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Tapentadol has μ-opioid receptor stimulating and noradrenaline reuptake inhibiting properties, and should be effective for neuropathic pain (NP). However, the efficacy of tapentadol for NP in cancer patients is unclear. Ashiya Municipal Hospital (Hyogo, Japan) enrolled five groups of Japanese cancer patients between January 1, 2013, and December 31, 2019. Patients with NP were administered tapentadol (n = 29), methadone (n = 32), oxycodone (n = 20), fentanyl (n = 26), or hydromorphone (n = 20). The primary endpoint was the difference in the verbal rating scale (VRS) scores between days 0 and 7. The secondary endpoint was the tolerability of each opioid. Before administering opioids among the five groups, there was no significant difference in the VRS score (p = 0.99). The mean reduction in the VRS score on day 7 was significantly greater in the tapentadol group than in the oxycodone group (p = 0.0024) and was larger than that of the methadone, fentanyl, and hydromorphone groups. Regarding safety, the discontinuation rate in the tapentadol group was the lowest of all groups (tapentadol vs. methadone vs. oxycodone vs. fentanyl vs. hydromorphone, 0.0% vs. 6.3% vs. 5.0% vs. 3.8% vs. 10.0%, respectively). This study suggests that tapentadol could be efficacious for cancer patients with NP, and a preferred option in cases that require immediate dose adjustment or for those at high risk for adverse effects. However, the pain intensity was evaluated without pain assessment scales specific to NP. Thus, we think that it is desirable to validate our findings using assessment scales, such as the painDETECT questionnaire in future.

Background: In view of the recent opioid crisis, ways to promote safe and effective opioid-related practices are needed. Faster intravenous (iv) opioid infusion rates can result in increased adverse effects and risk for nonmedical opioid use. Data on best practices regarding safe iv opioid administration for cancer pain are limited. This study examined iv opioid bolus infusion practices and perceptions about opioids in cancer pain among 4 groups of inpatient oncology nurses., Methods: An anonymous cross-sectional survey was conducted among oncology nurses working in medical, surgical, intensive care unit (ICU), and emergency department (ED) settings. An iv opioid bolus infusion speed less than 120 seconds was considered too fast., Results: The participant response rate was 59% (731 of 1234). Approximately 58%, 54%, and 58% of all nurses administered morphine, hydromorphone, and fentanyl, respectively, in less than 120 seconds. The median morphine infusion speeds were 55, 60, 60, and 85 seconds for ICU, surgical, ED, and medical unit nurses, respectively (P = .0002). The odds ratios for infusing too fast were 2.04 and 2.52 for ED (P = .039) and ICU nurses (P = .003), respectively, in comparison with medical unit nurses, and they were 0.27 and 0.18 with frequent (P = .003) and very frequent use of a timing device (P = .0001), respectively, in comparison with no use., Conclusions: More than half the nurses working in the inpatient setting reported administering iv opioids too fast. ICU nurses administered opioids the fastest. Nurses who frequently used a timing device were less likely to infuse too fast. Further research is needed to standardize and improve the safe intermittent administration of iv opioids to patients with cancer., (© 2019 American Cancer Society.)

