1. Seminar in Palliative Care September 26 – October 02, 2010 Salzburg, Austria in Collaboration with

2. The EPEC-O Curriculum is produced by the EPEC TM Project with major funding provided by NCI, with supplemental funding provided by the Lance Armstrong Foundation. Education in Palliative and End-of-life Care - Oncology The Project EPEC-O TM

3. Constipation Eugenie A.M.T. Obbens, MD PhD Pain & Palliative Care Service Memorial Sloan-Kettering Cancer Service

4. Constipation... Straining Straining Hard stool Hard stool Sensation of Sensation of Incomplete evacuation Anorectal obstruction Fewer than 3 BM / week Fewer than 3 BM / week 12 weeks duration > 2 symptoms 12 weeks duration > 2 symptoms

5. ... Constipation Epidemiology Impact: abdominal discomfort / pain, nausea and vomiting Impact: abdominal discomfort / pain, nausea and vomiting Prevalence: up to 90 % among cancer patients treated with opioids Prevalence: up to 90 % among cancer patients treated with opioids Prognosis: can limit prognosis if untreated Prognosis: can limit prognosis if untreated Management always possible

6. Key points 1.Pathophysiology 2.Assessment 3.Management

7. Pathophysiology Medications MedicationsOpioids Calcium-channel blockers Anticholinergic Decreased motility Decreased motility Ileus Ileus Mechanical obstruction Mechanical obstruction Metabolic abnormalities Metabolic abnormalities Spinal cord compression Spinal cord compression Dehydration Dehydration Autonomic dysfunction Autonomic dysfunction Malignancy Malignancy

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

9. Management General measures General measures Regular toileting Gastrocolic reflex Activity Specific measures Specific measuresSoftenersOsmoticsStimulantsLubricants Large volume enemas

10. Stool softeners ( Detergent laxatives ) Sodium docusate Sodium docusate Calcium docusate Calcium docusate Phospho-soda enema PRN Phospho-soda enema PRN

11. Stimulant laxatives Prune juice Prune juice Senna Senna Casanthranol Casanthranol Bisacodyl Bisacodyl

12. Osmotic laxatives Lactulose or sorbitol Lactulose or sorbitol Milk of magnesia ( other Mg salts ) Milk of magnesia ( other Mg salts ) Magnesium citrate Magnesium citrate Polyethylene glycol Polyethylene glycol Lederle FA, et al. Am J Med, 1990. Attar A, et al. Gut, 1999.

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

14. Constipation from opioids... Occurs with all opioids Occurs with all opioids Pharmacological tolerance develops slowly, or not at all Pharmacological tolerance develops slowly, or not at all Dietary interventions alone usually not sufficient Dietary interventions alone usually not sufficient Avoid bulk-forming agents in debilitated patients Avoid bulk-forming agents in debilitated patients Bagnol D, et al. Neuroscience, 1997.

15. ... Constipation from opioids Combination stimulant / softeners are useful first-line medications Combination stimulant / softeners are useful first-line medications Casanthranol + docusate sodium Senna + docusate sodium Prokinetic agents Prokinetic agents Opioid antagonists Opioid antagonists Sykes NP. Palliat Med, 2000.

16. Summary Use comprehensive assessment and pathophysiology-based therapy to treat the cause and improve the cancer experience

17. Bowel Obstruction

18. Bowel obstruction... Definition: mechanical or functional obstruction of the progress of food and fluids through the GI tract Definition: mechanical or functional obstruction of the progress of food and fluids through the GI tract

19. ... Bowel obstruction Impact: misery from nausea, vomiting and abdominal pain Impact: misery from nausea, vomiting and abdominal pain

20. Epidemiology Prevalence Prevalence 3 % of all advanced malignancies 11 – 42 % ovarian cancer 5 – 24 % colorectal cancer Prognosis – poor if inoperable Prognosis – poor if inoperable 64 days... Bowel obstruction Krebs HR, Goplerud DR. Am J Obstet Gynecol, 1987. Ripamonti S, et al. J Pain Symptom Manage, 2000.

