Palliation of Non-Pain

Symptoms in Cancer Care

Palliative Care

The physician who sees his role only as the curer of

disease or the battler against death is often helpless;

the physician who knows that his function is to help the

sick to the limit of his ability is almost always able to

offer something. In his care, the sick are protected from

helplessness, fear, and loneliness, agonies that are

worse than death.

ERIC J. CASSEL, THE HEALERS ART, 1976, Chapter 7

Create the Best Palliative Care & EOL Experience for Patient, Family & Caregivers

Provide family guidance, support

Clinician - calm, supportive, communicative, provide appropriate referrals

Psychosocial & spiritual concerns

Physical

Objectives

At the end of this lecture, participants should be able to assess and manage some common physical symptoms in the context of supportive and palliative care: Pain

Dyspnea/Breathessness

Restlessness/Agitation/Delirium

Nausea/Vomiting

Respiratory Tract Secretions

Listen to the patient.

Make a diagnosis before treating.

Reflex prescription of an antiemetic to every patient with

nausea and vomiting, for example, will not benefit the patient

who is vomiting because of fecal impaction or because of

hypercalcemia.

In palliative care, as elsewhere in Medicine, choosing the most

appropriate treatment depends on the underlying pathology.

General Principles of Palliative Care in Advanced Cancer

Terminally ill patients are likely to have multiple (~7 to11) symptoms, most of which will be actual or potential sources of distress.

Ask the patient to describe every symptom.

Enlist the patients help to assign priorities to his problems:

What distresses you the most? The patients priorities, not the doctors, should govern the treatment plan.

Explore the significance that each symptom has for the patient.

Track symptoms at every visit.

Dyspnea

Anorexia-Cachexia Syndrome

Nausea and vomiting

Pain

Weakness and fatigue

Constipation

Ascites

Infection

Insomnia

Anxiety

Terminal Restlessness

Overview Of Palliative Care of Advanced Cancers

Explanation is part of the treatment.

Know the drugs that you use and know them well.

The informed and judicious use of pharmacologic agents is

the cornerstone of palliative medicine.

Learn the characteristics of the drugs, lest untoward drug

reactions or interactions aggravate the patients suffering.

Put it in writing.

Keep It Simple Please

Whenever possible, use

portmanteau

medications, i.e.,

medications that will

accomplish more than

one objective.

Drug Indications in Palliative

Care

Haloperidol

Nause & vomiting (among the

most potent inhibitor of the CTZ)

Confusional states & delirium

Diphenhydramine Vomiting & metabolically

related nausea (acts on the

vomiting center, vestibular

apparatus & cholinergic receptors

peripherally)

To combat extrapyramidal

effects of haloperidol &

metoclopramide

To provide mild sedation

Better if regimens are:

OD or BID than q4h or

q6h

Low technology

comfort measures

(such as hot water

bottles), than more

complicated & more

intimidating devices.

Assessment instruments

Visual analog scale (VAS)

Numeric Rating Scale (NRS)

Symptom inventories

Careful records

Physical Aspects of Palliative Care

Dyspnea/Breathlessness

Dyspnea etiology

Dyspnea is common, affecting 50-70% of cancer patients with life-limiting illness

As disease worsens, breathlessness occurs more frequently on exertion and at rest

Dyspnea worsens during the dying process

Anxiety can aggravate the symptom and fuel a progressive spiral of cause and effect

Challenge Highly subjective, complicating assessment Sensation of breathlessness that arises from a

combinations of: Underlying pathology Signaling of neural pathways Patient perception of physical sensations

Patient experience varies widely and depends partly on: Disease, Ethnic/racial background, Previous experience Emotional state

Often seems out of proportion, must be treated as reported

Current

evidence supports the use of oral or parenteral opioids as the mainstay of dyspnea management, & of anxiolytics as adjuncts.

Kamal et al, J. of Palliative Medicine, 2012

Palliation of Respiratory Symptoms

Palliation of Respiratory Symptoms

Morphine and other opioids, given in small doses orally,

sublingually, or by injection, can provide dramatic relief for

many patients without causing respiratory depression.

- Ferraresi V., Am J Health-Syst Pharm.

2005;62(3):319-320.

Reduce anxiety Reduce sensitivity to

hypercapnea Improve cardiac

function Reduce concurrent

pain that may be a factor in producing anxiety and sensation of dyspnea

With proper titration, opioids can be used to relieve dyspnea by decreasing RR, while avoiding iatrogenic hypercarbia or hypoxia.

There were no events of respiratory depression or cognitive impairment in a frail, elderly population in a prospective study by Currow et al.