Background and Objectives: Although data exist for the efficacy of intrathecal therapy (ITT), there are no prospective data on patient-controlled intrathecal analgesia (PCIA) in refractory cancer pain. This study examines the effect of PCIA on cancer symptom scores, patient satisfaction, and analgesic efficacy with an emphasis on breakthrough pain (BTP)., Methods: Ninety-eight patients with refractory cancer pain prospectively completed questionnaires including the MD Anderson Symptom Inventory and a BTP survey before and after the implantation of an intrathecal pump., Results: Fifty-eight patients were included in the study group. Average "worst" pain scores decreased from 8.32 (SD, 1.73) pre-ITT to 4.98 (SD, 2.92) post-ITT, P < 0.001. Severe pain (numerical rating score ≥7) decreased from 84.2% to 35.2% (P < 0.001). Mean daily morphine equivalent dosing decreased from 805.3 mg/d to 128.2 mg/d, with 65.5% of patients discontinuing all nonintrathecal opioids. The mean MD Anderson Symptom Inventory symptom severity score decreased from 4.98 to 3.72 (P < 0.0001), and the symptom interference score from 6.53 to 4.37 (P < 0.001). Pain reduction was 46.8% with pre-ITT breakthrough medications and 65.2% with PCIA (P < 0.001). Median time to onset was 30 minutes with pre-ITT breakthrough medications and 10 minutes with PCIA (P < 0.001). Patient-controlled intrathecal analgesia, compared with conventional BTP medications, was "a lot better" in 60.7% and "a little better" in 28.6%. Overall pain control satisfaction was also improved, with 78.2% "a lot better" and 10.9% "I have no pain.", Conclusions: In patients with poorly controlled cancer pain, PCIA is associated with improved pain control, improved cancer-related symptoms, and high satisfaction. Compared with conventional BTP regimens, PCIA provides superior analgesia and a 3-fold faster onset of action.

Short acting oral morphine has recently been registered again in Hungary. Short acting oral morphine has two essential indications: dose titration at initiation of major analgesic therapy and treatment of breakthrough pain appearing beside round the clock major analgesic therapy. The clinical management of short acting oral morphine is summarised in this article.

Objective: Up to 90% of patients with advanced cancer experience intractable pain. For these patients, oral analgesics are the mainstay of therapy, often augmented with intrathecal drug delivery. Neurosurgical ablative procedures have become less commonly used, though their efficacy has been well-established. Unfortunately, little is known about the safety of ablation in the context of previous neuromodulation. Therefore, the aim of this study is to present the results from a case series in which patients were treated successfully with a combination of intrathecal neuromodulation and neurosurgical ablation., Design: Retrospective case series and literature review., Setting: Three institutions with active cancer pain management programs in the United States., Methods: All patients who underwent both neuroablative and neuromodulatory procedures for cancer pain were surveyed using the visual analog scale prior to the first procedure, before and after a second procedure, and at long-term follow-up. Based on initial and subsequent presentation, patients underwent intrathecal morphine pump placement, cordotomy, or midline myelotomy., Results: Five patients (2 male, 3 female) with medically intractable pain (initial VAS = 10) were included in the series. Four subjects were initially treated with intrathecal analgesic neuromodulation, and 1 with midline myelotomy. Each patient experienced recurrence of pain (VAS ≥ 9) following the initial procedure, and was therefore treated with another modality (intrathecal, N = 1; midline myelotomy, N = 1; percutaneous radiofrequency cordotomy, N = 3), with significant long-term benefit (VAS 1-7)., Conclusion: In cancer patients with medically intractable pain, intrathecal neuromodulation and neurosurgical ablation together may allow for more effective control of cancer pain., (Wiley Periodicals, Inc.)

Purpose: The objective of this study was to evaluate whether extended-release hydromorphone (osmotic-controlled release oral delivery system [OROS] hydromorphone) treatment provided pain relief in cancer patients whose pain was inadequately controlled by other analgesics., Methods: In this prospective, open-label, multicenter trial, patients who have sustained cancer pain with other analgesics were enrolled. After the baseline evaluation (visit 1), OROS hydromorphone was administered. Two evaluations (visits 2 and 3) were made: 29 ± 7 and 57 ± 7 days later, respectively. The primary end point was the pain intensity difference (PID) at visit 3 relative to visit 1 (expressed as percent PID)., Results: In total, 879 patients were screened and 432 completed all three visits. Of the 874 full analysis set patients, 343 (39.2 %) improved by more than 30 % PID. Of the 432 per-protocol patients, 282 (65.3 %) improved by more than 30 % PID. At visits 2 and 3, the degree of sleep disturbance, the number of awakenings, and the degree of sleep satisfaction were significantly better than at visit 1 (all P < 0.0001 for both visit 1-visit 2 and visit 1-visit 3). However, this pain relief was not associated with improved quality of life (P = 0.326 and P = 0.055 for visit 1-visit 2 and visit 1-visit 3, respectively)., Conclusions: This study suggested that active pain management using the strong opioid OROS hydromorphone was beneficial in the management of cancer pain that was not controlled by other analgesics.

