SYMPTOM CONTROL MEDICATION & THE DYING PERSON LITERATURE REVIEW, AUDIT RESULTS & NEW STANDARDS & GUIDELINES

27TH NOVEMBER 2014 SYMPTOM CONTROL MEDICATION & THE DYING PERSON GUIDELINE DEVELOPMENT GROUP

RUTH CLARK MOIRA WATSON DR AVERIL FOUNTAIN DR AMARA NWOSU PHILIP GREEN CHRISTINE RILEY DEBORAH JONES DR CLAIRE ROBINSON DR ANDREW KHODABUKUS SESSION OUTLINE

• Patient, Carer and Public Involvement • Literature Review • Existing Standards & Audit Results POWERPOINT • Updated StandardsPRESENTATION & Guidelines JULY 2012 V1.0 PROVENANCE

• 2006 – initial guidelines produced

• 6th March 2014 – Review meeting of CMPCNAG, majority quorate vote to review guidelines by e-Vote

• Meetings of membership of Symptom Control Medication & the Dying Person Guideline Development Group POWERPOINT – 29th April 2014 – 27th May 2014 PRESENTATION th – 24 July 2014 JULY 2012 – 2nd September 2014 – 3rd October 2014 V1.0 – 7th November 2014

POWERPOINT PATIENT, CARERPRESENTATION AND PUBLIC INVOLVEMENTJULY 2012 V1.0 PATIENT, CARER & PUBLIC INVOLVEMENT • PCPI representative Christine Riley – Experience of family members dying including her sister – Involved in review of our proposal and perspectives of issues pertinent to PCPI POWERPOINT

PRESENTATION

JULY 2012

V1.0 PATIENT, CARER & PUBLIC INVOLVEMENT THE ROLE OF MEDICATION • Medications use is ‘part and parcel’ of management dying.

• What the types of medications used are less important to PCPI

• What is more important is that there is a plan in place that these would addressPOWERPOINT symptoms to make the patient comfortable and that what the medications were forPRESENTATION – which symptom groupsJULY 2012 were being addressed. is communicated well with V1.0 the family.

PATIENT, CARER & PUBLIC INVOLVEMENT EXPERIENCE • Some families are distressed by the dying phase – they have no experience of it – no accurate POWERPOINT representation on the media of whatPRESENTATION it is

actually like. JULY 2012

V1.0 PATIENT, CARER & PUBLIC INVOLVEMENT AN EXAMPLE • Respiratory tract secretions – many families are distressed by this as no- one told them about this. • Therefore, if discussing use (or potential use) of medications for secretions, this mustPOWERPOINT include: – a discussion withPRESENTATION the family about what secretions are – and how they willJULY be 2012 managed. V1.0 PATIENT, CARER & PUBLIC INVOLVEMENT RECOMMENDATIONS 1 • Compassion by the clinical team is important. • Guidelines about communication and the link to informing family about discussion of the dyingPOWERPOINT phase can be included in the standards and guidelines. PRESENTATION

JULY 2012

V1.0 PATIENT, CARER & PUBLIC INVOLVEMENT RECOMMENDATIONS 2 • Dissemination of findings to public and patient groups was a positive thing. • Suggested ways that this could be facilitated, such as: – newsletters and talking/promotionPOWERPOINT of audit(s) at charity hospice events PRESENTATION – giving the public the opportunity to JULY 2012 participate/contribute in these. V1.0

CLAIRE ROBINSONPOWERPOINT AND AMARA NWOSU LITERATUREPRESENTATION REVIEW JULY 2012

V1.0 QUESTION

“What is the evidence for the use of medications to effectively control symptoms (pain, dyspnoea, pyrexia, N&V, agitation and secretions) in adult dying patients?” POWERPOINT PRESENTATION

JULY 2012

V1.0 LITERATURE REVIEW

Participants Adult humans in the dying phase (last hours to days of life) Intervention Medications used for symptom control Comparator - Control - Alternative management POWERPOINT- No treatment - Comparisons with other PRESENTATIONmedications Outcome Good symptom control JULY 2012

V1.0 SEARCH STRATEGY

• Pubmed • SCOPUS • CINALH • Cochrane database • Hand search(referencePOWERPOINT lists) PRESENTATION

JULY 2012

V1.0 SEARCH STRATEGY

1. (((((("Seizures"[Mesh] OR ("Psychomotor Agitation/analysis"[Mesh] OR "Psychomotor Agitation/diagnosis"[Mesh] OR "Psychomotor Agitation/drug therapy"[Mesh] OR "Psychomotor Agitation/prevention and control"[Mesh] OR "Psychomotor Agitation/therapy"[Mesh])) 2. OR ("Fever/analysis"[Mesh] OR "Fever/classification"[Mesh] OR "Fever/drug therapy"[Mesh] OR "Fever/therapy"[Mesh])) 3. OR "Pain Management"[Mesh]) 4. OR ("Dyspnea/analysis"[Mesh] OR "Dyspnea/classification"[Mesh] OR "Dyspnea/drug therapy"[Mesh] OR "Dyspnea/prevention and control"[Mesh] OR "Dyspnea/therapy"[Mesh])) 5. OR ((("respiratory tract secretions"[All Fields] OR "tracheobronchial secretions"[All Fields]) OR "bronchial secretions"[All Fields]) OR "death rattle"[All Fields])) 6. OR "nausea and vomiting"[All Fields]) 7. AND ((("end of life"[All Fields] OR "end of life care"[All Fields]) OR dying[All Fields]) 8. AND ((("palliative care"[AllPOWERPOINT Fields] OR "palliative medicine"[All Fields]) OR "supportive care"[All Fields]) OR ("Terminal Care/classification"[Mesh] OR "Terminal Care/nursing"[Mesh] OR "Terminal Care/prevention and control"[Mesh]PRESENTATION OR "Terminal Care/therapy"[Mesh]))) 9. AND ((Clinical Trial[ptyp] OR Comparative Study[ptyp] OR Case Reports[ptyp] OR Meta- Analysis[ptyp] OR systematic[sbJULY]) 2012 10. AND "humans"[MeSH Terms] AND English[lang]) V1.0

SELECTION CRITERIA

INCLUSION CRITERIA EXCLUSION CRITERIA Aged ≥ 18 years Aged ≤ 18 years Humans Animals Specifically about the dying Not specifically about dying phase. phase. Pharmacological Non-pharmacological management of symptoms. measures. Includes a patient related No patient related outcome outcome (e.g. POWERPOINTsymptom used (e.g. prevalence control, QOL, side effects, studies). survival) or to evaluate medication intervention.PRESENTATION Interventional, JULY 2012 Case reports, review observational, retrospective, articles, editorials,V1.0 letters. prospective, Delphi. English language. Non-English. Pubmed CINALH Scopus Cochrane References (n= 71) (n= 894) (n= 98) (n= 4) (n=24)

Exclusions of abstracts (n=40) Duplicates (n= 22) Review article (n=4) Scope beyond care of the dying (n=23) Articles after Articles selected Case report (n=1) duplicates removed for abstract after German (n=2) (n= 1069) titles screened Not about medications (n=2) (n= 71) Textbook (n=5) Editorial (n=1) Web resource (n=2)

POWERPOINTArticles selected for full text review Exclusions full text (n=20) (n= 31) PRESENTATIONReview article (n=8) Scope beyond care of the dying JULY 2012 Studies included in (n=5) the review (n=11) Case report (n=3) V1.0 Not about medications (n=4) RESULTS

Symptom Number of articles Pain 1 Dyspnoea 0 Agitation 1 Respiratory tract secretions 8 Nausea and vomiting 0 Pyrexia 0 Generic aboutPOWERPOINT use of key 1 medications in the dying PRESENTATION

JULY 2012

V1.0 QUALITY ASSESSMENT • Review included both quantitative and qualitative elements • Used a multi-methods assessment tool, devised by Hawker et al • The assessment tool consists of nine areas; Rated on a four-point scale from 1 (very poor) to 4 (good). – abstract and title – introduction and aims – methods and data; sampling – data analysis – ethics and bias – results; – transferability or generalizability – implications and usefulness. • Each paper scored (maximum of 36=good, and a minimum of 9=very poor) based on the methodological rigor. The POWERPOINTmethodological quality was assessed by A.C.N and CR. • Both authors agreed on the quality assessment of all studies. • Data were stored and analysedPRESENTATION using SPSS version 21. • The methodological quality scores are ordinal in nature; consequently Spearman JULY 2012 coefficient was chosen to measure pair-wise correlation of scoring between the

assessors. V1.0 QUALITY ASSESSMENT

Study Agreed score Back 2001 33 • Study quality ranged between 23 and 36. Bennett 1996 28

Campbell 2013 36 • Agreement between assessors Ellershaw 2002 34 was excellent. Hugel 2006 31 Hughes 2000 23 • Spearman coefficient = 0.9, p<0.0001). Kass 2003 28 POWERPOINT Lindqvist 2013 29 Stirling 1999 26 PRESENTATION Wildiers 2002 26 JULY 2012

Wildiers 2009 36 V1.0 Respiratory Tract Secretions

POWERPOINT PRESENTATION

JULY 2012

V1.0 BACK ET AL 2001

• DESIGN: Cohort study • PARTICIPANTS: Patients with death rattle. States similar age, diagnosis and gender both groups • SAMPLE: N =191, [Hyoscine (N= 128) compared with Glycopyrrolate (N= 63)] • METHOD: Scoring scale - noise volume initial, 30mins post drug, 1 hr post drug, every 4 hours. First group hyoscine hydrobromide 0.4mg. Second Group Glycopyrronium 0.2mg. Scale 0 = none, 1 = audible head of bed, 2 = end of bed, 3 = 10 steps away • RESULTS: Significant. P = 0.002 30min H HBr 56% improved vs Glyco 27%. Glyco group needed 2nd injection at 30mins. 1 hr and final scores similar. • LIMITATIONS: No exclusion criteria (could there be pseudo secretions in one group?). Groups separatedPOWERPOINT in time and less participants in second round. Increased chance of data collection bias. PRESENTATION

• Hyoscine HydrobromideJULY 2012 more effective for secretions at 30minutes, no overall difference. 'There is some evidence that reduction of noise relieves carer distress'. Should we consider usingV1.0 Hyoscine Hydrobromide first line for death rattle?

