Aerosol Delivery and Modern Mechanical Ventilation

Abstract

Aerosol delivery via a mechanical ventilator remains unregulated with no standards for drug delivery to intubated patients. Bench models predicting drug delivery have not been validated in vivo. For modern ventilator designs, we chose to identify, on the bench, the most important variables affecting aerosol delivery and to correlate in vitro predictions of aerosol delivery with in vivo end points independent of patient response. Test aerosols of albuterol and antibiotics were compared. Bench measurements of inhaled mass (percentage of nebulizer charge, mean +/- SEM) ranged from 5.7 +/- 0.5% to 37.4 +/- 1.6%, with breath-actuated nebulization and humidity identified as the most important factors determining aerosol delivery. In patients, sputum levels of deposited antibiotics varied from 1.10 to 19.6 microg/ml/mg. Variation in sputum levels correlated with predictions from the in vitro model. Aerosol delivery in ventilated patients can be efficient and reproducible only if defined ventilator parameters are tightly controlled. Key parameters can be determined via in vitro bench testing defining delivery standards for clinical trials of drugs with narrow therapeutic/toxicity ratios.

Aerosolized perfluorocarbon improves gas exchange and pulmonary mechanics in preterm lambs with severe respiratory distress syndrome

“…As compared with previous devices used to aerosolize PFC (12,15), this system bypasses the oropharynx, avoiding the high deposition that tends to occur within the endotracheal tube (18). Therefore, particles >5 µm can reach the lungs and have a therapeutic effect (14).…”

Effects of Heat and Humidification on Aerosol Delivery during Auto-CPAP noninvasive Ventilation

“…Humidifi cation of the ventilator circuit is one of the factors that were well studied for optimization of aerosol delivery in NIV patients [5][6][7][8][9][10][11]. Optimal humidifi cation of the inhaled gas could improve patient comfort, facilitate use of the mask, and improve bronchodilator effects in those requiring NIV [2].…”

“…Most studies of humidifi cation effects on aerosol delivery were in-vitro and all of them recommend switching off the humidifi er while delivering aerosol to NIV patients for better delivery [5][6][7][8][9][10][11]. However, the undesirable effect of inhaled dry gas, e.g.…”

In Vitro Evaluation of Aerosol Delivery by Different Nebulization Modes in Pediatric and Adult Mechanical Ventilators

“…1,2,[4][5][6] Aerosol delivery varies with different types of aerosol generators, brands of nebulizer used, and their position in the ventilator circuit. [6][7][8] Other authors reported that the higher the peak inspiratory flow, the greater the impact of inspiratory waveform on aerosol delivery.…”

“…1,2,[4][5][6] Aerosol delivery varies with different types of aerosol generators, brands of nebulizer used, and their position in the ventilator circuit. [6][7][8] Other authors reported that the higher the peak inspiratory flow, the greater the impact of inspiratory waveform on aerosol delivery. 5 Furthermore, factors improving aerosol delivery through mechanical ventilation in pediatric patients include larger endotracheal tubes (ETTs), use of metered-dose inhalers with spacers, synchronization with inspiration, use of heliox (80:20 helium-oxygen mixture) as a gas power source, and positioning a jet nebulizer distal to the ventilator circuit.…”