1. PALLIATIVE CARE SYMPTOM MANAGEMENT
Patricia Ford MD
Medical Director
Community Hospice of Saratoga

2. OBJECTIVES:
Review common non-pain symptoms experienced by patients with chronic, progressive and life-limiting illnesses
Identify causes of those symptoms
Learn interventions to treat symptoms using both drug and non-drug treatment modalities

3. COMMON SYMPTOMS Dyspnea Nausea/Vomiting Excess Secretions
Agitation/Delirium
Constipation

4. DYSPNEA
Definition: A subjective sensation of difficulty breathing; an abnormally uncomfortable awareness of breathing
25% of ambulatory patients and over 50% of inpatients have dyspnea

5. Mr Jones
78 yo with ES COPD on home hospice. Bed to chair with marked dyspnea. Dyspneic with conversation.
Meds: Advair, Spiriva, Combivent, prednisone 10 mg daily
Albuterol nebulizer was added – using this about 5 times/day with some relief
Continuous supplemental O2 at 2 lit/NC

6. Mechanism of Dyspnea
Hypoxemia, bronchoconstriction, hyper-inflation stimulate sensory receptors
CNS processes information – sends impulse to respiratory muscles
Mismatch between afferent information from various receptors and the respiratory motor activity - dyspnea

7. Causes of Dyspnea
tracheal obstruction, asthma, COPD, aspiration, diffuse primary or metastatic cancer, lymphangitic metastases, pneumonia, pleural effusion, pneumothorax, pulmonary drug reaction, radiation pneumonitis

8. Treating the Underlying Cause
COPD -
MDI’s not effective in severe cases
Aerochambers may help
Nebulizers are preferred
Inhaled steroids may be stopped in patients on chronic oral steroids
CHF – titrate nitrates/diuretics

9. DYSPNEA in Palliative Care
Non-Drug Treatments
Positioning - sitting up
Bedside fan
Pursed lip breathing
Humidified air
Noninvasive positive pressure mask

10. DYSPNEA Treatment with Oxygen
Think of oxygen as any other drug - not all dyspneic patients benefit
Pulse oximetry will generally not be of benefit in decision-making for treating terminal dyspnea
Masks and positive pressure devices are poorly tolerated; use nasal cannula or nasal high flow
For end of life, use 2-4 liters of oxygen; for continued dyspnea use drug therapy rather than using higher flow rates or face mask

11. High Flow O2 vs BiPAP for Dyspnea in Advanced Cancer
HFO: Delivers up to 40L/min humidified heated O2
Provides naso-pharygneal washout and positive distending pressure
Decreases airway resistance and the metabolic cost of breathing
BiPAP: Also assists ventilation and unloads respiratory muscles – may stimulate trigeminal nerve

12. Study Results Dyspnea improved with both – lasted for two hours
Non-significant decrease in resp rate
BiPAP – decreased heart rate
HFO – decreased BP and improved O2
No adverse effects – less trouble sleeping on HFO vs BiPAP

13. DYSPNEA Drug therapy – mainstay is opioids
Acutely increase exercise tolerance
Reduce minute ventilation
Reduce subjective sense of breathlessness
Small doses can be effective:
5-10 mg of oral morphine in opioid naïve patients; for severe dyspnea or when patients are unable to swallow, 1-5 mg morphine IV q 10 minutes
Other opioids are also useful for dyspnea

14. Opiate Titration
As with pain, titrate to comfort. (tachypnea may persist)
May use long acting preparations ex. Morphine sulfate extended release or fentanyl patch with short acting opiate for breakthrough dyspnea

15. Morphine and Respiratory Depression
Sedation precedes respiratory depression.
Low dose opioids can be used in advanced COPD to enhance quality of life.
Opioid dose can be titrated up at the end of life when needed for symptom control.
This is not euthanasia or assisted suicide.
Ethically, the use of these drugs is appropriate and essential, as long as the intent is to relieve distress, rather than shorten life.
There is no justification for withholding symptomatic treatment to a dying patient out of fear of potential respiratory depression.

