1. “Top Ten” Clinical Tips on Symptom Management for Patients with Advanced Cancer
Dr. José Pereira
Head Division of Palliative Care, University of Ottawa
Medical Chief, Palliative Care Service, Bruyère Continuing Care & The Ottawa Hospital
Provincial Medical Lead for Palliative Care, Cancer Care Ontario
Dr. Sandy Buchman
Palliative Care Consultant, Temmy Latner Centre, Toronto
& University of Toronto
Quality & Primary Care Engagement Lead, Palliative Care Program, Cancer Care Ontario

2. Faculty/Presenter Disclosure
Faculty: Dr. José Pereira
Program: 51st Annual Scientific Assembly
Relationship with commercial interests:
Grants/Research Support: Takeda (past) Education grant to conduct review of breakthrough pain
Speakers Bureau/honoraria: Nil to report
Consulting Fees: Nil to report
Other: Nil to report

3. Disclosure of Commercial Support
This program has NOT received financial support
This program has NOT received in-kind support (except for myself and my organization who have allowed me to be here to present on their time)
No potential for conflict(s) of interest to declare

4. Mitigating potential bias
Jose Pereira
Takeda: Product has very limited role & prohibitively expensive

5. Faculty/Presenter Disclosure
Faculty: Dr. Sandy Buchman
Program: 51st Annual Scientific Assembly
Relationship with commercial interests:
Grants/Research Support: Nil to report
Speakers Bureau/honoraria: Nil to report
Consulting Fees: Nil to report
Other: Nil to report

6. Disclosure of Commercial Support
This program has NOT received financial support
This program has NOT received in-kind support (except for myself and my organization who have allowed me to be here to present on their time)
No potential for conflict(s) of interest to declare

7. Mitigating potential bias
Sandy Buchman
Nil to declare

8. Any burning questions??

9. 1. Systematic Screening of Symptoms

10. Cancer patients experience many symptoms across the illness trajectory
Symptom Intensity & Tumor Stage (Non-hematological cancers)
N= 240
Median # of symptoms = 8 per patient
No evidence of disease
Local disease
Regional disease
Metastatic disease
No. of symptoms
9 (0-24)
7 (0-17)
6 (0-15)
10 (0-25)
Moderate to severe symptoms
4 (0-14)
3 (0-12)
6 (0-20)
BACKGROUND The current study was conducted to assess symptom prevalence and symptom intensity and their relation to quality of life in medical oncology patients at a Veterans Affairs medical center. METHODS Consecutive inpatients and outpatients were asked to complete the Functional Assessment Cancer Therapy (FACT-G), Memorial Symptom Assessment Scale (MSAS), and the Brief Pain Inventory. Symptoms then were analyzed by their relation to Karnofsky performance status (KPS) and quality of life. RESULTS Two hundred forty patients participated. The median number of symptoms was 8 per patient (range, 0-30 symptoms). The 5 most prevalent symptoms were lack of energy (62%), pain (59%), dry mouth (54%), shortness of breath (50%), and difficulty sleeping (45%). Patients with moderate intensity pain had a median number of 11 symptoms and patients with moderate intensity lack of energy had a median number of 13 symptoms. The number of intense symptoms increased as the KPS decreased (P < 0.001). Patients with moderately intense pain or fatigue also were more likely to experience nausea, dyspnea, and lack of appetite. The number of symptoms rated as present on the MSAS was found to correlate significantly with the FACT-G Sum Quality of Life score. CONCLUSIONS Intense symptoms were highly prevalent in this population. The presence of pain, lack of energy, or poor performance status should lead to comprehensive symptom assessment. Patients free of disease nevertheless still may experience intense symptoms. The number of symptoms present may be a helpful guide to quality of life. Routine comprehensive symptom assessment may identify a significant fraction of patients who urgently require intensive symptom palliation.
Cancer 2000;88: © 2000 American Cancer Society.
Chang VT et al. Symptom and Quality of Life Survey of Medical Oncology Patients: A Role for Symptom Assessment. Cancer 2000;88:

11. Symptoms are under-reported by patients unless standardized questionnaire used
White C, et al. ‘‘Now that You Mention it, Doctor ’’:Symptom Reporting and the Need for Systematic Questioning in a Specialist Palliative Care Unit, J Pall Med 2009; 12(5):

