Oral morphine in chronic cancer pain

Extensive clinical experience has been obtained in the use of opiates during the last decade in special units devoted to symptom control in advanced cancer. Important contradictions have emerged with the clinical pharmacological literature on opiates calling into question its relevance to the treatment of chronic pain. Specifically in the case of morphine it is clear that: it is a very effective analgesic given orally, dosage must be individualized, parenteral use or exotic analgesic 'cocktails' are usually unnecessary, and tolerance, dependence and respiratory depression are rarely common or serious problems which prevent effective pain control provided morphine is used appropriately in accordance with its pharmacological characteristics. Heroin is a suitable alternative to morphine (particularly for intramuscular administration) if differences in milligram potency are taken into account, but has no advantages in terms of either analgesic efficacy or side effects. This paper summarizes clinical experience in the use of oral morphine for cancer pain at St. Christopher's Hospice, any data from clinical investigations which support this approach, and comments on the areas of controversy which have emerged.     

Psychosocial influences on pain perceptions in cancer

This article provides an overview of the literature on the psychological and social factors that may affect a patient's perception and expression of pain. The author examines the experiences of people with cancer pain and looks at a range of factors, such as age and culture, that affect how patients perceive and describe their pain.     

Clinical observations on controlled-release morphine in cancer pain

The authors report the data from two studies on the use of controlled-release morphine sulphate tablets for cancer pain relief. This preparation allows just two administrations per day, in comparison with immediate release oral aqueous morphine solution. The first study, a randomized trial carried out on 70 patients suffering from advanced cancer pain, evaluated the analgesic efficacy and side effects of this drug. The second, an open study of 113 patients, assessed analgesic efficacy, incidence of side effects, and the effects of age on dose. The analgesia provided by controlled-release morphine administration proved to be superimposable to those of the oral aqueous morphine solution. Moreover, the use of controlled-release morphine was associated with a statistically significant reduction of some side effects. Ninety-one percent of patients needed controlled-release morphine every 12 hr, while 9% required it every 8 hr.     

Oral ketamine as an adjuvant to oral morphine for neuropathic pain in cancer patients.

To evaluate the role of oral ketamine as an adjuvant to oral morphine in cancer patients experiencing neuropathic pain, 9 cancer patients (5 men, 4 women) taking maximally tolerated doses of either morphine, amitriptyline, sodium valproate, or a combination of these drugs for intractable neuropathic pain, and reporting a pain score of >6 on a 0-10 scale, were studied prospectively to evaluate analgesia and adverse effects. Ketamine in the dose of 0.5 mg/kg body weight three times daily was added to the existing drug regimen. Patients were taught to maintain a pain diary wherein they daily recorded their pain, sedation, and vomiting scores, and other side effects. A decrease of more than 3 from the baseline in the average pain score, or a score of < or =3 was taken as a successful response. Seven patients exhibited a decrease of more than 3. Four patients experienced nausea, of which one had vomiting. Two developed loss of appetite. Eight patients reported drowsiness during the first two weeks of therapy (P = 0.001), and this gradually improved over the next two weeks in 5 of these 8 patients. Three patients withdrew from the study, two owing to excessive sedation and another due to a "feeling of unreality." None of the patients reported visual or auditory hallucinations. This experience suggests that low dose oral ketamine is beneficial and effective in the management of intractable neuropathic pain in patients with advanced cancer. However, its utility is limited in some patients by the adverse effects that accompany its use.     

Cocaine and morphine interaction in acute and chronic cancer pain

An evaluation of the analgesic, mood and side effects of the combination of intramuscular morphine and oral cocaine was conducted in 17 patients with postoperative pain and 19 others with chronic malignant pain for the purpose of assessing the therapeutic merits of so-called 'euphoriant' elixirs in the management of pain in cancer patients. The study was designed as a randomized and double-blind single dose but complete cross-over comparison of the combination of 10 mg intramuscular morphine and 10 mg oral cocaine with morphine alone, cocaine alone, and placebo. While patients clearly discriminated between the analgesic effects of morphine and placebo, there were no differences in the analgesic responses to cocaine and placebo, or in responses to morphine and the combination of morphine and cocaine in either patient group. Side effects were predominantly morphine-like and occurred in 59% of patients after the combination, 43% after morphine, 34% after cocaine and 25% after placebo. Interaction effects between cocaine and morphine were observed in terms of positive changes toward selected aspects of mood (e.g., cheerful, friendly) in postoperative patients but toward negative aspects of mood (e.g., sad, serious) in patients with chronic pain.     

