Dexmedetomidine Combined With Patient-Controlled Analgesia for Palliative Sedation in Terminal-Stage Cancer Patients With Refractory Pain: A Retrospective Analysis of Nine Cases.

Background: Cancer-related pain is a pervasive symptom affecting the quality of life in patients with malignant tumors. For those with refractory pain, palliative sedation combined with pain management is recommended. Dexmedetomidine (DEX), known for its unique "awake sedation" effect, remains relatively unexplored when used in conjunction with patient-controlled analgesia (PCA) for terminal-stage cancer patients. This study aimed to assess the safety and efficacy of DEX for palliative sedation with PCA in patients experiencing refractory pain. Methods: A retrospective analysis was conducted on terminal-stage cancer patients who received DEX for palliative sedation combined with PCA in a hospice ward between January 2020 and June 2023. Data collection included general patient information, laboratory tests, rating scales, pain and analgesia conditions, sedation details, palliative sedative effects, and changes in vital signs before and after sedation. Results: Nine patients with terminal-stage cancer received DEX palliative sedation at doses ranging from 0.2 to 1.0 µg/kg·h combined with PCA for refractory pain. After 1 h of sedation and at the maximum sedation dose, the Richmond Agitation-Sedation Scale scores significantly decreased (all p < 0.001). While heart rate, blood oxygen saturation, and respiratory rate remained stable, systolic blood pressure and diastolic blood pressure after 1 h of sedation were significantly lower than presedation levels (p = 0.040 and p = 0.044, respectively). Conclusion: DEX emerges as a promising option for palliative sedation in terminal-stage cancer patients. When used in conjunction with PCA, DEX has been shown to effectively, safely, and stably control refractory pain without inducing adverse effects such as respiratory/circulatory depression.

Intravenous Lidocaine for Refractory Pain in Patients With Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Multicenter Prospective Nonrandomized Pilot Study.

INTRODUCTION: Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively. METHODS: Multicenter prospective nonrandomized pilot study included patients with moderate or severe pain (Numeric Rating Scale ≥ 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5 mg/kg was followed by continuous infusion at 1.5 mg/kg/hr. The dose was raised every 15 minutes until treatment response (up to a maximum 2 mg/kg/hr) and consecutively administered for 2 hours. Primary outcome was the mean difference in pain severity, preinfusion, and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease ≥1.3 points was considered clinically relevant. RESULTS: Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day 1 was 1.1 (SD ± 1.3) points for patients with PDAC and 0.5 (SD ± 1.7) for patients with CP. A clinically relevant decrease in BPI on day 1 was reported in 9 of 29 patients (31%), and this response lasted up to 1 month. No serious complications were reported, and only 3 minor complications (vertigo, nausea, and tingling of mouth). Treatment with lidocaine did not impact quality of life. DISCUSSION: Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group.

Buprenorphine: Opioid Agonist-Antagonist for Refractory Pain of Sickle Cell Disease Patients During Hematopoietic Stem Cell Transplant, Uncontrolled By Full-Agonist Opioids.

BACKGROUND: Bone marrow transplant (BMT) offers potential cure for cancer and a spectrum of otherwise incur- able diseases. The BMT process can cause multi-systemic pain in patients with sickle cell disease (SCD) refractory to high-dose opioid analgesics during BMT because of their pre-existing opioid-tolerance. Because of frequent pain resulting in hyperalgesia and chronic opioid use, SCD patients undergoing BMT often experience excruciating pain uncontrolled by exceedingly high-dose opioids with severe and intolerable adverse effects. PURPOSE/HYPOTHESIS: There is a small but growing body of literature about the successful buprenorphine effect for SCD's chronic pain management that had failed sufficient pain relief by the traditional full-agonist opioids in the outpatient setting. However, the buprenorphine use for acute inpatient pain management has not been previously researched. Pilot prospective clinical trial with buprenorphine-based pain management for acute BMT-related pain was initiated for SCD patients' pain uncontrolled by full-agonist opioids. Procedures/data/observations: Buprenorphine was started as scheduled and as-needed analgesics, supplemented by full-agonist opioids upon consultation for uncontrolled BMT-related pain of SCD patients. Patients' 24-hour opioid requirement by morphine equivalent daily doses (MEDD) were assessed at 3 time points: 1)immediately before pain escalation; 2)consultation; 3)discharge. MEDDs were compared to those of patients treated with full-agonist opioids only. Cases treated by full-agonist opioids (morphine/hydromorphone/fentanyl/methadone/oxycodone) had MEDD escalation by 1230-16300% by discharge compared to immediately before BMT-related pain escalation. Buprenorphine-supported cases had significantly smaller MEDD increase by 220-317%. CONCLUSIONS/APPLICATIONS: Our case series suggests superior pain control by adding Buprenorphine prior to opioid dose escalation during BMT for SCD. Buprenorphine may provide the advantageous effect for other patients with complex pain background and experiencing difficult pain management during BMT due to pre-existing hyperalgesia and high opioid-tolerance. The evidence for buprenorphine's analgesic effect is moderate but growing, and more randomized controlled trials comparing the buprenorphine and other standard opioids are needed.

