Analgesic plasma concentrations of morphine in children with terminal malignancy receiving a continuous subcutaneous infusion of morphine sulfate to control severe pain

Three children with terminal malignancy received a continuous subcutaneous infusion of morphine sulfate for the control of severe pain, the morphine dose being adjusted until the patient and/or parent reported complete freedom from pain. Analgesic plasma morphine concentrations at the steady state in these patients ranged from 12.9 to 57 ng/ml (median 19.6 ng/ml) while receiving morphine doses of 0.45-2.0 mg/h (0.034-0.06 mg/kg/h). One patient, who received 2 mg morphine per hour for 12 days demonstrated a 2-fold variation in steady-state plasma concentration during this period.     

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.     

High-dose tramadol in comparison to low-dose morphine for cancer pain relief.

Cancer pain treatment following the World Health Organization guidelines is effective and feasible. However, the evidence supporting the use of opioids for mild to moderate pain on the second step of the analgesic ladder is widely discussed. The present evaluation compares the efficacy and safety of high doses of oral tramadol (> or = 300 mg/d) with low doses of oral morphine (< or = 60 mg/d). Patients were included in this nonblinded and nonrandomized study if the combination of a nonopioid analgesic and up to 250 mg/d of oral tramadol was inadequate. 810 patients received oral tramadol for a total of 23,497 days, and 848 patients received oral morphine for a total of 24,695 days. The average dose of tramadol was 428 +/- 101 mg/d (range 300-600 mg/d); the average dose of morphine was 42 +/- 13 mg/d (range 10-60 mg/d). Additional nonopioid analgesics were given on more than 95% of days. Antiemetics, laxatives, neuroleptics, and steroids were prescribed significantly more frequently in the morphine group; the use of other adjuvants was similar in both groups. The mean pain intensity on a 0-100 numerical rating scale (NRS) was 27 +/- 21 (95% CI 26-29) in the tramadol and 26 +/- 20 (95% CI 24-27) in the morphine group (NS). The analgesic efficacy was good in 74% and 78%, satisfactory in 10% and 7%, and inadequate in 16% and 15% of patients receiving tramadol and morphine, respectively (NS). Constipation, neuropsychological symptoms, and pruritus were observed significantly more frequently with low-dose morphine; other symptoms had similar frequencies in both groups. These data suggest that tramadol can be used for the treatment of cancer pain, when nonopioids alone are not effective. High doses of tramadol are effective and safe.     

Comparison of intermittent bolus with continuous infusion of epidural morphine in the treatment of severe cancer pain.

Twenty-eight patients with severe pain due to cancer, who could no longer obtain acceptable pain relief from optimised doses of oral opioids, were entered into a study which compared pain relief, satisfaction with pain therapy and estimates of neuropsychological functioning during treatment with spinally administered (i.e., epidural and intrathecal) morphine as either repeated bolus doses or as a continuous infusion. These measures of efficacy and side effects were repeated every 2 weeks until either the patient died (82% of patients), withdrew from the study or were no longer able to complete the tests due to deterioration of their condition. The mean (range) duration of treatment was 169 (6-537) days for those patients receiving continuous infusion and 140 (28-378) days for those patients receiving repeated bolus doses. There was no significant difference in visual analogue pain scores, pain relief scores and satisfaction scores between the bolus and infusion groups. Furthermore, low pain scores and high pain relief scores indicated that both treatment modalities provided effective pain control. Similarly, there was no significant difference between the two groups in the various tests used to assess depression or neuropsychological function (i.e., memory, vigilance, attention and processing). There was a significantly greater degree of dose escalation in patients receiving continuous infusion compared to patients receiving repeated bolus doses. For 6 patients in the infusion group the catheter was sited in the intrathecal space, as the dose requirements by the epidural route exceeded the delivery capacity of the pump. For 4 patients in the bolus group the catheter was similarly sited, due to pain on injection and leakage/blockage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of continuous intravenous infusion of morphine in the cancer pain relieving therapy

Oral morphine treatment for cancer pain relief is established as central parts of 'WHO Regimen'. But many terminal stage cancer patients suffer from swallowing difficulty and nausea, and require other administration routes of morphine. Continuous intravenous infusion(CIVI) of morphine is the most reliable route at these conditions. We have had good results from the treatment of over 600 cancer pain patients with CIVI-morphine method. We interpreted our practical methods of CIVI-morphine treatment and commented on recently introduced injection 'morphine--100 mg/10 ml prefilled syringe', Prepenon injection.     

