When to treat

• The recommendation to offer opioids, benzodiazepines, and oxygen to people with end-stage chronic obstructive pulmonary disease (COPD) that is unresponsive to other medical therapy is based on the National Institute for Health and Clinical Excellence (NICE) clinical guideline Management of chronic obstructive pulmonary disease in adults in primary and secondary care (partial update) [National Clinical Guideline Centre, 2010; NICE, 2010].

Opioids

• NICE [National Clinical Guideline Centre, 2010] identified one systematic review and meta-analysis of opioids for the palliation of breathlessness in terminal illness [Jennings et al, 2002]. Not all studies were of people with COPD, and most had methodological limitations, including small sample size and the potential for carry-over effects (in crossover trials). A statistically significant effect of opioids was demonstrated for breathlessness using non-nebulized opioids; however, when a subgroup analysis of nine COPD studies was done, no statistically significant difference between the treatment and control groups was found for breathlessness. In spite of this, the NICE guideline development group concluded that opioids are useful for palliating breathlessness in people in the end stages of COPD.
• Most review articles and textbooks recommend the use of morphine, but there was considerable variation in the starting dosage between trials and that recommended in review articles and textbooks (from 1 mg daily to 30 mg daily) [Jennings et al, 2002; Seamark et al, 2007; Abernethy et al, 2009; Rocker et al, 2009; Regnard and Dean, 2010]. Consequently, firm recommendations cannot be made; CKS recommends that specialist advice be sought or that regimens recommended in the CKS topic on Palliative cancer care - dyspnoea be used.

Benzodiazepines

• A recent Cochrane systematic review included three randomized controlled trials with 47 people with COPD in its meta-analysis [Simon et al, 2010]. No statistically significant effect was observed for benzodiazepines compared with control. The authors recommend a trial of benzodiazepines only in people who have not responded to opioids and non-pharmacological measures.
• Benzodiazepines were recommended by NICE on the basis of the expert opinion of the guideline development group [National Clinical Guideline Centre, 2010].
• Because few review articles or textbooks make suggestions on the choice and dosage of benzodiazepine specifically for people with end-stage COPD, CKS recommends that specialist advice should be sought or that regimens recommended in the CKS topic on Palliative cancer care - dyspnoea are used.

Oxygen

• Oxygen is recommended by NICE for the palliation of breathlessness not relieved by other therapies; this recommendation is based on the expert opinion of the guideline development group [National Clinical Guideline Centre, 2010].
• The recommendation to use short-burst oxygen is based on a report of the expert working group of the Scientific Committee of the Association of Palliative Medicine [Booth et al, 2004].
• The recommendation on the dose of oxygen is based on recommendations by the British Thoracic Society [British Thoracic Society, 2006] and a report of the expert working group of the Scientific Committee of the Association of Palliative Medicine [Booth et al, 2004].

Tricyclic antidepressants and major tranquilizers

• Although NICE also recommends (on the basis of the expert opinion of the guideline development group) the use of tricyclic antidepressants and major tranquilizers (antipsychotics), CKS could find no other expert opinion in favour of these drugs, or on recommended regimens. Consequently, CKS recommends that specialist advice should be sought if these drugs are being considered.