The Use of Morphine to Treat Cancer-Related Pain: A Synthesis of Quantitative and Qualitative Research

Article Outline

• Abstract
• Introduction
• Aims of the Synthesis
• Searching the Literature
  • Results of Searching
  • Inclusion and Exclusion
  • Determination of Quality
  • Data Extraction
• Conducting the Synthesis
  • Translating the Quantitative and Qualitative Research into One Another
  • The Development of Synthetic Constructs
• Results
  • The Synthesizing Arguments
    • Opioids and Opioid Concern
    • Using Opioids Is a Balancing Act and a Trade-Off
    • The Existential Meaning of Cancer and Cancer Pain
    • The Intersubjectivity of Pain
      • The Role and Influence of Health Care Professionals in the Management of Pain
      • The Role of Caregivers
      • The Management of Pain by the Patient
• Discussion and Interpretation
• Conclusion
• Acknowledgment
• References
• Copyright

Abstract 

Morphine is the most commonly used opioid for severe cancer-related pain. Despite its established effectiveness, it is often used cautiously in clinical practice, particularly outside specialist palliative care. This review identifies the key social, contextual, and physical concerns held by patients, carers, and health care professionals when using morphine, which might explain the caution taken in its use. The review used an approach called critical interpretive synthesis (CIS), which combines conventional systematic review techniques with methods for interpretative synthesis of qualitative research. An existing review examining the effectiveness of morphine and a guideline on its use were synthesized with 19 qualitative articles to establish understanding of how context of use can affect the established effectiveness of morphine. The article argues for the appropriateness of CIS for answering questions of this type. The results demonstrate that using morphine is a balancing act and a trade-off between pain relief and adverse effects. Deep-seated concerns regarding the symbolism of morphine, addiction, and tolerance are held by patients, carers, and clinicians, which influence prescription and use. Cancer pain is a referent for disease status and has existential meaning, with the introduction of morphine becoming a metaphor for impending death. Cancer pain is intersubjective, with its perception and reporting influenced by those with whom the patient interacts. By understanding the context and social meaning surrounding the use of morphine to treat cancer pain, health care professionals can begin to anticipate, acknowledge, and address some of the barriers to its use, thereby enhancing pain control.

Key Words: Morphine, cancer pain, systematic review methods, qualitative research

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Introduction 

Morphine has been used to relieve pain in cancer patients in one form or another for centuries. International developmental work, coordinated by the World Health Organization, created a global health policy document for the management of cancer pain entitled “Cancer Pain Relief,”¹ in which morphine was central. Global awareness of the benefits of morphine for the control of cancer pain increased as a consequence of the publication of this document, although the practice of regular administration of morphine advocated in the United Kingdom's first hospices took time to be established in other health care settings. Apprehension over the potential for tolerance and abuse of morphine lay at the heart of this slower uptake.²

Concerns regarding the use of morphine to relieve cancer-related pain that are prevalent at a global level also have manifested themselves at a micro level. Anxieties are common among patients, health care professionals, and carers,³ despite research demonstrating morphine's effectiveness as an analgesic.⁴, ⁵ Many of these concerns are deeply held and represent symbolic or social meanings that are detached from clinical effectiveness. The practical manifestation is that morphine may be prescribed in a suboptimal way, not prescribed at all, or regimens are not adhered to by patients. The outcome is inferior symptom control.

To begin to understand the incongruity between the effectiveness of morphine and its use in practice, research needs to be drawn together in a way that moves beyond some of the limitations associated with traditional approaches to systematic reviewing. Despite their scientific approach to evidence synthesis, systematic reviews have been accused of failing to address the nexus between research, practice, and policy, and the need to incorporate diversity in the kind of evidence included in syntheses has been promoted.⁶ At the level of primary research, it has been suggested that the clinical utility of trial findings may be enhanced by incorporating qualitative research.⁷ The same may be true for systematic reviews. By integrating qualitative and quantitative research at the level of synthesis, the findings from effectiveness research may be enhanced by providing more insightful understandings of interventions and the ways they may best be implemented and managed.⁸ Several methods for undertaking syntheses of diverse research methods have been developed,⁹ one approach to which is critical interpretive synthesis (CIS). CIS is a new method of reviewing, which draws on the processes of traditional systematic review methodology while incorporating a qualitative tradition of inquiry. Using CIS to synthesize a diverse body of evidence enables the generation of theory with strong explanatory power.¹⁰ It was considered that the processes involved in CIS could enable understanding of the complexity surrounding the construction of social meaning encompassing morphine use to be developed from the existing literature.

