In Vitro Study of Nebulizer Position Effects on Colistimethate Sodium Administration, Drug Deposition, and Filter Pressure Drop in Mechanical Ventilation.

Abstract

<h4>Background</h4>Colistimethate sodium (CMS) is increasingly being administered as aerosol therapy in mechanically ventilated patients. Although vibrating-mesh nebulizers (VMNs) are commonly used, the impact of repeated high-dose CMS administration on expiratory filter loading and circuit pressure drop has not been well defined. This study evaluated circuit deposition patterns and changes in expiratory filter pressure drop according to the nebulizer position.<h4>Methods</h4>A ventilator with adult settings and heated humidification was connected to an endotracheal tube and test lung. A VMN was positioned either at the Y-adapter or at the humidifier inlet. Two CMS vials (160 mg each) were diluted in 6 mL of saline and nebulized. Fourteen treatments were administered over 7 days in 5 independent experiments per group (no. <i>=</i> 5). Drug deposition was quantified by high-performance liquid chromatography. Pressure drop, defined as the difference between upstream and downstream pressure across the expiratory high-efficiency particulate air filter, was measured over repeated administrations and analyzed using a mixed repeated-measures model.<h4>Results</h4>The nebulizer position significantly altered deposition within the ventilator circuit. Placement at the Y-adapter resulted in greater exhalation valve deposition (28.35 ± 4.83 mg vs 5.83 ± 1.51 mg, <i>P</i> < .001) and increased pressure drop over time. A significant time-by-position interaction was observed (<i>P</i> = .01), with higher pressure drop after 14 treatments. In contrast, humidifier-inlet placement was associated with greater drug accumulation within the humidifier chamber (35.59 ± 6.21%) and a smaller increase in pressure drop.<h4>Conclusions</h4>During repeated high-dose CMS administration, the nebulizer position influenced circuit deposition patterns and expiratory filter pressure drop. Placement at the Y-adapter was associated with greater expiratory limb deposition and increased filter pressure drop over time, whereas humidifier-inlet placement shifted the drug accumulation proximally within the circuit.