Background: Chronic breathlessness is a disabling syndrome that profoundly impacts patients’ and caregivers’ lives. Driving is important for most people, including those with advanced disease. Regular, low-dose, sustained-release morphine safely reduces breathlessness, but little is known about its impact on driving.
Aim: To understand patients’ and caregivers’ (1) perspectives and experiences of driving with chronic breathlessness; and (2) perceived impact of regular, low-dose, sustained-release morphine on driving.
Design: A qualitative study embedded in a pragmatic, phase III, randomised, placebo-controlled trial of low-dose, sustained-release morphine (<=32 mg/24 h) for chronic breathlessness. Semi-structured interviews were conducted immediately after participants withdrew or completed the randomised, placebo-controlled trial. Informed by grounded theory, a constant comparative approach to analysis was adopted.
Setting/participants: Participants were recruited from an outpatients palliative care service in Adelaide, Australia. Participants included patients (n = 13) with severe breathlessness associated with chronic obstructive pulmonary disease and their caregivers (n = 9).
Results: Participants were interviewed at home. Eleven received morphine 8–32 mg. Three themes emerged: (1) independence; (2) breathlessness’ impact on driving; and (3) driving while taking regular, low-dose, sustained-release morphine.
Conclusion: Driving contributed to a sense of identity and independence. Being able to drive increased the physical and social space available to patients and caregivers, their social engagement and well-being. Patients reported breathlessness at rest may impair driving skills, while the introduction of sustained-release morphine seemed to have no self-reported impact on driving. Investigating this last perception objectively, especially in terms of safety, is the subject of ongoing work.
Objective: To explore medical doctors' experiences of, and attitudes to, use of morphine for palliative care at a tertiary hospital in Zambia.
Methods: A qualitative, exploratory case study was undertaken. Semi-structured interviews were used to collect data from 14 medical doctors working in the fields of oncology, paediatrics, and internal medicine at a tertiary hospital in Lusaka, Zambia, regarding their experiences and attitudes to prescribing morphine for palliative care. Thematic analysis of interview transcripts was carried out to establish common themes in the data. The study was approved by BSMS and UNZA research ethics committees.
Results: All participants agreed that doctors were becoming more comfortable with the prescribing of morphine, although experiences were notably different for doctors working in oncology, compared to other departments. Themes of difficulty discussing end-of-life, poor recognition of pain, and fear of patient addiction, were more prominent in the responses of non-cancer doctors. Morphine use was generally restricted to cancer and sickle cell disease patients, with most non-cancer doctors stating that they rarely prescribe morphine for outpatient use. Training in pain management, and the presence of a palliative care team, were perceived to be facilitators to morphine prescribing.
Conclusions: Although there is an increased willingness to prescribe morphine, limited knowledge of pain management, especially for non-malignant disease, underlies many of the findings in this study. Opportunity exists for professional development in pain management to further improve the acceptance and use of opioids in palliative care, especially for out-patients.
Purpose: Parenteral morphine is widely used for dyspnea of imminently dying cancer patients, but the outcomes to expect over time remain largely unknown. We examined outcomes after the administration of parenteral morphine infusion over 48 h in cancer patients with a poor performance status.
Methods: This was a multicenter prospective observational study. Inclusion criteria were metastatic/locally advanced cancer, ECOG performance status = 3–4, a dyspnea intensity = 2 on a Support Team Assessment Schedule, Japanese version (STAS-J), and receiving specialized palliative care. After initiating parenteral morphine infusion, we measured dyspnea STAS-J as well as Memorial Delirium Assessment Scale (MDAS), item 9, and Communication Capacity Scale (CCS), item 4, every 6 h over 48 h.
