Background: Continuous subcutaneous infusion (CSCI) via ambulatory infusion pump (AIP) is a valuable method of pain control in palliative care. When using CSCI, low-dose methadone as add-on to other opioids might be an option in complex pain situations. This study aimed to investigate the effects, and adverse effects, of CSCI for pain control in dying patients, with particular interest in methadone use.
Methods: his was an observational cohort study. Imminently dying patients with pain, admitted to specialized palliative inpatient wards and introduced on CSCI, were monitored daily by staff for symptoms (Integrated Palliative Care Outcome Scale - IPOS), sedation (Richmond Agitation and Sedation Scale – RASS), performance status (Eastern Cooperative Oncology Group - ECOG) and delirium (Confusion Assessment Method - CAM).
Results: Ninety-three patients with a median survival of 4 days were included. Of the 47 patients who survived =3 days, the proportion of patients with severe/overwhelming pain decreased from 45 to 19% (p < 0.001) after starting CSCI, with only a moderate increase in morphine equivalent daily dose of opioids (MEDD). Alertness was marginally decreased (1 point on the 10-point RASS scale, p = 0.001), whereas performance status and prevalence of delirium, regardless of age, remained unchanged.
Both patients with methadone as add-on (MET, n = 13) and patients with only other opioids (NMET, n = 34), improved in pain control (p < 0.05 and 0.001, respectively), despite that MET patients had higher pain scores at baseline (p < 0.05) and were on a higher MEDD (240 mg vs.133 mg). No serious adverse effects demanding treatment stop were reported.
Conclusions: CSCI via AIP is an effective way to reduce pain in dying patients without increased adverse effects. Add-on methadone may be beneficial in patients with severe complex pain.
This article discusses the practicalities of syringe drivers (subcutaneous continuous infusion pumps) for symptom control in patients requiring palliative or end-of-life care, which may form part of an advance care plan. It includes a discussion of palliative and end-of-life care, advance care planning, and when a syringe driver might be beneficial for the patient. It also provides step-by-step clinical guidance on setting up a syringe driver.
BACKGROUND: The marketing authorisation for many injectable drugs used in palliative care does not cover the frequently preferred subcutaneous route. Consequently, subcutaneous off-label drug administration is often practised.
AIM: To assess the use, safety and tolerability of subcutaneous label and subcutaneous off-label drug administration in a Danish hospice.
MATERIAL AND METHODS: Retrospective data from hospice inpatient records registered with subcutaneous drug administration. Prospective data of subcutaneous drug administration registered to hospice inpatients over a period of 2 months.
RESULTS: Drugs were administered subcutaneously to 90% of patients in both studied cohorts. Thirty different drugs were administered subcutaneously. Ten (33%) drugs were authorised for subcutaneous administration, 14 (47%) for intramuscular and 6 (20%) for intravenous administration only. A search in major palliative literature and scientific publications revealed that 11 of the 20 subcutaneous off-labelled drugs were administered with little to no support from these sources. In seven patients, 11 adverse drug reactions (ADRs) were registered. ADRs were all minor local reactions and led to drug discontinuation in two patients only.
CONCLUSION: Subcutaneous drug administration was frequently used in the hospice. Two-thirds of the drugs were administered subcutaneously off-label. The findings of only a few and minor ADRs indicate that the drugs identified in this study, although often subcutaneously off-label and with little support from palliative literature, were administered with acceptable safety and tolerability. Off-label treatment practised in the clinic should be identified, reported and serve as inspiration for future scientific research and incentives for extension of marketing authorisations.
Quality of life is a major consideration in children's palliative care, particularly at the end of life. Optimal symptom management is crucial in maintaining quality of life, with the aim being to ensure the child is as comfortable as possible. Ensuring adequate hydration will often be part of symptom management but may be associated with several practical and ethical challenges. Subcutaneous fluid administration in children's palliative care is relatively uncommon, so there is a lack of evidence on the topic. This article demonstrates that it is feasible to use subcutaneous fluid therapy in the children's hospice setting to address patients' hydration needs and manage their symptoms. It presents a case study of a child who received subcutaneous fluids in a children's hospice for dehydration and myoclonus. It uses the case study to discuss subcutaneous fluid therapy in the children's palliative care setting, including its indications and contraindications, administration, complications and important factors to consider.
Objectives: Common terminal phase symptoms include pain, dyspnoea, anxiety, terminal restlessness, nausea and noisy breathing. This study identified the proportion of community pharmacies across two Australian states stocking medicines useful in managing terminal phase symptoms, while exploring factors considered predictive of pharmacies carrying these medicines.
