1. Gastrointestinal Symptoms in Palliative Care Dr Peter Nightingale Macmillan GP

2. Introduction  Nausea and vomiting reported by 40-70%  Constipation reported by 50% of hospice inpatients  Dry mouth reported by over 75%

3. Overview  Nausea and vomiting  Pathways and receptors  Evaluation  Causes  Receptor-specific anti-emetics  Malignant intestinal obstruction  Causes  Clinical features  management

4. Overview  Constipation  Causes  Associated symptoms  Management/laxative guidance  Mouth care  Dry mouth  Oral candidiasis

5. Nausea and Vomiting

6. Which of the following is true?  A Cyclizine and metoclopramide is a logical combination of drugs  B Steroids are unhelpful in malignant bowel dysfunction  C Cyclizine and Haloperidol is a powerful combination of antiemetics  D Metoclopramide can help colicy pain in malignant bowel dysfunction

7. Definitions  Nausea  A feeling of the need to vomit  May be accompanied by autonomic symptoms  Retching  Rhythmic, laboured, spasmodic movements of the diaphragm and abdominal muscles  Vomiting  Forceful expulsion of gastric contents through the mouth

10. Table 2 Mechanism of action of drugs used in the treatment of nausea and vomiting 1 2 ClassDrug Dopamine 2 receptor antagonistMetoclopramide Domperidone Haloperidol 5-Hydroxytryptamine 3 antagonistOndansetron Granisetron Antihistaminic antimuscarinicCyclizine Dopamine 2 antagonist, antihistaminic, antimuscarinic, 5-hydroxytryptamine 2 antagonistLevomepromazine AntimuscarinicHyoscine hydrobromide BenzodiazepineLorazepam CannabinoidNabilone CorticosteroidDexamethasone Prokinetic 5-hydroxytryptamine 4, D2Metoclopramide Domperidone Antisecretory AntimuscarinicHyoscine butylbromide Glycopyrronium Somatostatin analogueOctreotide

11. Evaluation  Establish a likely cause  Examination  Thorough review of medication-do they need a PPI?(most do)  Check bloods where appropriate  Treat anything reversible  Non-drug measures  Set realistic goals  Identify the most likely pathway and receptors involved

12. Evaluation  Choose the most potent antagonist  Choose the most appropriate route of administration  Opt for regular rather than PRN dosing  Titrate the drug dose accordingly  Review regularly:  Have you identified the cause correctly?  Consider combined therapy

13. Causes of Nausea and Vomiting  Chemical  Drugs e.g. opioids  Metabolic disturbance Calcium and urea  Gastrointestinal  Gastric stasis  Stretch/distortion of GI tract ?correctable bowel obstruction  Cranial  Elevated ICP  Meningeal irritation  Skull mets  Other  XRT  Anticipatory and anxiety  Movement  Cough

14. Is a prokinetic (e.g.metoclopramide 10-20mg tds) indicated?  Promote gastric emptying  Useful in gastric stasis (large volume vomits-late in day-undigested food-little nausea-hiccoughs)  If not settling in 2 or 3 days or happening 2-3 times daily consider using a syringe driver

15. Is vomiting due to opioids or chemical/metabolic factors?  Haloperidol 1.5mg is drug of choice for opioid induced vomiting (can usually be stopped after 10- 14 days)  Some patients develop secondary gastric stasis so metoclopramide helps.  Alternative opioid indicated if nausea persists  Haloperidol 1.5-3mg is indicated for uraemia or hypercalcaemia

16. Is the patient still vomiting?  With vomiting more than 2-3 times daily then consider a syringe driver.  Cyclizine (25-50mg tds) is broad spectrum but can cause drowsiness and a dry mouth.  Haloperidol and cyclizine is a potent combination  Avoid cyclizine and metoclopramide (they oppose each others action)  Levomepromazine 3-25mg acts at multiple sites and is sedating at higher doses.  Dexamethasone 8mg daily has an anti emetic activity

17. Summary Points  Establish a cause  Reverse anything reversible  Choose the most appropriate receptor antagonist  Choose the most appropriate route of administration  Review regularly

18. Malignant Intestinal Obstruction

19. Incidence and Prognosis  Rates of up to 42% reported in ovarian cancer  Survival for several months without surgical intervention is possible

20. Causes of Obstruction  Organic (mechanical)  Intraluminal  Intramural  Extramural  May be multiple sites of obstruction  Functional (pseudo-obstruction)  Mesenteric or bowel muscle infiltration  Coeliac plexus infiltration

21. Clinical Features  Depends on level of obstruction  Usually insidious onset  Complete or partial (sub-acute)  Difficult to distinguish in practice  Abdominal pain  Constant background  Colic

22. Clinical Features  Vomiting +/- nausea  Abdominal distension  Absolute constipation  Diarrhoea  Borborygmi, normal or absent bowel sounds

23. Management  Try to anticipate and plan treatment in advance  Surgical intervention should be considered in all patients  Radiological investigations  To distinguish between severe constipation and obstruction  In patients considered for surgery

24. Medical Management  Appropriate drug regimen can provide excellent symptom relief  CSCI is route of choice for most drugs  IV fluids, NG tubes rarely needed  Allow to eat and drink little and often  Good mouth care vital  Realistic goals

25. Pain  Background pain  Opioids  Colic  May be relieved by opioids  Most need antispasmodic  Hyoscine butylbromide 20mg stat and PRN  Hyoscine butylbromide 60-120mg/24hr  Also has an antisecretory action

