End-of-Life Care

End-of-Life Care

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End-of-Life Care David Dupéré, MD, FRCPC Date of Revision: July 2015

Introduction

Patients at the end of life are confronted with many troubling symptoms (Table 1) requiring a team approach to care. This chapter provides management strategies for common end-of-life symptoms. The therapies presented are recommended by experienced palliative care teams and can be used in the home setting. Table 1: Symptoms at the End of Life

a

Symptom

Incidence (%)

Noisy and moist breathing

56

Pain

51

Urinary dysfunction

Restlessness and agitation Dyspnea

Nausea and vomiting Sweating

Jerking, twitching a

53 42 22 14 14 12

End of life refers to the final 48 hours of life.

Goals of Therapy

Limit physical and emotional suffering by adequately managing pain and other symptoms

Support the ability to enjoy remaining life while avoiding inappropriate prolongation of death

Investigations

History and physical exam to determine the nature and severity of symptoms

Detailed medication history including nonprescription medications, herbal remedies, vitamins and other natural therapies —having knowledge of the benefit of, or intolerance to, prior treatments can save time Minimal diagnostic testing helps to preserve quality of life—avoid invasive investigations whenever possible

Therapeutic Choices

Four rules are essential for optimal symptom management in the palliative setting: Any symptom is as distressing as a patient claims it to be.

Treatment risks, benefits and alternatives need to be discussed in the context of the dying patient's values, culture, goals and fears. Individualize medication choice and doses—preset recipes are not adequate.

Cause of symptoms is irrelevant and investigation is pointless when disease is advanced and death very near, unless detection would direct a useful change in symptomatic treatment.

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Therapeutic Choices

Patients' awareness of their own breathing is completely subjective, potentially distressing and easily misinterpreted; patient comfort is a priority and an observer's opinion or objective measurements are irrelevant. Manage effectively by choosing therapies that treat symptoms with the greatest impact on activities of daily living. Treat reversible causes or components when appropriate. Associated anxiety requires special management.

Nonpharmacologic Choices Oxygen is a potent symbol of medical care that clearly has a role in the hypoxic patient.2 Carefully consider oxygen use in the hypoxic patient who thinks they will not benefit or the nonhypoxic patient who thinks they will; try on a continuous or as-needed basis and ask the patient if it helps. Similarly, let the patient choose the flow rate. Sometimes a mask with compressed air flow provides a sense of security. Provide reassurance, information and support to the patient and family. Suggest relaxation therapies or breathing exercises.

Suggest physical therapies, e.g., exercise program to avoid deconditioning. Offer an electric fan for cool air flow to face.

Open a window; for bedbound patients, allow clear line of sight to the outside.

Pharmacologic Choices

Table 4 lists drugs used in the treatment of dyspnea.

Respiratory Sedatives Opioids Oral and parenteral opioids are effective and recommended in the management of breathlessness in end-of-life care.3,4 The acute situation may require frequent parenteral dosing (e.g., morphine 5–10 mg sc or iv Q30 minutes until settled). Otherwise, the usual dosing regimen involves Q4H dosing with Q1H breakthrough doses. There is no clear evidence for the role of nebulized opioids.3,4 Sublingual fentanyl has been shown to be effective for breathlessness.5,6 Onset is quick but duration of effect is only about 40–60 minutes.7 Sublingual fentanyl tablets are available in Canada, but the lowest available dose is higher than the usual starting dose of fentanyl for this indication. Some palliative care protocols use the parenteral formulation sublingually at a starting dose of 25–50 µg. This option can be beneficial in the home setting when parenteral access may be limited.8 Patients need access to a home care nurse or a pharmacy willing to prepare doses in advance. Intermittent dyspnea can be treated with intermittent opioids. If titrated to control dyspnea, opioids will not hasten death.9 Nonopioids Benzodiazepines such as clonazepam, diazepam, lorazepam and midazolam have been widely used to manage dyspnea in the palliative care setting, despite a lack of strong evidence of efficacy.10,11 Though their use is not validated, benzodiazepines may provide improved control of dyspnea compared to opioids in terms of duration of action, potency and reduced adverse effects, especially in the absence of pain or when there is a clear component of anxiety. Phenothiazines (e.g., promethazine, chlorpromazine) can effectively relieve refractory cases of dyspnea without causing respiratory depression.12 Corticosteroids have a specific role in the management of dyspnea resulting from obstructive lesions, lymphangitic carcinomatosis or COPD. CNS adverse effects may limit their utility.