Purpose: The effectiveness of an opioid rotation to parenteral hydromorphone in advanced cancer patients has never been investigated. Therefore, the purpose of this study was to investigate the analgesic efficacy and side effects of parenteral hydromorphone on serious cancer-related pain., Methods: We included 104 consecutive advanced cancer patients who were extensively pretreated with opioids. They were rotated to parenteral hydromorphone because they failed to achieve adequate pain relief on other opioids. Pain intensity and side effects were daily assessed. The moment of adequate pain control was defined as the first of at least 2 consecutive days when the mean pain intensity at rest was ≤ 4 (on a 0-10 numeric rating scale) and side effects were tolerable., Results: The reasons for rotation to parenteral hydromorphone were inadequate pain control with/without expected delivery problems due to high opioid dosages (n = 61) and intolerable side effects with persistent pain (n = 43). Adequate pain control was achieved in 86 patients (83%) within a mean of 5 days. Eight of 86 patients still had side effects, but these were scored as acceptable. The mean pain intensity at rest decreased from 5.4 [standard deviation (sd) = 2.1] to 2.4 (sd = 1.5; p < 0.001). The median failure-free treatment period was 57 days and covered a substantial part of the median survival of 78 days in the responding patients., Conclusions: In advanced cancer patients with serious unstable cancer-related pain refractory to other opioids, continuous parenteral administration of hydromorphone often results in long-lasting adequate pain control and should be considered even after extensive pretreatment with opioids.

The vast majority of cancer patients experience pain, and treatment with opioids offers the most effective option for pain management. Long-lasting opioid formulations are usually used as cancer pain management strategies. This review surveys the available literature on the only available once-daily sustained-release formulation of hydromorphone, and its use in cancer pain management. Sustained-release (SR) formulations have a more consistent opioid plasma concentration, thereby minimizing the peaks and troughs associated with immediate-release opioid formulations. OROS hydromorphone (Jurnista, Janssen Pharmaceuticals, NV, Beerse, Belgium) releases hydromorphone over a 24-hour dosing period. Studies comparing its efficacy with other opioids such as morphine and oxycodone found comparable results overall. Recent trials have provided evidence of decreased rescue medication use for breakthrough pain, a good safety profile, and quality of life benefits. It appears to be an efficacious and well-tolerated treatment. The pharmacokinetics of OROS hydromorphone are linear and dose-proportional, and only minimally affected by the presence or absence of food. In addition, the SR properties of OROS hydromorphone are maintained in the presence of alcohol, with no dose dumping of hydromorphone. This formulation shows promise as an addition to cancer pain management strategies, although further randomized, double-blind trials are needed to confirm this.

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.

This open-label, multicenter study assessed the efficacy and tolerability of conversion to once-daily OROS hydromorphone from previous opioid agonist therapy in patients with chronic cancer pain. Patients were stabilized on their previous therapy before conversion at a 5:1 ratio of morphine sulfate to hydromorphone hydrochloride. The OROS hydromorphone dose was titrated over 3 - 21 days to achieve effective analgesia and was maintained for up to 14 days. Efficacy was assessed using the Brief Pain Inventory (BPI). Adverse events and vital signs were monitored. Dose stabilization was achieved in 119 of the 127 (94%) patients who received the study medication; in 77%, stabilization was achieved with no titration steps. Mean BPI pain intensity ratings and BPI pain interference scores decreased significantly after OROS hydromorphone treatment compared with pretreatment values. Mean pain-relief level remained stable after conversion and throughout treatment with OROS hydromorphone. Adverse events were as expected for cancer patients receiving opioid agonists. There were no clinically significant changes in vital signs.

