Andrew Dickman

Four Essential Drugs Needed for Quality Care of the Dying: A Delphi-Study Based International Expert Consensus Opinion

PURPOSE The majority of dying patients do not have access to necessary drugs to alleviate their most common symptoms, despite evidence of drug efficacy. Our aim was to explore the degree of consensus about appropriate pharmacological treatment for common symptoms in the last days of life for patients with cancer, among physicians working in specialist palliative care. MATERIAL AND METHODS Within OPCARE9, a European Union seventh framework project aiming to optimize end-of-life cancer care, we conducted a Delphi survey among 135 palliative care clinicians in nine countries. Physicians were initially asked about first and second choice of drugs to alleviate anxiety, dyspnea, nausea and vomiting, pain, respiratory tract secretions (RTS), as well as terminal restlessness. RESULTS Based on a list of 35 drugs mentioned at least twice in the first round (n=93), a second Delphi round was performed to determine ≤ 5 essential drugs for symptom alleviation in the last 48 hours of life that should be available even outside specialist palliative care. There was ≥ 80% consensus among the participants (n=90) regarding morphine, midazolam, and haloperidol as essential drugs. For RTS, there was consensus about use of an antimuscarinic drug, with 9%-27% of the physicians each choosing one of four different drugs. CONCLUSION Based on this consensus opinion and other literature, we suggest four drugs that should be made available in all settings caring for dying patients with cancer, to decrease the gap between knowledge and practice: morphine (i.e., an opioid), midazolam (a benzodiazepine), haloperidol (a neuroleptic), and an antimuscarinic.

Educational interventions by pharmacists to patients with chronic pain: systematic review and meta-analysis.

ObjectiveWe hypothesized that educational interventions delivered by pharmacists to patients with chronic pain might improve pain-related outcomes and sought to establish “proof of concept” for this hypothesis. MethodsWe searched electronic databases and published literature for randomized studies that examined an educational intervention in relation to the management of chronic pain that was delivered by a pharmacist to an adult patient. Four studies were included that randomized 400 patients with chronic pain and which followed up patients between 1 and 16 weeks. ResultsPatients receiving these interventions experienced statistically significant benefits in the following outcomes compared with controls: a reduction in average pain intensity of 0.5 on a 0 to 10 rating scale, a reduction in adverse effects by more than 50%, and an improvement in satisfaction with treatment equivalent to approximately 1 point on a 0 to 10 rating scale. The interventions neither had effect on reducing interference from pain on daily life, nor on improving self-efficacy. DiscussionPharmacist-delivered educational interventions seem to reduce adverse events and improve satisfaction, but their clinical benefit on pain intensity is debatable. Our analysis suggests that the role of pharmacists may be important but a deeper understanding and evaluation of the active components of these interventions is needed within clinical trials before wider implementation into clinical practice can be recommended.

Complexity in Non-Pharmacological Caregiving Activities at the End of Life: An International Qualitative Study

In a qualitative study reported by Olav Lindqvist and colleagues, the range of nonpharmacological caregiving activities used in the last days of a patients life are described.

For Discussion NSAIDs: gastroprotection or selective COX-2 inhibitor?

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are effective adjuvant analgesics commonly encountered in palliative care. However, these drugs are associated with adverse effects that are primarily due to gastrointestinal toxicity, with resultant serious complications such as gastroduodenal perforations, ulcers and bleeds. This toxicity has been attributed to inhibition of cyclooxygenase-1 (COX-1). Factors known to increase this risk of toxicity include age above 65 years, classification of NSAID in terms of COX-1/COX-2 selectivity, previous history of complications and coadministration of aspirin, anticoagulants and corticosteroids. Selective inhibitors of cyclooxygenase-2 (COX-2) were developed in an attempt to reduce this association; trials to date confirm that these drugs do indeed have reduced incidence of gastroduodenal toxicity. Prior to the introduction of the COX-2 selective inhibitors, patients at high risk were often coprescribed a gastroprotective agent (such as misoprostol or a proton pump inhibitor) with a conventional NSAID. This review discusses the merits of both options and devises a treatment strategy for the safe and costeffective use of these drugs in the palliative care population.