BACK CONT

“Their literature review found that glycopyrrolate has a slower onset of action than hyoscine hydrobromide at equipotent doses (0.4mg vs 0.27 = equipotent). Increased use of diamorphine, midazolam and levomepromazine in glycopyyrolate group, therefore minimal cost saving in glycopyrrolate group (average £1.53 per patient). Possibly due to less sedative and anti-emetic effects of gylcopryyolate. To prove null hypothesis that both drugs are equally efficacious in 30 bedded unit would take 12 years or multi-centre study.” POWERPOINT PRESENTATION

JULY 2012

V1.0 BENNETT 1996

• DESIGN: Retrospective cohort • PARTICIPANTS: All deaths. • SAMPLE: N=100, 96 after exclusions • METHOD: Review notes and drug chart of 100 consecutive deaths in 48hrs preceding death. Chi squared/Fisher exact/Spearman's correlation coefficient used to analyse data • RESULTS: Patients receiving CSCI hyoscine and those without equally likely to receive PRN hyoscine in the 6 hours before death. Use of hyoscine related to longer duration of hospice stay and cerebral malignancy (both significant). • LIMITATIONS: LVF included. No data surrounding effectiveness of hyoscine. Retrospective therefore POWERPOINTdata not specific to study.

• Hyoscine hydrobromide is useful for type 1 death rattle (salivary secretions). Type 2 (bronchialPRESENTATION secretions) is associated with infection/cerebral disease.JULY 2012 High doses of Hyoscine Hydrobromide (1.6- 2.4mg/24hr) or other methods are likely to be required. V1.0 CAMPBELL ET AL 2013

• DESIGN: Prospective cohort • PARTICIPANTS: Terminally ill. Palliative performance scale = 10 (0=dead, 100 = normal) • SAMPLE: N= 90, 71 after exclusions • METHOD: Patient near death separated into groups - with/without rattle. Same scoring scale as Back. RDOS score for distress (HR, RR, accessory muscle use, paradoxical breathing, restless, grunt, nasal flare, facial expression). • RESULTS: No significant difference in RDOS score (distress) between those with and without rattle (58 patients). Small numbers however states significant. • LIMITATIONS: Three study sites (however inter, intra-rater reliability score > 0.90). Measurements taken daily - for a population with prognosis of hours to days this seems minimal. Also questionablePOWERPOINT inclusion criteria, PPS score 10 - how accurate is this. 18% of study discharged (hence, questionable inclusion criteria). Therefore cannot be reliable indicator of death. Patients recruited from wards of lead author who stated in text that shePRESENTATION does not prescribe anti secretory medications ?bias. JULY 2012 • Naturally occurring noise at end of life is not associated with patient V1.0 distress. Given the side effect profile of anti-secretory medication we should consider other methods of managing family distress without medicating patients.

HUGEL ET AL 2006

• DESIGN: Prospective with retrospective control. • PARTICPANTS: Patients supported by the LCP. Matched for age, sex and diagnosis. • SAMPLE: 132 (evaluate 77 as some had no observations) After matching only 34. • METHOD: Over 10 months all patients on LCP with secretions were analysed. Compared to hyoscine treatment 3 years prior. Given 0.2mg Glycopyrronium followed by CSCI 0.6mg/24hr. Increased to 1.2mg/24hr if 2 x PRN required. Hyoscine Hydrobromide 0.4mg. CSCI 1.2mg/24hr, increased 2.4mg/24hr if 2 x PRN required. 4 hourly patient assessment for effectiveness. SPSS 11.5 and McNemar and Wilcoxon used. • RESULTS: Glycopyrronium significantly longer dying phase and time from onset of secretions until death (24 vs 12 hours). 100% partial response Glycopyrronium vs 78% Hyoscine (significant).POWERPOINT Median time to resolution was 6 hours Glycopyrronium, 4 hours Hyoscine. • LIMITATIONS: Groups separated in time, may be differences in management/observer biasPRESENTATION over this time. Glycopyrronium newly introduced ? Increased education re:secretionsJULY 2012 . Small patient numbers.

• Patients treated with Glycopyrronium are at leastV1.0 as likely to respond as Hyoscine. No statistically significant difference in levels of agitation. KASS ET AL 2003

• DESIGN: Retrospective study • PARTICIPANTS: Patients supported by the LCP • SAMPLE: N=202, N=99 had secretions, N= 59 managed with hyoscine hydrobromide. • METHOD: Presence of secretions monitored 4 hourly. If present treated with Hyoscine Hydrobromide 0.4mg PRN and CSCI 1.2mg/24hrs. If RTS present 24hours later increased to 2.4mg/24hrs. Chi squared and simple linear regression used. • RESULTS: Lung cancer significant (p = 0.003) increased risk secretions. Prolonged dying phase significant increase secretions (p < 0.001). 64.4% responded to Hyoscine Hydrobromide. Mean time to permanent response 10.7 hours. • LIMITATIONS: Small number of participants, no sample size calculations. No control group. Details of those notPOWERPOINT receiving hyoscine not presented – reasons not discussed. Response to hyoscine could be chance/natural progression of secretions. Other causes of bronchial secretions not excluded e.g. pneumonia. High number of missing observations in PRESENTATIONhours preceding death introduces potential bias. Exclusions if not followed treatment regimeJULY 2012 may bias results.

• Patients with prolonged dying phase or lungV1.0 cancer are at increased risk of secretions. Treatment is not always effective. WILDIERS ET AL 2002

• DESIGN: Retrospective analysis • PARTICIPANTS: All consecutive deaths • SAMPLE: N=107 • METHOD: Over 10 months consecutive notes were analysed for patients who died. Hyoscine was used for rattle at 0.25mg every 4 hours SC or 1.0-2.5mg/24hrs IV continuous infusion. • RESULTS: 25/107 developed rattle (23%). Higher number of lung and brain malignancy. 76% of those with rattle died within 48 hours. 18/25 (75%) had good response. Those who didn't likely had infection. • LIMITATIONS: Lower incidence of rattle in this study compared to others possibly due to fluid restriction or retrospective data collection (? Underreported). Real rattle (secretions) responds wellPOWERPOINT to hyoscine, pseudo rattle (respiratory pathology) does not. PRESENTATION

• Lower incidence of rattleJULY in 2012 this study compared to others possibly due to fluid restriction or retrospective data collection (? Underreported). Real rattle (secretions) responds well to hyoscine, pseudo rattleV1.0 (respiratory pathology) does not.

WILDIERS ET AL 2009

• DESIGN: Randomised multicentre prospective trial. • PARTICIPANTS: Terminal patients who developed death rattle. Aged 18+. • SAMPLE: N=333 • METHOD: Randomly assigned (envelope)to 0.5mg atropine + 3mg/24hr IV-SC infusion/20mg hyoscine butylbromide + 60mg/24hrs IV-SC infusion/0.25mg hyoscine hydrobromide + 1.5mg/24hr IV-SC infusion. Given rattle intensity score (0-3) at 30mins 1/4/12/24 hrs then every 24 hours. SAS statistical analysis. • RESULTS: Death rattle effectively reduced at 1 hr atropine 42%/butylbromide 42%/ hydrobromide 37%. By 24hrs 76%/60%/68%. Less effective in those with lung cancer (32% vs 46%). Groups had similar median survival (23hrs). Consciousness decreased significantly more with hyoscine hydrobromide at 12 hours. • LIMITATIONS: No placeboPOWERPOINT arm to consider natural history of rattle. Would be ethically difficult to withhold anticholinergic as this is standard accepted practice. Not blinded, same staff administeringPRESENTATION medication and scoring rattle.

