W h i t e   P a p e r

Reservoir Bag in Medicator^® Aerosol Delivery System Does Not Contaminate the Nebulizer or the Patient

by Michael McPeck RRT, Ross Potter and Glenn Samford, Healthline Medical, Inc., Baldwin Park, CA

The Healthline Aerosol Medicine Medicator^® is a unique aerosol delivery system that has a tested efficiency in vivo of greater than twice that of many other liquid nebulizer systems.  The enhanced efficiency is due in part to the use of a special manifold and reservoir bag system that collects and stores most of the aerosol generated during the patient’s exhalation phase that would otherwise be wasted, and directs it to the patient on the subsequent inhalation.  However, the inclusion of the reservoir bag raises a question of whether any microbiologic contamination that may be present in the bag will be inhaled by the patient.  The design of the manifold is such that aerosols and particulate matter exhaled by the patient are (1) channeled through a specific exhalation port to atmosphere and (2) segregated from both the nebulizer and reservoir bag by a unidirectional diaphragm.  This feature was designed to insure that the reservoir bag does not become contaminated in the first place.  Nevertheless, we conducted a bench test using a radioactive tracer, Technetium-99 (^99mTc), as a readily detectable surrogate instead of bacteria, to confirm whether the Medicator^® presents a risk of transferring contaminated aerosol particles from its reservoir bag to either the nebulizer or the patient. 

Materials and Methods

The test bench setup (Fig. 1) consisted of a single Medicator^® manifold to which new, clean reservoir bags, nebulizers and High Efficiency Particulate Air (HEPA) filters were attached for testing.  The manifold was mounted such that its long axis was maintained parallel to the floor so that the reservoir bag hung perpendicular to the floor.  A total of 6 experiments were performed utilizing 4 different reservoir bags, 6 different small volume medication nebulizers (SVNs) and 6 different HEPA filters.  Three of the nebulizers were Healthline Aerosol Medicine’s Model 3A and three were Model 3A+.  

The 3A nebulizer has a rated efficiency of ~50%  (50% of nebulizer charge is completely nebulized).  The particle size distribution is as follows: 2% <0.2 µM, 62% between 0.2 and 1.0 µM, and 35% between 1.0 and 5.0 µM.  Therefore, this nebulizer is generally recommended for bronchodilator administration and upper airway therapy.  The 3A+ "fine particle" nebulizer has a rated efficiency of ~35 - 50%.   The particle size distribution is as follows: 7% <0.2 µM, 90% between 0.2 and 1.0 µM, and 3% between 1.0 and 5.0 µM and is consequently recommended for administration of aerosolized antimicrobials and other drugs with a targeted deposition at the endobronchial level. 

The HEPA filters had an efficiency rating of >99.9999% for a particulate challenge range of 0.3 to 10 µm for S. aureas bacteria (mean particulate size 1 µm) and Bacteriophage PHI X 174 virus (mean particulate size 0.027 µm).  The HEPA filters were placed at the location that would ordinarily be occupied by the patient mouthpiece so as to capture any particles that would have been inhaled by an actual patient.

A simulated human breathing pattern with quasi-sinusoidal airflow through the HEPA filter was produced by a PLV-100 ventilator set to create a tidal volume of 750 (+/- 20) mL at a rate of 12 breaths/minute with an inspiratory time fraction of approximately 20%.  (A large tidal volume at a high flow rate was deliberately chosen in order to provide maximum opportunity for contamination of the HEPA filter at the airway opening position).

For the first four test runs a new reservoir bag was inoculated with 3 mL of albuterol sulfate solution from a plastic unit dose vial to which ~2 mCi of ^99mTc had been added.  After the radioactivity had been introduced into the reservoir bag, the bag was placed in the well of a radioisotope calibrator to determine its radioactivity.  Then the bag was repeatedly rotated and partially inverted for one minute in such a way as to wet the internal sidewalls of the bag with the radioactive liquid.  Thereafter, the bag was attached to its port on the manifold and allowed to hang vertically.  Next, a new nebulizer, to which 3 mL of 0.083% albuterol sulfate solution from a plastic unit dose vial had been added, was attached to its port on the manifold.  Lastly, the HEPA filter was attached to the mouthpiece port on the manifold.  The nebulizer was operated from an oxygen cylinder at a flowrate of 7 L/min and, simultaneously, the other end of the HEPA filter was attached to the ventilator and the entire test setup was allowed to operate for a predetermined period of time that would assure that the nebulizer had run to dryness (15 mins for the 3A nebulizer and 20 minutes for the 3A+ nebulizer).  During each test run the HEPA filter “inhaled” aerosol generated by the system.  The use of ^99mTc as a tracer for bench testing aerosol delivery devices has been amply documented.