How is agitation and restlessness managed in the last 24 h of life in patients whose care is supported by the Liverpool Care Pathway for the Dying Patient

Background Guidance regarding the patient centred management of agitation and restlessness reinforces the importance of considering underlying causes, non-pharmacological approaches to treatment and judicious use of medications titrated to patient need. In contrast, recent reports in the literature suggest that the practice of continuous deep sedation until death is prevalent in the UK. Aim To use data from the National Care of the Dying Audit - Hospitals (NCDAH) to explore the administration of medication for management of agitation and restlessness in the last 24 h of life. Methods Hospitals submitted data from up to 30 consecutive adult patients whose care in the final hours/days of life was supported by the Liverpool Care Pathway for the Dying Patient (LCP). Data on the total dose received in the last 24 h of life PRN and the last dose prescribed for administration via continuous subcutaneous infusion (CSCI) for agitation and restlessness were submitted. Results 155 hospitals provided data from 3893 patients. Median total doses in the last 24 h for midazolam, haloperidol and levomepromazine, respectively, were: PRN only, 2.5, 1.5 and 6.25 mg; CSCI only, 10, 3 and 6.25 mg; PRN+CSCI, 15, 3 and 12.5 mg. Conclusion Only 51% of patients received medication to alleviate agitation and restlessness in the last 24 h of life. Median doses were low in comparison to doses recommended for continuous deep sedation, suggesting that there is no ‘blanket’ policy for continuous deep sedation at the end of life for patients whose care is supported by the LCP.

Identification of drug combinations administered by continuous subcutaneous infusion that require analysis for compatibility and stability

BackgroundA continuous subcutaneous infusion (CSCI) delivered via syringe pump is a method of drug administration used to maintain symptom control when a patient is no longer able to tolerate oral medication. Several classes of drugs, such as opioids, antiemetics, anticholinergics, antipsychotics and benzodiazepines are routinely administered by CSCI alone or in combinations. Previous studies attempting to identify the most-common CSCI combinations are now several years old and no longer reflect current clinical practice. The aim of this work was to review current clinical practice and identify CSCI drug combinations requiring analysis for chemical compatibility and stability.MethodsUK pharmacy professionals involved in the delivery of care to palliative patients in hospitals and hospices were invited to enter CSCI combinations comprised of two or more drugs onto an electronic database over a 12-month period. In addition, a separate Delphi study with a panel of 15 expert healthcare professionals was completed to identify a maximum of five combinations of drugs used to treat more complex, but less commonly encountered symptoms unlikely to be identified by the national survey.ResultsA total of 57 individuals representing 33 separate palliative care services entered 1,945 drug combinations suitable for analysis, with 278 discrete combinations identified. The top 40 drug combinations represented nearly two-thirds of combinations recorded. A total of 23 different drugs were administered in combination and the median number of drugs in a combination was three. The Delphi study identified five combinations for the relief of complex or refractory symptoms.ConclusionThis study represents the first step towards developing authoritative national guidance on the administration of drugs by CSCI. Further work will ensure healthcare practitioners have the knowledge and confidence that a prescribed combination will be both safe and efficacious.

The current evidence base for the feasibility of 48-hour continuous subcutaneous infusions (CSCIs): A systematically-structured review

Background A continuous subcutaneous infusion (CSCI) is an effective method of multiple drug administration commonly encountered in end of life care when the oral route is compromised. At present, current practice is to limit syringe driver infusion time to a maximum of 24 hours as dictated by available chemical stability data. However, the ability to deliver prescribed medication by a CSCI over 48 hours may have numerous benefits in both patient care and health service resource utilisation. Aim To examine and present the current evidence base for the stability of 48-hour multiple-drug CSCIs in current clinical practice. Design A systematically-structured review following PRISMA guidelines. Data sources Three electronic databases and the grey literature were searched with no time limits. Empirical studies reporting data on the chemical stability of continuous subcutaneous infusions or solutions stored in polypropylene syringes were included. Results Twenty-one empirical studies were included in this review reporting chemical compatibility and stability of 32 discrete combinations of twenty-four drugs tested at a variety of different drug concentrations. The majority of combinations reported were assessed as being chemically compatible. The greatest risk of clinically significant chemical degradation was observed with midazolam. Only one study reported the microbiological stability of the solution examined. Conclusions There is currently limited evidence for the physical, chemical and microbiological stability of solutions for continuous subcutaneous infusion over a period of 48 hours. More stability data is required before the use of 48-hour CSCIs can be evaluated for use within clinical practice.

