Dilemmas in Non-Pain Symptom Management at

the End of Life

Jean S. Kutner, MD, MSPH Gordon Meiklejohn Endowed Professor and Division Head

Division of General Internal Medicine Department of Medicine

University of Colorado School of Medicine

Dyspnea

Should I use opioids to treat dyspnea in a patient with end-

stage COPD?

What is the best next step? 61 yo woman with end-stage COPD c/o increasing dyspnea. Exam: 90/55, 100, 25; acrocyanosis, skin mottling, JVD. No audible breath

sounds. O2 sat = 84%. Meds: oral prednisone; inhaled anitcholinergic & sympathomimetic agents; O2

@ 4 lpm via nasal cannula. In addition to increasing her oxygen flow, what is the most appropriate next

step?

a)  Add lorazepam, starting at 0.5 mg po and increase as tolerated b)  Add olanzapine, starting at 2.5 mg po and increase as tolerated c)  Add morphine, starting at 5 mg po and increase as tolerated d)  Add morphine, starting at 5 mg nebulized and increase as tolerated

Dyspnea – American Thoracic Society Definition

“A subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity, not necessarily related to hypercapnia or hypoxia.”

Dyspnea – Patient Definition

“I feel like a fish wrapped in a wet paper towel.” (patient with end-stage COPD)

•  Complex physiological and psychological sensation

•  Usually multifactorial •  First treat underlying causes

– e.g. pleural effusions, anemia – Not always possible or consistent with patient

goals •  Often need symptomatic treatments

Dyspnea Measurement •  4 measurement types

–  Intensity –  Impact on activity and performance –  Health-related quality of life –  Qualitative descriptors

•  > 40 existing instruments –  Self-report (dyspnea) and observational (respiratory

distress) –  No one tool superior – USE SOMETHING AND USE

IT CONSISTENTLY!

Dyspnea - Treatment

“Paucity of randomized controlled trials on interventions for alleviation of

dyspnea in these distressed patients.” (J Clin Oncol. 2008. 26: 2396)

Dyspnea Pharmacologic Treatment

Opioids: RCTs, meta-analyses and systematic

reviews: – Strong evidence supporting oral and systemic

(IV and subq) opioids •  Most studies in COPD, but short duration studies •  Little evidence in cancer, HF

– Nebulized morphine: use not supported by currently available evidence

Beta-agonists •  Strong evidence for COPD

Oxygen •  COPD: Strong evidence supports use during

exercise •  Cancer: only positive benefit when hypoxemic

Benzodiazepines •  Possible beneficial effect when added to opioids

Dyspnea: Non-Pharmacologic Treatment

Recommend based on available evidence •  Neuroelectrical muscle stimulation (COPD) •  Chest wall vibration (COPD) •  Walking aids (COPD) •  Breathing training

Not enough evidence to recommend •  Acupuncture/acupressure •  Distractive auditory stimuli (music) •  Relaxation •  Fan •  Counseling and support programs •  Case management •  Psychotherapy

Nausea & Vomiting

Should I use a standard set of medications to treat nausea and

vomiting in a patients with end-stage disease?

What is the best next step?

50 yo man with metastatic esophageal cancer treated with 3rd line palliative chemotherapy, admitted to hospital with intractable n/v. normal daily BM. Trial of ondansetron at home ineffective.

Exam: moist mucus membranes; no oral thrush; no abd tenderness or distention, no HSM, normal BS. Labs normal. Films: no dilated bowel loops.

What is the best approach to treating this patient’s intractable n/v?

a)  IV fluids and NPO b)  Continue ondansetron, changing from po to IV c)  Add dopamine antagonist, such as haloperidol or prochlorperazine d)  Add anticholinergic, such as scopolamine or promethazine

Copyright restrictions may apply.

Wood, G. J. et al. JAMA 2007;298:1196-1207.

History and Physical Examination: Clues to Specific Etiologies of Nausea and Vomitinga

Copyright restrictions may apply.

Wood, G. J. et al. JAMA 2007;298:1196-1207.

Interrelationships Between Neural Pathways That Mediate Nausea and Vomiting

Copyright restrictions may apply.

Wood, G. J. et al. JAMA 2007;298:1196-1207.

Common Clinical Scenarios Associated With Nausea and Vomiting at the End of Life

Copyright restrictions may apply.

Wood, G. J. et al. JAMA 2007;298:1196-1207.

Antiemetics

N/V – Recommended Approach •  Careful hx and PE •  Mechanism-based treatment scheme

–  Administer the most potent antagonist to the implicated receptors

–  Address all potential underlying causes simultaneously

•  Consider anti-emetic side effect profile •  Schedule anti-emetics around the clock •  Adding a second agent preferable to switching

agents since is usually multifactorial

Small Bowel Obstruction

Should patients with end-stage cancer with a small bowel

obstruction undergo surgery?

