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Symptom Management in

Palliative CareMichael Aref, MD, PhD, FACP, FHMAssistant Medical Director of Palliative Medicine

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DISCLOSURES

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Disclosures

• None

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II

OBJECTIVES

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Objectives

• Identify models of pain. • Describe pain pathways. • Discuss how biochemical and neurohormonal mechanisms

are influenced by physical, psychological, social, and spiritual components of pain.

• Explain uses and complications of opioids in pain management, specifically constipation and nausea.

• Identify pharmacological targets for nausea management.• Review options for medical management of malignant

bowel obstruction and dysfunction.

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III

PAIN: MODELS

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Central Neuropathic• Non-dermatomal• Direct central nervous injury• Radiating or specific• Burning, prickling, tingling,

electric, shock-like or lancinating

Peripheral Neuropathic• Dermatomal• Direct peripheral nervous injury• Radiating or specific• Burning, prickling, tingling,

electric, shock-like or lancinating

Visceral (,)• C fiber activity• Distension, ischemia and

inflammation of organs• Diffuse, deep ache,

pressure, sickening, squeeze, dull or sharp

Types of PainPsychogenic• Pain that is caused, increased, or prolonged

by mental, emotional, or behavioral factors.Acute < 3 months

Chronic > 3 months

Malignant pain is due to a progressive disease that will lead to death.

Non-malignant pain is due to a non-threatening cause that may persist until, but is not the cause of, death.

1st

2nd

tramadoloxycodonemethadone

3rd

NeverOpioid?

2nd – 3rd

Somatic (,)• fiber activity• Skin and deep tissue

damage• Pinprick, stabbing or

sharp

Goldstein and Morrison, Evidenced-Based Practice of Palliative Care: Expert Consult, Ch 1, 2Mann and Carr, Pain: Creative Approaches to Effective Management

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4-Step Model of Pain

Transduction Transmission Perception Modulation

Acute stimulation in the form of noxious thermal, mechanical, or chemical stimuli is detected by nociceptive neurons.

Nerve impulses transferred via axons of afferent neurons from the periphery to the spinal cord, to the medial and ventrobasalthalamus, to the cerebral cortex.

Cortical and limbic structures in the brain are involved in the awareness and interpretation of pain.

Pain can be inhibited or facilitated by mechanisms affecting ascending as well as descending pathways.

Wyatt SA, Adjunct Approaches to Chronic Pain Management for Individuals with Substance Abuse Disorder, July 21, 2016

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Total Pain

Social

Psychological

Physical

•Role

•Relationships

•Occupation

•Financial cost

•Emotional response

•Comorbid mood disorder anxiety

•Adjustment to new baseline

•Cause?

•Associated symptoms

•Debility and fatigue

Superimposed on Maslow’s Hierarchy of Needs

Spiritual•Existential coping•Religious beliefs•Meaning of life/illness•Personal value

Interventional Pain ServiceOther SpecialtiesPharmacyPhysical Therapy

Social WorkFinancial NavigatorOccupational Therapy

ChaplaincyArt & Music Therapy

Social WorkPsychologyPsychiatry

Curr Opin Support Palliat Care. 2008; 2(2):110-3

Maslow AH, A Theory of Human Motivation, 1943

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IV

PAIN: PATHWAYS

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Nocioceptive Nerve Conduction Pathways

J Pain. 2010 Aug;11(8):701-9nobaproject.com/modules/touch-and-pain

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Peripheral Nerve and Spinal Neurotransmitters of Pain

Int Clin Psychopharmacol. 1995 Jan;9 Suppl 4:41-5Neuron. 2012; 76(1): 175-191Nat Rev Drug Discov. 2014 Jul;13(7):533-48www.rnceus.com

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OPIATES

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Procedural Interventions• Patient controlled analgesia pump

• Neurolysis

• Spinal stimulator

• Intrathecal pump

• Neurosurgery

Methadone PO

Fentanyl IV (0.05 mg = 50 mcg)

Hydromorphone IV (0.8 mg)

Hydromorphone PO (4 mg)

Oxycodone PO (10 mg)

Morphine PO (15 mg) Morphine IV (5 mg)

Hydrocodone PO (15 mg)

Tramadol PO (100 mg)

