Pain-relieving properties of topically applied morphine on arterial leg ulcers: a pilot study.

OBJECTIVE: To assess whether topical morphine is pharmacologically effective in relieving pain from ulcers caused by arterial insufficiency and identify whether this effect is centrally or peripherally mediated. METHOD: The analgesic effect of a topically applied hydrogel containing 0.5% of morphine was evaluated in a double-blind, placebo-controlled, three-way crossover pilot study involving nine patients with painful arterial leg ulcers. All patients had a baseline pain intensity of at least 5 on a 10-point numeric rating scale. They received the following three treatments in random order: morphine hydrogel plus a subcutaneous (SC) placebo infusion; placebo gel plus a SC infusion of 5mg morphine over six hours and a placebo gel plus a SC placebo infusion. Each treatment lasted one day. Pain was assessed during the first 24 hours after application of the hydrogel and the start of the subcutaneous infusion. RESULTS: There was a statistically significant difference between average baseline pain scores and those reported during treatment, but this difference was not clinically relevant. The three treatments did not differ in terms of the pain relief provided. CONCLUSION: Topical morphine does not have a clinically relevant analgesic effect in patients with painful arterial leg ulcers. Further research should focus on ulcers of other aetiology.

[Delirium is certainly not an unavoidable complication of pain control in the terminal phase of life]. / Delirium door pijnbestrijding in de terminale levensfase kan worden vermeden.

In three terminal patients, a man aged 19 years who suffered from progressive osteosarcoma, a man aged 71 years with a small-cell pulmonary carcinoma, and a 68-year-old woman with cerebral metastases from a mammary carcinoma, delirium developed due to increased dosage of opioids for seemingly intractable pain (the first two patients) and dexamethasone (third patient). The delirium subsided after opioid rotation, administration of drugs for neuropathic pain, and treatment with an antipsychotic, respectively. This enhanced the patients' quality of terminal life and quality of dying. In terminal patients, analgesics-induced delirium must be considered, diagnosed and treated without delay.

Itch: scratching more than the surface.

In origin, itch can be cutaneous ("pruritoceptive", e.g. dermatitis), neuropathic (e.g. multiple sclerosis), neurogenic (e.g. cholestasis), mixed (e.g. uraemia) or psychogenic. Although itch of cutaneous origin shares a common neural pathway with pain, the afferent C-fibres subserving this type of itch are a functionally distinct subset: they respond to histamine, acetylcholine and other pruritogens, but are insensitive to mechanical stimuli. Histamine is the main mediator for itch in insect bite reactions and in most forms of urticaria, and in these circumstances the itch responds well to H(1)-antihistamines. However, in most dermatoses and in systemic disease, low-sedative H(1)-antihistamines are ineffective. Opioid antagonists relieve itch caused by spinal opioids, cholestasis and, possibly, uraemia. Ondansetron relieves itch caused by spinal opioids (but not cholestasis and uraemia). Other drug treatments for itch include rifampicin, colestyramine and 17-alpha alkyl androgens (cholestasis), thalidomide (uraemia), cimetidine and corticosteroids (Hodgkin's lymphoma), paroxetine (paraneoplastic itch), aspirin and paroxetine (polycythaemia vera) and indometacin (some HIV+ patients). If the remedies specified fail, paroxetine and mirtazapine should be considered. Ultraviolet B therapy, particularly narrow-band UVB, may be superior to drug treatment for itch in uraemia.

[Continuous subcutaneous infusion in palliative care, an undervalued method]. / Continue subcutane infusie in de palliatieve zorg, een ondergewaardeerde methode.

Three patients, 2 men aged 55 and 54 years and a woman aged 86 years, were admitted to hospital for treatment of symptoms resulting from terminal disease (pain, agitation, nausea etc.). In all three patients, continuous subcutaneous infusion (CSI) of medication was successfully used to control the symptoms. Compared with intravenous infusion, the technique of CSI is easy to learn and is associated with fewer complications. Its reliability and ease-of-use make it a technique that can be used not only in a hospital setting, but also in general practice and nursing homes. Medication used in palliative care (e.g. morphine, haloperidol, metoclopramide, levomepromazine, midazolam) can often be administered safely by CSI. In palliative care, where goals should be accomplished with minimal burden to the patient, CSI must be considered the technique of choice in patients who are unable to swallow their medication.

