When delivering aerosol via mechanical ventilation, respiratory specialists have a number of device options from which to choose, but must be aware of factors that affect drug delivery and patient safety.
By Phyllis Hanlon
An international survey in 2013 revealed that more than 95% of intensivists use aerosol therapy during mechanical ventilation.[1] This method of drug delivery differs in several ways from inhaled drug delivery administered to spontaneously breathing patients. Respiratory specialists have a number of device options from which to choose, but must also be cognizant of several factors that could impact effective drug delivery and patient safety.
Metered Dose Inhalers
Muhammad Raza, MD, associate director of Respiratory Therapy at the Cleveland Clinic, indicated that metered dose inhalers (MDIs) can be an effective method for delivering aerosol but do have some inherent problems. “One is that they have to be delivered through a spacer, which has to be built in or separately bought for these inhalers. Not [every manufacturer] conforms to the same design,” he said, which adds to the cost. Additionally, the dose concentration could affect the molecule size the MDI produces. “The bigger the particle of aerosol, the more problems you have in delivering the medication effectively,” he said.
Studies have shown that MDIs are as effective as nebulizers in their ability to deliver medication; however, there are discrepancies in the number of puffs required to deliver adequate doses comparable to nebulization, according to Ann D. Cuccia, MPH, RRT-NPS, RPFT, AE-C, clinical associate professor, director of Clinical Education, Respiratory Care Program at Stony Book University.
Cuccia cited a study by Diot and colleagues[2] that showed 45 puffs were required to deliver a dose equivalent to a very high efficient nebulizer. “Whereas Dhand did a study[3] and showed that four puffs were all that was needed to achieve a clinically measurable effect in patients with COPD. The amount of puffs is not clearly defined,” she said.
Additionally, MDIs are “therapist intensive,” meaning the therapist has to remain at the bedside to administer medication and continually assess the patient. The therapist must time the actuations with inspiration and measure one minute between puffs. Cuccia said, “The technique of administration is important to ensure drug delivery.”
Cuccia noted that the cost factor related to current trends in length of stay may also influence the decision to use MDIs, which contain 200 actuations. She pointed out that nowadays patients spend just a few days in the hospital. “You have to throw the canister out after a few treatments [and this is] not cost effective,” she said.
Nebulizer Options
Hospitals also have three types of nebulizers for aerosol delivery from which to choose: ultrasonic, jet and vibratory mesh. Raza does not recommend ultrasonic nebulizers for multiple reasons. Critically ill patients typically receive a variety of aerosolized medications, including viscous drugs such as steroids, as well as antibiotics, anticoagulants, corticosteroids and sometimes Lasix, which ultrasonic nebulizers are unable to disperse adequately. He said that the ultrasonic nebulizer “…fails pretty drastically… due to limited consistency, [and is] affected by temperature and other factors.”
On the other hand, jet nebulizers have proven to be very reliable, low cost, simple to use and don’t require electronics, according to Cuccia. “There are some variations across different brands so knowing how a specific brand performs is important,” she said. Additionally, jet nebulizers can deliver drugs to the lung either continuously or intermittently. For the latter method, you must use a ventilator model that features the option of breath actuation, which has been shown to minimize expiratory losses, an important factor to consider especially when using expensive drugs.
Jet nebulizers do have some drawbacks, however. A 2016 study noted that these devices are often noisy, have poor dosing control and require changes in the ventilator settings for airflow and tidal volume.[4]
The third option, vibrating mesh nebulizers, which contain between 1,000 and 7,000 laser-drilled holes that vibrate at the top of a liquid reservoir and emit a fine mist of droplets, has experienced a rise in popularity lately. A report issued by Zion Market Research indicated that this market globally was valued at approximately $96.07 million in 2017. Furthermore, this segment is expected to generate $161.61 billion by the end of 2024.
Raza reported that Cleveland Clinic uses vibrating mesh nebulizers exclusively. “Mesh nebulizers have capacity to generate particles between 1 and 5 microns. If you look at the research done on nebulizers in mechanically ventilated patients, the smaller the particle, the easier it is to get delivered,” he said.
