Fundamentals of aerosol therapy in critical care

Abstract

Drug dosing in critically ill patients is challenging due to the altered drug pharmacokinetics-pharmacodynamics associated with systemic therapies. For many drug therapies, there is potential to use the respiratory system as an alternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy. Given that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local drug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence has restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size, molecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical ventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for optimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially improve clinical outcomes.

Fig. 1

Mechanisms of particle deposition

Fig. 2

Factors favourable for aerosol drug delivery in critically ill patients. Figure derived from references [19, 20, 25, 29, 31, 38, 45, 51, 81, 82, 91, 93, 130]. NIV non-invasive ventilation, HME heat and moisture exchanger, pMDI pressurized metered dose inhaler, AAD adaptive aerosol device, VMN vibrating mesh nebulizer, DPI dry powder inhaler, PEEP positive end-expiratory pressure

Fig. 3

Effects of regional lung aeration and pneumonia on drug concentration in lungs. a Relationship of lung aeration (%) to pulmonary concentration of amikacin (μg/g) for different routes of administration. b Relationship of route of drug administration to pulmonary concentration of amikacin (μg/g) for different severities of pneumonia. Pulmonary concentrations derived from homogenized lung tissue specimens measured by an immunoenzymatic method. Figure derived from Elman et al. [47]

Fig. 4

Comparison of lung concentration (measured by HPLC) of amikacin between aerosolized and intravenous administration. Measurement done 1 hour after the second administration performed 48 hours after bacterial inoculation. Diagram derived from the data of Goldstein et al. [49]

Fig. 5

Comparison of lung concentration (measured by HPLC) and bacterial burden of colistin between aerosolized and intravenous administration. Samples taken 1 hour after the third aerosol in the aerosol group and the fourth infusion in the intravenous group and 49 hours after the bacterial inoculation. Diagram derived from data of Lu et al. [112]