A systematic review of the use of opioids in the management of dyspnoea

Abstract

Background: Opioids are commonly used to treat dyspnoea in palliative medicine but there has been no formal evaluation of the evidence for their effectiveness in the treatment of dyspnoea. A systematic review was therefore carried out to examine this. Methods: The criteria for inclusion required that studies were double blind, randomised, placebo controlled trials of opioids for the treatment of dyspnoea secondary to any cause. The methods used to identify suitable studies included electronic searching of the literature, hand searching of the literature, and personal contact with relevant individuals and organisations. Random effects meta-analyses were performed on all included studies and on various subgroups (studies involving nebulised opioids or patients with chronic obstructive pulmonary disease (COPD)). Subgroups were compared using metaregression. Some studies included in the systematic review could not be included in the meta-analysis because insufficient data were presented. Results: Eighteen studies fulfilled the criteria for the review. The meta-analysis showed a statistically significant positive effect of opioids on the sensation of breathlessness (p=0.0008). Meta-regression indicated a greater effect for studies using oral or parenteral opioids than for studies using nebulised opioids (p=0.02). The subgroup analysis failed to show a positive effect of nebulised opioids on the sensation of breathlessness. The results of the subgroup analysis of the COPD studies were essentially similar to the results of the main analysis. Conclusion: This review supports the continued use of oral and parenteral opioids to treat dyspnoea in patients with advanced disease. There are insufficient data from the meta-analysis to conclude whether nebulised opioids are effective, but the results from included studies that did not contribute to the meta-analysis suggest that they are no better than nebulised normal saline.

Once-Daily Opioids for Chronic Dyspnea: A Dose Increment and Pharmacovigilance Study

“…[1,5] This current study supports the use of opioids for longer periods of time with no clinically significant respiratory compromise, and no evidence of tachyphylaxis.…”

“…[1,5] During the phase IV long-term effectiveness component of the study, the number of people still on opioids at three months, the dose of opioid at three months, and the number of dose changes since entry to this sub-study were recorded. Side-effects at any time causing cessation of the medication were a key secondary outcome.…”

“…[1,5] The effect of opioids on the subjective sensation of breathlessness is further supported by recent evidence demonstrating that blockade of endogenous opioids during exercise worsens the perception of breathlessness without changing the ability to exercise in people with chronic obstructive pulmonary disease (COPD). [6] While data supporting opioids for the treatment of refractory dyspnoea are clear, studies to date…”

Perspectives of patients, family caregivers and physicians about the use of opioids for refractory dyspnea in advanced chronic obstructive pulmonary disease

“…Retrospective data from a Saskatchewan database indicate a far lower prevalence of opioid prescribing toward the end of life among patients with COPD who have dyspnea than among patients with lung cancer. 32 The strongest evidence available at this time from clinical trials (a systematic review favouring the use of opioids 33 and a short-term randomized crossover trial 34 ) supports the experiences of the patients and family caregivers interviewed in our study (i.e., effective relief of dyspnea without evidence of respiratory depression). More recently, in a dose-increment and pharmacovigilance study involving 65 patients in Australia in which opioids were used for refractory dyspnea (mostly due to COPD), 35 there were no cases of respiratory depression during a mean follow up of three months, and 51% of patients reported a benefit sufficient for them to continue taking opioids.…”

Ensuring Breathing Comfort at the End of Life: The Integral Role of the Critical Care Nurse

“…Opioids are the mainstay medications for treating refractory dyspnea, but the evidence is limited to oral or parenteral morphine and fentanyl. 24 Nebulized opioids have not been rigorously tested. An effective dose regimen for dyspnea has not been empirically established, but based on anecdotal experience of this author, the initial dose is lower than what is typically recommended for a pain regimen.…”