• No significant differenceJULY 2012 in effectiveness between the 3 medications. Death rattle improved after 1 hour in 40%. V1.0 HUGHES ET AL 2000

• DESIGN: Prospective analysis • PARTICIPANTS: Patients in last days of life with noisy breathing. • SAMPLE: N=37 • METHOD: Consecutive case note analysis in 2 specialist palliative care units. Measured nurse reported scoring of severity of secretions and response to either hyoscine hydrobromide, hyoscine butylbromide or glycopyrrolate. Response to treatment noted and medication was titrated according to local guidelines. • RESULTS: Patient response to first dose of medication was 54% for hyoscine butylbromide, 46% for glycopyrrolate and 35% for hyoscine hydrobromide. • LIMITATIONS: Small sample, observational analysis, no details of numbers of patients receiving drug or reason different medications were used, limited statistical analysis, subjective scoringPOWERPOINT by different nursing staff – inter-rater bias.

• Antimuscarinic drugsPRESENTATION usefully contribute to the relief of retained secretions in the terminalJULY 2012 phase. First dose response was best for hyoscine hydrobromide. V1.0

Pain

POWERPOINT PRESENTATION

JULY 2012

V1.0 ELLERSHAW ET AL 2002 • DESIGN: Prospective study • PARTICIPANTS: Matched for age, sex, diagnosis. Last 3 days of life. • SAMPLE: N=94 • METHOD: Patients dying were separated into those already suing Fentanyl/Morphine. Fentanyl continues at end of life. Morphine converted to CSCI diamorphine. Four hourly pain assessed as acceptable/unacceptable. Chi-squared and t-test used. • RESULTS: Significant increased number of PRN analgesic doses in diamorphine group compared to Fentanyl in the last day of life. Fentanyl 85% required CSCI diamorphine. Diamorphine - only 47% required increase CSCI dose. • LIMITATIONS: How was pain assessed if dying? Observer variability likely. Are there other pain medications being used that would alter data between groups? POWERPOINT • Good pain control in both groups. Patients on the Fentanyl patch required less PRN morphinePRESENTATION in the last day of life. However as the diamorphine group usedJULY 2012 more PRN's and received less additional CSCI diamorphine this could explain this finding. “Fentanyl patches should continue in the dying phase.” V1.0

Agitation

POWERPOINT PRESENTATION

JULY 2012

V1.0 STIRLING ET AL 1999

• DESIGN: Retrospective analysis • PARTICIPANTS: All deaths in 3 year period • SAMPLE: N=688 control; N=60 phenobarbitone • METHOD: Case note analysis for all patients who died over a 3 year period who required phenobarbitone. Compared with patients who died without phenobarbitone use. Phenobarbitone given for physical or psychological distress (identified by descriptive terms in notes). Loading dose of 100-200mg IM. • RESULTS: Eight percent (60 patients) received phenobarbitone in the last week of life. The mean age of the phenobarbitone group (61.1) was significantly (p<0.001) lower than control (69.1). Phenobarbitone was used significantly more in patients with primary cerebral tumours. Median starting dose 1200mg/day (range 600-2400mg/day). 31 received loading dose. 10 received further IM stat after infusion started. 52 patients receiving CSCI sedative prior to Phenobarbitone. Median midazolam 30mg/24hr (range 5-180). Methotrimeprazine median 150mg/day. • LIMITATIONS: Large use ofPOWERPOINT other sedatives can make data difficult to interpret. Also 8% is a high proportion of patients receiving Phenobarbitone - they state it is used before maximal doses of other agents are reached toPRESENTATION avoid possible side effects. This makes it difficult to generalise results. JULY 2012 • Evidence in notes of phenobarbitone being effective for agitation in 47/50 V1.0 patients. PRN sedatives reduced from 144/24hrs to 54 doses post Phenobarbitone CSCI. No problems with tissue irritation at site of CSCI. Generic

POWERPOINT PRESENTATION

JULY 2012

V1.0 LINDQVIST ET AL 2013

• DESIGN: Questionnaire. Delphi. • PARTICIPANTS: 135 (90 responded) • METHOD: Questionnaires sent to physicians in Argentina, Germany, Italy, New Zealand, Slovenia, Sweden, Switzerland, the Netherlands and UK. Round 1 focus = essential drugs in last days of life. Round 2 = maximum 5 essential medications. Participants to have at least 3 years specialist palliative care experience. • RESULTS: Common medications chosen per symptom:- midazolam + lorazepam (anxiety) Dyspnoea + pain (morphine), nausea (metoclopramide 51%, haloperidol 36%), secretions (hyoscine 67%). Medication that should be available at end of life in any setting. Morphine 94%, midazolam 84%, haloperidol 80%. For secretions Glycopyrronium 27%, Hyoscine butylbromide 23% hyoscine hydrobromide 22%. • LIMITATIONS: No detailsPOWERPOINT as to how 'experts' were selected - this could introduce bias. Also the countries involved have developed palliative care services. PRESENTATION • There is a high level of consensus internationally that morphine, JULY 2012 midazolam, haloperiodol and an antimuscarinic should be available at end of life. Need individualised prescriptionsV1.0 for dying patients and knowledge about appropriate medication use. LINDQVIST CONT

• International access to opioids can be difficult due to legal constraints and HCP fears. • Whilst haloperidol is frequently used in palliative care it is discouraged in geriatric medicine. POWERPOINT • There is a lackPRESENTATION of research based literature

on pharmacologicalJULY 2012 treatment in the last

days of life. V1.0

SUMMARY

• Lack of studies examining medications used for symptom control of dying.

• Current clinical practice is extrapolated from evidence from non-dying patients, best practice and expert opinion.

• Secretions: – No strong evidence to demonstrate that pharmacological interventions help noisy breathing over placebo. No significant difference in effectiveness when comparing atropine, hyoscine butylbromide, hyoscine hydrobromide and glycopyrronium. – Campbell et al foundPOWERPOINT no evidence of respiratory distress associated with secretions. They question whether any pharmacological management is indicated given the risk of side effects from medications. This study used small numbers (71) so furtherPRESENTATION research into this would be useful.

JULY 2012 • Seizures – Stirling et al found phenobarbitone useful in managingV1.0 seizures and agitation at end of life after traditional sedatives had been trialled.

SUMMARY 2

• Pain – Ellershaw et al found it reasonable to continue Fentanyl patches in the dying phase, however as the 2 groups syringe drivers were not titrated equally it makes assessment of efficacy of fentanyl vs diamorphine difficult.

• Generic – Lindqvist found a consensus opinion amongst palliative care specialists that as a minimumPOWERPOINT at end of life morphine, midazolam and haloperidol should be available with an appropriate antimuscarinic for secretions. PRESENTATION

JULY 2012

V1.0 RESEARCH IDEAS

• Comparison of SC and buccal midazolam in management of agitation in the dying. • Use of CSCI Levetiracetam versus CSCI midazolam for the management of seizures in the dying. • Comparison of patient outcomes (e.g. symptom control, site reactions) for 24hr and 48hr CSCI medication delivery in the dying. • Comparison of SCPOWERPOINT analgesic requirements on account of adiposity (e.g. BMIPRESENTATION >30 vs BMI<30) in the dying phase. • Evaluation of the use of NSAIDs (e.g. ketorolac, JULY 2012 diclofenac) to manage sweats and pyrexia in the dying. V1.0

REFERENCES

1. Hugel H, Ellershaw J, Gambles M. Respiratory tract secretions in the dying patient: a comparison between glycopyrronium and hyoscine hydrobromide. J Palliat Med. 2006 Apr;9(2):279-84. PubMed PMID: 16629557. 2. Back IN, Jenkins K, Blower A, Beckhelling J. A study comparing hyoscine hydrobromide and glycopyrrolate in the treatment of death rattle. Palliat Med. 2001 Jul;15(4):329-36. PubMed PMID: 12054150. 3. Bennett MI. Death rattle: an audit of hyoscine (scopolamine) use and review of management. J Pain Symptom Manage. 1996 Oct;12(4):229-33. PubMed PMID: 8898506. 4. Wildiers H, Dhaenekint C, Demeulenaere P, Clement PM, Desmet M, Van Nuffelen R, Gielen J, Van Droogenbroeck E, Geurs F, Lobelle JP, Menten J; Flemish Federation of Palliative Care. Atropine, hyoscine butylbromide, or scopolamine are equally effective for the treatment of death rattle in terminal care. J Pain Symptom Manage. 2009 Jul;38(1):124-33. doi: 10.1016/j.jpainsymman.2008.07.007. Epub 2009 Apr 9. PubMed PMID: 19361952. 5. Stirling LC, Kurowska A, Tookman A. The use of phenobarbitone in the management of agitation and seizures at the end of life. J Pain Symptom Manage. 1999 May;17(5):363-8. PubMed PMID: 10355215. 6. Wildiers H, Menten J. Death rattle: prevalence, prevention and treatment. J Pain Symptom Manage. 2002 Apr;23(4):310-7. PubMed PMID: 11997200. 7. Ellershaw JE, Kinder C, Aldridge J, Allison M, Smith JC. Care of the dying: is pain control compromised or enhanced by continuation of the fentanyl transdermal patch in the dying phase? J Pain Symptom Manage. 2002 Oct;24(4):398-403. PubMed PMID: 12505208. POWERPOINT 8. Kåss RM, Ellershaw J. Respiratory tract secretions in the dying patient: a retrospective study. J Pain Symptom Manage. 2003 Oct;26(4):897-902. PubMed PMID: 14527758. 9. Lindqvist O, Lundquist G, Dickman PRESENTATIONA, Bükki J, Lunder U, Hagelin CL, Rasmussen BH , Sauter S, Tishelman C, Fürst CJ; OPCARE9. Four essential drugs needed for quality care of the dying: a Delphi-study based international expert consensus opinion. J Palliat Med. 2013 Jan;16(1):38-43. doi: 10.1089/jpm.2012.0205. Epub 2012 Dec 12. PubMed PMID: 23234300. JULY 2012 10. Campbell ML, Yarandi HN. Death rattle is not associated with patient respiratory distress: is pharmacologic treatment indicated? J Palliat Med. 2013 Oct;16(10):1255-9. doi: 10.1089/jpm.2013.0122. Epub 2013 Sep 18. PubMed PMID: 24047451. V1.0 11. Hughes A, Wilcock A, Corcoran R, Lucas V, King A. Audit of three antimuscarinic drugs for managing retained secretions. Palliat Med. 2000 May;14(3):221-2. PubMed PMID: 10858832.

