Acute pain management in patients with opiate maintenance treatment in primary care: a qualitative study

Background : Opiate use disorders are a worldwide disease. In the last 30 years, opiate maintenance treatment prescription changed patients’ and also changed physicians’ practice. General practitioners (GPs) have to deal with patients on OMT who are in acute pain. Both clinically and pharmacologically, the treatment of acute pain in patients with an opiate use disorder and an OMT(opiate maintenance treatment) differs from that given to patients with other conditions. As this situation is complex, it was important to explore whether GPs recognised this problem and whether they managed it effectively. Objective: To investigate how GPs identify and manage situations of acute pain in patients with opiate use disorders and OMT. Methods: semi-structured interviews were used as a data collection technique with a purposive sample of practising GPs. Data collection continued until saturation was reached. Analysis was undertaken using a thematic analysis method. Two independent researchers, working blind and pooling data, carried out the analysis. Results: The maximal variation of the sample and saturation of data were reached with 11 GPs. The thematic analysis resulted in 4 main themes: (1) the importance and difficulties of professional links , (2) the specific clinical reasoning , (3) the importance of the doctor-patient relationship and (4) the particular characteristics of OMT patients. Conclusion: The complexity of pain and opioid dependence represents significant challenges for GPs. These questions are particularly and isolated. seem line with general practice. The number of patients on OMT has increased was first GPs these situations and issue their own recommendations.

complex phenomenon and, in a large majority of cases, it is managed by GPs. We hypothesise that GPs who prescribe OMT are frequently exposed to situations of acute pain management for patients on OMT. There is very little literature about acute pain management in patients on OMT, especially in general practice. Consequently, the objective was to explore how GPs manage acute pain in patients receiving OMT.

Methods
Inclusion criteria were: GPs practising in the administrative region of this study (Finistere, Brittany, France) with personal experience of OMT management. A research committee, including GPs, a psychiatrist specialised in addictive disorders and methodologists was recruited. First, 3 GPs were recruited, having been identified as OMT prescribers from a local panel, identified by a local research committee of the University Department of General Practice. In the second stage, starting from these first three GPs, a snowball method was adopted. Recruitment stopped when saturation was observed. No one declined because of lack of interest in the study. Participants were contacted only for the study by phone, and the interview was face-to-face in GPs workplace, without any other participant. They were told that the study concerned management of OMT.

Data collection:
The research committee (GPs, psychiatrist -specialised in addictive disorders, methodologist, all trained and experimented in qualitative studies) constructed a qualitative interview guide consisting of 6 questions. It was tested on GPs and the duration if the interview was 1 hour. A GP researcher (MD, woman, trained on qualitative studies) interviewed all the participants in the study, between 24 th April and 25 th June 2015. All the interviews were recorded and transcribed in a second time by the interviewer. Transcripts were sent back to participants, none made any comments. It was his first experience of the GP researcher in qualitative studies, she was not particularly experienced on this specific topic.

Question
Could you tell us about the last patient on OMT you saw who was suffering from pain? What are your thoughts about the pain experienced by patients on OMT? Which difficulties do you encounter when evaluating the pain experienced by patients on OMT? Do you change your pain management when patients are receiving OMT? How do you feel about this type of patient consultation? Do you have anything further to add on this topic?

Ethical approval
Ethical approval was given by the ethical committee of the "Université de Bretagne Occidentale".

Data Analysis
As the research group was investigating GPs' thoughts about pain management for patients on OMT, a critical theory paradigm appeared to be the best possible research perspective [22]. The data analysis technique was based on a thematic analysis with an open coding followed by an axial coding and a selective coding [23] . A pair of researchers working blind, coded the transcripts independently and compared the results at each step of coding. Any discrepancies which occurred were forwarded to the research committee to be sorted out. When the axial coding had been completed, at least one third of the verbatim accounts for each axial code were translated to provide clear examples. This was undertaken to ensure the completeness and the consistency of the coding process. A selective coding was subsequently proposed.

Participants
Eleven GPs were interviewed in France (Finistere region). The social and professional profiles of the GPs are presented in Table 2.

