Paven D, Muret J, Beloucif S, Gatecel C, Kermarrec N, Guinard N, Mateo J
Department of Anesthesiology and Critical Care Medicine, U.F.R. de Médecine Lariboisière-Saint-Louis, Université Paris VII, France.
Anesthesiology. 1998 Nov;89(5):1157-65. doi: 10.1097/00000542-199811000-00016.
The partition of pulmonary blood flow between normal and shunting zones is an important determinant of oxygen tension in arterial blood (PaO2). 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 PaO2. Such a combination was tested in patients with hypoxia caused by focal lung lesions, distinct from the acute respiratory distress syndrome.
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 microg x 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 (FI(O2)) and positive end-expiratory pressure (PEEP) levels. Changes in blood gases and pulmonary and systemic hemodynamics were measured.
Systemic hemodynamic variables remained stable in all protocol conditions. Use of iNO improved arterial oxygenation and decreased intrapulmonary shunt. Almitrine similarly improved PaO2 but increased pulmonary artery pressure and right atrial pressure. Coadministration of iNO and almitrine improved PaO2 compared with each drug alone and with control. All patients responded (that is, they had at least a +30% increase in PaO2) to this coadministration. When the drug combination was continued, FI(O2) and PEEP could be reduced over 8 h. The hospital mortality rate was 33% and unrelated to hypoxia.
In hypoxemic focal lung lesions, iNO or low-dose almitrine markedly improved PaO2 to a similar extent. Furthermore, the coadministration amplified the PaO2 increase at a level that allowed reductions in FI(O2) and PEEP levels.
正常区域与分流区域之间肺血流的分配是动脉血氧张力(PaO2)的一个重要决定因素。作者推测,吸入一氧化氮(iNO)与阿米三嗪输注联合使用可能因其药理特性而具有额外作用,从而改善PaO2。在由局灶性肺部病变导致缺氧的患者中(有别于急性呼吸窘迫综合征)对这种联合用药进行了测试。
纳入15例尽管接受了最佳治疗但仍患有缺氧性局灶性肺部病变的患者,并依次接受以下治疗:(1)5 ppm的iNO;(2)在使用iNO期间进行低剂量阿米三嗪输注(5.5±1.7微克·千克⁻¹·分钟⁻¹);(3)单独输注阿米三嗪(停用NO)。然后重新引入iNO,我们研究联合用药在降低吸入气中氧分数浓度(FI(O2))和呼气末正压(PEEP)水平方面的效果。测量血气、肺和全身血流动力学的变化。
在所有方案条件下,全身血流动力学变量均保持稳定。使用iNO可改善动脉氧合并降低肺内分流。阿米三嗪同样可改善PaO2,但会增加肺动脉压和右心房压。与单独使用每种药物及对照组相比,iNO与阿米三嗪联合使用可改善PaO2。所有患者对这种联合用药均有反应(即他们的PaO2至少增加30%)。当继续使用药物组合时,FI(O2)和PEEP可在8小时内降低。医院死亡率为33%,与缺氧无关。
在低氧性局灶性肺部病变中,iNO或低剂量阿米三嗪在相似程度上可显著改善PaO2。此外,联合用药可在一定程度上放大PaO2的升高幅度,从而使FI(O2)和PEEP水平降低。