12. Symptoms: Patient reporting versus systematic assessment
Total symptoms identified: 2,397
Of these, only 14% (322) were volunteered
Figure 2: Fifty-five (17%) of the 322 volunteered symptoms were mild, 104 (32%) moderate, and 163 (51%) severe; 292 (91%) were distressing (Fig. 2). One thousand (48%) of the
2,075 systematically assessed symptoms were mild, 716 (35%) moderate, and 359 (17%) severe; 1,101 (53%) were distressing. Fifty-five (6%) of the 1,055 mild symptoms
were volunteered, 104 (13%) of the 820 moderate, and 163 (31%) of the 522 severe (Fig. 2).
Figure 3: Two hundred ninety-two (21%) of the 1,393 distressing symptoms were volunteered
The ten most common symptoms In descending order, fatigue, dry mouth, pain, anorexia, weight loss, early satiety, insomnia, dyspnea, drowsiness,
and constipation were the ten most common symptoms identified overall (Table 2). Pain was the most frequently volunteered symptom, followed by fatigue, anorexia, dizziness, vomiting, headache, dyspnea, nausea, cough, and bad dreams. In contrast, the most common assessed symptoms were dry mouth, weight loss, fatigue, early satiety, anorexia,
insomnia, drowsiness, dyspnea, constipation, and depression (see Table 2). Less than 10% of patients volunteered early satiety, drowsiness, dry mouth, insomnia, and weight loss.
Abstract Purpose: This study examined symptoms reported by patients after open-ended questioning vs those systematically assessed using a 48-question survey. Materials and
methods: Consecutive patients referred to the palliative medicine program at the Cleveland Clinic Foundation were screened. Openended questions were asked initially
followed by a 48-item investigatordeveloped symptom checklist. Each symptom was rated for severity as mild, moderate, or severe. Symptom distress was also evaluated. Data were
collected using standardized preprinted forms. Results: Two hundred and sixty-five patients were examined and 200 were eligible for assessment. Of those assessed, the median age
was 65 years (range 17–90), and median ECOG performance status was 2 (range 1–4). A total of 2,397 symptoms were identified, 322 volunteered and 2,075 by systematic
assessment. The median number of volunteered symptoms was one (range zero to six). Eighty-three percent of volunteered symptoms were moderate or severe and 17% mild.
Ninety-one percent were distressing. Fatigue was the most common symptom identified by systematic assessment but pain was volunteered most often. The median number of symptoms found using systematic assessment was ten (0–25). Fifty-two percent were rated moderate or severe and 48% mild. Fifty-three percent were distressing. In total, 69% of 522 severe symptoms and 79% of 1,393 distressing symptoms were not volunteered. Certain symptoms were more likely to be volunteered; this was unaffected by age, gender, or race. Conclusion: The median number of symptoms found using systematic assessment was tenfold higher (p<0.001) than those volunteered. Specific detailed symptom inquiry is essential for optimal palliation in advanced disease.
Homsi J, et al. Symptom evaluation in palliative medicine: Patient report vs systematic assessment. Support Care Cancer 2006;14:444–453.

13. Edmonton Symptom Assessment Scale (ESAS)

14. ISAAC II ESAS R Patient Self-Report Functional Status (ECOG)
Additional questions
Beginning process of tailoring kiosk to clinics & needs

15. Clinicians can fail to recognize 50-80% of patients concerns during consultation
Significantly reduced symptom distress across a number of symptoms

18. Patient referred by med oncology outpatient clinic
Seen at Supportive & Palliative Care Outpatient Clinic
78 year old man
Recently diagnosed gastric/gastroesophageal junction cancer
Undergoing EXF chemotherapy treatment in preparation for surgery
Referred for suggestions regarding severe constipation
Tried many different laxatives and combinations of laxatives
Not on an opioid
Very good funcational status (PPS 90% ECOG 1/2)
Farmer, stoic
Explore anxiety: became tearful– apologised for being tearful, described fear about what lay ahead and fear of unknown.
We stopped all laxatives, and started PEG
Supportive counseling
Returned 2 weeks later: much improved, less fear

