High impact aerosol technology offers higher efficiency, but is not ready for prime time.

The therapeutic administration of medical aerosols has been a standard adjunct to treatment of critically ill patients since positive-pressure mechanical ventilators were introduced over 60 years ago, and most ventilators can operate a jet nebulizer in synchrony with mechanically delivered breaths. However, for the first 40 years, little was known about the efficiency of aerosol delivery during mechanical ventilation.1 Most of what we know about the science of aerosol delivery in critical care environments has been brought to light since 1987. At that time, several investigators reported scintigraphic studies demonstrating that in mechanically ventilated patients, aerosol deposition (1–3%)2–4 can be an order of magnitude less than that achieved in ambulatory patients (10–30%).5,6 Subsequent research identified substantial barriers to efficient and consistent aerosol delivery, related to the presence of artificial airways, and the range of variables associated with mechanical ventilation caused diminishing expectations that perceived barriers could be overcome.7,8 Much of what we now know about aerosol delivery during mechanical ventilation has come from in vitro models,9,10 which allow researchers to isolate variables and to determine the roles of those variables in reducing or improving aerosol delivery efficiency, in a way that would be difficult or impossible under clinical conditions. Bench testing allows rapid iterative evaluation of specific variables, at low cost, and in increments and ranges that would not be practical or well tolerated in patients. In vitro models have yielded information that has resulted in substantial benefits in vivo. Bench studies of variables associated with jet nebulizers during mechanical ventilation of adults have led to order-of-magnitude improvements, through changes in clinical practices, increasing aerosol efficiency to 15–22% in vivo.11–12 This was accomplished with a nebulizer that creates very small particles, with a relatively low inspiratory flow, high tidal volume, and a nonhumidified ventilator circuit, for administration times of up to 40 min. The desire for more efficient pulmonary delivery may be balanced by clinicians’ concerns about the impact of the required ventilatory parameters. Other research has suggested that large tidal volume13 and administration of dry and cold gas to the lungs when bypassing the upper airway14 may have adverse effects. Whether or not these new techniques were widely adopted, the successful application of principles learned from in vitro testing demonstrated pioneering techniques to improve clinical aerosol delivery and break the 10% barrier, showing that aerosol delivery to adults during mechanical ventilation could be as efficient as aerosol delivery to ambulatory patients. The challenge of efficient aerosol delivery to low-birthweight infants is even greater than with adults.15 The only scintigraphic study in low-birthweight infants16 found deposition of 1% when using either jet nebulizer or metered-dose inhaler in both spontaneously breathing and mechanically ventilated infants. This confirmed animal models (2 kg rabbits) of infant ventilation that reported similar pulmonary delivery.17 Fok and colleagues also demonstrated that this low level of deposition efficiency was sufficient for clinical response to bronchodilators in both infants and rabbits.18,19 These studies demonstrated that mechanical ventilation does not necessarily decrease aerosol delivery efficiency, compared to nonintubated spontaneously breathing patients. However, this finding elevates the challenge to improve aerosol deposition efficiency for infants both on and off the ventilator.