Clinical observation of the treatment of refractory cancer pain with cancer pain information platform and IDDS under home analgesia mode: A retrospective study.

To evaluate the effectiveness and safety of a cancer pain information platform combined with semi-implantable intrathecal drug delivery systems among the patients with refractory cancer pain under a "home analgesia" model. This was a retrospective study. A total of 49 patients underwent semi-implantable intrathecal drug delivery systems with patient-controlled analgesia in conjunction with the establishment of a cancer pain information platform. Numeric rating scales (NRS), Bruggrmann comfort scale (BCS), high-quality sleep duration, and opioid-related adverse effects were recorded at various time points and analyzed: the day on admission (T0), the day of discharge (T1), 30 days post-discharge (T2), 60 days post-discharge (T3), 90 days post-discharge (T4), 120 days post-discharge (T5), 150 days post-discharge (T6), 180 days post-discharge (T7), and the day before death (T8). Compared with T0, NRS significantly decreased and BCS significantly increased at T1 to T8 time points (P < .05). However, NRS and BCS did not show differences at T1 to T8 time points (P > .05). The duration of high-quality sleep was significantly extended, and the incidence of opioid-related adverse effects was significantly reduced. Postoperative complications included 1 case of cerebrospinal fluid leakage, 3 cases of infection at the butterfly needle insertion site, 6 cases of hospital readmission for equipment malfunction, and no cases of respiratory depression. Eleven patients continued standardized antitreatment after IDDS surgery. The mean survival time for all patients was 135.51 ±â€…102.69 days, and the survival rate at T7 was 30.61%. The cancer pain information platform combined with semi-implantable IDDS is beneficial for the pain management of refractory cancer patients under the "home analgesia" model, improving their quality of life.

A nationwide neurosurgical inter-disciplinary service for cancer-related refractory pain.

PURPOSE: Neurosurgical ablative procedures, such as cordotomy and cingulotomy, are often considered irreversible and destructive but can provide an effective and individualized solution for cancer-related refractory pain, when all other approaches have been unsuccessful. This paper provides an in-depth exploration of a novel approach to managing refractory cancer pain. It involves an interdisciplinary team led by a neurosurgeon at a renowned national referral center. METHODS: a retrospective analysis of the medical records of all sequential patients who underwent their initial evaluation at our interdisciplinary refractory cancer pain clinic from February 2017 to January 2023. RESULTS: A total of 207 patients were examined in the clinic for a first visit during the study period. All patients were referred to the clinic due to severe pain that was deemed refractory by the referring physician. The mean age was 61 ± 12.3 years, with no significant sex difference (P = 0.58). The mean ECOG Performance Status score was 2.35. Conservative measures had not yet been exhausted in 28 patients (14%) and 9 patients were well controlled (4%). Neurosurgical ablative procedures were recommended for 151 (73%) of the patients. Sixty-six patients (32%) eventually underwent the procedure. 91 patients (44%) received a negative recommendation for surgery. Thirty-five patients (17%) were referred for further invasive procedures at the pain clinic. CONCLUSION: An Interdisciplinary cooperation between palliative care specialists, pain specialists, and neurosurgeons ensures optimal patient selection and provides safe and effective neurosurgery for the treatment of refractory cancer-related pain.

Analgesic treatment for refractory cancer pain caused by gastric cancer bone metastasis: A case report and literature review.

