Advanced Symptom Management

Transcription

1 Advanced Symptom Management Janet Bull, MD, FAAHPM Four Seasons Symptom Management o Objectives Define symptom clusters and the role of cytokines Identify different clusters and treatment options Describe individual symptoms and management based on evidence Symptom Clusters Symptom clusters are 3 or more coexisting symptoms which are related to one another and occur concurrently. Appear to have a synergistic effect on patient outcome. J Natl Cancer Inst Monogram 2004

2 Sickness Behavior o Adaptive response to illness preserve energy o In chronic illness can be maladaptive leading to a multitude of symptoms such as malaise, depression, anorexia and cachexia Symptom Clusters Etiologies o Cytokine sickness elevated levels of pro-inflammatory cytokines such as IF, IL-2, IL-8 and TNF Cancer, 2003;97 Cleeland Brain Behav Immun. 2007;21 Dantzer o Chemotherapeutic agents which activate the cytokine-related pathways. Increase in IL-6, IL-8, and IL-10 Cytokine 2004;25 Pusztai Literature Review Symptom Clusters o Research in infancy o Clusters not yet well defined o Studied more in breast, lung cancer o Multiple methods for analysis used o Multiple assessment tools used o Examined 7 indvidual papers o MDASI most commonly used Fan et al. Curr Oncol 2007

3 ? Genetic Component o Polymorphisms in cytokine genes o Account for variability in pain response o NSC Lung Cancer patients o Part of future in determining treatment with cytokine directed therapies o Reyes-Gibby, Cancer Epidermial Biomarkers Prev 2007;16 Symptom Clusters o Pain (80%) o Fatigue (90%) o Weight loss (80%) o Lack of appetite (80%) o Nausea, vomiting (90%) o Anxiety (25%) o Shortness of breath (50%) o Confusion-agitation (80%) Bruera Treating Symptom Clusters o Look for a medication that treats multiple symptoms rather that single symptom treatment targeted approach o Reduce polypharmacy o Less medications = less side effects

4 Pain Cluster o Fatigue o Sleep deprivation o Pain o Depression J Pain Symptom 2006; Pain Cluster o Estimated to occur in 25% advanced cancer patients o Synergistic effect on prognosis and functional status o One symptom may cause exacerbation of others ie pain worsens sleep, fatigue, depression o Improvement in one symptom may improve others o Rule out individual symptom etiologies Pain Cluster treatment o Cognitive behavior therapy psychotherapy, music therapy, imagery, hypnosis o Nutritional therapy o Integrative acupuncture, massage o Exercise - aerobic (20-30 min/d) o Medications Fleishman JCNI Monograms 2004;

5 Fatigue Multifactorial o Anemia o Hypogonadism o Medications/chemo/radiation treatments o Autonomic dysfunction o Depression o Deconditioning o Cachexia o Poor nutrition o Pain Use of ESA in Cancer Patients o FDA approved to treat chemo related anemia o Increase in Hgb by 2gr achieved in 60 % of pts o 4-8 weeks to achieve maximum benefit o Meta-analysis of 51 clinical trials Increased risks of VTE (1.57 risk) Increased risks of mortality (1.1 risk) Increased risks of MI in cardiac and renal patients o No conclusive data that fatigue is improved 14 Psychostimulants o Methylphenidate (ritalin) - many small studies benefits - appetite, insomnia, anxiety better - may improve pain and depression - dose 5 30 mg BID o Modafanil (provigil) - studies show improvement with fatigue and depression in ALS, HIV and MS - dose mg q am

6 Corticosteroids Multiple uses o Fatigue o Pain nociceptive, neuropathic and bone metastasis o Spinal cord compression o Increased intracranial pressure o Nausea o Anorexia o Visceral obstruction/capsular distension o Bowel obstruction o Lymphedema Corticosteroids o Inhibit cytokines o Pulse therapy 8-16 mg taper down o Low dose 1-2 mg/day o Can increase insomnia so dose no later than 1-2 pm o Long term toxicity Case Study o Patient with stage IV NSCLC with bone metastasis. Presents with fatigue, depression, anorexia, bone pain, and insomnia. Best treatment option would be a. Erythropoietin stimulating agent (epogen) b. Morphine sulfate c. Megesterol acetate (megace) d. Dexamethasone (decadron) e. Methylphenidate (ritalin)

