Inpatient Palliative Medicine Update

David Dupere MD, FRCPC

Head, Division of Palliative Medicine

Department of Medicine

QEII Health Sciences Centre

Halifax, Nova Scotia

Disclosures

Book chapter in Compendium of Therapeutic Choices, Canadian Pharmacists Association.

There will be off-label recommendations for some of the medications mentioned today.

• Prognostication and the Transition to Palliation

• Nausea and Vomiting Control

• In Support of Palliative Sedation

• Changes in End of Life Symptom Management

Chances of dying during the average Canadian lifespan

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 / life-extending efforts

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

Transitions To Palliation-The Cost of Dying in Canada

Palliative Care is YOU !

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 scenariosvs.

– Times of crisis

• Worst possible time to make difficult decisions• Is usually when the ‘BIG’ decisions are actually made…

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

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

Lau, F. et al. Using the Palliative Performance scale to Provide Meaningful Survival Estimates. J Pain Sympt Manage: 2009; July, 38(1), 134-144.

The better Trigger?-The ‘Surprise Question’

“Would I be surprised if this patient died within the next year?”

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.’

…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

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

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

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.

• Well meant…

• 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

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’

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”

…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 Controlor, “Whaaa... Ondanestron is NOT the true ‘Super’ anti-nauseant?”

Useful: Gupta et al. Nausea and vomiting in advanced cancer- the Cleveland Clinic Protocol. J Support Oncol. 2013 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;39:756–767.

Cortex

• CTZ

Vestibular

GI

VOMITING

CENTRE• serotonin release from mucosal

enterochromaffin cells

• obstruction/constipation

• stasis

• inflammation

• motion• CNS lesions

• drugs, metabolic

• sensory input

• anxiety, memory

• meningeal irritation

• increased ICP/ CNS

lesion• dorsal vagal complex

Vomiting Center

(Central Pattern Generator)

Cortex

• CTZ

Vestibular

GI

VOMITING

CENTRE• serotonin release from mucosal

enterochromaffin cells

• obstruction/ constipation

• stasis

• inflammation

• motion• CNS lesions

• drugs, metabolic

• sensory input

• anxiety, memory

• meningeal irritation

• increased ICP/ CNS

lesion• dorsal vagal complex

Muscarinic

Neurokinin-1

Histamine

Serotonin

Cannabinoid

Dopamine

Vomiting Center

(Central Pattern Generator)

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 cancerSupport Care Cancer 12(2004):432-440

1. GI stasis -

causes symptoms

• Drugs– Opioids/ constipation

• ‘Squashed stomach syndrome’– tumour, enlarged liver, ascites

• Gastric/ bowel obstruction– tumour

• Epigastic discomfort

• Fullness

• Early satiety

• Exacerbated by eating / relieved by vomiting

• Large volume vomits (undigested food)

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

2. Chemically-induced nausea -

causes symptoms• 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

• Constant nausea

• Vomiting is variable in volume & timing

• May be other features of drug toxicity

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)

Intracranial – management

• Correct the correctibles:– radiation, surgery

• dexamethasone 4- 8mg s/c qAM• haloperidol 0.5- 1mg po/sc/iv q6-12h

• Vestibular:– dimenhydrinate 25-100mg po/sc/iv/pr q4-6h– scopolamine patch (Transderm-V®)

RECEPTOR ANTAGONISM

D2 H1 AchM 5HT2 5HT3 5HT4 CB1 + 2 NK1

Metoclopramide +++ + ++

Domperidone ++++ +

Haloperidol ++++ +

Methotrimeprazine ++++ +++ ++ +++

CPZ ++++ ++ +

Olanzapine ++ + + +++ ++

Prochlorperazine ++ +

Dimenhydrinate + ++++ ++

Ondansetron ++++

Granisetron ++++

Scopolamine + + ++++

Dronabinol, Nabilone,

Sativex(++)**Agonist

Aprepitant +++

Summary • Episodic nausea/ vomiting…Dimenhydrinate.

• GI stasis– metoclopramide

• Chemically-induced– haloperidol

• Chemo/ Radiation– ondansetron

• Intracranial– steroids, dimenhydrinate, haloperidol

• Consider additional or 2nd line treatment

• Don’t forget the effect of constipation, anxiety , pain

Palliative Sedation

or ‘If you can’t shake it off, why not just sleep it off?’

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

Moral difference between allowing death and actively taking life

• context

• choice of medication

• titration practice

= INTENT

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: 1.3- 4 days– range: 0.1- 11 days

» Cowan and Walsh Support Care Cancer 2001

Midazolam

• Short acting benzodiazepine

• Onset of sedative effects after IM/SC administration is approx. 15 minutes

• Peak sedation after 30-60 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 2.5-5 mg sometimes suggested

• Costly?

Methotrimeprazine

• Highly sedating phenothiazineantipsychotic– Good ‘sleeping pill’ ??

• Antiemetic activity

• Analgesic activity?– May also potentiate morphine

analgesia

• Anti-cholinergic effects

• Extrapyramidal effects rare

• QT interval prolongation rare

• Palliative Sedation

– Intermittent SC injection

– Interval q2-12h

– Both dose and interval need to be titrated

• Dose range quoted 50-250 mg/24 hours

(Chater at al)

End-of-Life Orders

Standard / ‘Standing’ Orders for End-of-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 - for terminal secretions» E.g. Scopolamine 0.4 mg. s/c q2h prn.

• Sedation - for any distress» E.g. Midazolam 1-2.5-5 mg. s/c q1h prn.

Ativan 2 mg. s/l q4h prn.

Methotrimeprazine 12.5–50 mg. s/c q4h prn.

Secretions

• Scopolamine/ glycopyrrolate

– E.g. Scopolamine 0.4 mg. s/c q2h prn.

– Alternative: Glycopyrrolate 0.4 mg s/c q2hr prnif patient still ‘conscious’

– Scopolamine should be used regularly q4hr if secretions are established

X

• 25-50% of patients in the terminal stage exhibit noise from respiratory/oral secretions or ‘death rattle’

• Most commonly occurs in last 24-48 h of life

Secretions-Scope of Symptom

• 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

Secretions-Non-Pharmacological Treatment

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.

• Perceived pressures to prescribe anticholinergics from colleagues and carers.

• Drugs often prescribed to ‘do something’ even though benefit perceived to be minimal.

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

• 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.

Campbell ML, Yarandi HN. Death rattle is not associated with patient respiratory distress: is pharmacologic treatment

indicated? J Pall Med 2013 Oct; 16(10)

• Scopolamine vs placebo given q4h

• Tendency of scopolamine to reduce death rattle in 1st 10 h but not statistically significant

• Small sample size, 31 subjects

Likar et al. A clinical study examining the efficacy of scopolamine-hydrombromide in patients with death rattle (a randomised double-blind,

placebo-controlled study). J Pall Med 2002;3:15

• 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

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

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

‘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

Cochrane Collaboration-2009

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?

Secretions-Future

• There is not support for early initiation of antimuscarinics to prevent worsening of secretions as recommended by some

• Routine use should be discouraged

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 non-invasive 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.

Proposed ManagementThanks: Dr. Jeff Dempster

Standard / ‘Standing’ Orders for End-of-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 - for terminal secretions» E.g. Scopolamine 0.4 mg. s/c q2h prn.

• Sedation - for any distress» E.g. Midazolam 1-2.5-5 mg. s/c q1h prn.

Ativan 2 mg. s/l q4h prn.

Methotrimeprazine 12.5–50 mg. s/c q4h prn.

X

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

Not afraid of Questions…