16. Mr Jones
78 yo with ES COPD on home hospice. Bed to chair with marked dyspnea. Dyspneic with conversation.
Meds: Advair, Spiriva, Combivent, prednisone 10 mg daily
Albuterol nebulizer was added – using this about 5 times/day with some relief
Continuous supplemental O2 at 2 lit/NC

17. Treatment Modifications
Discontinue spiriva/advair/combivent
Albuterol/ipratropium nebulizer q 4h
Albuterol nebulizer prn
+/- increase supplemental O2 to 3 lit/NC
Morphine 5 – 10 mg po q 1 hr prn
Fan across the face prn/relaxation techniques/ pursed lip breathing

18. Role of Anxiolytics
Anxiolytics- benzodiazepines (e.g. lorazepam) may help relieve the anxiety associated with dyspnea
Possibly blunt ventilatory drive
When combined with opioids, will produce additive sedative/CNS depressant effects which may or may not be desirable

19. Nausea/Vomiting Occurs in 62% of cancer patients
Present in 40% opioid treated patients
Under reported and under treated
Anorexia may represent chronic low grade nausea

20. The Case of Mrs. Rubio
72 yo with lung cancer with metastases to adrenals, bone and brain
Disease progression despite treatment
Recent whole brain radiation
Admitted to hospice – 30 lb weight loss, fatigue and weakness
Pain well managed on MS Contin 60 mg bid + MSIR for BTP
Occasional nausea – prn promethazine

21. Common Causes of Nausea and Vomiting in Hospice patients
Chemical: metabolic, drugs, infections
Visceral and serosal causes: bowel obstruction, GI bleed, enteritis, constipation
Increased intracranial pressure, anxiety, meningeal irritation
Labyrinth disorders

22. Mechanisms of Nausea Chemicals
Affect D2, 5HT3, NK1 receptors – stimulate the chemoreceptor trigger zone
Mechanical/GI
Affect 5HT3, mechanoreceptors and chemical receptors in GI tract – peripheral pathways
Labyrinth disorders – Achm, H1 – stimulates the vestibular system
Cortex – anxiety, meningeal irritation, increased ICP
Stimulate the vomiting center in the brainstem

23. NAUSEA / VOMITING Common causes of nausea Obstruction Gastritis, GERD
Gastric stasis
GI infection
Constipation
Abdominal carcinomatosis, extensive liver metastases
Acute effect of abdominal radiation or chemotherapy
Ascites – squashed stomach syndrome

24. NAUSEA / VOMITING Other causes of nausea Often multi-factorial
CNS - elevated ICP, posterior fossa tumors/bleed, infectious or neoplastic meningitis
Drugs - opioids, chemotherapy, antibiotics
Metabolic - hypercalcemia, liver failure, renal failure, sepsis
Psychological - anxiety, pain, conditioned response (e.g. anticipatory nausea/vomiting)
Often multi-factorial

25. NAUSEA / VOMITING Treatment with Non-Drug Therapy
GI drainage for obstruction
Fluid management – GI obstruction may improve by reducting parenteral fluids to decrease GI secretions

26. Non-pharmacologic Interventions
Avoid strong food smells
Small frequent meals
NPO during and for a while after periods of vomiting occur.
Wrist bands
Relaxation techniques - imagery, music, distraction, games
Accupuncture/accupressure

27. NAUSEA / VOMITING – Drug Therapy
Try to match the cause of nausea with the most appropriate drug class
If primary cause is Stimulation of CTZ :
Start with aD2 receptor antagonist:
metoclopramide, prochlorperazine or haloperidol
If ineffective, add a 5HT3 antagonist:
odansetron, mirtazapine

28. Other Treatments for Nausea
Anxiety – may add benzodiazepine
Elevated ICP – glucocorticoid
Gastric Stasis – metoclopramide
Constipation – treat the constipation
Bowel Obstruction – octreotide, venting PEG tube, surgery
Vestibular – scopalamine patch

29. The Case of Mrs. Rubio
72 yo with lung cancer with metastases to adrenals, bone and brain
30 lb weight loss – anorexia may represent chronic low grade nausea
Morphine may contribute to nausea
Recommendations:
Consider dexamethasone
Odansetron + prochlorperazine around the clock
Consider opiate rotation

