Key considerations on nebulization of antimicrobial agents to mechanically ventilated patients

Abstract

Nebulized antibiotics have an established role in patients with cystic fibrosis or bronchiectasis. Their potential benefit to treat respiratory infections in mechanically ventilated patients is receiving increasing interest. In this consensus statement of the European Society of Clinical Microbiology and Infectious Diseases, the body of evidence of the therapeutic utility of aerosolized antibiotics in mechanically ventilated patients was reviewed and resulted in the following recommendations: Vibrating-mesh nebulizers should be preferred to jet or ultrasonic nebulizers. To decrease turbulence and limit circuit and tracheobronchial deposition, we recommend: (a) the use of specifically designed respiratory circuits avoiding sharp angles and characterized by smooth inner surfaces, (b) the use of specific ventilator settings during nebulization including use of a volume controlled mode using constant inspiratory flow, tidal volume 8 mL/kg, respiratory frequency 12 to 15 bpm, inspiratory:expiratory ratio 50%, inspiratory pause 20% and positive end-expiratory pressure 5 to 10 cm HO and (c) the administration of a short-acting sedative agent if coordination between the patient and the ventilator is not obtained, to avoid patient's flow triggering and episodes of peak decelerating inspiratory flow. A filter should be inserted on the expiratory limb to protect the ventilator flow device and changed between each nebulization to avoid expiratory flow obstruction. A heat and moisture exchanger and/or conventional heated humidifier should be stopped during the nebulization period to avoid a massive loss of aerosolized particles through trapping and condensation. If these technical requirements are not followed, there is a high risk of treatment failure and adverse events in mechanically ventilated patients receiving nebulized antibiotics for pneumonia.

Study of the disposition of nebulized tobramycin

“…We used the laser diffractometer which is a validated technique for the assessment of aerosol particle size distribution [202] and an established technique for the nebulized mass study [66]. Recent recommendations have been to place the VMN 10-15 cm from the Y-piece [19]. The VMN was placed just before the Y-piece in the inspiratory limb to mimic local and international practices [203] as well as the manufacturer's recommendations.…”

“…A shorter nebulization time is preferable to prevent adverse effects of the recommended ventilator settings that might be used to optimise aerosol delivery during nebulization [19]. Depending on the drug and delivery systems, there could be large variations in nebulization time from long (mean duration 47 minutes for teicoplanin [139]) to short (4.5 minutes for aztreonam [259]).…”

“…Although there are a number of delivery devices available, VMN is recommended for nebulized antibiotic therapy in mechanically ventilated patients [192,193]. We As recommended by expert consensus, humidification was turned off for the experiments [194]. The tips of the tracheal tubes were placed in the receptacle of the laser diffractometer (Spraytec, Malvern Instruments, UK) using a silicone adaptor.…”

“…Tobramycin 500 mg/5 ml (Tobra-day®, Phebra, Australia) yielding a concentration of 100 mg/ml. Recent guidelines support the use of a vibrating mesh nebulizer (VMN) for aerosolised antibiotic therapy with MV [19,193]. Accordingly, disposable VMNs (Aeroneb pro, Aerogen Inc., Galway, Ireland) were employed for the study.…”

“…Numerous in vitro and in vivo studies have attempted to study the effects of these different factors with a view to generate data to guide optimal settings. Consequently, expert groups have made recommendations for the appropriate use of nebulized antibiotics with mechanical ventilation [19]. However, dosing schedules for nebulized antibiotics remains an ongoing concern.…”