POWERPOINT EXISTING PRESENTATIONSTANDARDS & AUDIT RESULTS JULY 2012 V1.0 DATA COLLECTION

Period • Data Collection 1st July – 14th September Collection Method • Case Note AuditPOWERPOINT • Evaluation ofPRESENTATION Professional Practice JULY 2012 • Disseminated to all SPCGsV1.0 EVALUATION OF PROFESSIONAL PRACTICEPOWERPOINT CASE NOTEPRESENTATION REVIEW JULY 2012

V1.0 DEMOGRAPHICS

EVALUATION OF CASE NOTE PROFESSIONAL PRACTICE REVIEW • 13 SPSG • 11 SPSG • 110 Complete • 277 Complete Responses Responses  Home – 23%  Home – 6%  Hospice – 42%  Hospice – 63%  Hospital – 32% POWERPOINT  Hospital – 31%

• CNS – 41% PRESENTATION • Doctor – 38% JULY 2012 • Other – 20% V1.0 DEMOGRAPHICS CASE NOTE REVIEW Age of Dying Person

27.4%

23.1% 21.3%

POWERPOINT12.6%

PRESENTATION7.6% 6.9% JULY 2012

V1.0 0.4% 0.7% DEMOGRAPHICS CASE NOTE REVIEW Primary Diagnosis Causing Death Gastrointestinal Disease Renal Disease 3% Infectious Disease 2% 6% Other Heart Disease 5% Other Neurological 1% Respiratory Disease 1% 4%

Dementia 2%

Cerebrovascular Disease 1%

POWERPOINT PRESENTATION

JULY 2012

V1.0

Cancer 75% In the last hours/days of life all medication should be reviewed and non-essential drugs should be discontinued. POWERPOINT[Grade D] STANDARDPRESENTATION 1 ANDREWJULY 2012 V1.0 KHODABUKUS STANDARD 1 CASE NOTE REVIEW WERE ALL MEDICATIONS REVIEWED WHEN THE PATIENT WAS RECOGNISED TO BE DYING AND CONSIDERED TO BE IN THE LAST HOURS TO DAYS OF LIFE?

All Care Settings Hospital Unknown 2% Yes 76.7% 66 No 17.4% 15 Unknown 5.8% 5 No answered question 86 9%

Hospice Yes 93.1% 162 No 6.3% 11 POWERPOINTUnknown 0.6% 1 answered question 174 PRESENTATION Home JULY 2012 Yes 100.0% 17 Yes No 0.0% 0 89% Unknown V1.0 0.0% 0 answered question 17 STANDARD 1 CASE NOTE REVIEW WERE ALL NON-ESSENTIAL DRUGS DISCONTINUED WHEN THE PATIENT WAS RECOGNISED TO BE DYING AND CONSIDERED TO BE IN THE LAST HOURS TO DAYS OF LIFE? All Care Settings Hospital Unknown 2% Yes 72.1% 62 No 22.1% 19 Unknown 5.8% 5 No answered question 86 13%

Hospice Yes 89.7% 156 No 9.8% 17 POWERPOINTUnknown 0.6% 1 answered question 174 PRESENTATION Home JULY 2012 Yes 100.0% 17 No 0.0% 0 Yes Unknown V1.0 0.0% 0 85% answered question 17 NON-SPC INVOLVEMENT SPC INVOLVEMENT

POWERPOINT PRESENTATION

JULY 2012

V1.0 Standard 1  In the last hours/days of life all medication should be reviewed • Higher achievement if and non-essential drugs should be SPC involved discontinued. [Grade D]

POWERPOINT PRESENTATION

JULY 2012

V1.0 All patients should be prescribed medications “as required”, for the symptoms most commonly experienced in the last days/hours of life. - Pain - Agitation - Respiratory tract secretions - Nausea and vomiting - Breathlessness POWERPOINT[Grade D] STANDARDPRESENTATION 2 RUTH CLARKJULY 2012 V1.0 STANDARD 2 CASE NOTE REVIEW PAIN - PRESCRIPTIONS

300

250

200

150 Home Hospital POWERPOINT Hospice 100 PRESENTATION

50 JULY 2012

V1.0

0 None Paracetamol Paracetamol IV Paracetamol PR Ketorolac sc Opioid Oral Opioid sc Other Oral STANDARD 2 CASE NOTE REVIEW BREATHLESSNESS- PRESCRIPTIONS

160

140

120

100

Home 80 Hospital POWERPOINT Hospice 60 PRESENTATION 40 JULY 2012

20 V1.0

0 None Opioid oral Opioid sc Lorazepam SL Midazolam SC Other STANDARD 2 CASE NOTE REVIEW NAUSEA & VOMITING- PRESCRIPTIONS

160

140

120

100

80

Home 60 Hospital POWERPOINT Hospice 40

20 PRESENTATION

JULY 2012 0

V1.0 STANDARD 2 CASE NOTE REVIEW AGITATION - PRESCRIPTIONS

300

250

200

150

Home Hospital 100 POWERPOINT Hospice 50 PRESENTATION

JULY 2012 0

V1.0 STANDARD 2 CASE NOTE REVIEW SECRETIONS - PRESCRIPTIONS

250

200

150

Home Hospital Hospice 100 POWERPOINT PRESENTATION 50 JULY 2012

V1.0

0 None Glycopyrronium sc Hyoscine Hyoscine butylbromide Octreotide sc Other hydrobromide sc sc

CASE NOTE REVIEW PYREXIA - PRESCRIPTIONS

250

200

150

Home Hospital Hospice 100 POWERPOINT PRESENTATION

50 JULY 2012

V1.0

0 None Paracetamol oral Paracetamol IV Paracetamol PR Ibuprofen oral Ketorolac sc Other STANDARD 3 CASE NOTE REVIEW PAIN - ADMINISTRATIONS

200

180

160

140

120

100 Home Hospital Hospice 80 POWERPOINT 60 PRESENTATION 40 JULY 2012

20 V1.0

0 None Paracetamol Paracetamol IV Paracetamol PR Ketorolac sc Opioid Oral Opioid sc Other Oral STANDARD 3 CASE NOTE REVIEW BREATHLESSNESS- ADMINISTRATIONS

250

200

150

Home Hospital Hospice 100 POWERPOINT PRESENTATION

50 JULY 2012

V1.0

0 None Opioid oral Opioid sc Lorazepam SL Midazolam SC Other STANDARD 3 CASE NOTE REVIEW NAUSEA & VOMITING- ADMINISTRATIONS

250

200

150

Home 100 Hospital POWERPOINT Hospice 50 PRESENTATION

JULY 2012 0

V1.0 STANDARD 3 CASE NOTE REVIEW AGITATION - ADMINISTRATIONS

250

200

150

Home 100 Hospital POWERPOINT Hospice 50 PRESENTATION

JULY 2012 0

V1.0 STANDARD 3 CASE NOTE REVIEW SECRETIONS - ADMINISTRATIONS

160

140

120

100

80 Home Hospital Hospice 60 POWERPOINT

40 PRESENTATION

JULY 2012 20 V1.0

0 None Glycopyrronium sc Hyoscine Hyoscine butylbromide Octreotide sc Other hydrobromide sc sc

CASE NOTE REVIEW PYREXIA- ADMINISTRATIONS

300

250

200

Home 150 Hospital POWERPOINT Hospice 100 PRESENTATION

JULY 2012 50

V1.0

0 None Paracetamol oral Paracetamol IV Paracetamol PR Ibuprofen oral Ketorolac sc Other  Standard 2 • According to the standards All patients should be medication should be prescribed prescribed for areas 1-5, this medications “as was not achieved for any required”, for the symptoms most area commonly – pain (96.4%), experienced in the – agitation (95.7%), last days/hours of life. – nausea and vomiting (91.7%) - Pain – secretions (93.5%) - Agitation – shortness of breath the worst - Respiratory POWERPOINT(61%). tract secretions - Nausea and vomiting • Pyrexia,PRESENTATION which is not listed in - Breathlessness the standards, had a poor [Grade D] rateJULY 2012 of prescribing (31%).

