Effects of palliative intrathecal analgesia on patients with refractory cancer bone pain.

This study examined the effects of intrathecal analgesia (ITA) using an extracorporeal pump with a subcutaneous port system in cancer patients with bone metastasis. Among the patients who died of cancer with bone metastasis at the palliative care unit of our institution, 11 who received ITA were selected. Changes in pain, opioid doses, the palliative prognostic index (PPI), and Eastern Cooperative Oncology Group Performance Scale　after ITA were assessed. Pain, opioid doses, and PPI decreased after ITA (P = 0.002, 0.002, and 0.017). ITA for cancer patients with increased PPI due to refractory cancer bone pain decreased pain, opioid doses, and PPI.(100 words).

Oral ketamine for neuropathic cancer pain.

Optimal pain management in patients with advanced cancer often requires multiple pharmacological interventions and multimodal approach. Ketamine is an anaesthetic agent with increasing evidence supporting its use for pain. Due to its N-methyl-D-aspartate antagonism and its activity at opioid receptors, it is an adjuvant to traditional analgesics. Ketamine has a safety profile with limited experience of oral prolonged use in patients with cancer. We report a case of a 40-year-old man with refractory neuropathic cancer-related pain. Opioid rotation to methadone was previously performed, coanalgesics were added, the patient was reluctant to invasive anaesthetic techniques and his pain was poorly controlled. Ketamine was added to attenuate pain keeping functionality. This is a report of a patient with refractory cancer pain treated with methadone and ketamine orally during months, without reported side effects. Ketamine's use to treat pain is increasing along with its evidence of efficacy for long-term oral use.

Ketamine subcutaneous continuous infusion for non-cancer neuropathic pain at home: a case report.

OBJECTIVE: Ketamine is a drug that can effectively treat neuropathic pain by blocking the N-methyl-D-aspartate receptor. It has been studied as a supplement to opioids for cancer pain, but its effectiveness for non-cancer pain is still limited. However, despite its usefulness in managing refractory pain, ketamine is not commonly used for home-based palliative care. METHODS: A case report of a patient with severe central neuropathic pain who was treated with a subcutaneous continuous infusion of morphine and ketamine at home. RESULTS: The introduction of ketamine in the patient's treatment plan effectively controlled pain. Only one possible ketamine side effect was observed and easily treated with pharmacological and non-pharmacological measures. CONCLUSIONS: We have found success in using subcutaneous continuous infusion of morphine and ketamine to alleviate severe neuropathic pain in a home setting. We also observed a positive impact on the patient's family members' personal, emotional and relational well-being after ketamine was introduced.

Topical Diclofenac to Manage Opioid-Refractory Pain in a Rare Pancreatic Fibrosarcoma.

Pancreatic cancer is often diagnosed at an advanced stage and is frequently associated with severe pain. Traditional pain management in this condition may be improved with the use of topical diclofenac. A 39-year-old man with advanced pancreatic fibrosarcoma metastatic to the thoracic spine presented to the hospital with severe abdominal pain refractory to escalating doses of opioids. A celiac plexus block produced significant, yet inadequate, pain reduction. Satisfactory pain control and opioid de-escalation were ultimately achieved with the application of topical diclofenac gel to an area of bony metastasis. This case illustrates the potential for pain control using topical diclofenac in patients with pancreatic soft tissue tumors and vertebral metastases. Topical diclofenac may exert antitumoral effects and targeted application may improve absorption, leading to improved pain control. The use of topical diclofenac for pain management in metastatic pancreatic cancer presents an interesting tool that should be considered in similar cases.

Persistent pain and its predictors after starting anti-tumour necrosis factor therapy in psoriatic arthritis: what is the role of inflammation control?