Methods: Community pharmacies from across the states of New South Wales (NSW) and South Australia (SA) were concurrently mailed a survey. Respondents were asked questions relating to medicines stocked, expiry date of stock, awareness of people with palliative care needs and demographic characteristics of the pharmacy. A ‘prepared pharmacy’ was defined as a pharmacy that held medicines useful in the management of terminal phase symptoms.
Results: The proportion of prepared pharmacies across NSW and SA was 21.9%. Multiple logistic regression demonstrated eight predictors of prepared pharmacies, of which awareness of people with palliative needs using their service was the strongest.
Conclusions: One-fifth of community pharmacies carry formulations useful in managing terminal phase symptoms. The main factor associated with this was awareness of people with palliative needs using the pharmacy. Strategies that engage with pharmacists in anticipation of the terminal phase are critical, supporting people with palliative needs to remain at home to die, if desired.
Background: Intravenous lidocaine infusions have been shown to be effective for cancer related pain, but access is restricted to acute care settings. If able to be shown to be safe and effective, the subcutaneous route could expand access to residential hospices or patients' homes.
Objectives: This randomized, double-blind, placebo controlled, 2 × 2 crossover trial evaluated the effectiveness, safety, toxicity, and impact on quality of life of a limited duration subcutaneous lidocaine infusion (SCLI) for chronic cancer pain.
Mthods: Patients with the life expectancy of three months or more, who were experiencing cancer-related pain with a worst severity of at least 4 on a 0–10 scale despite a trial of at least one opioid and appropriate adjuvant analgesic, received two subcutaneous infusions at least a week apart; lidocaine 10 mg/kg over 5.5 hours and saline placebo. The primary outcome was either a reduction in worst pain intensity of two points out of 10 or a reduction in 24 hours opioid dose of at least 30% without worsening of pain scores, in seven days.
Results: The SCLI was only effective for two subjects. One of these subjects experienced a drop in worst pain score and the other experienced a reduction in opioid dose.
Conclusions: A weight-based subcutaneous infusion of lidocaine does not achieve sufficiently predictable blood levels for determining lidocaine responsiveness. This study does not allow any conclusion to be drawn on whether or not lidocaine would have been more effective had it been titrated to higher blood levels.
BACKGROUND: Depressive disorders are common among cancer patients. Ketamine can quickly relieve depression, and its subcutaneous administration appears to be as effective as and probably safer than its standard intravenous administration. Herein, we report a case verifying the antidepressant effect of a subcutaneous esketamine formulation.
CASE PRESENTATION: A 65-year-old male with metastatic abdominal tumor reported sadness, weight loss, fatigue, hopelessness, insomnia, inattention, and reduced motivation. His scores on the visual analogical scale for pain and Montgomery-Asberg depression rating scale were 8/10 and 30/60, respectively.
POSSIBLE COURSES OF ACTION: Monoaminergic antidepressants are effective, but their response is slow for end-of-life care.
FORMULATION OF A PLAN: Esketamine was preferred because it possibly contributes to pain relief. It can repeatedly be infused intravenously, but was subcutaneously administered twice a week for safety reasons.
OUTCOME: The patient showed continuous mood improvement, achieving depression remission on day 7. Pain relief was observed but without stability. His vital signs remained stable, and he remained calm, without major complaints.
LESSONS FROM THE CASE: Repeated subcutaneous esketamine injections are possibly safe and effective in pain and depression relief in palliative care cancer patients.
VIEW ON RESEARCH PROBLEMS, OBJECTIVES, OR QUESTIONS GENERATED BY THE CASE: Placebo-controlled studies with similar cases are needed to establish efficacy and safety.
OBJECTIVES: The purpose of this quality improvement (QI) project was to improve the overall process of implementing continuous subcutaneous infusion of opioids (CSCIOs) at the West Palm Beach Veterans Affairs Medical Center and characterize their use in the hospice unit.
METHODS: A retrospective chart review from July 2014 to August 2017 was conducted to identify patients who had received CSCIO. Results were analyzed with descriptive statistics.The business philosphy, LEAN methodology "The 5 Whys" was utilized to identify the root causes for delayed infusion timeliness and corrections were implemented by August 2018. Follow-up retrospective time study completed from September 2018 to February 2019.
