Mary Anne Kenny reports from this year’s Cephalon Palliative Care Symposium, which focused on quality in training and research
At this year’s Cephalon Palliative Care Symposium, held on 16-17 April, experts spoke about the latest advances in cancer pain management and in palliative care education.
Dr Tony O’Brien, Consultant in Palliative Medicine, Marymount Hospice, Cork chaired the event and welcomed the opening speaker – Dr Eduardo Bruera, Medical Oncologist, Chair of the Department Palliative Care and Rehabilitation Medicine, The University of Texas, MD Anderson Cancer Center, USA. His presentation was called, ‘Cancer pain assessment and management – is there anything more to be done?’
Pain management
In cases of advanced cancer, 80 per cent or more of patients have pain, he said. Good control is achieved in over 80 per cent or more of these patients and strong opioids are needed by 80 per cent of these, in turn.
The emerging view is that multiple levels of production are involved in pain symptoms, including immune response, target organ response, metabolic changes, endothelial changes and tumour by-products.
“Patients’ methods of expressing pain are influenced by cognitive status, mood, beliefs, culture and biography,” said Dr Bruera. Factors that influence pain expression include nociception (variable), somatisation (mood-personality), coping chemically, opioid tolerance, neuropathic pain (decreased response) and incidence pain.
When using rapid-onset opioids to treat breakthrough pain, oral/subcutaneous breakthrough medications work in the majority, but Dr Bruera stressed the large cost differential. Also, concerns regarding dosing and addictive potential are not resolved.
Referring to neuropathic pain, he said the response to opioids ≅ 66 per cent and adjuvants ≅ 35 per cent, ‘but always try the opioid first’. Pain intensity has cancer-related elements (tumour growth, infection, ischaemia, fracture) and patient-related elements (mood change, chemical coping, opioid tolerance, delirium). The ‘three big issues’, said Dr Bruera, are somatisation, chemical coping and delirium.
“When it comes to chemical coping, it must be remembered that in advanced head and neck cancer, over 47 per cent of patients are alcoholics under the CAGE questionnaire. In breast cancer, this figure is 18 per cent. Dose escalation must be prevented and any psychiatric issues must be ruled out.”
Somatisation is the diagnostic criterion for affective disorders and the ‘meaning’ of the patient’s pain. This is aggravated by stressors, is indicated by high-intensity expression (e.g. pain (e.g. ‘10/10’ pain score) and has multiple symptoms. “Some 85 per cent of cancer patients experience delirium before death,” said Dr Bruera. “Disinhibition in emotions is common. Opioids can cause delirium, so dose escalation must be monitored. Increased pain can also cause hyperalgesia or delirium.”
For mild pain, NSAIDs or acetaminophen should be used. For moderate pain, add opioids ± adjuvants. For severe pain, add strong opioids ± adjuvants.
Opioid-induced neurotoxicity (OIN) must be borne in mind. “This means severe sedation; cognitive failure; hallucinosis/delirium, myoclonus/grand mal seizures and hyperalgesia/allodynia,” he said.
To manage an acute episode, he recommended: rotate opioids, increase elimination (hydration) and stop drugs such as NSAIDs and tricyclics. For agitation, try haloperiodol (midazolam) and monitor frequently. OIN could be dose related (somatisation, alcoholism/drugs or tolerance) or pain related (neuropathic or incidental).
Dr Bruera said methadone was the ‘most exciting opioid in the last decade’. “It’s used in poor pain control and OIN. However, it requires more complex rotation and initiation, so a review of all cases of initiation (5mg every 12 hours) or rotation must be carried out. “Methadone is effective when other opioids fail and when started as a new opioid. Used by an experienced team, its success rate is extremely high.”
He concluded by explaining that the solo practice approach, where cancer care and palliative care are largely supplied separately, should be replaced with the integrated approach between the oncologist and palliative care team early in the trajectory of illness.
Breakthrough cancer pain
Dr O’Brien spoke on ‘Break-through Cancer Pain’. He differentiated the different types of cancer pain: background/persistent, which requires around-the-clock (ATC) medication; and breakthrough pain, which needs as-required medication.
In 2009, the Association for Palliative Medicine of Great Britain and Ireland (APM) Guidelines defined BTcP as: “Transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain.” BTcP may occur frequently; it has a rapid onset; has a short duration (~30 minutes); is moderate-severe in intensity; has worse psychological/functional outcomes; and has a less positive response to opioid therapy.
“The traditional treatment is to establish the baseline ATC opioid dose per 24 hours. One-sixth is given orally [four-hour dose equivalent] and the rescue dose is titrated in line with the baseline dose,” he said. The strengths of traditional treatment were: a fixed-dose ratio, it was mostly the same molecule and it was a secondary measure of analgesia efficacy. Its weaknesses were: delayed onset and offset, toxicity risk and profile mismatch.
The APM Guidelines (Davies et al, 2009) state: assess for the presence of BTcP; assess the characteristics of this pain; assess the patient/individualise treatment; treat the underlying cause, if possible; avoid precipitating factors; and optimise ATC medication. The guidelines also state that opioids are the rescue medication of choice and that the oral route is not preferred. Determine the dose by individual titration. “Non opioids may be a useful adjunct and you should consider non-pharmacological prescriptions and also interventional drugs,” said Dr O’Brien.
