COPD (Chronic obstructive pulmonary disease) is of public health concern associated with high disability, prevalence, and mortality rates. According to Zheng et al. (2018), COPD management majorly depends on inhaled drugs, which include ICs (inhaled corticosteroids), LABA (long-acting Beta adrenoceptor agonists), and LAMA (long-acting muscarinic receptor antagonists). The management often begins with monotherapy, then dual or triple therapy, depending on symptom control strategies. Studies have indicated bronchodilators are the cornerstone pharmacological management options for COPD, endorsed as primary treatment for all GOLD group patients. However, these standard regimens can fail, thus necessitating the need for opioid use. Additionally, various studies have found opioids effective in managing breathlessness, via RR (respiratory rate) reduction, without hypoxia or hypercapnia causation. This paper will focus on the effectiveness of opioid use in COPD management for patients presenting with breathlessness and critique some research findings on the same.
Opioids effectiveness
Opioids are usually prescribed for patients with COPD to combat symptoms such as SOB (shortness of breath), where the standard COPD regimens have failed. This state of SOB is often regarded as refractory dyspnea, in which opioids are used as an off-label pharmacotherapy strategy for its management. These medications are advised against use among older adults because they stand a higher chance of experiencing adverse effects of these medications, such as respiratory depression. Opioids are also linked to potentially harmful side effects among COPD patients, some of whom present with advanced respiratory symptoms. SOB, in many instances, affects the brain parts responsible for thinking, feeling, and memory, affecting patients differently, even if their LFTs (lung function tests) results are similar. Opioids, on the other hand, affect the brain regions responsible for emotional regulation, including anxiety and fear. They also have the capability of altering how SOB affects an individual patient. This effect is achieved by prescribing and administering opioid dosages of much lower quantities or doses than those administered for pain control. For instance, 1mg of oral morphine syrup equals administering one-fourth of acetaminophen with no.3 codeine.
Moreover, in a study by Vozoris et al. (2020), refractory dyspnea is often encountered and is a major challenge in most COPD patients, usually occurring in more than half of patients with advanced disease. This form of dyspnea also profoundly implicates the patient’s quality of life and contributes to major psychological effects. The study further narrates that, although opioids are administered as off-label medications for COPD patients, there are various theoretical studies supporting their role in refractory dyspnea management. They achieve their therapeutic role by binding to their receptors, abundantly found in the medulla, which is the center origin of respiratory rhythm. Theoretically, opioids are believed to be able to lessen refractory dyspnea via minute ventilation reduction or dull the respiratory response to hypercapnia or hypoxemia chemoreceptor stimulation. The opioid receptors are also located in the deeper region of the cerebral cortex, including the thalamus and insula, where opioid action on them can help modulate dyspnea perception Vozoris et al., (2020). With this evidence, some advanced guidelines for dyspnea and COPD management advocated for opioid use in COPD patients. However, some physicians are reluctant to use them due to the potential risks associated with their use on the respiratory system.
According to Vozoris (2020), two practices are applicable in prescribing opioids for refractory dyspnea in COPD, as outlined in the literature. The first practice involves using a once-daily dosing of 10-30mg oral sustained-release morphine tablet. The second practice involves using an immediate-release, standing dosing morphine, kicking off with 0.5mg two times a day. The studies have argued that using sustained-release once-daily morphine to manage refractory dyspnea is a superior prescription to the immediate-release morphine liquid preparation. The reason is that short-acting formulations are associated with a poor but steady state of the blood vessels with a greater peak in the blood, which increases the suboptimal risk response and adverse effects.
