Management Of Refractory Cancer Pain Research Articles

Management of Refractory Cancer Pain with Intrathecal Drug Delivery and Spinal Cord Stimulation.

Intrathecal pumps (ITPs) are indicated for refractory cancer pain and decrease systemic opioid requirements. While not yet indicated for cancer pain, spinal cord stimulators (SCSs) are used off-label for cancer pain, with increasing evidence of their efficacy. A retrospective chart review was conducted of patients who underwent both ITP and at least SCS trial for cancer pain. Primary outcomes were pain numeric rating scale (NRS) and daily morphine equivalents (MEQs). Seventeen patients were identified. Both ITP and SCS were associated with significant decreases in pain ratings at the 3-month follow-up, but this decrease became nonsignificant subsequently. ITP, but not SCS, was associated with a significant decrease in MEQ. ITP and SCS may both provide efficacy for cancer pain, but the opioid-sparing effects of SCS may be limited. ITP and SCS may potentially be complementary in their ability to provide relief from cancer-related pain.

More time in a community setting: A service evaluation of the impact of intrathecal drug delivery systems on place of care of patients with cancer pain.

Intrathecal Drug Delivery Systems are underutilised in the management of refractory cancer pain despite evidence of their efficacy. Not all patients who are offered this treatment modality accept it. There is no current evidence that indicates if the use of intrathecal drug delivery systems impacts on place of care for patients with cancer related pain. This service evaluation compared place of care, place of death and morphine equivalent daily dose at end of life for patients in whom Intrathecal Drug Delivery was successfully established versus those who chose comprehensive medical management. A retrospective longitudinal cohort study of 45 patients with cancer pain comparing those who had ongoing analgesia successfully delivered via an implanted Intrathecal Drug Delivery System (n = 28) with those who continued to receive comprehensive medical management (n = 17). There was a markedly greater time spent in the community in the intrathecal group than the medical management group (median 126.5vs 25.5 days; p = 0.002) and a lower morphine equivalent daily dose at end of life (median 127.5vs 440.0 p = 0.022). In patients with advanced cancer, the successful establishment of intrathecal analgesia is associated with more time in the community and a lower morphine equivalent daily dose at end of life. The study has low numbers, and the sample was retrospectively selected. Nevertheless, these findings suggest the initial investment of time in an inpatient setting may be beneficial. Further research is required, using larger, prospective studies of patient outcomes in this setting.

Cost-Effectiveness and Cost–Utility Analyses in Thailand of Continuous Intrathecal Morphine Infusion Compared with Conventional Therapy in Cancer Pain: A 10-year Multicenter Retrospective Study

ABSTRACT Background Because of the high initial cost of intrathecal drug delivery (ITDD) therapy, this study investigated the cost-effectiveness and cost–utility of ITDD therapy in refractory cancer pain management in Thailand over the past 10 years. Methods The retrospective study was conducted in patients with cancer pain who underwent ITDD therapy from January 2011 to 2021 at three university hospitals. Clinical outcomes included the numerical rating scale (NRS), Palliative Performance Scale, and the EQ-5D. The direct medical and nonmedical as well as indirect costs were also recorded. Cost-effectiveness and cost–utility analyses were performed comparing ITDD therapy with conventional therapy (extrapolated from costs of the same patient before ITDD therapy) from a societally oriented economic evaluation. Results Twenty patients (F:M: 10:10) aged 60 ± 15 years who underwent implantation of an intrathecal percutaneous port (IT port; n = 15) or programmable intrathecal pump (IT pump; n = 5) were included. The median survival time was 78 (interquartile range = 121–54) days after ITDD therapy. At 2-month follow-up, the incremental cost-effectiveness ratio (ICER)/pain reduction of an IT port (US$2065.36 (CA$2829.54)/2-point NRS reduction/lifetime) was lower than for patients with an IT pump (US$5479.26 (CA$7506.58)/2-point NRS reduction/lifetime) compared with continued conventional therapy. The ICER/quality-adjusted life years (QALYs) gained for an IT port compared with conventional treatment was US$93,999.31(CA$128,799.06)/QALY gained, which is above the cost-effectiveness threshold for Thailand. Conclusion The cost-effectiveness and cost–utility of IT port therapy for cancer pain was high relative to the cost of living in Thailand, above the cost-effectiveness threshold. Prospective cost analysis studies enrolling more patients with diverse cancers that investigate the benefit of early ITDD therapy with devices over a range of prices are warranted.

Controversies in intrathecal drug delivery for cancer pain

Pain and suffering related to cancer are challenging issues that continue to deserve consideration for treatment optimization. Advances in analgesic management and control of the underlying cancer have improved symptom...

