https://immattersacp.org/weekly/archives/2014/02/11/6.htm

Low-dose opioids may safely reduce breathlessness in severe COPD

Lower doses of opioids do not appear to increase hospital admissions or death in patients with very severe chronic obstructive pulmonary disease (COPD) and may safely reduce symptoms, according to a new study.


Lower doses of opioids do not appear to increase hospital admissions or death in patients with very severe chronic obstructive pulmonary disease (COPD) and may safely reduce symptoms, according to a new study.

Researchers performed a population-based longitudinal consecutive cohort study at medical centers in Sweden that prescribed long-term oxygen therapy. Included patients were 45 years of age and older, began oxygen therapy for physician-diagnosed COPD, and were entered into a nationwide database between Oct. 1, 2005, and June 30, 2009. The study's objective was to examine the safety of benzodiazepines and opioids in patients who had very severe COPD. The main outcome measures were the relationship between benzodiazepines and opioid therapy and admission and mortality rates, with adjustment for age, sex, arterial blood gases, body mass index, performance status, previous admissions, comorbid conditions and concurrent medications. The study results were published online Jan. 30 by BMJ.

A total of 2,249 patients, 59% of whom were women, were included in the study. At baseline, 535 patients (24%) were taking benzodiazepines, 509 (23%) were taking opioids, and 200 (9%) were taking both drugs. Overall, 1,681 patients (76%) were admitted to the hospital, and 1,129 (50%) died during 1.1 years of follow-up.

No association was found between benzodiazepines and opioids and increased rates of hospital admission (hazard ratios, 0.98 [95% CI, 0.87 to 1.10] and 0.98 [95% CI, 0.86 to 1.10], respectively). A dose-response trend toward increased mortality was seen for benzodiazepines (hazard ratio, 1.21 [95% CI, 1.05 to 1.39]) and for higher doses of opioids (hazard ratio, 1.21 [95% CI, 1.02 to 1.44]). However, this association was not seen with lower doses of opioids, defined as less than or equal to 30 mg of oral morphine equivalents per day (hazard ratio, 1.03 [95% CI, 0.84 to 1.26]). Lower concurrent doses of benzodiazepines and opioids were not associated with increased rates of hospital admission or mortality (hazard ratios, 0.86 [95% CI, 0.53 to 1.42] and 1.25 [95% CI, 0.78 to 1.99], respectively). The same associations were seen in patients who were naive to the study drugs and in those who were hypercapnic.

The authors noted that they could not rule out residual confounding and that patients may not have taken all drugs as prescribed, among other limitations. However, they concluded that their study supports the safety of lower doses of opioids to reduce symptoms of breathlessness in patients with severe respiratory disease and indicates that benzodiazepines should not be used as first-line therapy for symptom reduction in this population.

“Sustained release morphine should be considered as a first line treatment and should be initiated at a low dose regularly and titrated upward over days and weeks, balancing beneficial and adverse effects,” the authors wrote. “Titration up to 30 mg morphine daily might safely improve breathlessness in over 60% of patients, with a mean decrease of 35% in the intensity of breathless from the person's own baseline.” The authors stressed that higher opioid doses for control of symptoms should be balanced against a potentially increased risk for adverse effects and that all patients should receive adequate follow-up for their clinical condition and symptoms.