Aerosol delivery and modern mechanical ventilation: in vitro/in vivo evaluation

Am J Respir Crit Care Med. 2003 Nov 15;168(10):1205-9. doi: 10.1164/rccm.200210-1167OC. Epub 2003 Jul 31.


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.

Publication types

  • Evaluation Study

MeSH terms

  • Administration, Inhalation*
  • Aerosols / administration & dosage
  • Aerosols / analysis
  • Albuterol / administration & dosage*
  • Albuterol / analysis
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / analysis
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / analysis
  • Humans
  • In Vitro Techniques
  • Models, Biological
  • Predictive Value of Tests
  • Reproducibility of Results
  • Respiration Disorders / therapy*
  • Respiration, Artificial / methods*
  • Sputum / chemistry


  • Aerosols
  • Anti-Bacterial Agents
  • Bronchodilator Agents
  • Albuterol