NonPain Symptom Management

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Non-Pain Symptom Management

• Gary Hsin, M.D.
• Stanford Hospice
• Palo Alto, CA
• Saint Agnes Medical Center
• May 6, 2006

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Some Non-Pain Symptoms

• Ageusia, Akathisia, Anhedonia, Anorexia,
  Anxiety, Asthenia, Bleeding, Bowel, obstruction,
  Bronchorrhea, Cachexia, Colic, Confusion,
  Constipation, Convulsion, Cough, Crying, Death
  rattle/secretions, Delirium, Diarrhea, Dizziness,
  Drooling, Dry skin, Dysarthria, Dysgeusia,
  Dyspepsia, Dysphagia, Dysphoria, Dyspnea,
  Dysuria, Edema, Failure to thrive, Fatigue, Fear,
  Fecal incontinence, Fever, Flatulence, Halitosis,
  Hallucination, Hearing loss, Hiccups, Impotence,
  Incontinence, Irritability, Memory loss,
  Mucositis, Myoclonus, Nausea, Odor, Palpitation,
  Panic attack, Photosensitivity, Polydipsia,
  Polyuria, Pruritus, Restlessness, Sexual
  dysfunction, Sialorrhea, Sleep disorder,
  Stomatitis, Ulcer, Urinary frequency, Urinary
  incontinence, Visual problem, Vomiting, Xerosis,
  Xerostomia
• Index, Oxford Textbook of Palliative Medicine

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Learning Objectives

• Increase understanding of how physical and mental
  factors affect symptomatology
• Be able to use this understanding in the
  treatment of patients suffering from nausea and
  vomiting, and dyspnea

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Outline

• Symptom analysis checklist
• Nausea and Vomiting
• Dyspnea
• Terminal Syndrome Characterized by Retained
  Secretions

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Symptoms as Clues

• A physical or mental phenomenon, circumstance or
  change of condition arising from and accompanying
  a disorder and constituting evidence for it
  specifically a subjective indicator perceptible
  to the patient and as opposed to an objective one
  (compare with sign).
• The New Shorter Oxford English Dictionary

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From the Patients Perspective

• A symptom is what is bothersome

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Disease as a Clue to the Symptom

• Questions to ask
• How does the disease give rise to the symptom?
• What cognitive, affective, and spiritual
  components are involved?

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Symptom Analysis Checklist

• Physiological Factors
• Local
• Central

• Mental Factors
• Cognitive
• Affective
• Spiritual

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Patient with pain symptoms due to metastatic bone
cancer

• Physiological factors
• Local
• Central

• Mental Factors
• Cognitive
• Affective
• Spiritual

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Nausea Vomiting

• What were you taught about antiemetics?

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Nausea Vomiting As Protective Mechanisms

• Serial barriers
• 1. Sight, smell, taste
• 2. Chemoreceptors and mechanoreceptors
• 3. Brain receptors
• 4. Message to vomit residual gut contents

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A Central Final Pathway for Nausea
(???)
(Dopamine, Serotonin)
CNS
CTZ
VOMIT CENTER (Acetylcholine, Histamine)
Vestibular Apparatus
GI Tract
(Acetylcholine, Histamine)
(Acetylcholine, Histamine, Serotonin
mechanoreceptors)
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Receptor Affinity Common Antiemetics
Drug Receptors Dopamine Musc.
Chol. Histamine Scopolamine
gt10,000 .08 gt10,000 Promethazine
240 21 2.9 Prochlorperazine
15 2100 100 Chlorpromazine 25 130 28 Metoclo
pramide 270 gt10,000 1,000 Haloperidol 4.2 gt10
,000 1,600 Potency K1 (nanomolar) The lower
the number, the stronger this agent is at
blocking this receptor Adapted from Peroutka
and Snyder, 1982
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Causes of Nausea and Vomiting