7 Potential therapies o Bupropion (Wellbutrin) o L- Carnitine o Androgen replacement therapy o Cytokine receptor antagonists Harris, Supportive and Palliative Care 9/08 vol Anorexia Cachexia Syndrome o Anorexia o Cachexia (tissue wasting) >5% wt loss/6 months (obese pt >10%) o Chronic nausea o Early satiety earliest sign o Asthenia/fatigue profound weakness, listlessness 20 Impact of Anorexia-Cachexia o Occurs in up to 80% of advanced cancers o Cause of death in 20% cancer patients o Highest in GI and lung cancers (at diagnosis) o Shortened survival o Loss of skeletal muscle + fat o Albumin marker o Psychological component Inui, CA Cancer J Clin :72

8 Treatment of Cachexia/Asthenia o Megestrol Acetate (Megace) 160 mg TID better appetite, less fatigue, improved sense of well-being, and increased weight (fat) o Dexamethasone (Decadron) 2-6 mg q am better appetite, less fatigue, improved sense of well-being o Methylphenidate (Ritalin) 5-20 mg BID better appetite, less fatigue, improved sense of well-being Bruero 2005 o Dronabinol (Marinol) mg TID Megestrol Acetate o Review of 33 trials (4,123 patients) o Meta-analysis showed a benefit in regard to improved appetite and weight gain o Unable to demonstrate improved QOL o Unable to define optimal dosage Cochrane Database Syst Rev 2005/April 5/20025 o Low dose Megace 60 mg BID effective Am J Hosp Pall Med 2005/5 Potential New Therapies for Cachexia o Melatonin 20 mg/day potent antioxidant and antitumor effects inhibited by light, stimulated by dark improves appetite, sleep, pain o Thalidomide 100 mg/day expensive, patent soon to expire improves appetite, well-being and nausea Bruero 08 (Cachexia Cluster Study) o SARM Selective Androgen Receptor

9 Dysphagia Identify Etiology o Xerostomia XRT, disease, or drugs o Oral candidiasis o Bacterial infection o Viral infection o Mucositis o Reflux esophagitis o Systemic dehydration Dysphagia Treatments o Saliva substitute o Pilocarpine 5mg TID o Nystatin/Diflucan o Mouthwash lidocaine/mso4/tetracycline hydrocortisone/maalox/benedryl o Proton pump inhibitor Nausea and Vomiting o Occurs in 50-60% terminally ill patients o High incidence GI, pancreatic, ovarian cancer o May need IV fluids for dehydration o 75% time etiology is clear o Treatment successful 80-90% o Include non-pharmacologic treatment o Don t use shotgun approach

10 Nausea and Vomiting o History early satiety, persistent nausea or post meds or eating, constipation, associated with movement or dizziness, dysphagia, pain or confusion present o Physical candidiasis, papilledema, ascites, hepatomegaly, decreased BS, abdominal mass or distension, impaction, neurological signs Nausea and Vomiting o Determine etiology Metabolic/chemical drugs, electrolytes Gastroparesis Bowel obstruction Vestibular Visceral Cortical (pain/anxiety/memories) Cranial (brain mets) Nausea and Vomiting o Chemical/metabolic hypercalcemia, uremia, hyponatremia, drugs, chemo, renal and liver failure meditated by CMTZ treat with haloperidol, prochlorperazine o Gastroparesis mediated by dysfunction of autonomic NS treat with metoclopramide

11 Nausea and Vomiting o Gastroparesis Metoclopramide (reglan) o Chemical Haloperidol/5HT3 antagonists (zofran) o Bowel Obstruction Dexamethasone + Octeotride + Hyoscamine o Vestibular Meclizine, Scopalamine o Visceral - Dexamethasone o Cortical Benzodiazepines o Cranial Cyclizine + Dexamethasone o Unclear Prochlorperazine/Haloperidol Nausea and Vomiting o Other helpful medications cannabinoids benzodiazepines antihistamines neuroleptics Single agent successful 2/3rds Multiple agents 1/3 rd Stephenson, Support Care Cancer Case Study o Patient with multiple organ failure presents with nausea and vomiting. Electrolytes show a hyponatrimia and increased BUN/Cr. Best treatment option would be a. Promethazine (phenergan) b. Haloperidol (haldol) c. Metoclopromide (reglan) d. Scopolomine patch e. Dexamethasone