This article has two purposes. It aims to make sense of the concerns surrounding the use of morphine to treat cancer-related pain in a way that is helpful to policy and practice. In addition, it is a case study and a critique of CIS as a potential method for reviewing qualitative and quantitative research. Given that effectiveness reviews examining the use of morphine to treat cancer pain already exist, it was considered that there was little point in replicating work. Instead, two effectiveness articles were used as a framework into which qualitative research exploring the social, cultural, regulatory, professional, and patient issues surrounding use of morphine for relief of pain caused by cancer was examined, integrated, and interpreted. A more detailed report on the methods is available elsewhere.¹¹ The articles selected for the CIS were 1) a Cochrane Systematic Review—Oral Morphine for Cancer Pain⁴—a systematic review of 54 randomized controlled trials reporting the analgesic effect of oral morphine; and 2) the European Association for Palliative Care (EAPC) recommendations for morphine and alternative opioids in cancer pain,¹² which draw together different types of quantitative research evidence in the form of guidelines. These articles were chosen as they are contemporary syntheses of the effectiveness data on the use of morphine to treat cancer-related pain.

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Aims of the Synthesis 

The aims of the synthesis are:

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Searching the Literature 

The initial search of the literature concentrated on searching electronic databases with a highly structured search strategy. In conjunction with an information specialist, a search strategy was designed that combined recognized search terms for morphine (predominantly based on the search terms used by the Cochrane Pain, Palliative and Supportive Care Group for the oral morphine for cancer pain review), with a search strategy to identify qualitative research using broad-based terms.¹³, ¹⁴

The search was run in MEDLINE and was refined through an iterative process.¹⁵ This involved key terms identified from potentially relevant articles in the preliminary search being incorporated into a revised search strategy. The search was adapted for and run in OvidSP Medline (1950–2008), CINAHL (1982–2008), EMBASE (1980–2008), PsychINFO (1967–2008), HMIC (Health Management Information Consortium, May 2008), and Web of Science SSCI (1956–2008).

Electronic searching was supplemented by reference chaining, hand searching of journals known to publish qualitative research in palliative care, and contact with experts.

Results of Searching 

The inclusion criteria for obtaining full text of an article were 1) the article described the results of empirical qualitative research, 2) the article referred to the use of morphine or other opioids to treat cancer-related pain, and 3) the article was published in English.

The electronic searches yielded a total of 2886 records. Abstracts of 225 records were retrieved. Of these, 30 full-text articles were obtained.

A further 10 records were identified through reference chaining, hand searching, and contact with experts, of which seven were obtained in full text.

Inclusion and Exclusion 

Because of the relatively small amount of qualitative research in this area, the aim was to include all articles that matched the inclusion criteria, and not sample articles from a larger pool as has been undertaken with broader topics.¹⁰ Thirty-seven full-text articles were retrieved and read to determine whether they matched the inclusion criteria outlined earlier. At this point, 18 articles were excluded, as they did not meet the inclusion criteria. There were two main reasons for exclusion; articles were not reports of qualitative research or they did not deal explicitly with issues related to cancer pain or the use of opioids. Nineteen qualitative articles, reporting on 15 studies were included in the synthesis (Fig. 1, Table 1).

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• Fig. 1 

  Process of study selection.

Table 1. Included Qualitative Research

Determination of Quality 

It is acknowledged that appraisal of the quality of qualitative research remains a contentious issue, about which there is little consensus.³⁵ Quality appraisal was undertaken in this review to have an objective record of the quality of the identified qualitative research matched against predetermined criteria. A quality-appraisal checklist was chosen for use in this synthesis.³⁶ The checklist consists of nine questions, each of which has four subcategories (Table 2). A protocol provides descriptors for each category. The system allows for the calculation of a summed score of methodological quality that ranges from nine (very poor) to 36 (good). The descriptors provide the potential to produce a transparent and explicit scoring of each article.

Table 2. Quality Appraisal Checklist³⁶

Each article was assessed for quality by the author. A cross-section of the articles was checked again for accuracy of assessment.

Most articles were assessed to be of reasonable to good methodological quality, with scores ranging from 19 to 34 (Table 1). No article was excluded on grounds of quality. Those of weaker quality, that is, with lower scores, were included, as it was considered that each article had relevance to the synthesis.

Data Extraction 

Each article that was included was subjected to data extraction. A pro forma data extraction tool was devised to enable the summary of information on the aim of the research, participants, methodology, methods of data collection, methods of analysis, and key results. Successful completion of the data extraction form was dependent on the clarity of reporting within articles. Key elements of this information were then transferred into the qualitative software ATLAS-Ti (ATLAS-ti Scientific Software Development Gmbh, Berlin, Germany) to ensure that all findings remained linked to the context of the study from which they were drawn.