Understanding pruritus in systemic disease.

Many pruritic conditions do not originate in the skin, but are the result of systemic abnormality. Among the diseases that can cause pruritus are renal insufficiency, cholestasis, Hodgkin's lymphoma, polycythemia vera, solid tumors, and many others. Other pruritic conditions appear to be iatrogenic; opioid-induced pruritus may be the most important in palliative medicine. Successful treatment of the underlying condition usually relieves itch. But, with time, many diseases progress and treatment of the cause will be impossible. Topical treatments may be of limited value. Strategies involving systemic treatments include use of antidepressants, oral opioid antagonists, or cholestyramine. There is no one cure for all pruritic symptoms. Better understanding of mechanisms of pruritus may help develop better treatments.

Ethical considerations in the treatment of pain in a hospice environment.

Most people treated in hospices suffer from pain. The hospice environment offers them a place where they may feel safe and get rest before they die. This particular environment was originally created to solve the many problems terminal patients encountered in busy modern hospitals. However, it is clear that solving some problems frequently means creating new ones. For people who are about to complete their life's journey, a hospice is a place of care and autonomy. Previous losses and severe spiritual distress complicate most of the severe pain conditions seen in hospices. In this paper, some specific ethical problems encountered in hospice practice will be discussed. Patients' autonomy with all its advantages and disadvantages will be highlighted. Acceptance of death may result in an active and creative attitude. Although scientific evidence of the processes taking place is still lacking, the modern hospice may be seen as a complementary, main-stream institution contributing to the development of whole medicine.

[Pruritus in cancer: uncommon, but sometimes worse than the pain]. / Jeuk bij kanker: zeldzaam, maar soms erger dan pijn.

Three patients, two females aged 45 and 56 years with metastasized breast carcinoma and one man aged 88 years with inoperable bronchial carcinoma, suffered from severe pruritus. This was only alleviated after treatment with paroxetine, a serotonin re-uptake inhibitor, or with tropisetron, a serotonin antagonist. The youngest woman then could be given chemotherapy, after which clinical recovery occurred, the other patients died, one week and 3 months, respectively, after start of the treatment. Pruritus is a relatively rare symptom in malignancies, but may be worse than pain. In the development and transmission of pruritus signals, in cholestatic icterus as well, serotonin appears to play a more important part than histamine.

Hospice and euthanasia in The Netherlands: an ethical point of view.

This contribution is a report of a two months' participant observation in a Dutch hospice. The goal of the observation was to gain an overview of moral decisions in a hospice in which euthanasia, a tolerated practice in the Netherlands, is not accepted as an option. In an introduction, the development of palliative care in the Netherlands will be briefly presented. Subsequently, various moral decisions that were taken during the participant observation are presented and analysed by means of case reports. Attention is especially drawn to decisions that directly or indirectly relate to euthanasia. These moral decisions will be clarified in the light of the philosophy behind the concept of palliative care as it has evolved since the foundation of St Christopher's Hospice, London in 1967.

Potential uses of topical opioids in palliative care--report of 6 cases.

Opioids used topically may exercise several useful clinical effects. Opioids may cause immediate local analgesia and also may work indirectly through decreasing the inflammation process. In this article we describe six patients treated with topical opioids because of cutaneous pain due to tumor infiltration. skin ulcers of malignant and non-malignant origin, severe oral mucositis, pain due to knee arthrosis and severe tenesmoid pain. In all but one case, topical morphine provided rapid relief which lasted usually for 7-8 h. The side effects of topical opioids were none or minimal. Possible mechanisms of topical analgesia are discussed.

Paroxetine for pruritus in advanced cancer.

Pruritus associated with malignancy may be one of the most bothersome symptoms in advanced cancer. Its control is still difficult to achieve and is a challenge to palliative medicine specialists. We describe five patients suffering from pruritus of different etiologies who responded rapidly to administration of paroxetine, a serotonin reuptake inhibitor, in a dose-dependent manner. Two patients experienced transient but severe nausea and vomiting. We suggest that paroxetine's antipruritic effect may be explained by rapid downregulation of the 5-HTs receptors, which may have an important role in the generation of pruritus and pain.