Acute response to inhaled Nitric Oxide (NO) in Acute Respiratory Distress Syndrome (ARDS)

Purpose: Describe the acute physiologic response to inhaled NO in ARDS and assess the association of acute response with clinical outcome variables. Methods: Double-blind, placebo-controlled, 28 day phase II study in patients with ARDS. Patients were randomized to receive 0, 1.25, 5, 20, 40, or 80 ppm inhaled NO. Physiologic variables were measured while ventilator management was held constant. Response was defined as a ≥20% increase in PaO2 compared to baseline. Results. A total of 177 patients (68% male) were enrolled with mean age 48 years and mean APACHE II 17. The acute patient response to inhaled NO during the first 4 hr period is described below. % Response 0 ppm 1.25 ppm 5 ppm 20 ppm 40 ppm 80 ppm All INO 30 min 9 57 47 59 65 50 56 1 hr 16 64 56 71 65 43 63 2 hr 22 59 47 46 70 50 55 4 hr 24 45 62 62 63 57 59 Change in responsiveness to inhaled NO over the 4 hr period is detailed below. 0 ppm 1.25 ppm 5 ppm 20 ppm 40 ppm 80 ppm Lost 4% 24% 3% 17% 12% 14% Gained 19% 10% 18% 21% 8% 29% In the 5 ppm group, there was a significant decrease in the time to meet extubation criteria. However, acute response to inhaled NO (as defined) was not associated with a beneficial effect on time to meet extubation criteria, days alive off mechanical ventilation (through dy 28) or mortality. Conclusion: Acute response to inhaled NO in ARDS patients (as defined) is highly dynamic over time and does not predict clinical outcome. Clinical implications: Criteria used to classify ARDS patients as responders to inhaled NO are arbitrary and do not reflect physiologic changes over time.