Effects of morphine on cancer pain and tumor growth and metastasis

Management of pain is a great problem in patients with cancer. Morphine is a principal axis in drug therapy of pain, especially at the end stage of cancer. We developed an animal model of cancer pain and examined the effects of morphine on cancer pain and tumor growth and metastasis. Orthotopic inoculation of B16-BL6 melanoma cells into the hind paw of B16BL/6 mice produced hyperalgesia and spontaneous pain-like behavior; moderate hyperalgesia was apparent on day 7-10 post-inoculation(early phase), and the hyperalgesia became severe from day 14 post-inoculation(late phase). Morphine inhibited hyperalgesia on the both phases, but higher doses were needed on the late phase. When morphine at analgesic doses was administered daily from day 16 post-inoculation, tolerance was developed for analgesia after the sixth administration. Such morphine administration of morphine suppressed tumor growth and metastasis. Sciatic neurectomy, which was performed to block the pain signaling from the tumoral tissue, also suppressed tumor growth and metastasis. Management of cancer pain may be important not only to quality of life but also to cancer treatment itself.     

Low morphine doses in opioid-naive cancer patients with pain

Cancer pain can be managed in most patients through the use of the analgesic ladder proposed by the World Health Organization. Recent studies have proposed to skip the second "rung" of the ladder by using a so-called "strong" opioid for moderate pain. However, usual doses of strong opioids commonly prescribed for the third rung of the analgesic ladder may pose several problems in terms of tolerability in opioid-naive patients. The aim of this multicenter study was to evaluate the efficacy and tolerability of very low doses of morphine in advanced cancer patients no longer responsive to nonopioid analgesics. A sample of 110 consecutive opioid-naive patients with moderate-to-severe pain were given oral morphine at a starting dose of 15 mg/day (10 mg in those older than 70 years). Doses were then titrated according to the clinical situation. Pain intensity, morphine doses, symptom intensity, quality of life, and the requirement for dose escalation were monitored for a period of 4 weeks. The treatment was effective and well tolerated by most patients, who were able to maintain relatively low doses for the subsequent weeks (mean dose 45 mg at Week 4). Only 12 patients dropped out due to poor response or other reasons. The use of very low doses of morphine proved to be a reliable method in titrating opioid-naive advanced cancer patients who were also able to maintain their dose, in a 4-week period, below the dose level commonly used when prescribing strong opioids.     

Intravenous morphine for emergency treatment of cancer pain

Despite the wide use of the World Health Organization (WHO) analgesic ladder for the relief of cancer pain, it is not uncommon to find patients presenting with severe pain to palliative care centres. This is more so in the developing world, where facilities for pain relief are few and the health care system is not well organized. It has been the practice in a pain and palliative care clinic in south India to give repeated boluses of 1.5 mg of morphine intravenously every 10 min to patients presenting with severe pain. An audit of the procedure was undertaken by a retrospective study of 793 case notes. Seventy-nine per cent of patients had total relief of their pain with intravenous morphine. Three per cent of patients experienced side-effects during the procedure. These included nausea and vomiting, itching, giddiness, restlessness, dyspnoea, chest pain, disorientation and a feeling of uneasiness. Thirty-two per cent of patients had drowsiness, which was one of the end-points of the procedure. It is concluded that intravenous morphine in repeated boluses of 1.5 mg every 10 min is a safe and effective method of managing cancer pain emergencies in a clinical setting in a developing country.     

Experience with oral morphine for cancer pain relief

The authors report a prospective survey of 88 patients with cancer pain who were treated with oral morphine solution during a period of 140 days at the Pain Relief Unit, Kidwai Memorial Institute of Oncology, Bangalore. A high percentage of pain relief was achieved at the end of the first week of titrated therapy; relief was maintained at satisfactory levels throughout the study period in a majority of patients (86%). Interruption of oral morphine administration was necessitated by intractable vomiting in two patients. The majority of patients (65%) did not manifest any side effects, and appropriate medication successfully managed those who did. Oral morphine therapy for cancer pain offers effective pain relief with minimal side effects in the majority of patients.     

A retrospective study on the use of oral morphine in cancer pain

The authors report a retrospective study of 390 cancer pain patients tested with oral morphine during a four-month period. Initial pain scores were reduced to one half after one week of treatment and then maintained throughout the study period. Mean daily dosages of morphine were lower in those patients 65 years and older. No significant changes in performance in relation to therapy were noted except for an increase in hours of sleep. An accurate titration of dosage and continued control of side effects are the main requirements of this method of administration. The presence of side effects and the cause of interruption of treatment are reported.     