V1.0

Medications should be administered by the appropriate route which may include subcutaneous if oral route is not available POWERPOINT[Grade D] STANDARDPRESENTATION 3 PHIL GREENJULY 2012 & MOIRA V1.0 WATSON STANDARD 3 PROFESSIONAL PRACTICE WHAT ROUTE OF DRUG ADMINISTRATION WOULD YOU RECOMMEND FOR SYMPTOM CONTROL IN SOMEONE WHO IS DYING IN YOUR HEALTHCARE SETTING? Hospital

All Care Settings Subcutaneous Injection 97.1% 34 Oral 20% 7 Other 40% 14 There were no respondents who chose IM, Intranasal or IV injection 100% 90% answered question 25 80% Hospice 70% 60% Subcutaneous Injection 100% 46 50% Oral 39.1% 18 40% Other 89% 41 30% POWERPOINTThere were no respondents who chose IV 20% injection 10% answered question 46 0% PRESENTATIONHome

JULY 2012 92% 23 Subcutaneous Injection Oral 36% 9 V1.0 Other 64% 16 There were no respondents who chose IV injection answered question 25 STANDARD 3 PROFESSIONAL PRACTICE IF THE PATIENT HAS A PEG/RIG/NG WOULD YOU ADVISE USE OF THIS ROUTE TO ADMINISTER DRUGS FOR SYMPTOM CONTROL IN THE LAST HOURS OR DAYS OF LIFE? All Care Settings Hospital Yes 31% No 69% answered question 35

Hospice Yes 52% 48% Yes No answered question 46 POWERPOINT44% No 56% PRESENTATIONHome 40% JULY 2012 Yes No 60% answered question 25 V1.0 STANDARD 3 PROFESSIONAL PRACTICE IF THE PATIENT HAS INTRAVENOUS ACCESS VIA A PERIPHERAL CANNULA [VENFLON], WOULD YOU ADVISE USE OF THIS ROUTE TO ADMINISTER DRUGS FOR SYMPTOM CONTROL IN THE LAST HOURS OR DAYS OF LIFE? All Care Settings Hospital Yes 20% No 80% answered question 35

Yes 14% Hospice Yes 13% No 87% POWERPOINT answered question 46

PRESENTATIONHome 4% No JULY 2012 Yes 86% No 96% answered question 25 V1.0 STANDARD 3 PROFESSIONAL PRACTICE IF THE PATIENT HAS INTRAVENOUS ACCESS VIA A PERIPHERALLY INSERTED CENTRAL CATHETER (PICC) OR OTHER CENTRAL LINE, WOULD YOU ADVISE USE OF THIS ROUTE TO ADMINISTER DRUGS FOR SYMPTOM CONTROL IN THE LAST HOURS OR DAYS OF LIFE?

All Care Settings Hospital Yes 14% No 86% answered question 35

Yes Hospice 17% Yes 26% No 74% POWERPOINT answered question 46

PRESENTATIONHome No 4% 83% JULY 2012 Yes No 96% answered question 25 V1.0 Standard 3  Medications should be administered by the appropriate route • Appropriate use of which may include subcutaneous if oral routes route is not available [Grade D] • Subcutaneous route the preferred route

POWERPOINT

PRESENTATION

JULY 2012

V1.0 A syringe driver should be available in any health care setting if required for the management of symptoms at the end of life. POWERPOINT[Grade D] STANDARDPRESENTATION 4 AVERIL FOUNTAINJULY 2012 V1.0 STANDARD 4 CASE NOTE REVIEW WAS A CONTINUOUS SUBCUTANEOUS INFUSION VIA A SYRINGE DRIVER PRESCRIBED WHEN THE PATIENT WAS RECOGNISED TO BE DYING AND CONSIDERED TO BE IN THE LAST HOURS TO DAYS OF LIFE?

Yes – as an Hospital All Care Settings anticipatory prescription Yes – as an anticipatory prescription 5.8% 9% Yes – for immediate use 45.3% No – not needed 40.7% No – already in use 8.1% answered question 86 No – already Hospice in use 28% Yes – as an anticipatory prescription 8.0% POWERPOINTYes – for immediate use 40.8% No – not needed 11.5% 39.7% Yes – for No – already in use PRESENTATIONimmediate use answered question 174 43% Home JULY 2012 No – not 35.3% needed Yes – as an anticipatory prescription 20% V1.0 Yes – for immediate use 58.8% No – not needed 5.9% 0.0% No – already in use answered question 17 STANDARD 4 CASE NOTE REVIEW IF A CONTINUOUS SUBCUTANEOUS INFUSION VIA A SYRINGE DRIVER WAS NEEDED FOR SYMPTOM CONTROL, WAS IT AVAILABLE AT THE TIME OF REQUEST WITHIN YOUR HEALTH SETTING? All Care Settings Hospital Yes 61.7% No 0.0% Not Applicable (e.g. already in use for 37.5% symptom control) answered question 86

Not Applicable Hospice (e.g. already in use for Yes 60.4% symptom No 0.0% control) POWERPOINTNot Applicable (e.g. already in use for 39.6% 38% symptom control) answered question 174 PRESENTATIONYes 62% Home JULY 2012 94.1% Yes V1.0 0.0% No No Not Applicable (e.g. already in use for 0% 5.9% symptom control) answered question 17 STANDARD 4 CASE NOTE REVIEW AT THE TIME OF DEATH WAS A CONTINUOUS SUBCUTANEOUS INFUSION VIA A SYRINGE DRIVER IN USE?

All Care Settings Hospital Unknown Yes 52.3% 0% No 47.7% Unknown 0.0% answered question 86

Hospice No 25% Yes 85.1% POWERPOINTNo 14.9% Unknown 0.0% PRESENTATION answered question 174 Yes Home JULY75% 2012 82.4% Yes V1.0 No 17.6% Unknown 0.0% answered question 17 Standard 4  A syringe driver should be available in any health care setting if required for the management of • Available in all settings symptoms at the end of life. [Grade D]

POWERPOINT PRESENTATION

JULY 2012

V1.0 If a syringe driver is not available medications should be administered by the most appropriate route. POWERPOINT[Grade D] STANDARDPRESENTATION 5 DEBORAHJULY 2012JONES V1.0 STANDARD 5 PROFESSIONAL PRACTICE HOW ARE SYRINGE DRIVERS FOR CONTINUOUS SUBCUTANEOUS INFUSION ACCESSED IN YOUR PLACE OF WORK? 120

100

80

60 Percentage

40 POWERPOINT

20 PRESENTATION

JULY 2012

0 Kept on ward/community Accessed via specialist palliative Accessed via e.g. central V1.0 Don’t know (district) nursing team care team equipment library or stores Home 84 0 12 4.5 Hospice 97.8 0 4.3 0 Hospital 25.7 28.6 54.3 0 STANDARD 5 PROFESSIONAL PRACTICE WHEN ARE SYRINGE DRIVERS FOR CONTINUOUS SUBCUTANEOUS INFUSION AVAILABLE IN YOUR PLACE OF WORK? 120

100

80

60 Percentage POWERPOINT 40 PRESENTATION 20 JULY 2012

0 V1.0 (9am-5pm) 24 hours a day Don't know other Home 4 92 4 4.5 Hospice 0 100 0 0 Hospital 25.7 74.3 0 3 STANDARD 5 PROFESSIONAL PRACTICE HOW DO PATIENTS IN RESIDENTIAL OR NURSING HOMES WITHIN YOUR SPECIALIST PALLIATIVE CARE SERVICE GROUP AREA ACCESS SYRINGE DRIVERS FOR CONTINUOUS SUBCUTANEOUS INFUSION?

80

70

60

50

40 Percentage 30 POWERPOINT 20 PRESENTATION 10 JULY 2012

0 Through community (district) Expected to have their own stock PalliativeV1.0 care team don't know nursing teams Home 68 32 24 4 Hospice 53.5 20.9 11.6 2.8 Hospital 41.2 5.9 14.7 47.1 STANDARD 5 PROFESSIONAL PRACTICE HOW DO PATIENTS IN MENTAL HEALTH TRUSTS AND SERVICES WITHIN SPECIALIST PALLIATIVE CARE SERVICE GROUP AREA ACCESS SYRINGE DRIVERS FOR CONTINUOUS SUBCUTANEOUS INFUSION?

70

60

50

40

30 Percentage POWERPOINT 20 PRESENTATION 10 JULY 2012

0 Through community (district) Through a syringe driver loan Expected to have their own V1.0 Don't know nursing teams scheme facilitated by SPCT Home 60 12 20 20 Hospice 33.3 6.7 8.9 53.3 Hospital 36.4 0 18.2 45.5 Standard 5 ? If a syringe driver is not available medications should No instances in the case be administered by the most appropriate note audit where a route. syringe driver was [Grade D] unavailable

POWERPOINT PRESENTATION JULY 2012

V1.0 The medication needs of patients approaching the end of life should be reviewed daily. POWERPOINT[Grade D] STANDARDPRESENTATION 6 AMARA NWOSUJULY 2012 V1.0 STANDARD 6 CASE NOTE REVIEW HOW OFTEN WAS THE PATIENT’S MEDICATION REVIEWED?