OBJECTIVE: While considerable focus has been placed on pain due to inflammation in psoriatic arthritis (PsA), less is reported on pain despite inflammation control. Here, we aimed to investigate the occurrence/predictors of persistent pain, including non-inflammatory components, after starting anti-tumour necrosis factor (anti-TNF) therapy. METHOD: Bionaïve PsA patients starting a first anti-TNF therapy 2004-2010 were identified (South Swedish Arthritis Treatment Group register; N = 351). Outcomes included unacceptable pain [visual analogue scale (VAS) pain > 40 mm], and unacceptable pain despite inflammation control (refractory pain; VAS pain > 40 mm + C-reactive protein < 10 mg/L + ≤ 1 swollen joint of 28), assessed at 0, 3, 6, and 12 months. Baseline predictors were estimated by logistic regression. RESULTS: Upon starting anti-TNF therapy, 85% of patients reported unacceptable pain, falling to 43% at 3 months and then remaining stable. After 12 months, refractory pain constituted 63% of all unacceptable pain. Higher baseline VAS pain/global, worse physical function and lower health-related quality-of-life were associated with a higher risk of unacceptable/refractory pain at 12 months. More swollen joints and higher evaluator's global assessment were associated with a lower risk of 12-month refractory pain. CONCLUSIONS: A substantial proportion of PsA patients reported unacceptable pain throughout the first anti-TNF treatment year. At 12 months, refractory pain constituted about two-thirds of this remaining pain load. More objective signs of inflammation at anti-TNF initiation were associated with less future refractory pain. This highlights insufficient effect of biologics in patients with inflammation-independent pain, warranting alternative treatments.

The Use of Ketamine for Malignant and Nonmalignant Chronic Pain in Children: A Review of Current Evidence.

Chronic pain in children continues to pose significant challenges. The pharmacological approach most often revolves around trials and errors, expert opinions, and extrapolation of adult study findings. Ketamine is one of the agents used for chronic pain, especially with a neuropathic component. This article aims to provide an overview of its properties and highlight the current evidence for its use in malignant and nonmalignant chronic pain management. A search on the use of ketamine for chronic pain in children up to 18 years of age covering the period from January 1, 2000, to December 14, 2022, was performed through PubMed, Cochrane Library, EBSCO, EBM Review, Wiley, BMJ, Web of Science, Google Scholar, and the Saudi Digital Library. 218 articles were found and 42 underwent full review. Currently, the evidence about ketamine efficacity and safety for chronic pain management is at best of moderate to low quality. The heterogeinity of ketamine infusion protocols and frequent concomitant use of other analgesics make it difficult to draw robust conclusions. The long-term effect of prolonged usage also remains a concern. Nevertheless, with careful monitoring, the drug may be a reasonable choice for malignant and nonmalignant pain management in selected cases, especially for refractory pain not responding to conventional approaches.

Dexmedetomidine use for patients in palliative care with intractable pain and delirium: A retrospective study.

Patients seen by the palliative care team often have difficult and intractable symptoms. The current standard of practice to manage these symptoms is the deeply sedating midazolam continuous subcutaneous infusion for patients who are expected to expire within hours to days. Dexmedetomidine provides sedation but lacks evidence in palliative care use. This study describes continuous subcutaneous infusion of dexmedetomidine's effect on refractory pain and delirium. Retrospective, observational chart review and conducted in accordance with SQUIRE (quality improvement study). Twenty adult patients (18 years of age or older) with metastatic cancer disease admitted to three palliative complex care units of Fraser Health who received continuous subcutaneous infusion of dexmedetomidine between January 2017 to August 31, 2019. Average length of dexmedetomidine use was 9 days (1/3 length of stay). Eight of the 13 patients with pain symptoms exhibited an overall decline in pain. Four of the 6 patients with delirium had an initial decrease in delirium, but it did not last beyond the first day. Despite progressive clinical deterioration, adjunctive medications decreased or remained the same for 53% of as needed medications and 65% for regularly scheduled medications. Forty-five percent of patients had ≥50% days of rousable sedation. Hypotension occurred in 85% of patients. Dexmedetomidine provided benefit in managing intractable pain while allowing patients to remain rousable, but only had a short effect on delirium symptoms.

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.

BACKGROUND: 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. AIMS: 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. SETTING/PARTICIPANTS: 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). RESULTS: 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). CONCLUSION: 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.

Managing intractable pain with neuraxial infusion at home.

A case study of a 9-year-old child with complex pain secondary to metastatic liver cancer, who eventually required intrathecal drug delivery (ITDD) of analgesia. Multi-modal symptom control strategies were deployed to achieve the child's and parental wishes for end-of-life care (EoLC) at home using ITDD. The following recommendations are made for nursing practice in paediatric palliative care (PPC); rigorous risk assessment, exemplary communication with the identification of a coordinating team, timely training needs assessment and the delivery of training from hospital based experts in ITDD practice, comprehensive symptom management plan and 24/7 access to specialist palliative care teams were essential for safe nursing practice. In this case, robust risk assessment and mitigations enabled challenges to be safely addressed with a successful outcome, extending the boundaries of PPC home care.

