Barriers to Prescribing Opioids in the Management of Chronic Breathlessness in COPD: A Review

Abstract

In people with COPD breathlessness is a common symptom and if mistreated can result in poor physical health and reduced quality of life. While it is important to manage the breathlessness using non-pharmacological management, persistent breathlessness may be treated with opioids. However, some physicians are reluctant to prescribe opioids to manage breathlessness in COPD. The aim of this review is to report the views, attitudes and barriers (if any) of healthcare professionals towards using opioids to manage chronic breathlessness in COPD. A review of the relevant literature was undertaken, using CINAHL, ScienceDirect and PubMed databases. The selected literature was assessed for quality of study design and methods used. Eleven studies (three qualitative, three mixed-methods and five quantitative) were reviewed and three themes were identified. Opioid use for refractory breathlessness in COPD is likely under prescribed by health care professionals working in areas other than palliative care. Additionally, there is a lack of confidence in using opioids except in those with palliative care experience, who are more likely to believe opioids may be helpful. Barriers identified are a lack of training, education, inadequate guidelines and concerns surrounding respiratory depression and other side effects. Research on this topic is mainly comprised of interviews or surveys and is low to moderate quality. Further clinical trials are needed on this topic including the opinions of all prescribing health care professionals involved in the care of these patients. Additionally, guidelines should offer further advice on when to start opioids and which patients would benefit most from opioids.

Keywords:

• COPD
• breathlessness
• palliative care
• respiratory care
• prescribing

Introduction

Chronic obstructive pulmonary disease (COPD) affects around 65 million people worldwide including 1.2 million people in the United Kingdom [1]. The prevalence of COPD is increasing in the UK [2] and remains the third most common cause of death worldwide in 2019 [3]. COPD is characterised by symptoms of dyspnoea or breathlessness, cough and sputum production. Breathlessness can negatively affect a person’s physical and mental health and impair quality of life [4]. Consequently, knowledge of symptom management in COPD is important as patients with COPD are often more breathless than those with advanced lung cancer. In addition, they often live with extreme breathlessness for longer [5]. It has long been known that to manage a patient’s breathlessness it is important to optimise the patients well-being first. These methods involve smoking cessation, pulmonary rehabilitation, encouraging nutritional intake to avoid malnutrition and breathing techniques [6, 7]. Nevertheless, despite these efforts’ breathlessness remains an incapacitating symptom for patients even at rest. A combination of non-pharmacological and pharmacological management is needed [4]. A trial by Verberkt et al. [8] found that regular low dose opioids improved disease specific health status in patients with moderate to severe breathlessness. The use of opioids to reduce dyspnoea has been investigated but its effectiveness remains controversial [9]. The exact action of opioids on breathlessness is unclear since they may work peripherally or centrally to reduce the sensation of breathlessness [6]. Ekström et al. [5] demonstrated that low dose-opioids were safe in COPD but higher doses were related with an increased risk of mortality. A Cochrane review which examined the use of opioids in COPD reported that opioids may be of benefit to patients but that the quality of the evidence was low [10]. Furthermore, Lanken et al. [11] state that opioids along with care coordination can be beneficial towards improving breathlessness. Similarly, NICE [12] recommends using opioids in those with dyspnoea. They also suggest that health care professionals should examine whether a laxative or anti-emetic should also be prescribed. However, doctors may be hesitant to prescribe opioids to manage breathlessness in COPD [13].

Therefore, it is unclear if there is a consensus of views of health care professionals on the use of opioids to manage chronic breathlessness while caring for patients with COPD.

The aim of this review is to report the views, attitudes and barriers (if any) from the perspective of health care professionals towards the use of opioids in managing chronic breathlessness in COPD.

Methods

A review was undertaken in order to examine and quality assess available literature on the subject [14]. Database searches were conducted by EK between February to April 2021, using multiple literature searches of the CINAHL, ScienceDirect and PubMed databases. Multiple search words and search strings were used and included “Chronic Obstructive Pulmonary disease” (OR “COPD” OR “Chronic Obstructive Lung Disease), “Opioid” (“Pharmacological management”), “Breathlessness” (OR “Dyspnoea”), “Opinion” (“Attitude” OR “View” OR “Belief” OR “Barrier”), “Respiratory team”, “Palliative care team”. These search words were then linked together with Boolean search words, AND/OR in different combinations to search the databases. The filter ‘full text’ was applied which ensured that only literature available in full to download was presented [15]. If the option was available when searching, then only peer reviewed research was included. Research pre-dating 2002 was excluded as over time views may have changed and non-English language studies were omitted. Grey literature was also searched with the aim to reduce publication bias. Literature searches of Open Grey and the World Health Organisation International Clinical Trials Registry Platform (ICTRP) were undertaken in order to obtain relevant research. Finally, leading journals were searched for research that was pertinent to the study including Thorax and the European Respiratory Journal via online editions for publications. Reference lists of papers published on the topic were also scanned for other studies.

