Background: The partition of pulmonary blood flow between normal and shunting zones is an important determinant of oxygen tension in arterial blood (Pa-O2). The authors hypothesized that the combination of inhaled nitric oxide (iNO) and almitrine infusion might have additional effects related to their pharmacologic properties to improve Pa-O2. Such a combination was tested in patients with hypoxia caused by focal lung lesions, distinct from the acute respiratory distress syndrome. Methods: Fifteen patients with hypoxic focal lung lesions despite optimal therapy were included and successively treated with (1) 5 ppm iNO, (2) low-dose almitrine infusion (5.5 +/- 1.7 mu g.kg(-1).min(-1)) during iNO, and (3) almitrine infusion alone (with NO turned off). Then iNO was reintroduced and we studied the effect of the coadministration in reducing the fractional concentration of oxygen in inspired gas (FIO2) and positive end-expiratory pressure (PEEP) levels. Changes in blood gases and pulmonary and systemic hemodynamics were measured. Results: Systemic hemodynamic variables remained stable in all protocol conditions. Use of iNO improved arterial oxygenation and decreased intrapulmonary shunt. Almitrine similarly improved Pa-O2 but increased pulmonary artery pressure and right atrial pressure. Coadministration of WO and almitrine improved Pa-O2 compared with each drug alone and with control. All patients responded (that is, they had at least a +30% increase in Pa-O2) to this coadministration. When the drug com bination was continued, FIO2 and PEEP could be reduced over 8 h. The hospital mortality rate was 33% and unrelated to hypoxia. Conclusions In hypoxemic focal lung lesions, iNO or low-dose almitrine markedly improved Pa-O2 to a similar extent. Furthermore, the coadministration amplified the Pa-O2 increase at a level that allowed reductions in FIO2 and PEEP levels.