Intrathecal Drug Delivery Systems for Cancer Pain Control: Insights on Current Contemporary Practices in the US.

OBJECTIVES: Among patients with cancer with moderate to severe, intractable pain, intrathecal drug delivery using an intrathecal drug delivery system (IDDS) offers effective pain control. In this study, we evaluate the trends of IDDS therapy among patients with cancer, associated comorbidities, complications, and outcomes, using a large representative US administrative inpatient data base. MATERIALS AND METHODS: The Nationwide Inpatient Sample (NIS) data base contains data from 48 states and the District of Columbia. The NIS was used to identify patients with cancer who underwent IDDS implantation between 2016 and 2019. Patients with cancer with intrathecal pumps for the treatment of chronic pain were identified using administrative codes. Baseline demographics, hospital characteristics, type of cancer associated with IDDS implantation, palliative care encounters, hospitalization costs, length of stay, and prevalence of bone pain were evaluated in the study. RESULTS: A total of 22,895 (0.32%) individuals with hospital admission for IDDS surgery were included for analysis among 7.06 million individuals with cancer in the final cohort. The IDDS cohort consisted of patients predominantly in the 65-to-79 years age group (40.49%), female sex (50.42%), and Caucasian ethnicity (75.82%). The top five cancers in patients receiving IDDS were lung (27.15%), colorectal (24.9%), liver (16.44%), bone (8.01%), and liver (7.99%) cancer. In addition, the length of stay was six days (interquartile range [IQR] four-nine days) and the median cost of hospital admission was $29,062 (IQR $19,413-$42,261) in the patients who received an IDDS. These factors were greater than those in patients without IDDS. CONCLUSIONS: A very few patients with cancer received IDDS in the US during the study period. Despite recommendations supporting its use, there are significant racial and socioeconomic disparities in IDDS use.

Assessment of Initial Depressive State and Pain Relief With Ketamine in Patients With Chronic Refractory Pain.

Importance: Repeated ketamine administration is common in treatment-refractory chronic pain, but ketamine analgesic and antidepressant effects are poorly understood in patients with chronic pain with depression symptoms. Objective: To determine clinical pain trajectories with repeated ketamine administrations, exploring whether ketamine dose and/or pretreatment depressive and/or anxiety symptoms may mediate pain relief. Design, Setting, and Participants: This nationwide, multicenter, prospective cohort study included patients in France with treatment-refractory chronic pain who received repeated ketamine administration, over 1 year, according to ketamine use in their pain clinic. Data were collected from July 7, 2016, through September 21, 2017. Linear mixed models for repeated data, trajectory analysis, and mediation analysis were performed from November 15 to December 31, 2022. Interventions: Ketamine administration in cumulative dose (milligrams) over 1 year. Main Outcomes and Measures: Primary outcome was mean pain intensity (0-10 on the Numerical Pain Rating Scale [NPRS]), assessed every month for 1 year by telephone, after inclusion in the hospital. Depression and anxiety (Hospital Anxiety and Depression Scale [HADS]), quality of life (12-item Short Form Health Survey [SF-12]), cumulative ketamine dose, adverse effects, and concomitant treatments were secondary outcomes. Results: A total of 329 patients (mean [SD] age, 51.4 [11.0] years; 249 women [75.7%] and 80 men [24.3%]) were enrolled. Repeated ketamine administration was associated with a decrease of NPRS (effect size = -0.52 [95% CI, -0.62 to -0.41]; P < .001) and an increase of SF-12 mental health (39.7 [10.9] to 42.2 [11.1]; P < .001) and physical health (28.5 [7.9] to 29.5 [9.2]; P = .02) dimension scores over 1 year. Adverse effects were in the normal range. There was a significant difference between patients without and with depressive symptoms in pain diminution (regression coefficient, -0.04 [95% CI, -0.06 to -0.01]; omnibus P = .002 for interaction of time × baseline depression [HADS score ≤7 or >7]). The mediation model showed that ketamine dose was not associated with pain diminution (r = 0.01; P = .61) and not correlated with depression (r = -0.06; P = .32), and that depression was associated with pain diminution (regression coefficient, 0.03 [95% CI, 0.01-0.04]; P < .001), whereas ketamine dose was not (regression coefficient, 0.00 [95% CI, -0.01 to 0.01]; P = .67). The proportion of reduction of pain mediated by baseline depression was 64.6%. Conclusions and Relevance: The findings of this cohort study on chronic refractory pain suggest that depression (and not ketamine dose or anxiety) was the mediator of the association of ketamine with pain diminution. This finding provides radically new insights on how ketamine reduces pain primarily by dampening depression. This reinforces the need for systematic holistic assessment of patients with chronic pain to diagnose severe depressive symptoms where ketamine would be a very valuable therapeutic option.

