Aerosol Delivery to a Critically Ill Patient: A Big Issue Easily Solved by Developing Guidelines
Nowadays, therapeutic aerosols are commonly delivered to mechanically ventilated patients by nebulizers and pressurized metered dose inhaler attached to an adapter or a spacer. Studies with asthmatics and chronic obstructive pulmonary disease patients have confirmed that aerosol delivery during mechanical ventilation is feasible. They have also reported that the inhaled drugs administered during mechanical ventilation provide greater and faster clinical outcomes than when delivering during spontaneous unassisted breathing. Researchers studied factors that would affect aerosol delivery during mechanical ventilation. Even with the tremendous amount of publications in this area, there have still been no recommendations or guidelines released to help respiratory therapists in their decision as to when to deliver aerosol to ventilated patients. Mostly, respiratory therapists read the literature and decide accordingly what to do and which device to use for their patients. This puts the patients at risk of receiving a sub-therapeutic or toxic dose of the inhaled aerosol. Some studies raise an alarm of physician decision upon reading any released publication related to aerosol delivery in mechanical ventilation without a trusted recommendation and guidelines. This increases the need for the development of recommendations and guidelines, by a trusted board or society, for aerosol delivery to such critically ill patients. To summarize, inhaled drugs administered to critically ill patients is of benefit compared to taking the patient off the ventilator and delivering during spontaneous unassisted breathing. However, dependable guidelines are needed to optimize aerosol delivery.
KeywordsFill volume HFNC Humidification Non-invasive ventilation pMDI Spacer Ventilator setting Vibrating mesh nebulizers
Therapeutic aerosols are commonly administered to mechanically ventilated patients [1, 2, 3, 4]. These agents are delivered by nebulizers [5, 6, 7, 8] and a pressurized metered-dose inhaler (pMDI) attached to an adapter or spacer through ventilator circuits [6, 9, 10, 11].
Studies in patients with stable asthma  and chronic obstructive lung disease (COPD)  have confirmed that aerosol delivery during mechanical ventilation is feasible and provides great and fast clinical outcomes [7, 14].
Researchers have studied factors that would affect aerosol delivery during mechanical ventilation, e.g., aerosol generators, add-on devices, patient interfaces, patient-related factors, ventilator-related factors, and circuit-related factors [9, 10, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26]. They even studied the effect of the design of the nebulizer reservoir chamber on aerosol delivery  and fugitive aerosol effect on surrounding healthcare provider [25, 28].
Most of these studies concluded that aerosol delivery is much better when using a vibrating mesh nebulizer (VMN) in a dry non-humidified circuit [18, 19, 29]. The position of the nebulizer in the ventilation circuit varied according to the ventilation setting, type of ventilator, and ventilation circuit used.
Even with the tremendous amount of publications in this area, still no recommendations or guidelines have been released to help respiratory therapists in their decisions when delivering aerosol to ventilated patients.
Mostly, respiratory therapists read the literature and decide accordingly what to do and which device to use for their patients. This puts the patients at risk of receiving a sub-therapeutic or toxic dose of inhaled aerosol. The aim of the present mini-review is to show how important the development of guidelines for aerosol delivery to cortically ill patients is.
Effect of Fill Volume and Humidity on Aerosol Delivery
An example of the need of such important guidelines is our last finding regarding the effect of fill volume of respiratory solution, placed in the nebulizer reservoir chamber, on delivered aerosol [25, 31, 32].
Another example of the need of such important guidelines was our new finding, which opposes all the previously published literature. Previous literature has suggested switching off the humidifier while delivering aerosol to ventilated patients to increase lung deposition [18, 19, 29]. This would let the patient face the risk of inhaling dry gas, which has a harmful effect on the lungs . These risks are even greater if the clinician fails to turn on the humidifier upon conclusion of aerosol administration.
The Use of Spacer with Nebulizer
These studies and others raise an alarm of physician decision upon reading any released publication related to aerosol delivery in mechanical ventilation without good trusted recommendations and guidelines. These recommendations and guidelines need to be developed by a trusted board or society for aerosol delivery to such critically ill patients.
Aerosol Delivery to Patients Using High-Flow Nasal Cannula (HFNC)
Another critically ill patient who would benefit from the delivery of aerosol is the patient using a high-flow nasal cannula (HFNC). In practice, the nasal cannula is the most popular tool used for providing critically ill patients with supplemental oxygen [37, 38, 39, 40].