The chemical compatibility and stability of drug combinations administered by continuous subcutaneous infusions used in end of life care

Introduction In 2007, the National Patient Safety Agency recommended that healthcare staff need to have full technical information about compatibility of commonly used mixtures used in specialist areas only (National Patient Safety Agency 2007). In 2008, the Commission on Human Medicine (CHM) recommended that research should be commissioned to develop authoritative national advice on mixing of medicines to encompass compatibility and stability data (Commission on Human Medicines, 2008). In the UK, a continuous subcutaneous infusion (CSCI) is considered to be the preferred method of drug administration to maintain symptom management at the end of life. Despite this common practice, compatibility data are lacking. Analysis of national practice identified commonly used drug combinations administered by CSCI that were included in this study. Aims/objectives To determine the chemical compatibility/stability of a total of 40 commonly encountered drug combinations. A CME T34 syringe pump was used to simulate infusion of the syringe preparation over a 24 hour period. The combinations were analysed by High Performance Liquid Chromatography-Diode Array Detection (HPLC-DAD). Results Thirty combinations were identified as compatible by HPLC-DAD. These combinations also remained clear and free from visible particulate matter and the pH remained constant over the monitored period. Four combinations will require additional analysis as variances were detected during the testing procedure. Conclusion This research is the first step towards providing technical information required by healthcare staff for the mixing of injectable medicines in the same syringe. References Commission on Human Medicines. Outcome of the consultation exercise on proposals for regularising the position of those mixing and administering medicines in palliative care. London: MHRA; 2008. http://webarchive.nationalarchives.gov.uk/20141205150130/ http://mhra.gov.uk/publications/consultations/medicinesconsultations/mlxs/con033523. Accessed June 3, 2016. National Patient Safety Agency. Promoting safer use of injectable medicines; 2007. http://www.nrls.npsa.nhs.uk/resources/?entryid45=59812. Accessed June 3, 2016.

Letter to the Editor re ‘Characteristics of breakthrough cancer pain and its influence on quality of life in an international cohort of patients with cancer (BMJ Support Palliat Care 2016;6:344–52)’

Hjermstad et al 1 report an association between ‘high’ background pain intensity and breakthrough cancer pain. However, we would suggest that their results demonstrate that patients with uncontrolled background have more flares of pain than patients with well-controlled background pain. Thus, we would question the criteria used to identify patients with breakthrough cancer pain in their study. We acknowledge the lack of consensus regarding the definition of breakthrough cancer pain, although this group has previously stated that …

THE CLINICAL AND STRATEGIC IMPACT OF GENERIC DOCUMENTATION FOR ANTICIPATORY PRESCRIBING AT THE END OF LIFE

Background The End of Life (EoL) Care Strategy (2008) recommends that consistent ‘co-ordination of care’ and ‘delivery of high quality services in all locations’ is essential across a healthcare economy. Due to historical development and redesign of community services within a large healthcare economy in the North West of England, there were three different community policies for anticipatory medication at the EoL and five different prescription and authorisation forms. Collaborative working is essential to develop consistent, high standard EoL care while minimising potential risk in all care settings. Aim To assess the clinical impact of generic documentation for ‘Just in Case 4 Core Drugs’ (JiC4CD) anticipatory prescribing at the EoL across a healthcare economy. Method A multidisciplinary group of clinical experts from all the key stakeholder organisations reviewed the existing processes and documentation, and an ideal clinical pathway was agreed. A Task and Finish group designed and implemented new documentation in line with this pathway, including: prescribing guidance single prescription and authorisation booklet JiC4CD pack (issued from community, hospital and hospice pharmacies) audit form Results The clinical impact of the JiC4CD booklet and pack was demonstrated with regard to: EoL symptom control prescribing and administration clinical incidents crisis domiciliary visits and unplanned hospital admissions place of death carer satisfaction healthcare professional satisfaction Facilitating factors and barriers to implementation are discussed. Conclusion Single generic documentation for JiC4CD anticipatory medications across a healthcare economy not only has a positive impact on individual patients, but the process also demonstrated benefits of cross-organisational partnership collaboration to achieve ‘high quality care for all adults at the EoL’.