Inclusion criteria were studies that were related to the assessment of the use of opioids to manage breathlessness in COPD. Any study design was included and the studies could take place in any setting. Exclusion criteria were studies that examined breathlessness management with opioids in conditions other than COPD, however studies that looked at other conditions as well as COPD could be included. Other exclusion criteria were studies that primarily examined the use of other pharmacological treatments such as benzodiazepines and studies that examined the benefit of one opioid treatment over another.

The assessment of the studies for inclusion, quality assessment and data extraction were completed in a three step process. The first step involved assessing the identified studies for inclusion suitability using the PICOSS tool to assess each research paper by title and abstract [16]. Step two comprised of examining the entire article using PICOSS and quality assessment (Tables 1 and 2). A validated and reliable quality assessment tool using 18-points was used to assess the studies [17]. Using this tool a numerical value is applied to each point on a range of 0-2 with 0= not explained/done, 1= partly and 2 = yes. A score of 20 or less indicates poor quality. The studies that used mixed-methods were assessed using the qualitative and quantitative section, providing a maximum score of 46 points, a score below 26 indicating lower quality studies.

Table 1. Study design and quality assessment score.

Study	Type of study Sample size, n	Characteristics Country Setting Specialism	Comparison	Outcome measurements	Bias	QAS (Max 36)
Gaspar et al. (2014). [20]	Survey 136 doctors	Portugal Respiratory Specialists and fellows	Not described	The number who prescribe opioids	Selection bias (low response rate and using a respiratory body to send out surveys) Responder Bias.	26
Hadjiphilippou et al. (2014). [19]	Semi-structured questionnaire 65 doctors	UK District Hospital Medical physicians: range of experience	Compare management for patients with heart failure, COPD, lung cancer and the dying patient	Prescribing of opioids for breathlessness Barriers	Selection bias Reporting bias	20
Janssen et al. (2015). [22]	Cross-sectional observational study 146 doctors	The Netherlands Respiratory consultants and residents	Those who prescribe opioids to 20% or less of their patient’s vs those who prescribe opioids to 20% or more of their patients with advanced COPD	Attitudes towards using opioids in COPD for breathlessness Barriers to using opioids	Responder bias	31
Krajnik et al. (2020). [25]	Survey 450 doctors	Europe 348 respiratory medicine physicians, 102 palliative care physicians	Palliative care physicians versus respiratory physicians in management of patients with ILD, COPD and lung cancer	Management of the patients Palliative care knowledge	Selection bias Reporting bias	11
Politis et al. (2021). [30]	Survey 148 GPs	Australia General practitioners	The results from each GP were compared with age, location, sex, experience, palliative care experience.	Management of breathlessness Barriers towards using opioids	Selection bias	26
Smallwood et al. (2018). [24]	Questionnaire 577	New Zealand, Australia and the United Kingdom Palliative care physicians in the three countries, Respiratory physicians in Australia and New Zealand	Comparison of the two groups Comparisons in the groups e.g. years of experience.	Management approaches Prescribing habits Barriers to using opioids in COPD	Responder Bias	29
Young et al. (2010). [27]	Semi-Structured qualitative interview 18 doctors	Canada 3 Palliative Care, 3 Internal Medicine, 4 Respiratory Medicine 8 Family Medicine physicinas	Differences in management between the four groups	Attitudes towards prescribing opioids in COPD Barriers towards prescribing opioids in COPD	Reporting bias	13
Young et al. (2012). [29]	Semi-structured interview 18 health care professionals	Canada 10 family medicine physicians 8 respiratory therapists	Comparison of experience and practice setting	Views on managing breathlessness in COPD Barriers		30

Table 2. Study design and quality assessment score for mixed method studies.