Pain is experienced by a majority of cancer patients. As life expectancy has increased in developed and developing countries, cancer-related pain has become a major health concern. Despite the use of the three-step analgesic ladder proposed by the World Health Organization, pain still remains under treated. Morphine, the gold standard against which all other opioids has been compared is considered the first choice for management of cancer-related pain. However, recently focus has shifted to the use of hydromorphone, a semi-synthetic derivative of morphine, which is more potent, more soluble and has a comparable side-effect profile. This review focuses on the use of hydromorphone for the management of cancer-related pain emphasizing on the various routes of administration as well as dosage forms, and providing a direction for the preference of a particular route depending on the need for a rapid effect and the individual's situation. Various approaches used to modify the release of hydromorphone from the drug delivery systems with the perspective of improving patient compliance are also being discussed.

Purpose: In this prospective clinical trial we examined the technique of opioid rotation to oral sustained-release hydromorphone for controlling pain and symptoms in outpatients with cancer pain., Methods: Before and after rotation, 50 patients were assessed by Numerical Analog Scales [Numerical Rating Scales (NRS)], or as categorical parameters, and analyzed by descriptive and confirmatory statistics (ANOVA, Wilcoxon, chi)., Results: Rotation was successful in 64% of patients experiencing pain (60%), and gastrointestinal (32%) and central (26%) symptoms under oral morphine (38%), transdermal fentanyl (22%), tramadol (20%), oxycodone (12%), or sublingual buprenorphine (8%). NRS of pain (4.1 to 3.2; P=0.015), gastrointestinal symptoms, especially defecation rates (P=0.04), and incidence of insomnia improved after an increase in morphine-equivalent doses from 108.9 to 137.6 mg/d without modifying concomitant analgesics or coanalgesics., Conclusions: Switching the opioid to oral hydromorphone may be a helpful technique to alleviate pain and several symptoms, but it is still not clear to what extent the underlying mechanisms, such as the technique of rotation itself, better dose adjustment, or using a different opioid have an impact.

A substantial number of patients with cancer suffer considerable pain at some point during their disease, and approximately 25% of cancer patients die in pain. Providing effective pain management for patients with severe pain that impacts quality of life can present the oncologist or palliative care specialist with complex clinical challenges that often require multifaceted therapeutic measures. This paper presents multidisciplinary consensus-based recommendations for the treatment of intractable cancer pain using intrathecal drug delivery systems, which offer rapid and effective pain relief with less toxicity relative to oral or parenteral administration. Intrathecal drug delivery systems can be highly effective in a variety of patient settings, including cases of refractory pain, diminished performance status, poor tolerability of oral medications, polyanalgesia for complex pain, and inadequate dosing due to addiction concerns. The use of implantable or external systems is discussed, as well as implantation procedures, drug titration recommendations, and management of potential side effects. The authors offer a newly developed algorithm for delivering intraspinal analgesia in patients with cancer. The intent is that increased understanding of available options for truly effective pain management in the oncology and palliative care arena and the benefits of multidisciplinary cooperation will translate into genuine improvements in patient quality of life and a measurable decrease in the number of patients who suffer needlessly in their final days.

The successful use of methadone in cancer pain has been supported by numerous case reports and clinical studies. Methadone is usually used as a second or third line opioid medication. As the use of methadone increases we are facing the challenge of converting methadone to other opioids as part of sequential opioid trials. Data on the equianalgesic ratios for the substitution of other opioids for methadone are lacking. We present prospective data on 13 consecutive rotations from methadone to a different opioid. The opioid rotation was followed by escalation of pain and/or severe dysphoria, not controlled by a rapid increase in the dose of the second opioid, in 12 of the 13 patients. Only one patient was successfully maintained on the second opioid after the discontinuation of methadone, while 12 patients required a switch back to methadone. We conclude that opioid rotation from methadone to another opioid is often complicated by worsening pain and dysphoria. These symptoms may not improve despite upward titration of the second opioid. A uniformly accepted conversion ratio for substituting methadone with another opioid is currently not available. More data on the rotation from methadone to other opioids are needed.