Results: We enrolled 167 patients (median survival = 4 days). The mean age was 70 years, 80 patients (48%) had lung cancer, and 109 (65%) had lung metastases. The mean STAS-J scores decreased from 3.1 (95% confidence interval (CI) = 3.0–3.2) at the baseline to 2.1 (95%CI = 1.9–2.2) at 6 h, and remained 1.6–1.8 over 12–48 h. The proportion of patients with dyspnea relief (STAS-J = 1) increased to 39% at 6 h, and ranged between 49 and 61% over 12–48 h. In contrast, up to 6.6 and 20% of patients showed hyperactive delirium (MDAS item 9 = 2) and an inability to communicate (CCS item 4 = 3), respectively, over 48 h.
Conclusions: Overall, terminal dyspnea was relatively well controlled with parenteral morphine, though a significant number of patients continued to suffer from dyspnea. Future efforts are needed to improve outcomes following standardized dyspnea treatment using patient-reported outcomes for imminently dying patients.
CONTEXT: Morphine is recommended as the first-line pharmacological therapy for cancer dyspnea. However, the detailed practice of morphine has not been evaluated, and consensus about other opioids for cancer dyspnea has not been established.
OBJECTIVES: To explore the physician-reported practice of opioid for cancer dyspnea.
METHODS: Nationwide mail-questionnaire survey was conducted among 536 Japanese certified palliative care physicians. We randomly selected 268 and asked the following: 1) how the physicians themselves initiate and use morphine for cancer dyspnea, 2) opioid choice for dyspnea in patients who have already used opioid other than morphine regularly, and 3) opioid choice for dyspnea in patients with various degrees of renal impairment in their daily practice.
RESULTS: Overall, 192 physicians responded (response rate, 71.6%). The major (58.3%) practice of initiating morphine was "immediate-release morphine as needed" in opioid-naïve patients and the mean % increase when they titrate morphine for cancer dyspnea was 29.4±11.3% of the baseline dose. Although "titrate baseline oxycodone" was the most frequent (42.3%) for low-to-moderate-dose regular oxycodone cases, "stepwise switch to morphine" (30.0%) and "add morphine on baseline oxycodone" (27.1%) were the more frequent practices for high-dose regular oxycodone. Regardless of the baseline dose, "add morphine on baseline fentanyl" was the most frequent practice for regular transdermal fentanyl cases. Oxycodone was the most frequent choice in renal insufficiency cases, regardless of its degree.
CONCLUSIONS: Among Japanese palliative care physicians, using oxycodone for cancer dyspnea was relatively popular practice, while fentanyl was not. Oxycodone was the most preferred opioid for cancer dyspnea in the setting of renal insufficiency among Japanese palliative care physicians. We should conduct studies to confirm the safety and effectiveness of these opioid practices for cancer dyspnea.
An 86-year-old white female was admitted to hospice care with lung cancer. Even with optimal medical management, she suffered from dyspnea and required opioid therapy. However, the patient had a true morphine and hydromorphone allergy. She was administered nebulized fentanyl for symptomatic relief of dyspnea with good effect and she did not experience any allergic response.
L'analgésie morphinique par voie médullaire est une technique récemment découverte qui a connu rapidement un grand développement et qui actuellement entre dans la phase où l'on redéfinit les justes indications. Parmi celles-ci l'analgésie des cancéreux algiques parvenus au stade terminal de leur maladie est à retenir. La découverte de récepteurs morphiniques au niveau de la moelle a conduit à injecter un morphinique à proximité de ces centres, c'esta-à-dire dans l'espace souas arachnoïdien, chez l'animal tout d'abord puis chez l'homme. L'injection dans l'espace péridural a été ensuite essayée avec succès. C'est essentiellement de cette technique qu'il s'agit ici, qui peut désormais être utilisée, sous certaines conditions, de façon simple en dehors du milieu hospitalier autorisant ainsi le retour à domicile.
BACKGROUND: Two representative samples of primary care physicians (N = 600) and medical oncologists (N = 300) in France were surveyed about their attitudes toward and knowledge about cancer pain management.
METHODS: The survey was conducted by telephone with a questionnaire based on a model developed by the University of Wisconsin-Madison Pain Research Group. It was designed to assess physicians' estimates of the prevalence of pain among patients with cancer, their practice in prescribing analgesics, their training in cancer pain management, and the quality of care received by cancer patients in their own practice and in France.