Clinical reasoning
Subthemes identified were pain evaluation, difficulties in prescription management and lack of evaluation of efficacity or treatment.

Difficulties in prescription management
With regard to prescribing analgesics, a wide variety of practices were described by physicians: Non opioid painkiller analgesics (paracetamol) were the most frequently cited.
Weak opioids were widely used by some doctors, and not at all by others: "I felt that pharmacologically it could not work, that we would not have a satisfactory result, because of the competition from substitution treatments, so a priori with the receptors being saturated, it did not seem appropriate to me". Strong opioid painkillers were also described in various ways: Many of the doctors interviewed avoided this prescription. In contrast, there were others who used morphine in combination with MSOs. However, one reported using lower doses. Others still preferred to stop buprenorphine to prescribe morphine. As mentioned above, doctors also prescribed multimodal analgesia, with extensive use of anti-inflammatory drugs, and sometimes antidepressants, for neuropathic pain.
Regardless of their prescription, doctors stressed the importance of using a second category of medication for analgesic treatment. The reasons given were: -Clarification of the indications: "I prefer to prescribe analgesics;, ultimately, I prefer to dissociate the use of analgesics for analgesic purposes, from a specific analgesic, used for withdrawal, (..) the buprenorphine retains its status as a substitution treatment ".
-Clarification of the provisional aspect of this prescription: "the fact that a (..) second molecule (..) has been prescribed indicates the provisional nature of the treatment".
Some physicians described prescribing OMT fractionation, with or without an increase in daily dosage. Others associated a Non opioid painkiller or weak opioid analgesic with OMT: "when you have to give them morphine, to be sure that methadone is effective I divide it in 2, and then I add either tramadol, or Acupan â, or another level 2 medication, avoiding level 3 analgesics".
However, many doctors mentioned their reluctance to split MSO for analgesic purposes. Many doctors spoke of the need to call on colleagues in difficult therapeutic situations.
They first mentioned the colleagues in the same general practice: "the fractionation of buprenorphine which I had already done, but then found, after discussing it with colleagues, that they would have done the same". They also mentioned the use of addiction networks "the centre for drugs, of course, for the whole aspect of toxic sideeffectives and drug treatment", the pain centre ("pain centres of the La Cavale Blanche, the maritime hospital, are quite likely to help us with this issue" and hospitalisation "if the pain is so severe that she cannot sleep, well I hospitalise her".

Lack of evaluation of care effectiveness
Most of the doctors interviewed described the effectiveness of their pain management as good: "Well, they are in less pain. They are better, so they are happy". Some physicians evaluated the effectiveness of pain management through the use of a pain scale and they re-evaluated it after treatment. However, many of them described an evaluation which was based on the absence of repeated requests for painkillers: "I don't get much feedback but, if I don't see them again, I assume that is because they are fine".
They described difficulties in assessing the effectiveness of their management because of the lack of feedback from patients "I rarely get feedback" and there is not enough time to see them again in a timely consultation " we would have to be able to see the patient again the next day, the day after, and in current practice, that's almost impossible in town or city practices, they don't come back, or they move on".
Finally, opinions were divided regarding the effectiveness of codeine. Some physicians described variable patient feedback. Others said they had noticed codeine efficacy: "so it's true that, pharmacologically, it shouldn't work except that it can actually work". In addition, they did not observe withdrawal syndrome by combining codeine and buprenorphine: "in my daily professional life, I have never had codeine-Subutex withdrawal, never, ever..".

Complex therapeutic relationship
A relationship that is often of high quality Most physicians described a relationship of trust with patients: "it is a relationship of trust that is established over time".
The doctors were more confident with patients known to the practice: "someone who is followed up, with whom there is trust, it goes smoothly, it's not too stressful". Doctors also stressed their attention to pain. They noted the importance of letting the patient know "so that they can also see that their pain is being taken into account".
This idea was in line with that of the overall management of the patient in general Complex contact: The doctors interviewed mentioned patients with complex psychological profiles: They were described as having "a particular psychological profile".
There was a distance between them, maintained by the patient: "year after year we still manage to discuss a little bit when we know their history, but for those whose history we don't know, who come to us, they never, or very rarely, tell us what has happened...".
At the time, the GPs being interviewed deplored the role of the doctor, which sometimes boiled down to merely prescribing: "they see us a supplier in some ways".
They also mentioned a difficulty in maintaining a link with these patients because of cancelled appointments and medical nomadism.
Finally, the doctors described the difficulty of providing care in response to a patient's request to be treated solely by their GP: "And often the difficulty comes from the fact that, just because they are causing you problems and you feel your competence is being stretched to its limit in caring for them, they do not want to leave you… you are their only contact and you remain so, therefore you have to solve things that are sometimes much more complex than you would like".
A specific patient population.