The use of ketamine in the management of refractory cancer pain in a palliative care unit.

Ketamine has been used as an adjuvant to opioid therapy for the management of refractory cancer pain but the current evidence is insufficient to draw any conclusions regarding its efficacy. We aimed to assess the response to ketamine in patients with refractory cancer pain treated in an oncology palliative care unit. Patients with refractory cancer pain despite opioid dose escalation were selected for a trial of parenteral ketamine infusion according to a local protocol. The medical records of those patients treated between January 2004 and December 2018 were retrospectively reviewed. The primary endpoint of the study was a favorable response to ketamine, defined as a reduction in regular opioid dose with no increase in pain intensity or a reduction in pain intensity by ≥2 points on the numerical rating scale (NRS) with a stable regular opioid dose. The secondary endpoint was adverse events associated with ketamine. Among the 70 patients, mean pain score on NRS improved from 7.0 to 4.0 after ketamine (P<0.001). Forty-nine patients had a reduction of pain score by ≥2 points on NRS, 33 had ≥50% reduction in pain intensity. The median decrease in regular opioid dose was 25.5%, and the mean difference was -133.2 mg (P=0.002). A favorable response to ketamine was observed in 52 patients (74.3%). The use of more than one coanalgesic (odds ratio 3.451; 95% CI: 1.087-10.960; P=0.036) was associated with a favorable response to ketamine on multivariate analysis. Adverse events were mostly mild, with the commonest being drowsiness (45.7%), hypertension (34.3%) and nightmares (25.7%). Only five and three patients required temporary suspension and early termination of ketamine infusion respectively. These data demonstrated the efficacy and safety of ketamine in a population of patients with refractory cancer pain. The use of more than one coanalgesic was associated with a favorable response to ketamine. Further large and multicentered studies are warranted to confirm these data.

Tailoring of neurosurgical ablative procedures in the management of refractory cancer pain

IntroductionNeurosurgical ablative procedures can offer immediate and effective pain relief for patients suffering from refractory cancer pain. However, choosing the appropriate procedure for each patient may not be straightforward and...

Successful Multimodality Management of Refractory Cancer Pain on Shoulder Caused by Lung Cancer Metastasis and Resistant to Analgesics: A Case Report

Cancer pain is an inevitable symptom burden for 66% of cancer patients [1]. The traditional cancer pain management is depending on the principle of three-step analgesic ladder developed by WHO in 1986, which recommends the administration of opioid and nonopioid analgesic [2].

終末期がん患者の難治性疼痛に対し，リドカイン持続静脈内投与が著効した1例

【緒言】リドカインは末梢神経に対し興奮抑制作用を示すことで鎮痛効果を発揮する．とくに神経障害性疼痛を主体とした難治性疼痛やモルヒネ不耐症に対する疼痛マネジメントにおいて有効である．【症例】51歳，女性．終末期の食道がんに起因する難治性疼痛が持続し，オピオイド増量による効果も乏しく，副作用の出現が目立っていた．疼痛に対しリドカイン持続静脈内投与を開始（150 mg/日）したところ，徐々に疼痛は軽減しオピオイドも減量することが可能となった．リドカインによる副作用はみられなかった．【結論】終末期の難治性疼痛およびモルヒネ不耐性を示す患者に対するリドカイン持続静脈内投与は，疼痛マネジメントとして有効であることが示唆された．

Interventional options for the management of refractory cancer pain--what is the evidence?

Pain is the most common symptom in cancer patients. Standard pain treatment according to the WHO three-step analgesic ladder provides effective pain management in approximately 70-90% of cancer patients. Refractory pain is defined as not responding to "standard" treatments. Interventional analgesic techniques can be used in an attempt to control refractory pain in patients in whom conventional analgesic strategies fail to provide effective pain relief or are intolerable due to severe adverse effects. This systematic review aims to provide the latest evidence on interventional refractory pain management in cancer patients. Systematic literature search in Cochrane, EMBASE and PubMed including reviews and randomised controlled trials (RCTs) and non-randomised controlled trials in the absence of reviews. Neuraxial analgesia may play a role in refractory cancer pain management. Paravertebral blocks decrease the incidence of persistent post-surgical pain after breast cancer. Coeliac plexus blocks improve pain scores in refractory pancreatic cancer pain for up to 4 weeks after the intervention with fewer burdensome side effects as compared to opioids. Cordotomy has mainly been studied in mesothelioma, and the case series suggest possible benefit for pain at the expense of a relatively high risk of side effects. Overall, very few RCTs have been conducted on interventional pain techniques. In reality, it is very difficult to undertake large controlled trials for a number of reasons. Therefore, today's best evidence for practice may be from large case series of comparable patients with careful response and toxicity evaluation and follow-up.

