Drug dosing in critically ill patients is challenging due to the altered drug pharmacokineticsââ?¬â??pharmacodynamics\nassociated with systemic therapies. For many drug therapies, there is potential to use the respiratory system as an\nalternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy.\nGiven that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local\ndrug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence\nhas restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size,\nmolecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical\nventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for\noptimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially\nimprove clinical outcomes.\nAbbreviations: ARDS, Acute respiratory distress syndrome; CF, Cystic fibrosis; COPD, Chronic obstructive pulmonary\ndisease; DPI, Dry powder inhaler; ED, Emitted dose; EUCAST, European Committee on Antimicrobial Suceptibility\nTesting; FDA, Food and Drugs Administration; FiO2, Fraction of inspired oxygen; FPF, Fine particle fraction; HH, Heated\nhumidifier; HME, Heat and moisture exchanger; kDa, Kilodaltons; MIC, Minimum inhibitory concentration;\nMV, Mechanical ventilation; MW, Molecular weight; NIV, Non- invasive ventilator; PaO2, Partial pressure of oxygen;\nPD, Pharmacodynamics; PEEP, Positive end-expiratory pressure; PK, Pharmacokinetics; pMDI, Pressurized metered dose\ninhaler; VHC, Valved holding chamber; VMN, Vibrating mesh nebulizer
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