Is there a place for inhaled nitric oxide in the therapy of acute pulmonary embolism?
Tanus-Santos JE., Theodorakis MJ.
Acute pulmonary embolism (PE) is a serious complication resulting from the migration of emboli to the lungs. Although deep venous thrombi are the most common source of emboli to the lungs, other important sources include air, amniotic fluid, fat and bone marrow. Regardless of the specific source of the emboli, very little progress has been made in the pharmacological management of this high mortality condition. Because the prognosis is linked to the degree of elevation of pulmonary vascular resistance, any therapeutic intervention to improve the hemodynamics would probably increase the low survival rate of this critical condition. Inhaled nitric oxide (iNO) has been widely tested and used in cases of pulmonary hypertension of different causes. In the last few years some authors have described beneficial effects of iNO in animal models of acute PE and in anecdotal cases of massive PE. The primary cause of death in massive PE that is caused by deep venous thrombi, gas or amniotic fluid, is acute right heart failure and circulatory shock. Increased pulmonary vascular resistance following acute PE is the cumulative result of mechanical obstruction of pulmonary vessels and pulmonary arteriolar constriction (attributable to a neurogenic reflex and to the release of vasoconstrictors). As such, the vasodilator effects of iNO could actively oppose the pulmonary hypertension following PE. This hypothesis is consistently supported by experimental studies in different animal models of PE, which demonstrated that iNO decreased (by 10 to 20%) the pulmonary artery pressure without improving pulmonary gas exchange. Although maximal vasodilatory effects are probably achieved by less than 5 parts per million iNO, which is a relatively low concentration, no dose-response study has been published so far. In addition to the animal studies, a few anecdotal reports in the literature suggest that iNO may improve the hemodynamics during acute PE. However, no prospective, controlled, randomized clinical trial addressing this issue has been conducted to date. Future investigations addressing the effects of iNO combined with other drugs such as vasoconstrictors and inhibitors of phosphodiesterase III or V, may increase the responsiveness to iNO in acute PE.