• Vestibular
• Obstruction
• Mind/Motility
• Infection
• Toxins

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V-Vestibular Apparatus

• Nausea with head movement
• Motion sickness, medications
• Mediated by acetylcholine and histamine receptors
• Medications
• Phenergan/Promethazine
• Scopolamine (patch, injection)

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O-Obstruction

• Mechanical Obstruction
• Most common cause constipation
• May be caused by external or internal obstruction
• Functional Obstruction Opioids
• Medications
• Treat underlying cause Constipation
• Functional obstruction Promotility agents-
  Reglan
• Other mechanical obstruction Bowel rest or
  Somatostatin analogue (Octreotide)

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M-Mind

• Emotional, cognitive aspects of nausea
• anxiety, anticipation, associations
• Medications
• Benzodiazepine Lorazepam (poor solo agent)
• Cognitive therapy relaxation

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M - Motility/Dysmotility

• Medications Prokinetics
• Reglan (upper only)
• Motilin agonists (erythromycin)
• Senna (lower only)

• Multiple causes
• Opioids
• Anticholinergic drugs
• Stomach/bowel compression, infiltration
• Upper intestinal dysmotility-very common, under
  appreciated

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I - Infection

• Gut and adjacent organ inflammation can trigger
• Mediated via chemoreceptors acetylcholine,
  histamine receptors

• Medications
• Treat acute GI infections and inflammation
• Anticholinergic antihistaminic agents

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T - Toxins

• Most important drugs we give
• Various mechanisms of inducing nausea
• Local irritant
• NSAIDs
• Changing blood levels (via CTZ)
• Opioids
• Toxic blood levels
• Digoxin

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M-Medications
Chemotherapy Opioids

• Receptors
• Brain/CTZ
• 5HT3 (serotonin receptors), NK1 (neurokinin
  receptors)
• GUT 5HT3
• Medications
• 5HT3 Receptor antagonists i.e. Odansetron

• Receptors
• Brain/CTZ
• D2 (dopamine receptors)
• GUT Dopamine local opioid receptors, Decreased
  gut motility
• Medications
• Promotility agents - Metoclopramide
• Dopamine antagonists
• Haloperidol
• Prochlorperazine

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Prochlorperazine vs Promethazine
Randomized control trial uncomplicated
nausea/vomiting in ER. N 84

• At 30 and 60 minutes prochlorperazine better on
  VAS (p lt 0.05)
• Time to relief shorter prochlorperazine
• Fewer treatment failures prochlorperazine (p
  0.03)
• No difference in EPS, but less sedation
  prochlorperazine (p0.002)

Ernst, A. A., S. J. Weiss, et al. (2000).
"Prochlorperazine versus promethazine for
uncomplicated nausea and vomiting in the
emergency department a randomized, double blind
clinical trial." Ann Emerg Med 36(2) 89-94.
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Cannabinoids

• Bind CB1 receptors in the dorsal vagal complex of
  medulla
• Appear to decrease fundic tone and antral
  motility
• Stimulate appetite
• Can be very effective, but side-effects often
  limiting (especially elderly)

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Newer Agents Neurokinin 1 Antagonists

• Blocks binding of substance P to neurokinin 1
  receptors in gut and medulla
• Newer agents i.e. Aprepitant
• Especially useful in late phase cisplatin
  toxicity (not mediated by serotonin binding 5HT3
  receptors)
• May also be useful for vertigo, post-operative
  nausea, and bowel obstruction

Hesketh, P. J., R. J. Gralla, et al. (1999).
"Randomized phase II study of the neurokinin 1
receptor antagonist CJ- 11,974 in the control of
cisplatin-induced emesis." J Clin Oncol 17(1)
338-43.
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Other Agents

• Antidepressant, mirtazapine
• Blocks 5HT3 receptors
• Anxiolytic, based on binding of 5HT2 receptor
• Kast, R. E. (2001). "Mirtazapine may be useful in
  treating nausea and insomnia of cancer
  chemotherapy." Support Care Cancer 9(6) 469-70.