Study	Type of study and Sample size, n	Characteristics Country Setting Specialism	Comparison	Outcome measurements	Bias	QAS (Max 46)
Carette et al. (2019). [26]	Mixed method approach with a qualitative survey and an observational study. 120 patients 46 doctors	France Respiratory Physicians	Comparison between the doctors based on experience as a doctor, location of work and age	Views on opioids use in COPD Prescribing of opioids in COPD Barriers	Responder bias	30
Ecenarro et al. (2018). [23]	Cross-sectional descriptive non-controlled study 386	Spain Respiratory Physicians	Comparison between the doctors based on experience	Prescribing habits for opioids	Selection Bias	31
Rocker et al. (2012). [28]	Mixed-method semi-structured interview 47 (n = 8 patients, n = 11 care givers, n-28 doctors)	Canada Respiratory physicians, n = 6, Palliative care physicians, n = 6, Internal medicine physicians, n = 6, Family medicine physicians, n = 10	Comparison between the group of doctors	Attitudes towards opioid use Views towards using opioids Barriers	Selection bias	37

The third step involved using PICO to data extract the relevant information from the article. As a result, themes and results were established.

Results

The databases search yielded a total of 2,406 papers which were subsequently scanned by title and filtered down to 11 studies for detailed review (Figure 1). Including the grey literature search, a total number of 19 publications were found. However, on assessment of these by title, none were found suitable. Searching the journal Thorax produced no suitable papers while three articles were found in the European Respiratory Journal. From hand searching various reference lists 5 papers were identified. This led to a total of 20 papers being identified but on further inspection duplicates were noted. When the duplicates were removed 16 papers remained.

Figure 1. PRISMA: search strategy [18].

After step one it was found that 9 studies were suitable, 5 not, and 2 needed further review. Of the 5 excluded studies, one examined general opinions of opioid use in end-of-life care, another study was a randomised controlled trial on integrated team working. Two studies observed opioid prescribing, while one study was a conference abstract of an included study. After step two, the 2 undecided studies were deemed suitable for inclusion. Therefore 11 studies were included in the review, of which 5 were quantitative in nature, 3 were qualitative and 3 used mixed-methods.

Within the 11 international studies three main themes were identified, 1; Self-reported prescribing habits in normal practice, 2; The views and knowledge of managing chronic breathlessness in COPD and the use of opioids, and 3; The barriers of using opioids in chronic breathlessness. After quality assessment four studies scored less than 20 (low quality), two studies were moderate quality and three were considered high quality. Two of the mixed method studies were moderate quality while one was of high quality (Table 1 and Table 2).

Theme 1: Self-reported prescribing habits in normal practice

A semi-structured survey undertaken at a district hospital in the United Kingdom examined the attitudes and experiences of physicians who attended education events towards the use of opioids to manage breathlessness [19]. There were sixty-five responses and the physicians varied in experience ranging from foundation year doctors to consultants. Some selection bias may be present as the total population is not mentioned. In addition, a convenience sample was used meaning the sample was not very specific [14]. Other issues that were not explained were the topic of the study day, because if they were related to the topic of the study then perhaps the medics had a greater interest so would be more confident in this area. Additionally, the speciality of the medics was not mentioned as this may have improved or reduced their confidence with using opioids in breathlessness management. Of the 65 physicians, 49 (75%) reported to have prescribed opioids to manage breathlessness. However, 44 of these were when the patient was dying. For COPD patients, 21 respondents had prescribed opioids for breathlessness in the past. It was not clear how many COPD patients the sampled physicians treat or have treated and there is no mention of whether the experience level of the doctors or any other variables were associated with the results.

In Portugal, Gaspar et al. [20] surveyed respiratory consultants and fellows working in respiratory medicine who were registered with the Portuguese Pneumology Society. The authors requested that any physicians who had not worked clinically in the previous year did not complete the survey. Of the 464 surveys sent, they received 136 responses (29%), but the authors were not able to establish how many respondents were excluded based on the criteria mentioned. The survey had been piloted on the six respiratory doctors to assess validity [21]. The survey asked one question about palliation of symptoms as ‘How often treated, Dyspnoea (namely using opioids)’. The authors reported that 8.8% of the sample stated they never use opioids for dyspnoea while 7.4% always did. Over twenty percent (21.3%) said they rarely do, 32.4% said occasionally and 30.1% reported frequent use of opioids for breathlessness. However, the responses were self-reported so there is a risk of inadequate self-reporting [14]. In addition, the authors recognised that the way in which they phrased the question around opioids may have been confusing and could have led to inaccurate reports from the doctors.

Janssen et al. [22] conducted a cross-sectional observational study in the Netherlands sending a survey to respiratory consultants and residents. Half (50%) of the doctors reported that they prescribed opioids for the management of dyspnoea in advanced COPD for 20% or less of their patients. Additionally, 18.5% of the doctors reported never prescribing opioids for patients with advanced COPD who had refractory breathlessness.