RATIONALE: Patients with bone metastasis-associated cancer pain often experience a complex mix of pain types. Consequently, the use of multimodal combination therapy is essential. While monitoring for common adverse reactions in pain treatment, it is also crucial to be vigilant for the rare but serious serotonin syndrome. PATIENT CONCERNS: A 53-year-old female with metastatic gastric cancer was hospitalized due to severe, uncontrolled thoracic and cervical pain. During the titration of her cancer pain medication, she developed serotonin syndrome. DIAGNOSES: He was diagnosed with refractory cancer pain and serotonin syndrome. INTERVENTIONS: The complete process of cancer pain medication in a patient with gastric cancer and bone metastasis was analyzed, with a primary focus on the selection of analgesic medications, adjustment of opioid dosages, and prevention and treatment of medication-associated adverse reactions. OUTCOMES: The patient's cancer pain was well controlled, with the prompt management of adverse reactions. Furthermore, by adjusting the medication regimen, intolerable adverse reactions were prevented. LESSONS: In clinical settings, personalized analgesic regimens must be developed for patients with cancer pain to enhance patient compliance with medication, prevent the occurrence of severe adverse reactions, and improve the overall quality of life of patients with cancer. Healthcare professionals should pay increased attention to ADRs associated with opioid medications, whereas pharmacists should assist them in promptly identifying ADRs.

Methadone versus other opioids for refractory malignant bone pain: a pilot randomised controlled study.

PURPOSE: Refractory cancer-induced bone pain (CIBP) affects a patient's functional capacity and quality of life, but there is limited evidence to guide opioid choice. We assessed the feasibility, tolerability and possible efficacy of methadone rotation (MR) compared to other opioid rotations (OOR) in this cohort. METHODS: Adults with CIBP and worst pain intensity ≥ 4/10 and/or opioid toxicity graded ≥ 2 on the Common Terminology Criteria for Adverse Events were randomised 1:1 to methadone or another opioid rotation. Standardised assessment tools were used at pre-defined study time points up to 14 days. RESULTS: Of 51 eligible participants, 38 (74.5%) consented, and 29 (76.3%, MR: 14, OOR: 15) completed the fourteen days follow-up post-opioid rotation. Both groups displayed significant reduction in average (MR: d = - 1.2, p = 0.003, OOR: d = - 0.8, p = 0.015) and worst pain (MR: d = - 0.9, p = 0.042, OOR: d = - 0.6, p = 0.048) and total pain interference score (MR: d = - 1.1, p = 0.042, OOR: d = - 0.7, p = 0.007). Oral morphine equivalent daily dose was reduced significantly in MR compared to the OOR group (d = - 0.8, p = 0.05). The incidence of opioid-related adverse events following MR was unchanged but lower in the OOR group (d = 0.9, 95% CI 0.1,1.7, p = 0.022). There were no within-group or between-group differences in satisfaction with analgesia at the end of the study. CONCLUSION: This pilot study demonstrated that MR and OOR in patients with refractory CIBP are feasible, safe and acceptable to patients. Appropriately powered multi-centre randomised controlled studies are needed to confirm the efficacy of MR and OOR in this cohort. TRIAL REGISTRATION: ACTRN12621000141842 registered 11 February 2021.

Effectiveness of Radiofrequency Ablation of the Genicular Nerves of the Knee for the Management of Intractable Pain from Knee Osteoarthritis.