Codeine PO (100 mg)

Ibuprofen PO (1100 mg)

Acetaminophen PO (3610 mg)

Salicylate (choline magnesium trisalicylate)

Ascending WHO Analgesic LadderAdjuncts

• Anticonvulsants

• Neuropathic pain + muscle spasm = gabapentin

• Neuropathic pain + anxiety - depression = pregabalin

• Post-operative pain + anxiety - depression = pregabalin

• Antidepressants (SNRI, TCA)

• Muscle spasm + anxiety = diazepam

• Depression anxiety + neuropathic pain = duloxetine

• Baclofen

• Cyclobenzaprine (muscle relaxant, fibromyalgia)

• Corticosteroids

• Ketamine

Interventions

• Transcutaneous electrical nerve stimulation

• Acupuncture

• Art / Music Therapy

• Massage

• Physical Therapy

• Psychological Treatment

Procedures

• Nerve blocks

Canadian Family Physician 2010; 56(6):514-517Opioid tablet images WebMD

Chronic painNon-malignant pain

Malignant pain

Morphine IV comes in 4 and 6 mg

Actually 120 mg of codeine

Sedation36-72 hours

Nausea / VomitingPruritus

7-10 days

ConstipationFlushing / Sweating

Never

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Descending WHO Analgesic Ladder

0

100

200

300

400

500

0 2 4 6 8 10 12 14 16 18 20 22 24 26

Ora

l Mo

rph

ine

Eq

uiv

ale

nts

Days

10% wean everyday

20% wean everyday

50% wean everyday

Acute Pain

Acute painChronic pain without controlAcute crises of chronic pain

paincommunity.org/blog/wp-content/uploads/Safely_Tapering_Opioids.pdfAAPM 2005USVA 2003

Hydromorphone 1 mg IV every hour

Oxycodone-APAP 10-325 mg PO every 2 hours

Hydrocodone-APAP 10-300 mg PO every 2 hours

Morphine 30 mg PO every 3 hours

Slow wean, if:• Tachycardia• Diaphoresis, lacrimation, salivation• Diarrhea

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VI

PAIN CASE #1

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Case• 23-year-old white female with chronic abdominal pain, nausea, and

food aversion secondary to multiple surgeries for hereditary pancreatitis and complications thereof.

• Non-malignant abdominal pain managed with progressive increases in opiates, now on high-dose opiates, 200 mcg/hr fentanyl patch with 4-8 mg of hydromorphone as needed every 2-3 hours.

• Mother strong advocate for patient.

• Consulted for pain management.

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How is she NOT dead?

19CDC Grand Rounds, January 13, 2012 / 61(01);10-13

Dose and Overdose

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Course

• Basal opiates increased and discharged home.

• Patient seen on subsequent hospitalizations for other complications, e.g. line infection, portal vein thrombosis. Abdominal pain continues to worsen without change in pathology.

• Having built a relationship with patient, discussed concerns that opiates were worsening her pain. Agreeable to weaning off opiates.

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Narcotic Bowel Syndrome

• The pain worsens or incompletely resolves with continued or escalating dosages of narcotics.

• There is marked worsening of pain when the narcotic dose wanes and improvement when narcotics are reinstituted (“Soar and Crash”).

• There is a progression of the frequency, duration and intensity of pain episodes.

• The nature and intensity of the pain is not explained by a current or previous gastrointestinal diagnosis:

– A patient may have a structural diagnosis (e.g., inflammatory bowel disease, chronic pancreatitis) but the character or activity of the disease process is not sufficient to explain the pain.

Chronic or frequently recurring abdominal pain that is treated with acute high dose or chronic narcotics and all of the following:

Clin Gastroenterol Hepatol. Oct 2007; 5(10): 1126–1122.

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VII

PAIN CASE #2

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Case

• 72-year-old white male with metastatic pancreatic cancer, admitted for pain control.

• Patient has been on rapidly escalating doses of morphine. Delirious, in his lucid moments he weeps, morphine has been aggressively increased. In the past 24 hours he developed intermittent jerking of his limbs.

• Consulted for pain management.

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Course

• Patient was switched to fentanyl, but at 75% equianalgesic dose.

• Pain controlled, delirium improved, myoclonic jerks resolved.