Pharmacological options for the management of refractory cancer pain-what is the evidence?

Refractory cancer pain that does not respond to standard opioid and/or co-analgesic therapy occurs in 10-20% of patients. Risk factors include young age, neuropathic pain type, incident pain, psychological distress, previous opioid use, high tolerance, a history of addiction and impaired cognition. The management of patients with refractory pain remains a challenge. Treatment options include opioid manipulation (parenteral delivery, rotation, combination, methadone and buprenorphine), non-opioids and co-analgesics (paracetamol, non-steroidal anti-inflammatory agents, antidepressants and anticonvulsants), NMDA receptor antagonists, cannabinoids, lignocaine and corticosteroids. The evidence of benefit for any of these agents is weak, and each additional agent increases the risk of adverse events. Evidence-based guidelines cannot, therefore, be developed at present. New approaches are recommended including targeted opioid therapy, multimodal analgesia, a goal-oriented approach to pain management and increasing use of the multidisciplinary team and support services.

Methadone Rotation for Cancer Patients with Refractory Pain in a Palliative Care Unit: An Observational Study

Methadone has been reported to be as effective as morphine for cancer pain management. It is commonly used as an alternative opioid in case of insufficient relief. Our aim was to assess efficacy and tolerance of opioid rotation to methadone for refractory cancer pain management in palliative care unit (PCU) inpatients. All the patients undergoing opioid rotation to methadone from 2008 to 2011 in two PCUs (Lyon and Nice, France) were included. Pain assessments were undertaken on day 0 (D0), day 3 (D3), day 7 (D7), and day 14 (D14) using a visual analogue scale (VAS; 0-10) and the Douleur Neuropathique 4 (DN4) scale for neuropathic pain. Patients reported pain relief using a 4-point Likert scale (1=no relief; 4=important relief ). Nineteen patients (7 females) with a median age of 55 (Q1-Q3; 44-58) underwent methadone rotation. The most common type of cancer was gastrointestinal. Seventeen patients had a diagnosis of mixed pain syndromes. Morphine equivalent daily dose (MEDD) prior to switching was 480 mg (Q1-Q3; 100-1021), and at least two nonmethadone opioid rotations had already been done for 13 patients. Between D0 and D7, the VAS score decreased by 4 points (p<0.001). The DN4 score became negative on D7 for 11 of 17 patients (65%). On D7, 16 of 18 patients (89%) expressed moderate to greater than moderate pain relief. Methadone was discontinued in one patient on D7 because it was deemed ineffective and for 8 patients, who were unable to take oral drugs, it was discontinued after D14. Our results suggest that methadone is effective and well tolerated for refractory cancer pain.

Surgical/Radiological Interventions for Cancer Pain

Pain is a major morbidity associated with cancer and up to 20% patients require invasive procedures for pain relief. Ablative techniques can be directed towards the spinal cord and brain to palliate pain or modify its perception. Anterolateral cordotomy, myelotomy, DREZotomy and cingulotomy are useful interventions for the management of refractory cancer pain. Advanced imaging modalities, including intraoperative computed tomography (CT) guidance, have increased safety and efficacy of these interventions. In this paper, authors review the recent literature regarding surgical interventions for the management of cancer pain.

Value of Repetitive Transcranial Magnetic Stimulation of the Motor Cortex in the Management of Refractory Cancer Pain in Palliative Care: A Case Report

Nathalie Denis, Jean Paul Nguyen, Edwige de Chauvigny, Gérard Dabouis, Emmanuelle Kuhn, Aurélie Lepeintre, Sylvie Raoul, Jean-Jacques Labat, Jean-Pascal Lefaucheur and Julien Nizard-Value of Repetitive Transcranial Magnetic Stimulation of the Motor Cortex in the Management of Refractory Cancer Pain in Palliative Care: A Case Report

Intrathecal infusion of bupivacaine and clonidine provides effective analgesia in a terminally ill child

The intrathecal infusion of drugs to provide analgesia for terminally ill children with refractory pain is a rarely utilized but very effective technique. A number of pharmacological agents, most commonly opioids and local anesthetics, have been administered intrathecally for this purpose. However, tachyphylaxis and neuraxial opioid-related side effects can limit their utility. The alpha-2 agonist clonidine is commonly used to augment local anesthetic techniques for postsurgical pain in children and for the management of refractory cancer pain in adults, but there is only a single report of the use of clonidine intrathecally in a terminally ill child. We present the case of the youngest reported child to have received intrathecal analgesia for terminal care: a 3-year-old boy with advanced pelvic rhabdomyosarcoma, whose refractory pain was managed effectively with an intrathecal infusion of bupivacaine and preservative-free clonidine.

