Inpatient Palliative Medicine Update

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Todd Richard
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1 Inpatient Palliative Medicine Update David Dupere MD, FRCPC Head, Division of Palliative Medicine Department of Medicine QEII Health Sciences Centre Halifax, Nova Scotia

2 Disclosures Book chapter in Compendium of Therapeutic Choices, Canadian Pharmacists Association. There will be off-label recommendations for some of the medications mentioned today.

3 Prognostication and the Transition to Palliation Nausea and Vomiting Control In Support of Palliative Sedation Changes in End of Life Symptom Management

4 Chances of dying during the average Canadian lifespan

5 Transitions To Palliation Do everything until there is nothing more that can be done and then give comfort care only Vs. Integrative Palliative Care initiated at the time of diagnosis, independent of prognosis, and delivered in concert with curative / lifeextending efforts

6 Transitions to Palliation Chronic condition management requires timely transition to palliative and end of life care Examples are COPD, CHF and Diabetes Simply observing gradual deterioration is not good enough: Preferences for EOLC cannot be predicted as reliably as for acute care Access to palliative care services may not always be possible or necessary, but some degree of palliative care need will be universal.. Structuring services appropriately is challenging

7 Transitions To Palliation- The Cost of Dying in Canada

8 Palliative Care is YOU!

9 When should goals be established? Routine visit (in setting of chronic, life-limiting disease), but Difficult to schedule sufficient time for thorough discussion Difficult to anticipate all possible scenarios vs. Times of crisis Worst possible time to make difficult decisions Is usually when the BIG decisions are actually made

10 The Trigger- Would my pt benefit from a palliative approach? Ask Does the patient have an advanced long term condition, a new diagnosis of a progressive life limiting illness or both? Look for one or more general indicators Poor performance status Progressive weight loss (>10% over past 6 months) Two or more unplanned admissions in past 6 months Pt in HLC or requires significant care at home

11 Also Look for two or more disease-related indicators: Heart disease (SOB at rest, renal impairment, cardiac cachexia, NYHA class IV heart failure, two or more admission for IV therapy in past 6 months etc) Kidney disease (egfr <15ml/min, conservative treatment on basis of co-morbidities, new life-limiting condition such as cancer etc) Respiratory disease (severe airway obstruction, LT Oxygen therapy, SOB at rest, low BMI, repeated admissions etc) Liver disease (alb <25, ascites, HCC) Cancer (poor performance status, persistent symptoms) Also for neurological disease and dementia

12 Lau, F. et al. Using the Palliative Performance scale to Provide Meaningful Survival Estimates. J Pain Sympt Manage: 2009; July, 38(1),

13 The better Trigger?- The Surprise Question Would I be surprised if this patient died within the next year?

14 Haydar, S. et al. Using the Surprise Question To Identify Those with Unmet Palliative Care Needs in Emergency and Inpatient Settings: What do Clinicians Think? J Pall Med 2017; 20(7) In this setting, clinicians indicated that use of the SQ is feasible, acceptable, and useful in facilitating advance care planning discussions among teams, patients, and families. Many reported that SQ use influenced goals of care, but concern regarding accuracy was a barrier. Additional research examining SQ accuracy and predictive ability is warranted.

15 a wide degree of accuracy. White, N et al. How accurate is the Surprise Question at identifying patients at the end of life. A systematic review and meta-analysis. BMC Med 2017; 15:139

16 Palliative Care is YOU Prognostication, leads to: Advance Care Planning, leads to: End of Life Care Profile of quality end of life care is low Not just the remit of Specialist Palliative Care puts the onus on everyone to think about their own practice and their own services Essential component of health service planning

17 The Communication of Prognosis: Physician s Barriers to Truthful Disclosures 1. Stress of dealing with families of responding to emotion of honesty causing depression / harm / death of own negative feelings about prognostication / death 2. Inadequate Training difficulty starting a discussion about the topic inadequate skills at prognosticating 3. Timing patient not sick enough to talk about end-of-life no time to devote to such a discussion

18 Communication about dying and the economy with truth Censoring of information in an attempt to protect from potentially hurtful, sad or bad news. Misguided belief that what people do not know will not harm them. Short-term benefits vs. Denying the patient and family the opportunity to reorganize and adapt their lives towards attaining more achievable goals, realistic hopes and aspirations. Fallowfield et al. Palliative Medicine,2002 Well meant

19 The Communication of Prognosis Explore the patient s / family s understanding of their prognosis- have they asked?- have they been told? Patient/ Family s notable key factors: degree of nutritional intake: full, partial, minimal, none percentage of time spent in bed/lying down: none, 25-50%, 50-75%, all temporal pattern of energy loss: compared to 2 weeks ago, 2 months ago

20 The Communication of Prognosis I d say Friday, February 2, 2018 around 2:15 pm- give or take 10 minutes Days- Weeks- Months Or Years

21 leads to: Advance Care Planning Private Insurance coverage? Will/ Power of Attorney in place? Substitute Decision Maker? DNAR? Preferred Place of Death- hospital?

