Palliative Care: Introduction and Symptom Management

Palliative Care
Written By Sydney Oesch

Episode Notes

  1. What is Palliative Care?

    1. Prioritizes the management of symptoms in a patient-centered way

    2. NOT the same as Hospice care

    3. NCCN definition of goal of PC: “to anticipate, prevent, and reduce suffering; promote adaptive coping; support the best quality of life for patients/families/caregivers, regardless of the stage of the disease.”

    4. Screen at first visit for PC needs and prn

    5. Available inpatient, outpatient; some hospital systems have inpatient hospice often run by palliative care team

    1. Evidence

      1. ENABLE III, 2015

        1. Phase 3 trial

        2. Outcomes for patients w/ advanced care after early vs delayed initiation (3 months later) of PC

        3. Early PC group

          1. Improved one-year survival rates

          2. Decreased depression and stress burden in caregivers

        4. No difference in patient-reported QOL, symptom impact, or mood

      2. Other studies

        1. Decreased use of aggressive care measures at end of life

        2. Decreased health costs for patients over their disease course

    2. Approach to PC

      1. TEAM: Time (an extra hour per month), Education, Assessments, Management (with an interprofessional team)

  2. Pain

    1. Define it

      1. Acute vs chronic

      2. Total pain: physical, spiritual, psychological, social

      3. Identify source, contributing/exacerbating factors, chronicity

    2. Neuropathic

      1. Stems from damage (i.e. chemo induced) of the somatosensory nervous system hich leads to abnormal neural excitability; Can also be due to nerve compression from growing tumors

      2. Symptoms: numbness, burning, tingling/pricking, dysesthesias

      3. First-choice med: non-opioid

        1. Duloxetine first-line choice

          1. SNRI

          2. Only medical management that improves patient-reported scores for pain, function, and quality of life

          3. Starting dose: 20-30 mg daily; can uptitrate to 60 mg daily

      4. Second-choice meds

        1. Desipramine

          1. Tricyclic antidepressant

        2. Gabapentin

          1. Avoid in patients w/ depressed mood

          2. Sedating

          3. Starting dose: 100-300 mg nightly; can up-titrate to 300-1200 mg TID

      5. Other options

        1. Anticonvulsants

        2. Oral analgesics: cannabinoids, alpha-2 adrenergic agonists

        3. Topic analgesics: lidocaine, botulinum toxin injection

        4. NMDA receptor antagonist: Ketamine

        5. GABA receptor agonist: Baclofen

      6. Opioids

        1. Can reduce neuropathic pain by 33%

        2. Methadone

          1. Cochrane review concluded not enough evidence to support methadone use for this indication

          2. Tricky to prescribe due to long half life

    3. Acute pain management

      1. Multimodal analgesia

        1. Scheduled administration of OTC analgesics (tylenol, ibuprofen)

          1. Emphasize the different mechanisms of action to decrease resistance to these

        2. Sometimes other meds like gabapentin or muscle relaxants

        3. Opioids for breakthrough pain

        4. Consider regional anesthesia or local analgesics

          1. Epidurals, transversus abdominis plane blocks

          2. Injected liposomal bupivacaine

        5. Lots of literature on ERAS principles

      2. Opioid Needs and Avoidance of Over-Prescribing

        1. University of Michigan study on prescribed opioids

          1. Intervention: ask the patient how many tabs they think they will need

          2. Significantly reduced the number of tablets prescribed, and majority of patients still had leftover tabs

        2. Another option: have a standard number of tablets prescribed for each procedure, with a lower starting prescription, while letting the patient know you can send more if they need more

        3. New persistent opioid use/dependence occurs in 6% of postoperative patients

    4. Chronic Cancer-Related Pain

      1. First-choice med: opioids

      2. Initial dosing considerations: type of pain, current use of opioids, whether patient has chronic opioid tolerance

        1. Is it that the the dose o the med given isn’t adequately controlling the pain, or is it that the dose controls the pain initially but doens’t last long enough?

      3. Calculations

        1. Each med has an oral morphine equivalent (OME) - convert all opioids to this standard

          1. IV and PO formulations for the same drug (i.e. Dilaudid) will have different OMEs

      4. Acute increase in need can be seen w/ disease progression, procedure, infection or necrosis of a tumor

        1. Timing

          1. Immediate release PO: peak effect 60 minutes 

          2. IV bolus: peak effect 15 minutes

          3. SQ bolus: 30 minutes

        2. How Much?

          1. If opioid tolerant: start with initial dose 10-20% of total OMEs taken in last 24 hours → reassess pain at peak effect (see above) → repeat dose, increase dose by 50-100%, or continue w/ dose and schedule