Response Response Hospital Less often Other Percent Count than daily All Care Settings (please Daily 80.2% 69 1% specify) More often than daily 14.0% 12 1% Less often than daily 2.3% 2 Other (please specify) 3.5% 3 answered question 86

Response Response Hospice Percent Count Daily 56.9% 99 More often than daily 44.3% 77 More often Less often than daily 0.0% 0 than daily Other (please specify) 0.0% 0 35% POWERPOINT answered question 174 Response Response Home PRESENTATIONDaily Percent Count 63% Daily 41.2% 7 More often than daily 58.8% 10 JULY 2012 Less often than daily 0.0% 0 Other (please specify) 5.9% 1 V1.0 answered question 17 STANDARD 6 CASE NOTE REVIEW OPIOID DOSES AT THE TIME OF DEATH

Diamorphine Morphine via Oxycodone via Alfentanil via Fentanyl Buprenorphine via CSCI/24hrs CSCI/24hrs CSCI/24hrs patch/hr patch/hr CSCI/24hrs

Number 59 51 55 22 5 1

15 mg 30 mg 30 mg 1.75 mg 50 micrograms/ 5 Median (10 mg in (10 mg in NCDAH (15 mg in NCDAH (1.1 mg in micrograms/hr hr NCDAH 2014) 2014)POWERPOINT 2014) NCDAH 2014) 10mg – 10mg – 20mg – 0.5 mg – Interquartile N/A N/A Range 30mg 120mgPRESENTATION 80mg 4mg

JULY 2012 112.40 5 29.07 mg 110.95 mg 58.23 mg 2.87 mg micrograms/ Mean V1.0 micrograms/hr hr STANDARD 6 CASE NOTE REVIEW BENZODIAZEPINE, PHENOBARIBITONE & NEUROLEPTIC DOSES AT THE TIME OF DEATH

Midazolam via Clonazepam via Phenobarbitone Levomepromazine Haloperidol via CSCI/24hrs CSCI/24hrs via CSCI/24hrs via CSCI/24hrs CSCI/24hrs

Number 162 8 4 60 22

10mg 18.75mg 4mg

1mg 500mg Median (10 mg in NCDAH (12mg in NCDAH (2mg in NCDAH 2014) POWERPOINT 2014) 2014)

Interquartile 10mg – 0.5 mg – 250mg – 12.5mg – 2.38mg – Range 20mg PRESENTATION1mg 2325mg 25mg 5mg JULY 2012

Mean 16.30mg 1025mg 58.23mg V1.0 30mg 4.48mg STANDARD 6 CASE NOTE REVIEW ANTI-EMETIC DOSES AT THE TIME OF DEATH*

Metoclopramide Ondansetron via Cyclizine via via CSCI/24hrs CSCI/24hrs CSCI/24hrs

Number 19 6 34

40mg 150 mg Median 16 mg (30mg in NCDAH 2014) (150mg in NCDAH 2014) POWERPOINT Interquartile 30mg – 60mg 7mg – 16mg 150mg – 150mg Range PRESENTATION

JULY 2012

Mean 47.89 mg 12.67 mg V1.0 138.24 mg

* Excluding haloperidol, levomepromazine due to dual use STANDARD 6 CASE NOTE REVIEW ANTI-SECRETORY DOSES AT THE TIME OF DEATH*

Hyoscine Hyoscine Glycopyrronium Octreotide via butylbromide via hydrobromide via via CSCI/24hrs CSCI/24hrs CSCI/24hrs CSCI/24hrs

Number 11 62 23 13

80mg 1.2 mg 1.2mg 600 micrograms Median (60mg in NCDAH (1mg in NCDAH 2014) (1mg in NCDAH 2014) 2014) POWERPOINT 400 micrograms Interquartile Range 60mg – 120mg 1.2mg – 2.4mg 1.2mg – 2.4mg – 1000 PRESENTATION micrograms JULY 2012

Mean 79.32 mg 1.17 mg V1.01.52 mg 823 micrograms STANDARD 6 CASE NOTE REVIEW OTHER MEDICATION DOSES AT THE TIME OF DEATH

Ketamine via Dexamethasone CSCI/24hrs via CSCI/24hrs

Number 1 6

Median 200mg 1 mg POWERPOINT Interquartile N/A 0.875mg – 9mg Range PRESENTATION

JULY 2012

Mean 200mg V1.03.92 mg Standard 6  The medication needs of patients approaching the end The vast majority of life should be reviewed daily. reviewed daily or more [Grade D] often

POWERPOINT

PRESENTATION

JULY 2012

V1.0 POWERPOINT REVISED GUIDELINESPRESENTATION FOR USING SYMPTOM CONTROLJULY 2012 MEDICATION IN THE DYING PERSON V1.0

DRAFT GUIDELINES

Section 4 Guideline Recommendations 4.1 Recognising the Likelihood of Dying

• Symptom control in a dying person – as in any other situation – requires holistic assessment, considered intervention and a review of the effectiveness of interventions made Furst 2005. What can make the care of the dying person different is the presence of new symptoms like respiratory tract secretions, the loss of the oral route of administration of medication and the need to achieve rapid symptom control in a potentially uncertain, unstable and emotionally charged time Furst 2005, LACDP 2014. Therefore, the recognition that someone is possibly or likely to be dying is crucial LACDP 2014 [Level 4]. POWERPOINT • Care and symptom control in a dying person is a continuum, meaning there should be continual assessment of the condition, needs and wishes of the dying person with an appropriatePRESENTATION response LACDP 2014 [Level 4].

JULY 2012 • Further guidance is available in the Network’s “Care of the dying patient and their Families” and the Leadership Alliance for the CareV1.0 of the Dying Person’s Report “One Chance to Get It Right” MCCN 2010,LACDP 2014. DRAFT GUIDELINES

4.2 Medication Review and Anticipatory Prescribing • When the likelihood of dying is recognised, all medication should be reviewed by the responsible clinician or an appointed delegate LACDP 2014 [Level 4]. • This review should consider Ellershaw 2001 Ellershaw 2002, Furst 2005, LACDP 2014: – current and anticipated symptom burden – available routes of administration of medications and how these may change as someone dies; i.e the loss of intravenous access – current and anticipated organ function; i.e. is there a clinically significant risk of renal or hepatic impairment? – the dying person’s diseases and medications used in their therapy • This review should result in individualised, documented decisions regarding which current medications are considered essential and those considered inessential for symptom control in the dying phase; this should be communicated following the principles in Decision Making below LACDP 2014. POWERPOINT • Medication to control symptoms that can occur in dying people should be prescribed in anticipation of the symptoms occurring. Ellershaw 2001 Ellershaw 2002, Furst 2005 [Level 4]. • The timing of this prescriptionPRESENTATION will vary depending on care setting and the clinical course of illness. It should be individualised and consider the likelihood of dying occurring, discussion with the person and thoseJULY important 2012 to them and logistics (e.g. the expiry date of medication and renewal of stock). Ellershaw 2001 Ellershaw 2002, Furst 2005 [Level 4]. V1.0 DRAFT GUIDELINES

4.3 Decision Making • The recognition that dying may occur – and how an individual should be supported through this – may have been identified through advance care planning NHS EoLCP 2011. This is a voluntary process and it may be that this did not or could not take place, for example a catastrophic cerebral haemorrhage. As an ongoing process the dying person should be involved as much as they want to be in decisions about: – the reason, – the choice and – the route of symptom control medications in the dying phase Ellershaw 2001 Ellershaw 2002, Furst 2005, LACDP 2014 [Level 4]. • If a decision-specific capacity assessment shows they are unable to be involved in treatment decisions in accordance with the 2005 Mental Capacity Act, any available advance care plans, Advance Decisions to Refuse Treatment and Lasting Power of Attorney for Health and WelfarePOWERPOINT should be consulted LACDP 2014 [Level 4]. • In addition to this, and especially if these measures are not in place, those important to the dying person should be involved in the dying person’s care. Their ongoing involvement entails considering what thePRESENTATION wishes of the dying person would be in decisions around the reason, choice and route of symptom control medications in the dying phase. LACDP 2014 [Level 4]. JULY 2012 • All these discussions should be documented in the clinical record LACDP 2014 [Level 4]. V1.0 DRAFT GUIDELINES

4.4 Routes of Administration • The process of dying is often characterised by the unreliability or loss of the oral route for medicines administration Lichter 1990, Ellershaw 2001 Ellershaw 2002, Furst 2005, An alternative route is therefore needed. The subcutaneous route is recommended for parenteral use in the dying because it has fewer complications compared with intravenous use Radbruch 2011 [Level 2+]. • A subcutaneous access port should be sited to avoid repeated skin puncture. A “safer sharp” needle or system should be used to reduce risk of needlestick injury. (http://www.hse.gov.uk/pubns/hsis7.pdf) [] • If regular administration of medicines in needed, a continuous subcutaneous infusion (CSCI) should be used, using a syringe driver. Ellershaw 2002 [Level 4] • If a syringe driver is not available to administer a CSCI, it may be necessary to prescribe regular subcutaneous injections to cover the 24 hour dose. Ellershaw 2002 [Level 4] • Increasingly, long term medicationPOWERPOINT delivery routes (e.g. percutaneous enterostomy, peripherally inserted central catheter (PICC)) are being used to deliver medications to people with advanced illness. If present in the dying phase these routes should be evaluated on an individualPRESENTATION basis to determine whether they are appropriate to be used to deliver medications for specific problems. This may be favoured in certain instances (e.g. to control seizures with a specificJULY 2012 intravenous antiepileptic) [] [Level 4].