Nausea and Vomiting Control or, Whaaa... Ondanestron is NOT the true Super antinauseant? Useful: Gupta et al. Nausea and vomiting in advanced cancer- the Cleveland Clinic Protocol. J Support Oncol.

22 Nausea and Vomiting Control or, Whaaa... Ondanestron is NOT the true Super antinauseant? Useful: Gupta et al. Nausea and vomiting in advanced cancer- the Cleveland Clinic Protocol. J Support Oncol Mar, 11(1):8-13. Davis MP, Hallerberg G: A systematic review of the treatment of nausea and/or vomiting in cancer unrelated to chemotherapy or radiation. J Pain Symptom Manage 2010;39:

mucosal enterochromaffin cells obstruction/constipation stasis inflammation

23 Cortex sensory input anxiety, memory meningeal irritation increased ICP/ CNS lesion CTZ drugs, metabolic dorsal vagal complex GI serotonin release from mucosal enterochromaffin cells obstruction/constipation stasis inflammation Vomiting Center VOMITING CENTRE (Central Pattern Generator) Vestibular motion CNS lesions

Histamine drugs, metabolic dorsal vagal complex Serotonin

enterochromaffin cells obstruction/ constipation stasis

24 Cortex sensory input anxiety, memory meningeal irritation increased ICP/ CNS lesion GI CTZ Muscarinic Neurokinin-1 Histamine drugs, metabolic dorsal vagal complex Serotonin Cannabinoid Dopamine serotonin release from mucosal enterochromaffin cells obstruction/ constipation stasis inflammation Vomiting Center VOMITING CENTRE (Central Pattern Generator) Vestibular motion CNS lesions

25 The Mechanistic Approach- Is it? 1. GI stasis 2. Chemically-induced 3. Intracranial Glare et al. Systematic review of the efficacy of anti-emetics in the treatment of nausea in patients with far-advanced cancer Support Care Cancer 12(2004):

26 1. GI stasis - causes Drugs Opioids/ constipation Squashed stomach syndrome tumour, enlarged liver, ascites Gastric/ bowel obstruction tumour symptoms Epigastic discomfort Fullness Early satiety Exacerbated by eating / relieved by vomiting Large volume vomits (undigested food)

27 1. GI stasis - management Prokinetic agent: metoclopramide 10-20mg po/sc/iv q4-8h Also consider: Steroids: dexamethasone 4-8mg s/c qam for 7 days Domperidone (less side effects but not sc) PPI to reduce acidity LAXATIVES

28 2. Chemically-induced nausea - causes Drugs (10%? on initiation of opioids) antibiotics, anticonvulsants, antidepressants, cytotoxics, steroids, digoxin, NSAID s Metabolic renal or hepatic failure, hypercalcemia, hyponatremia, ketoacidosis Toxins ischemic/obstructed bowel, tumour effect, infection symptoms Constant nausea Vomiting is variable in volume & timing May be other features of drug toxicity

29 2. Chemically-induced nausea - management Correct the correctibles. Haloperidol 0.5-1mg po/sc/iv q6-12h Chemo/ Radiation: ondansetron 4-8 mg po/sc/iv q8h Also consider: metoclopramide 10-20mg po/sc/iv q4-8h Useful: Diggs, M. et al. Pharmacovigilance in Hospice/ Palliative Care: Net Effect of Haloperidol for Nausea and Vomiting. J Pall Med 2017 (soon to be published)

30 Intracranial management Correct the correctibles: radiation, surgery dexamethasone 4-8mg s/c qam haloperidol 0.5-1mg po/sc/iv q6-12h Vestibular: dimenhydrinate mg po/sc/iv/pr q4-6h scopolamine patch (Transderm-V )