Ecenarro et al. [23] undertook a cross-sectional descriptive non-controlled study in Spain using a mixed-method approach. The survey was sent to members of the Spanish Society of Pulmonology and Thoracic Surgery. Like Gaspar et al. [20] the authors only wanted responses from those who had worked clinically in the past year. The response rate was 32% (n = 386) however, it is not clear how many doctors could not complete the study based on the inclusion criteria. The authors had tested the survey on a small group of doctors to ensure its suitability. The survey asked about symptom management and the use of opioids to manage dyspnoea. The authors report that 4% of physicians never used opioids while 10.7% rarely did, 32.4% sometimes used opioids, 40.8% often did and 12.1% always. However, most of the respondents worked in university hospitals and had more than 20 years’ experience so they may not represent the general medical population. Additionally, two-thirds of the doctors said they spend very little time or no time at all managing patients with end-stage COPD which could affect their knowledge.

Smallwood et al. [24] reported that palliative care physicians were more likely to regularly (81%) or occasionally (19%) prescribe opioids for management of COPD related breathlessness, whereas 35.6% of respiratory physicians regularly do and 55.4% occasionally do.

Krajnik et al. [25] undertook a study which involved European wide respiratory and palliative care physicians completing an online survey which also included three case vignettes on lung cancer, interstitial lung disease (ILD) and advanced COPD. The actual recruitment population was not mentioned but there were 348 responses from respiratory physicians and 102 responses from palliative care physicians. Survey creation was not described nor how the study was circulated, or how if it was tested prior to being sent out. The respiratory physicians recommended rehabilitation and exercise for the COPD patients whereas the palliative care physicians favoured the use of medication. However, it is not mentioned what medication they would use. However, 92% of palliative care physicians always or often use opioids in COPD in comparison to 39% of respiratory physicians. Forty percent of the respondents said they read non-cancer related palliative care guidelines. These doctors were more likely to recommend the use of opioids in advanced COPD (χ2 = 12.58, p = 0.0004). However, it would have been clearer if the authors provided information on the proportion of respiratory physicians that read these guidelines.

From these studies it can be concluded that the prescribing of opioids in the management of chronic breathlessness in advanced COPD is likely underused by health care professionals working in areas other than palliative care.

Theme 2: the views and knowledge of managing chronic breathlessness in COPD and the use of opioids

Carette et al. [26] undertook a mixed-method study to examine the characteristics of patients that experience difficult-to-manage breathlessness, as well as to assess the use of opioids by respiratory doctors for this problem. The study included 120 patients who had been recruited to a national cohort study but lived in the Lorraine region of France and 46 doctors that worked in the same region. The response rate was 52%. The doctors were sent a survey that was developed for the study but it was not mentioned whether the survey was tested on a smaller sample for validity. The authors report that 50% of the surveyed doctors thought opioids could be used to manage breathlessness in COPD but 48% thought they would be better for hospitalised patients whereas 24% were of the opinion that outpatients would benefit. However, 30% of doctors would be reluctant to prescribe opioids for COPD-related breathlessness. Ninety-four per cent of the doctors were more likely to recommend pulmonary rehabilitation for breathlessness management. The authors did not compare the doctors responses to the data provided on the actual use of different treatment options. This could have improved the understanding of management by different groups. It is also not mentioned whether the sample was a true representation of the recruitment population.

Hadjiphilippou et al. [19] mention that 55 of 65 (85%) physicians were aware that opioids could be used to manage severe breathlessness. However, where they were asked to rate their confidence in using opioids for breathlessness management; heart failure, the dying patient, advanced cancer and COPD, COPD was the area in which they were the least confident.

Smallwood et al. [24] examined the knowledge and attitudes of respiratory physicians in Australia and New Zealand and palliative care physicians in Australia, New Zealand and the United Kingdom towards the management of breathlessness in COPD. They were all specialists or specialist trainees. The authors conducted the study by trialling a survey on thirty doctors. It was then disseminated at palliative care meetings and online by three different agencies. Three quarters (74.9%) of the palliative care physicians recommended using opioids to manage the patient in the case vignette in comparison to 41.2% of the respiratory specialists which was significantly different (p < 0.0001). It was found that the respiratory doctors who recommended using opioids tended to be younger (p = 0.002) and had worked for a shorter time in respiratory care (p = 0.001). These associations were not found when compared with the palliative care doctors. The authors report that the characteristics of the respondents were similar to those found in the census. This means the sample likely represents the population.