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Conducting the Synthesis 

CIS is a method of reviewing that enables the synthesis of diverse bodies of literature. It draws on meta-ethnography, an established method for synthesizing qualitative research,³⁷ but adaptations are made for the incorporation of quantitative research. Reviews that have used CIS have synthesized a wide spectrum of research methods.¹⁰ This review made further adaptations to CIS to specifically synthesize effectiveness research with qualitative research. CIS involves the following stages:

Translating the Quantitative and Qualitative Research into One Another 

Central to this review was the interface between the effectiveness and qualitative literature, as this represented a significant adaptation to CIS methodology. A pragmatic method was required that ensured that the findings from the Cochrane Systematic Review and the EAPC guidelines guided the translation and synthesis of concepts and themes from the qualitative research articles. Practically, this was done using a grid. The headings of the columns in the grid were the findings from the EAPC guidelines and Cochrane Review (20 columns). Each row of the grid represented a qualitative research article (19 rows). The findings from each qualitative article were identified and then compared with the recommendations from the effectiveness literature. Where there was a match, the corresponding cell of the grid was populated with the qualitative finding. A sample of the grid is shown in Table 3. Not all cells of the grid were populated with findings. Some columns of the grid, which represented more technical aspects of morphine use, for example, one headed “buccal, sublingual, and nebulized routes for morphine are not recommended,” contained no data. Others were highly populated when qualitative findings addressed effectiveness recommendations, for example, “successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects.”

Table 3. Sample From Within the Integrative Grid

As the integrative grid was developed, it became apparent that the qualitative research addressed issues wider than those specifically mapped in the grid and these findings needed to be incorporated into the overall synthesis. A second extraction of findings occurred using the computer software Atlas-Ti.

The Cochrane Review and EAPC recommendations directed the second translation, which facilitated a more detailed examination of the qualitative findings in each cell and enabled the translation of these findings between articles. Additional qualitative findings, which provided context to the effectiveness recommendations, were identified through this process. For example, a translation developed from 16 of the qualitative articles that was not identified in the effectiveness literature was “the role and influence of health care professionals in the management of pain.” It was found that health care professionals can have a direct impact on patients' analgesic treatment choices and consequently the success of their pain control. This was one of several findings that provided contextual information for the recommendations arising from the effectiveness literature that have the potential to influence clinical practice. The development of findings into translations is documented in Table 4.

Table 4. The Synthetic Constructs

The Development of Synthetic Constructs 

Synthetic constructs are developed from the translations that arise from the findings within the primary articles. Fourteen synthetic constructs were created from 255 translations (Table 4) through the process of RTA. Translations were attributed to synthetic constructs through a process of identifying unifying ideas within them, which built into constructs. An example of how the synthetic construct “Trade-off/Balancing Act” was built from translations is shown in Fig. 2.

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• Fig. 2 

  The synthetic construct “Trade-off/Balancing Act” (boxes represent translations).

Because of the interrelated nature of the topic, some translations featured in more than one synthetic construct. For example, the translation “fear of dying in pain” featured within the synthetic constructs “the influence of cancer pain on patients,” “meaning of pain,” and “end of life.” This interrelationship between the synthetic constructs, and subsequently the synthesizing arguments, is a key feature of this synthesis.

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Results 

The higher-order interpretations developed within a CIS are expressed as synthesizing arguments created out of the synthetic constructs. It was essential to ensure that the initial focus of the synthesis drove the development of the synthesizing arguments. The findings from the effectiveness data were constantly compared with the theoretical developments from the primary qualitative research, much reflecting the iterative process used during the formation of the translations and synthetic constructs. In achieving this integration between qualitative and quantitative research at the level of synthesis, it is hoped that the results will have direct relevance to clinical practice and policy development, the potential for which has been identified by other authors.³⁸

Four synthesizing arguments were developed: opioids and opioid concern, using opioids as a balancing act and a trade-off, the existential meaning of cancer and cancer pain, and the intersubjectivity of pain. The distribution of synthetic constructs between the synthesizing arguments is shown in Fig. 3.

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• Fig. 3 

  Development of the synthesizing arguments. HCPs = health care professionals.

A mediating factor that ran through all of the synthesizing arguments was the synthetic construct of “control,” and as such, is presented as an overarching part of the synthesis. The essence of the synthetic construct “control” is that patients can perceive cancer pain to be enormous, exceeding all sense of control. Achieving pain control was optimal to patients' sense of self-control. Pain medication, when used well, helped patients to achieve that sense of self-control and to transcend to a new level of health.²³, ²⁴, ²⁸ Control of cancer-related pain is at the core of this synthesis, and once the synthetic construct “control” was developed from the primary research, it made sense that it became a mediating factor for all the synthesizing arguments, rather than feeding into them individually.

