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, nit ric oxide, and almitrine bismesylate, each acting by a different mecha nism to improve arterial oxygenation, could exert additive beneficial effects when used in combination in patients with severe acute respira tory distress syndrome (ARDS). Design: Prospective, nonrandomized, int erventional study. Setting: Medical and surgical intensive care units at a university tertiary care center. Patients: Twelve patients with A RDS and severe hypoxemia, defined as Pao(2)/Fio(2) of less than or equ al to 150 and Fio(2) of greater than or equal to 0.6, with pulmonary a rtery occlusion pressure of <18 mm Hg. Interventions: Inhaled nitric o xide (20 parts per million for 15 mins) in the supine and prone positi on, and intravenous almitrine bismesylate while prone (1 mg/kg/hr for 60 mins), alone or combined with nitric oxide. Measurements and Main R esults: Hemodynamic, blood gas, and gas exchange measurements were per formed at sequential time points as follows: a) baseline supine; b) ni tric oxide in the supine position; c) after return to baseline supine; d) after 30 mins prone; e) after 120 mins prone; f) nitric oxide whil e prone; g) after return to baseline prone; h) almitrine bismesylate p rone; and i) nitric oxide and almitrine bismesylate combined, for 15 m ins prone. Patients were considered responders to the prone position i f a gain in PaO2 of greater than or equal to 10 torr (greater than or equal to 1.3 kPa) or a gain in the Pao(2)/Fio(2) ratio of greater than or equal to 20 was observed. Seven patients (58%) responded to being turned prone. Compared with supine baseline conditions, nitric oxide a nd supine position increased arterial oxygen saturation from 89 +/- 4 (SD)% to 92 +/- 3% (p < .05) and nitric oxide plus prone position incr eased arterial oxygen saturation (94 +/- 3% vs. 89 +/- 4%, p < .05) an d decreased the alveolar-arterial oxygen difference from 406 +/- 124 t orr (54 +/- 16 kPa) to 387 +/- 108 torr (51 +/- 14 kPa) (p < .05). Alm itrine bismesylate increased Pao(2)/Fio(2) vs. baseline (122 +/- 56 vs . 84 +/- 21, p < .05). Almitrine bismesylate decreased the alveolarart erial oxygen difference vs. baseline from 406 +/- 124 torr (53.9 +/- 1 6.5 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 no t improve oxygenation. However, the combination of nitric oxide and al mitrine bismesylate increased Pao(2)/Fio(2) vs. nitric oxide supine an d 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 furth er improvement in Pao, compared with the prone position alone, with Pa O, increasing from 78 +/- 12 torr (10.3 +/- 1.6 kPa) to 111 +/- 55 tor r (14.7 +/- 7.3 kPa) (p < .05), which was not the case when either nit ric oxide or almitrine bismesylate was added separately. Heart rate an d cardiac output were increased by almitrine bismesylate compared with all other measurements. Mean pulmonary arterial pressure was decrease d by nitric oxide (27 + 7 vs. 30 +/- 7 mm Hg nitric oxide supine vs. b aseline 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 su pine, 33 +/- 8 mm Hg baseline prone, and 29 +/- 7 mm Hg nitric oxide p rone; p < .05). The increase in mean pulmonary arterial pressure was t otally abolished by nitric oxide (31 +/- 5 vs. 35 +/- 9 mm Hg, p < .05 ). Minute ventilation, respiratory system compliance, physiologic dead space, and Pace, remained unchanged. Conclusion: In ARDS patients with severe hypoxemia, arterial oxygenation can be improved by combining t he prone position, nitric oxide, and almitrine bismesylate, without de leterious effects.