Young, et al. [27] undertook a semi-structured interview in Canada, and presented the information as an abstract. The benefit of this style of interview is that it is not overly structured and allows the participant to speak more freely and allow the interviewer to follow themes as they emerge [14]. The sample consisted of 18 doctors from three centres who specialised in palliative care medicine (n = 3), internal medicine (n = 3), family medicine (n = 8) and respiratory medicine (n = 4). The exact recruitment population is not mentioned, and it is not mentioned if saturation was achieved. It is reported that the palliative care doctors felt comfortable to use opioids in COPD management of breathlessness. However, the other doctors expressed mixed feelings in being able to do so and were hesitant in using opioids to manage breathlessness in COPD. There is also the risk of reporting bias as not all of the outcomes were mentioned, such as years of experience.

Rocker et al. [28] reports that the doctors stated they were unhappy with not being able to provide the appropriate level of care for the patients.

“I think it’s more than a placebo. I really do … I have an interest in dyspnea and I know that it can be modified by a number of different factors when it gets to the brain and my thinking is that that’s where morphine works, is to modify that sensation, and so I think it’s more than a placebo. I’m still hoping as to whether it really works, but I believe it should.” — Physician 4, Respirology

“I think it’s a great idea but I haven’t read the data … I’ve never, never done it but it makes good sense. We do it in acute settings. We give morphine nebules or morphine intravenous when patients are acutely dyspneic. I don’t know why it’s not used more often, but I hardly ever see it.” — Physician 8, Internal Medicine.

Doctors that did prescribe opioids found they were helpful for the patient. Doctors that did not prescribe opioids thought they might be helpful and also thought palliative measures were not used enough.

Like Rocker et al. [28] doctors in the study conducted by Young et al. [29] reported that they are frustrated when managing COPD patients with difficult breathlessness. The participants also mention that ineffective treatment of breathlessness negatively impacts a patient’s quality of life. The majority of the participants were of the opinion that opioids may reduce breathlessness for the patient even if they did not use them.

“Actually, using the opiates was very beneficial, immediately gave them a sense of relief, relaxed their muscles. Oxygen levels were actually improved because they were more relaxed and didn’t have that sensation that they couldn’t get their breath. Even if they did look breathless they didn’t have that sensation …. Very valuable, very valuable intervention, yes. There was never a situation that I didn’t feel it was helpful. There were many situations that I felt it was started too late. It could have been introduced much earlier. (RT 07)”

Politis et al. [30] found in a survey which included a case-vignette of a patient with severe COPD and refractory breathlessness that 65.7% of GP’s would add in an additional treatment medication. From this group 25.6% would add in immediate release morphine. The remainder of the group suggested using alternative medication. GPs were four times more likely to recommend an opioid if they had received some form of palliative care post-graduate education (OR = 3.7, 95%, CI =1.5-9.1, p = 0.003). No association with age or other variables were found. Meanwhile, 54.7% of the GP’s believed that opioids could have a role in managing severe breathlessness in COPD but only 48.2% of them had used opioids for this reason. The GP’s that had post-graduate education or experience in palliative care were three times more likely to have prescribed opioids for severe breathlessness in COPD (OR = 2.8, 95%, CI =1.3-5.8, p = 0.006).

In conclusion doctors are frustrated with not being able to manage patients with chronic breathlessness secondary to COPD-induced breathlessness. There appears to be a lack of confidence when using opioids in COPD. Nevertheless, doctors with some palliative care experience or those working in palliative care medicine are more likely to view opioids as beneficial.

Theme 3: the barriers of using opioids in chronic breathlessness

It is pertinent to determine and understand potential barriers to prescribing and using opioids to alleviate chronic breathlessness.

Hadjiphilippou, Odogwu and Dand [19] stated that forty of the physicians were concerned about prescribing opioids for breathlessness. Forty-four felt further information was needed before prescribing opioids for breathlessness. The doctors mainly wanted advice on the practical aspects such as type of opioid, dosing and regimes. This is similar to the data from Young, et al. [27] where the reported barriers were a lack of training, insufficient education and absence of guidelines. Furthermore, Smallwood et al. [24] identified that 11.3% of doctors reported knowledge or lacking experience as a barrier to using opioids in refractory breathlessness in COPD. These barriers were more commonly reported by respiratory specialists rather than palliative care physicians (p < 0.0001 for both). Additionally, Young et al. [29] undertook semi-structured interviews in Canada with 18 participants made up of family medicine doctors (n = 10) and respiratory therapists (n = 8). The participants were from a mixture of rural and urban areas. Similar findings were reported including a lack of knowledge and education surrounding opioids and COPD. Respiratory therapists with palliative care experience felt more comfortable with the use of opioids but still felt unsure due to lack of education and were concerned the family doctor would not be amenable.

