Aerosol delivery and modern mechanical ventilation: in vitro/in vivo evaluation.
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.
Miller
Dorisanne D
DD
Department of Respiratory Care, University Hospital, State University of New York, Stony Brook, NY 11794-8172, USA.
Amin
Mohammad M
MM
Palmer
Lucy B
LB
Shah
Akbar R
AR
Smaldone
Gerald C
GC
D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage / Q000032:analysis; D000420:Albuterol / Q000008:administration & dosage* / Q000032:analysis; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000032:analysis; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012120:Respiration Disorders / Q000628:therapy*; D012121:Respiration, Artificial / Q000379:methods*; D013183:Sputum / Q000737:chemistry
D000336:Aerosols; D000900:Anti-Bacterial Agents; D001993:Bronchodilator Agents; D000420:Albuterol