Additive beneficial effects of the prone position, nitric oxide, and almitrine bismesylate on gas exchange and oxygen transport in acute respiratory distress syndrome.

OBJECTIVE To test the hypothesis that prone position ventilation, nitric oxide, and almitrine bismesylate, each acting by a different mechanism to improve arterial oxygenation, could exert additive beneficial effects when used in combination in patients with severe acute respiratory distress syndrome (ARDS). DESIGN Prospective, nonrandomized, interventional study. SETTING Medical and surgical intensive care units at a university tertiary care center. PATIENTS Twelve patients with ARDS and severe hypoxemia, defined as PaO2/FIO2 of < or = 150 and FIO2 of > or = 0.6, with pulmonary artery occlusion pressure of < 18 mm Hg. INTERVENTIONS Inhaled nitric oxide (20 parts per million for 15 mins) in the supine and prone position, and intravenous almitrine bismesylate while prone (1 mg/kg/hr for 60 mins), alone or combined with nitric oxide. MEASUREMENTS AND MAIN RESULTS Hemodynamic, blood gas, and gas exchange measurements were performed at sequential time points as follows: a) baseline supine; b) nitric oxide in the supine position; c) after return to baseline supine; d) after 30 mins prone; e) after 120 mins prone; f) nitric oxide while prone; g) after return to baseline prone; h) almitrine bismesylate prone; and i) nitric oxide and almitrine bismesylate combined, for 15 mins prone. Patients were considered responders to the prone position if a gain in PaO2 of > or = 10 torr (> or = 1.3 kPa) or a gain in the PaO2/FIO2 ratio of > or = 20 was observed. Seven patients (58%) responded to being turned prone. Compared with supine baseline conditions, nitric oxide and supine position increased arterial oxygen saturation from 89 +/- 1 (SD)% to 92 +/- 3% (p < .05) and nitric oxide plus prone position increased arterial oxygen saturation (94 +/- 3% vs. 89 +/- 4%, p < .05) and decreased the alveolar-arterial oxygen difference from 406 +/- 124 torr (54 +/- 15 kPa) to 387 +/- 108 torr (51 +/- 14 kPa) (p < .05). Almitrine bismesylate increased PaO2/FIO2 vs. baseline (122 +/- 58 vs. 84 +/- 21, p < .05). Almitrine bismesylate decreased the alveolar-arterial oxygen difference vs. baseline from 406 +/- 124 torr (53.9 +/- 16.5 kPa) to 386 +/- 112 torr (51.3 +/- 14.8 kPa) and vs. nitric oxide and supine position from 406 +/- 111 torr (53.9 +/- 14.7 kPa) to 386 +/- 112 torr (51.3 +/- 14.8 kPa) (p < .05). Prone position alone did not improve oxygenation. However, the combination of nitric oxide and almitrine bismesylate increased PaO2/FIO2 vs. nitric oxide supine and nitric oxide prone conditions (147 +/- 69 vs. 84 +/- 25 and 91 +/- 18, respectively; p < .05). In patients responding to the prone position (n = 7), combining nitric oxide and almitrine bismesylate led to further improvement in PaO2 compared with the prone position alone, with PaO2 increasing from 78 +/- 12 torr (10.3 +/- 1.6 kPa) to 111 +/- 55 torr (14.7 +/- 7.3 kPa) (p < .05), which was not the case when either nitric oxide or almitrine bismesylate was added separately. Heart rate and cardiac output were increased by almitrine bismesylate compared with all other measurements. Mean pulmonary arterial pressure was decreased by nitric oxide (27 +/- 7 vs. 30 +/- 7 mm Hg nitric oxide supine vs. baseline supine and 29 +/- 7 vs. 33 +/- 8 mm Hg nitric oxide prone vs. baseline prone, p < .05) and increased by almitrine bismesylate (36 +/- 9 vs. 30 +/- 7 mm Hg baseline supine, 27 +/- 7 mm Hg nitric oxide supine, 33 +/- 8 mm Hg baseline prone, and 29 +/- 7 mm Hg nitric oxide prone; p < .05). The increase in mean pulmonary arterial pressure was totally abolished by nitric oxide (31 +/- 5 vs. 36 +/- 9 mm Hg, p < .05). Minute ventilation, respiratory system compliance, physiologic deadspace, and PaCO2 remained unchanged. CONCLUSION In ARDS patients with severe hypoxemia, arterial oxygenation can be improved by combining the prone position, nitric oxide, and almitrine bismesylate, without deleterious effects.