He listed some of the current and future treatment options: oral transmucosal fentanyl citrate (OTFC, Actiq); fentanyl buccal tablet (Effentora); sublingual fentanyl (Abstral); buccal film (disc) fentanyl (Onsolis); intra-nasal fentanyl spray (Instanyl); intra-nasal fentanyl spray with pectin (Nasalfent); and inhaled fentanyl products.
Fentanyl is highly lipophilic, crosses membranes rapidly and is quickly distributed into the central nervous system – an equilibrium process with a three- to five-minute distribution half-life. It has an extensive first-pass metabolism and no pharmacologically active metabolites.“Looking at Effentora, we have a fentanyl buccal tablet using OraVescent delivery technology. When it comes to oral transmucosal delivery, it provides greater absorption across the buccal mucosa than OTFC and swallowed tablets.”
Nearly half of the Effentora dose is directly absorbed across the buccal mucosa, he said, whereas less than a quarter of the dose of OTFC is absorbed. “Start at the lowest dose. If there’s satisfactory pain relief, no further action is needed. If adequate pain relief isn’t achieved, repeat the dose after 30 minutes. Use the higher dose for subsequent episodes to a maximum of four treatment episodes per day.
“All new BTcP treatments use fentanyl,” Dr O’Brien concluded. “It has a fast onset/offset of action and its profiles closely mirror the profile of BTcP, which should avoid toxicity issues.Pain education
Prof Philip Larkin, Professor of Clinical Nursing (Palliative Care) at University College Dublin and Our Lady’s Hospice, Harold’s Cross, asked, ‘How well do we teach our healthcare professionals to manage breakthrough pain?’
We must teach about BTcP as a precursor to more severe pain, as part of a spectrum/multiplicity of pain and continuing functional impairment, with regard to poor quality of life, he said. “If end-of-dose failure is related to declining analgesic levels and presumably inadequately controlled background pain, how does that fit with current definitions of BTcP? And what’s the evidence for how well we teach breakthrough pain management?”
A study that carried out pre- and post-test evaluation of educational intervention around pain management (n=197) showed markedly improved scores in understanding opiates and clinical use [P<0.001] (Bauwens et al, 2001). However, Alvarez & Agra (2006) carried out a systematic review of educational interventions for primary-care physicians. Reviewing 18 studies, they concluded that although improved knowledge was demonstrated, there was little evidence of improved practice. “Barriers to education around BTcP management include: a gap between theory and practice; insufficient focus on skill development; lack of academic standardisation in programmes; and lack of institutional support for change,” said Prof Larkin.
The European Association for Palliative Care recommends the division of the palliative medical education syllabus for undergraduates as follows: basics of palliative care – 5 per cent; pain and symptom management – 55 per cent; psychosocial and spiritual aspects – 20 per cent; ethical and legal issues – 5 per cent; communication – 10 per cent; teamwork and self-reflection – 5 per cent.
“Innovation, consistency, cost-effectiveness, vision, stability and marketability are necessary,” said Prof Larkin. “We must utilise e-learning, coaching and mentoring. Educators must understand how influencing change in an institutional situation leads to better clinical practice. The way forward is through partnership, setting standards and norms and developing competencies.”
The problem, he said, is that there has been no systematic collation of curricula across Europe to identify palliative care content, topics taught, hours of delivery and assessment strategy. He advocated need a ‘ketamine-based’ approach – short bursts of focused learning activity can be as useful as lengthy programmes in understanding best practice in pain management.
“Education is about preparing people to face clinical challenges, such as BTcP, and being able to respond to them, rather than trying to solve them,” Prof Larkin concluded.
Respiratory secretions
Helen Ely, Clinical Nurse Specialist in Palliative Care in Roscommon Hospital, spoke on ‘The Management of Respiratory Tract Secretions in the Dying Patient’. In the terminal phase of illness, airway secretions may accumulate, resulting in gurgling and rattling noises during inspiration and expiration, she explained. These are often described as a ‘death rattle’ and the secretions may be salivary or bronchial.
Secretions can accumulate because swallowing and coughing reflexes are decreased or absent; secretions are excessive/abnormal; cilia do not function properly to move up the respiratory tract; or the patient may be in a supine position.
“The presence of audible respiratory secretions is a strong predictor of death,” said Ely. “In the Wildiers & Menton (2002) study of over 100 patients, 48 per cent experienced the symptom within 24 hours of death and 76 per cent died within 48 hours of onset. However, we must differentiate the problem of respiratory secretions as a sign of impending death from alternative situations, in which more active approach may be appropriate.”
Management of secretions includes both non-pharmacological (re-positioning of the patient, oropharyngeal suctioning and decreasing parenteral fluids) and pharmacological methods. Anticholinergic drugs reduce saliva production and have some effect on reducing secretions. These should be provided at first sign of noisy secretions, as they are less effective at drying up existing secretions. The choice of anticholinergic – such as glycopyrronium, hyoscine hydrobromide or butylbromide – is based on the patient’s needs and properties of the drug, she said.
Once a person’s consciousness is reduced to the point where they have no cough reflex, they are unlikely to be aware of, or distressed by, accumulated respiratory secretions. “The focus is on family or caregivers, to reduce distress for who witness noisy secretions. A survey of 195 bereaved family members found that 78 per cent had been distressed by their loved one’s ‘death rattle’ [Morita et al, 2004].”
She concluded that the management of respiratory secretions is complex, but the goal is always a comfortable and dignified death for the patient.
l The views expressed are those of the presenters and do not necessarily reflect those of Cephalon Pharma (Ireland) Ltd.
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