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Pain

Therapeutic Choices

Determine the cause. Differentiate nociceptive (somatic, visceral) from neuropathic (dysesthetic, neuralgic) pain to guide the choice of treatment (see Neuropathic Pain). Measure the pain intensity. Numeric rating scales that ask patients to grade their pain on a scale of 0 (no pain) to 10 (worst pain) are easy to use, reproducible and validated.13,14

Review multidimensional aspects of pain. Assess response to, and adverse effects of, previously used analgesics as well as coping skills, past drug/alcohol abuse, concerns about addiction, metabolic abnormalities, cognitive impairment and finances.

Pharmacologic Choices

Table 4 lists drugs used in the treatment of pain. A step-wise approach to pain management is mandated in all cases (see Acute Pain and Neuropathic Pain for discussions of acute pain and neuropathic pain). For mild pain, nonopioid analgesics can be tried (e.g., acetaminophen, ASA, other NSAIDs) with or without an opioid. In the acute palliative care setting, opioids (e.g., morphine and hydromorphone) are usually the mainstay of therapy. Titrate opioid doses gradually to achieve adequate pain control without opioid toxicity.

Use Q4H dosing (po/sc/iv/pr) for dose titration. The acute situation may require more frequent parenteral dosing (e.g., morphine 5–10 mg sc or iv Q30 min until settled).

A breakthrough dose (estimated as 10% of the total 24-hour dose) ordered as Q1H PRN allows for control of interdose pain and provides essential dosing information to help with opioid titration. Regularly review and adjust doses to a new Q4H dose = (all Q4H + all PRN doses in previous 24 hours)/6.

There is no ceiling effect or maximum safe dose for opioids. Patients' response to opioids can vary greatly and doses in the hundreds of milligrams Q4H may be required. Side effects may be the limiting factor. Educate patients and caregivers about anticipated side effects of opioid use (Table 2).

Opioid toxicity can result from altered opioid metabolism (e.g., dehydration, renal failure) and may respond to a dose reduction or, when possible, a correction of the altered metabolism. Significant toxicity requires a switch to another opioid at 50–75% of the equianalgesic dose. Avoid meperidine as its neurotoxic metabolite can accumulate in patients with reduced renal function, possibly causing seizures. Adjuvant drugs (Table 3) may be useful in specific pain syndromes (e.g., corticosteroids in bone pain or hepatic capsular pain). Table 2: Management of Adverse Effects of Opioids Category

Effects

Comments

Management

General

Nausea

Very common, tolerance develops in 2–3 days

Dimenhydrinate or metoclopramide PRN (see Nausea in Adults)

Constipation

Ongoing treatment is mandatory

Daily laxatives (e.g., softener + stimulant, polyethylene glycol + stimulant) (see Constipation in Adults)

Somnolence

Very common, tolerance develops in 2–3 days

Reassure patient

Pruritus

Less common

Antihistamines; may require a change of opioid

Dry mouth

Less common

Chew gum; suck on hard candy or ice chips; use saliva substitutes

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Category

Effects

Comments

Management

Neurotoxic

Myoclonus

Uncommon in early titrated opioid use

May require change of opioid

Delirium

See myoclonus

See myoclonus

Visual hallucinations

See myoclonus

See myoclonus

Table 3: Adjuvant Analgesics Type/Description of Pain Bone pain

Suggested Drug Treatment NSAID with cytoprotection (e.g., naproxena 500 mg BID po/pr with misoprostol 200 µg BID po or omeprazole 20 mg daily po15) Severe cases: dexamethasone 4–8 mg QAM po/sc/iv

Closed space pain

Dexamethasone as for bone pain

Pleuritic pain

NSAID as for bone pain

Neuropathic pain

See Neuropathic Pain

Burning/dysesthetic

Add tricyclic antidepressant (TCA),b e.g., amitriptyline, desipramine or nortriptyline 25 mg BID–TID po; increase gradually up to 150 mg/day if necessary

Shock-like/lancinating

Add gabapentina 300 mg QHS po; increase gradually up to 1200 mg TID if necessary or pregabalina 50–150 mg BID po; titrate weekly by 50–150 mg/day up to a maximum of 600 mg/day Severe cases: dexamethasone as above for severe bone pain

a b

Dosage adjustment may be required in renal impairment; see Dosage Adjustment in Renal Impairment. Decrease doses of TCAs by 50% in the presence of hepatic or renal impairment or in the frail elderly.