            1. Be wary of stacking opioids!

      5. Patient Controlled Analgesia (PCA)

        1. Total: patient-delivered boluses, nurse delivered boluses +/- basal rate

          1. Nurse dose should be 2x patient-delivered dose (reserved for uncontrolled pain)

          2. Lockout should never be more frequent than q 15 min (remember opioid stacking and peak effect!)

            1. If they need more, increase bolus dose or basal rate

        2. Set expectations - trying to get to tolerable level for ADLs, not pain level zero

      6. Transition to Oral Meds

        1. Calculate total OMEs from PCA → prescribe 50-75% of dose taken IV

          1. Split the dosing between long acting and short acting meds

        2. Avoid opioid products combined w/ other agents like tylenol

      7. Procedural Options

        1. Can consider invasive pain control options in pts w/ short life expectancies

          1. Hypogastric plexus neurolysis: neuropathic pain which doesn’t respond to or not amenable to conservative options

          2. Spinal cordotomy: unilateral cancer pain

  3. Nausea, Vomiting

    1. Incidence

      1. Up to 50% of patients w/ advanced cancer will have significant nausea or vomiting

    2. Differential Diagnosis: VOMIT

      1. Vestibular, Obstruction/constipation, dysMotility, Infection/Inflammation, Toxins

    3. Chemo-Induced Nausea/Vomiting (CINV)

      1. Timing Definitions

        1. Acute: occurs w/i 24 hrs of administration

        2. Delayed: >24 hours after administration

        3. Anticipatory: pre-chemo response after having prior episode of CINV

      2. Risk of Emetogenesis

        1. High emetogenicity: >90% chance of acute CINV

          1. Includes: cisplatin, carboplatin AUC >4, cyclophosphamide, dacarbazine, doxorubicin >= 60 mg/m2, ifosfamide >= 2 g/m2, Enhertu

        2. Moderate: 30-90%

        3. Low: 10-30%

      3. Risk Mitigation

        1. If high emetogenic potential, prescribe 3-drug antiemetic combo: steroid, NK1 receptor antagonist, 5-HT3 blocker

    4. Neuroscience

      1. Anatomy-ish

        1. Chemoreceptor trigger zone

          1. located in area postrema and nucleus tractus solitarius in dorsal brainstem outside of blood brain barrier

          2. Inputs from vagal nerve, splanchnic nerves, direct input from blood/CSF

          3. Sends signals to…

        2. Central pattern generator or “vomiting center” in the medulla

          1. Communicates to the vagal nerves, triggering emesis

      2. Pathways

        1. Peripheral: results from release of serotonin from enterochromaffin cells of small intestine → bind to 5HT3 receptors of vagal and splanchnic nerves