What is the best next step?

75 yo woman with advanced ovarian cancer, admitted to the hospital because of a small bowel obstruction with abdominal distention, crampy abdominal pain and nausea/vomiting. She has stated that her primary goal is to at home and be comfortable. She has significant cachexia and poor functional status.

In addition to administering a corticosteroid, what is the most appropriate next step?

a)  Add an opioid b)  Add octreotide c)  Undergo surgical treatment d)  Add scopolamine

Distention-secretion-motor activity causing GI sx in SBO

PG= prostaglandins; VIP = vasoactive intestinal peptide

Ripamonti, C. 2001

Management - Surgery

•  No consensus on indications for conservative vs. surgical treatment in advanced cancer patients

•  Surgery only benefits selected patients with mechanical obstruction

•  Consider whether palliative surgery is technically feasible and whether pt is likely to benefit –  Operative mortality 9 – 40% –  Complication rates 9 – 90%

Contraindications to surgery (end-stage cancer patients)

Absolute •  Recent laparotomy – further

corrective surgery not possible •  Previous abdominal surgery

demonstrating diffuse metastatic cancer

•  Involvement of proximal stomach

•  Intra-abdominal carcinomatosis with severe motility problem

•  Diffuse palpable intra-abdominal masses

•  Massive ascites rapidly recurring after drainage

Relative •  Symptomatic extra-abdominal

metastases •  Extensive extra-abdominal

malignant disease •  Poor general performance

status •  Poor nutritional status •  Advanced age in association

with cachexia •  Previous radiotherapy of the

abdomen or pelvis

Management - Stents •  Useful: patients

with advanced metastatic disease and poor surgical risk

•  Contraindications: presence of multiple stenoses, peritoneal carcinomatosis

Management – NG suction

•  Use only as a temporary measure - to reduce large amount of secretions before start of pharmacologic treatment

•  Not justified if sx controlled by medications alone

•  Intrusive and distressing for patients and families

•  Complications common

Management: Pharmacologic tx •  Goal: relieve nausea, vomiting and pain •  Antiemetics: refer to nausea / vomiting talk

–  Metoclopramide - for functional obstruction –  Haldoperidol – potent suppressor of chemoreceptor trigger zone –  Corticosteroids – also reduce peri-obstruction edema

•  Antisecretory: –  Anticholinergics (hyoscyamine, glycopyrrolate, scopolamine,

atropine) –  Somatostatin analogues (octreotide) – more effective

•  Pain –  Titrate opioid to relief –  Add hyoscyamine for colic

Management: Venting Gastrostomy

•  Consider if drugs not successful •  Allows patient to maintain oral intake and

active lifestyle without inconvenience and discomfort of NGT.

Management: IV fluids and nutrition

•  IV hydration –  Intensity of dry mouth and thirst independent of

quantity of oral and IV hydration •  Use local measures (sips, ice chips, mouth care)

–  Intensity of nausea lower in with 1 L/day IV hydration –  Increased bowel secretions with more hydration –  Balance benefits and burdens

•  TPN –  Role in this setting controversial – limited indications –  Consider functional status, prognosis

Fatigue

Are there any effective treatments for fatigue in the setting of

advanced illness?

What is the best next step? 72 yo man with ischemic cardiomyopathy and severe COPD. He has not smoked for the past 2 years, since his last MI. Gradual progression of CHF despite intensive medical regimen. Has been hospitalized for several episodes of pneumonia and CHF exacerbations. O2-dependent and struggles with his ADLs, tiring easily and requiring a wheelchair for excursions outside his home. He has told you that he does not want to be “kept alive by machines” but that he is afraid of dying alone and in pain. He complains of decreased energy (“I’m sleeping all the time”) and anorexia (“I just don’t feel like eating”). He also has become more short of breath.

. What is the most appropriate next step?

a)  Add an opioid b)  Transfuse 2 u prbc c)  Add methylphenidate d)  Maximize CHF and COPD therapy

Fatigue (Asthenia)

•  Profound tiredness occurring after usual or minimal effort

•  Physical, mental or emotional manifestations

•  Often the most distressing symptom •  Influences: sense of well-being, ADLs,

relationships with family and friends, daily performance

Fatigue

Includes: – Muscle weakness – Lethargy – Sleepiness – Mood disturbance (depression) – Cognitive disturbance (difficulty concentrating)

Causes of Fatigue in Advanced Illness

FATIGUE

Drug effects

Anemia

Cachexia Chronic hypoxia Dehydration

Endocrine disorders

Infection

Metabolic & electrolyte

Neurologic disorders

Physical symptoms (pain)