Terminal Delirium and Agitation

Therapeutic Choices

Patients often exhibit increasing confusion, drowsiness and/or restlessness and moaning with progressive multi-organ failure. Identify and eliminate reversible causes (e.g., dehydration, visual or hearing impairment)16 although this is rarely successful. Palliative sedation: Consider heavy sedation to render the patient unaware of a severe symptom (e.g., pain, dyspnea, restlessness, hemorrhage) when a usual intervention has not provided an acceptable level of comfort.17 Midazolam and methotrimeprazine are commonly used. Review the option with the patient and/or caregivers and explain that this usually involves cessation of nutrition and hydration. Never give opioids as sedatives.

Nonpharmacologic Choices

Reassure and educate the caregivers about the possibility of delirium and agitation.

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Pharmacologic Choices

Table 4 lists drugs used in the treatment of delirium and agitation. Optimize doses or discontinue current medication (e.g., sedatives).

Haloperidol is the mainstay of treatment for delirium. If doses >20 mg/day are ineffective, consider more sedating agents such as methotrimeprazine or midazolam in regular doses or as a continuous infusion if necessary.

Respiratory Secretions

Therapeutic Choices

Pooling of secretions is common with decreased levels of consciousness. This symptom (unfortunately named “death rattle”) is usually of no consequence to the patient but can be quite distressing to the caregivers.

Nonpharmacologic Choices

Educate the caregivers that the patient is unaware of the distressful breathing sounds and it is not a source of suffering. Position patient semi-prone if possible.

If possible and not too distressing for the patient, use mouth swabs to remove secretions directly.

Pharmacologic Choices

Table 4 lists drugs used in the treatment of respiratory secretions. Regular use of anticholinergics at the onset of this symptom decreases secretions; there is no effect on built-up secretions. Scopolamine is the usual choice but is sedating. To avoid sedation, glycopyrrolate may be given.18

.....

Therapeutic Tips

At the end of life, goals of care focus on achieving patient comfort. Discontinue interventions that do not play a role in supporting comfort (e.g., blood work, vital signs, blood glucose monitoring). Often the routine medical approach (e.g., iv fluid rehydration19) is best replaced by what truly keeps the patient comfortable (e.g., good mouth care to control thirst). Choose medications with the goal of providing comfort. Most medications used to treat chronic diseases (e.g., antianginal agents) rarely have a role at end of life and should be discontinued. Opioids and medications with sedating properties are frequently required and their use should be guided solely by any ongoing need to control symptoms.

Successful end-of-life care in the home requires 24-hour access to a supportive multidisciplinary team ready to deal rapidly with issues as they arise.

Drug Table Table 4: Drugs for End-of-Life Symptoms Class

Drug

Indications

Dosage

Adverse Effects

Comments

Analgesics

morphine M.O.S., Morphine HP Injection, MS-IR, Statex, generics

Pain, dyspnea

PO, immediaterelease: 5–10 mg Q4–6H po + appropriate

Nausea, vomiting, constipation, sedation, drowsiness, confusion, respiratory depression, urinary

Highly individual dosing requirements. Dose escalation based on

Costa $

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Class

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Indications

Dosage

Adverse Effects

Comments

PRN use

retention, dry mouth, myoclonus.

pain relief and adverse effects.

PO, immediaterelease: 2–4 mg Q4–6H + appropriate PRN use

Nausea, vomiting, constipation, sedation, drowsiness, confusion, respiratory depression, urinary retention, dry mouth, myoclonus.

Highly individual dosing requirements. Dose escalation based on pain relief and adverse effects.

$

SL: 25–50 µg (0.5–1 mL parenteral solution 50 µg/mL) Q1H PRN

Nausea, vomiting, constipation, sedation, drowsiness, confusion, respiratory depression, urinary retention, dry mouth, myoclonus.