12 Bowel Obstruction o Most frequently in ovarian/gi cancers o Can be partial or complete o Treatments surgery over 50% die within 2 months consider venting gastrostomy with high grade proximal obstruction medications often need to give sq/iv goal of care? Treatment for Bowel Obstruction o Opioids titrate to relief o Prokinetics metoclopramide* o Anticholinergics o Anti-inflammatory - dexamethasone o Antiemetics haloperidol, compazine o Laxatives o Octeotide reduces gut secretions * May worsen if complete obstruction Constipation o High prevalence o Definition of OIC < 3 SBM/wk o Little evidence on best treatment o Multiple therapies often needed o Stop fiber if little po intake o Prophylactic treatment with opioids

13 Constipation - Etiologies o OIC most common o Malignancy o Autonomic dysfunction o Metabolic abnormalities o Decreased mobility o Mechanical obstruction o Ileus o Spinal cord compression Treatment for Constipation o Softener (detergent laxative) docuosate, phosphosoda o Lubricant stimulants glycerin sup, oils o Stimulant laxatives senna, bisacodyl, o Osmotic agents lactolose/mom/mg citrate o Prokinetic agent - metoclopramide o Large volume enemas soap suds, warm water New Treatment for Constipation o Partial Opioid Antagonists block GI opioid receptors, not centrally oral nalaxone alvimopan methylnaltrexone sq injection (Relistor)

14 Spinal Cord Compression o Pain o Sensory loss o Motor dysfunction o Autonomic/sphincter dysfunction bladder most common o True emergency - MRI Back pain and leg weakness think SCC Spinal Cord Compression o Treatments goal is to preserve neurological function and decrease pain o Treatment depends on prognosis and QOL o Dexamethasone pain rx and edema o XRT o Surgery Dyspnea o Discuss the role of opioids in treating dyspnea o Examine the data on nebulized morphine

15 Dyspnea Multifactorial o Hypoxia o Tumor o Congestive heart failure o Anemia o COPD o Pleural effusions o Pulmonary embolism o Anxiety o Deconditioning Systemic Opioids in the Treatment of Cancer-Related Dyspnea Author No. of Level of Assessment (reference) Pts Opioid Drug Disease Study Evidence Findings Bruera et al 10 Morphine sc Advanced Acute I VAS + (82) 50% higher than regular scheduled dose cancer Mazzocato et al (86) 9 Morphine sc Advanced cancer + 5 mg if opioid naïve or ½ daily oral dose Acute I VAS and Borg Scale Allard et al 33 Morphine Advanced Acute I VAS +/+ (87) 25% or 50% of 4 hr opioid dose by same route cancer Bruera et al 20 Morphine sc Advanced Acute III VAS + (83) 5 mg bolus or 2.5 times the regular dose cancer Cohen et al 8 Morphine I.V. bolus, mean Advanced Acute III Categoric + (84) dose 5.6 mg/h cancer al Scale Ventafridda 5 Morphine sc Advanced Acute III VAS + et al (85) 10mg Chlorpromazine sc 25mg cancer 44 Treatment of Refractory Dyspnea with Long-acting Sustained MSO4 o Randomized study 48 pts with COPD o 20 mg sustained MSO4 vs placebo o Improvement noted in dyspnea scores and sleep in patients on morphine Abernethy et al, BMJ 9/02

16 Comparison of Subcutaneous to Nebulized Morphine o Small study 11 patients o Both equally effective in lowering dyspnea scores o Nebulized MSO4 less sedating Bruera, J Pain Symptom Manage 2005, vol 29 issue 6 Nebulized Morphine Beneficial? o Results of multiple studies inconclusive o Opioid receptors on the sensory nerves in the respiratory tract o Dosage range from 1-50 mg q 4 hours o Low systemic absorption o Appears to help cough Dyspnea Role of Anxiolytics o Data is mixed regarding efficacy o Use if anxiety is a key component o Agents - Lorazepam (ativan) mg po/sq/iv - Midazolam (versed) mg sl/sq/iv