Kamal et al, J. of Palliative Medicine, 2012

Palliation of Dyspnea: Opioids (Morphine)

Opioid dosing for dyspnea Opioid nave:

Start at 20mg QD, sustained release morphine (assuming drug availability and no contraindications)

Increase to twice a day after 5-7 days if well tolerated

Opioid-tolerant, on morphine or opioid equivalent: Increase opioid by 20% of total daily dose every 3-5 days until

breathlessness is relieved or side effects

Patients with a morphine contraindication: Long acting oxycodone - 10mg QD Increase to BID after 5-7 days, as tolerated, if needed

Patients with AKI or CKD: Fentanyl

Severe, acute dyspnea: 2-5mg IV morphine every 5-10 minutes

Evidence Meta-analysis of 9 studies on use of opioids through 2001 to evaluate

effect on reliving dyspnea1: Highly statistically significant effect of oral and parenteral opioids on sensation of

breathlessness

Pooled effect size - 0.31, 95% CI -0.50 to -0.13, p=0.0008

Eight-day, randomized, double-blind, crossover clinical trial of 48 patients with refractory dyspnea2 20mg oral morphine sulfate (24-hr. sustained release) or placebo

1 outcome breathlessness sensation on a 100mm VAS

Mean baseline morning dyspnea score 43 (SD 26)

Morphine mean improvements of 6.6mm in morning (p=0.011) and 9.5mm in evening (p=0.006)

Relative improvement over baseline 15-22%

Morphine did not supress respiratory rate

Main side-effect was constipation 1Jennings AL et al. Thorax 2002;57:939-44. 2Currow DC, Abernethy AP et. al. British Medical Journal 2003;21; (327:1288c..

Other drugs for dyspnea-related symptoms

Benzodiazepines for patients with dyspnea that is aggravated by anxiety Midazolam, Alprazolam- short-acting Clonazepam- longer-acting control

Anti-tussives for coughing Anti-cholinergics (hyoscine n-butyl-bromide) to

minimize secretions Diuretics Bronchodilators Corticosteroids

Oxygen and non-pharmacologic management of dyspnea

Palliative oxygen -often prescribed but not effective

Recent multi-national, randomized controlled trial - palliative O2 found no difference in breathlessness with patients who received medical air through nasal cannulae

Fan

Psychosocial support to alleviate axiety and distress

Patient positioning

Pursed lip breathing

Relaxation techniques (e.g. massage, guided imagery)

Discuss symptom management with family, alleviate concerns, opioids may hasten death

Summary: Palliation of Dyspnea

Assessment is complicated due to highly subjective nature

Oral and parenteral opioids have a significant effect on breathlessness

Morphine alleviates sensation of breathlessness without reducing respiratory rate, but causes constipation

Medical gas may benefit, but not specifically oxygen

Physical Aspects of Palliative Care

Restleness/Agitation/Delirium

Identifying delirium Occurs in 28% to 83% of patients at EOL

Characterized by disturbance of consciousness, cognition, and perception.

Source of distress for the patient, loved ones, and care team.

Indirect result of various factors associated with the patients underlying cancer: Treatment side effects, metabolic disordering, nutritional deficiency, or infections

Opioid side-effects appear to be most common cause

Identifying Delirium

Two types of delirium:

Agitated/hyperactive delirium

Hypoactive delirium

Assessment scales:

Delirium Rating Scale

Confusion Assessment Method

Delirium Symptom Interview

Memorial Delirium Assessment Scale

Mini-Mental State Examination (MMSE)

Management

Discontinue all non-essential medication, especially psychoactive ones

Ensure not due to pain, urinary retention, or constipation.

Presence of family and loved ones, and familiar surroundings, help ease delirium

Avoid sedation or treating agitation, instead try to restore to baseline mental state

IV or oral Haloperidol - start at 0.5 mg bid

Other options: Chlorpromazine, Risperidone, and Olanzapine

Generally more expensive, no data showing they are more effective or safer

May use benzodiazepines (lorazepam, midazolam) but can worsen delirium

Physical Aspects of Palliative Care

Nausea / Vomiting (N/V)

Etiology

Some cancer patients continue to experience nausea and vomiting after treatment has been discontinued

N/V troubles up to 70% of cancer patients at EOL

Attempt to determine underlying cause and appropriate course to ease patients discomfort

N/V Contributing Factors

Opioid pain medications

Autonomic failure

Peptic ulcer disease

Constipation

Bowel obstruction

Metabolic abnormalities

Increased intracranial pressure

Pain

Strategies to consider

Select first-line anti-emetic and administer via a suitable route e.g. oral or if not, intravenous, SC, and intramuscular routes

Use anti-emetics regularly

Add second-line or combination therapy if symptoms persist

Address other, reversible, causes of N/V separately Hypercalcemia

Optimize renal function

Stop emetogenic therapies if possible

Treat delayed gastric emptying

Manage bowel obstruction

Management

Need to consider potential mechanism(s) of N/V and the site(s) of action

Metoclopramide for chronic nausea if bowel obstruction is not an issue

Dexamethasone and other corticosteroids can augment metoclopramide, 5-HT3 antagonists, and other anti-emetics effects