Intravenous titration with morphine for severe cancer pain: report of 28 cases.

BACKGROUND: In a multicenter study, 28 patients with cancer pain and insufficient pain relief with analgesic treatment according to step II of the guidelines of the World Health Organization (WHO) were switched to oral slow-release morphine. METHODS: Patients received intravenous morphine through a patient-controlled pump (PCA) for the first 24 hours (bolus = 1 mg, lockout interval = 5 minutes, maximum dose = 12 mg/hour). From day 2 patients were treated with oral slow-release morphine. Daily doses were calculated from the requirements of the day before. Breakthrough pain was treated with PCA until stable doses were reached (<2 boluses/day) and then with oral immediate-release morphine solution. Pain intensity was reported in a diary four times a day, in addition to mood, activity, and quality of sleep once daily. RESULTS: Mean duration until adequate pain relief reported (<30 on a 101-step numerical scale; NRS) was 5 hours (range = 80-620 minutes). Mean pain intensity was reduced from 67 NRS to 22 NRS. Mean doses of oral morphine were 133 mg/day initially and then 154 mg/day on day 14. Serious adverse events such as respiratory depression were not observed. Two patients terminated the study due to progressive symptoms of gastrointestinal obstruction. Seventy-five percent of the patients evaluated the effectiveness of the analgesic regime as good. CONCLUSIONS: Dose finding with intravenous PCA may be appropriate for a small minority of patients with severe pain. Higher treatment costs and the risk of complications are drawbacks of this method compared with conventional oral titration.     

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.     

A randomized double-blind crossover comparison of continuous and intermittent subcutaneous administration of opioid for cancer pain

ABSTRACT Although the preferred route of opioid administration is oral, patients with cancer often require an alternative route. Options include continuous subcutaneous infusion (CSCI) or regularly scheduled intermittent subcutaneous injections (ISCI). CSCI maintains steady drug levels, theoretically avoiding the "bolus effect" of nausea and sedation immediately post-dose, and breakthrough pain prior to the next dose. However, portable infusion pumps can be costly to use. The Edmonton Injector is an inexpensive portable device for ISCI. CSCI and ISCI have not been directly compared. The objective of this trial was to compare CSCI and ISCI of opioid for treatment of cancer pain. Patients were recruited from two tertiary palliative care units. Eligibility criteria included stable cancer pain requiring opioid therapy, need for parenteral route, and normal cognition. Patients were randomly assigned to receive opioid by CSCI by portable pump or ISCI by Edmonton Injector for 48 hours, followed by crossover to the alternative modality for 48 hours. During each phase, placebo was administered by the alternative modality. The study was closed after 12 patients were entered, due to slow accrual. Eleven patients completed the study. There were no differences between CSCI and ISCI in mean visual analogue score (VAS) for pain, nausea or drowsiness; categorical rating score of pain; number of breakthrough opioid doses per day; global rating of treatment effectiveness; or adverse effects. In all cases, patients and investigators expressed no preference for one modality over another. Further research is required to confirm that opioid administration by CSCI and ISCI provide similar analgesic and adverse effects.     