19. 2. Useful Clinical Tools

20. The Palliative Performance Scale (PPS)
ECOG
Palliative Performance Scale (PPS) %
Ambulation
Activity & Evidence of Disease
Self-Care
Intake
Level of Consciousness
100
Full
Normal activity
No evidence of disease
Normal 1 90
Evidence of disease 80
Normal activity with effort Evidence of disease
Normal/
Reduced 2 70
Unable to do normal work Evidence of disease 60
Unable to do house work Significant disease
Occasional Assistance
Full or Confusion 3 50
Mainly Sit/Lie
Unable to do any work
Considerable Assistance 40
Mainly in Bed
As Above
Mainly Assistance
Full or Drowsy or Confusion 4 30
Totally Bed Bound
Total Care 20
Minimal Sips 10
Minimal/nil
Drowsy or Coma
Stable
Transitional
E-of-life

21. Palliative Alerts ILLNESS TRAJECTORY IN PROGRESSIVE CANCER % Death
Encourage patient to see family physician regularly or find one.
Advance care planning. Discuss code status
Review treatment plan
Explore pt’s understanding of illness, discuss prognosis & goals of care.
Establish plans to deal with emergencies (e.g. pain crisis)
Ensure ESAS & PPS/ECOG done at each visit.
Initiate home care
DNR & Advanced directives %
Discuss preferred versus optimal place of death based on needs & circumstances
Consult Palliative Care Team as needed
For some patients the decline may be more gradual while for others it may be more precipitous
Death
ILLNESS TRAJECTORY IN PROGRESSIVE CANCER

22. Prognosticating using the PPS in Cancer Patients
Lau F, Downing M, et al. J Pain, PainSympt Manage. 2009;38(1)

23. Transitioning
End-of-life

25. Cancer Care Ontario Symptom Management Guidelines
Mobile Smartphone App & Pocket Guides:
Symptom screening tools
Family physicians and other primary care providers need the support and access to resources that will support their involvement at an early stage and all along the continuum. To support clinicians CCO has developed symptom management guidelines for each of the dimensions of ESAS that we are trying to manage. They are available as full evidence-based guides-to-practice, in a condensed pocket guide format and as assessment and care planning algorithms. All of the formats are accessible for viewing or downloading on CCO’s website:
Manage the symptoms strategy:
The focus of the initiatives in the strategy is to help primary care providers provide earlier, better symptom management in a disease trajectory. A specific aim is to have PCPs providing symptom management in response ESAS to using the evidence based tools and supports provided by CCO in the same way that they provide diabetes management based on A1c results, in day to day practice

26. 3. Palliative Care Earlier Than Later

27. Old model of Palliative Care

28. Palliative Care: Earlier in illness, not only at end-of-life

29. Palliative and End of Life Trajectories  

30. Palliative and End of Life Trajectories  

31. Palliative and End of Life Trajectories  

32. 4. Selecting an analgesic: The WHO Ladder

33. Pain: A Multidimensional construct
“I have
pain”

34. Spiritual & existential
Total Suffering/Pain
Several domains merging
Pain
Spiritual & existential
Other symptoms
Total
Suffering
Victor Frankl, the Concentration camp survivor, wrote in his seminal book on meaning in the face of suffering (Man’s search for meaning): “Man lives in three dimensions: the somatic, the mental, and the spiritual. The spiritual dimension cannot be ignored, for it is what makes us human.”
Suffering can occur in several of these domains, can originate in any one or more of them and often encompasses them all simultaneously. The other term that is often used is “Total Pain”, a concept first proposed by the founder of modern-day hospice and palliative care, Dame Dr. Cicely Saunders. Michael Kearner in his seminal book called “Mortally Wounded” calls it “soul pain”.
Psychological
Cultural
Social & financial