Benzodiazepines often effective

If bowel obstruction present, consider centrally active drugs like haloperidol and dimenhydrinate

Octreotide

Refractory nausea may respond to palliative sedation with midazolam

Causes of N/V

Anti-emetic Class of drug Example dose schedule

Common side-effects

Chemotx Acute emesis(24h) Ondansetron and/or Dexamethasone

5-HT3 antagonist

Corticosteroid

Ondansetron - 16mg PO, dexamethasone 8mg, daily in single or dividied doses

Constipation, headache Agitation/insomnia, gastric irritant

Prochlorperazine Dopamine antagonist

10mg PO or IV every 6 hours

Sedation, EPS

Anticipatory Lorazepam Benzodiazepine 12 mg PO or IV prn, max 4 mg/24 h

Sedation

Iatrogenic, e.g. opiates

Metaclopramide

Haloperidol

Prokinetic Dopamine antagonist

10mg PO or IV every 8 hours prn 1.53 mg PO every 8 hours prn

Agitation Sedation, extrapyramidal effects (EPS)

Gastric irritation including Radiotx

Lansoprazole Ondansetron

Prochlorperazine

Proton pump inhibitor 5-HT3 antagonist

Dopamine

30 mg PO daily 4-8 mg PO every 8 hours prn

10mg PO or IV every 6 hours prn

Constipation, headache

Sedation, extrapyramidal

Physical Aspects of Palliative Care

Respiratory Tract Secretions

Situation

Common at EOL - occurring in up to 90% of unconscious patients1-4

Respiratory tract secretions are a strong predictor of death - 48% within 24-hours and 76% within 48-hours of onset

May not be distressing to patient at EOL but troubling for those at the bedside

Cause- oscillatory movements of accumulated bronchial mucosa and salivary secretions that the patient is unable to clear

Avoid using the term death rattle with family, consider congestion instead

Non-pharmacologic treatment

Reposition - supine to lateral recumbent with head slightly raised

Suction sparingly - most secretions are below the larynx and inaccessible & frequent suctioning can be unsettling to patient and family

Communication with the family about what is happening

Pharmacologic management

Anticholinergic/antisecretory agents (Hyoscine n-butyl- bromide 10-20 mg p.o. or IV q6h-q8h), may be effective in reducing saliva and mucus production - use at first sign since they are not effective on existing secretions

Muscarinic receptor blockers; use sparingly side effects are substantial Scopolamine patch

Glycopyrrolate

Atropine

Terminal Care: Nutrition & Hydration

During the last days of life, patients tend naturally to take in less and less food and fluid.

Hunger is rare in the last days of life.

Thirst occurs more commonly, but without relation to dehydration, and can usually be controlled by simple measures (e.g., moistening the lips, giving small sips of fluids or small amounts of crushed ice to suck).

Enteral feeding should be stopped when the patient can no longer swallow reliably.

Terminal Care: Hydration

In most cases, parenteral (IV) fluids should not be given in the last hours of life.

Allowing the patient to become slightly dehydrated may prevent or ameliorate many otherwise distressing problems in the last hours:

Consequence of IV

Hydration

Symptoms

Respiratory secretions Cough Pulmonary congestion

Sensations of choking & drowning

Urine Output Bedwetting, bedpans, catheters

Gastrointestinal secretions Vomiting

Total body water Edema, ascites, pleural effusions

Serum urea Awareness Distress, Pain threshold

Psychosocial Support of the Patient and the Family

In addition to anxiolytics and antidepressants, supportive counseling, spiritual counseling, and family support can help counter feelings of depression and anxiety

There is nothing more that can be done does not exist in the lexicon of palliative medicine

There is always something that can be done, even if it is simply to sit beside the patient and hold her hand and offer a few words of comfort and solidarity.

1) To see the patient & the family through

- the physical & emotional stages of terminal illness

2) To ease their burden along the way

- to walk alongside, not to give orders from above

3) To be there

- when symptoms arise, when hard questions have

to be faced, when fear & loneliness threaten

TASKS OF THE MULTIDISCIPLINARY

PALLIATIVE CARE TEAM

TASKS OF THE MULTIDISCIPLINARY

PALLIATIVE CARE TEAM

To apply to the care of the chronically-ill,

the terminally-ill, &

the dying

the same high standards

of clinical analysis &

decision-making as are

demanded in the care of

patients expected to

get well

Death is not extinguishing the light;

it is putting out the lamp because the Dawn has come.

- Rabindranath Tagore

ACKNOWLEDGEMENT:

Some content of the slides adapted from:

Amy P. Abernethy, MD Division of Medical Oncology

Department of Medicine

Duke University Medical Center, USA