Opioid rotation in the management of refractory cancer pain.

Opioid rotation in the management of refractory cancer pain.

Acute Decreases in Cerebrospinal Fluid Glutathione Levels after Intracerebroventricular Morphine for Cancer Pain

Intracerebroventricular (ICV) morphine administration is effective for the management of refractory cancer pain. Recent preclinical observations of acute depletion of the major endogenous intracellular antioxidant glutathione (GSH) in brain and peripheral organs after ICV morphine in rodents led us to apply microchemical methods to profile the neurochemical effects of ICV morphine in three patients treated for intractable cancer pain. Assessment of morphine, morphine-6-glucuronide, and a panel of endogenous compounds and metabolites in ventricular and cisternal cerebrospinal fluid (CSF) demonstrated transient, postdose increases in morphine and morphine-6-glucuronide in ventricular and cisternal CSF, accompanied by acute decreases in CSF GSH levels. Significant changes were also observed in the CSF levels of 4-hydroxybenzoic acid, homovanillic acid, 5-hydroxyphenyllactic acid, and uric acid. These pilot clinical observations of acute central GSH depletion after ICV morphine suggest a novel mechanism for neuropsychiatric toxicity or preclinical findings, such as hyperalgesia or increased motoric activity observed in nonhuman species after central morphine administration. Because ICV morphine is a mainstay of treatment for refractory cancer pain, elucidation of a mechanism's (or mechanisms') mediating a potential pro-oxidant state in the central nervous system induced by ICV morphine is important. Implications We observed acute decreases in glutathione levels in cerebrospinal fluid sampled from patients after intracerebroventricular doses of morphine for intractable cancer pain. Such doses may, by depleting the antioxidant glutathione, render the central nervous system vulnerable to damage from oxidative stress.

Acute Decreases in Cerebrospinal Fluid Glutathione Levels after Intracerebroventricular Morphine for Cancer Pain

Intracerebroventricular (ICV) morphine administration is effective for the management of refractory cancer pain. Recent preclinical observations of acute depletion of the major endogenous intracellular antioxidant glutathione (GSH) in brain and peripheral organs after ICV morphine in rodents led us to apply microchemical methods to profile the neurochemical effects of ICV morphine in three patients treated for intractable cancer pain. Assessment of morphine, morphine-6-glucuronide, and a panel of endogenous compounds and metabolites in ventricular and cisternal cerebrospinal fluid (CSF) demonstrated transient, postdose increases in morphine and morphine-6-glucuronide in ventricular and cistemal CSF, accompanied by acute decreases in CSF GSH levels. Significant changes were also observed in the CSF levels of 4-hydroxybenzoic acid, homovanillic acid, 5-hydroxyphenyllactic acid, and uric acid. These pilot clinical observations of acute central GSH depletion after ICV morphine suggest a novel mechanism for neuropsychiatric toxicity or preclinical findings, such as hyperalgesia or increased motoric activity observed in nonhuman species after central morphine administration. Because ICV morphine is a mainstay of treatment for refractory cancer pain, elucidation of a mechanism's (or mechanisms') mediating a potential pro-oxidant state in the central nervous system induced by ICV morphine is important. We observed acute decreases in glutathione levels in cerebrospinal fluid sampled from patients after intracerebroventricular doses of morphine for intractable cancer pain. Such doses may, by depleting the antioxidant glutathione, render the central nervous system vulnerable to damage from oxidative stress.

Use of a new novel infusion system for the intrathecal delivery of morphine sulfate in refractory cancer pain management

Use of a new novel infusion system for the intrathecal delivery of morphine sulfate in refractory cancer pain management

Intraspinal therapy in the management of refractory cancer pain

Intraspinal catheter delivery systems are presently utilized in patients with both cancer and non-cancer indications. Patients with cancer pain conditions and a limited life expectancy presently have the widest applicability for the systems. Placement of these systems and subsequent management of the patient's pain represent two different aspects to the care involved with intraspinal catheters. Once the skills are developed for placement of these catheters the practitioner must then develop the skill for subsequent management of the patients' pain. Management issues are much more complex and difficult than placement technique alone. Cancer pain is dynamic in nature and requires a complete knowledge of available agents, routes of administration, and the ability to deal with potential risks and complications. This chapter focuses on these issues, allowing the pain management practitioner a better understanding of catheter systems indicated in particular patient populations. It also describes catheter systems and the subsequent management of pain in patients who have had these systems implanted.