1. EPE C for VE T E R A N S EPE C for VE T E R A N S Education in Palliative and End-of-life Care for Veterans is a collaborative effort between the Department of Veterans Affairs and EPEC ® Module 6a GI Symptoms

2. Objectives Discuss pathophysiology of common GI symptoms in palliative care Discuss assessment strategies Describe management strategies

3. Nausea/vomiting... Definition nausea is an unpleasant subjective sensation of being about to vomit vomiting is the reflex expulsion of gastric contents through the mouth

4. ... Nausea/vomiting Impact very distressing: awareness of nausea inability to keep food or fluids down acid and bitter tastes unpleasant smells of vomitus

5. Pathophysiology … Nausea subjective sensation (easily learned) stimulation gastrointestinal lining, CTZ, vestibular apparatus, cerebral cortex Vomiting neuromuscular reflex

6. … Pathophysiology Cortex Vestibular apparatus GI tract Chemoreceptor Trigger Zone (CTZ) Neurotransmitters l Neurokinin l Serotonin l Dopamine l Acetylcholine l Histamine Vomiting center

7. Assessment When Acute versus chronic Intermittent or constant Associated with sights or smells Eating patterns Bowel patterns Medications

8. Chemotherapy- associated nausea/vomiting Acute < 24 hours chemoreceptor trigger zone serotonin release in the gut Delayed 24 hours (may be days) unclear mechanism

9. Chemotherapy emetogenicity Emetogenic Class Examples of MedicationsIncidence of acute vomiting ICapecitabine, RituximabMinimal (<10%) IIGemcitabine, PaclitaxelLow (10-30%) III Doxorubicin, Carboplatin Mild (30-60%) IVModerate (80-90%) VCisplatin, high dose cyclophophamide High (>90%)

10. Management Dopamine antagonists Antihistamines Anticholinergics Serotonin antagonists Neurokinin antagonists Prokinetic agents Antacids Cytoprotective agents Other medications

11. Medications … Dopamine antagonists Haloperidol Metoclopramide Prochlorperazine Histamine antagonists Diphenhydramine Meclizine Hydroxyzine

12. … Medications … Acetylcholine antagonists Scopolamine Serotonin antagonists Granisetron Ondansetron Neurokinin-1 antagonists Aprepitant

13. … Medications Prokinetic agents Metoclopramide Antacids H2 receptor antagonists Proton pump inhibitors Dexamethasone 6-20 mg PO daily Tetrahydrocannabinol 2.5-5 mg PO tid Anti-anxiety agents

14. Summary

15. Constipation Definition straining hard stool sensation of incomplete evacuation fewer than 3 BM / week 12 weeks duration > 2 symptoms

16. Pathophysiology Medications opioids calcium-channel blockers anticholinergic Decreased motility Ileus Mechanical obstruction Metabolic abnormalities Spinal cord compression Dehydration Autonomic dysfunction Malignancy

17. Assessment Specifically ask about bowel function Establish what is normal for patient

18. Management General measures regular toileting gastrocolic reflex activity Specific therapies softenersosmotics stimulantslubricants large volume enemas

19. Stool softeners Sodium docusate Calcium docusate

20. Stimulant laxatives Prune juice Senna Bisacodyl

21. Osmotic agents Lactulose or sorbitol Milk of magnesia (other Mg salts) Magnesium citrate Polyethylene glycol

22. Lubricants/enemas Glycerin suppositories Phosphate enema Oil retention enema Tap water, 500–1,000 ml

23. Opioid-induced constipation... Occurs with all opioids Pharmacological tolerance develops slowly, or not at all Dietary interventions alone usually not sufficient Avoid bulk-forming agents in debilitated patients

24. ... Opioid-induced constipation Combination stimulant / softeners are useful first-line medications casanthranol + docusate sodium senna + docusate sodium Prokinetic agents Opioid antagonists

25. Summary

26. Diarrhea Definition: stool that is looser than ‘normal’ and /or increased in frequency

27. Pathophysiology Secretory Osmotic Inflammatory Infectious

28. Assessment Medical history laxative use previous antibiotics last BM Physical examination Tests: C. diff. if recent hospitalizations or antibiotics

29. Specific types of diarrhea Medication-related diarrhea C. Difficile Diarrhea associated with enteral feeding dietary supplements Pancreatic insufficiency-associated diarrhea

30. Management Avoid gas-forming foods e.g. milk (lactose) Increase bulk Transient, mild diarrhea attapulgite bismuth salts

