Aerosolised Drug Administration in the Ventilated Patient: In-Vitro and In-Vivo Correlates

Abstract

ABSTRACT

The use of drugs administered via the airways for the treatment of ventilated patients in an intensive care setting is common. The spectrum of drugs administered this way include bronchodilators, steroids and antimicrobial agents. Despite the administration of these agents directly into a ventilator circuit which communicates directly with the patients lungs, the evidence available suggests that the lung deposition from aqueous aerosols is poor with only 1.2-2.8% of the nebuliser dose reaching the lungs. A variety of factors affect the delivery of drug to the lung: the type of nebuliser used, the nebuliser efficiency, the particle size of the aerosol, the ventilator settings (respiratory rate, tidal volume and inspiratory time) and the position of the nebuliser in the ventilator circuit. A number of these have been explored in-vitro with the results showing that depending on the ventilator settings, the addition of a spacer, the type of nebuliser (e.g. jet or ultrasonic) and the humidification of the circuit, deposition in the lungs may be increased two to three fold. The use of in-vitro circuits provides an indication of the modifications to the circuit that can be tested in-vivo. We have demonstrated that the addition of a spacer to the circuit using an inspiratory actuated jet nebuliser can improve delivery to the lungs by approximately 30% although overall delivery was still poor. A comparison between a jet nebuliser and an ultrasonic nebuliser showed greater deposition with the ultrasonic device. The ultrasonic device was also easier to use in the ventilator circuit because alterations to the ventilator settings were not required to maintain the expiratory minute volume constant, as is the case with a jet nebuliser. The use of in-vitro methods does appear to reflect what will be observed in-vivo. A number of agents administered via the airway may not have an immediate effect on airway resistance or gas exchange. Thus it is important that the amount of drug delivered can be calculated to ensure that the use of a particular agent is not abandoned purely because of failure to deliver a sufficient dose.