A National Survey of Institutional Guidelines for the Use of Ketamine, Lidocaine, and Dexmedetomidine for Refractory Pain.

Background: Although opioids are used first line for cancer pain and commonly for complex noncancer pain, there are risks associated with their use and not effective for all types of pain. There's a need to identify and develop clinical practice guidelines for nonopioids for the treatment of refractory pain. Methods: Our study collected information from national clinical practice guidelines for ketamine, lidocaine, and dexmedetomidine with the aim to identify consensus among the different practices. Results: Fifteen institutions nationally participated in the study and only nine of those institutions had guidelines and were permitted by their health system to share them. Of the institutions that participated, 44% had guidelines for ketamine and lidocaine, and only two institutions (22%) had guidelines for ketamine, lidocaine, and dexmedetomidine for refractory pain. There were variations in restriction of the level of care and prescribers, dosing, and determination of efficacy. There were trends of consensus in monitoring for side effects. Conclusion: This study serves as a starting point for a snapshot of the use of ketamine, lidocaine, and dexmedetomidine for refractory pain, but further studies and increased participation of institutions are needed to develop consensus clinical practice guidelines.

Intrathecal drug delivery for cancer pain at the end of life: a case study.

Two-thirds of patients with advanced cancer have pain and, of these, approximately 10-20% do not respond to conventional pain management approaches. This case study concerns a hospice patient who received intrathecal drug delivery for intractable cancer pain at the end of life. This involved working in partnership with a hospital-based interventional pain team. Despite side-effects and complications associated with intrathecal drug delivery and the requirement for inpatient nursing care, intrathecal drug delivery was the best option for the patient. The case identifies the importance of a patient-centred approach to decision-making, effective partnerships between hospice and acute hospital teams, and nurse education as key factors contributing to the provision of safe and effective intrathecal drug delivery.

Intrathecal pain pumps in pain relief.

Chronic pain is a significant global health issue, described as a bio-psychosocial phenomenon that hampers the integration of body, mind, and social functions. To relieve chronic intractable pain, intrathecal drug-delivery devices (IDDDs) are the last resort after conventional treatment options have been exhausted. This article outlines the indications, pharmacological agents, types, techniques, preparation of the patient, and complications of IDDDs for the management of challenging chronic pain (non-neoplastic and cancer-related pain) conditions in patients who have not responded well to a commonly used conventional line of treatment.

Long-Term Dexmedetomidine Use and Safety Profile in Palliative Care: A Case Report.

There is a lack of report of conscious sedation used as a last resort therapy for alleviating severe symptoms. To achieve this goal, dexmedetomidine appears to be a promising option. We report a case of successful two-month long treatment of intravenous (IV) dexmedetomidine added to hydromorphone for intractable cancer pain, restlessness, severe sleep disorder, anxiety, and craving symptoms in a 40-year-old man with active polysubstance use, receiving escalating doses of opioids for intractable abdominal cancer pain together with benzodiazepines. Under dexmedetomidine infusion at 1.2 µg/kg/hour, his symptoms markedly decreased. He could sleep at night and find respite during the day while continuing walking, eating, and other activities. Long-term conscious sedation with IV dexmedetomidine was well tolerated. We did not observe anxiety or agitation rebound during short periods of discontinuation of the infusion. Neither side effects nor tolerance were observed over time. Further research is needed to investigate the indications for conscious sedation and analgesia with dexmedetomidine in palliative patients with a prognosis that is longer than few weeks or uncertain.

The Complex Association of Daily Opioid Dose with Visits for Pain in Sickle Cell Disease: Tolerance or Treatment-Refractory Pain?