The Synthesizing Arguments 

The EAPC guidelines and Cochrane Review promote morphine as the drug of choice when starting a patient on an opioid to treat cancer pain. The EAPC recommendations discuss unfounded fears associated with morphine that have limited uptake and caused widespread avoidance of the drug. Despite the recommendations highlighting that carefully documented clinical experience has shown that these fears are unfounded,³⁹ synthesizing the qualitative research unveiled deep-seated concerns among patients, carers, and health care professionals over commencing and continuing morphine and other opioids.

The predominant concern was not related to opioids directly but to the implications for health associated with the commencement of morphine and other opioids. The introduction of morphine is perceived as a representation of worsening disease and death. Patients, carers, and health care professionals viewed the commencement of morphine to treat cancer-related pain as a last resort in the disease process. Morphine is viewed negatively, being seen as a “death sentence,”¹⁹ hastening death¹⁹, ²⁹, ³¹ and having a stigma associated with its use.¹⁸, ²³ There were strongly held beliefs among patients, carers, and health care professionals that once morphine was instigated, doses would increase, and sedation and a hastened death would follow.¹⁹, ²⁹, ³³ This association was particularly strong when opioids were given parenterally through a syringe driver.¹⁶, ²⁹

For some patients, it was not preconceived concerns but previous experience that led to reluctance to commence morphine. Patients who had prior exposure to opioids for other conditions were left with complex and ingrained resistance to use opioids again to relieve even severe cancer pain because of their former negative experiences.¹⁸, ²³

Also cited as a barrier to commencing morphine were concerns over its addictive potential and the development of tolerance and possibilities of abuse.¹⁷, ¹⁸, ¹⁹, ²⁰, ²², ²³, ²⁶, ²⁷, ³⁰, ³³ Anxieties over addiction to morphine were held by patients, health care professionals, carers, and nursing and medical students. Patients discussed how family members, pharmacists, and physicians voiced concerns to them over the possibility of addiction, although this did not necessarily influence patients' analgesic management. Carers also perceived that health care professionals’ fears concerning addiction led to hesitancy to prescribe morphine, which contributed to an under-utilization of morphine. The clinical impact of these concerns was that morphine was not prescribed, was prescribed but not taken, was taken at subprescribed levels, or was withheld by caregivers.¹⁷, ²⁰, ²⁷

Reluctance to use morphine because of concerns over the development of tolerance to its effects also influenced uptake of use. This is integrated with the anxiety associated with perpetually increasing doses of morphine mentioned previously. Patients and carers were concerned that morphine would lose its effect and, therefore, fail to provide adequate relief.¹⁷, ²³, ²⁷ These concerns led to patients being disinclined to start morphine and other opioids.

The Cochrane Review and EAPC guidelines promote morphine as the first choice of opioid (EAPC recommendation one) and that it should be taken regularly throughout the day (EAPC recommendations three, four, and seven) as either normal or modified-release preparations. Synthesizing the qualitative research exposed a more complex picture surrounding morphine use, which does not fit with this regular pattern and is highly influenced by patients' experiences of adverse effects.

It was predominantly the perspectives of patients that led to the development of this argument. Patients perceived that a trade-off occurred between managing pain and managing the consequences of managing pain.¹⁶, ¹⁹, ²², ²³ Patients considered that if they took morphine or other opioids to relieve pain, this action may result in them experiencing adverse effects more detrimental to the functioning of daily life than would occur if their pain remained unrelieved. As a result, patients grappled with internal conflicts of wanting pain relief but wishing to maintain functionality in their lives. Only one article provided a refutation to this view, reporting that a large number of participants in their study took morphine regularly to increase functioning through the relief of pain.¹⁷

The balancing act and the trade-off associated with taking morphine were related strongly to the adverse effects patients associated with opioid use. Adverse effects were perceived as a burden and were either tolerated to achieve pain relief or avoided by not taking morphine and experiencing pain, or by using nonpharmacologic measures to try and relieve pain.¹⁶, ¹⁷, ¹⁸, ¹⁹, ²⁰, ²², ²³, ²⁷, ³⁰ The adverse effects mentioned most frequently related to cognitive effects, for example, mental clouding and sleepiness.¹⁶, ¹⁷, ¹⁹ In addition, patients talked of a loss of dignity, personal autonomy, and sense of self once morphine was started. Patients felt that inadequately managed opioid side effects led them to being deprived of meaningful life.¹⁶