RESULTS: Of the 107 patients identified, 7 were excluded and 100 were reviewed. The mean age was 73 years, 94% male, and 86% Caucasian. A total of 55 veterans received morphine with an average final infusion rate of 2.5 mg/h. A total of 45 Veterans received hydromorphone with a final infusion rate of 1.3 mg/h. The average infusion duration until death was 5 days. Pharmacy verified 94 (94%) orders and nursing verified 55 (55%) orders within 1 hour (gold standard). Sixteen (16%) patients received CSCIO within 1 hour. The 5 Whys identified nursing order verification and pharmacy lack of visual STAT order notification for priority as the potential sources for infusion timeliness improvement. The follow-up time study confirmed improvement in pharmacy delivery time from 29% to 75% on time.
CONCLUSION: Pharmacist-led intervention directed to improve CSCIO processes in an inpatient hospice unit utilizing LEAN QI methodology increased timeliness of pharmacy CSCIO delivery.
Background: Among palliative care (PC) patients who are administered paracetamol, the subcutaneous (SC) route is often an alternative to the intravenous (IV) route. Yet pharmacological and clinical data on whether these are equivalent pharmacokinetically are lacking. Many French palliative teams are now empirically using paracetamol by the SC route, but there are no data to support this practice. This trial aims to compare the pharmacokinetic (PK) parameters of paracetomol between the IV and SC routes in PC patients.
Methods/design: This is a randomized, open, crossover study in two PC centers. The primary endpoints are AUC0-t, AUC0-8, Cmax, Vd, and t1/2. All adverse events will be reported for a safety analysis. Twenty adult PC patients with an IV device having spontaneous pain not related to care, with a numeric pain rate scale > 3/10, or having a systematic prescription of paracetamol as the usual treatment will be included. All patients also have to meet all eligibility criteria.
Conclusion: This is the first study comparing PK parameters for IV paracetamol versus SC paracetamol in PC patients.
Despite its complex pharmacology and its associated stigma from opioid addiction treatment, methadone remains a viable analgesic option for seriously ill adults and children. Oral methadone is the preferred route of administration and typically can be accomplished via methadone tablets, soluble tablets, or oral solutions of various concentrations. Still, select patients may be unable to tolerate oral methadone. This Fast Fact reviews nonoral formulations of methadone. See Fast Facts #75, 86, and 171 for additional methadone prescribing information.
Proton pump inhibitors (PPIs) have become the agents of choice for acid-related diseases. In some clinical situations, PPI therapy by oral or intravenous route may be difficult especially among elderly and patients in palliative care. Off-label PPI subcutaneous injection could be the last alternative to improve patient relief, despite limited published data. We report a case of linitis plastica, peritoneal carcinomatosis and occlusive syndrome who suffered from painful regurgitations which rapidly improved after subcutaneous pantoprazole. No related adverse effects were observed during PPI therapy. Despite some limitations, this report suggests that off-label subcutaneous pantoprazole could be an interesting alternative route when intravenous infusion may be difficult or harmful for elderly and patients in palliative care. Nevertheless, clinical safety and efficiency data on larger populations are needed to validate this use in such population.
Background: Abrupt withdrawal of pharmacological therapies for myasthenia gravis can exacerbate muscle weakness and even trigger myasthenic crisis. Such medications should ideally be continued, but how this can be achieved in patients approaching the end of life, particularly when enteral administration is compromised, has not been defined.
Case History: An 83-year-old man with a history of generalized myasthenia gravis and palliative metastatic anal adenocarcinoma was admitted to his local hospital with general decline, where he was considered by more than one physician to be actively dying from his cancer. In the days preceding admission, the patient had not taken his medications consistently, including the acetylcholinesterase inhibitor, pyridostigmine, for the management of his myasthenia gravis.
Case Management and Outcome: Reintroduction of the patient's usual myasthenia therapy improved his clinical condition to the point where he was no longer thought to be dying. When enteral administration of pyridostigmine was no longer possible, the patient was successfully converted to neostigmine, which was administered as a continuous subcutaneous infusion.
Conclusion:Undertreated myasthenia gravis can lead to a rapid deterioration in a patient's clinical condition, and such patients may be mistakenly diagnosed as dying. Undertreated myasthenia gravis should therefore be considered as a potentially reversible cause of acute deterioration, especially in patients with complex comorbidities. The use of neostigmine as a continuous subcutaneous infusion may have a role in the management of such patients, particularly when enteral administration of acetylcholinesterase inhibitors is no longer possible.
AIMS AND OBJECTIVES: To evaluate the availability of, adherence to, and perceived usefulness of guidelines and protocols for managing hydration and subcutaneous hydration in palliative care settings.