17 Terminal Secretions o 92% of dying individuals o Due to accumulation of fluids in the upper airways o Repositioning appears to improve sx o Oropharyngeal suctioning? stimulate more secretions Terminal Secretions o Anticholinergics glycopyrrolate (robinul) po/sq hyoscyamine (levsin) po/sq/iv/patch atropine ophthalmic drops o 30 studies involved in review o Slight improvement with hyoscyamine, but not statistically significant Hiller, Cocharne Database Review 2008 Delirium DSM-IV Definition o Disturbance of consciousness with reduced ability to focus, sustain, or shift attention o Change in cognition or development of a perceptual disturbance o Develops over a short period of time and tends to fluctuate during the course of a day o Typically has an underlying medical cause

18 Common Causes of Delirium o Drugs - anticholinergics, sedatives and opioids o Infections o Metabolic disorders o End-organ disease uremia, hepatic failure o Dehydration o Hypercarbia/hypoxia o CNS involvement o Urinary retention or fecal impaction Prevalence at EOL Delirium 237 hospice inpatients with cancer o 213/237 (90%) had at least one episode of delirium before death o Median survival from delirium onset to death is 10 days o Etiology - 42% dehydration - 29% liver failure - 25% medication Morita T. J Pain Symptom Manage 2001 Types of Delirium o Hypomotor 25% o Hypermotor 25% o Mixed 50%

19 Hypomotor Delirium o Consider psychostimulants o PCU at McGill University- advanced cancer patients All patients had psychomotor retardation 14 patients pretreatment MMSE 21 post treatment MMSE 28 Improvement seen after first dose Delirium Advantages of Hydration o Improvement in agitated delirium o Increased elimination of drugs Important to start when cognitive function starts to decline and oral intake is very diminished Improvement in Patient Scores of Target Symptoms with Hydration 51 randomized patients Treatment Group Placebo Group Symptom Total # Improvement (%) Total # Improvemen t (%) P Value Hallucinations 11 9 (82%) 14 7 (50%) Myoclonus (83%) 17 8 (47%) Fatigue (54%) (62%) Sedation (83%) 15 5 (33%) 0.05 Total (73%) (49%) 0.006

20 Delirium - Hydration o Hypodermoclysis subcutaneous infusion o Can give continuous, bolus or overnight o Usual dose 1 liter q hs o Subcutaneous edema common side effect o Consider with agitated delirium Atypical Antipsychotics Review o Review of 5 trials - 1,570 patients o Behavioral and psychological symptoms of dementia (BPSD) improved over placebo o All effective in decreasing BPSD o Side effects were high somnolence, abnormal gait, inc cardiovascular events o Little data on long-term impact of newer antipsychotics PC- FACS 7/2005 Cochran Database Treatment of Delirium o Haloperidol (Haldol) treatment of choice usual dose.5 5 mg q 6 hr po, sq, IV o Chlorpromazine (Thorazine) sedating. dose mg q 6 hr po, pr, IM o Olanzapine (Zyprexa) md/d o Risperidone (Risperdal).5 2 mg qd or BID o Quetiapine (Seroquel) mg BID

21 Delirium NCCN Guidelines Look for underlying cause (meds, constipation) 2. Med: Haloperidol 0.5 1mg PO/SL/SQ/IV q 1 hr 3. Alternate Meds: Risperidone 05.-1mg PO/SL bid Olanzapine mg PO/SL daily Quetiapine mg PO bid 4. Add 0.5 2mg Lorazepam q 4-6 h PO/SL/SQ/IV prn refractory agitation 5. Titrate dose of effective medication 6. Support caregiver Case Study o Patient with end stage cardiac disease is admitted to the hospice inpatient unit with confusion, agitation, and restlessness. Best treatment options would include a. Methylphenidate (ritalin) b. Haloperidol (haldol) c. Chlorpromazine (thorazine) d. Quetiapine (seroquel) e. Lorazepam (ativan) Questions? jbull@fourseasonscfl.org