Multiple dosing studies of opioids for dyspnoea among patients with COPD
| Study | Population | Opioid dose regimen (vs placebo) | Setting | Duration of follow-up | Outcome measure | Overall effect on dyspnoea | Side effects |
| Eiser et al 199130 | n = 18 (pink puffer, mean FEV1 36%) | Diamorphine 2.5 or 5 mg orally qid | Pre and 2 week exercise testing in study centre | 2 weeks ×3, crossover, no washout | VAS for dyspnoea 6 min walk | NS | 4 withdrew (chest infection, itching, constipation, headache), mild nausea: ‘several’ constipation or vomiting:3/14 |
| Poole et al 199822 | n = 16 (FEV1 <1.5 l) | Morphine SR 10–20 mg od or bid | Pre and 6 week exercise testing in study centre | 6 weeks ×2, plus 2 week washout | CRQ for quality of life, 6 min walk | NS overall, but mastery scale favored placebo; 6 min walk test worse with morphine | Opioid withdrawal syndrome:4/16; patients on morphine “more likely to report nausea, anorexia, constipation or drowsiness” (p = 0.004) |
| Johnson et al 198332 | n = 19 (FEV1 <1.2, MRC ⩾3) | Dihydrocodeine 15 mg orally 30 min pre-exercise, up to tid | Pre and 1 week pedometer testing in the home | Weekly, cross over×3 (third week alternate day codeine) | VAS for dyspnoea Pedometer distance | Dyspnoea reduced by18%, walk distance up 17% | Similar in placebo and treated groups |
| Woodcock et al 198123 | n = 12 (MRC >3) | Dihydrocodeine 1 mg/kg orally od vs oxygen, alcohol or caffeine 45 min before exercise | Exercise testing (treadmill, in hospital) | 4 consecutive days | VAS for dyspnoea | 20% reduction in dyspnoea, 18% increase in exercise tolerance 45 min after codeine | Nausea and vomiting 5/16; constipated/drowsy 2/16 |
| Woodcock et al 198231 | n = 16 (mean FEV1 0.75) | Dihydrocodeine 30 mg or 60 mg tid | Exercise testing at 2 weeks in study centres | 2 weeks crossover ×3 | Oxygen consumption (bicycle ergometer), 6 min walk | “A few patients reported considerable benefit”, Lower oxygen consumption (p<0.05) | 5 withdrew (nausea and vomiting). Opioid withdrawal syndrome (2 on 60 mg dose), constipation (2/11) |
| Abernethy et al 200325 | n = 48 (COPD n = 42) | Morphine SR 4-day crossover versus placebo | Clinical study in the community | 4 days | VAS for dyspnoea at day 4 | Better dyspnoea scores both mornings (p = 0.01) and evening (p<0.05) | More constipation with morphine. Other side effects not significant |
| Currow et al 200934 | n = 68 (48 with COPD, modified MRC ⩾2) | Morphine SR 10–20–30 mg od | Open-label dose-finding long-term clinical study in the community | Mean 3 months; 18.5 patient years of data | VAS for dyspnoea | 51% of patients found sufficient benefit over long term to choose to continue | Constipation 6%, nausea 6%, confusion/drowsiness/lethargy/dizziness 12% |
bid, twice a day; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 s; MRC, Medical Research Council; NS, not significant; od, once daily; SR, sustained release; tid, three times a day; VAS, visual analogue scale.