A young population
Doctors agreed that this is quite a young patient population: "it is often patients who are still quite young".

Relationship between consumers
They mentioned links between consumers in the context of trafficking or misuse of OMT: "they gave their capsules to everyone".

Perception of their own bodies
One doctor mentioned patients having a different perception of their own body compared with the general population: "they have notions about their own body which are not be the same as other people's".

Pain experienced
Opinions about pain were divided. Thus, some doctors did not observe any specificity in the pain: "I do not get the impression that they suffered more pain than other patients".
Other doctors referred to their knowledge of acquired hyperalgesia, and described having observed this lowering of the pain perception threshold: "They feel increased pain".
On the other hand, the doctors mentioned a more important psychological aspect of the pain: "In terms of pain, we are just as concerned about understanding emotional pain, the mental component of the physical pain." Others, on the contrary, mentioned a better tolerance of pain: "that's what it says, that they would be hypersensitive to pain compared with a standard population, I admit that I didn't particularly experience that, I even saw some who were quite resistant to pain".

Relationship to drugs and meds
Immediate satisfaction: The physicians interviewed described a request for immediate pain relief from patients: "these patients are often still at the…the impetuous stage of expecting rapid results". In this context, they observed excessive consumption and the search for repeated and symptomatic medication in relation to painkillers: " it is precisely (..)the addictive attitude that I am trying to remove with regard to medication, and that is the main difficulty".

Patient knowledge of pharmacology
Interviewees reported a good understanding of pharmacology by patients: "They know, they can generally manage pharmacology, many of them at least know which drug to use and how to use it, in the normal way, that is ".

Perception of meds and drugs
The physicians interviewed agreed that these patients had a specific attitude towards drugs: "they also have a somewhat specific attitude towards drugs". Thus, one doctor stated that the prescribed drugs were considered a highly addictive risk by some patients: "the drugs they are prescribed are often ultimately experienced as even more addictive, more addictive than their own substance of choice". They had a strong awareness of tolerance to painkillers: "Yes, but I am addicted to drugs, I don't like taking products anymore". In this context, they described frequent refusals of paracetamol.

Self-medication
Opinions were divided on the frequency of self-medication. One doctor noted an uncontrolled and indiscriminate use of products by some patients. Another mentioned a modified intake of analgesics adopted by stabilised patients: "those who are really well stabilised or who take small or regular doses and who are consistent (..) take analgesics more easily".
They observed self-medication with OMT: "those who overuse for analgesic purposes tend not to take it, or to take it in 2 doses easily, morning and evening, or in case of pain which is a little more acute, they split the medication, also for analgesic purposes" They mentioned guilt expressed by patients on this subject : "I don't know if they feel guilty (..)But (..) they justify their increase in buprenorphine and they apologise for taking it (..) or try to clear themselves of the pain by taking, buprenorphine, that's it, and they don't necessarily think about taking anything else, other than buprenorphine".

Potential for misuse:
Physicians described difficulties arising from the misuse of several analgesic active ingredients, such as nefopam, tramadol and morphine.

Low investment in care
Care provision seemed constrained The doctors interviewed spoke of patients who felt the treatment they received was holding them back "patients with OMT follow-up in specialized care constantly talk, among themselves, about how they are being kept drug-dependent".

Observance
One doctor mentioned that some patients adhered somewhat better to treatment than the general population. However, most of the doctors interviewed mentioned that it was difficult to obtain compliance: "I try, of course, to ensure that they take buprenorphine once a day in the morning and not on demand, which is complicated".
They went on to mention the need for a more important framework for prescribing: "Some patients had a rather unusual attitude towards drugs so, for these people, prescribing needed to be extremely precise ".