HFNC is better tolerated than the non-invasive ventilation with a mask and can provide a wide extent of oxygen concentrations as needed .
Recently, there has been a growing trend towards delivering aerosol medications using HFNC. The possibility of such therapeutic combination in a clinical setting is still argued.
Aerosol delivery through the nose is advantageous over oral inhalation, as it can improve both patient comfort and compliance by simply using a cannula to administer frequently dosing drugs and also drugs nebulized over long times .
We validated this by delivering aerosol to COPD patients using oxygen flow rate (5 l/min) in adult nasal-cannula to compare both the pulmonary and systemic bioavailability of different aerosol generators. Aerosol generators were placed immediately after the humidification chamber within the circuit .
To summarize, inhaled drugs administered to critically ill patients during mechanical ventilation or HFNC is of benefit compared to taking the patient off the ventilator and delivering during spontaneous unassisted breathing. However, dependable guidelines are needed to optimize aerosol delivery.
Credit for this work and others must go to Beni-Suef University Clinical pharmacy department young members who have done all the experimental work. Credit also must go to James B. Fink and Patricia Dailey. Without their help we would not have done any of this work.
No funding or sponsorship was received for this study or publication of this article.
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Mohamed E. A. Abdelrahim has nothing to disclose.
Compliance with Ethics Guidelines
This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
- 2.Holt S, Heullit M, Berlinski A, Chavez A. Albuterol delivery via MDI/spacer in a spontaneously breathing pediatric tracheostomy model: does bagging improve drug delivery? Am J Respir Crit Care Med. 2011;183:A3383.Google Scholar
- 10.ElHansy MHE, Boules ME, Farid H, Chrystyn H, El-Maraghi SK, Al-Kholy MB, El-Essawy AFM, Abdelrahman MM, Said ASA, Hussein RRS, Rabea H, Abdelrahim MEA. In vitro aerodynamic characteristics of aerosol delivered from different inhalation methods in mechanical ventilation. Pharm Dev Technol. 2017;22(6):844–9.CrossRefGoogle Scholar
- 15.Hussein RRS, Ali AMA, Salem HF, Abdelrahman MM, Said ASA, Abdelrahim MEA. In vitro/in vivo correlation and modeling of emitted dose and lung deposition of inhaled salbutamol from metered dose inhalers with different types of spacers in noninvasively ventilated patients. Pharm Dev Technol. 2017;22(7):871–80.CrossRefGoogle Scholar
- 25.Saeed H, Mohsen M, Fink JB, Dailey P, Salah Eldin A, Abdelrahman MM, Elberry AA, Rabea H, Hussein RRS, Abdelrahim MEA. Fill volume, humidification and heat effects on aerosol delivery and fugitive emissions during noninvasive ventilation. J Drug Deliv Sci Technol. 2017;39:372–8.CrossRefGoogle Scholar
- 26.Mohsen M, Elberry AE, Salah Eldin A, Hussein RR, Abdelrahim EM. Effects of heat and humidification on aerosol delivery during auto-CPAP noninvasive ventilation. Arch Pulmonol Respir Care. 2017;3(1):11–5.Google Scholar
- 28.Sarhan RM, Elberry AA, Abdelwahab NS, Rabea H, Salem MN, Abdelrahim MEA. Effect of a nebulizer holding chamber on aerosol delivery. Respir Care. 2018 (in press).Google Scholar
- 31.Saeed H, Ali AMA, Elberry AA, Salah Eldin A, Rabea H, Abdelrahim MEA. Modeling and optimization of nebulizers’ performance in non-invasive ventilation using different fill volumes: comparative study between vibrating mesh and jet nebulizers. Pulm Pharmacol Ther. 2018 (in press).Google Scholar
- 32.Saeed H, Mohsen M, Salah Eldin A, Elberry AA, Abdelwahab NS, Hussein RRS, Rabea H, Abdelrahim MEA. Effects of fill volume and humidification on aerosol delivery during single limb non-invasive ventilation. Respir Care. 2018 (in press).Google Scholar
- 48.Harb HS, Elberry AA, Rabea H, Fathy M, Abdelrahim MEA. Performance of large spacer versus nebulizer T-piece in single limb non-invasive ventilation. Respir Care. 2018 (in press).Google Scholar