Sleep disturbance

Psychological/ spiritual distress

Additional Mechanisms of Fatigue in CHF

•  Reduced cardiac output •  Reduced oxygen delivery

– Sufficient but not essential •  Impaired muscle blood flow

–  Impaired arteriolar vasodilation •  Abnormal skeletal muscle

–  Impaired capacity to utilize oxygen

Fatigue - Multidimensional Assessment

•  Pattern: onset, duration, intensity, aggravating and alleviating factors

•  Description (e.g. exhaustion, tired) •  Type and degree of disease •  Treatment history •  Medications •  Sleep and/or rest patterns •  Nutrition: intake, appetite, weight change

Fatigue - Assessment •  Effect of fatigue on ADLs •  Quality of life •  Impact on personal well being, family

dynamics, work, intimacy, social life, outlook

•  Evaluation for depression •  Complete physical examination •  Other contributing factors (e.g. anemia,

dyspnea, muscle wasting)

Fatigue - Therapeutic Approach

FATIGUE

General Measures Specific Measures (e.g.)

Pharmacologic Non-pharmacologic

Hypoxemia Anemia Medications

Fatigue - Therapy

•  Goals – Decrease level of fatigue – Allow patient to function maximally with a

stable level of fatigue •  Since fatigue usually multicausal,

correcting underlying reversible causes may or may not improve subjective sensation of fatigue

Fatigue - Specific Measures

•  Maximize therapy for underlying disease •  Address potentially reversible underlying

causes (e.g. metabolic abnormalities, anemia) IF consistent with overall goals of care for the patient.

•  Review prescribed and OTC medications, supplements, and herbals

•  Assess and treat depression and anxiety

Fatigue - General Pharmacologic Measures

Corticosteriods – Potential mechanism: Central euphoriant

effect and inhibition of tumor-induced substances

– RCT’s (cancer patients): •  Improved activity level •  Decreased weakness •  Effect wanes after 2 - 6 weeks

– No studies in non-cancer patients – Recommendation:

•  Dexamethasone 2 - 32 mg po q day

Fatigue - General Pharmacologic Measures

Psychostimulants –  Few studies –  Several RCTs of methylphenidate: cancer patients

•  3 day, double-blind cross over study – Methylphenidate (10 mg AM, 5 mg noon) improved

fatigue vs. placebo •  4 weeks, target dose methylphenidate 54 mg/d

– No improvement overall –  Subgroup analysis: more fatigue or more advanced

disease – improved fatigue •  Secondary review of clinical trials: higher levels of fatigue

predicted response –  Recommendation: Methylphenidate (Ritalin), 2.5 - 10 mg po

AM and noon for cancer fatigue, especially if due to increasing opioid doses

Modafinil •  GABA inhibitor •  Few studies: advanced neurologic dz (MS,

ALS, myotonic dystrophy, Parkinson’s), HIV/AIDS, opioid-induced sedation – Variable results

•  Recommendation: start with 200 mg/day, titrate up to 400 mg/day

Fatigue - General Non-Pharmacologic Measures

•  Educate patient and family •  Give patient permission to rest •  Promote energy conservation - adaptive

devices, assistance in the home, eliminate non-essential activities

•  Schedule important activities during more energetic time periods

•  Physical and occupational therapy as tolerated

Depression

Aren’t all terminally ill patients depressed? How do I know when I

should treat someone at the end of life for depression?

What is the best next step?

After evaluating your patient with CHF and COPD, you become concerned that his fatigue and anorexia are due to depression.

What are indications that he has depression that should be treated?

a)  His fatigue b)  His anorexia c)  His dyspnea d)  His anhedonia

Depression at the end of life: Assessment

•  Prevalence varies (3.7 – 58%), depending on type and stage of disease, setting and population

•  Screening for depression advocated by ACP, USPSTF, NIH, EAPC

•  Often coexists with pain – adequate treatment of pain important

Short Screen for Depression Sx 1)  In the past 2 weeks, have you been worn out or had

too little energy, even when you haven’t been doing a lot?

2)  During the past 2 weeks, have you often been bothered by a lack of interest or pleasure in doing things?

3)  In the past 2 weeks have you been feeling depressed or sad at all?

4)  In the past 2 weeks, have you: a)  Talked or moved more slowly than is normal for you? b)  Had to be moving some part of your body all the time – that is,

you were so restless you couldn’t sit still? Yes to #1 and to both #2 and #3 – follow up Yes to #1, to either #2 or #3 and to either #4a or #4b –

follow up

Robinson, 2005

Depression at the end of life: Treatment

•  Very few studies •  Antidepressants probably underused and

underdosed in palliative care settings •  Insufficient evidence for psychostimulants •  Some evidence for tricyclics and SSRIs

–  Consider adjuvant and side effects •  Buproprion may have positive effects on fatigue

and depression •  Some evidence for non-pharmacologic

–  Group or individual therapy, hypnotherapy, meditation, existential therapy, complementary medicine

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