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SUMMARY

• Optimal treatment of nausea and vomiting depends
  upon a good understanding of underlying
  physiology in order to
• Provide maximal symptomatic relief
• Avoid undesirable side-effects

One size does NOT fit all
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Dyspnea

• Difficulty in breathing
• Associated with lung or heart disease
• Shortness of breath, Air hunger
• Subjective difficulty or distressed breathing

Excerpted from The American Heritage Dictionary
of the English Language, Third Edition, 1992
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Dyspnea Signs

• Patient breaks up sentence to pause for breath
• Tachypnea
• Nasal flaring
• Cyanosis
• Accessory Muscle Use
• Neck (Scalene, sternocleidomastoid)
• Chest and abdominal muscle use

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Dyspnea

• Causes
• Airway
• Cardiac
• Pulmonary
• De-conditioning
• Pain
• Neuromuscular
• ENT disorders
• Psychogenic

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Symptom Analysis Checklist

• Physiological Factors
• Local
• Central
• Mental
• Cognitive
• Affective
• Spiritual

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Exercise 1 The Runner

• Are you dyspneic? Short of breath?
• What is your O2 saturation level?
• What is happening locally in you chest?
• What do you think about your run?
• Any spiritual importance?
• Are you suffering?

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Exercise 2 Lung Cancer

• Imagine that you have lung cancer, on top of
  pre-existing COPD
• You are getting winded with the least possible
  exercise
• Coming back from the bathroom to the bed you are
  now very dyspneic
• You wish there was a window you could open
• The nurse measures your O2 Sat
• There is a low-pitched beeping sound, which you
  know is not good
• The nurse looks distressed and rushes from the
  room

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Dyspnea in the Dying

• Common
• 70 of patients in last 6 weeks of life Reuben
  Mor, 1986
• Care has traditionally focused more on lung
  physiology than central processes
• Not always correlated with oxygen level

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Treating Dyspnea

• Physiological Factors
• Local Fan, cool breeze
• Central WOB may be particularly responsive to
  low dose opioids
• Mental factors
• Cognitive Education, reframing
• Affective Emotional support, benzodiazepines for
  panic sensation

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Pharmacological Management

• Opioids
• Naïve 2mg SC/IV morphine (or equivalent) Q12
  hours PRN.
• May need to have long-acting opioid if dyspnea is
  persistent
• Chronic increase total daily dose by 25
• Allow for break through dose of medication PRN
  for exacerbation

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Pharmacological Management

• Anxiolytics (Benzodiazepines)
• Alprazolam .25-1mg PO q3-8h
• Lorazepam .5-2mg PO/PR/IV
• Diazepam (basal with frequent Lorazepam use)
• Psychotropic (i.e. Haloperidol, Quetiapine)
• Hyperventilation, Restlessness
• TCA or SSRI (i.e. Paroxetine, Mirtazapine)

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Self Management skills

• Reduce need for exertion, save energy, Pursed lip
  breathing
• Assistive devices
• Reposition Upright or with compromised lung down
• Meditation, biofeedback, guided imagery,
  cognitive behavioral therapy

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Terminal Syndrome Characterized by Retained
Secretions

• Relative lack of cough
• Not always associated with dyspnea
• Deep suctioning ineffective
• Hydration may flood lungs
• Because patient is unable to cough
• Use of antibiotics, IV fluids controversial

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Treatment

• Gentle suction
• For some patients this can be helpful, for other
  this can be difficult and disturbing
• Drying agents
• Anticholinergic agents
• Scopolamine tertiary agent
• 0.4mg SC/IV Q4hrs PRN
• 1.5mg patch delivers 1mg over 72hrs
• Glycopyrrolate quaternary agent
• 0.10.2mg IM/IV Q4hrs PRN
• 0.51mg Nebulized Q4hrs PRN