Conflicts arose for patients as pain increased, with the accompanying perception that disease and its associated pain were in control. Patients considered that this could only be countered by taking morphine, which then controlled them. Many patients continued to take morphine but struggled with conflict while doing so. Others reported that they would experience pain or resort to nonpharmacologic methods of pain relief rather than experience multiple side effects.²³

A temporal aspect also existed within the trade-off. Patients reported arriving at a point in their disease process where they considered they had no choice but to commence morphine. Before this point, patients felt able to tolerate their pain, in order not to experience side effects. Once pain was considered so severe that taking opioids was the only option, the trade-off between analgesia and side effects became acceptable. Often this point was reached only when death was perceived as imminent. The decision to commence opioids was not only due to the severity of a patient's pain but also out of concern for others who were witnessing their pain.¹⁹ This concept of “altruistic” opioid-taking also features within the synthesizing argument “intersubjectivity of pain” and is a significant influence in patients' decision-making processes when deciding to take morphine.

When patients experienced severe pain, the meaning of pain was interpreted in several ways, many of which overlapped:

From these statements emerges a picture of cancer and pain being inextricably linked by patients. What is also apparent is that cancer pain is interpreted as a referent for the status of disease, with worsening pain being equated to worsening disease, emphasizing that the final stages of life are near. This trajectory continues with the perception that pain will intensify as death approaches, and at this point, death will be a release from the experience of pain. A patient's interpretation of the meaning of cancer pain is, therefore, a dynamic and temporal process. A point in the disease process may, therefore, be reached in which the experience of cancer pain takes on existential meaning.

Interwoven among the associations between cancer, cancer pain, and the end of life is the role of morphine and other opioids. Arising from this construct was the implication that starting morphine to relieve cancer pain also epitomized deteriorating disease and represented the end stages of illness, demonstrated in the quotes “morphine is a last resort” and “morphine is a death sentence.” Synthesizing these two elements develops the argument that disease status is linked with severity of cancer pain, and the introduction of morphine to help treat this pain becomes associated with and inextricable from the existential fears surrounding cancer. This argument begins to identify why patients may consider the offer of a prescription of morphine (EAPC recommendation one) to be a potential death sentence and why patients may be reluctant to take it.

The existential nature of patients' pain was also felt by carers and health care professionals. Caregivers were concerned about the extent to which a patient's pain would worsen and whether it might cause death. Pain became seen as a metaphor for death, and while family members wished to avoid death, it was also seen as a way in which relief from pain may be achieved. Nurses reported the stress associated with witnessing patients in pain and how they experienced relief when patients died.²¹ Nurses described how patients and their families would utter a “cry for help,” referring to urgent and often emotional requests to try and gain control of intense pain or suffering or over the experience, time, or place of dying.³¹

Some patients, carers, and nurses sought rationale for the occurrence of cancer and cancer pain through spiritual and religious means. For some, this instilled comfort, whereas for others, spiritual conflict ensued.¹⁶, ²⁰, ²¹, ²², ²⁴, ³⁴ Although it was clear that some of the individuals interviewed drew on religious and spiritual resources to try and understand their illness, this was not common. The exception was one article, which found that support from religion was at the core of African-American people's experience of dealing with cancer and pain.²⁴

This synthesizing argument represents how cancer pain affects more than just the person experiencing it and how its perception and reporting are influenced by those who interact with the patient. The title of this synthesizing argument is drawn from a theme identified in an article exploring medical and nursing students' knowledge and attitudes toward cancer pain management.³³

Each synthetic construct is reported separately as they are the largest synthetic constructs and individually have important implications for practice.

The Role and Influence of Health Care Professionals in the Management of Pain 

Three main groups of health care professionals were represented in the qualitative research: doctors, nurses, and, to a lesser extent, pharmacists. The doctors consisted of primary care physicians and oncologists, whereas the nurses primarily worked in community settings.

The way in which pain was assessed and the way in which details of its cause and treatment were communicated were predominant features of the synthesis, which subsequently influenced patients' treatment choices. Nurses played an active role in the management of cancer pain. It was viewed as a challenge to relieve, and nurses felt rewarded and fulfilled when it was.²¹, ²² Teamwork between nurses, physicians, patients, and their caregivers was considered crucial to successful pain management, although nurses reported that physicians lacked knowledge about pain management and appropriate prescribing.²² Nurses also expressed frustration with their limited ability to prescribe analgesics,²⁰ although practice is being extended. For example, in the United Kingdom, nurses are now able to prescribe analgesics, including opioids, if they have undergone appropriate training.⁴⁰

There was some evidence among health care professionals of a fear of using opioids and concerns over adverse effects and addiction. Articles reported that these concerns were implicitly or explicitly communicated to patients, their carers, and also to nursing and medical students in teaching.¹⁸, ¹⁹, ²⁰, ²³, ³¹, ³³ Community pharmacists also conveyed negative messages regarding the use of morphine. Pharmacists reinforced associations between worsening disease and the introduction of morphine. One account told of a pharmacist “preaching” to a patient the risk of addiction associated with her morphine prescription every time it was collected.²³ Patients and carers internalized such interactions, which led to reinforced views of stigma and negative associations with the use of morphine.