BACKGROUND: The knee joint is one of the most common diseases in elderly individuals. This is a progressive and debilitating condition. The purpose of knee osteoarthritis treatment is to manage pain, increase mobility, and improve the quality of life. OBJECTIVES: This study evaluated the therapeutic effect of radiofrequency thermocoagulation (RFTC) on the genicular nerves in patients with intractable pain due to knee osteoarthritis, as well as its effects on pain severity and magnetic resonance imaging (MRI) findings. STUDY DESIGN: A prospective outcome study. SETTING: The outpatient clinic of a single academic medical center. METHODS: We conducted a prospective study. Fifty consecutive patients with intractable knee pain due to osteoarthritis were enrolled and underwent ultrasound (US)-guided RFTC of the genicular nerves (medial superior genicular nerve, medial inferior genicular nerve, and lateral superior genicular nerve). Pain severity was measured using the Numeric Rating Scale (NRS), and knee osteoarthritis-associated symptoms were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at pretreatment and one, 3, and 6 months after RFTC treatment. We also analyzed the relationship between therapeutic outcomes and pain severity based on pre-treatment and knee MRI findings. RESULTS: No dropouts were observed. The most significant reduction in knee symptoms associated with knee osteoarthritis was observed after one month of treatment; however, at 3 and 6 months, there was a rebound effect, leading to a decrease in therapeutic efficacy. Nonetheless, there was still a noticeable decrease in symptoms due to knee osteoarthritis compared to those prior to RFTC treatment. The effect of RFTC treatment was better when pre-treatment pain was relatively less severe, knee effusion was not severe, there were no meniscal tears in the middle or posterior zones, no bone marrow edema in the middle and posterior zones of the femur and tibia, and no severe cartilage defects in the posterior femur and middle and posterior tibia. LIMITATIONS: We conducted our study without a control or a placebo group. CONCLUSION: RFTC of the genicular nerve is a good therapeutic option for controlling intractable pain following knee osteoarthritis. In addition, we found that a lower level of pain prior to treatment, along with the absence or lesser degree of knee joint effusion, as well as an absence or less severe middle or posterior knee pathologies associated with knee osteoarthritis, can predict a more favorable therapeutic outcome.

Ganglion impar block in chronic cancer-related pain - A review of the current literature.

Oncologic chronic pain is often difficult to control, especially in anatomical areas with multiple and complex innervation, such as the pelvic/perineal region. The ganglion impar block (GIB) is a procedure with growing interest and varied applicability. It has been used in several benign and malignant causes of pelvic and perineal pain refractory to pharmacological treatment. We conducted a review of all articles published in PUBMED® until the 30th of October 2022 regarding GIB in oncologic pain. 19 articles were identified with a total of 278 patients. Both chronic cancer pain and chronic postcancer treatment pain patients were included. We reviewed the various techniques, approaches, and therapeutic options that were employed. No serious adverse effects were reported. GIB appears to be an effective and safe procedure that should be considered in patients with intractable perineal cancer-related pain.

Calciphylaxis and Intractable Pain in a Veteran with Psychological Trauma History.

Guidelines are lacking for patients with calciphylaxis on renal replacement therapy, often leading to difficulty optimally treating these patients. A 60-year-old male veteran receiving hemodialysis presented with calciphylaxis of the left lower extremity and intractable pain. His condition was complicated by chronic back pain, long-term opioid therapy, and psychological trauma history. He was ultimately transferred to a calciphylaxis treatment center but was unable to tolerate further treatments due to sepsis and hemodynamic instability. He was transitioned to comfort measures and died in the hospital. Addressing complicated pain physiologies and complex trauma is challenging even in well-resourced tertiary medical centers. Despite the availability of calciphylaxis therapies and trauma-informed care, there remains a high rate of suffering and mortality in this patient population. There is much work to be done in this cohort, particularly when considering the implications of past traumatic experiences on health care engagement and pain management.

Everything old is new again. revisiting hypophysectomy for the treatment of refractory cancer-related pain: a systematic review.

Cancer-related pain is a common and debilitating condition that can significantly affect the quality of life of patients. Opioids, NSAIDs, and antidepressants are among the first-line therapies, but their efficacy is limited or their use can be restricted due to serious side effects. Neuromodulation and lesioning techniques have also proven to be a valuable instrument for managing refractory pain. For patients who have exhausted all standard treatment options, hypophysectomy may be an effective alternative treatment. We conducted a comprehensive systematic review of the available literature on PubMed and Scielo databases on using hypophysectomy to treat refractory cancer-related pain. Data extraction from included studies included study design, treatment model, number of treated patients, sex, age, Karnofsky Performance Status (KPS) score, primary cancer site, lead time from diagnosis to treatment, alcohol injection volume, treatment data, and clinical outcomes. Statistical analysis was reported using counts (N, %) and means (range). The study included data from 735 patients from 24 papers treated with hypophysectomy for refractory cancer-related pain. 329 cancer-related pain patients were treated with NALP, 216 with TSS, 66 with RF, 55 with Y90 brachytherapy, 51 with Gamma Knife radiosurgery (GK), and 18 with cryoablation. The median age was 58.5 years. The average follow-up time was 8.97 months. Good pain relief was observed in 557 out of 735 patients, with complete pain relief in 108 out of 268 patients. Pain improvement onset was observed 24 h after TSS, a few days after NALP or cryoablation, and a few days to 4 weeks after GK. Complications varied among treatment modalities, with diabetes insipidus (DI) being the most common complication. Although mostly forgotten in modern neurosurgical practice, hypophysectomy is an attractive option for treating refractory cancer-related pain after failure of traditional therapies. Radiosurgery is a promising treatment modality due to its high success rate and reduced risk of complications.