35. WHO Analgesic Ladder Weak opioids Codeine
First ask participants if they are acquainted with the WHO ladder and ask them to briefly describe its applications.
Step 1 is for “mild” pain (1-3/10 and not affecting functioning or quality of life significantly), Step 2 is for “moderate” pain (4-6/10 with moderate impact on functioning and quality of life) and Step 3 is for “severe” pain. Note that one may “go directly” to Step 2 or even Step 3 if pain is severe.
Ask the learners to give examples of drugs for each step.
Step 1: Aspirin, NSAI, acetaminophen
Step 2: Codeine, Percocet & Percodan (i.e combinations of oxycodone with aspirin or acetaminophen). While oxycodone is a strong opioid and is 1 and ½ to 2 times more potent than morphine, the combinations with aspiriin or acetaminophen does not allow one to increase the dose of oxycodone to the degree one could if it was oxycodone alone.
Step 3: Morphine, oxycodone, hydromorphone, fentanyl, methadone. Note, do not use meperidine.
Some have suggested the addition of a fourth ladder for those with intractable pain. Treatments at this level should include intraspinal treatments, special nerve blocks such as celiac plexus blocks for pancreatic and gastric cancer-related pain and cordotomies.
Weak opioids
Codeine
Percocet®, Percodan®, Oxycocet®
Oxycodone limited by presence of aspirin or acetaminophen
Strong opioids
Morphine, hydromorphone, oxycodone, fentanyl, methadone
Do NOT use:
Meperidine
Pentacozine, propoxyphene

36. Selecting between different opioids
Morphine remains first line strong opioid
Inter-individual variability between opioids
No large studies to demonstrate that one opioid is superior to another
Less constipation with fentanyl
Clinical significance?
Renal impairment
May still use morphine but reduce dose/prolong dosing intervals & monitor
Fentanyl & buprenorphine
Beware of methadone

37. Short-acting Long-acting
Opioid Formulations
Short-acting
formulations
for
Opioid-naïve patients
Pain crises
Long-acting
formulations
Reserve for stable situations
Add short-acting opioids for breakthrough pain
While the general rule is to use short-acting or immediate release formulations when initiating opioid therapy in an opioid-naïve patient or when there is a pain crisis, there are some select and unique situations when long-acting (or controlled release formulation) would be preferred when initiating opioid treatment. E.g. A patient who will be non-compliant if required to take medications every 4 hours. They would prefer the convenience of taking medications every 12 hours (morphine, hydromorphone, oxycodone and codeine) and every 72 hours (fentanyl patches).
Some investigators have more recently challenged the notion that opioid treatment should be initiated only with a short-acting formulation (Vielvoye-Kerkmeer AP et al. JPSM 2000; 19: ; Klepstad P, et al. Pain 2003; 101: )

38. Opioid Neurotoxicity Clinical Presentation Mechanism unclear
Myoclonus, hallucinations, cognitive impairment, delirium, severe somnolence, dysesthesia, allodynia
Mechanism unclear
Management strategies
Switching opioid (opioid rotation)
Decreasing opioid dose (if pain is well controlled)
Hydration
Clinically, this syndrome presents in a variety of ways. It may manifest as only myoclonus or hallucinations or a combination of the clinical presentations listed. Other causes for cognitive impairment or somnolence or myoclonus should be ruled out as the causes of these are often multifactor.
Accumulation of opioid metabolites are often cited as being the cause. However, the opioids themselves may also cause neurotoxicity. This explains why opioids that are supposed to be devoid of active metabolites such as fentanyl and methadone may also cause neurotoxicity.
Toxicity does not seem to be mediated by the opioid receptors. Therefore, opioid antagonists (e.g. naloxone) are not used to reverse toxicity (unless there are signs of narcotization -i,.e. bradypnea of less than 8/min, pin-point pupils and difficulty awakening/arousing patient).
PS: Although it is often stated that fentanyl and methadone have not active metabolites, this inactivity refers to analgesia. Neurotoxicity-related activity has not been fully explored with these opioids. In the case of morphine, it is known that morphine-3-glucuronide provides no analgesia but appears to cause neurotoxicity. Morphine-6-glucoronide on the other hand provides both analgesia and neurotoxicity and other side effects such as nausea.
Neurotoxicity should not deter clinicians from prescribing these medications. However, clinicians should be attentive to these side effects and manage them promptly and appropriately should they occur.