Ongoing diligent patient assessment is the most important step in the equianalgesic conversion process. The conversion must take into account individual patient characteristics such as age, renal function, side effects, and the patient's pain syndrome. In addition, if the opioid dose is not adequate to begin with, the conversion dose is less likely to be effective. In all situations, once the patient is converted, liberal titration and adjustment or individualized doses for each patient are required to ensure that the conversion transition is smooth and provides the patient with the analgesia needed to adequately manage the pain. Nurses play a major role in the assessment of patients receiving opioids for pain management. Inadequate pain management despite escalating doses, untoward side effects, loss of a route of administration, and sometimes cost and reimbursement issues necessitate an opioid conversion or rotation. Nurses also play a role in recommending the change and ensuring that patients receive the correct dose.

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., (Copyright 2001 Cancer Research Campaign.)

Background: Some patients with cancer pain may develop uncontrolled adverse effects, including generalized myoclonus, delirium, nausea and emesis, or severe sedation before achieving adequate analgesia during opioid dose titration. Sequential therapeutic trials should be considered to determine the most favorable drug., Methods: Recent literature was taken into account when reviewing the rationale and potential of opioid rotation., Results: When aggressive attempts to prevent adverse effects fail, drug rotation should be considered, because sequential therapeutic trials can be useful in identifying the most favorable drug. Different mechanisms, including receptor activity, the asymmetry in cross-tolerance among different opioids, different opioid efficacies, and accumulation of toxic metabolites can explain the differences in analgesic or adverse effect responses among opioids in a clinical setting., Conclusions: When pain is relieved inadequately by opioid analgesics given in a dose that causes intolerable side effects despite routine measures to control them, treatment with the same opioid by an alternative route or with an alternative opioid administered by the same route should be considered. Opioid rotation may be useful in opening the therapeutic window and for establishing a more advantageous analgesia/toxicity relationship. By substituting opioids and using lower doses than expected according to the equivalency conversion tables, it is possible in the majority of cases to reduce or relieve the symptoms of opioid toxicity in those patients who were highly tolerant to previous opioids while improving analgesia and, as a consequence, the opioid responsiveness., (Copyright 1999 American Cancer Society.)

Background: The use of oxycodone to treat chronic cancer pain has been hampered by its short elimination half-life, which necessitates administration every 4 hours. This study compared the clinical efficacy and safety of a novel oxycodone formulation with that of hydromorphone in the treatment of cancer pain., Methods: In a double-blind crossover study, 44 patients with stable cancer pain were randomized to controlled-release oxycodone or controlled-release hydromorphone, each given every 12 hours for 7 days. Pain intensity, nausea, and sedation were assessed by patients four times daily, and breakthrough analgesia was recorded., Results: Thirty-one patients completed the study (18 women, 13 men; mean age, 56 +/- 3 years) and received a final controlled-release oxycodone dose of 124 +/- 22 mg per day and a final controlled-release hydromorphone dose of 30 +/- 6 mg per day. There were no significant differences between treatments in overall Visual Analogue Scale (VAS) pain intensity (VAS 28 +/- 4 mm vs. 31 +/- 4 mm), categorical pain intensity (1.4 +/- 0.1 vs. 1.5 +/- 0.1), daily rescue analgesic consumption (1.4 +/- 0.3 vs. 1.6 +/- 0.3), sedation scores (24 +/- 4 mm vs. 18 +/- 3 mm), nausea scores (15 +/- 3 mm vs. 13 +/- 3 mm), or patient preference. Two patients experienced hallucinations on controlled-release hydromorphone, but none did while receiving controlled-release oxycodone., Conclusions: Controlled-release oxycodone demonstrated excellent pharmacodynamic characteristics, analgesic efficacy, and safety as compared with controlled-release hydromorphone and represents an important new therapeutic option for cancer pain management.