BACKGROUND: Hydration at the end of life and the use of a subcutaneous route to hydrate generate some controversy among health professionals for different reasons. Having guidelines and protocols to assist in decision making and to follow a standard procedure may be relevant in clinical practice.
DESIGN: Cross-sectional telephone survey, with closed-ended and open-ended questions designed specifically for this study.
METHODS: Data were obtained from 327 professionals, each from a different palliative care service. Mean, standard deviation, minimum and maximum were calculated for continuous variables; frequency distributions were obtained for categorical variables. A qualitative content analysis was performed on the open-ended questions. The article adheres to the STROBE guidelines for reporting observational studies.
RESULTS: Only 24.8% of the participants had guidelines available to assist in making decisions regarding hydration, and 55.6% claimed to follow them "always or almost always". Of the participants, 38.8% had subcutaneous hydration protocols available, while 78.7% stated that they "always or almost always" followed these protocols. The remaining participants considered the protocols useful tools despite not having them available.
CONCLUSIONS: Only 25% of the participants' services had guidelines for hydration, and less than 40% had protocols for subcutaneous hydration. However, adherence was high, especially in cases where protocols existed. Among the participants who did not have guidelines and protocols, attitudes were mostly favourable, but mainly as a reference and support for an individualized clinical practice.
RELEVANCE TO CLINICAL PRACTICE: Guidelines and protocols on hydration in palliative care may be more useful as a solid reference and support for individualized practice than as instruments for standardizing care. From this perspective, their development and availability in palliative care services are recommended.
BACKGROUND: Intractable pruritus affects an estimated 83% of patients with advanced cutaneous T-cell lymphoma. Palliative care strategies to improve outcomes for these patients are lacking. Lignocaine antagonises kappa opioid antagonist-induced scratching in mice models and may relieve cutaneous T-cell lymphoma-pruritus.
PRACTICE CHALLENGE: The aim of this retrospective case series was to evaluate our clinical experience with low-dose continuous subcutaneous infusion lignocaine for intractable pruritus associated with cutaneous T-cell lymphoma, from 2000 to 2015. The study received approval from Retrospective Review Panel, Division Cancer Medicine, 12 October 2015, V1.1.
METHOD: Baseline demographics including cutaneous T-cell lymphoma diagnosis and management, comorbidities, and pruritus-related evaluation including onset, severity, past and current therapies were collected. Response categories (Complete, Partial, No, Unknown) were devised for the study, based on severity of pruritus, impact on sleep and mood. The mean of responses was calculated for each patient and across the series.
OUTCOME: Nineteen patients received continuous subcutaneous infusion lignocaine, in 45 treatment episodes, ranging from 1 to 70 days (interquartile range = 5). Baseline mean number of adjuvants was 3.9 (range, 1–9). Across the series, complete response was achieved, on average, 26.7% days, partial response 49.4%, no response 16.1% and unknown response 9.2%. Drowsiness was documented in four patients. Three patients died during continuous subcutaneous infusion due to disease progression.
LESSONS: Continuous subcutaneous infusion lignocaine offers another therapeutic option in cutaneous T-Cell lymphoma-related intractable pruritus.
FUTURE RESEARCH: Prospective studies using validated assessment tools and systematic approaches to pruritus management are required.
BACKGROUND: While the majority of seriously ill people wish to die at home, only half achieve this. The likelihood of someone dying at home often depends on the availability of able and willing lay carers to support them. Dying people are usually unable to take oral medication. When top-up symptom relief medication is required, a clinician travels to the home to administer injectable medication, with attendant delays. The administration of subcutaneous injections by lay carers, though not widespread practice in the UK, has proven key in achieving home deaths in other countries. Our aim is to determine if carer-administration of as-needed subcutaneous medication for four frequent breakthrough symptoms (pain, nausea, restlessness and noisy breathing) in home-based dying patients is feasible and acceptable in the UK.
METHODS: This paper describes a randomised pilot trial across three UK sites, with an embedded qualitative study. Dyads of adult patients/carers are eligible, where patients are in the last weeks of life and wish to die at home, and lay carers who are willing to be trained to give subcutaneous medication. Dyads who do not meet strict risk assessment criteria (including known history of substance abuse or carer ability to be trained to competency) will not be approached. Carers in the intervention arm will receive a manualised training package delivered by their local nursing team. Dyads in the control arm will receive usual care. The main outcomes of interest are feasibility, acceptability, recruitment rates, attrition and selection of the most appropriate outcome measures. Interviews with carers and healthcare professionals will explore attitudes to, experiences of and preferences for giving subcutaneous medication and experience of trial processes. The study has obtained full ethical approval.