30. Pearls in Treating Nausea
Make the anti-emetic around the clock
Use combination therapy when needed – work on different receptors
Promethazine is only a weak anti-emetic
Manage constipation if present

31. EXCESS SECRETIONS
Respirations may become congested or gurgling, especially when death is imminent
Caused by a decline in the gag reflex function and reflexive clearing of the oropharynx
Secretions from the tracheobronchial tree accumulate and the patient is too weak or unable to swallow or expectorate the secretions
Often the healthcare professionals and the family members are more affected by the noisy breathing than the patient

32. EXCESS SECRETIONS Treatments
Suctioning the patient is not recommended, as it is ineffective and often uncomfortable for the patient
Turn the patient on his/her side
Elevate the head of the bed
Reassure the family of the patient’s comfort
Educate the family about the etiology of the breathing
Anticholinergics, such as scopolomine, glycopyrrolate and hyoscyamine can be useful in reducing secretions

34. Treatment of oral secretions
Drug
Trade name
Route
Starting dose
Onset
Hyoscyca-mine
Scopala-mine
Trans-dermal
1patch
12 hrs
Atropine
Multiple
Sub-lingual
1 drop
30 min
Glycopyr-rolate
Robinul
Oral
1 mg
SC, IV
.1 mg

35. Common Errors Using both scopalamine and atropine
Adding an anti-cholinergic then treating subsequent agitation with benzodiazepines
Adding atropine for respiratory congestion in a patient that is not terminal.

36. AGITATION / DELIRIUM
Definition - An acute altered level of consciousness associated with:
Reduced attention and memory
Perceptual disturbances
Incoherent speech
Altered sleep-wake cycles

37. The Case of Mr. Coons
45 year old with ESLD secondary to Hepatitis C and alcoholic liver disease
Ascites requiring frequent paracentesis
Hepatic encephalopathy resistant to lactulose and rifaximin
Increased agitation – lorazepam makes it worse

38. Confusion Assessment Method
Digit span-repeat 3, then 4, then 5 numbers
Read letters – patient taps with ‘A’
Can a rock float? Are there fish in the sea? Is one pound more than two pounds? Do you use a hammer to pound a nail?
“Hold up this many fingers” each hand

39. AGITATION / DELIRIUM Hyperactive Delirium Hypoactive Delirium
Agitated, picking at clothes and bed covers, rambling and loud incoherent speech
Hypoactive Delirium
Quiet, sleepy, little spontaneous movement, soft incoherent speech

40. AGITATION / DELIRIUM D – drugs E – eyes and ears L – low flow states
I – Intracranial
R – retention
I – infection
U – under – hydration/nutrition/sleep
M – metabolic and toxic

41. AGITATION / DELIRIUM Treatment - Non-Drug Quiet, peaceful room
Family member present to relieve anxiety
Avoid physical restraints
Assess for unresolved psychological or spiritual issues, unfinished business
Holistic therapy

42. AGITATION / DELIRIUM Treatment with Drug Therapy
The primary drug class for terminal delirium are the major tranquilizers (e.g. haloperidol)
Although benzodiazepines are commonly used, they may lead to paradoxical worsening of the delirium
Dosing is similar to opioids for pain – give enough to reduce the target symptom, there is no maximum dose
Starting dose of haloperidol is 1-2 mgs, can be given every hour as needed to reduce symptoms until the patient has stabilized, then converted to a dose given every 6-12 hours

43. Atypical Antipsychotics
Risperidone mg taken BID to q 6 hrs
Caution with renal failure
Olanzapine mg taken daily
Not in CNS malignancy, hypoactive, over 70
Quetiapine 12.5 – 50 mg taken bid
Dosing 4 pm and hs – most sedating
Aripiprazole 5-15 mg taken q am
Useful for hyperactive – can cause insomnia

44. The Case of Mr. Coons
45 year old with ESLD secondary to Hepatitis C and alcoholic liver disease
Ascites requiring frequent paracentesis
Hepatic encephalopathy ‘resistant to lactulose and rifaximin’
Increased agitation – lorazepam makes it worse