Purpose: To evaluate the safety and efficacy of a new slow-release preparation of hydromorphone (SRH) in the treatment of cancer pain., Patients and Methods: Ninety-five adult patients from three Canadian Palliative Care Centers with no evidence of mental impairment received treatment for cancer pain with an oral opioid analgesic. After informed consent was obtained, patients underwent titration to a stable dose of immediate-release hydromorphone (IRH) for 48 hours, and were then randomized to receive IRH or SRH for 5 days in a double-blind basis. During day 6, a crossover took place, and patients received the alternate drug for 5 days. Pain intensity was assessed using a visual analog scale (VAS) and ordinal scale (OS). Side effects were assessed using VAS. Patients and investigators made a blinded global rating of efficacy a blinded final choice between SRH and IRH., Results: In 75 assessable patients, pain intensity of the VAS and OS were (mean +/- SD) 27 +/- 21 and 1.3 +/- 0.6 on IRH, versus 29 +/- 21 (P = .13) and 1.3 +/- 0.6 (P = .19) on SRH, respectively. The total number of extra doses of opioids, global rating, and final blinded choice by both patients and investigators were not significantly different between IRH and SRH. Differences in side effects were not significant., Conclusion: Our findings suggest that SRH is as safe and effective as IRH in the treatment of cancer pain.

Background: The short elimination half-life of hydromorphone necessitates 4-hourly dosing to maintain optimal levels of analgesia in patients with chronic cancer pain. The purpose of this study was to compare the clinical efficacy and safety of controlled release hydromorphone administered every 12 hours and immediate release hydromorphone administered every 4 hours in patients with chronic severe cancer pain., Methods: Forty-eight patients with stable chronic severe cancer pain were randomized, in a double-masked crossover study, to controlled release hydromorphone every 12 hours or immediate release hydromorphone every 4 hours for 7 days each. Pain intensity was assessed using a visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain Questionnaire. Nausea and sedation were also assessed using a VAS. Assessments were made by the patient four times a day at 7:00 a.m., 11:00 a.m., 3:00 p.m., and 7:00 p.m. Use of rescue hydromorphone also was recorded by the patient., Results: Forty-five patients completed the study (26 women, 19 men; mean age, 57.1 +/- 13.6 years) and received a mean daily dose of 76 +/- 133 mg (range, 6-768 mg). There were no significant differences between controlled release hydromorphone and immediate release hydromorphone in overall VAS pain intensity scores (19 +/- 14 vs. 20 +/- 14 mm), ordinal pain intensity scores (1.2 +/- 0.8 vs. 1.2 +/- 0.8) and pain scores by day of treatment or time of day. The daily rescue analgesic consumption during controlled release hydromorphone and immediate release hydromorphone did not differ significantly overall (1.1 +/- 1.1 vs. 1.0 +/- 1.1 doses per day) or with respect to time of day. There were no significant differences in overall VAS sedation scores (18 +/- 18 mm vs. 19 +/- 18 mm) and in overall mean VAS nausea scores (12 +/- 15 mm vs. 11 +/- 14 mm) between controlled release hydromorphone and immediate release hydromorphone., Conclusions: Controlled release hydromorphone administered every 12 hours is as effective as immediate release hydromorphone administered every 4 hours in the management of patients with chronic severe cancer pain. The benefits of controlled release hydromorphone lie in the convenience of its capsule formulation, which can be sprinkled on soft food, and its 12-hour duration of action, which allows patients uninterrupted sleep and improved compliance.

In this pilot randomized, double-blind, cross-over study, the effectiveness and safety of hydromorphone administration by continuous subcutaneous (s.c.) infusion (mode A) and by continuous basal rate s.c. infusion + PCA (mode B) were compared in 8 cancer patients. Patients experimented with each infusion mode during 48 h. Statistical analysis was performed on data collected in 7 patients during 36 h from 22:00 h on day 1 to 10:00 h on day 3 and from 22:00 h on day 3 to 10:00 h on day 5. Mean hydromorphone dose +/- S.D. was 56.6 +/- 30.1 and 40.4 +/- 24.5 mg/36 h for modes A and B, respectively. There was no statistically significant difference observed in mean pain intensity, but the absence of significant difference may be related to the small sample size and high individual variability. Both methods provided adequate overall pain control in most patients. However, a large interindividual variation was detected. Indeed, some patients reported in the subjective questionnaire that they felt marked discomfort during hydromorphone administration with mode B. Only 2 patients chose mode B at the end of the study, but it was interesting to note that those 2 patients were the youngest of the group. This study demonstrated the effectiveness and safety of both modes of hydromorphone administration. The data suggest that it may be possible to identify particular cancer patients which can really benefit from an association of a basal rate infusion and PCA for opiate administration.