DISCUSSION: This study will rehearse the procedures and logistics which will be undertaken in a future definitive randomised controlled trial and will inform the design of such a study. Findings will illuminate methodological and ethical issues pertaining to researching last days of life care.
Sudden cessation of baclofen can produce a withdrawal syndrome even if it was previously orally administered. We present the case of a man who exhibited signs of baclofen withdrawal syndrome during palliative sedation. Attempts were made to induce muscle relaxation with ever-increasing doses of benzodiazepine. Ultimately, control over the withdrawal syndrome was regained by using a continuous subcutaneous infusion (CSCI) of dexmedetomidine, a highly selective a2 adrenergic agonist. Very limited published reports concerning CSCI of dexmedetomidine exist. To our knowledge, this is the first case to report its use as an adjunctive agent to treat baclofen withdrawal syndrome through the subcutaneous route in the palliative care setting.
BACKGROUND: Treating chronic, uncontrolled, cancer pain with subcutaneous ketamine in patients unresponsive to opioids and co-analgesics remains controversial, especially in light of recent evidence demonstrating ketamine does not have net clinical benefit in this setting.
AIM: To evaluate the cost-effectiveness of subcutaneous ketamine versus placebo in this patient population.
DESIGN AND SETTING: A within-trial cost-effectiveness analysis of the Australian Palliative Care Clinical Studies Collaborative's randomised, double-blind, placebo-controlled trial of ketamine was conducted from a healthcare provider perspective. Mean costs and outcomes were estimated from participant-level data over 5 days including positive response, health-related quality of life (HrQOL) measured with the Functional Assessment of Chronic Illness Therapy-Palliative Care (FACIT-Pal), ketamine costs, medication usage and in-patient stays.
RESULTS: There was no statistically significant difference in responder rates, but higher toxicity and worse HrQOL for ketamine participants (mean change -3.10 (standard error (SE) 1.76), ketamine n = 93; 4.53 (SE 1.38), placebo n = 92). Estimated total mean costs were AU$706 higher per ketamine participant (AU$6608) compared with placebo (AU$5902), attributable to the cost of higher in-patient costs as well as costs of ketamine administration. The results were robust to sensitivity analyses accounting for different medication use costing methods and removal of cost outliers.
CONCLUSION: The findings suggest subcutaneous ketamine in conjunction with opioids and standard adjuvant therapy is neither an effective nor cost-effective treatment for refractory pain in advanced cancer patients.
Lymphedema is a challenging condition that occurs as a complication to many life-limiting medical conditions. It has a number of associated symptoms including pain, functional impairments, and emotional distress. Majority of treatment interventions have been studied and applied outside of the palliative care context. Subcutaneous drainage is a technique that has been used in some case reports for the lower extremity and sacrum with good results. This report describes an adapted technique of subcutaneous drainage for treating upper extremity lymphedema in the palliative setting.
BACKGROUND: Dyspnea is common in interstitial lung disease (ILD) patients and often refractory to conventional treatment. Little is known regarding the safety of systemic morphine in ILD patients.
OBJECTIVE: The objective of this study is to evaluate the safety of a single subcutaneous morphine injection and to determine the recommended dose of morphine for alleviating dyspnea in ILD patients.
DESIGN: We conducted a dose-escalation Phase I study for investigating the recommended dose of a single subcutaneous morphine injection to alleviate dyspnea in ILD patients.
SETTING/SUBJECTS: Eligible subjects were ILD inpatients with dyspnea at rest who were refractory to conventional dyspnea treatment. The morphine doses used were 1 mg and 2 mg in cohort 1 and cohort 2, respectively. The primary endpoint was dose-limiting toxicity, which was defined as (1) respiratory depression, that is, 30% reduction of respiratory rate and 10 Torr increase of PaCO2 compared with baseline; (2) hypotension, that is, 20% reduction of systemic blood pressure compared with baseline and presentation of hypotension-related symptoms; or (3) grade 3, 4, or 5 treatment-emergent adverse events graded by Common Terminology Criteria for Adverse Events (version 4).
RESULTS: A total of six patients were enrolled, with three patients each in cohorts 1 and 2. No dose-limiting toxicities were observed; three patients experienced worsened somnolence, but no patients experienced sedation.
CONCLUSION: We conclude that 2 mg of morphine has a tolerable safety profile in ILD patients with dyspnea, and can be tested in further clinical trials.