Highly individual dosing requirements. Dose escalation based on pain relief and adverse effects.

$$$$

IV/SC: 2.5–5 mg Q4–6H + appropriate PRN use Analgesics

hydromorphone Dilaudid, generics

Pain, dyspnea

IV/SC: 1–2 mg Q4–6H + appropriate PRN use Analgesics

fentanyl generics

Dyspnea

Ask patient to hold liquid under tongue for about 10 min without swallowing if possible

Costa

Antiemetics

dimenhydrinateb Gravol Preparations, generics

Nausea, vomiting

PO/IM/PR: 25–50 mg Q4–6H PRN

Sedation, anticholinergic effects, confusion. The elderly may be particularly susceptible.

Additive sedation with other sedating medications.

po/pr: $ im: $$

Antiemetics

metoclopramide Metonia, generics

Nausea, vomiting

PO/SC: 5–10 mg Q4–6H PRN

Diarrhea, abdominal cramps and distention, headache, hyperprolactinemia, drowsiness, fatigue, extrapyramidal effects.

Additive sedation with other sedating medications.

po: $ sc: $$

Antiemetics

prochlorperazine

Nausea, vomiting

PO/IM/PR: 5–10 mg Q4–6H PRN

Sedation, anticholinergic effects (dry mouth, blurred vision,

Additive sedation with other sedating

po/pr: $ im: $$

generics

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Class

https://www.e-therapeutics.ca/print/new/documents/CHAPTER/en/c0118 Drug

Indications

Dosage

Adverse Effects

Comments

constipation, nasal congestion, urinary retention), extrapyramidal effects, hypotension, hypersensitivity; pancytopenia (rare).

medications.

Rarely causes sedation or delirium.

Costa

Antimuscarinics

glycopyrrolate generics

Respiratory secretions

SC: 0.2–0.6 mg Q2–4H PRN

Dizziness, blurred vision, dry mouth, urinary retention.

$$$$ /4 doses

Antimuscarinics

scopolamine (hyoscine hydrobromide)b generics

Respiratory secretions

SC: 0.3–0.8 mg Q2–4H PRN

Sedation, dizziness, blurred vision, dry mouth, urinary retention.

Antipsychotics

haloperidol generics

Agitation, nausea

PO/SC: 0.5–2 mg Q4–8H PRN

Sedation, extrapyramidal effects.

Antipsychotics

methotrimeprazine Nozinan, generics

Agitation, nausea, adjuvant analgesia

PO/SC: 5–10 mg Q4–6H PRN

Sedation, extrapyramidal effects.

po: $ sc: $$

Antipsychotics

chlorpromazine generics

Dyspnea, nausea

PO/SC: 10 mg Q6H

Sedation, extrapyramidal effects. Hypotension with im/iv administration.

$

Benzodiazepines

midazolam generics

Agitation, dyspnea

SC: 1–2 mg Q30 min to Q1H PRN

Sedation, hypotension, transient apnea.

$$$

Benzodiazepines

lorazepam Ativan, generics

Agitation, dyspnea

PO/SL: 1–2 mg Q6–8H PRN

Sedation (up to 80%), dizziness.

$

Benzodiazepines

clonazepam Rivotril, generics

Agitation, dyspnea

PO: 0.25–0.5 mg Q8–12H PRN

Sedation, dizziness.

$

Corticosteroids

dexamethasone Dexasone, generics

Nausea, dyspnea, adjuvant analgesia

PO/SC: 4–8 mg daily

Mood changes, increased appetite, GI irritation, ulceration, fluid

$

$$$ /4 doses

Usual drug of choice.

$

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Class

Drug

Indications

Dosage

Adverse Effects

Comments

retention, weight gain, may mask signs of infection. a b

Costa

Cost of 1-day supply, unless otherwise specified; includes drug cost only. Available without a prescription.

Dosage adjustment may be required in renal impairment; see Dosage Adjustment in Renal Impairment.