Objective: To provide guidelines for the institution and maintenance of a continuous subcutaneous narcotic infusion program for cancer patients with chronic pain through an analysis of the narcotic requirements and treatment outcomes of patients who underwent such therapy and a comparison of the costs of two commonly used infusion systems., Design: Retrospective study., Setting: Tertiary care facilities and patients' homes., Patients: Of 481 patients seen in consultation for cancer pain between July 1987 and April 1990, 60 (12%) met the eligibility criteria (i.e., standard medical management had failed, and they had adequate supervision at home)., Intervention: Continuous subcutaneous infusion with hydromorphone hydrochloride or morphine started on an inpatient basis and continued at home whenever possible., Outcome Measures: Patient selectivity, narcotic dosing requirements, discharge rate, patient preference for analgesic regimen, side effects, complications and cost-effectiveness., Results: The mean initial maintenance infusion dose after dose titration was almost three times higher than the dose required before infusion (hydromorphone or equivalent 6.2 v. 2.1 mg/h). Eighteen patients died, and the remaining 42 were discharged home for a mean of 94.4 (standard deviation 128.3) days (extremes 12 and 741 days). The mean maximum infusion rate was 24.1 mg/h (extremes 0.5 and 180 mg/h). All but one of the patients preferred the infusion system to their previous oral analgesic regimen. Despite major dose escalations nausea and vomiting were well controlled in all cases. Twelve patients (20%) experienced serious systemic toxic effects or complications; six became encephalopathic, which necessitated dose reduction, five had a subcutaneous infection necessitating antibiotic treatment, and one had respiratory depression. The programmable computerized infusion pump was found to be more cost-effective than the disposable infusion device after a break-even point of 8 months., Conclusions: Continuous subcutaneous infusion of opioid drugs with the use of a portable programmable pump is safe and effective in selected patients who have failed to respond to standard medical treatment of their cancer pain. Dose titration may require rapid dose escalation, but this is usually well tolerated. For most communities embarking on such a program a programmable infusion system will be more cost-effective than a disposable system.

To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned.

Morphine and hydromorphone infusions of 6 or more (average 25.75) days in duration were used with increasing frequency (up to 7%) by our oncology inpatients. Eighty-six percent of the 135 inpatients we reviewed realized good pain control with dose rates up to 700 morphine-equivalent (ME) mg/h. Local toxicity occurred on only 10 occasions. Systemic side effects secondary to the infusion were reported 75 times and were generally readily reversed. Myoclonus was seen in 11% of our patients at dose rates as low as 60-90 ME mg/h. Adjuvant therapies were not used as frequently as might be warranted. We believe that narcotic infusions, particularly subcutaneous ones, are safe and effective. Further prospective trials are needed to clarify how they should be combined with other therapies to control cancer pain that is poorly responsive to narcotics, and to better understand the etiology and management of serious side effects.

Fifty-six patients with chronic pain due to advanced cancer were treated with an sc infusion of morphone (34 patients) or hydromorphone (22 patients) using a portable disposable infusor. The infusion was maintained for 26 +/- 14 days. Twenty-five patients (45%) were discharged to the home for a mean period of 18 days (range, 2-138). The mean daily increase in dose was 2.6% +/- 1.4% of the initial dose. The sc site needed to be changed every 8 days (range, 2-31). Local toxicity consisted of infection in two patients (3%), chemical irritation in three (5%), and bleeding in one (2%). After 48 hours of treatment, 54 of 56 patients (96%) preferred the sc infusion to their previous parenteral treatment. We conclude that this is a safe and simple method for the administration of narcotics to inpatients and outpatients.

