Masood 1995.
| Methods | Double blind, randomised, crossover study Exercise study Incremental cycle ergometer |
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| Participants | Stable severe COPD with disabling breathlessness 12 men ADLs limited by breathlessness FEV1 < 1.51 Exclusion criteria: exacerbations needing antibiotics, change in oral steroid dose or hospital admission within 2 months, overt cardiac disease, contra‐indication to exercise testing, pCO2 > 7.0, use of opioids, benzodiazepines, or other sedative agent within 1 month |
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| Interventions | Morphine 10 mg nebulised or morphine 25 mg nebulised or morphine 1 mg intravenous or morphine 2.5 mg intravenous or placebo nebulised or placebo intravenous 15 minutes before exercise tests Each test was separated by at least 48 hours |
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| Outcomes | Heart rate Respiratory rate VO2 RER SaO2 VAS for breathlessness Exercise duration Plasma morphine levels Ventilation |
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| Notes | Nebulised Beta 2 agonist given before exercise tests Authors conclude no significant effect of opioid compared with placebo on exercise tolerance or breathlessness The primary outcome did not include standard deviation therefore could not be included in the meta‐analysis |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The study authors did not state the methods of random sequence generation. |
| Allocation concealment (selection bias) | Unclear risk | The study authors did not state the methods of allocation concealment. |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | The study authors did not state whether or not they blinded participants and personnel. |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | The study authors did not state the methods of blinding of outcome assessment. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | All recruited participants remained in the study. |
| Selective reporting (reporting bias) | Low risk | The study authors presented all primary and secondary outcomes described in methods. |
| Other bias | Low risk | We judged that this trial appeared to be free of other sources of bias. |
| Size bias | High risk | This study had a small sample size, and was at high risk of bias; there were < 50 participants per arm |