At the end of the designated time period the oxygen flow to the nebulizer was stopped and the ventilator was disconnected from the test setup.  The HEPA filter was disconnected and placed in the radioisotope calibrator for measurement, followed by the nebulizer and the reservoir bag.  Because ^99mTc has a half-life of 6.02 hours, any measurements of ^99mTc activity at this time were corrected for decay in order to accurately correlate with the initial activity of ^99mTc placed in the reservoir bag.

Two runs were conducted with two different 3A nebulizers, and two runs were conducted with two different 3A+ nebulizers.  After the first and second test run, with a 3A and 3A+ nebulizer, in that order, the reservoir bags were set aside after measurement for approximately one hour.  Then, each bag was suspended on a ring stand under a portable hair dryer that directed a stream of heated air at ~65 °C into the bag opening.  Internal bag temperature ranged between 55 and 60 degrees °C.  Each bag was exposed to the heated air for ~5 minutes in order to dry the sides of the bag internally.  Thereafter, each bag was placed in the radioisotope calibrator for radioactivity measurement and then placed back on the manifold with either a new 3A or 3A+ nebulizer plus new HEPA filter.  Four the last two test runs, the bags were then exposed to albuterol aerosol by running a new nebulizer for 10 minutes, during which time they received periodic manual manipulation so as to theoretically dislodge any dried radioactive solution particles adhered to the sidewalls.  Thereafter, the HEPA filter was disconnected and placed in the radioisotope calibrator for measurement, followed by the nebulizer and the reservoir bag.  Any measurements of ^99mTc activity at this time were corrected for decay.  Finally, after measurement, the two bags were cut open with scissors and visually examined to verify that the sidewall surfaces of the bags had dried (although there was still liquid in the bottom “tail” of the bags).

Results

The results are summarized in Table 1.  The most obvious finding was that the radioactivity that was intentionally placed in the bags did not contaminate either the nebulizer (0 mCi) or the HEPA filter (0 mCi), as determined by measuring these system components in the radioisotope calibrator following the period of nebulization.  A further confirmation of this finding was established by mass balance calculation of the mean amounts of radioactivity in the reservoir bags before and after the nebulization period which showed a mean difference of only 0.032 mCi, essentially nil, which was well within the measurement accuracy of the radioisotope calibrator.  

Table 1.  Results of bench studies.  Bag, filter and nebulizer readings in mCi after correction for decay where applicable.  Runs 1-4 were on new reservoir bags; runs 5&6 were on previously used reservoir bags from runs 1 and 2 respectively that had been exposed to drying air for ~ 5 minutes then retested using new nebulizers that were loaded with albuterol solution.  Neither the HEPA filters nor the nebulizers had any measurable radioactivity.  By mass balance (Bag Loss column), there was no significant loss of radioactivity from the reservoir bags.

Discussion

The inclusion of a reservoir device in any aerosol delivery system raises legitimate questions as to whether (1) that reservoir might become contaminated by either the patient (e.g., sputum) or some other means and (2) that reservoir might function in such a way as to introduce microorganisms into either the nebulizer and/or the patient.  Reintroduction of the patient’s own organisms could be hazardous if those organisms have had an opportunity to thrive and develop a greater concentration per unit volume.  It is incumbent upon aerosol delivery device manufacturers to answer that question to the satisfaction of practitioners using the product. 

While it was not practical to use test microoganisms for this study, the use of an easily measured radioactive tracer can act as a surrogate for aerosolized microbiologic contamination.  This study was designed to determine if contamination inside the reservoir bag (represented by the radiolabeled albuterol solution) would reach either the nebulizer or the patient during the normal course of a typical treatment session (10 - 15 minutes).  The results suggest that would not be the case.  However, it should be noted that the patented design of the manifold includes a uni-directional flow control diaphragm to ensure that the aerosol that is exhaled by the patient is directed out through the exhalation port, through a filter, and does not enter the part of the manifold to which the nebulizer and the bag are attached.  Therefore, it can be concluded that, even though it is unlikely for contamination to reach the reservoir bag in the first place, contamination of the reservoir bag will not result in contamination of either the nebulizer or the patient.

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