Presentation on theme: "“Top Ten” Clinical Tips on Symptom Management for Patients with Advanced Cancer Dr. José Pereira Head Division of Palliative Care, University of Ottawa."— Presentation transcript:
1 “Top Ten” Clinical Tips on Symptom Management for Patients with Advanced Cancer Dr. José PereiraHead Division of Palliative Care, University of OttawaMedical Chief, Palliative Care Service, Bruyère Continuing Care & The Ottawa HospitalProvincial Medical Lead for Palliative Care, Cancer Care OntarioDr. Sandy BuchmanPalliative Care Consultant, Temmy Latner Centre, Toronto& University of TorontoQuality & Primary Care Engagement Lead, Palliative Care Program, Cancer Care Ontario
2 Faculty/Presenter Disclosure Faculty: Dr. José PereiraProgram: 51st Annual Scientific AssemblyRelationship with commercial interests:Grants/Research Support: Takeda (past) Education grant to conduct review of breakthrough painSpeakers Bureau/honoraria: Nil to reportConsulting Fees: Nil to reportOther: Nil to report
3 Disclosure of Commercial Support This program has NOT received financial supportThis 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 PereiraTakeda: Product has very limited role & prohibitively expensive
5 Faculty/Presenter Disclosure Faculty: Dr. Sandy BuchmanProgram: 51st Annual Scientific AssemblyRelationship with commercial interests:Grants/Research Support: Nil to reportSpeakers Bureau/honoraria: Nil to reportConsulting Fees: Nil to reportOther: Nil to report
6 Disclosure of Commercial Support This program has NOT received financial supportThis 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 BuchmanNil to declare
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: 2,397Of these, only 14% (322) were volunteeredFigure 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 the2,075 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 symptomswere 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 volunteeredThe 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 andmethods: Consecutive patients referred to the palliative medicine program at the Cleveland Clinic Foundation were screened. Openended questions were asked initiallyfollowed by a 48-item investigatordeveloped symptom checklist. Each symptom was rated for severity as mild, moderate, or severe. Symptom distress was also evaluated. Data werecollected using standardized preprinted forms. Results: Two hundred and sixty-five patients were examined and 200 were eligible for assessment. Of those assessed, the median agewas 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 systematicassessment. 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.
18 Patient referred by med oncology outpatient clinic Seen at Supportive & Palliative Care Outpatient Clinic78 year old manRecently diagnosed gastric/gastroesophageal junction cancerUndergoing EXF chemotherapy treatment in preparation for surgeryReferred for suggestions regarding severe constipationTried many different laxatives and combinations of laxativesNot on an opioidVery good funcational status (PPS 90% ECOG 1/2)Farmer, stoicExplore anxiety: became tearful– apologised for being tearful, described fear about what lay ahead and fear of unknown.We stopped all laxatives, and started PEGSupportive counselingReturned 2 weeks later: much improved, less fear
20 The Palliative Performance Scale (PPS) ECOGPalliative Performance Scale (PPS)%AmbulationActivity & Evidence of DiseaseSelf-CareIntakeLevel of Consciousness100FullNormal activityNo evidence of diseaseNormal190Evidence of disease80Normal activity with effort Evidence of diseaseNormal/Reduced270Unable to do normal work Evidence of disease60Unable to do house work Significant diseaseOccasional AssistanceFull or Confusion350Mainly Sit/LieUnable to do any workConsiderable Assistance40Mainly in BedAs AboveMainly AssistanceFull or Drowsy or Confusion430Totally Bed BoundTotal Care20Minimal Sips10Minimal/nilDrowsy or ComaStableTransitionalE-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 statusReview treatment planExplore 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 careDNR & Advanced directives%Discuss preferred versus optimal place of death based on needs & circumstancesConsult Palliative Care Team as neededFor some patients the decline may be more gradual while for others it may be more precipitousDeathILLNESS 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)
25 Cancer Care Ontario Symptom Management Guidelines Mobile Smartphone App & Pocket Guides:Symptom screening toolsFamily 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 practicehttps://www.cancercare.on.ca/toolbox/symptools/
33 Pain: A Multidimensional construct “I havepain”
34 Spiritual & existential Total Suffering/PainSeveral domains mergingPainSpiritual & existentialOther symptomsTotalSufferingVictor 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”.PsychologicalCulturalSocial & 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, acetaminophenStep 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 opioidsCodeinePercocet®, Percodan®, Oxycocet®Oxycodone limited by presence of aspirin or acetaminophenStrong opioidsMorphine, hydromorphone, oxycodone, fentanyl, methadoneDo NOT use:MeperidinePentacozine, propoxyphene
36 Selecting between different opioids Morphine remains first line strong opioidInter-individual variability between opioidsNo large studies to demonstrate that one opioid is superior to anotherLess constipation with fentanylClinical significance?Renal impairmentMay still use morphine but reduce dose/prolong dosing intervals & monitorFentanyl & buprenorphineBeware of methadone
37 Short-acting Long-acting Opioid FormulationsShort-actingformulationsforOpioid-naïve patientsPain crisesLong-actingformulationsReserve for stable situationsAdd short-acting opioids for breakthrough painWhile 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, allodyniaMechanism unclearManagement strategiesSwitching opioid (opioid rotation)Decreasing opioid dose (if pain is well controlled)HydrationClinically, 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 lineTCA, gabapentin, pregabalinStart low & go slowTrial of at least 5-7 days before increasing doseMonitor for side effectsNNT=3-42nd linePregabalin, corticosteroids3rd lineKetamine, lidocaine
40 Adjuvants for Bone Pain NSAIDsLimited use in severe painRenal and gastro-intestinal side effectsLimitations of Cox-2 specific NSAIDs recently notedSteroidsUseful in pain crisesRadiotherapy75% to 85% response rate (decreased pain)Few side effects with palliative therapyResponse within 1 to 2 weeks (maximum response up to 4 weeks later)Duration of analgesia is several monthsPalliative 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 BisphosphonatesReduction of skeletal events (good evidence)Management of more acute pain with parenteral infusion (some controversy)CalcitoninNot effectivePalliative 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.