RESULTS: Barriers to adequate cancer pain management are prevalent and consistently more common among primary care physicians than among medical oncologists. Although 85% of primary care physicians and 93% of medical oncologists express satisfaction with their own ability to manage cancer pain, 76% of primary care physicians and 50% of medical oncologists report being reluctant to prescribe morphine for cancer pain. Both groups cite fear of side effects as their main reason to hesitate to prescribe morphine. Concerns about the risk of tolerance (odds ratio [OR], 1.15-2.52), perceptions that other effective drugs are available (OR, 1.11-2.41), perceptions that morphine has a poor image in public opinion (OR, 0.96-2.07), and the constraints of prescription forms (OR, 1.12-2.26) contribute significantly to physicians' infrequent prescription of morphine, as are being female (OR, 1.01-2.03) and being an older oncologist (OR, 1.09-2.51).
CONCLUSIONS: This study (1) confirms the existence among French physicians of attitudinal barriers and knowledge deficits previously reported in other countries that can impede cancer pain management, (2) identifies new barriers to the proper prescription of morphine for cancer pain control, and (3) reveals discrepancies in physicians' attitudes and knowledge about pain control which suggest a need for the systematic evaluation of cancer patients' care.
BACKGROUND: Children and infants with impaired swallow or compromised enteral absorption require alternative routes for administration of analgesia. Recent clinical guidance and practice for paediatric palliative care teams, who often treat such children, supports buccal morphine sulphate as a fast acting, effective and easily administered agent for pain relief. However, a consideration of the physicochemical properties and potency of morphine would suggest that it is not a suitable candidate for delivery via the transmucosal route, raising questions about its use in children and infants.
AIM: To explore the permeability of buccal morphine sulphate in an established ex vivo porcine buccal mucosa as a necessary step in examining efficacy for use in children with life-limiting conditions and life-threatening illnesses.
DESIGN: A permeation study conducted with morphine sulphate in an ex vivo porcine buccal tissue model. Flux values and pharmacokinetic data were used to calculate the plasma values of morphine that would result following buccal administration in a 20kg child.
RESULTS: Results show that the estimated steady state plasma values of morphine sulphate following buccal administration in this model do not achieve minimum therapeutic concentration.
CONCLUSION: These data strongly suggest that morphine sulphate is not suitable for buccal administration and that further research is needed to establish its efficacy in relief of pain in children with life-limiting conditions and life-threatening illnesses.
BACKGROUND: Dyspnea is common in interstitial lung disease (ILD) patients and often refractory to conventional treatment. Little is known regarding the safety of systemic morphine in ILD patients.
OBJECTIVE: The objective of this study is to evaluate the safety of a single subcutaneous morphine injection and to determine the recommended dose of morphine for alleviating dyspnea in ILD patients.
DESIGN: We conducted a dose-escalation Phase I study for investigating the recommended dose of a single subcutaneous morphine injection to alleviate dyspnea in ILD patients.
SETTING/SUBJECTS: Eligible subjects were ILD inpatients with dyspnea at rest who were refractory to conventional dyspnea treatment. The morphine doses used were 1 mg and 2 mg in cohort 1 and cohort 2, respectively. The primary endpoint was dose-limiting toxicity, which was defined as (1) respiratory depression, that is, 30% reduction of respiratory rate and 10 Torr increase of PaCO2 compared with baseline; (2) hypotension, that is, 20% reduction of systemic blood pressure compared with baseline and presentation of hypotension-related symptoms; or (3) grade 3, 4, or 5 treatment-emergent adverse events graded by Common Terminology Criteria for Adverse Events (version 4).
RESULTS: A total of six patients were enrolled, with three patients each in cohorts 1 and 2. No dose-limiting toxicities were observed; three patients experienced worsened somnolence, but no patients experienced sedation.
CONCLUSION: We conclude that 2 mg of morphine has a tolerable safety profile in ILD patients with dyspnea, and can be tested in further clinical trials.
