ALBUTEROL DELIVERY IN AN INFANT VENTILATOR-LUNG MODEL: NEBULIZATION VS. MDI/SPACER.
Ralph A. Lugo, PharmD, Kathy Poll, RRT, Jim Keenan, BS, RRT, John W. Salyer, RRT, BS, MBA, FAARC, Madolin Witte, MD. University of Utah College of Pharmacy and School of Medicine, Primary Children's Medical Center, Salt Lake City, Utah.
Background: Mechanically ventilated infants with lung disease often receive aerosolized albuterol (ALB). Many institutions deliver ALB via nebulization, however administration by metered dose inhaler (MDI) may be more efficient and less costly. Replacing nebulized ALB with MDI in ventilated infants requires that equivalent doses be determined. This bench study compared ALB delivery via nebulizer and MDI/spacer in an infant ventilator-lung model. The objective was to determine equivalent doses of nebulized ALB and ALB administered by MDI and spacer.
Methods: The model consisted of a Bird VIP ventilator in a volume cycled mode with settings to simulate a 5-kg infant with moderate lung disease: VT 50 mL (10 mL/kg), PIP 30 cm H2O, rate 15, Ti 0.6 sec, PEEP 4 cm H2O, FiO2 0.4, ventilator flow 7 L/min, and gas conditioned to 34° C. The circuit was attached to a 4-mm endotracheal tube (ETT) and a pediatric test lung (Vent AidÒ TTLÒ): compliance = 3.26 mL/cm H2O and resistance = 142 cm H2O/L/s. A Sims breathing filter (# 2832) was placed between the ETT and test lung to collect ALB. The nebulized solution consisted of 1.5 mL of ALB (5mg/mL) + 1.5 mL 0.9% NaCl. The solution was nebulized (AirlifeÒ Misty-NebÒ) from 2 locations, 135 cm from the ETT and at the circuit wye. ALB MDIs (VentolinÒ) were tested under 2 conditions: 1) actuation into an ACEÒ spacer placed in-line between the circuit wye and the ETT; and 2) actuation into an ACEÒ spacer attached to the ETT and an anesthesia bag followed by manual ventilation (rate 15, PIP 30 cm H20). Each MDI experiment was conducted by actuating 10 different ALB canisters twice with 30 sec. between actuations. Five replicates were performed for each experimental condition. Filters were rinsed with 50 mL of 50% methanol solution and ALB concentration were analyzed chromatographically (HPLC) (99.1% accuracy and CV < 3.3%, n=9).
Results: Mean (SD) ALB delivery (%) is presented below.
Method of Administration
ALB 5 mg/mL
Nebulized at wye
ALB 5 mg/mL
Nebulized at 135 cm
In-line ACEÒ spacer
ACEÒ + manual ventilation
*p=0.06 compared to ALB nebulized at wye (t-test); ?p=0.001 compared to both nebulized groups (ANOVA on Ranks with Tukey post hoc test). Conclusion: The efficiency of ALB delivery following actuation of VentolinÒ MDI into an ACEÒ spacer was superior to nebulizing ALB solution; however, manual ventilation resulted in significant variability in drug delivery. To determine equivalent doses between nebulized ALB and MDI, percent delivery was multiplied by the ALB dose for each dosage form. In this infant ventilator-lung model, 1 puff of VentolinÒ MDI (100 mg) into an in-line ACEÒ spacer delivers approximately the same amount of aerosolized albuterol as nebulizing 0.25 mL (1250 mg) of albuterol solution (5 mg/mL).