimum alveolar recruitment is achieved by the addition of PEEP. PEEP and INO have a synergistic effect on PaO2/FIO2. Patients who fail to respond to INO may benefit from an optimum PEEP trial.