Long-term spinal administration of morphine in cancer and non-cancer pain: a retrospective study

Records of 313 patients who had been treated with spinal morphine via an implanted Port-A-Cath were reviewed. In 284 cases the Port-A-Cath was implanted for epidural delivery of morphine in patients with cancer-related pain. These patients were treated for a mean of 96 (range 1-1215) days. There was a wide variation in dose requirements, minimum daily dose ranging from 0.5 to 200 mg and maximum daily dose from 1 to 3072 mg. However, there was no clear trend to increasing dose as period of epidural morphine administration increased. The most frequent complications were pain on injection (12.0% incidence), occlusion of the portal system (10.9%), infection (8.1%) and leakage of administered morphine such that it did not all reach the epidural space (2.1%). In all but 1 case infections were limited to the area around the portal or along the catheter track. All infections resolved without sequelae following removal of the portal and/or administration of antibiotics. In 17 patients Port-A-Caths were implanted for the intrathecal delivery of morphine to control cancer-related pain. These patients also exhibited wide variations in morphine dose requirements. Port-A-Caths were also implanted for delivery of spinal morphine in 12 patients with chronic pain which was not related to cancer and which failed to respond to other therapies. These patients were treated for a mean of 155 (range 2-575) days. Port-A-Caths were removed from 7 of these patients, primarily due to infection (2 cases) and inadequate pain relief and pain on injection (2 cases).     

A long-term survey of morphine in cancer pain patients.

We surveyed 550 cancer patients who experienced pain and were treated with morphine for a total of 22,525 treatment days. Sufficient pain relief was achieved during more than 80% of this time using an average oral morphine dose of 82.4 mg--significantly lower than other studies. The use of this low dose, which was possible due to the concomitant administration of nonopioids and specific coanalgesics in most patients, resulted in a low incidence of side effects. Constipation and nausea/vomiting were the most common of these side effects. Physical dependence posed no practical problem in discontinuation of morphine treatment. Long-term opioid intake and development of tolerance did not appear to be linked; an increase in morphine dosage was most often explained by progression of the terminal disease. Addiction was a negligible problem, with only one observed case.     

Oral morphine and respiratory function amongst hospice inpatients with advanced cancer

Background Respiratory depression is the opioid adverse effect feared most by physicians. This may hinder adequate dosing in cancer pain. The study was conducted to examine the respiratory function of patients with advanced cancer receiving significant doses (>100 mg/24 h) of oral morphine.Patients and methods Consecutive pain-free hospice inpatients with advanced cancer receiving high-dose immediate-release oral morphine were evaluated. A single assessment of respiratory rate (RR), arterial blood gas (ABG), and peak flow rate (PFR) was made at assumed morphine steady state. Venous blood was drawn for a trough morphine plasma level.Results Of 31 patients who consented to examination, 20 completed the study assessment; 12 had chronic bronchitis. The median morphine dose was 30 mg 4-hourly (range 20 to 90 mg). Only one patient had evidence of ventilatory impairment.Conclusions Morphine does not commonly cause chronic ventilatory impairment when given in this way in this population even in the presence of pre-existing or concurrent respiratory disease. Oral morphine given repeatedly in individualized dosage is a safe and efficacious analgesic in the majority of those with advanced cancer.The Harry R. Horvitz Center for Palliative Medicine is a World Health Organization demonstration project in palliative medicine.     

Intravenous morphine for rapid control of severe cancer pain

This randomized controlled trial compared intravenous route with oral route for initial dose titration of morphine in 62 patients with end-stage cancer and severe pain. Patients in the intravenous group received 1.5 mg intravenous bolus doses of morphine every ten minutes till pain relief was total or until they became drowsy. After that they got oral morphine at a dose equal to the total initial intravenous requirement four-hourly. Patients in the oral group got oral morphine 5 mg doses (if opioid-na?ve) or 10 mg (if already on weak opioid) four-hourly. Patients in both groups had the option to receive rescue doses of their regular oral dose as and when needed, if necessary hourly. Twenty-seven of 31 in the intravenous group had either total or satisfactory pain relief by the end of one hour, whereas only eight of 31 in the oral group had a similar result. After 24 hours and later both groups had similar results. There was no immediate serious side effect in any of the patients. The late side effects were similar in the two groups. In the intravenous group, the ratio of initial intravenous dose requirement to the subsequent regular single oral dose after two days centred around 1:1 (range 1:0.5-1:3.3). This study found the intravenous method to be safe, effective and superior to the traditional method in providing immediate relief to severe cancer pain.     