INTRODUCTION: Opioids are used for acute and chronic pain in patients with sickle cell disease. How outpatient opioid regimens relate to acute care visits is of interest given the risks of high opioid doses and high hospital utilization. A prior study by our group suggested that outpatient opioid treatment for chronic pain could contribute to a vicious cycle of treatment-refractory acute pain, greater acute care utilization, and escalating opioid doses. The present larger naturalistic observational study was undertaken to determine whether the results were reliable across multiple acute care settings. METHODS: One year of clinical data on patients (n = 291) followed in the Sickle Cell Center for Adults (August 2018 to July 2019) were extracted, including visits to the emergency department, visits to the infusion center, and inpatient admissions. Outpatient opioid dosage was used to predict acute care treatment in generalized linear models that were controlled for patient, disease, and treatment characteristics. RESULTS: Outpatient opioid dosage predicted dosage during visits but did not predict visit length or pain relief. Higher outpatient opioid dosage was associated with greater number of visits. However, in post hoc analyses, this relationship was nonlinear, with a clear positive association only for those prescribed the lowest 50% of dosages. DISCUSSION: Higher outpatient opioid dosage predicted higher dosages during acute care visits to achieve the same pain score improvement, which is more consistent with opioid tolerance than with treatment-refractory pain. The relationship of outpatient opioid dosage with number of acute care visits was more complex, which suggests that opioid consumption at lower levels is driven by intermittent acute pain and opioid consumption at higher levels is driven by chronic pain.

Comparison of external system and implanted system in intrathecal therapy for refractory cancer pain in China: A retrospective study.

INTRODUCTION: Intrathecal therapy (ITT) via an implanted system was demonstrated for the treatment of refractory cancer pain for decades. Recently, the dissemination of ITT is enhanced in an external system way in Asia for a lower implantation cost. This study compares the efficacy, safety, and cost of the two ITT systems in refractory cancer pain patients in China. METHODS: One hundred and thirty-nine cancer pain patients who underwent implantation of the ITT system were included. One hundred and three patients received ITT via the external system (external group), while 36 patients received ITT via the implanted system (implanted group). A 1:2 propensity score matching procedure was used to yield a total of 89 patients for the final analysis. Medical records of included patients were retrospectively reviewed and pain scores, incidences of complications, and costs were compared. RESULTS: ITT via the external system provided pain relief as potent as ITT via the implanted system but was less time-consuming in the implantation phase (13 vs. 19 days, p < .01). Nausea/vomiting and urinary retention were the most frequent adverse events in both external and implanted groups (32.14%, 16.07% vs. 36.36%, 21.21%). No significant difference was found in the incidences of all kinds of complications. Compared to the implanted group, the external group cost less for the initial implantation (7268 vs. 26,275 US dollar [USD], p < .001) but had a significant higher maintenance cost (606.62 vs. 20.23 USD calculated monthly, p < .001). CONCLUSIONS: ITT via the external system is as effective and safe as that via the implanted system and has the advantage of being cheap in the upfront implantation but costs more during the maintenance process in China.

Intrathecal Drug Delivery for the Treatment of Cancer-Associated Chronic Pain in Children.

OBJECTIVES: Management of refractory cancer-associated pain can be particularly challenging. Regional anesthesia is an alternative modality to treat acute and chronic refractory pain. Intrathecal (IT) drug delivery of opioids and other adjuncts has been used to treat refractory cancer-associated pain. This method has been shown to be relatively safe and effective, often associated with fewer systemic side effects when compared to oral or IV opioid administration. While intrathecal drug delivery systems (IDDS) are regularly used in the adult cancer population for the treatment of refractory, chronic pain, there is limited evidence of similar use in the pediatric setting. MATERIALS AND METHODS: We performed a systematic review using conventional Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology to identify studies reporting IT drug delivery for the treatment of pediatric cancer-related pain. The primary outcome was satisfaction with analgesia categorized as "satisfactory" or "unsatisfactory." Functional benefits, previous systemic pharmaceutical interventions, previous non-IT regional interventions, indication for IT drug delivery, IT drugs used, and method of delivery were collected. RESULTS: A total of 11 studies were identified, describing 16 patients with cancer-related pain treated with IT drug delivery. The average age of the cohort was 12.25 years, with ages ranging from 3 to 19 years. Most patients were adolescent (10/16). All patients had cancer diagnoses, with most patients suffering from solid tumor pain (14/16). Nearly all patients achieved satisfactory analgesia through IT drug delivery (15/16) and most reported functional benefits in addition to analgesia (13/16). Majority received IT drugs via external catheters (9/16). One severe complication of respiratory depression was reported, which resolved following naloxone administration. CONCLUSIONS: There exist children with cancer whose pain is refractory to the standard approaches and may benefit from IT drug delivery. The existing data, although limited and of low tier evidence, suggest that IT drug delivery has been effective in the pediatric cancer population.