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.

Challenges to heart failure medication prescribing post-hospitalization.

OBJECTIVES: To determine the prevalence of heart failure (HF) medication prescribing on discharge post-HF-related admission. METHODS: A retrospective audit was conducted for 216 HF admissions over a period of 6 months; medication data from electronic records were collected for analysis. KEY FINDINGS: The prevalence of HF medication prescribing on discharge was: 32.9% (95% confidence interval: 26.6-39.6) renin-angiotensin-aldosterone system inhibitors, 10.6% (6.9-15.6) angiotensin receptor-neprilysin inhibitors, 31.5% (25.4-38.1) HF-specific beta-blockers, 42.6% (35.9-49.5) aldosterone receptor antagonists, and 11.6% (7.6-16.6) sodium-glucose cotransporter-2 inhibitors. CONCLUSION: HF medication prescribing remains relatively low despite the known benefits and recommendations listed in the guidelines.

Methadone rotation versus other opioid rotation for refractory cancer induced bone pain: protocol of an exploratory randomised controlled open-label study.

BACKGROUND: A third of patients with advanced cancer and bone metastasis suffer from cancer induced bone pain (CIBP), impeding quality of life, psychological distress, depression and anxiety. This study will evaluate the impact of an opioid rotation, comparing methadone rotation with other opioid rotation in patients with refractory CIBP. METHODS: This open-label randomised controlled trial will recruit cancer patients with CIBP and inadequate pain control despite established baseline opioid and/or intolerable opioid side effects from cancer and palliative care services. Participants will be at least 18 years old, with a predicted prognosis of greater than 8 weeks, meet the core diagnostic criteria for CIBP, have a worst pain score of ≥ 4 of 10 from CIBP and/ or have opioid toxicity (graded ≥ 2 on Common Terminology Criteria for Adverse Events). Participants will have sufficiently proficient English to complete questionnaires and provide informed consent. Participants will be randomised 1:1 to be rotated to methadone to another opioid. The primary objective is to examine the impact of opioid rotation in improving CIBP by comparing analgesic efficacy, safety and tolerability in the two arms. Secondary objectives will assess changes in the intensity, duration and frequency of breakthrough pain, requirement of breakthrough analgesia, overall opioid escalation index, and time taken to observe improvement in pain reduction, pain interference and quality of life. DISCUSSION: Laboratory studies suggest the involvement of neuropathic involvement in the mechanism of CIBP, though there remains no clear evidence of the routine use of neuropathic agents. Methadone as an analgesic agent may have a role to play in this cohort of patients, thus warranting further exploratory studies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry No: ACTRN12621000141842. Registered 11 February 2021.

The role of methadone in cancer-induced bone pain: a retrospective cohort study.

PURPOSE: Cancer-induced bone pain (CIBP) can be challenging to manage in advanced cancer. The unique properties of methadone may have a role in refractory CIBP. We aimed to evaluate the analgesic effects of methadone for CIBP when other opioids are ineffective or intolerable. METHODS: A retrospective study of palliative care inpatients rotated to methadone from another opioid for CIBP over a 4-year period. Primary outcome was ≥ 30% reduction in pain intensity (11-point numeric rating scale) from baseline to completion of methadone rotation (MR). Secondary outcomes were ≥ 50% reduction in pain intensity and changes in long-acting and breakthrough opioid requirements. RESULTS: Ninety-four eligible patients completed MR for the following reasons: poor pain control (72.3%), opioid toxicities (4.3%) or both (23.4%). On completion of MR, 70.2% and 53.2% achieved a ≥ 30% and ≥ 50% reduction in pain respectively, with mean pain intensity score reduced from 5.6 (SD = 2.1) at baseline to 2.6 (SD = 2.5) (p < 0.001). Mean calculated daily methadone dose pre-MR was 25.7 mg (SD = 10.9), with 72.3% of patients requiring a lower dose on completion of MR (mean 17.0 mg, SD = 8.5). The mean number of breakthrough opioid analgesia used a day reduced from 3.4 (SD = 2.3) to 1.8 (SD = 1.7) (p < 0.001). CONCLUSIONS: MR for CIBP may result in reduction in pain intensity, when other opioids are ineffective or intolerable, with patients requiring reduced overall dosing of their long-acting opioid and frequency of breakthrough opioid use.

Propofol for palliative sedation.

Palliative sedation is the intentional use of sedatives to manage refractory symptom(s), such as pain and/or terminal restlessness. This case report describes the successful use of propofol, an ultra-fast-acting anaesthetic agent commonly used for anaesthesia induction and maintenance to manage refractory agitated delirium in an acute inpatient palliative medicine setting.