A related concern for health care professionals was the perceived potential for morphine prescribed for therapeutic purposes being abused within a domestic environment. Nurses particularly felt the responsibility for assessing that the home environment was safe²⁰, ³³ and that neither the patient nor their family was at risk of abusing a legitimate prescription.

The Role of Caregivers 

Caregivers take on a multitude of roles when caring for a patient with cancer pain. In the eight studies included in this part of the synthesis, reports of caregiving involved complex responsibilities, conflicts, concerns, suffering, loss, and grief.¹⁹, ²⁰, ²¹, ²², ²⁶, ²⁷, ³⁴

Much of the responsibility that carers assume when assisting in the management of a patient's pain has overlap with those of health care professionals, including assessing pain and intervening to relieve it. Carers took responsibility for choice of analgesic (opioid or nonopioid), timings and frequency of administration, record keeping, and communication with health care professionals. These responsibilities continued at night, with caregivers having to wake up to administer medication, even if a patient took control of their analgesia during the day.²⁰, ²², ²⁷, ³⁴

Assuming such responsibility led carers to feel conflict and concern. Feelings of conflict arose over how much control to assume with regard to analgesia and how much to surrender to patients and nurses. Carers also felt conflict when balancing a patient's need for analgesia against concerns over side effects and addiction and when balancing requests for analgesia from the patient over perceived need. The “dose juggling” responsibility assumed by carers also included secretly increasing opioid doses beyond those considered acceptable by the patient, when the carer assessed that pain was increasing. Also carers often struggled with conflict over meeting their own personal needs vs. meeting those of their loved ones.²⁰, ²², ²⁷, ³⁴

Some of the carers’ concerns in relation to addiction were picked up through the implicit and explicit concerns communicated by health care professionals. Some carers stated that they would only accept a prescription of morphine from trusted professionals. Some health care professionals gave information to dispel fears about addiction and dependency, but carers still remained skeptical.¹⁹, ²⁰, ²³, ²⁶, ²⁷

Inability to relieve pain caused caregivers to feel angry and powerless and led to concerns for the future, to further deterioration, and to concerns about how they would manage. Unrelieved pain evoked fear and suffering among carers, along with a sense of helplessness and futility. Death was sometimes seen as the only potential release from pain, despite it being feared. Many carers expressed a wish to be able to share or endure the pain on behalf of their relative.²⁰, ²¹, ²², ²⁶, ²⁷, ³⁴

Patients appeared to be aware of their carers’ anguish, describing how they wished to protect their carers from the distress of witnessing their pain and how this caused conflict when they felt the need to describe their pain to get help.²⁸

The Management of Pain by the Patient 

Two factors predominated in how patients managed their pain. The first was how patients tried to reduce their pain through prescribed analgesic regimens and other nonpharmacological methods. The second featured the way in which patients communicate pain to others.

Although most associations between cancer pain and opioids were negative, some were positive. For example, when death drew near, patients viewed the availability of potent opioid drugs as a blessing. Patients also reported living a parallel existence, in which they strived to live while also developing strategies to ensure a comfortable death. These strategies included the use of strong opioid drugs to manage pain at the end of life.¹⁶ Some patients were able to draw positive experiences from their cancer pain. Patients described how the impetus for dealing with everyday life with cancer and cancer pain stemmed from the transcendental experience of living with the pain, which gave new meaning, strength, potential, and control. Some patients began to accept their pain as an around-the-clock phenomenon that was part of everyday life.²⁴

It has already been discussed that using opioids is viewed as a balancing act and a trade-off between managing pain and managing the consequences of managing pain. The synthesis also identified that patients use other resources to try and control their pain. Some patients sought to maintain control over their pain by altering the way in which prescribed analgesia was taken. There were several reports that indicated that patients would take opioids on an “as required” basis rather than regularly as prescribed.¹⁸, ²³, ²⁵, ³⁰ The use of regular analgesics did not fit with some patients' self-image and led to conflict, guilt, and a constant struggle to justify their use. Consequently, patients would reserve the use of opioid analgesics until it was perceived to be absolutely necessary, leading to “as required” usage. This contradicts recommendations from the effectiveness data that optimal pain control is achieved through regular doses of opioids, but it is clearly a strategy used by patients that requires consideration by clinicians prescribing and assessing the effectiveness of analgesic regimens.