BACKGROUND: Morphine can cause central nervous system side effects which impair driving skills. The legal blood morphine concentration limit for driving is 20 µg/L in France/Poland/Netherlands and 80 µg/L in England/Wales. There is no guidance as to the morphine dose leading to this concentration.
AIM: The in silico (computed) relationship of oral morphine dose and plasma concentration was modelled to provide dose estimates for a morphine plasma concentration above 20 and 80 µg/L in different patient groups.
DESIGN: A dose-concentration model for different genders, ages and oral morphine formulations, validated against clinical pharmacokinetic data, was generated using Simcyp®, a population-based pharmacokinetic simulator.
SETTING/PARTICIPANTS: Healthy Northern European population parameters were used with age, gender and renal function being varied in the different simulation groups. In total, 36,000 simulated human subjects (100 per modelled group of different ages and gender) received repeated simulated morphine dosing with modified-release or immediate-release formulations.
RESULTS: Older age, women, modified-release formulation and worse renal function were associated with higher plasma concentrations. Across all groups, morphine doses below 20 mg/day were unlikely to result in a morphine plasma concentration above 20 µg/L; this was 80 mg/day with the 80 µg/L limit.
CONCLUSION: This novel study provides predictions of the in silico (computed) dose-concentration relationship for international application. Individualised morphine prescribing decisions by clinicians must be informed by clinical judgement considering the individual patient's level of impairment and insight irrespective of the blood morphine concentration as people who have impaired driving will be breaking the law. Taking into account expected morphine concentrations enables improved individualised decision making.
BACKGROUND: International Association for Hospice and Palliative Care implemented Opioid Price Watch (OPW) to monitor availability, dispensing prices and affordability of opioids. We found that opioids with complex delivery mechanisms [fentanyl transdermal (TD) patches, sustained-release (SR) morphine, and SR oxycodone] had lower dispensing prices than immediate-release (IR) morphine formulations.
OBJECTIVE: Identify the extent that SR and TD formulations are dispensed at lower prices than generic IR morphine and the possible reasons to explain this observation.
DESIGN: Using OPW data for 30-day treatment Defined Daily Dosages, we identified where SR and TD formulations are dispensed at lower prices than IR morphine. Then we analyzed national lists of essential medicines (EML) in middle- and low-income countries to answer two questions: (1) Do they have opioids included? If yes, (2) Which ones? We then sought information on selection, budget allocation, and procurement for EML. OPW participants confirmed/verified the EML information.
RESULTS: Eighteen countries reported higher dispensing prices for IR morphine (oral and/or injectable) than TD or SR formulation. Injectable morphine was highest in seven and lowest in two (range: $74-$742). SR morphine was the least expensive, while TD fentanyl was second. Median dispensing price for IR oral morphine was higher than SR morphine. The EML for 10 countries include opioids in TD and/or SR formulations.
CONCLUSIONS: Opioids in expensive formulations are being favored over IR morphine both at the dispensing level and in their inclusion in national EML. Governments must take decisions based on efficacy, safety, and cost-effectiveness of medications.
BACKGROUND: The ethics of hastened death are complex. Studies on physicians' opinions about assisted dying (euthanasia or assisted suicide) exist, but changes in physicians' attitudes towards hastened death in clinical decision-making and the background factors explaining this remain unclear. The aim of this study was to explore the changes in these attitudes among Finnish physicians.
METHODS: A questionnaire including hypothetical patient scenarios was sent to 1182 and 1258 Finnish physicians in 1999 and 2015, respectively. Two scenarios of patients with advanced cancer were presented: one requesting an increase in his morphine dose to a potentially lethal level and another suffering a cardiac arrest. Physicians' attitudes towards assisted death, life values and other background factors were queried as well. The response rate was 56%.