Maximizing Delivery
Jay Graham, MBA, RRT, clinical specialist for Vyaire Medical’s western region, noted that his company’s AirLife Brand Misty Max 10 disposable nebulizer produces a continuous low and high flow with a full 10cc capacity that enables the device to supply a larger volume of medication over a longer period of time. “The Misty Max 10 standard nebulizer delivers medication with a particle size of 1-5 micron,” he said. “It’s very efficient to use on the vent itself.”
Furthermore, the high output rate speeds up treatment times and supports consistent medication delivery. Other features are built in for patient safety, maximum drug delivery with minimal residual volume. Graham pointed out that the Misty Max 10 nebulizer is equipped with a bacteria filter that uses a reservoir and one-way valves to administer aerosolized medication; the aerosol is contained within the nebulizer system instead of freely flowing into the surrounding air. “Drug delivery is maximized because the patient on ventilatory support has enough positive pressure driving the drug to the lungs,” he said.
Cuccia reported that mesh nebulizers also offer the option of continuous delivery over several hours via infusion pump with vasodilators. “This provides therapists an alternative to nitric oxide, which can be very expensive,” she said. “Mesh nebulizers also have low residual volume and don’t require wall gas to drive the nebulizer.”
Cuccia pointed out that while a vibratory mesh nebulizer offers several benefits, the cost could exceed budgetary restraints. “If the patient is receiving a bronchodilator, which is inexpensive, it may not be cost effective to spend the money on a vibrating nebulizer. Every department has to look at how they feel they need to deliver the drug,” she said.
Challenging Factors
Regardless of whether a hospital decides to use a jet or vibratory mesh nebulizer, there are certain factors to consider that might affect performance.
According to Cuccia, active humidification has been shown to decrease delivery by as much as 40 to 50%. “Our group was the first to report the effects of humidification on aerosol delivery 20 years ago,” she said.5 This study found that including active humidification while delivering aerosol medications to patients on mechanical ventilation significantly reduced output by a mean of 41 +/- 3.5%, although it did not affect particle distribution.[5]
Raza pointed out that line obstruction can diminish the ability of medication to reach the lungs. For instance, medications such as antibiotics and vasodilators, may cause a filter clogging issue. The patient’s own secretions may also line and obstruct the tube. “A smaller lumen, either by tube size or if mucus is making it small artificially, will affect delivery too,” he said.
Residual or dead volume poses another challenge to effective drug delivery. Raza explained that his department has created a calculation to avoid dead volume. “You have to have in mind how much volume you’ll have left at the end of therapy,” he said. “On a certain nebulizer, if the dead volume is to be 2.5 mL, then you give 3.5 mL of the drug. If you don’t know the dead volume, you might be giving just one-third of the drug to the patient.”
Ventilator Role
A 2016 study indicated that therapists should carefully monitor choice of ventilator mode — in other words, pressure versus volume-controlled, inspiratory time and flow, tidal volume, duty cycle, and respiratory rate. Additionally, the patient may require increased sedation if these settings are changed.[6]
Cuccia noted that some vents don’t offer breath actuation, which offers better efficiency. “The drug is delivered only on inspiration. You’re not wasting medication in the expiratory limb of the circuit,” she said.
Additionally, the position of the nebulizer in the circuit can affect therapy. When the nebulizer is placed close to the ventilator versus closer to the patient, this position has been shown to decrease losses and increase drug deposition. Furthermore, Cuccia reported that when using breath actuation, the pressure and the flow driving the nebulizer in the ventilator are not standardized across all ventilator brands. “If you are using a different ventilator and a different nebulizer, it could change delivery,” she said.
Raza’s department recently purchased Getinge’s Servo-i and Hamilton Medical’s Hamilton-G5 after careful review. The latter is a little bit higher end from standpoint of taking care of certain sub-segments of sick patients, he added.
