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Am Fam Physician. 2004;69(7):1782-1783

Between 50 and 70 percent of patients requiring palliative care suffer from distressing dyspnea caused by a combination of physiologic and psychologic factors. As the underlying disease progresses, deconditioning, cachexia, panic, depression, and insomnia can exacerbate breathlessness. Because opioids are associated with respiratory depression and hypercapnia, they rarely are used to treat dyspnea. Nevertheless, some physicians have found them effective, and Australian consensus guidelines for palliative care indicate that opioids contribute to the management of refractory dyspnea. Abernethy and colleagues evaluated the use of sustained-release oral morphine in the management of refractory dyspnea.

They studied 48 patients attending hospital clinics for respiratory, cardiac, general, or palliative medicine in Australia. These patients had refractory dyspnea at rest despite optimal medical treatment but had not been treated previously with long-term opioids. Patients were required to have creatinine levels within twice the normal range; to have stable needs for medication and oxygen; and to be free of confusion, substance abuse, or contraindications to opioids. After data were gathered, including activity levels, patients were assigned randomly to receive 20 mg of oral sustained-release morphine or an identical placebo for four days. Patients then were switched to the alternative treatment. All patients were prescribed anticonstipation medication for the eight days of the study. The primary outcome was patient perception of dyspnea recorded on a visual analog scale. Other outcomes included the level of morning dyspnea, exercise tolerance, respiratory rate, pulse, oxygen saturation, insomnia, nausea, confusion, constipation, appetite, somnolence, and well-being.

Five patients withdrew during the placebo treatment, and five withdrew during the opioid therapy. About one half of the withdrawals were attributed to opioid therapy, mainly because of nausea, but one patient requested morphine therapy for pain during the placebo period. The 38 patients who completed the study were mainly elderly men who used supplemental oxygen for chronic obstructive pulmonary disease (COPD). More than 70 percent were unable to carry out any work activities. After four days, patients taking morphine reported a highly significant improvement in dyspnea on visual analog scales and improvement in sleep. Exertional performance and overall sense of well-being were not significantly different during morphine therapy. Respiratory rates, sedation, vomiting, confusion, and anorexia were similar during the morphine treatment compared with the placebo therapy. Side effects generally were mild and transient. Constipation, the most common side effect, often began to resolve by the fourth day.

The authors conclude that oral sustained-release morphine can benefit patients with intractable breathlessness who already receive optimal conventional therapy. No evidence of respiratory depression was found, and side effects were predictable and controllable. The authors call for larger studies to evaluate the safety of morphine therapy and to clarify the side effects, but stress that oral sustained-release morphine could provide significant relief to severely ill patients with COPD.

editor's note: The authors are careful to point out that until safety is confirmed and other studies are done, the message of this study is not that opiates are fine to use in patients with COPD, but that they might have a role as an adjunctive therapy in selected situations. The opportunity to relieve breathlessness and the fear of suffocation in very ill patients is compelling, and these patients were willing to risk side effects and respiratory depression for the chance to relieve dyspnea. The study makes one wonder how many other potentially beneficial treatments we withhold or do not consider because of principles ingrained during our training. While the principles remain true, perhaps we apply them too rigorously and do not spend sufficient effort in calculating the risks and benefits of all available therapies for individual patients.—a.d.w.

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