Vozoris (2020) conducted an evidence-based study review on the effectiveness of opioid use in refractory dyspnea among COPD patients. The study states that three randomized meta-analyses, double-blind and placebo RCTs (randomized controlled trials), have been conducted on therapeutic opioid use among dyspneic patients with COPD. Most of the meta-analysis used ten to twenty subjects, and the intervention consisted of short-acting opioids administered for several days. The earliest study that had been conducted by Jennings et al. delineated no major reduction in dyspneic scores with opioids administration vs. placebo. However, this first study evaluated nebulized and non-nebulized opioids, which have been constantly reported as having reduced effectiveness in reducing SOB among COPD patients Vozoris et al., (2020). The second study by Ekstrom et al. reported a significant upgrade in dyspnea scores after administering non-nebulized opioids vs. placebo. This second trial involved COPD patients and singly considered the use of nebulized and non-nebulized opioids. However, the positive results identified in this study were on a smaller scale.
The third and most recent meta-analysis was by Barnes et al., which like Jennings et al., reported no major reductions in dyspnea scores after opioids use vs. placebo in COPD patients. This study was, however, criticized for using an inappropriate methodology with data that could not be accounted for properly. These three meta-analyses from their findings concluded that opioid use showed no significant improvement in exercise capacity that was objectively measured in patients with advanced COPD. Following the abovementioned metanalysis, a major clinical trial was conducted, which involved an evaluation of per oral sustained-release 20mg morphine use for seven days. This medication was administered among 284 subjects who presented with chronic dyspnea of mMRC class and above, with sixty percent having COPD and the rest having other chronic conditions (Vozoris et al., 2020). The results revealed no significant differences in the initial outcome between morphine vs. placebo groups. There were also no significant differences in patients with dyspnea mMRC class 3 in both primary and secondary after-effects of morphine vs. placebo use.
Compared to the primary study conducted by Keogh & Williams (2021), this study review by Vozoris (2020) was meticulously conducted via a review of the condition, various RCTs (randomized control trials), and meta-analysis conducted to examine the effectiveness of opioid use in the management of breathlessness in COPD. This research is more reliable because it incorporates various study data and reviews, thus broadening its reliability. The research diversity also decreases the risk of biasness due to the reliability of the availability of data from various sources. It also contains detailed reviews on the effectiveness and respiratory-related side effects of opioid use, with a clear synthesis of the broadly acquired, evidence-based sources. On the other hand, the research by Keogh & Williams (2021) focuses on describing the barriers facing opioid use in managing COPD-related breathlessness. In an attempt to drive the objective home, it gives less-detailed evidence on the effectiveness of opioid use in managing COPD-related SOB. The systemic review was also presided by one individual, limiting the inclusion and selection criteria of the studies reviewed.
Conclusion
COPD is a disease of major public health concerns due to the high mortality and complication rates associated with the condition. Various studies have been conducted to combat this menace, and the GOLD standard has been implemented for this, including inhaled bronchodilators. These primary regimens may fail to effectively manage breathlessness in COPD patients, which necessitated the need for research on the use of opioids to manage SOB. Various studies have ascertained the effectiveness of opioid use in SOB management among COPD patients but with minimal significance. These results have therefore raised doubts about the need for opioid use, considering the respiratory effects it also predisposes the patients to, including respiratory depression.
References
Keogh, E., & Williams, E. M. (2021). Barriers to Prescribing Opioids in the Management of Chronic Breathlessness in COPD: A Review. COPD: Journal of Chronic Obstructive Pulmonary Disease, pp. 1–10. https://doi.org/10.1080/15412555.2021.2000956
Le, T. T., Park, S., Choi, M., Wijesinha, M., Khokhar, B., & Simoni-Wastila, L. (2020). Respiratory events associated with concomitant opioid and sedative use among Medicare beneficiaries with chronic obstructive pulmonary disease. BMJ Open Respiratory Research, 7(1), e000483. https://doi.org/10.1136/bmjresp-2019-000483
Opioids for Shortness of Breath in Advanced Chronic Obstructive Pulmonary Disease (COPD) Patient & Family Guide. (n.d.). https://www.nshealth.ca/sites/nshealth.ca/files/patientinformation/1892.pdf
Vozoris, N. T. (2020). Opioid utility for dyspnea in chronic obstructive pulmonary disease: a complicated and controversial story. Annals of Palliative Medicine, 9(2), 571–578. https://doi.org/10.21037/apm.2019.11.04
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