Patients use various physical and cognitive techniques to reduce pain, sometimes alongside prescribed medication or as an alternative. Physical measures included use of cold, heat, massage, positioning, and touch. Cognitive strategies involved talking, distraction, relaxation, comparison with others who were less fortunate (particularly by females), or against their own condition (“it could be worse”).¹⁷, ²², ²⁵, ²⁷ Most physical and cognitive strategies also involved input from caregivers, which was generally perceived as a positive benefit by both parties.

Patients also managed how others perceived their pain by altering the way in which they communicated its intensity. Patients reported making an active choice as to how much pain they reported to carers or health care professionals. This selective disclosure of pain intensity was attributed to several differing factors. As already reported, where patients had a good relationship with their health care team, pain was talked about openly, and good pain management followed. Counter to this, negative feelings toward the health care team led to reluctance to report pain, even when it was severe. Patients felt a need to prove how severe their pain was when relationships were poor, reported feeling abandoned by health care professionals, and recalled being told there was “nothing that could be done” about their pain. The degree of confidence and trust that patients had in health care professionals influenced decision making on reporting of pain, treatment choices, and commencement of opioids.¹⁶, ¹⁷, ¹⁹, ²², ²⁸

Often patients did not disclose the full extent of their pain to carers, who were usually family members. Pain was managed through endurance and stoicism, and its existence was either hidden from family members or denied. Patients did not want to frighten or burden carers with the extent of the pain they were dealing with.²⁰, ²⁴, ²⁶, ²⁸ Pain was perceived as a private and personal matter and as one difficult to understand by those who had not suffered it.²³

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Discussion and Interpretation 

This article explores the use of morphine to treat cancer-related pain through synthesizing systematic reviews of the effectiveness of morphine with qualitative research exploring the social, cultural, regulatory, professional, and patient issues surrounding use of morphine. Through the process of CIS, a critique of the social meaning and context surrounding morphine in light of the effectiveness literature was developed. The four synthesizing arguments 1) opioids and opioid concern, 2) using opioids is a balancing act and a trade-off, 3) the existential meaning of cancer and cancer pain, and 4) the intersubjectivity of pain, mediated by the concept of control, represent a complex account of the way in which morphine and other opioids are perceived and used in clinical practice.

CIS is an approach to synthesis that is in its methodological infancy and has not previously been used with a focused clinical topic such as this one. This article is a case study, which has the potential to be applied to other questions that require the synthesis of a broad literature. The synthesis tried to locate debates surrounding the use of morphine to treat cancer-related pain in the realities of how people live their lives. Developers of policy and practice need to be able to understand the kind of tensions that exist between the effectiveness of interventions and their implementation in practice and need to be able to reference an evidence base that has systematically drawn on diverse sources of evidence to enable them to do this.⁴¹ Thousands of systematic reviews of the effectiveness of interventions exist. Although many reviews will not lend themselves to the kind of integration with qualitative research undertaken here, this article has demonstrated the possibility of synthesizing qualitative research with existing systematic reviews of effectiveness through the process of CIS. If the potential for this method is realized through its use with other research questions, then some of the broader debates that surround the understanding of clinical effectiveness may begin to be answered in a way that can enhance policy and practice.

A detailed critique of using CIS is provided elsewhere,¹¹ but suffice to say that the processes involved in the synthesis undoubtedly affect the outcome. The findings of this synthesis must, therefore, be interpreted in light of its neoteric methodology and the adaptations to it that will undoubtedly follow as others modify its use with different research questions.

The articles identified and selected for inclusion in this review influence the results and how they can be interpreted. The systematic review and guidelines were purposefully chosen as contemporary syntheses of the effectiveness of morphine to treat cancer-related pain. The qualitative research was predominantly selected through electronic searching using validated methods;¹⁴ however, it is known that the indexing of qualitative research is poor, and this may have led to bias in the selection or exclusion of articles. Limitations on the set of qualitative articles included in this synthesis include the fact that the majority view represented is that of patients, followed by carers, and then health care professionals, most of whom were nurses. Fourteen of the 19 included articles were based on research carried out in the United States, four in the United Kingdom (one joint with Kenya), and one in Sweden. This may be a reflection of the search strategy used in this synthesis, but may also be an indicator of the way in which qualitative research is funded and health care professionals are driving the qualitative research agenda within different countries.