RESULTS: The morphine dose was increased by 25% and 34% of the physicians in 1999 and 2015, respectively (p < 0.001). Oncologists approved the increase most infrequently without a significant change between the study years (15% vs. 17%, p = 0.689). Oncological specialty, faith in God, female gender and younger age were independent factors associated with the reluctance to increase the morphine dose. Euthanasia, but not assisted suicide, was considered less reprehensible in 2015 (p = 0.008). In both years, most physicians (84%) withheld cardiopulmonary resuscitation.
CONCLUSION: Finnish physicians accepted the risk of hastening death more often in 2015 than in 1999. The physicians' specialty and many other background factors influenced this acceptance. They also regarded euthanasia as less reprehensible now than they did 16 years ago.
Opioids are first-line therapy for cancer-related pain. In addition, corticosteroids are commonly utilized as adjuvant analgesics for pain and other symptoms in the oncology setting with limited supporting data. A retrospective analysis was conducted evaluating adult hospitalized patients receiving opioids who received once-daily dexamethasone on the recommendation of a specialty palliative care team during their hospitalization from January 1, 2015, to January 1, 2016. Primary end point was to describe prescribing patterns of dexamethasone in this patient population and secondarily examining any effect on oral morphine equivalent daily dose (MEDD), numeric pain score (NPS), and unwanted effects at 24 and 48 hours after the first dose of dexamethasone. Fifty-nine patients received an average dose of 13 mg (SD = 10) of dexamethasone for cancer-related pain, primarily acute pain (n = 36, 61%). Many died before hospital discharge or soon thereafter (n = 28, 47.5%). Although not statistically significant, our study shows a decrease of 23% and 19% in MEDD and NPS, respectively, without change in WBC after dexamethasone. A specialty palliative care team most often used once-daily dexamethasone for cancer-related pain in patients near the end of life. There were trends toward lower MEDD and NPS, but more robust studies are needed for validation.
Parenteral potent opioid availability is becoming an issue in acute pain management. Two opioids, nalbuphine and buprenorphine, are available which can be substituted for hydromorphone, fentanyl, and morphine. There are advantages and disadvantages in using these 2 opioids which are discussed, and potential dosing strategies are outlined.
BACKGROUND: End-of-life care is important in general hospitalization care. However, the clinical impact of using vasopressors on the length of the actively dying process is still controversial.
METHODS: We reviewed patients who were hospitalized in general wards and died before discharge. We classified the patients into 2 groups: those who received vasopressors (RVs) and those who did not receive vasopressors (NRV). We analyzed the factors associated with the length of hospital stay (LOS) and the length of the actively dying process.
RESULTS: In all, 745 participants, 10.01% of all admitted patients, were analyzed. Of them, 225 patients were RV group, and the remaining 520 were NRV group. Age and gender were comparable in the 2 groups. The use of vasopressors was associated with an admission diagnosis of sepsis and absence of Do-Not-Resuscitate consent and parenteral use of morphine. In multivariable analysis, a high Barthel index score, the absence of cancer and cardiopulmonary resuscitation (CPR), and no receipt of vasopressors were independent factors for LOS. For the length of the actively dying process, a longer duration of inotropic agent, the receipt of vasopressors, and the absence of CPR were independent factors.
CONCLUSION: In-hospital mortality is not uncommon during hospitalization in a general ward. The length of the actively dying process is extended by the use of vasopressors. Further prospective study is required for cautious evaluation of the pros and cons of using vasopressors at the end of life during hospitalization.
Opioids are a high-risk medicine frequently used to manage palliative patients' cancer-related pain and other symptoms. Despite the high volume of opioid use in inpatient palliative care services, and the potential for patient harm, few studies have focused on opioid errors in this population.
OBJECTIVES: To (i) identify the number of opioid errors reported by inpatient palliative care services, (ii) identify reported opioid error characteristics and (iii) determine the impact of opioid errors on palliative patient outcomes.
METHODS: A 24-month retrospective review of opioid errors reported in three inpatient palliative care services in one Australian state.