From February 1985 until January 1987, 108 consecutive patients with pain due to advanced cancer requiring parenteral narcotics were treated with a subcutaneous infusion of morphine (62 patients) or hydromorphone (46 patients). Mean maximal daily dose of morphine and hydromorphone was 305 mg (range, 80-3000 mg) and 310 mg (range, 40-4024 mg), respectively. The infusion was maintained for a mean of 31 +/- 16 days (range, 2-156). Seventy patients were treated with a portable pump. Of these patients, 33 (45%) were discharge home for a mean of 29 +/- 20 days. Eighty-six of one hundred eight (86/108, 80%) patients experienced adequate pain control (less than two extra doses of analgesics per day). The duration of the site of the infusion was 7 days (range, 2-31). The mean daily increase in those was 2.4 +/- 1.6% of the initial dose (only 15% of patients needed an increase more than or equal to 5% per day). Systemic toxicity consisted of respiratory depression in two patients, severe sedation in six, and confusion in three; all patients improved upon reduction of the daily dose of narcotics. Local toxicity consisted in infection in two patients, bleeding in one, and chemical irritation in six. Cost analysis shows that subcutaneous infusion reduced costs by either allowing home discharges, or replacing intravenous infusion. The authors conclude that this method is safe and effective in patients admitted and at home, and should be considered the first choice when parenteral analgesia is required.

Few significant side effects have been reported from the treatment of cancer pain by subcutaneous infusion of opioids. In this prospective year-long study, 8 of 13 patients treated by this technique experienced painful chronic focal toxicity, manifested by induration, erythema and subdermal necrosis during subcutaneous analgesia therapy. A hydraulic-irritation effect is suggested.

To assess the safety, efficacy, and use of continuous iv infusion (CI) of opioids for cancer pain, we reviewed the clinical experience of 36 patients who received 46 CIs. CI was always preceded by a period of repetitive dosing of opioids. Morphine was used in 36 CIs, methadone in four, hydromorphone in four, oxymorphone in one, and levorphanol in one. Mean doses during CI were the morphine equivalent of 17 mg/hour (range, 0.7-100) at the start, 69 mg/hour (range, 4-480) at the maximum, and 52 mg/hour (range, 1-480) at termination. Pain relief was acceptable during 28 CIs, unacceptable during 17, and unknown during one. There were few toxic effects other than sedation. Twenty-five patients died, 12 resumed im or oral opioids, six continued CI with a different opioid (yielding analgesia in two), and outcome was undetermined in three. This review suggests that (a) CI is safe, (b) analgesia may require rapid escalation of infusion rates, (c) patient response varies and lack of acceptable analgesia may occur in up to one-third, (d) ineffective CI with one drug may be followed by success with another, (e) CI should be preceded by a period of repetitive iv boluses with the same drug, and (f) guidelines can be developed which incorporate pharmacokinetic principles.

Twenty-five patients with pain due to advanced cancer were randomized to receive patient-controlled sc injections (PCIs) of hydromorphone (HM) versus continuous sc infusion (CSCI) of HM by means of a Pharmacia 5200 pump. Each self-injection of HM during PCI was equivalent to 4 hours of CSCI. After 3 days, a crossover occurred, and patients received the alternate treatment for 3 days. During both phases of the study, patients could request extra doses of HM from their nurses. In 22 patients able to be evaluated, pain intensity (visual analogue, 0-100 mm) at 9:00 a.m. and 4:00 p.m. was 31 +/- 23 and 28 +/- 18 mm, respectively, on PCI versus 28 +/- 18 and 27 +/- 17 mm, respectively, on CSCI [P = not significant (NS)]. The total dose of HM was 168 +/- 197 and 181 +/- 234 mg on PCI and CSCI, respectively (P = NS). No significant difference was found in nausea, drowsiness, or number of hours of sleep. The total number of extra doses of HM was 6 +/- 7 on CSCI versus 2 +/- 3 on PCI (P = .007). At the end of the study, patients chose PCI and CSCI in seven and 10 cases, respectively (P = NS; 5 patients expressed no preference). We conclude that both methods were similar in regard to effectiveness and toxic effects in short-term hospital use.