31. Management of persistent diarrhea Codeine Diphenoxylate/atropine Loperamide Cholestyramine Tincture of opium

32. Summary

33. Bowel obstruction Definition: mechanical or functional obstruction of the progress of food and fluids through the GI tract Prevalence range from 6% (ovarian cancer) to 48% (colorectal cancer) Prognosis – poor if inoperable

34. Pathophysiology Intraluminal mass Direct infiltration External compression Carcinomatosis Adhesions

35. Assessment Symptoms continuous distension pain 92% intestinal colic 72-76% nausea/vomiting 68-100% Abdominal radiograph dilated loops, air-fluid levels CT scan staging, treatment planning

36. Management Surgical evaluation Standard intravenous fluids nasogastric tube - intermittent suction Inoperable stent placement

37. Analgesics opioids Antiemetics haloperidol Steroids dexamethasone Pharmacological management

38. Antisecretory agents DrugDoseNotes Octreotide10 mcg/hr SQ/IV cont. infusion or 100 mcg SQ q 8 h Minimal adverse effects; titrate daily Scopolamine50-200 mcg/hr cont. infusion or 0.1 mg SQ q 6 h Anticholinergic effects may be dose-limiting; titrate daily Glycopyrrolate0.2 to 0.4 mg SQ q 2 to 4 h; titrate Anticholinergic effects possible

39. Anticholinergics Antispasmodic and antisecretory Scopolamine 50-200 mcg/hr 0.1 mg sc q 6 h and titrate Glycopyrrolate 0.2-0.4 mg sc q 2 to 4 h and titrate

40. Octreotide... Polypeptide analog of somatostatin serum half-life = 2 h Relieves symptoms of obstruction

41. ... Octreotide Octreotide 10 mcg/hr continuous infusion Titrate to complete control of n/v If NG tube in place, clamp when volume diminishes to 100 cc and remove if no n/v Try convert to intermittent sc Continue until death

42. Summary

43. Ascites … Definition: accumulation of fluid in the abdomen 10% caused by malignancy Other etiologies: heart failure cirrhosis renal failure

44. ... Ascites Prognosis: mean survival with malignant ascites < 4 months if chemo-responsive cancer (e.g. new dx ovarian ca) 6 months – 1 year

45. Pathophysiology... Normal physiology: intravascular pressure = extravascular pressure no extravascular fluid accumulation Ascites: fluid influx increases fluid outflow decreases fluid accumulates

46. ... Pathophysiology Elevated hydrostatic pressure (e.g., congestive heart failure, cirrhosis) Decreased osmotic pressure (e.g., nephrotic syndrome, malnutrition) Fluid production > fluid resorption (infections, malignancy)

47. History & symptoms ankle swelling weight gain nausea discomfort Physical exam bulging flanks flank dullness shifting dullness fluid wave Assessment

48. Diagnostic imaging If physical exam is equivocal Detects small amounts of fluid, loculation ‘Ground Glass’ X-ray CT scan

49. Management Goal: to relieve the symptoms With little or no discomfort: don’t treat Before intervening, discuss prognosis, benefits, risks

50. Sodium and fluid balance Sodium and severe fluid restriction difficult for patients discuss benefits, burdens & other treatment options first

51. Diuretics Effective Well-tolerated Treatment goals: remove only enough fluid to manage the symptoms slow & gradual diuresis

52. Selecting a diuretic Spironolactone 100-400 mg/day Amiloride 10-40 mg/day Furosemide 100-300 mg/day

53. Therapeutic paracentesis Indications: respiratory distress diuretic failure rapid symptomatic relief Safe In clinic or home

54. Summary

55. Mucositis Definition: mucosal barrier injury may affect the entire GI tract Impact oral erythema, ulceration, pain, infection diarrhea (if it affects entire GI tract) decreased oral intake Prevalence 40% of patients on chemotherapy 100% with stem cell transplants

56. Pathophysiology Direct injury Secondary infection Graft versus host disease (GVHD)

57. Assessment History pain and its effect on the patient eating and drinking Physical examination orthostatic blood pressure and pulse weight evaluate affected oral mucosa

58. Management... l Diminish mucosal delivery, e.g., oral cryotherapy l Modify epithelial proliferation, e.g., growth factors l Reduce infections, inflammatory complications l Reduce, inhibit pro-inflammatory cytokines

59. ... Management Oral hygiene Diet (minimize contact with food) Local anesthetics Systemic analgesics

60. Summary