          1. Responsible for acute CINV

        2. Central: results from release of substance P → binds NK-1 receptors in central nervous system

          1. Responsible for delayed CINV

    5. Agents by Mechanism

      1. NK1 Receptor Antagonists

        1. Aprepitant (PO), Fosaprepitant (IV)

        2. More efficacious for delayed CINV

        3. Used to prevent acute and delayed CINV

          1. Typically in combo w/ serotonin receptor antagonists and glucocorticoids

        4. Inhibit CYP3A4 pathway

          1. Dose reduce glucocorticoids

      2. Serotonin receptor (5HT3) antagonists

        1. 1st gen: Ondansetron, granisetron, dolasetron

        2. Palonosetron: higher binding affinity, longer half life

        3. Side effects: headaches, dizziness, constipation, QTc prolongation, serotonin syndrome

      3. Typical antipsychotics (Dopamine receptor antagonists)

        1. Prochlorperazine, haloperidol, metoclopramide

        2. Tell patients you’re using it for n/v to avoid hesitancy!

        3. Can cause extrapyramidal symptoms or acute dystonia

          1. Treatment is diphenhydramine

        4. Haloperidol

          1. Starting dose: 0.5-1 mg PO or IV

          2. Doesn’t decrease gut motility or cause sedation

          3. Can cause QTc prolongation, but not usually at this low dose

        5. Metoclopramide

          1. Stimulates 5HT4 receptors and D2 antagonist

          2. Useful w/ dysmotility

      4. Atypical antipsychotics (5HT2, D2)

        1. Olanzapine

          1. Can cause sedation and drowsiness - start w/ nighttime dose

          2. Transaminitis, hyperglycemia, dyslipidemia

          3. Can stimulate appetite - adjunct for cancer-related anorexia

      5. Others

        1. Vestibular causes: scopolamine (acetylcholine), phenergan (histamine), meclizine (histamine)

        2. Constipation: laxatives

        3. Anticipatory CINV or procedure/infusion anxiety: Benzos

  4. Constipation

    1. History is Key

      1. What are the symptoms, etiology, how habits relate to normal patter

      2. Goal: formed, soft bowel movement that doesn’t requiring straining every 1-2 days

      3. Rule out fecal impaction or bowel obstruction before starting treatment

    2. Stimulant Laxatives

      1. Relatively fast onset of action

      2. Prescribe these whenever you write an opioid prescription

      3. Senna

        1. Starting dose: 2 tabs at bedtime; can up-titrate to 6 tabs BID

      4. Dulcolax

    3. Osmotic Laxatives

      1. Miralax, lactulose milk of magnesia magnesium citrate, sorbitol

      2. Need to be taken with water/increased hydration

        1. May be difficult for patients with early satiety

      3. Avoid Mg citrate in patients w/ renal insufficiency

    4. Colace

      1. Stool softener, ineffective as single agent

      2. Can help w/ pain w/ defecation, but not very effective for constipation

    5. Suppositories

      1. Biacodyl, glycerin

      2. 15 minute onset

    6. Enemas

      1. Fleets enemas contain sodium phosphate and can lead to hyperphosphatemia in setting of renal failure

    7. Mu-opioid Receptor Antagonists

      1. Expensive

      2. Contraindicated in setting of bowel obstruction

      3. Alvimopan

        1. Give before any exposure to opioids

      4. Methylnaltrexone (Relistor)

        1. Can use when other agents have failed

  5. Anorexia/Cachexia Syndrome

    1. Definitions

      1. Anorexia: loss of appetite or desire to eat

      2. Cachexia: physical wasting and loss of muscle mass, even with preserved appetite and caloric intake

        1. Due to elevated inflammatory cytokines and tumor-derived factors which cause proteolysis of muscles

    2. Evaluation

      1. History

        1. Dry mouth?  Jaw or dental issues? GERD? Oropharyngeal candidiasis? Pain? Early satiety? Depression? Nausea? Constipation? Fatigue? Medications?

      2. Exam

        1. Thrush due to immunocompromised?

    3. Management

      1. Dependent on prognosis and GOC

      2. Years or Years to Months

        1. Address reversible causes as above

        2. Consider dietician, psychiatry, nutrition support

          1. Consider appetite stimulant if these dont work

      3. Recommend small, frequent, calorie-dense meals w/ high protein supplmenetation

    4. Pharmacologic Management

      1. Gastroparesis or slow gut → metoclopramide

      2. Isolated anorexia → olanzapine, dexamethasone

        1. ASCO: can trial short-term trial of low-dose corticosteroids to improve appetite, but are not likely to improve weight

          1. Benefit reserved for patients with weeks to short months

      3. Megace?

        1. Studies show no improvement in QOL, rare increases in weight, increased risk of VTE and death w/ higher doses

        2. Removed from NCCN guidelines!

      4. Cannabinoids

        1. Limited data about efficacy

        2. Can induce delirium

      5. Mirtazapine

        1. Good for pts w/ anorexia symptoms and depression

    5. Education

      1. Educate patients and families that anorexia is not uncomfortable especially at the end of life and is different than starvation

    6. Artificial Nutrition?

      1. Generally not recommended: can increase infection, does not improve survival, does not improve QOL

      2. Rare exceptions: prolonged anorexia/NPO status in a postop patient or other patient with good prognosis who is expected to regain ability to self-feed/sustain

  6. Fatigue

    1. Most common symptom - up to 80% of our patients

    2. Assess and manage any modifiable underlying causes

    3. Non-pharmacologic

      1. Expectation setting, energy conservation techniques exercise

      2. Exercise is a category I recommendation and is the most effective treatment!

      3. Yoga, massage, cognitive behavioral therapies

    4. Pharmacologic

      1. Stimulants: methylphenidate - can take daily or prn

      2. Steroids only at end of life, only for shor term use

  7. Grief and Depression

    1. Use validated screening tools: PHQ-2 → PHQ-9 if PHQ-2 positive

    2. “Are you experiencing mostly bad days, or a combination of bad and good days?”

    3. Can also directly ask if they think they may be depressed

    4. Treat w/ standard of care therapies, including nonpharmacologic and pharmacologic interventions

  8. Sleep/Wake Disturbances

    1. Delirium

      1. Often occurs in the evening, especially in older, hospitalized patients

      2. Prevention!!!: sleep hygiene

      3. Can present like a clinical change

      4. Avoid benzos in the hospital - can precipitate

    2. Pharmacologic

      1. Avoided unless threat of harm to patient or others

      2. Haloperidol is first line: 0.5 - 1 mg PO or IV


Reference List

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2. Wright AA, Zhang B, Alaka Ray M, et al. Associations Between End-of-Life Discussions, Patient Mental Health, Medical Care Near Death, and Caregiver Bereavement Adjustment. JAMA 2008;300(14):1665.

3. Nicholson AB, Watson GR, Derry S, et al. Methadone for cancer pain. Cochrane Database of Systematic Reviews 2017;2017(2); doi: 10.1002/14651858.CD003971.PUB4/MEDIA/CDSR/CD003971/IMAGE_T/TCD003971-AFIG-FIG03.PNG.

4. Vilkins AL, Sahara M, Till SR, et al. Effects of Shared Decision Making on Opioid Prescribing after Hysterectomy. Obstetrics and Gynecology 2019;134(4):823–833; doi: 10.1097/AOG.0000000000003468.

5. Nelson G, Fotopoulou C, Taylor J, et al. Enhanced recovery after surgery (ERAS®) society guidelines for gynecologic oncology: Addressing implementation challenges-2023 update-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). Gynecol Oncol 2023;173:58–67; doi: 10.1016/j.ygyno.2023.04.009.

6. Roeland EJ, Bohlke K, Baracos VE, et al. Management of Cancer Cachexia: ASCO Guideline. 2020.

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Sydney Oesch
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