39. Adjuvants for neuropathic pain
1st line
TCA, gabapentin, pregabalin
Start low & go slow
Trial of at least 5-7 days before increasing dose
Monitor for side effects
NNT=3-4
2nd line
Pregabalin, corticosteroids
3rd line
Ketamine, lidocaine

40. Adjuvants for Bone Pain
NSAIDs
Limited use in severe pain
Renal and gastro-intestinal side effects
Limitations of Cox-2 specific NSAIDs recently noted
Steroids
Useful in pain crises
Radiotherapy
75% to 85% response rate (decreased pain)
Few side effects with palliative therapy
Response within 1 to 2 weeks (maximum response up to 4 weeks later)
Duration of analgesia is several months
Palliative radiotherapy is one of the most useful adjuvant therapies for bone pain (and other pains where a large mass is causing the pain and is amenable to radiotherapy-e.g. brachial plexopathy from a large mass in the supraclavicular region). Patients should be explained that palliative radiotherapy does not cause the severe side effects that radical, high dose radiotherapy causes.
Regular administration of bisphosphonates have been shown to decrease skeletal complications (defined as need for radiotherapy, pain and hypercalcemia), especially in multiple myeloma, breast cancer and prostate cancer (especially zoledronic acid). The three bisphosphonates that are generally used in cancer care, clodronate, pamidronate and zoledronic acid, are generally given intravenously every 3 to 6 weeks. Clodronate can also be given subcutaneously and orally (daily). Oral administration however is generally not tolerated very well.
Bisphosphonates are best used if the patient has several painful areas due to multiple bone metastases.
The role of bisphosphonates in managing an acute bone pain crises is less clear.

41. Adjuvants for Bone Pain
Bisphosphonates
Reduction of skeletal events (good evidence)
Management of more acute pain with parenteral infusion (some controversy)
Calcitonin
Not effective
Palliative radiotherapy is one of the most useful adjuvant therapies for bone pain (and other pains where a large mass is causing the pain and is amenable to radiotherapy-e.g. brachial plexopathy from a large mass in the supraclavicular region). Patients should be explained that palliative radiotherapy does not cause the severe side effects that radical, high dose radiotherapy causes.
Regular administration of bisphosphonates have been shown to decrease skeletal complications (defined as need for radiotherapy, pain and hypercalcemia), especially in multiple myeloma, breast cancer and prostate cancer (especially zoledronic acid). The three bisphosphonates that are generally used in cancer care, clodronate, pamidronate and zoledronic acid, are generally given intravenously every 3 to 6 weeks. Clodronate can also be given subcutaneously and orally (daily). Oral administration however is generally not tolerated very well.
Bisphosphonates are best used if the patient has several painful areas due to multiple bone metastases.
The role of bisphosphonates in managing an acute bone pain crises is less clear.

42. 5. Managing Breakthrough Pain

43. Breakthrough Pain (BTP)
Treatment
Use a short acting opioid formulation
Use same opioid as background treatment if possible
Exceptions: Fentanyl patch
10% of total daily dose
Then titrate breakthrough dose (5% to 20%)
Transient exacerbation of pain on a background of well controlled baseline pain.
Variable in intensity, duration, frequency & cause
Types
Unpredictable
Predictable
Incident Pain
“End-of-Dose” failure not BTP

44. Breakthrough pain
Breakthrough dose needs titration (5-20%) once baseline pain controlled
Role of new sublingual formulations of fentanyl very limited
Expensive
Patient must be on at least 60mg of oral morphine per day
Limited role

45. 6. Management of Dyspnea

46. Is this patient short of breath?
The patient shown on this slide has advanced obstructive airway disease. His posture suggests that he is short of breath and he appears to be using accessory breathing muscles. However, dyspnea is a subjective symptom. A caregiver cannot assume he is short of breath simply by observing him. The patient needs to be specifically asked whether he is short of breath or not.
This slide highlights that palliative care is not reserved only for those patients with cancer. This particular patient was indeed experiencing very severe shortness of breath.

47. This is the chest X-ray of a patient with advanced lung cancer
This is the chest X-ray of a patient with advanced lung cancer. Note the “white-out” of the left lung. White out of he lung fields often suggests a large pleural effusion. However, in this patient, the lung “white-out” is secondary to lung collapse. The clue to this is the trachea that is deviated towards the “white-out”; i.e. the trachea is pulled towards the collapse. In the case of an effusion, the trachea is generally pushed away from the “white-out”. Thoracentesis would not be helpful in this case as lung collapse is the problem with this patient. This particular patient underwent a chest CT scan. An obstruction was noted in a large bronchus. A stent was inserted in the bronchus under bronchoscopy and the dyspnea relieved. Unfortunately, some patients present with this complication late in the course of their diseases and are not amenable to such measures. Comfort care takes precedence.