V1.0 DRAFT GUIDELINES 4.5 Symptoms • Symptom control in a dying person – as in any other situation – requires holistic assessment, considered intervention and a review of the effectiveness of any intervention made Lichter 1990, Ellershaw 2001 Ellershaw 2002, Furst 2005. • These key principlesPOWERPOINT are reviewed in depth in each of the Network’s guidelines. In this section we pullPRESENTATION together the main considerationsJULY 2012faced when someone is dying. V1.0

DRAFT GUIDELINES

4.5.1 Pain • Further information on managing pain in palliative care is available in the following Cheshire and Merseyside Palliative and End of Life Care Strategic Clinical Network Guidelines: CancerPOWERPOINT-Related Breakthrough Pain, Corticosteroids, Ketamine, Methadone, Neuropathic Pain,PRESENTATION Non-Steroidal Anti- InflammatoryJULY Drugs, 2012 Opioid Substitution, Substance Misuse, TransdermalV1.0 Opioids. DRAFT GUIDELINES

4.5.1.1 Pain: Medication Review • If the dying person regularly uses an oral strong opioid: – this should be converted to a CSCI using the principles in Guidelines for Opioid Substitution. Ellershaw 2002, Twycross 2012 [Level 4] • If the dying person regularly uses a transdermal strong opioid: – this should be continued in the dying phase with no further titrations in patch dose Ellershaw 2002 TD [Level 4] – If two “as required” doses of strong opioid are needed in a 24-hour period a continuous subcutaneous infusion of strong opioid should be commenced alongside the transdermal strong opioid patch Ellershaw 2002 TD. [Level 4] – The starting dose of the opioid in the continuous subcutaneous infusion (CSCI) should be equivalent to the “asPOWERPOINT required” doses used in the last 24 hours, excluding those used to manage incident pain Ellershaw 2002 TD. [Level 4] – The CSCI and corresponding “as required” doses of SC strong opioid should be titrated according to “as required” use and the patch changed as usual, again with no further titrations in patchPRESENTATION dose Ellershaw 2002 TD [Level 4] JULY 2012

V1.0 DRAFT GUIDELINES

• If the dying person regularly uses methadone as opioid substitute maintenance therapy: – Administer via a separate CSCI to avoid the symptoms of withdrawal and do not alter the dose MCCN 2010, Twycross 2012 – Other opioids used to control pain and breathlessness should be converted to a CSCI as usual MCCN 2010 • If the dying person regularly uses methadone as analgaesia therapy:POWERPOINT – For discussion • If the dying personPRESENTATION regularly uses ketamine as analgaesia JULY 2012 – For discussion V1.0 DRAFT GUIDELINES • If the dying person regularly uses an oral adjuvant analgaesic without a subcutaneous equivalent (e.g amitriptyline, gabapentin or pregabalin) – the impact of this stopping due to loss of the oral route should be assessed. Ellershaw 2002, Twycross 2012 [Level 4] – There is insufficientPOWERPOINT evidence to recommend the use of other subcutaneous medication to replace the loss of oral adjuvantPRESENTATION analgaesia without a subcutaneous equivalent. In practice, clonazepam has been used and its use asJULY a 2012substitute adjuvant analgaesic should be discussed with Specialist PalliativeV1.0 Care. [] DRAFT GUIDELINES

• If the dying person regularly uses corticosteroids: – it is usually appropriate to discontinue these in the dying phase unless they have been necessary in achieving good symptom control e.g managing headaches and cancer pain Twycross 2012 [Level 4, []] – for patients unable to take oral dexamethasone, doses <8mg can be given by bolus subcutaneous injection see corticosteroids for reference Twycross 2012 [Level 4, []] – if a CSCI is necessary,POWERPOINT dexamethasone should be administered via a separate syringe driver to prevent precipitation DickmanPRESENTATION 2010 [Level 4]

JULY 2012

V1.0 DRAFT GUIDELINES

4.5.1.2 Pain: Anticipatory Prescribing • If the dying person takes oral strong opioids for breakthrough pain: – this should be prescribed as a subcutaneous dose using the principles in Guidelines for Opioid Substitution. 3, 6 [Level 4] • If the dying person uses rapid onset transmucosal fentanyl citrate for breakthrough pain: – This should continue to be prescribed and administered as tolerated and in accordance with the brand-specific guidance (see Guidelines for Cancer-Related Breakthrough Pain) Guidelines for Cancer-Related Breakthrough Pain. Transmucosal fentanyl brands should not be switched to offer a different route of administration (e.g. from a sublingual preparation to a nasal preparation) as they are not the same formulation. Guidelines for Cancer-Related Breakthrough Pain – An appropriate subcutaneousPOWERPOINT dose of an injectable opioid should be prescribed based on their background strong opioid dose using the principles in Guidelines for Opioid Substitution. Ellershaw 2002, Twycross 2012 [Level 4] • If the dying person is PRESENTATIONnot using strong opioids: – Morphine is the subcutaneousJULY 2012 analgesia of choice in the dying phase and should be prescribed 2.5mg – 5mg SC 2-4 hourly PRN Ellershaw 2002, Twycross 2012 – If the dying person is allergic or intolerant of morphine,V1.0 or if the eGFR is <30mls/min an alternative opioid should be prescribed MCCN 2010

DRAFT GUIDELINES

4.5.1.3 Pain: Continuing Review • The effectiveness of the use of “as required” doses is needed to review Ellershaw 2002: – The dose used – The need to increase background analgaesiaanalgesia via a CSCI • If two or more “as required” doses of strong opioid are needed over 24 hours, a continuous subcutaneous infusion (CSCI) should be considered,POWERPOINT if not already in place Ellershaw 2002 [Level 4]. • Doses used to managePRESENTATION incident pain should not be used to calculate an increase in CSCI opioid [] • If a syringe driver JULYis not2012 available to administer a CSCI, it may

be necessary to prescribe the subcutaneousV1.0 opioid every 4 hours to cover the 24 hour dose. Ellershaw 2002 [Level 4] DRAFT GUIDELINES

4.5.2 Breathlessness • Further information on managing breathlessness in palliative care is available in the following Cheshire and Merseyside Palliative and End of Life Care Strategic Clinical Network Guidelines: Breathlessness, Oxygen, Pleural Effusions

4.5.2.1 Breathlessness: Medication Review • If the dying person regularly uses an oral strong opioid for breathlessness: – this should be convertedPOWERPOINT to a CSCI/24hrs using the principles in Guidelines for Opioid Substitution. Ellershaw 2002, Twycross 2012 [Level 4] • If the dying person regularlyPRESENTATION uses an oral or sublingual benzodiazepine for breathlessness: JULY 2012 – this should be converted to a CSCI/24hrs of midazolam at a dose of 5mg – 10mg Ellershaw 2002, Furst 2005 [Level 4] V1.0

DRAFT GUIDELINES

4.5.2.2 Breathlessness: Anticipatory Prescribing • Strong opioids and benzodiazepines are the drugs of choice in the management of breathlessness in the dying person. Jennings 2001 [Level 2+] • The dying person who is breathless and already established on a long-acting opioid may benefit from an “as required” dose of opioid that is lower than the usual one sixth of the total daily dose of opioid. Allard 1999 [Level 2+] • Immediate release opioids may be more helpful than long-acting opioids in relieving breathlessness. Jennings 2001, Allard 1999 [Level 3] • Morphine is the first line parenteral strong opioid for patients with breathlessness. – In opioid naïve patients the appropriate “as required” dose is 1.25mg–2.5mg subcutaneously prescribed 2-4 hourly. EllershawPOWERPOINT 2002, Furst 2005, Jennings 2001 Allard 1999 [Level 4] • Midazolam is the benzodiazepine of choice for breathlessness associated with anxiety in the dying person. – The “as required” dose ofPRESENTATION midazolam is 2.5mg subcutaneously. A CSCI may be required. Starting dose should be titrated according to need. Ellershaw 2002, Furst 2005 [Level 4] – The dying person with anJULY eGFR 2012 of <30mls/min should be prescribed a reduced dose of midazolam i.e a starting dose from 1mg SC MCCN 2010 – It can be helpful to prescribe and record “as required” doses of opioids for pain and breathlessness separately for those patients who require “as required” dosesV1.0 for both symptoms. This can be useful when titrating the prescribed regular dose of opioids. [] DRAFT GUIDELINES