Legend:

$ <$5

$$ $5–25

$$$ $25–45

$$$$ $45–65

Suggested Readings

Canadian Coalition for Seniors' Mental Health. Guideline on the assessment and treatment of delirium in older adults at the end of life. Toronto (ON); 2010. Available from www.ccsmh.ca/pdf/guidelines/NatlGuideline_DeliriumEOLC.pdf. LeGrand SB. Delirium in palliative medicine: a review. J Pain Symptom Manage 2012;44(4):583-94. Lo B, Rubenfeld G. Palliative sedation in dying patients: “we turn to it when everything else hasn't worked”. JAMA 2005;294(14):1810-6. Morrison RS, Meier DE. Clinical practice. Palliative care. N Engl J Med 2004;350(25):2582-90. Quigley C. The role of opioids in cancer pain. BMJ 2005;331(7520):825-9. Stevenson J, Abernethy AP, Miller C et al. Managing comorbidities in patients at the end of life. BMJ 2004;329(7471):909-12. University of Toronto, Faculty of Medicine, Continuing Education. Ian Anderson continuing education program in end-of-life care. Toronto (ON): University of Toronto. Available from: www.cme.utoronto.ca/endoflife/.

References 1. Lichter I, Hunt E. The last 48 hours of life. J Palliat Care 1990;6(4):7-15. 2. Bruera E, de Stoutz N, Velasco-Leiva A et al. Effects of oxygen on dyspnoea in hypoxaemic terminal-cancer patients. Lancet 1993;342(8862):13-4. 3. Jennings AL, Davies AN, Higgins JP et al. Opioids for the palliation of breathlessness in terminal illness. Cochrane Database Sys Rev 2001;(4):CD002066. 4. Viola R, Kiteley C, Lloyd NS et al. The management of dyspnea in cancer patients: a systematic review. Support Care Cancer 2008;16(4):329-37. 5. Benitez-Rosario MA, Martin AS, Feria M. Oral transmucosal fentanyl citrate in the management of dyspnea crises in cancer patients. J Pain Symptom Manage 2005;30(5):395-7. 6. Gauna AA, Kang SK, Triano ML et al. Oral transmucosal fentanyl citrate for dyspnea in terminally ill patients: an observational case series. J Palliat Med 2008;11(4):643-8. 7. Zhang H, Zhang J, Streisand JB. Oral mucosal delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet 2002;41(9):661-80. 8. Harlos M. Palliative care incident pain and incident dyspnea protocol. Winnipeg (MB): Palliative Medicine, University of Manitoba; 2002. Available from: www.palliative.info/incidentpain.htm. 9. Gallagher R. Killing the symptom without killing the patient. Can Fam Physician 2010;56:544-6. 10. Simon ST, Higginson IJ, Booth S et al. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev 2010;20(1):CD007354. 11. Wedzicha JA, Wallis PJ, Ingram DA et al. Effect of diazepam on sleep in patients with chronic airflow obstruction. Thorax 1988;43(9):729-30. 12. O'Neill PA, Morton PB, Stark RD. Chlorpromazine--a specific effect on breathlessness? Br J Clin Pharmacol 1985;19(6):793-7. 13. McCaffery M, Pasero C. 0-10 numeric pain rating scale. In: Pain: clinical manual. St. Louis (MO): Mosby; 1999. p. 16. 14. Hawker GA, Mian S, Kendzerska T et al. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant

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https://www.e-therapeutics.ca/print/new/documents/CHAPTER/en/c0118 Osteoarthritis Pain (ICOAP). Arthritis Care Res (Hoboken) 2011;63(Suppl 11):S240-52. 15. Singh G, Triadafilopoulos G. Appropriate choice of proton pump inhibitor therapy in the prevention and management of NSAID-related gastrointestinal damage. Int J Clin Pract 2005;59(10):1210-7. 16. Casarett DJ, Inouye SK et al. Diagnosis and management of delirium near the end of life. Ann Intern Med 2001;135(1):32-40. 17. Cherny NI, Radbruch L. European Association for Palliative Care (EAPC) recommended framework for the use of sedation in palliative care. Palliat Med 2009;23(7):581-93. 18. Wildiers H, Menten J. Death rattle: prevalence, prevention and treatment. J Pain Symptom Manage 2002;23(4):310-7. 19. Bruera E, Hui D, Dalal S et al. Parenteral hydration in patients with advanced cancer: a multicenter, double-blind, placebocontrolled randomized trial. J Clin Oncol 2013;31(1):111-8.

CPhA assumes no responsibility for or liability in connection with the use of this information. For clinical use only and not intended for for use by patients. Once printed there is no quarantee the information is up-to-date. [Printed on: 03-02-2016 07:14 PM] RxTx, Compendium of Therapeutic Choices © Canadian Pharmacists Association, 2016. All rights reserved

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