Low-Dose Morphine Associated with COPD Improvement

Cornelia Verberkt, Msc

Investigators confirmed that low-dose administration of morphine may indeed have a role in palliative treatment for chronic breathlessness, a symptom of chronic obstructive pulmonary disease (COPD). 

A team, led by Cornelia Verberkt, MSc, at Maastricht University, assessed the effects of regular, low-dose, oral sustained-release morphine through reference to the COPD Assessment Test (CAT) scores, respiratory outcomes, and breathlessness in patients. They found that test scores improved after administration of the opioid, indicating an improvement in disease-specific health status among severe or even simply moderate patients.

Furthermore, low-dose morphine treatment also appears to be safe in patients with moderate to very severe COPD. Respiratory rate decreased without a change in partial pressure of carbon dioxide (PCO2).

The investigators used a population sample from the double-blind Morphine for Treatment of Dyspnea in Patients with COPD (MORDYC) study for analysis. The sample included 124 individuals who had been randomized and assigned 1:1 to receive either 10 mg of morphine or placebo twice daily for 4 weeks. There was also a possibility for individuals to increase rate of administration from 2 to 3 times daily following a one- or two-week period.

The MORDYC trial had recruited patients from a pulmonary rehabilitation center and 2 general hospitals throughout The Netherlands, following patient completion of a pulmonary rehabilitation program.

For this study, the team assessed individuals who were outpatients with COPD and moderate to very severe chronic breathlessness—which was scored 2-4 on a scale according to the modified Medical Research Council (mMRC). The mean age of participants was 65.4 years with 60 (54%) being men.

The investigators acknowledged one of the study’s limitations was a low response rate for informed consent (27%), which led them to expand eligibility criteria to include mMRC grade 2 patients.

The primary outcomes of the study were CAT score and PCO2 with a secondary outcome as breathlessness in the previous 24 hours.

Results showed that the difference in CAT score was 2.18 points lower in the morphine group (95% CI, -4.14 to -0.22; P = .03). 

The team reported that the difference in respiratory rate between the two treatment groups was –1.46, favoring the morphine group (95% CI, –2.84 to –0.09; P = .04). They considered this finding significant.

The difference in PCO2 was 1.19 mm Hg higher for those receiving morphine (95% CI, -2.70 to 5.07; P = .55), thus indicating that there were no clinically relevant differences in alveolar ventilation.

Although breathlessness remained unchanged, worst breathlessness improved in patients with mMRC grades 3-4. The investigators noted that the morphine group improved 1.33 points better than the placebo group (95% CI, -2.50 to -0.16; P = .03)

The difference of mean breathlessness between both groups (-1.31) was not considered significant (95% CI, -2.5 to -0.16; P = .03), which suggests a potential lack of power in the study. 

Both treatment groups experienced similar cases of adverse events (37% in morphine vs 58% in placebo group). Common adverse events were nausea, vomiting/retching, drowsiness, constipation, and sleepiness.

In terms of next steps for future studies, they suggested that only patients with mMRC grade 3 and 4 should be included.

“Our results should be confirmed in a future RCT only including patients with severe to very severe chronic breathlessness and optimized pharmacological and nonpharmacological treatment of their COPD,” they wrote. “Given the low response rate, a multicenter approach should be considered.”

The study, “Effect of Sustained-Release Morphine for Refractory Breathlessness in Chronic Obstructive Pulmonary Disease on Health Status: A Randomized Clinical Trial,” was published online in JAMA Internal Medicine.