Delays in providing somatic management :
The physicians interviewed agreed about the delays that patients were experiencing in their somatic management. They identified delays for acute pathologies ("he broke his metatarsus, he only came 4 days later because he was in pain"), dental care ("they had to go to the dentist for 6 months") and check-ups requested by their general practitioner ("we make them have check-ups, most of the time they do not go for them").

OMT and pain in general practice
In this study, GPs identified specific difficulties and limits in the management of acute pain in patients on OMT treatment in primary care. Pain is a frequent intercurrent event, destabilising the theoretical observance of OMT (14,17). Opiate maintenance treatment management requires a core that corresponds to that at the heart of general practice (18). Two thirds of OMT are prescribed by GPs in France (19). In general practice, among a population of patients on OMT, over 25% had associated somatic disorders (20). In this study, GPs reported that it was a rare situation. However, they were aware of the acute pain in opiate-dependent patients and were concerned about the specificities in this patient population. They reported a lack of training and a lack of recommendations, or guidance for modifying treatment in these complex situations. These findings correspond to the deficiencies identified in literature, where very few articles dealt with the management of pain in patients on OMT , and the majority were only concerned with methadone (21). France is an exception, among the world, in allowing buprenorphine to be prescribed by any practitioner (22), and therefore GPs have to handle the management of long-term buprenorphine treatment, including management of pain in patients with buprenorphine.

Empiricism
GPs stated that decisions about prescribing were based on empiricism rather than protocol which probably induced interpersonal variability in pain management, as reported in a study conducted in an A & E department (23). Moreover, beyond the absence of consensual pain-management guidelines for opioid-dependent patients, the preconceptions of caregivers about this addictive disorder, and about patients on OMT, are another limiting factor. GPs in this study described a complex relationship, with mistrust of certain patients and a fear of being manipulated in a trafficking or misuse of OMT or analgesics scenario. These negative representations probably hinder medical reasoning and reduce the effectiveness of management (24)(25)(26). These negative representations were also described as a limiting factor in professional network relationships, between GPs and pharmacists. Case-by-case management should have an evolving network of professionals available, and consistent guidance to patients, especially between the prescribing GPs and the pharmacists, but also between hospital and primary care, to improve the management of these situations.
However, despite these limitations, management of pain in opiate-dependent patients on OMT corresponds to the central core of general practice. GPs have to be involved in patient follow-up, to improve access to OMT and a patient-centred program, as recommended by European consensus (27). One GP mentioned developing a closer relationship with the patient through managing the patient's pain, with an evaluation centred on the patient, including variables not directly linked to opiate-dependence.

Evaluation
GPs did not report any exploration of the intensity of pain using a visual analogic scale, as recommended by many protocols. They said that they used a global clinical evaluation and the functional consequences of the evaluation. Their evaluation was also based on patients' descriptions of the types of pain experienced and distinguished between psychological and nociceptive components of pain. This corresponds to literature: a study in general practice in 2014 showed that only 50% of GPs in the survey used a validated pain assessment scale for a patient on OMT, and 94% of them relied mainly on questioning patients (28).
The GPs interviewed interpreted the absence of a new consultation or complaint at the next consultation as an indication that the initial management had been effective.
However, when faced with patients in pain, they found that 40% of patients on OMT did not ask for help compared with 28% in the general population (29). Moreover, GPs identified patients who had a specific perception of their own bodies; they identified the care required for patients on OMT, for patients with hyperalgesia and also for those patients who had a greater tolerance of painful symptoms; they identified a lack of investment in care which frequently caused a delay in accessing treatment.. The lack of pain reassessment is particularly problematic in this patient population on OMT. The risk of pain being undertreated is significantly high (30) and acute pain, that is not sufficiently relieved, exposes the patient to a 2.3 times higher risk of premature discontinuation of treatment (31).

