Since the introduction of high-flow nasal cannula therapy (HFNC), interest has grown in the delivery of aerosolized medications through this interface.1 This is not surprising because many patients requiring HFNC also require inhaled medications such as bronchodilators or pulmonary vasodilators, and an interruption of their HFNC would be inconvenient and potentially dangerous. Moreover, conventional delivery of aerosolized medications by a mouthpiece or face mask involves oral inhalation, which can lower the effectiveness of HFNC. Although transnasal aerosol delivery through HFNC has become common practice at many centers throughout the world, high-quality data regarding the efficacy and most effective methods are lacking.2 In this issue of Respiratory Care, two primary research manuscripts are included related to these topics.
In the manuscript written by Li et al, the authors conducted several in vitro experiments to evaluate the effects of different HFNC devices, circuits, nebulizers, and nebulizer locations on aerosolized medication delivery at different simulated breathing patterns and HFNC flow settings. They found that vibrating mesh nebulizers generated a higher inhaled dose than small-volume nebulizers (SVNs) in almost all scenarios, with the exception of during the highest HFNC settings when nebulizers are also placed proximal to the nasal cannula. They also found that that placement of nebulizers proximal to the humidifier resulted in an equal or greater dose than placement proximal to the nasal cannula with the exception of during low HFNC flow and distressed breathing.3
These findings are consistent with the performance of vibrating mesh nebulizers compared to SVNs in other interfaces, such as for conventional aerosolized medication delivery through a mask or mouthpiece and also with regards to optimal nebulizer placement in ventilator circuits.4,5 This is certainly useful information for bedside clinicians considering transnasal aerosolized medication delivery for their patients receiving HFNC. Also, the delivered medication dose decreased significantly as HFNC flow increased, at some settings by up to four-fold. For patients on these higher flows, other inhaled medication delivery methods may be worth considering (particularly for those patients in acute distress that are not responding to transnasal delivery).
However, this study is not without limitations. As with any in vitro study, it is not possible to ascertain that these findings will translate in vivo. That is particularly relevant in this study due to potential involvement of the sinonasal passages in which transnasally delivered medications could deposit.6,7 These passages vary significantly in surface area between patients and disease states that could lead to significant variation in deposition of delivered medications.8 In vivo studies, ideally comparing transnasal aerosolized medication delivery to conventional aerosolized medication delivery during HFNC with either pulmonary deposition or physiologic response as an end point, would be helpful in determining the optimal method of inhaled pulmonary medication delivery to subjects receiving HFNC.
Beuvon et al conducted an in vivo study that evaluated the effects of transnasal aerosolized bronchodilator delivery during HFNC on pulmonary function for patients experiencing a severe exacerbation of COPD.9 Worth noting, this study used a vibrating mesh nebulizer placed proximal to the humidifier chamber, which was the device and location with the highest delivered dose in the in vitro study by Li et al.3 These authors found that transnasal aerosolized bronchodilator delivery during HFNC resulted in a significant increase in lung function in their study population. This certainly supports the notion that this delivery method results in the desired intrapulmonary deposition in clinically relevant doses.
However, similar to Li et al, this study also lacks a comparison to conventional aerosolized medication delivery. Although previous studies have demonstrated non-inferiority between conventional aerosolized medication delivery without HFNC and transnasal aerosolized medication delivery during HFNC, it would be helpful to compare both delivery methods during HFNC to determine if one is superior.10,11
A key concern unaddressed by either of these manuscripts is safety. It is likely that transnasal delivery of aerosolized medications during HFNC results in a higher level of sinonasal deposition of the aerosolized medications than conventional delivery, even if an adequate amount of medication is delivered to the lower airways to elicit the desired clinical response from the patient. It is important to consider the local effects of these medications that are not intended for sinonasal delivery, particularly when delivering aerosolized medications not formulated for inhalation such as intravenous vasodilators, antibiotics, and antifungal medications repurposed for pulmonary delivery.11-13 Just because we can do something, does not mean we should…even if it works. That said, we applaud the authors’ efforts to add to the growing body of evidence to support the feasibility and potential usefulness of delivering aerosolized pulmonary medications transnasally during HFNC.
Footnotes
- Correspondence: Michael D Davis RRT PhD FAARC, 1044 W. Walnut Street R4-472, Indianapolis, Indiana 46202. E-mail: MDD1{at}iu.edu
Dr Davis is funded by NIH/NHLBI 1 PO1 HL128192, 1 PO1 HL158507-01, and Indiana CTSI UL1TR002529. Dr Davis is a cofounder of Airbase Breathing Company and patent holder of Optate. Dr Saunders is funded by the Cystic Fibrosis Foundation 1st and 2nd Year Clinical Fellowship Grant.
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