RECEPTOR ANTAGONISM D 2 H 1 Ach M 5HT 2 5HT 3 5HT 4 CB 1 + 2

Dimenhydrinate + ++++ ++ Ondansetron ++++ Granisetron ++++

31 RECEPTOR ANTAGONISM D 2 H 1 Ach M 5HT 2 5HT 3 5HT 4 CB NK 1 Metoclopramide Domperidone Haloperidol Methotrimeprazine CPZ Olanzapine Prochlorperazine ++ + Dimenhydrinate Ondansetron ++++ Granisetron ++++ Scopolamine Dronabinol, Nabilone, Sativex (++)* *Agonist Aprepitant +++

Radiation ondansetron Intracranial steroids, dimenhydrinate,

32 Summary Episodic nausea/ vomiting Dimenhydrinate. GI stasis metoclopramide Chemically-induced haloperidol Chemo/ Radiation ondansetron Intracranial steroids, dimenhydrinate, haloperidol Consider additional or 2 nd line treatment Don t forget the effect of constipation, anxiety, pain

33 Palliative Sedation or If you can t shake it off, why not just sleep it off?

34 Palliative Sedation the intention of deliberately inducing and maintaining deep sleep, but not deliberately causing death in very specific circumstances 1. For the relief of one or more intractable symptoms when all other possible interventions have failed and the patient is perceived to be close to death, or 2. For the relief of profound anguish (possibly spiritual) that is not amenable to spiritual, psychological, or other interventions, and the patient is perceived to be close to death. Chater et al

35 Moral difference between allowing death and actively taking life context choice of medication titration practice = INTENT

36 Palliative Sedation in palliative medicine- definition and review of the literature drugs used Midazolam 221/328 (case series) and 6/14 (case reports) Methotrimeprazine, Chlorpromazine, Haldol indications agitation/restlessness 26% pain 21% confusion 14% respiratory distress 12% muscle twitching/myoclonus 11% anguish 9% time to death median: days range: days» Cowan and Walsh Support Care Cancer 2001

37 Midazolam Short acting benzodiazepine Onset of sedative effects after IM/SC administration is approx. 15 minutes Peak sedation after minutes Elimination half life in healthy volunteers is 1-3 hours Elimination is prolonged in CHF, CRF and hepatic dysfunction-3-6 hours Dosing should not be based on pharmacokinetic values Should be titrated to a given clinical effect Starting doses in palliative care literature vary from 1-6 mg/hr Loading dose mg sometimes suggested Costly?

38 Methotrimeprazine Highly sedating phenothiazine antipsychotic Good sleeping pill?? Antiemetic activity Analgesic activity? May also potentiate morphine analgesia Anti-cholinergic effects Palliative Sedation Intermittent SC injection Interval q2-12h Both dose and interval need to be titrated Dose range quoted mg/24 hours Extrapyramidal effects rare QT interval prolongation rare (Chater at al)

39 End-of-Life Orders

40 Standard / Standing Orders for Endof-Life Care A core of medications have been found to be useful at the end-of-life: Opioid - for pain or dyspnea» E.g. Morphine 1-2mg. s/c q1h prn. Anti-secretion Sedation - for terminal secretions» E.g. Scopolamine 0.4 mg. s/c q2h prn. - for any distress» E.g. Midazolam mg. s/c q1h prn. Ativan 2 mg. s/l q4h prn. Methotrimeprazine mg. s/c q4h prn.

41 Secretions Scopolamine/ glycopyrrolate X E.g. Scopolamine 0.4 mg. s/c q2h prn. Alternative: Glycopyrrolate 0.4 mg s/c q2hr prn if patient still conscious Scopolamine should be used regularly q4hr if secretions are established

42 Secretions-Scope of Symptom 25-50% of patients in the terminal stage exhibit noise from respiratory/oral secretions or death rattle Most commonly occurs in last h of life

43 Secretions-Non-Pharmacological Treatment Repositioning on different sides Oropharyngeal suctioning if unconscious Reassurance of family members Patient will not suffocate from this Does not indicate shortness of breath Considered a normal part of the dying process

44 Secretions-Pharmacological Treatment Atropine- subcut, sublingual Glycopyrrolate- subcut, oral not available Scopolamine hydrobromide subcut,transdermal Hyoscine butylbromide- po, subcut Potential side-effects: urinary retention,blurred vision, confusion, dry mouth,tachycardia Aim to decrease ongoing production of secretions but does not affect those already present Antimuscarinic agents inhibit salivation at low doses. Bronchial secretions have multiple system inputs- these secretions only partially decreased by antimuscarinics.