21. Key points 1.Pathophysiology 2.Assessment 3.Management

22. Pathophysiology... Intraluminal mass Intraluminal mass Direct infiltration Direct infiltration External compression External compression Carcinomatosis Carcinomatosis Adhesions Adhesions Other Other

23. ... Pathophysiology 2 liters / day orally 2 liters / day orally 8 liters / day gastric & intestinal secretions 8 liters / day gastric & intestinal secretions Obstruction causes accumulation Obstruction causes accumulation Peristalsis causes distention, pain, nausea, and vomiting Peristalsis causes distention, pain, nausea, and vomiting

24. Assessment Symptoms Symptoms Continuous distension pain 92 % Intestinal colic 72 – 76 % Nausea / vomiting 68 – 100 % Abdominal radiograph Abdominal radiograph Dilated loops, air-fluid levels CT scan CT scan Staging, treatment planning

25. Differentiating small vs. large bowel obstruction S / Sx Small-highSmall-lowLarge Onset Acute, severe Progressive Abdominal pain VariableVariable Mild, steady Bowel sounds Diminished Hyperactive; diminished Bowel movement Short-termShort-termConstipation VomitingSevere Mild / moderate None; severe

26. Management... Medical Opioids Opioids Morphine – 89 % control Antiemetics Antiemetics Prochlorperazine – 13 % control Steroids SteroidsDexamethasone

27. ... Management Surgical Surgical evaluation Surgical evaluation Standard Standard Intravenous fluids Nasogastric tube – intermittent suction Inoperable Inoperable Stent placement Venting gastrostomy

28. Antisecretory agents DrugDoseNotes Octreotide 10 mcg / h SQ / IV cont. infusion or 100 mcg SQ q 8 h Minimal adverse effects; titrate daily Scopolamine ( hyoscine hydrobromide ) 10 mcg / h SQ / IV cont. infusion or 0.1 mg SQ q 6 h Anticholinergic effects may be dose - limiting; titrate daily Glycopyrrolate 0.2 to 0.4 mg SQ q 2 to 4 h; titrate Anticholinergic effects possible

29. Anticholinergics Antispasmodic and antisecretory Antispasmodic and antisecretory Scopolamine Scopolamine 10 – 100 mcg / hr SC / IV 0.1 mg SC q 6 h and titrate Glycopyrrolate Glycopyrrolate 0.2 - 0.4 mg SC q 2 – 4 h and titrate Baines M, et al. Lancet, 1985. Davis MP, Furste A. J Pain Symptom Manage, 1999.

30. Somatostatin 14 amino acid polypeptide 14 amino acid polypeptide Serum half-life = 3 minutes Central action Central action Inhibits release of GH and thyrotropin Peripheral action Peripheral action Inhibits glandular secretion Pancreas, GI tract

31. Octreotide... Polypeptide analog of somatostatin Polypeptide analog of somatostatin Serum half-life = 2 hr Relieves symptoms of obstruction Relieves symptoms of obstruction Ripamonti, et al. J Pain Symptom Manage, 2000. Mercadante, et al. Supportive Care Cancer, 2000. Fainsinger RL, et al. J Pain Symptom Manage, 1994.

32. ... Octreotide Octreotide 10 mcg/h continuous infusion Octreotide 10 mcg/h continuous infusion Titrate to complete control of N / V 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 If NG tube in place, clamp when volume diminishes to 100 cc and remove if no N / V Try convert to intermittent SC Try convert to intermittent SC Continue until death Continue until death

33. ... Octreotide Side effects Side effects Mostly none Dry mouth Biliary sludge / stones Studies in other palliative care settings Studies in other palliative care settings Subcutaneous administration Subcutaneous administration

34. Conclusions Considerable symptom control challenge Considerable symptom control challenge Surgery for selected cases Surgery for selected cases Pharmacological management relieves symptoms in many patients Pharmacological management relieves symptoms in many patients Antisecretory agents represent a significant advance Antisecretory agents represent a significant advance

35. Summary Use comprehensive assessment and pathophysiology-based therapy to treat the cause and improve the cancer experience