Continuous morphine infusions for cancer pain in resource-scarce environments: comparison of the subcutaneous and intravenous routes of administration

Acute onset of severe pain in cancer patients may be due to multiple causes. Irrespective of the etiology, adequate analgesia has to be provided as quickly as possible. The standard practices of relieving pain by using syringe pumps (syringe drivers) or infusion pumps may not be feasible in resource-scarce developing nations where many cancer patients first present at advanced stages of disease for management. This study compared the efficacy of the subcutaneous and intravenous routes of morphine administration continuously using a simple and economic technique for cancer pain management. Both routes were found to be equally effective in producing good analgesia without side effects. The drip method is a cost-effective way of providing subcutaneous morphine infusion for cancer patients and is applicable for both inpatients and home care.     

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.     

硫酸吗啡控释片与硫酸吗啡缓释片对重度癌痛患者镇痛效果的比较

背景吗啡是WHO倡导的治疗中重度癌症疼痛的首选药物.硫酸吗啡控释片与硫酸吗啡缓释片是口服长效吗啡.该药对解除肿瘤患者的疼痛、提高生活质量十分重要.目的观察硫酸吗啡控释片与硫酸吗啡缓释片对重度癌痛的止痛效果及对患者生活质量的影响.设计以患者为研究对象的病例分析.单位一所大学附属第一医院肿瘤科、外科、内科、中医科.对象1995-10/1998-06暨南大学附属第一医院确诊肿瘤伴重度疼痛的住院患者参加此次试验.方法182例经病理证实的中晚期重度癌痛患者,95例服用硫酸吗啡控释片,12例因药物的副作用、死亡、出院而失访,83例符合标准进入试验.87例服用硫酸吗啡缓释片,25例因药物的副作用、死亡、出院而失访,62例符合标准进入试验.初始剂量均为30 mg口服,每12 h 1次;据实际镇痛效果来调整用量,直到达到满意的镇痛效果.主要观察指标疼痛强度、疼痛缓解率及完全缓解率、缓解时间、副作用、治疗前后生活质量评分.结果硫酸吗啡控释片、硫酸吗啡缓释片的镇痛有效率分别为95%,94%.完全缓解率分别为82%,80%.镇痛有效时间分别为(9.1±4.1)h,(8.7±4.4)h.两药镇痛效果及镇痛有效时间经统计学处理差异无显著性意义(P＞0.05).治疗后分别有62例(75%),47例(76%)生活质量较前提高一个等级,治疗前后生活质量评分硫酸吗啡控释片组分别为(34.6±11.5),(52.6±13.0)分(P=0.000);硫酸吗啡缓释片组分别为(37.7±9 7),(49.8±12.9)分(P=0.000),治疗前后患者生活质量差异有显著性意义.两药对骨痛、内脏痛、软组织浸润痛效果好,对神经痛效果欠佳.结论硫酸吗啡控释片或硫酸吗啡缓释片对重度癌痛止痛效果相似,镇痛时间长,副作用小,改善了患者的生活质量.     

Intravenous morphine titration to treat severe pain in the ED

Purpose

We assessed the safety of intravenous morphine titration in the emergency setting.

Methods

A total of 621 consecutive adult patients admitted in the ED with acute severe pain (visual analogue scale pain score >70) were included. Intravenous morphine titration was administered as a bolus of 2 (body weight ≤60 kg) or 3 mg (body weight >60 kg) with 5-minute interval between each bolus. Pain relief was defined as a visual analogue pain score of 30 or lower.

Results

The dose of morphine administered was 0.16 ± 0.10 mg/kg and the median number of boluses was 3. Pain relief was obtained in 512 (82%) patients. Morphine-induced adverse events occurred in 67 patients (11%) without severe adverse event. Titration was interrupted before pain relief had been obtained in 107 (17%) patients. In the remaining 514 patients, pain relief was obtained in 507 (99%) patients. Two variables were significantly associated with no pain relief: major protocol deviation (odds ratio, 17.3; 95% confidence interval, 10.0-30.1) and morphine-induced adverse effect (odds ratio, 13.0; 95% confidence interval, 6.7-25.3).

Conclusion

Intravenous morphine titration is a safe and effective option for severe pain when used according to a strict protocol.     

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.