43 Breakthrough Pain (BTP) TreatmentUse a short acting opioid formulationUse same opioid as background treatment if possibleExceptions: Fentanyl patch10% of total daily doseThen titrate breakthrough dose (5% to 20%)Transient exacerbation of pain on a background of well controlled baseline pain.Variable in intensity, duration, frequency & causeTypesUnpredictablePredictableIncident Pain“End-of-Dose” failure not BTP
44 Breakthrough painBreakthrough dose needs titration (5-20%) once baseline pain controlledRole of new sublingual formulations of fentanyl very limitedExpensivePatient must be on at least 60mg of oral morphine per dayLimited role
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 ScreenAssessIdentify and treatunderlying causesif possible andif appropriateTreatmentof symptomCommunicate:Explain situationto patient and familyand 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 OxygenOpioidsAdjuvant therapies
51 Non-Pharmacological Management Use a fanPosition: lean forward, head upAvoid exacerbating activitiesNormalizing 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.
53 Nausea & Vomiting: mechanisms Brain cortex(rare)Transmitter: GABA, AchCauses: Anxiety, anticipatory nauseaAnti-emetic: AnxiolyticChemoreceptor Trigger ZoneNeuro-transmitter: Dopamine, 5HT3CausesDrugs (chemotherapy, opioids, SSRIs)Toxins (infections, cytokines)Biochemical (hypercalcemia, uremia)Anti-emetic:1st line: Metoclopramide, domperidone2nd line: Haloperidol (small dose)3rd line: ondansetronVomiting CentreTransmitter: Ach, DopCauses: co-ordinates vomiting reflexAnti-emetic: Same as CTZKnowledge 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 tractNeuro-transmitter: Dopamine, 5HT3Causes: Tumors & tumor bulk, Obstruction, ileus, constipationAnti-emetic: Same as CTZVestibular apparatus (rare)Neuro-transmitter: HistamineCauses: Motion sicknessAnti-emetic: Antihistamine
54 Selecting an anti-emetic Depends on underlying mechanism1st line agents:Usual (one of the following)Metoclopramide 10mg PO QID PO/SubcutDomperidone 10mg TID PO (max dose 30mg/day)In case of bowel obstruction (one of the following)Haloperidol 0.5-1mg subcut BIDDimenhydrinate2nd line agents:DexamethasoneOndansetronMethotrimeprazineCannibinioidsIf 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 formMixed formHypoactive formAXON: MOVED FROM SLIDE 14Meagher 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 episodeOn average, 3 causes per episodeE.g. opioid neurotoxicity, dehydration and hypercalcemiaConsider several causes concurrentlySometimes the causes are unclear or cannot be foundUrinary retention aggravates deliriumConsider underlying dementias in very elderly patientsLawlor 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 DrugsOpioidsAnticholinergic drugs such as tricyclic antidepressantsAnticonvulsantsBenzodiazepinesInfectionsDehydrationMetabolic/Organ failureRenal or liver failure, hypercalcemia, hyponatremiaHypoxemiaBrain disease: metastases or primary brain tumorsBZP 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.
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 lineMildModerateSevereHaloperidol 0.5mg or 1mg po or subcut OD or BIDPLUSHaloperidol 0.5mg or 1mg PO /subcut q1hr PRNHaloperidol 2mg or 2.5mg po or subcut BID to TIDHaloperidol 2mg PO /subcut q1hr PRNORMethotrimeprazineSingle dose of midazolam 2.5mg to 5mg subcut statHaloperidol 5mg subcut statThen 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 lineMethotrimeprazine 2nd lineNewer atypical antipsychotics reserved for:Pts requiring longer term treatmentPts with EPS on haloperidolOlanzapine 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 distressingPatients 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:
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 cancerChallengeSomatic symptoms non-specificWeight loss, fatiguePervasice 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)
70 Airway “rattle” at end of life Differentiate between upper and lower airway secretions.Upper airway secretions:If mild to moderate:Reposition & reassure familyIf severeReposition, reassure, anticholinergicGlycopyrrolate 0.4mg Subcut q2 hrs prnOR Scopolamine 0.4mg Subcut q 4 hrs prnLower airway secretions (Pulmonary edema)Furosemide 20mg-40mg subcut stat
71 End of Life “Comfort measures” (last hrs/days) Avoid blanket ordersNo need to start “morphine drip” if there was no pain beforeNo need to start midazolam drip if there is no refractory symptom and palliative sedation is not required