4.5.2.3 Breathlessness: Continuing Review • If morphine is effective, a CSCI should be commenced at a dose of 5mg-10mg over Ellershaw 2002, Furst 2005 Jennings 2001 24 hours. . POWERPOINT , Allard 1999 [Level 4] PRESENTATION

JULY 2012

V1.0 DRAFT GUIDELINES

4.5.3 Excessive Respiratory Tract Secretions • Inability to clear secretions from the oropharynx and trachea often results in noisy respiration as the secretions oscillate up and down with expiration and inspiration. . Bennett 2002, Furst 2005 [Level 4] • Non-pharmacologicalPOWERPOINT measures are an important part of the management of respiratory tractPRESENTATION secretions and may simply Furst 2005 include a changeJULY 2012 of position. [Level

4] V1.0 DRAFT GUIDELINES

4.5.3.1 Excessive Respiratory Tract Secretions: Medication Review • Early use of anti-cholinergic agents may be helpful in dying people with disease known to be associated with an increased incidence of respiratory tract secretions. Examples include primary malignancy of the lung or brain, severe heart failure and non-cancer respiratory disease. Kass 2003 [Level 4]

4.5.3.2 Excessive Respiratory Tract Secretions: Anticipatory Prescribing • Hyoscine hydrobromide, glycopyrronium and hyoscine butylbromide are all available for the management of excessive respiratory tract secretions. Twycross 2012 There is no conclusive evidence regarding evidence of efficacy to favour a particular drug.POWERPOINT Bennett 2002, Furst 2005, Kass 2003, Back 2001, Hugel 2006, Wildiers 2002, Wildiers 2009, Hughes 2000 [Level 4] Table 17.1 gives further details of clinical situations where a particular drug may be selected e.g. renal impairment. • Pulmonary oedema mayPRESENTATION be the cause of excessive respiratory tract secretions. Consider the use of parenteral furosemide under the guidance of specialist palliative JULYcare. 2012 Furst 2005 [Level 4]

V1.0 DRAFT GUIDELINES

Table 17.1 Anticholinergic drugs used in the management of respiratory tract secretions Twycross 2012, Bennett 2002, Furst 2005, Kass 2003, Back 2001, Hugel 2006, Wildiers 2002, Wildiers 2009, Hughes 2000 [Level 4] As Required SC Drug CSCI Dose/24hours Notes Dose

Drug crosses blood brain barrier. Risk of Hyoscine 1200micrograms- 400 micrograms sedation or agitation Hydrobromide 2400micrograms increased if eGFR <30mls/min

Risk of transient bradycardia, followed by tachycardia, with POWERPOINTrescue doses of 400 1200micrograms- Glycopyrronium 200 micrograms micrograms. 2400micrograms This is the preferred PRESENTATIONdrug in eGFR <30mls/min at a halved dose. 20 JULY 2012

Risk of bradycardia. Hyoscine 20 mg 60mg-240 mg ShortV1.0 duration of Butylbromide action. (60 minutes) DRAFT GUIDELINES 4.5.3.3 Excessive Respiratory Tract Secretions: Continuing Review • It is important to talk to relatives giving explanation and reassurance, as this symptom may cause considerable distress to the family. Back 2001, Campbell 2013 [Level 4] • An “as required” dose of an anti-cholinergic drug should be givenPOWERPOINT as soon as respiratory tract secretions develop. They do not relieve symptoms secondary to secretionsPRESENTATION that are already in place. Regular administrationJULY 2012 or a CSCI, should be Furst 2005 started as soon as possible. V1.0 [Level 4] DRAFT GUIDELINES

4.5.4 Restlessness and Agitation • Further information on managing restlessness and agitation in palliative care is available in the following Cheshire and Merseyside Palliative and End of Life Care Strategic Clinical Network Guidelines: Agitation, Delirium, Spiritual Care 4.5.4.1 Restlessness and Agitation: Medication Review • Possible reversible causes of the agitation should be sought and managed appropriately. Examples include urinary retention, opioid toxicity, nicotine withdrawal, constipation and noise. Furst 2005 4.5.4.2 Restlessness and Agitation: Anticipatory Prescribing • Midazolam 2.5mg as required should be prescribed and administered subcutaneously if a patient is agitated. Furst 2005 [Level 4] • The dying person with an eGFR of <30mls/min should be prescribed a reduced dose of midazolam. A suitable startingPOWERPOINT dose would be 1.25mg midazolam “as required” subcutaneously. If this is effective, and two or more doses of midazolam are required in a 24-hour period, commence a subcutaneous infusion of midazolam 5mg over 24 hours. Twycross 2012 [Level 4] PRESENTATION • Patients who are paranoid and / or hallucinating may require haloperidol. It is advisable to Vella 2004 start with a low dose initiallyJULY e.g. 2012 2.5mg 12 hourly as required subcutaneously. [Level 3]

• The maximum dose of haloperidol that should be administeredV1.0 subcutaneously over 24 hours is 10 mg. Higher doses of haloperidol risk causing extra-pyramidal side effects. Twycross 2012 [Level 4]

DRAFT GUIDELINES

4.5.4.3 Restlessness and Agitation: Continuing Review • If a reversible cause for the agitation is found, the patient should continue to be monitored for any further agitation and additional “as required” doses of midazolam administered as needed. It may not be necessary to commence a CSCI of midazolam at this stage. Ellershaw 2002 [Level 4] • If a CSCI is required it should be commenced at a dose of midazolam 10mg-30mg over 24 hours, or the dose should be calculated according to the number of “as required” doses given in the last 24 hours. Ellershaw 2002, Dickman 2011 [Level 4] • If the patient is still agitated at a dose of 30mg of midazolam over 24 hours via a CSCI, specialist palliative care advice should be sought. MCCN 2010 [Level 4] • Agitated patients who do not respond fully to midazolam may benefit from the addition of levomepromazine. Twycross 2012 [Level 4] • If two or more doses of haloperidolPOWERPOINT are required in a 24-hour period, commence a subcutaneous infusion of haloperidol 5mg over 24 hours. Vella 2004, Dickman 2011 [Level 4] • In severe cases, phenobarbital may be used for the management of agitation in the last days/hours of life but should only be administered under the guidance of specialist palliative care. Stirling 1999 [LevelPRESENTATION 3] JULY 2012

V1.0 DRAFT GUIDELINES

4.5.5 Nausea and Vomiting • Further information on managing nausea and vomiting in palliative care is available in the following Cheshire and Merseyside Palliative and End of Life Care Strategic Clinical Network Guidelines: Bowel Obstruction, Nausea and Vomiting. 4.5.5.1 Nausea and Vomiting: Medication Review • Those who have previously been nauseated and who are established on anti-emetic medication should continue on an anti-emetic. This should be converted to an appropriate equivalent and be prescribed regularly and parenterally. The subcutaneous route is recommended. Ellershaw 2002 [Level 4] 4.5.5.2 Nausea and Vomiting: Anticipatory Prescribing • All patients should be prescribedPOWERPOINT an anti-emetic to be administered as required in the event of nausea or vomiting developing in the last days / hours of life. Ellershaw 2002 [Level 4] • For the dying person who become nauseated or are vomiting, levomepromazine may be the most effective anti-emetic to prescribePRESENTATION due to its multiple methods of action. Kennett 2004 [Level 3] • Cyclizine may theoretically exacerbate symptoms of heart failure and should be avoided in patients with this condition. JULYTan 1988 2012 [Level 3] • Patients who are dying with advanced renal dysfunction should be prescribed haloperidol 0.5mg – 1.5mg subcutaneously “as required” for nausea. [Level 4]TwycrossV1.0 2012 4.5.5.3 Nausea and Vomiting: Continuing Review • If haloperidol “as required” is effective, and two or more doses of haloperidol are required in a 24- hour period, commence a CSCI of haloperidol 1.5mg to 3mg over 24 hours. [Level 4]Twycross 2012 DRAFT STANDARDS Section 5: Standards 1. When dying is recognised all medication should be reviewed and non-essential drugs should be discontinued. Ellershaw 2002 [Grade D] 2. People who are dying should be prescribed medications “as required”, for the following Ellershaw 2002 symptoms: POWERPOINT [Grade D] – Pain. – Breathlessness.PRESENTATION

– Excessive respiratoryJULY 2012 tract secretions. – Restlessness and agitation. – Nausea and vomiting. V1.0

DRAFT STANDARDS

3. Medications should be administered by the appropriate route which may include subcutaneous if oral route is not available. Radbruch 2011 [Grade B] 4. The available medication routes (which may include intravenous and gastrostomy access) should be reviewed with a documented plan about their appropriateness for drug administration in the dying phase. MCCN 2014 [Grade D] 5. A syringe driver for continuous subcutaneous infusion should be available in any health care setting if required for the management of symptoms in thePOWERPOINT dying phase. [Grade D] 6. A process to access a syringe driver should be in place to access a syringe driver. [Grade D] 7. If a syringe driver PRESENTATIONis not available medications should be administered by theJULY most 2012 appropriate route. [Grade D] 8. The medication needs of a dying person should be reviewed daily. [Grade D] V1.0