The influence of other methodological aspects on the outcome of a CIS, for example, critical appraisal of studies, quality assessment, the role of an integrative grid in guiding translation of studies, the order in which to compare articles, and the incorporation of context and the effect of synthesis across studies on the outcome of a synthesis of qualitative and quantitative research, are not known and are open to evaluation.

Previous criticism of syntheses of qualitative research has included lack of transparency due to the inherent subjectivity of interpretation.³⁸ An underlying aim of this synthesis was to maximize the transparency of its processes to enable the reader to determine how synthetic constructs and arguments were developed. It was hoped that by using computerized software (Atlas-Ti) designed to enable researchers to manage large volumes of textual data, elements of an audit trail were possible.

The practical outcomes that arise from the CIS are grounded in the synthesizing arguments. The experience of cancer pain and its treatment is intersubjective, that is, the manner in which patients communicate about their pain is moderated in reference to other people, previous memories, prior experience of pain, and expectations of health care professionals, carers, and society in general. This can affect the way pain is assessed and subsequently managed. Health care professionals need to be aware that the way they communicate about pain, its potential cause, and treatment may influence patient disclosure about pain and the type of analgesia accepted. The importance of good communication between health care professionals, patients, and carers to achieve good pain control is acknowledged in cancer pain management guidelines.⁴² The recommendations have been advocated as “good practice points” (i.e., based on clinical experience of guideline developers). As a result of this synthesis, the guidance can now be said to be grounded in research evidence.

Concern over the use of opioids permeates the synthesis, and these apprehensions appear to limit the way in which morphine is prescribed, accepted, and taken, affecting the quality of patients' pain control. Despite years of use and publications to the contrary,², ⁴³, ⁴⁴ misconceptions regarding the addictive potential of morphine, problems of tolerance, and its identity as an end-of-life drug remain. Reluctance to prescribe morphine when clinically indicated has been identified as bad practice in cancer pain management.⁴⁵ This clearly is a challenge that needs addressing through education of health care professionals, particularly those providing generalist palliative care services. Research has highlighted that when improvement in knowledge and skills of the use of opioids to treat cancer-related pain occurs, optimal prescribing of opioids follows.⁴⁶ This is pertinent in light of current policy developments in England to extend the provision of end-of-life care services in community settings and secondary health care.⁴⁷

As cancer progresses, tension becomes apparent as the focus of care shifts from managing cancer, to managing pain, and to managing a good death. Although pain and advanced cancer are not synonymous, three-quarters of all patients with cancer experience pain.⁴⁵ The synthesis emphasizes the symbolic meaning that morphine has in relation to the trajectory of cancer and the imminence of death. The prescription of morphine and other opioids can be interpreted as a signal of the final stage of the disease process. Given that the average length of treatment with morphine before death is 50 days,⁴⁸ this interpretation may represent a reality, although some patients may take morphine for months or years.⁴⁵ Clinicians need to be aware that the act of suggestion of commencing morphine to treat cancer pain may be inextricably linked with existential meaning by some patients and they should be prepared to anticipate and address patients' concerns and, within this, be aware of the significance of the intersubjectivity of pain highlighted earlier.

The prescription of morphine and other opioids can cause adverse effects, although these do not generally limit its use.⁴⁵ The synthesis showed that unless adverse effects are anticipated, explained, and treated prophylactically, they may influence the way in which patients take opioids. The EAPC guidelines state that successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects. The Cochrane Review reports that adverse effects leading to treatment withdrawal were experienced by only 4% of participants in the included studies. The evidence arising from qualitative research findings indicates that adverse effects themselves were reported more frequently than this and are a barrier to continued opioid use and effective analgesic control. This guidance is number 15 of 20 within the EAPC framework, and future guidelines may wish to raise the prominence of the problem of adverse effects, given the barrier they can create to effective pain management. Professional support is necessary to encourage the patient and family during the period of initial adverse effects, alongside pharmacologic management wherever relevant.⁴⁵ A set of guidelines briefly mentions routine prescription of laxatives for constipation⁴² but does not acknowledge any of the side effects identified as problematic within this synthesis and which caused patients to alter their morphine intake.

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Conclusion 

This article has identified a number of key social, contextual, and physical associations that create tension and concern for patients with cancer, their carers, and health care professionals when using morphine and other opioids to treat cancer-related pain. The article achieved this by synthesizing qualitative and quantitative research using the method of CIS. These tensions and concerns have the potential to adversely affect the management of cancer pain unless acknowledged and addressed by health care professionals.

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Acknowledgment 

The author thanks Karl Atkin for supervision and advice on earlier drafts of this article.

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