Influence of diluent volume of colistimethate sodium on aerosol characteristics and pharmacokinetics in ventilator-associated pneumonia caused by MDR bacteria.

Objectives: Nebulized colistimethate sodium (CMS) can be used to treat ventilator-associated pneumonia caused by MDR bacteria. The influence of the diluent volume of CMS on aerosol delivery has never been studied. The main objectives of the study were to compare aerosol particle characteristics and plasma and urine pharmacokinetics between two diluent volumes in patients treated with nebulized CMS. Methods: A crossover study was conducted in eight patients receiving nebulized CMS every 8 h. After inclusion, nebulization started with 4 million international units (MIU) of CMS diluted either in 6 mL (experimental dilution) or in 12 mL (recommended dilution) of normal saline in a random order. For each diluent volume, CMS aerosol particle sizes were measured and plasma and urine samples were collected every 2 h. Nebulization time and stability of colistin in normal saline were assessed. Results: The mass median aerodynamic diameters were 1.4 ±âŸ0.2 versus 0.9 ±âŸ0.2 µm (P < 0.001) for 6 and 12 mL diluent volumes, respectively. The plasma area under the concentration-time curve from 0 to 8 h (AUC0-8) of colistinA+B was 6.6 (4.3-17.0) versus 6.7 (3.6-14.0) µg·h/mL (P = 0.461) for each dilution. The total amount of colistin and CMS eliminated in the urine represented, respectively, 17% and 13% of the CMS initially placed in the nebulizer chamber for 6 and 12 mL diluent volumes (P = 0.4). Nebulization time was shorter [66 (58-75) versus 93 (69-136) min, P = 0.042] and colistin stability was better with the 6 mL diluent volume. Conclusions: Nebulization with a higher concentration of CMS in saline (4 MIU in 6 mL) decreases nebulization time and improves colistin stability without changing plasma and urine pharmacokinetics or aerosol particle characteristics for lung deposition.

Aerosol delivery and humidification with the Boussignac continuous positive airway pressure device.

BACKGROUND: A simple method for effective bronchodilator aerosol delivery while administering continuing continuous positive airway pressure (CPAP) would be useful in patients with severe bronchial obstruction. OBJECTIVE: To assess the effectiveness of bronchodilator aerosol delivery during CPAP generated by the Boussignac CPAP system and its optimal humidification system. METHODS: First we assessed the relationship between flow and pressure generated in the mask with the Boussignac CPAP system. Next we measured the inspired-gas humidity during CPAP, with several humidification strategies, in 9 healthy volunteers. We then measured the bronchodilator aerosol particle size during CPAP, with and without heat-and-moisture exchanger, in a bench study. Finally, in 7 patients with acute respiratory failure and airway obstruction, we measured work of breathing and gas exchange after a ß(2)-agonist bronchodilator aerosol (terbutaline) delivered during CPAP or via standard nebulization. RESULTS: Optimal humidity was obtained only with the heat-and-moisture exchanger or heated humidifier. The heat-and-moisture exchanger had no influence on bronchodilator aerosol particle size. Work of breathing decreased similarly after bronchodilator via either standard nebulization or CPAP, but P(aO(2)) increased significantly only after CPAP aerosol delivery. CONCLUSIONS: CPAP bronchodilator delivery decreases the work of breathing as effectively as does standard nebulization, but produces a greater oxygenation improvement in patients with airway obstruction. To optimize airway humidification, a heat-and-moisture exchanger could be used with the Boussignac CPAP system, without modifying aerosol delivery.