• Patient died on in-patient hospice.

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Opiate-Induced Hyperalgesia

• Increasing sensitivity to pain stimuli (hyperalgesia). Pain elicited from ordinarily non-painful stimuli, such as stroking skin with cotton (allodynia).

• Worsening pain despite increasing doses of opioids.• Pain that becomes more diffuse, extending beyond the

distribution of pre-existing pain.• Presence of other opioid hyperexcitability effects: myoclonus,

delirium or seizures.• Can occur at any dose of opioid, but more commonly with

high parenteral doses of morphine or hydromorphone and/or in the setting of renal failure.

www.mypcnow.org/blank-h5muh

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VIII

CONSTIPATION

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Constipation Prevention and Management Options

Non-pharmacological ways to prevent and treat constipation

1. Optimize oral hydration

2. Physical activity

3. Scheduled visits to the commode

4. Privacy when using the commode

Yakima Valley Anti-Constipation Fruit Paste

1 lb pitted prunes4 oz senna tea leaves (at health foods store)1 lb raisins1 lb figs1 cup lemon juice

1. Prepare tea; use about 2 1/2 cups boiled water, add to tea leaves and steep for 5 minutes.

2. Strain tea and remove tea leaves.3. Place 2 cups of tea, or amount left, in large pot.4. Add all of the fruit to the tea.5. Boil fruit and tea for 15 - 20 minutes, until soft.6. Remove from heat and add lemon juice. Allow to cool.7. Use hand mixer/blender or food processor to turn fruit and tea

mix into a paste.8. Place in glass jars or Tupperware and place in freezer (paste will

not freeze but will keep forever in freezer also very long in fridge).

DOSAGE: 1 - 2 Tablespoons per day

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Bowel movement frequency normal for you without needing

other as needed medications

Bowel movement frequency normal for you without needing

other medications

Bowel movement frequency normal for you without other

medications

Bowel movement frequency normal for you without needing

other medications

All opiates cause constipation and unlike other side effects this does

not improve with time!

Start senna 1 tablet twice daily plus as needed adjunct*

Increase senna to 2 tablets twice daily plus

as needed adjunct*

Increase senna to 4 tablets twice daily plus

as needed adjunct*

Continue senna 4 tablets twice daily and add MiraLax daily plus

as needed adjunct*

Contact your provider for other

pharmacological options for managing

your constipation

No changes

No changes

No changes

No changes

Yes

Yes

Yes

Yes

No

No

No

No

*Adjunct medications should be used if there is no bowel movement in the last 48 hours, firstly:

• MiraLax 17g 1-2 times daily

If no relief or unable to tolerate MiraLax consider:

• Bisacodyl suppository 10 mg daily

• Glycerin suppository daily

• Soaps suds or tap water enema daily

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IX

CONSTIPATION CASE

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Case

• 52-year-old white female with history of Ehlers-Danlossyndrome, lumbar stenosis with radiculopathy, anxiety, fibromyalgia, and opiate-induced constipation.

• She is followed in the ambulatory palliative care clinic.

• She is on high-doses of opiates and normally has issues with constipation, she took extra doses of her bowel regimen and developed diarrhea with nausea and vomiting. She has mild acute kidney injury and CT abdomen/pelvis without contrast reveals colitis.

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ColonoscopyAcute presentation of inflammatory bowel disease suggestive of severe ulcerative pan-colitis favored over infections colitis (especially in light of negative GPP stool tests).

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Course

• Pathology however consistent with acute ischemic colitis. Confirmed at Mayo.

• CTA abdomen and pelvis showed no hemodynamically significant stenosis or occlusion. Aorta normal diameter.

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Follow-Up Colonoscopy

4 months later

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Acute Ischemic Colitis

• Ehlers-Danlos does have a higher incidence of ischemic colitis but due to vascular malformations (aneurysms, dissections, fistulas).

• Increased incidence of inflammatory bowel disease (CD > UC) in Ehlers-Danlos.

• Case report of lubiprostone induced ischemic colitis.• Constipation causes increased intraluminal pressure that reduces blood

flow, predisposing the patient to regional colonic wall ischemia.• Relative risk for ischemic colitis 2.78 times higher for patients with

constipation. Constipation is more prevalent in younger patients with ischemic colitis.