‘I guess the thing is I don’t have enough experience in doing that yet [opioid use for advanced COPD] and there hasn’t been enough studies out, enough physicians that are on board with it yet’. (RT 05)

‘I think, you know, having a CME [continuing medical education] event where someone talked about that would be helpful. I think it would be very useful. I mean the thing is that right now, it feels to me like going out on a limb if I were to say, okay, my next patient is really in trouble, I’m going to start them on morphine, you know, but if I felt that … if I went to such an event, I would feel more confident, I think, that that’s acceptable treatment’. (FP 16)

Lack of guidelines was another issue:

‘I don’t think there’s any guideline telling us to use morphine, so it may be more individual case for using morphine, but for quality treatment for cancer pain, it’s almost a standard to use a narcotic, opioid, to treat pain. So, we’re more ready to use opioids for cancer patients. For COPD patients maybe there’s more reluctance in using it because it’s not in the guidelines that tell us to do it. So then there needs to be guidelines that really show who should be on it, and who shouldn’t be on it, and it shouldn’t be left for everyone to decide on their own because then there may be some patient that doesn’t really need to go on the opioid and end up using It’. (FP 06)

‘You’d have to make sure that [acute episode] was all ruled out before you used that [opioid], I wouldn’t just start it. So, I’d be looking and if it was, everything else was ruled out, then I’d be inclined to try it. It wouldn’t look too good if you gave them morphine to deal with a bout of pneumonia: Sorry, doctor, your licence has just been revoked’. (FP 13)

Rocker et al. [28] reported similar findings following semi-structured interviews with the aim to examine doctors’ attitudes towards the use of opioids as well as the experiences of patients and care givers on the use of opioids for COPD related breathlessness. A mixed-methods approach was undertaken to gather both qualitative and quantitative data. The study included 8 patients, 11 care givers and 28 doctors (respiratory n = 6, palliative care n = 6, internal medicine n = 6, family medicine n = 10). The doctors (including palliative care doctors) reported fears over using opioids which related to respiratory depression.

A lack of knowledge and education is a barrier to prescribing opioids.

“I mean when I went to medical school, we were taught to never consider opioids in people with COPD. We were going to kill them. It was like if you gave them one dose of morphine, they would be dead and it would be your fault. That was the teaching. So it was a revelation to me, I don’t know, five, seven years ago to go to a CME thing and have people talking about using opioids and starting to use it, and certainly in terms of dealing with anxiety and breathlessness.” — Physician 13, Family Medicine

“In my generation of physicians when you were in med school that was hammered in, ‘Well you can’t do this. You’re going to have respiratory depression.’ I’m sure there is a 10-year generation where that was hammered into you, just like, ‘Don’t use a beta-blocker in heart failure.’ So you have to relearn. I think it’s just a matter of re-learning and being comfortable using it. — Physician 21, Family Medicine

“So, I’m not concerned with respiratory depression if a patient is started on an appropriate low dose, titrated appropriately, and monitored appropriately.” — Physician 3, Palliative Medicine

“I worry about it all the time. People overdose, old and frail people really easily, when they [other health professionals] are not used to giving opioids. So they hear about giving opioids for shortness of breath and they lay it on to them and even the people who have pain, that scares me if they’re people that don’t understand that 5 mg of morphine is not the same as 5 mg of Dilaudid or, you know, they don’t know how to convert to the fentanyl patch. So I worry about it all the time when other people are doing it. I don’t worry about when I do it, no.” — Physician 11, Palliative Medicine

Fear of scrutiny from drug monitoring boards for prescribing opioids also hindered the prescribing of the drugs. Although the study was of high quality, it is not clear how transferable the results are given the use of a convenience sample [14].

In Carette et al. [26], 66% of participants reported that they were worried about side effects including respiratory depression. Fear over respiratory depression was reported in most of the studies that discussed barriers [19, 27, 29, 30]. Young et al. [29] states that there was a reluctance to prescribe opioids which related to concerns surrounding respiratory depression, and several participants felt it would be beneficial to start opioids in the hospital rather than the community, as the patient could be monitored.

