The Effects of Low-Dose Morphine on Sleep and Breathlessness in Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial
Authors List
Thomas J. Altree1*, Alison Pinczel1, Kelly Loffler1, Anna Hudson1, David C. Currow2,3, Sutapa Mukherjee1, Peter G. Catcheside1, Danny J Eckert1
1. Adelaide Institute for Sleep Health and FHMRI Sleep Health, College of Medicine and Public Health, Flinders University, Adelaide, Australia; 2. University of Technology Sydney (UTS), Faculty of Health, Improving Palliative, Aged and Chronic Care through Clinical Research and Translation (IMPACCT), Ultimo, NSW, Australia; 3. Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, Australia.
Introduction
Low-dose slow-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, efficacy varies between patients and is difficult to predict. Preliminary findings suggest that beneficial effects of low-dose morphine on breathlessness may be mediated, at least in part, by improvements in sleep. However, this has not been objectively investigated. Accordingly, the goal of the current study was to quantify the effects of low-dose morphine on sleep and breathlessness in people with COPD. We hypothesized that low-dose morphine would improve 1) sleep and 2) breathlessness and the extent of these changes would be related.
Methods
22 people with COPD and breathlessness (modified medical research council score ≥2) were enrolled in a double-blind, randomized, cross-over design trial (ACTRN12621000752864). Participants received either 20mg slow-release morphine daily for 3 days or placebo with a one-week washout between interventions (order randomized). During each arm, a level 3 in-home sleep study was performed at night 1 (ApneaLink) to assess acute effects of morphine on oxygenation and sleep disordered breathing, and in-laboratory overnight polysomnography was conducted at night 3 when morphine was in steady pharmacokinetic state. Breathlessness Now questionnaire scores and externally applied resistive loads to breathing were performed before and after sleep at both night 3 visits (placebo and 20mg morphine). Next morning driving performance was also quantified using the AusEd driving simulator task.
Results
Of the 22 participants recruited (50% women), 19 participants completed the study protocol. The mean±SD BMI and FEV1 of the participants was 26±6 kg/m2 and 50±21% predicted, respectively. Baseline arterial blood gas values were as follows: PaO2= 72±14 and PaCO2= 40±7 mmHg. Mean COPD Assessment Test scores were 16±4 (i.e., overall medium symptom burden). Initial analysis, limited to night 1 in-home level 3 sleep study testing, did
not show any systematic worsening of sleep disordered breathing with morphine versus placebo (e.g., AHI = 7±12 vs. 9±18 events/h, p=0.34 and %time with SpO2<90% 47±39 vs. 42±38%, p=0.22).
Conclusions
These initial findings indicate that low-dose morphine does not acutely systematically worsen sleep disordered breathing in people with COPD and breathlessness. These findings have important safety implications for the use of low-dose morphine in people with COPD.
Research Funding Source: This study was funded by the National Health and Medical Research Council of Australia (1065571)
Thomas J. Altree1*, Alison Pinczel1, Kelly Loffler1, Anna Hudson1, David C. Currow2,3, Sutapa Mukherjee1, Peter G. Catcheside1, Danny J Eckert1
1. Adelaide Institute for Sleep Health and FHMRI Sleep Health, College of Medicine and Public Health, Flinders University, Adelaide, Australia; 2. University of Technology Sydney (UTS), Faculty of Health, Improving Palliative, Aged and Chronic Care through Clinical Research and Translation (IMPACCT), Ultimo, NSW, Australia; 3. Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, Australia.
Introduction
Low-dose slow-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, efficacy varies between patients and is difficult to predict. Preliminary findings suggest that beneficial effects of low-dose morphine on breathlessness may be mediated, at least in part, by improvements in sleep. However, this has not been objectively investigated. Accordingly, the goal of the current study was to quantify the effects of low-dose morphine on sleep and breathlessness in people with COPD. We hypothesized that low-dose morphine would improve 1) sleep and 2) breathlessness and the extent of these changes would be related.
Methods
22 people with COPD and breathlessness (modified medical research council score ≥2) were enrolled in a double-blind, randomized, cross-over design trial (ACTRN12621000752864). Participants received either 20mg slow-release morphine daily for 3 days or placebo with a one-week washout between interventions (order randomized). During each arm, a level 3 in-home sleep study was performed at night 1 (ApneaLink) to assess acute effects of morphine on oxygenation and sleep disordered breathing, and in-laboratory overnight polysomnography was conducted at night 3 when morphine was in steady pharmacokinetic state. Breathlessness Now questionnaire scores and externally applied resistive loads to breathing were performed before and after sleep at both night 3 visits (placebo and 20mg morphine). Next morning driving performance was also quantified using the AusEd driving simulator task.
Results
Of the 22 participants recruited (50% women), 19 participants completed the study protocol. The mean±SD BMI and FEV1 of the participants was 26±6 kg/m2 and 50±21% predicted, respectively. Baseline arterial blood gas values were as follows: PaO2= 72±14 and PaCO2= 40±7 mmHg. Mean COPD Assessment Test scores were 16±4 (i.e., overall medium symptom burden). Initial analysis, limited to night 1 in-home level 3 sleep study testing, did
not show any systematic worsening of sleep disordered breathing with morphine versus placebo (e.g., AHI = 7±12 vs. 9±18 events/h, p=0.34 and %time with SpO2<90% 47±39 vs. 42±38%, p=0.22).
Conclusions
These initial findings indicate that low-dose morphine does not acutely systematically worsen sleep disordered breathing in people with COPD and breathlessness. These findings have important safety implications for the use of low-dose morphine in people with COPD.
Research Funding Source: This study was funded by the National Health and Medical Research Council of Australia (1065571)