When the Servo-i was first launched, the device utilized an ultrasonic nebulizer, according to a Getinge representative. “In order to operate the nebulizer, the ventilator had to have related software installed. A few years later, we partnered with Aerogen, which utilizes vibratory mesh technology,” she said. “We were able to operate the Aerogen by utilizing the same software that operated the ultrasonic nebulizer, meaning that just an Aerogen adapter that locked onto the Servo was needed.”
The Servo-i allows the clinician to set the default settings they prefer in most situations. For example, the end user can program the vent to start up in a certain mode with the settings use most often. “The ventilator can be configured to show I-time or I:E ratio as the set parameter. We leave it to the clinician and their preferences,” the representative said.
Cuccia emphasized that the most important factor to consider with aerosol delivery is knowledge and understanding of the performance or characteristics of the device you are using. “It’s critical to have standards of use based on review from published studies, or a consultant — someone from the manufacturer, using information from published studies, in vivo or in vitro, looking at placement and how to use the device, and manufacturer recommendations for use, not just cost,” she said.
“A patient could overdose or under-dose if you use the device incorrectly. Having a standard for use based on sound evidence, knowing the medication is being delivered in effective way, will help ensure maximum drug delivery to the lungs, and patient safety.”
RT
Phyllis Hanlon is a contributing writer to RT. For more information, contact [email protected].
References
- Ehrmann S, Roche-Campo F, Sferrazza Papa GF, et al. “Aerosol therapy during mechanical ventilation: an international survey.” Intensive Care Med. 2013 Jun; 39(6):1048-56 doi: 10.1007/s00134-013-2872-5. Epub 2013 March 23.
- Diot P, Morra L, Smaldone GC. (1995). Albuterol delivery in a model of mechanical ventilation. Comparison of metered-dose inhaler and nebulizer efficiency. American Journal of Respiratory and Critical Care Medicine, 152:4; 1391-1394.
- Dhand R, Duarte AG, Jubran A, et al. “Dose-response to bronchodilator delivered by metered-dose inhaler in ventilator-supported patients.” American Journal of Respiratory and Critical Care Medicine. 154:2; 388-393.
- Dhanani J, Fraser JF, Chan HK, et al. “Fundamentals of aerosol therapy in critical care.” Critical Care. 20:269. doi: 10.1186/s13054-016-1448-5.
- O’Riordan TG, Greco MJ, Perry RJ, Smaldone GC. “Nebulizer function during mechanical ventilation1-3.” Am Rev Respir Dis. 1992. 145:1117-1122.
- Bassetti M, Luyt CE, Nicolau DP, Pugin J. “Characteristics of an ideal nebulized antibiotic for the treatment of pneumonia in the intubated patient.” Intensive Care. 2016. 6:35. doi: 10.1186/s13613-016-0140-x.
There were several things about this article that I wanted to comment on.
A couple of times there is reference to the particle size produced by a nebulizer. It’s my opinion that particle size is not an especially important determinant of the effectiveness of an aerosol delivery device. First of all, there are several ways to measure particle size and it’s hard to know if all manufacturers are using the same method. Also, I think the amount of drug actually delivered (inhaled mass) is a more important consideration. The comment on a nebulizer’s dead volume supports this. Ask yourself, what is the advantage of a device that produces small particles if it has a high dead volume.
This article mentions how the position of a jet nebulzer can influence aerosol delivery. Ari and Fink demonstrated that aerosol delivery from an MDI and vibrating mesh nebulizer is also influenced by where these devices are placed in the ventilator circuit (Influence of nebulizer type, position, and bias flow on aerosol delivery Respir Care. 2010 Jul;55(7):845-51).
The article also mentions how patients should be carefully monitored . It seems to me that all ventilator patients require carful monitoring so I found that coment somewhat redundant but more bothersome was the fact that it fails to mention how this should be done for the patient receiving aerosol therapy. Some mention could have been made on where changes following aerosol therapy could be anticipated. This could include patients work of breathing and breath soulnds. It could also include changes in ventilator parameters (peak airway pressure, exhaled tidal volume, airway resistance) or ventilator waveforms (expiratory limb of the flow vs time waveform. Note: I didn’t find any mention of the use of waveforms for this purpose in Bill Pruitts article either.