Intrathecal morphine delivery at prepontine cistern to control refractory cancer-related pain: a case report of extensive metastatic and refractory cancer pain.

BACKGROUND: Extensive metastatic and refractory cancer pain is common, and exhibits a dissatisfactory response to the conventional intrathecal infusion of opioid analgesics. CASE PRESENTATION: The present study reports a case of an extensive metastatic esophageal cancer patient with severe intractable pain, who underwent translumbar subarachnoid puncture with intrathecal catheterization to the prepontine cistern. After continuous infusion of low-dose morphine, the pain was well-controlled with a decrease in the numeric rating scale (NRS) of pain score from 9 to 0, and the few adverse reactions to the treatment disappeared at a low dose of morphine. CONCLUSIONS: The patient achieved a good quality of life during the one-month follow-up period.

Palliative Radiofrequency Ablation Therapy for Intractable Cancer-Related Pain Due to Malignant Psoas Syndrome: Case Report.

Uncontrollable cancer pain is a highly feared and debilitating symptom. The effectiveness of radiofrequency ablation (RFA) for osseous metastases with intractable cancer-related pain refractory to pharmacological therapy has been reported previously. This case report is the first to demonstrate the use of RFA to achieve pain relief in a patient suffering severe pain caused by para-aortic lymph node metastasis. A 55-year-old male complained of intractable pain in the left groin and perineum due to malignant psoas syndrome caused by metastatic para-aortic lymph nodes. The pain was refractory to medications including opioids and nerve blocks. Considering the dermatome indicating referred pain and the imaging findings, RFA of the area of invasion was performed at the L3 level. The severe pain was relieved within 24 hours without any complications. Opioids were tapered at each postoperative outpatient visit. We discuss the use of RFA for control of intractable cancer-related pain refractory to medication, including opioids.

Effectiveness of CT-guided percutaneous cordotomy in intractable cancer pain: Experience in 14 patients.

BACKGROUND: Severe and treatment-resistant pain is a major issue for patients with cancer. Cordotomy is an effective approach for addressing severe cancer-related pain. It is based on blocking the transmission of pain by damaging the lateral spinothalamic tract. METHODS: Computed tomography guided cordotomy was performed on 14 patients who did not respond to medical and interventional pain management methods. RESULTS: Fourteen patients with cancer pain underwent CT-guided percutaneous cordotomy. Pain relief was reported in 86% of the patients. The visual analog scale values before and after cordotomy were compared and a significant difference was found (p = 0.0001). The improvement in the Karnofsky Performance Scale score of the patients was found to be statistically significant (p = 0.0001). CONCLUSION: We believe that CT-guided cordotomy, performed by experienced hands in a team of experienced individuals and applied to the right patients, is an effective treatment. However, it is crucial to exercise extreme caution regarding potential side effects and serious complications during the cordotomy procedure.

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.

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.

Ultrasound-guided pericapsular nerve group and obturator nerve phenol neurolysis for refractory inpatient hip cancer metastasis pain: a case report

Abstract Introduction: Bone cancer metastasis may produce severe and refractory pain. It is often difficult to manage with systemic analgesics. Chemical neurolysis may be an effective alternative in terminally ill patients. Case report: Female terminally ill patient with hip metastasis of gastric cancer in severe pain. Neurolytic ultrasound-guided blocks of the pericapsular nerve group and obturator nerve were performed with 5% phenol. This led to satisfactory pain relief for 10 days, until the patient's death. Discussion: This approach may be effective and safe as an analgesic option for refractory hip pain due to metastasis or pathologic fracture in terminally ill patients.