“You don’t know until you try them and doing that in the community setting is, it’s not without its problems, and I think a lot of physicians would be nervous about that.” (FP 14)

A cross-sectional observational study in the Netherlands aimed to explore the attitudes of respiratory consultants and residents and included 146 responses (111 consultants and 35 residents) [13]. The average number of barriers to prescribing opioids were 1.9. yet, 24% of participants mentioned more. Firstly, and most common, was the resistance of the patients themselves to having opioids. The next most common barrier was the potential side effects of opioids, including nausea, constipation and drowsiness. The barrier ranked third was the risk of respiratory depression. The fourth barrier consisted of two concerns which were insufficient experience with prescribing opioids, and of being unsure who would benefit from the opioids therapy. The lack of scientific evidence on the benefit of opioids in severe breathlessness in patients with COPD was next. The sixth and seventh ranked barriers were the risk of the patient developing opioid addiction or dependence and the lack of scientific evidence on regarding safety concerns. The last barrier was the belief that opioids are only indicated in terminally ill patients. It is important to note that the participants recruited mostly physicians from academic hospitals, so may not be fully representative of those working in other areas. Furthermore, the sample size represented less than 25% of the physician population.

A survey undertaken by Politis et al. [30] with general practitioners (n = 148 of 900) in Australia reported fears over gastrointestinal side effects (16.1%) and sedative effects (10.2%). The survey was piloted on 12 GP’s to ensure it was suitable prior to use.

Discussion

This review aims to examine the views, attitudes and barriers towards the use of opioids in managing chronic breathlessness in COPD. Consequently, the self-reported prescribing habits of doctors were assessed in seven studies that varied in quality (Table 1 and 2). Gaspar et al. [20] reported that 8.8% of respiratory doctors never prescribe opioids for COPD-related refractory breathlessness, while only 7.4% always do. This is similar to the findings Ecenarro et al. [23] reported, where 4% of respiratory doctors never recommend opioids but 12.1% always do. Additionally, Janssen et al. [22] state that 18.5% of the respiratory doctors never prescribe opioids for management of breathlessness in COPD, while 50% do for 20% or less of their patients. Those who prescribe opioids to less than 20% of their patients with advanced COPD who remained breathless tended to be older, work in university hospitals and were less likely to have oncology as a subspeciality. Hadjiphilippou Odogwu and Dand [19] found that medical doctors were more likely to prescribe opioids to the dying patient (n = 44) than a patient with COPD (n = 21). Smallwood et al. [24] found that palliative care doctors were more likely to prescribe opioids for COPD management regularly (81%) than respiratory doctors (35.6%). These findings were consistent with those reported by Krajnik et al. [25] where 92% of palliative care doctors report to always or often use opioids for COPD related breathlessness, whereas only 39% of respiratory doctors do. It is also mentioned that those who do prescribe opioids are more likely to have read non-cancer related palliative care guidelines. It is clear that the self-reported prescribing of opioids among non-palliative care doctors is low. This is despite GOLD [31] reporting that opioids alleviate breathlessness and NICE [32] recommending opioid use in end-stage COPD when breathlessness is not managed sufficiently by non-pharmacological methods. Furthermore, it is recommended to complete a thorough assessment and create a management plan for patients with chronic breathlessness and opioids can be part of this plan. If this is not completed, then health care professionals are working in an unethical manner [33]. This review supports the view that this is not the case, so it can be speculated that patients are being undertreated.

