Ben-Aharon, I., Gafter-Gvili, A., Leibovici, L., & Stemmer, S.M. (2012). Interventions for alleviating cancer-related dyspnea: A systematic review and meta-analysis. Acta Oncologica (Stockholm, Sweden), 51, 996-1008.

The objective of this meta-analysis and systematic review was to evaluate the role of different interventions to alleviate dyspnea.

• Databases used were CENTRAL, EMBASE and PubMed.
• Search keywords were opiate, benzodiazepine, furosemide, steroids, oxygen, or pharmacological and dyspnea or breathlessness.
• Studies were included if they were randomized controlled trials assessing patients with terminal cancer with dyspnea in which an intervention was compared with no intervention, placebo, or an alternative intervention.
• No exclusion critera were stated.

A total of 829 references were retrieved. The specific method of evaluation was not described, but the small sample size of most studies was noted.

• The final number of studies included was 18.
• Of the specifics included, sample sizes ranged from 9–38.
• All studies involved patients with end-stage disease.

Patients were undergoing end-of-life care.

• Meta-analysis of three trials comparing opiods with placebo yielded a weighted mean difference of -1.31 (95% CI, -2.49, -0.13), showing a statistically significant benefit with opioids. 
• Studies tended to show better results with nebulized opiods rather than subcutaneous administration. 
• Analysis of six trials of oxygen showed lack of benefit. 
• Standard mean difference was -0.3 (95% CI, 1.06, 0.47).
• Two studies compared midazolam to morphine and the combination of both drugs.
• One study showed that addition of midazolam to morphine improved results.
• Two small studies concluded that furosemide did not improve dyspnea.

• Opioids are effective in reducing dyspnea and may work better if nebulized. 
• The addition of midazolam to opioid may improve results. 
• Oxygen and furosemide were not effective in reducing dyspnea.

• Relatively few studies used each intervention. 
• Opioid trials were limited by lack of dosage information and various types of opioids used. 
• In studies evaluating oxygen, hypoxemia was not routinely evaluated. 
• Method of measuring dyspnea varied across studies.

Findings provide guidance regarding effectiveness of interventions for dyspnea in patients with cancer. These results demonstrate the effectiveness of opioids. Findings also confirm those of others that palliative oxygen is of no benefit for this symptom. Some reviews continue to suggest the use of palliative oxygen. This is not supported by evidence, and home oxygen therapy is generally not covered by insurance for patients who do not have hypoxemia. Unnecessary use can be costly to the patient. Evidence is limited regarding the effects of the addition of hypnotics to opioids in managing dyspnea. This is an area that could benefit from additional research.