Abstract
Background:
Colistin is used to treat gram-negative infections in critically ill patients. Optimal delivery and particle size distribution of aerosolized colistin during mechanical ventilation has not been reported. This in vitro evaluation explores the impact of aerosol device and dilution on aerosol colistin administration during mechanical ventilation.
Methods:
A Servo-i ventilator (Maquet) operated in volume control (500 mL, 20 breaths/min, PEEP 5 cm H2O, Ti 1.0s) with heated humidification at 37°C was connected to an endotracheal tube (7.5mm), inline with a collecting filter connected to a lung model with compliance of 0.04 L/cm H2O and resistance of 5 cm H2O/L/s (Michigan Instruments). A vibrating mesh nebulizer (VMN, Aerogen) and a pneumatic jet nebulizer (JN, Galemed) powered oxygen at 8 L/min were placed at the inlet of the heated humidifier chamber. Two concentrations of Colistin methanesulfate (CMS) 156 mg (1 million unit) and 312 mg were dissolved in 6 mL distilled water. Drug was placed in both nebulizers, and two concentrations in the JN (JN-156 and JN-312). The inhaled mass distal to ETT was collected on filter (n=5). An Anderson cascade impactor (Thermo Scientific) determined median aerodynamic diameters (MMAD) and fine particle fraction (n=3). The collected drug was eluted from filter and impactor and analyzed by HPLC. Statistical analyses were performed with ANOVA and Scheffepost hoc test with a significance level of P< .05.
Results:
Table below shows inhaled dose and particle size distribution and performance (mean ± SD) with VMN and JN. The inhaled mass was significantly greater with VMN. The particle size was ranged 2.03- 2.26 µm among three groups, without significant difference (P= . 434). The nebulization time was 2 folds longer than JNs, while residual volume was significantly lower (P<0.001).
Conclusions:
The VMN delivered greater inhaled mass than JN with both 156 and 312 mg, despite longer administration time.
Table: CMS deposition, particle size distribution and nebulizer performance
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