Advances in aerosol delivery in intubated and non-intubated critically ill patients
James B. Fink PhD 1
1Aerogen Pharma Corp., 1660 S. Amphlett Blvd, Suite 360, San Mateo, CA, USA 94402
Medical aerosols are commonly prescribed for treatment of critically ill patients requiring ventilator support, both on and off the ventilator. To date, no medications have been specifically approved for administration to mechanically ventilated patients.
The efficacy of these aerosols are limited by factors such as artificial airways, mechanical ventilatory support, administration of high flow oxygen, respiratory parameters and severity of disease. Aerosol drug approvals (and drug labels) are based on clinical trials conducted with moderately ill patients at home. Both in vitro and in vivo studies reveal that standard jet nebulizer delivery during mechanical ventilation provide lung delivery less of 2 – 3% of dose in adults (< 1% with infants), compared to the 10 – 12 % achieved with devices used in approval trials. In the ICU, patients often require different aerosol delivery devices and delivery strategies (dose volumes and frequencies) than those on their label to achieve desired therapeutic outcomes. With advancements of methods delivery to the lungs > 40% of nominal doses can be delivered to adults and infants lungs during mechanical ventilation. Therapeutic administration of aerosol to the lungs with both low and high flow nasal oxygen have resulted in up to 30% lung dose. These levels of pulmonary drug delivery efficiency should be sufficient to support drug/device development for both intubated and non-intubated adults and infants. These new methods and their implications will be reviewed.