Boyden, J.Y., Connor, S.R., Otolorin, L., Nathan, S.D., Fine, P.G., Davis, M.S., & Muir, J.C. (2015). Nebulized medications for the treatment of dyspnea: A literature review. Journal of Aerosol Medicine and Pulmonary Drug Delivery, 28, 1–19. 

STUDY PURPOSE: To complete a thorough systematic review of the evidence available in the literature regarding the use of nebulized medications in the treatment of dyspnea in chronic obstructive pulmonary disease (COPD), cancer, interstitial lung disease (ILD), and cystic fibrosis

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 39
• TOTAL PATIENTS INCLUDED IN REVIEW = Not combined for evaluation, not quantified
• SAMPLE RANGE ACROSS STUDIES: 1–100, also included literature reviews
• KEY SAMPLE CHARACTERISTICS: Studies varied widely, including studies examining medications, examining medication delivery (jet nebulizers), and reviewed literature reviews. Studies on children as well as adults with a variety of lung illnesses were included.

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Pediatrics, elder care, palliative care

Results delineated by disease populations.

• Cancer: Findings were mixed with 12 publications supporting use, 8 inconclusive/insignificant, and one recommendation against use. Studied drugs included morphine, fentanyl, hydromorphone, and furosemide. Mixed results existed with both.
• For COPD: Medications reviewed included opioids and furosemide, again with mixed results. Favorable results were observed with jet nebulizers and fentanyl and furosemide. All morphine studies were negative.
• IPF: Of seven studies, three were high quality, and all of these were studies that included subjects with multiple diseases, one of which was IPF. Results were mixed (two inconclusive and one positive).
• Cystic fibrosis: Four studies were included. All were positive, but all had low-quality evidence (case reports).  
• Healthy: These were studies in which dyspnea was induced experimentally—two reviews; four double-blind, randomized trials of furosemide; and three positive.
• Terminal/end-stage populations: Three looked at cystic fibrosis, two looked at end-stage ILD/IPF, one at end-stage COPD, and eight at end-stage cancer. None was high-quality. Positive results with various agents existed, but, again, no high-quality studies existed.
• In all studies, results with morphine were mixed, and there were more positive studies with hydromorphone, fentanyl, and furosemide, but these were not of high quality.

Although many studies evaluated nebulized medications, this review included a wide variety of studies with varied goals, including systemic reviews, evaluation of opioids and furosemide, and delivery via ultrasound versus jet nebulizer across many disease processes and populations. The authors of this review suggested considering the use of nebulized medications on a case-by-case basis. No broader recommendations can be made at this point.

• Mostly low quality/high risk of bias studies
• High heterogeneity
• Low sample sizes

The oncology nurse should be aware of the use of nebulized medications as a delivery method for dyspnea but that there has not been any high-quality evidence to support the use of any specific medication. Although the delivery method may be more acceptable, the increased cost and lack of evidence do not support its use at this time.