• Use of laxatives during ischemic colitis increases risk of perforation.

Discussion

World J Gastroenterol. 2013 Jan 14;19(2):299-303Front Surg. 2017; 4: 47Aliment Pharmacol Ther (2007) 25:681–692.

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NAUSEA

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NauseaCause Receptors Drug Classes Examples

Vestibular Cholinergic, HistaminicAnticholinergic,Antihistaminic

Scopolamine patch, Promethazine

ObstipationCholinergic, Histaminic, likely 5HT3

Stimulate myenteric plexus Senna products

MotilityCholinergic, Histaminic, 5HT3, 5HT4

Prokinetics which stimulate 5HT4 receptors

Metoclopromide

Infection/InflammationCholinergic, Histaminic, 5HT3, Neurokinin 1

Anticholinergic, Antihistaminic, 5HT3 antagonists, Neurokinin 1 antagonists

Promethazine (e.g. for labyrinthitis), Prochlorperazine

Toxins Dopamine 2, 5HT3Antidopaminergic, 5HT3 Antagonists

Prochlorperazine, Haloperidol, Olanzapine,Ondansetron

Fast Facts www.mypcnow.org/blank-ggr79

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NAUSEA CASE

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Case

• 77-year-old white male recently diagnosed with Stage IB, T2 N0 M0 metastatic pancreatic adenocarcinoma. Past medical history otherwise significant for heart disease and chronic obstructive pulmonary disease.

• Presents with nausea and vomiting intractable to ondansetron, promethazine, prochlorperazine, and metoclopramide. Possibly alleviated some by lorazepam.

• He describes his nausea and vomiting as being precipitated by hiccoughs that occur after drinking or eating small amounts which then causes substernal pain, regurgitation, and dyspnea.

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Course

• Chlorpromazine 25 mg IV Q6H PRN for hiccoughs.

• No change in nausea with olanzapine and haloperidol.

• One time dose of fosaprepitant did alleviate refluxing of food or drink after eating for about 24 hours.

• Scheduled chlorpromazine 25 mg PO BID.

• Added diltiazem 30 mg PO Q6H.

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Esophageal Spasm

• The patient had essentially been refractory to “all” drug targets to manage nausea.

• Symptomatology used to guide management rather than definitive testing (e.g. esophageal manometry).

• More comfort focused care means avoiding invasive testing and limiting non-invasive testing to highest yield studies.

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MALIGNANT BOWEL OBSTRUCTION

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Malignant Bowel Obstruction

• Prevalence 5-25% in ovarian carcinoma or colorectal cancer, in advanced ovarian cancer frequency up to 42%.

• Imaging of choice: CT abdomen and pelvis with contrast (ACR Appropriateness Criteria Rating 9) followed by without contrast (ACR 7). X-ray abdomen and pelvis is ACR 5.

Partial or Complete

www.cancer.gov/resources-for/hp/education/epeco/self-study/module-3/module-3e.pdfacsearch.acr.org/docs/69476/Narrative/

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Management

• Venting gastrostomy is definitive management.

• Dexamethasone 6-16 mg IV may bring about resolution of bowel obstruction.

• Dexamethasone + ranitidine = octreotide

• Dexamethasone + octreotide + metoclopramide– MBO: Pain and nausea improved within 24 hours, PO intake

within 48 hours

– MBD: 84% of patients had improved pain and nausea within 24 hours, PO intake within 1-4 days

Inoperable

Support Care Cancer. 2009 Dec;17(12):1463-8Am J Hosp Palliat Care. 2016 May;33(4):407-10

Support Care Cancer. 2009 Dec;17(12):1463-8Am J Hosp Palliat Care. 2016 May;33(4):407-10

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BUY ONE GET ONE FREE

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Some Considerations

• Opioid-induced nausea = haloperidol PRN (max 2 mg TID) + olanzapine QHS

• Superficial somatic pain + minimize opioids = lidocaine topical

• Deep somatic pain = orphenadrine

• NSAID + renal impairment = diclofenac topical

• NSAID + bleeding risk = choline magnesium trisalicylate

• Pruritus + anxiety = hydroxyzine

Two symptoms for the price of one

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THANK YOU

QUESTIONS? CONCERNS? COMMENTS?