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Published on: July 29, 2014
Harms of Morphine for Chronic Breathlessness in Relation to Dose, Duration and Titration Phase
Magnus Ekström1, Fatima Alameri1, Sungwon Chang2
1Respiratory Medicine (M.E., F.A.), Allergology and Palliative Medicine, Department of Clinical Sciences Lund, Lund University, Sweden.
Context:
Morphine to treat severe chronic breathlessness might increase adverse events (AEs).
Objectives:
We aimed to evaluate the risk of AEs in relation to dose, duration and titration phase of regular, low-dose sustained-release (SR) oral morphine for chronic breathlessness in people with chronic obstructive pulmonary disease (COPD).
Methods:
Secondary analysis of a double-blind, randomized, trial of SR morphine titrated to 0-32 mg/day over three weeks in people with COPD and chronic breathlessness. Risk of AEs by morphine or placebo dose, duration and titration phase (initiation, stable dose or up-titration) was analyzed using multivariable generalized estimating equation (GEE) models.
Results:
We included 156 people (49% female) of whom 100 (64%) experienced any AE during week 1: 64% of those on 8 mg/morphine/day; 78% on 16 mg/morphine/day; and 48% on placebo. In multivariable analysis, the AE risk was highest the first week of morphine treatment and decreased in week two (adjusted rate ratio [aRR] 0.71; 95% confidence interval (CI) 0.54, 0.94) and week three (aRR 0.49; 95% CI 0.37, 0.67). Over the three weeks, the AE risk was similar between titration phases, and there was no statistically significant trend with higher morphine doses (P-values>0.10). Most AEs did not require treatment discontinuation or dose reduction and resolved by the end of titration.
Conclusion:
In people with COPD and severe chronic breathlessness, the risk of AEs was highest during the first week of treatment in a dose-related fashion but did not differ by titration phase or by dose of once-daily SR morphine between 8 and 32 mg/day. Trial registration NCT02720822.
Insights
The risk of adverse events (AEs) from sustained-release oral morphine for chronic breathlessness in COPD patients was highest in the first week of treatment. Most AEs were mild and resolved without dose adjustment.
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Clinical Trials
Background:
- Severe chronic breathlessness in COPD patients can be treated with morphine.
- Morphine use may increase the risk of adverse events (AEs).
Purpose of the Study:
- To evaluate the risk of AEs associated with regular, low-dose sustained-release (SR) oral morphine for chronic breathlessness in COPD patients.
- To assess the relationship between AEs and morphine dose, treatment duration, and titration phase.
Main Methods:
- Secondary analysis of a double-blind, randomized trial involving SR morphine titration (0-32 mg/day over three weeks) in COPD patients.
- Multivariable generalized estimating equation (GEE) models were used to analyze AE risk based on morphine dose, duration, and titration phase (initiation, stable dose, up-titration).
Main Results:
- Of 156 participants, 64% experienced AEs in week 1.
- AE risk was highest during the first week of morphine treatment, decreasing significantly in weeks 2 and 3.
- No statistically significant trend in AE risk was observed with increasing morphine doses (8-32 mg/day) or across different titration phases.
Conclusions:
- The highest risk of AEs occurred during the initial week of SR oral morphine treatment for chronic breathlessness in COPD patients.
- AE risk did not significantly differ based on titration phase or daily morphine dose (8-32 mg).
- Most AEs were manageable and resolved by the end of the titration period.
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