In the setting of mechanical ventilation, recent studies have cast doubt on the ability of nebulizer systems to deliver adequate amounts of medication. We therefore studied ventilator-related and nebulizer-related factors that could potentially affect the amount of aerosol inhaled by an intubated subject. Utilizing two separate protocols, we used a bench model of a ventilator circuit, radiolabeled (technetium pertechnetate, Tc-99m) saline droplets and a filter technique to measure the percentage of radioaerosol delivered. First, we compared four commercially available jet nebulizers and found that there were significant differences In rate of aerosol production between systems, ranging from 3 to 37%. Delivered aerosol was measured at different ventilator settings, and it was found that the duty cycle can potentially influence output by sevenfold. Some nebulizers were also sensitive to changes in the initial volume of solution placed in the nebulizer. The Inclusion of a humidification device significantly reduced output by a mean of 41 +/- 3.5%, but it did not affect particle distribution. Endotracheal tube diameter was not an Important variable. Then, with the effects of the above variables established, a separate series of experiments was performed to test whether the use of different radiolabeling compounds can confound the measurement of inhaled drugs. Two nebulizers (AeroTech II and Twin Jet) and pentamidine as the test drug were studied with fixed ventilator settings, treatment time, endotracheal tube size, and volume fill. No humidification was used. The nebulizer solution was labeled with Tc-99m which was bound to either human serum albumin (HSA) or sulfur colloid (SC). To assess the accuracy and precision of these radioisotopes as indices of drug delivery, we sampled aerosol particles from the inspiratory line using a cascade impactor. Each stage of the cascade was analyzed for drug activity (using high performance liquid chromatography) in nanograms and radioactivity in microcuries. The quantities of drug and radioactivity captured in the aerosol were expressed as percentages of the initial amounts placed In the nebulizer. Using linear regression analysis, there was a close correlation between the radiation inhaled and the pentamidine inhaled for both radioaerosols. However, the slope of the regression line for HSA followed a line of identity, whereas for SC the slope was 0.339. This indicates that if the nebulizer output of drug and radiolabel were assumed to be equivalent, as in most previous studies, the use of SC would underestimate drug inhaled by a factor of 3:1. Similar findings occurred with both nebulizers. We conclude that nebulized aerosol delivery during mechanical ventilation is influenced by the type of nebulizer, the treatment time, the duty cycle, the volume fill of the nebulizer, and the presence of a humidification device. In addition, measurement of drug delivery can be grossly underestimated depending on the choice of radiolabel. If these factors are defined, however. nebulizer systems can be highly efficient In delivering medication to intubated, mechanically ventilated subjects.