45. Mr Coons
Haldol 1 mg q 1 hr x 3 doses then 2 mg q 6 hrs around the clock
Correct hyponatremia
Lactulose – ‘do not hold’
Discontinue diazepam and zolpidem
Improve pain management
Indwelling Pleurx catheter to manage ascites

46. Constipation
“Constipation” can mean different things to different people
Acute: recent decrease in frequency or increase in difficulty starting a bowel movement, duration less than 6 months
Chronic: less than 3 BM’s per week, duration more than 6 months

47. Constipation
In addition to complaining of “constipation”, patients also complain of:
Stool that is small or hard
Stool that is not completely evacuated
Increased gas
Abdominal or rectal pain
Change in stool character
Anorexia and early satiety

48. Causes of Constipation
Drugs
Opioids
Anti-cholinergics: (antidepressants, neuroleptics, anti-emetics, anti-histamines)
Metabolic
Hypercalcemia, diabetes, hypothyroidism, uremia
Neurologic
Spinal cord lesions

49. Causes of Constipation (cont’d)
Mechanical
Obstruction or pseudo-obstruction (Ogilvie’s)
Ascites
Carcinomatosis

50. Causes of Constipation (cont’d)
Miscellaneous
Pain - generalized or rectal
Lack of privacy or awkward positioning (bedpan)
Loss of normal bowel routine
Lack of fluid intake
Delirium

51. Opioid-Induced Constipation
Little tolerance to constipation develops
Start bowel protocol when opioids are initiated
Optimal dose is unknown
Fentanyl and methadone may cause less constipation than morphine
Methylnaltrexone (Relistor©) - Sub Q injection to reverse OI constipation

52. Constipation: Key Assessment Issues
Fecal Impaction?
Constipation vs. Obstruction?
Neurological Process?
Fluid/Electrolye problem?

53. Management of Constipation
General measures
Increase fluid intake
Restore daily bowel routine
Ensure privacy
Ensure a comfortable position
Reverse treatable causes
Prophylaxis when possible

54. Drug Therapy for Constipation
Laxatives/Stimulants
Bulk agents
Lubricants
Hyperosmotic agents
Prokinetic drugs
“Natural” laxatives
Enemas

55. Laxatives / Stimulants
Senna
Bisacodyl (Dulcolax ®)
Detergent laxatives “wetting agents”
Colace ®, Surfak ®
Castor oil is a detergent laxative that is not recommended for use.

56. Lubricants Mineral Oil
Can be used for fecal impaction or acute constipation
Causes malabsorption with prolonged use
Do not use with docusate products

57. Hyperosmotic and Saline Agents
Agents that pass through the small bowel and draw water into the colon
Sugars: lactulose, sorbitol, mannitol, glycerin
Saline agents: Polyethylene glycol
(Miralax ®), magnesium, sulfate, and phosphate preparations

58. Enemas
Saline (Fleets®)
Tap water or soap suds
Oil-retention
Other

59. Natural Laxatives Prunes or prune juice Dates and figs Raisins Apples
Senna
Other

60. Pearls in Treating Constipation at the End of Life
Do not add fiber in patient with poor fluid intake (soft impaction)
Poor motility is common – senna is useful
Docusate is generally ineffective alone
Miralax works well, but can cause dehydration

61. REFERENCES
Wood GJ et al Mgt of intractable nausea nad vomiting in patients at the end of life JAMA 2007; 298(10)
Breitbart W, Alici Y, Agitation and Delirium at the End of Life JAMA Dec 2008
McPhee et al, Care at the Close of Life: Evidence and Experience, JAMA Archives and Journals 2011
Panke, J., Coyne, P. (2006) Conversations in Palliative Care. Pittsburgh, PA: Hospice and Palliative Nurses Association

62. References continued
Wrede-Seaman, L. (2005) Symptom Management Algorithms A handbook for Palliative Care. Yakima, Washington: Intellicard
Weissman, D.(2006) Palliative Care: Presentations for Medical Educators. Medical College of Wisconsin
Hui, D et al. (2013) High-Flow Oxygen and Bilevel Positive Airway Pressure for Persistent Dyspnea in Patients with Advanced Cancer: A Phase II Randomized Trial. Journal of Pain and Symptom Management Vol 46 No. 4, October 2013