The place of painkillers
The GPs interviewed were concerned by the risk of destabilisation of opiate-dependent patients, about observing OMT only in terms of pain, so they focused on opiate analgesics and on the WHO levels of painkillers. The study showed level 2 painkillers (WHO) were widely prescribed and in particular paracetamol + codeine. This prescription may seem surprising from doctors skilled in prescribing OMT. Opiates are contraindicated in combination with the BHD or NX-BHD (32). The combination of level 2 painkillers (WHO) with methadone is not recommended either because it is not effective (32,33). This use of the adjunct of an opioid analgesic to OMT varies in literature. It has been developed by specialists in addictology and pharmacology, aiming to increase the dosage with fractionation, in order to benefit the patient by means of the analgesic efficacy of OMT.
These discrepancies were also identified in previous studies: in general practice , 50% of GPs reported using a level 2 analgesic prescription combined with OMT (34), and in the emergency department, 19% of physicians reported prescribing level 2 analgesics combined with OMT (31), which was comparable with yet another study (23). A two-year follow-up of 1182 patients on OMT also found that the most prescribed analgesic, after non-steroidal anti-inflammatory drugs, was a combination of paracetamol + codeine, representing 9% of the analgesics prescribed (35).
No consensus exists in literature about the management of acute pain in opiate-dependent patients on OMT, and certainly none in general practice. Some authors proposed protocols (24,32,33,36) based on pharmacology. Most agreed on avoiding the prescription of level 2 analgesics and on the interest in using co-analgesics (non-steroidal anti-inflammatory drugs, antidepressants, anxiolytics...). While it is stated that existing pain management protocols are not widely applied (19,27), the factors limiting application were not well known, and this applied particularly in general practice. The prescription of level 2 painkillers reflects a certain empiricism in a situation identified as quite rare, complex in evaluation and lacking a reference guide. However, despite pharmacological interactions and risks, physicians interviewed in this study reported their feelings on the analgesic efficacy of codeine in combination with buprenorphine and/ or Methadone. However, in patients on OMT, analgesic treatment, exposes patients to an increased risk of undesirable effects, misuse, tolerance and dependence (30,31,37).

OMT management
GPs were concerned about the risk of opioid dependence in OMT management. They reported fear of treatment destabilisation and of poor compliance with treatment so they preferred to add another analgesic rather than increasing and splitting OMT during the day, as tends to be recommended in literature (38). This is in line with a previous work, where 41% of the GPs questioned were familiar with the possibility of using OMT for its analgesic effect, but only 43% of them actually used it for analgesic purposes. The reason given by physicians for not prescribing was fear of an uncontrolled resumption of MSO consumption (28). The GPs interviewed here had a global approach to the management of their patients, whom they were monitoring both for addictive disorders and for medical follow-up. In terms of addictive disorders, they described how they countered the tendency of many patients to split OMT. They felt that asking the patient to split his or her treatment in the alleviation of pain, was inconsistent with their previous discussions. They preferred to prescribe a second active ingredient to clarify the temporary aspect and indications of this treatment. This fractionation of MSO for analgesic purposes seemed to receive a varied response from the patients. Thus, in this study, the doctors interviewed described reluctance on the part of the patients. They stated that some patients were not (or did not feel) sufficiently stabilised to have the ability to split the MSO without slipping into uncontrolled consumption. However, a study showed that 61% of the patients in the survey were aware of the fractionation of OMT for analgesic purposes; 68% considered it effective and 58% of them used it regularly (28).

Implications
contributed to this early saturation. Finally, none of the physicians interviewed was a prescriber of BHD NX. As a result, it was not possible to assess the difficulties associated with this drug.

Conclusion
This study showed that GPs' overall care has specific characteristics in the context studied. The complexity of pain and opioid dependence represents significant challenges for clinicians and patients. It is hard to achieve a balance between pain relief and opiate Existing protocols do not seem to be in line with general practice. However, obtaining clear recommendations for care will be increasingly important in the future. Indeed, the number of patients on OMT has increased since it was first marketed, and these patients experience more pain than the general population. General practitioners will increasingly have to deal with these situations and will have to issue their own recommendations. It will, therefore, be valuable to evaluate the prescribing practices of general practitioners and their effectiveness on pain, as well as the sustainability of substitution, using quantitative methods. It will then be necessary to assess the feasibility of, or need for, a set of recommendations adapted to general practice.