Seven of the studies examined the views of the participants on the use of opioids to manage severe breathlessness in COPD (Table 1 and 2). Two studies of high-quality mention that the participants felt frustrated at not being able to remedy the symptoms of breathlessness for the patient [28–29]. Furthermore, participants recognised that ongoing poorly managed breathlessness negatively affected the quality of life of the patient [29]. Some physicians (n = 55) were aware of the benefit of using opioids for breathlessness, yet they were more confident to use them for the dying patient, patients with heart failure, or a patient with cancer than COPD [19]. However, the speciality of these physicians is not mentioned. A moderate quality study by Politis et al. [30] used a case-vignette to examine what treatment GPs would add in for a patient with ongoing breathlessness. Around twenty six percent (25.6%) of them would add an immediate release morphine but these doctors were four times more likely to have palliative care experience. Similarly, a case-vignette showed that 75% of palliative care doctors would add in opioids to the management of a similar patient but only 41% of respiratory doctors would. These respiratory doctors tended to be younger and have worked in respiratory care for a shorter time. Many of the studies reported that the participants were of the opinion that opioids may be helpful for patients with refractory dyspnoea secondary to COPD. Nevertheless, Carette et al. [26] report that of the 64 patients with severe breathlessness, none were in receipt of opioid therapy. Nevertheless, patients with COPD can develop debilitating breathlessness and usual methods to manage it can become ineffective. As a result, comfort and maintaining quality of life should be the main priority [6] and state that oral morphine can be used to manage breathlessness due to COPD. Booth and Johnson [34] report that the patient should be optimised and non-pharmacological management treatments accessed. However, they also recommend that opioids are prescribed by healthcare professionals who have knowledge in this area. Therefore, given the evidence that the palliative care team are potentially more confident in using opioids, perhaps the teams providing care to these patients should consider a referral to palliative care. This comes as patients have reported that opioids alleviate their breathlessness and thus improved their quality of life. Patients’ care givers described how their loved ones experienced reduced anxiety, depression and stress when treated with opioids to manage breathlessness [28]. Consequently, perhaps in the clinical setting it would be appropriate to discuss with the patient about referral to the palliative care team to begin symptom management.

Many of the studies mentioned that a barrier towards prescribing opioids is the lack of education and guidelines to support their use. Given the nature of COPD, it is often challenging to classify patients as being ‘end-stage’. The guidelines don’t state what type of opioid, the route or dose to use for chronic breathlessness in COPD. Also, respiratory depression was the main barrier to prescribing opioids [19, 24, 26, 29, 30]. However, a systematic review which included 16 studies with a total of 271 participants and examined the effect of opioids on COPD related breathlessness and exercise found that there were no adverse effects with the use of opioids. No associated respiratory depression was found. Three studies measured arterial blood gases and one noted a rise in PaCO₂ but this did not go higher than 5.3 kPa [5]. This is similar to the results from a larger systematic review and meta-analysis that showed no clinically significant adverse effects from using opioids to manage breathlessness. The meta-analysis showed a rise in PaCO₂ of 0.27 kPa (95% CI, 0.08-0.45 kPa) and four non-serious episodes of respiratory depression was noted out of the 1064 patients [35]. In addition, Janssen et al. [22] mention that doctors were concerned about other side effects like constipation. Politis et al. [30] mention this alongside potential sedative effects. The side effects noted in a systematic review were nausea, constipation and light-headedness [5]. Despite this it has been acknowledged and recommended to prescribe a bowel stimulant, stool softener, and anti-emetic [11]. These are practices that can be implemented after discussion with the patient.

This review is limited to eleven studies, two of which were abstracts offering a small amount of information, and included four studies of low quality. These four studies support the findings of the other higher quality studies. Furthermore, many of the studies reported survey data. Survey data informs current practice but does not provide a rationale for this [21]. Furthermore, as surveys and interviews are self-reported it does not guarantee that the participant is telling the truth [14]. The literature search methods were those commonly used for systematic reviews but were performed by one person, limiting the selection and inclusion process.

The Royal College of Nursing [36] reported that there were more than 54,000 nurse prescribers in the UK. Many nurses, physiotherapists are non-medical prescribers and play a significant role in the management of COPD patients. Their opinions were not considered or reported in the reviewed studies. Future research would benefit if their views on the topic were documented. In addition, further randomised control trials are needed to examine the long-term benefit of opioids along with the different types of opioids that can be used.

Conclusion

This study has examined the views, attitudes and barriers towards the use of opioids to manage chronic breathlessness in COPD. It appears that physicians specialising in respiratory medicine are less likely to prescribe opioids regularly or often for patients with severe breathlessness in COPD than those specialising in palliative care. Furthermore, physicians express frustration at an inability to resolve chronic breathlessness but were of the opinion that opioids may help patients. Nevertheless, many were reluctant to prescribe opioids. The main barriers appear to be the worry over the risk of respiratory depression as most studies mentioned this. Additionally, guidelines and education around the use of opioids for management are lacking. A common opinion was that pharmacological therapy should not be used as an easy fix to manage breathlessness and that a holistic approach should be taken with time spent encouraging and educating the patient on how to manage breathlessness using non-pharmacological means. However, it is not appropriate for patients to suffer with breathlessness and a combination of pharmacological and non-pharmacological management can be combined. If opioids are commenced the patient should be reviewed to assess whether there has been beneficial. Additionally, doses should be increased, decreased or stopped as necessary [34].

Conflict of interest

The authors have no conflict of interest in regard to the subject of this review.

Additional information

Funding

No funding was received.