RESULTS: Of the 55 opioid errors identified, 84% reached the patient. Most errors involved morphine (35%) or hydromorphone (29%). Opioid administration errors accounted for 76% of reported opioid errors, largely due to omitted dose (33%) or wrong dose (24%) errors. Patients were more likely to receive a lower dose of opioid than ordered as a direct result of an opioid error (57%), with errors adversely impacting pain and/or symptom management in 42% of patients. Half (53%) of the affected patients required additional treatment and/or care as a direct consequence of the opioid error.
CONCLUSION: This retrospective review has provided valuable insights into the patterns and impact of opioid errors in inpatient palliative care services. Iatrogenic harm related to opioid underdosing errors contributed to palliative patients' unrelieved pain. Better understanding the factors that contribute to opioid errors and the role of safety culture in the palliative care service context warrants further investigation.
RATIONALE: Intrathecal therapy, with a low complication rate, has become an alternative to standard pain management for treatment of neuropathic cancer pain.
PATIENT CONCERNS: Here, we reported a late-stage cancer patient with intractable neuropathic pain in his right neck, shoulder, and upper limb.
DIAGNOSES: The pain started 2 years ago when the patient was diagnosed as squamous cell carcinoma with metastasis to right supraclavicular lymph nodes.
INTERVENTIONS: Cervical intrathecal infusion of morphine and bupivacaine with patient control analgesia by external pump was performed. The intrathecal catheter was located at the level of C6 vertebra. The initial concentration of bupivacaine and morphine were both 1 mg/mL with infusion rate of 0.3 mL/h and bolus of 0.3 mL. Subsequently, the concentrations increased to 2 mg/mL (bupivacaine) and 1.33 mg/mL (morphine), with infusion rate to 0.6 mL/h and bolus to 0.5 ml.
OUTCOMES: The pain intensity decreased from numerical rating scale 6 to 7 to 2 to 3 at rest, and from 10 to 5 to 6 of breakthrough pain.
LESSONS: In conclusion, cervical intrathecal infusion requires low concentration but high doses of bupivacaine and morphine, which is safe and effective in cancer patients with refractory pain and short life expectancy.
CONTEXT: With prevalence of non-communicable diseases and life expectancy rising in Senegal, the need for palliative care is likely growing. No national palliative care needs assessments have been carried out.
OBJECTIVES: To assess the capacity and need for palliative care in Senegal.
METHODS: A multi-component assessment of availability and demand for palliative care was conducted in two tertiary and two regional hospitals in Senegal in 2015 with approval from Senegal's National Ethics Committee for Health Research. The assessment consisted of (1) an inpatient hospital census; (2, 3) surveys of inpatients and outpatients with life-limiting illness; (4) a knowledge, attitudes, and practices survey among healthcare workers; and (5) a facility survey to assess availability of palliative care medications.
RESULTS: Nearly half (44.4%) of all inpatients (n=167) had an active life limiting illness. Among them, 56.6% reported moderate to severe pain in the past three days, 2.3% of whom received morphine and 76.7% received weak or no pain medication. Inpatients also experienced moderate to severe dyspnea (42.1%), fatigue (66.5%), nausea (16.5%) and drowsiness (42.1%). 39.2% of all outpatients (n=395) reported moderate to severe pain, and 52.8% said the treatment they had received relieved their pain only partially or not at all. Two-thirds of all doctors reported feeling comfortable prescribing pain medicines, however 83.0% rarely or never prescribed morphine. Two of four hospitals reported no use of morphine in 2014.
CONCLUSION: There is significant need for palliative care in Senegal. Training of healthcare workers and ensuring availability of relevant medications should be prioritized.
In agonising, crippling pain from lung cancer, Mr S came to the palliative care service in Calicut, Kerala, from an adjoining district a couple of hours away by bus. His body language revealed the depth of the suffering.
We put Mr S on morphine, among other things. A couple of hours later, he surveyed himself with disbelief. He had neither hoped nor conceived of the possibility that this kind of relief was possible.
Mr S returned the next month. Yet, common tragedy befell patient and caregivers in the form of a stock-out of morphine.