45 Hirsch et al. Influences on the decision to prescribe or administer anticholinergic drugs to treat death rattle: A focus group study. Palliative Med 2012;27(8):732 Perceived pressures to prescribe anticholinergics from colleagues and carers. Drugs often prescribed to do something even though benefit perceived to be minimal.

46 Campbell ML, Yarandi HN. Death rattle is not associated with patient respiratory distress: is pharmacologic treatment indicated? J Pall Med 2013 Oct; 16(10) No difference in patient respiratory distress comparing those with and without death rattle. No correlation in intensity of death rattle and respiratory distress. 58% of patients treated for death rattle did not show a decrease in intensity.

47 Likar et al. A clinical study examining the efficacy of scopolaminehydrombromide in patients with death rattle (a randomised double-blind, placebo-controlled study). J Pall Med 2002;3:15 Scopolamine vs placebo given q4h Tendency of scopolamine to reduce death rattle in 1 st 10 h but not statistically significant Small sample size, 31 subjects

48 Heisler et al. Randomized Double-Blind Trial of Sublingual Atropine vs. Placebo for the Management of Death Rattle. J Pain Symptom Manage. 2013;45(1):14 Noise reduction at 4 hours in 39.7% and 51.7% of subjects treated with atropine and placebo respectively, not significant at any time point. 160 subjects, well designed

49 Wildiers et al. Atropine, Hyoscine Butylbromide, or Scopolamine are Equally Effective for the Treatment of Death Rattle in Terminal Care. J Pain Symptom Manage 2009;38(1):124 Randomized open label trial of bolus dose of agent followed by continuous infusion of same agent Decrease in 1 hour in 42%, 42% and 37% for atropine, hyoscine butylbromide and scopolamine respectively. Improved effectiveness over time to 76%, 60% and 68% at 24 hours. No placebo group Median survival after start of therapy 23.9 h

50 Cochrane Collaboration-2009 No evidence to show that any intervention, be it pharmacological or non-pharmacological, was superior to placebo in the treatment of noisy breathing.we acknowledge that in the face of heightened emotions when death is imminent, it is difficult for staff not to intervene.patients need to be closely monitored for lack of therapeutic benefit and adverse effects while relatives need time, explanation and reassurance to relieve their fears and concerns. No update since then

51 Secretions-Future Are non-placebo controlled trials simply showing the natural history of improvement over time? We aren t ethically bound to offer futile treatment such as resuscitation so why offer agents that appear to be no better than placebo? Do we continue to use potentially futile drugs that do have cost/risk associated with them? If it is felt more evidence is needed do we at least limit the use of these medications?

52 There is not support for early initiation of antimuscarinics to prevent worsening of secretions as recommended by some Routine use should be discouraged

53 Proposed Management Thanks: Dr. Jeff Dempster Family/caregiver education that noisy respiratory secretions are a normal part of dying and not distressing to a comatose patient. Repositioning and time are the most appropriate noninvasive strategies. Not all symptoms can be controlled. Antimuscarinics are not routinely used. If a decision is made to use a pharmacological agent then Atropine 1% opthalmic drops, 2 drops sl q2h prn is the least invasive option. Using multiple pharmacologic agents is not recommended.

54 Standard / Standing Orders for Endof-Life Care A core of medications have been found to be useful at the end-of-life: Opioid - for pain or dyspnea» E.g. Morphine 1-2mg. s/c q1h prn. Anti-secretion Sedation X - for terminal secretions» E.g. Scopolamine 0.4 mg. s/c q2h prn. - for any distress» E.g. Midazolam mg. s/c q1h prn. Ativan 2 mg. s/l q4h prn. Methotrimeprazine mg. s/c q4h prn.

55 Transitioning towards palliation: Clarifies realistic and appropriate goals of care with patients / families Helps families to select medical treatments and care settings that meet their goals Coordinates care across multiple subspecialties and disciplines Facilitates transitions within and from hospital Enhances continuity across venues of care

56 Not afraid of Questions

Nausea and Vomiting in Palliative Care

Nausea and Vomiting in Palliative Care Definitions Nausea - an unpleasant feeling of the need to vomit Vomiting - the expulsion of gastric contents through the mouth, caused by forceful and sustained contraction