48. Management Approach to Dyspnea
Screen
Assess
Identify and treat
underlying causes
if possible and
if appropriate
Treatment
of symptom
Communicate:
Explain situation
to patient and family
and reassure +
Management hinges on performing three simultaneous tasks: identifying the underlying causes and treating these if possible and if appropriate, symptom-targeted measures and communicating with the patient and family. This is similar to managing delirium and nausea. +

49. Pharmacological Measures to Control Dyspnea?
Elicit responses from the participants. Write these on a flip-chart.

50. Pharmacological Measures to Control Dyspnea
Oxygen
Opioids
Adjuvant therapies

51. Non-Pharmacological Management
Use a fan
Position: lean forward, head up
Avoid exacerbating activities
Normalizing the emotional response to dyspnea is important for both patients and their caregivers. Caregivers can make the situation worse by reacting with fear and anxiety when their loved one becomes short of breath.
Moving air (fans) work be stimulating specific peri-oral receptors that, when stimulated, decrease the sensation of being short of breath.

52. 7. Management of Nausea

53. Nausea & Vomiting: mechanisms
Brain cortex(rare)
Transmitter: GABA, Ach
Causes: Anxiety, anticipatory nausea
Anti-emetic: Anxiolytic
Chemoreceptor Trigger Zone
Neuro-transmitter: Dopamine, 5HT3
Causes
Drugs (chemotherapy, opioids, SSRIs)
Toxins (infections, cytokines)
Biochemical (hypercalcemia, uremia)
Anti-emetic:
1st line: Metoclopramide, domperidone
2nd line: Haloperidol (small dose)
3rd line: ondansetron
Vomiting Centre
Transmitter: Ach, Dop
Causes: co-ordinates vomiting reflex
Anti-emetic: Same as CTZ
Knowledge of the emesis pathways and their associated neurotransmitters and receptors assists in identifying an appropriate anti-emetic regimen. The Chemoreceptor Trigger Zone (CTZ) is particularly important in palliative care. Drugs such as opioids and SSRIs, metabolic causes and infections tend to trigger nausea and emesis through this area. The GI tract is also important, as is the Vomiting Centre. Note that dimenhydrinate, for example, would be a poor choice as anti-emetic for opioid-induced nausea as dimenhydrinate (Gravol) is largely an anti-histamine while treatment of opioid-induced nausea requires a dopamine agent with GO pro-motility effects.
Gastro-intestinal tract
Neuro-transmitter: Dopamine, 5HT3
Causes: Tumors & tumor bulk, Obstruction, ileus, constipation
Anti-emetic: Same as CTZ
Vestibular apparatus (rare)
Neuro-transmitter: Histamine
Causes: Motion sickness
Anti-emetic: Antihistamine

54. Selecting an anti-emetic
Depends on underlying mechanism
1st line agents:
Usual (one of the following)
Metoclopramide 10mg PO QID PO/Subcut
Domperidone 10mg TID PO (max dose 30mg/day)
In case of bowel obstruction (one of the following)
Haloperidol 0.5-1mg subcut BID
Dimenhydrinate
2nd line agents:
Dexamethasone
Ondansetron
Methotrimeprazine
Cannibinioids
If antidopamine agent: monitor for EPS & akitisea

55. 8. The Management of Delirium in patients with advanced cancer

56. CLINICAL PRESENTATION Clinical Subtypes
Delirium presents in one of three forms.
Hyperactive form
Mixed form
Hypoactive form
AXON: MOVED FROM SLIDE 14
Meagher D. Motor subtypes of delirium: Past, present and future. Int Rev Psychiatry 2009;21:59-73;
Lawlor P et al. Occurrence, causes and outcomes of delirium in advanced cancer patients: a prospective study. Archives of Internal Medicine. 2000;160:

57. CAUSES OF DELIRIUM Causes per episode
Often multifactorial etiology per episode
On average, 3 causes per episode
E.g. opioid neurotoxicity, dehydration and hypercalcemia
Consider several causes concurrently
Sometimes the causes are unclear or cannot be found
Urinary retention aggravates delirium
Consider underlying dementias in very elderly patients
Lawlor P, et al. Occurrence, causes and outcomes of delirium in advanced cancer patients. Archives of Internal Medicine. 2000;160:
Bruera E et al. Impact of delirium and recall on the level of distress in patients with advanced cancer and their family caregivers. Cancer 2009;115:

58. Common Causes of Delirium in Palliative Care
Drugs
Opioids
Anticholinergic drugs such as tricyclic antidepressants
Anticonvulsants
Benzodiazepines
Infections
Dehydration
Metabolic/Organ failure
Renal or liver failure, hypercalcemia, hyponatremia
Hypoxemia
Brain disease: metastases or primary brain tumors
BZP withdrawals (uncommon)
Full bladder (aggravates)
Note that benzodiazepines often worsen delirium in this patient population and should not be used for managing the symptoms of delirium, unless midazolam is required to control very severe delirium that does not respond to the other modalities.

59. Overall management approach

60. Role of benzodiazepines in Palliative Care
Appear to worsen delirium in palliative patients.
Generally avoided.
Breitbart W et al. Double-blind trial of haloperidol vs chlorpromzine vs lorazepam in palliative AIDS pts. J Am Psych 1996;153(2):

61. DELIRIUM Management Guidelines. Cancer Care Ontario 2010

62. Pharmacological management
Symptom Management- 1st line
Mild
Moderate
Severe
Haloperidol 0.5mg or 1mg po or subcut OD or BID
PLUS
Haloperidol 0.5mg or 1mg PO /subcut q1hr PRN
Haloperidol 2mg or 2.5mg po or subcut BID to TID
Haloperidol 2mg PO /subcut q1hr PRN OR
Methotrimeprazine
Single dose of midazolam 2.5mg to 5mg subcut stat
Haloperidol 5mg subcut stat
Then titrate dose if initial dose ineffective
(see “moderate” doses)
Follow with haloperidol 2.5mg or 5mg q 30min PRN subcut
(max of 10-15mg /day)

63. The Role of the Atypical versus Traditional Antipsychotic medications
Haloperidol remains 1st line
Methotrimeprazine 2nd line
Newer atypical antipsychotics reserved for:
Pts requiring longer term treatment
Pts with EPS on haloperidol
Olanzapine can be given SC

64. The Myth of the “PLEASANT CONFUSION”
54% of pts whose delirium resolved recalled the delirium experience.
78%: delirium as highly distressing
Patients with hypoactive delirium were just as prone to experiencing distressing delirium as those with hyperactive delirium.
Breitbart W et al. The Delirium experience: Psychosomatics. 2002;43:

65. 9. Depression at the End of Life

66. Diagnosing depression in palliative care context
What is the prevalence of a major depression in patients with advanced disease?

67. Diagnosing depression in palliative care context
What is the prevalence of a major depression in patients with advanced disease?
10-15%
25% in pancreas cancer
Challenge
Somatic symptoms non-specific
Weight loss, fatigue
Pervasice Worthlessness, guilt, hopelessness, death wish

68. Management Supportive Counseling in all
Pharmacological management in some (where ability function is affected)
Citalopram (sedating)
Venlafaxine (stimulating)
Mirtazapine (sedating, appetite stimulation)
Duloxetine (if requires adjuvant analgesic)
Methylphenidate (short onset of action)

69. 10. Airway secretions

70. Airway “rattle” at end of life
Differentiate between upper and lower airway secretions.
Upper airway secretions:
If mild to moderate:
Reposition & reassure family
If severe
Reposition, reassure, anticholinergic
Glycopyrrolate 0.4mg Subcut q2 hrs prn
OR Scopolamine 0.4mg Subcut q 4 hrs prn
Lower airway secretions (Pulmonary edema)
Furosemide 20mg-40mg subcut stat

71. End of Life “Comfort measures” (last hrs/days)
Avoid blanket orders
No need to start “morphine drip” if there was no pain before
No need to start midazolam drip if there is no refractory symptom and palliative sedation is not required

72. QUESTIONS??