Intraventricular morphine administration for control of chronic cancer pain

Twenty cancer patients with severe chronic pain have been treated with intraventricular morphine sulfate. Adequate pain relief until death was achieved in 10 patients; 1 patient has been treated for 9 months and is still being treated. In 2 patients, the effects of the morphine sulfate on their unilateral pelvic pain wore off after 4 and 6 months because of tumor progression. At that time, they underwent chordotomy procedures elsewhere. The treatment was discontinued in 4 patients for reasons other than inadequate pain relief, such as medical complications or resolution of pain. In 3 patients, the procedure was abandoned when emotional and psychological factors interfered with pain control. Dose requirements of intraventricular morphine sulfate varied greatly, depending on the total daily dose of systemic narcotic intake at the onset of the study. Intraventricular morphine sulfate is a feasible and reliable method to achieve pain relief in selected cancer patients with severe chronic pain when the maximum tolerated dose of systemic narcotic analgesics has become insufficient to control their pain.     

Effect of intravenous administration of paracetamol on morphine consumption in cancer pain control

Objective  

The present study aimed to examine the effectiveness of intravenous administration of paracetamol added to morphine in the control of cancer pain and its possible contribution as reduction of opioid consumption and opioid-related side effects.     

Physician attitudes and beliefs about use of morphine for cancer pain

The recent literature asserts that mistaken physician beliefs and attitudes are critical barriers to adequate cancer pain relief. To determine the prevalence of 12 proposed myths or misconceptions about morphine use in cancer pain management (CPM), we surveyed all physicians engaged in direct patient care in Duluth, Minnesota (N = 243). A 62% response was obtained. Many physicians misunderstood concepts of morphine tolerance, both to analgesia (51%) and to side effects (39%). Many were unaware of the use of adjuvant analgesics (29%), efficacy of oral morphine (27%), and nonexistent risk of addiction in CPM (20%). Analysis of result by physician age and specialy groups confirmed significant levels of misunderstanding in all subsets. Strategies to change physician attitudes and beliefs regarding morphine in CPM should focus on tolerance concepts, dosing schemes, safety, efficacy, lack of addictive risk, use of drug combinations, and the fact that cancer pain can be relieved.     

Long-term patterns of morphine dosage and pain intensity among cancer patients

Cancer pain remains a worldwide problem and some patients continue to be undermedicated because of concerns about tolerance and drug dependence. The aim of this study was to document the morphine intake of patients with chronic cancer pain in an inpatient palliative care unit and to describe the long-term pattern of morphine use and pain intensity in this patient population. With IRB approval and written informed consent, patients admitted over a 64-week period to the palliative care unit at the Royal Victoria Hospital, Montreal, were candidates for this study. Cancer patients receiving morphine for 30 days or longer who were able to complete the pain scale were included. Excluded were patients with a confused or clouded sensorium. Daily pain intensity was recorded by the PPI (0-5 scale) of the McGill pain questionnaire. The daily morphine consumption was recorded and the occurrence and intensity of breakthrough pain were also recorded. Of the 35 potential candidates for study, 17 patients with a mean age of 59 (14) years completed the study. Patients were followed up for a mean of 82 (52) days. The mean (S.D.) daily morphine dosage at study entry was 135 (127) mg, and the daily morphine dose at study completion was 244 (240) mg. There was no evidence that any patient rapidly developed tolerance to morphine. Pain was well controlled for most patients. For 10 of 17 patients, 93% reported PPI scores of either 0 or 1. Occasional breakthrough pain was experienced by 4 of these 10 patients. Four other patients reported 79% of their PPI scores as either 0 or 1, and 18% of the PPI scores as either 2 (discomforting) or 3 (disturbing), Thus 82% of patients had good to excellent pain control. Three of 17 patients spent more than four months in the unit and had less than good pain control. All of these patients had neuropathic cancer pain. These results support the conclusion that pain was well controlled for most cancer patients, and that increases in daily morphine dose, when it occurred, generally developed over a period of weeks to months, and a pattern of rapid escalation in morphine dose did not occur.     

吗啡静脉自控镇痛用于晚期癌性疼痛效果观察

目的总结吗啡静脉自控镇痛(PCIA)在晚期癌性疼痛治疗中应用经验。方法40例Ⅳ期中到重度癌性疼痛患者静脉输入吗啡治疗,采用视觉模拟评分法(VAS)或0~10数字疼痛强度分级法(NRS)对疼痛程度进行评估,使用生活质量(QOL)评价,观察记录不良反应。结果大部分患者在PCIA镇痛期间,疼痛明显缓解,但随着时间的延长,吗啡剂量的增大,平均初始剂量为(70.4±21.7)mg/d,治疗终点的剂量为(286.3±95.5)mg/d,平均治疗时间(38.3±12.1)天。生活质量均有一定程度的改善,不良反应较轻。结论PCIA可安全用于晚期癌性疼痛治疗,具有使用方便、疗效确定、不良反应轻等优点。