Ultrasonic versus jet nebulization of iloprost in severe pulmonary hypertension

Abstract

Inhalation of iloprost, a stable prostacyclin analogue, is a promising perspective in the treatment of pulmonary hypertension. In initial clinical studies, a conventional jet nebulizer system was successfully used to decrease pulmonary vascular resistance and pressure, requiring however, up to twelve inhalations of 12-15 min per day. The aim of this study was to investigate if the application of an equal dose of iloprost at a drastically reduced duration of inhalation with the use of a more efficient ultrasonic nebulizer, leads to comparable haemodynamic effects, without escalation of side effects. The physical features of the jet nebulizer system (Ilo-Neb) and the ultrasonic nebulizer (Multisonic Compact) were characterized by laser diffractometry and a Tc99m-tracer technique. Mass median aerodynamic diameters were 3.2 microm for the jet and 3.9 microm for the ultrasonic nebulizer. Total output (mean+/-SD) was 60+/-7 microL.min(-1) (jet) and 163+/-15 microL.min(-1)(ultrasonic), and efficiency of the devices was 39+/-3% (jet) and 86+/-5% (ultrasonic). Based on these data, a total inhalative dose of 2.8 microg iloprost was delivered by jet nebulization within 12 min and by ultrasonic nebulization within 4 min, in 18 patients with severe primary and secondary pulmonary hypertension (New York Heart Association class III and IV), in a randomized crossover design. Haemodynamics were assessed by right heart catheterization. Inhalation with the ultrasonic device and jet nebulizer, reduced mean+/-SEM pulmonary artery pressure from 54.3+/-2.1 to 47.1+/-2.0 and from 53.5+/-2.2 to 47.0+/-2.2 mmHg, respectively, and mean+/-SEM pulmonary vascular resistance from 1,073+/-109 to 804+/-87 and from 1,069+/-125 to 810+/-83 dyn.s.cm(-5), respectively. Both modes of aerosolization were well tolerated. In conclusion, due to the markedly higher efficiency and output of the ultrasonic device, wastage of drug is largely avoided and the duration of inhalation can be shortened to one-third, with comparable haemodynamic effects and without enforcing side effects.