Chronic pain of moderate to severe intensity occurs in 19% of adult Europeans, seriously affecting the quality of their social and working lives. Very few were managed by pain specialists and nearly half received inadequate pain management. Although differences were observed between the 16 countries, we have documented that chronic pain is a major health care problem in Europe that needs to be taken more seriously.

Summary An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated. http://www.bjcancer.com Daytime drowsiness, dizziness or mental clouding commonly occur at the start of treatment but resolve when patients are stabilized (usually within a few days). For most patients receiving stable doses of morphine effects on cognitive and psychomotor function are minimal. In particular, there are data indicating that patients' driving ability is not significantly impaired, in alert patients receiving a stable dose (Vainio et al, 1995). Similarly, nausea and vomiting, which occur in up to two-thirds of patients when morphine is started, usually resolve. The main continuing adverse effect from morphine is constipation, and the prophylactic use of a laxative is almost always required. Morphine: limitationsThe systemic availability of morphine by the oral route is poor (20-30%) and this contributes to a sometimes unpredictable onset of action and great interindividual variability in dose requirements and response (Glare and Walsh, 1991). Active metabolites may contribute to toxicity, particularly in patients with renal impairment (McQuay and Moore, 1997). And some types of pain do not always respond well or completely to morphine, notably neuropathic pain. However, none of the alternatives to morphine has so far demonstrated advantages which would make it preferable as the first line oral opioid for cancer pain. Morphine remains our first choice but for reasons of familiarity, availability and cost rather than proven superiority.2. The optimal route of administration of morphine is by mouth. Ideally, two types of formulation are required: normal release (for dose titration) and modified release (for maintenance treatment) CThe oral route is the simplest and most acceptable to patients.There is large interindividual variation in kinetics (Säwe, 1986) and dynamics in cancer patients whose pain will also vary in severity so that the dose must be titrated against effect for each patient, and the starting dose will be determined by previous analgesic treatment. Patients changing from regular administration of a step 2 opioid (in combination with a non-opioid) will usually start with 10 mg every 4 hours. If step 2 of the analgesic ladder is omitted 5 mg every 4 hours may suffice, whereas patients converted from another step 3 opioid will require more. During dose titration it is preferable to use a formulation of morphine that has a rapid onset and a short duration of action to allow steady state to be achieved as quic...

Successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects. By these criteria, a substantial minority of patients treated with oral morphine (10% to 30%) do not have a successful outcome because of (1) excessive adverse effects, (2) inadequate analgesia, or (3) a combination of both excessive adverse effects along with inadequate analgesia. The management of excessive adverse effects remains a major clinical challenge. Multiple approaches have been described to address this problem. The clinical challenge of selecting the best option is enhanced by the lack of definitive, evidence-based comparative data. Indeed, this aspect of opioid therapeutics has become a focus of substantial controversy. This study presents evidence-based recommendations for clinical-practice formulated by an Expert Working Group of the European Association of Palliative Care (EAPC) Research NETWORK: These recommendations highlight the need for careful evaluation to distinguish between morphine adverse effects from comorbidity, dehydration, or drug interactions, and initial consideration of dose reduction (possibly by the addition of a co analgesic). If side effects persist, the clinician should consider options of symptomatic management of the adverse effect, opioid rotation, or switching route of systemic administration. The approaches are described and guidelines are provided to aid in selecting between therapeutic options.

The method for cancer pain relief proposed by the World Health Organization (WHO) consists of guidelines for a three-step treatment, from non-opioids to weak and then strong opioids, according to need. Adjuvant drugs can be added to each step. This report presents the 2-year experience of the WHO Collaborating Centre at the National Cancer Institute of Milan in the use of this method. This retrospective study shows that a correct use of the analgesic ladder can reduce pain to a third of its initial intensity. The use of non-opioids had an average duration of 19.2 days; in 52% of the cases treatment was discontinued due to inefficacy and in 42%, to side effects. Weak opioids were administered on an average for 28.0 days. A shift to Strong opioids was made in 92% of the cases due to inefficacy and in 8% because of side effects. Treatment with strong opioids lasted for an average of 46.6 days and can be considered the mainstay of cancer pain therapy. Performance status was not altered considerably during the study and hours of sleep were doubled. The analgesic ladder proved efficacious in 71% of the cases. Neurolytic procedures had to be used in 29%. The authors conclude that analgesics, as proposed by WHO, are the most suitable treatment arm in controlling pain in palliative treatment for advanced cancer patients. Lack of availability or underuse of opioids constitute the real obstacle to the application of this method.

The lack of control of physical suffering among cancer patients in the last days or hours of life is a common medical problem but it is rarely discussed in an open fashion. We carried out a prospective study of the dying of 120 terminal cancer patients assisted by a home care team. We documented how long it was before death that physical symptoms, unendurable to the patient and controllable only by sedation-inducing sleep, appeared. In 63 patients (52.5%), unendurable symptoms due to tumor progression or irreversible acute organic phenomena appeared, on average two days before death. Of the 63 patients, 47 had only one uncontrollable symptom, 15 had two symptoms and one patient had three symptoms. The most common symptoms included dyspnea (33 patients), pain (31), delirium (11), and vomiting (5). The most frequent symptoms were dyspnea in lung and head and neck disease; pain in breast, gastrointestinal tract, colon-rectum, and male genitourinary tract cancer; and vomiting in female genitourinary tract malignancies. Data reported emphasize the clinical relevance of physical symptoms in the last days of life in terminal cancer patients and how these serve to indicate imminent death. More than 50% of these patients die with physical suffering that is controllable only by means of sedation.

Sixty-six patients, surgically treated for head and neck cancer and free of disease, were interviewed at the outpatient clinic from 6 months to 8 years after surgery. The patients were divided by the physician into two groups, according to the patients' degree of disfigurement, i.e., minor (24 patients, 36%, minor disfigurement group = MDG) or extensive (42 patients, 64%, extensive disfigurement group = EDG). Subsequently, the patients were interviewed with close-ended questions. The following subjective aspects were assessed: self-image; relationship with the partner, family, and friends; and the overall impact of the therapy. The results of the study showed a significantly higher impact in the EDG versus the MDG as regards a changed self-image (57% vs 25%, P less than 0.05), a worsened relationship with the partner (27% vs 0%, P less than 0.05), a reduced sexuality (74% vs 39%, P less than 0.01), and an increased social isolation (36% vs 12%, P less than 0.05). On the whole, 18% of the subjects stated that the disadvantages of therapy outweighed the advantages, and 30% fell that the difficulties encountered were "too harsh." In such cases, the opportunity of setting up a rehabilitation program offering psychosocial support should be considered.

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