26. Nausea and Vomiting  If no colic and passing flatus try prokinetic  Metoclopramide 40-100mg/24hr  Stop if develop colic  If patient has colic prokinetics are contraindicated  Cyclizine +/- haloperidol

27. Somatostatin Analogues  Octreotide inhibits secretion of numerous hormones  Resultant reduction in volume of GI secretions  More rapidly effective than hyoscine  Duration of action 8 hours  Administer via CSCI or SC bolus  Side effects: dry mouth and flatulence

28. Laxatives  Stop stimulant, osmotic or bulk-forming laxatives  If likely to be constipated try phosphate enema and a softener e.g. docusate sodium 100-200mg bd

29. Corticosteroids  Cochrane review 1999 (Feuer and Broadley)  May relieve peri-tumour oedema  Resultant improvement in symptom control  Trial of dexamethasone  8mg daily SC  Review after 5-7 days  Stop or reduce dose according to response

30. Gastroduodenal Obstruction  Duodenum  Often caused by pancreatic tumour  Usually functional  Try metoclopramide first  Pylorus  Antisecretory drugs mainstay of treatment  Steroids  Consider NGT or venting gastrostomy

31. Constipation

32. Definitions  The passage of small, hard faeces infrequently and with difficulty  The passage of hard stools less frequently than the patient’s own normal pattern

33. Prevalence in Palliative Care  A frequent cause of distress in terminally ill patients  50% of patients admitted to Palliative Care Units report constipation  80% require laxatives  90% of terminally ill patients on opioid analgesics are constipated

34. Physiology  Food residue usually in the small bowel for 1-2hr and in the colon for 2-3 days  In constipated patients colonic transit can be greatly prolonged (4-12 days)  Most of the colon’s action is mixing  Forward movement 6x/day  The frequency and strength of peristaltic contractions are influenced by meals and activity

35. Causes of Constipation  Cancer  e.g. hypercalcaemia, intra- abdominal disease  Debility  Weakness  Immobility  Poor nutrition  Treatment  Drugs e.g. opioids, anticholinergics  Concurrent disease  e.g. anal fissure  Neurological disease  Immobility  Loss of rectal sensation and anal tone

36. Effects of Opioids  Increased sphincter tone  Suppress forward peristalsis  Increase water and electrolyte absorption in the small and large bowel  Impaired defaecation reflex

37. Associated Symptoms  Flatulence  Bloating  Abdominal pain  Feeling of incomplete evacuation  Anorexia  Overflow diarrhoea  Confusion  Nausea and vomiting  Urinary dysfunction  Restlessness  Can mimic bowel obstruction by tumour

38. Assessment and Examination  Pattern of bowel movements  Access to toilet, etc  Halitosis  Faecal leak  Confusion  Abdominal distension  Visible peristalsis  Palpable colon  PR / stomal examination

39. Management  Prevention is better than waiting until intervention is needed  The aim is to achieve comfortable defaecation rather than any particular frequency and without the need for enemas or suppositories

40. General Measures  Diet  Increase fluid intake  Privacy  Commode rather than bed-pan  Mobilise if possible  Stop or reduce constipating drugs where possible

41. Oral Laxatives  Softeners  Surfactants/wetting agents e.g. docusate, poloxamer  1-3 days latency  Osmotic laxatives e.g. lactulose, Movicol  3 day latency  Lactulose: bloating, colic and flatulence  Need to increase fluid intake  Movicol better tolerated and more effective

42. Oral Laxatives  Softeners  Bulk-forming agents e.g. Fybogel, Normacol  Stool normalisers  Large fluid intake required  Can exacerbate constipation in the terminally ill and those on opioids

43. Oral Laxatives  Stimulants  e.g. senna, bisacodyl, danthron, sodium picosulphate  Induce peristalsis  6-12 hr latency  Can cause colic and severe purgation  Especially useful in opioid induced constipation

44. Oral Laxatives  Combinations  More effective and better tolerated than either alone for opioid induced constipation  Codanthramer = poloxamer + danthron  Codanthrusate = docusate + danthron  Discolouration of urine with danthron and may cause a rash

45. Equivalent Doses (Regnard, 1995)  3 codanthrusate capsules  15ml codanthrusate suspension  6 codanthramer capsules  4 codanthramer strong capsules  30ml codanthramer suspension  10ml codanthramer strong suspension  2 senna tabs + 200mg docusate  10ml senna liquid + 10ml lactulose

46. Rectal Measures  Ensure adequate oral laxatives  Undignified and inconvenient  Suppositories  Glycerol softens and lubricates  Bisacodyl stimulates  Usually given in combination  30mins to work

47. Rectal Measures  Enemas  Micro-enemas  Phosphate enemas  Evacuates stools from the lower bowel  Arachis oil enema  Softens hard and impacted stools  May need high enema if stools higher than the rectum

48. Faecal Impaction  Empty rectum/loaded colon  Oral stimulant and softener +/- high enema  Movicol  Soft faeces  Bisacodyl suppositories  Hard faeces  Oral laxatives  Suppositories and osmotic enemas first  Arachis oil retention enema  Manual evacuation may be necessary

49. Laxative Guidance  Prescribe daily stimulant AND softener, especially if on opioids  Escalate dose until bowels opened  If maximum dose ineffective reduce by half and add an osmotic agent  If bowels not opened for three days use rectal measures  Continue daily oral laxatives

50. Summary Points  Constipation should be considered in all palliative care patients  Prophylactic laxatives for patients on opioids are essential  Consider PR examination in all constipated patients  Remember non-drug measures  Titrate oral laxative dose according to response

51. Mouth Care

52. Dry Mouth  Reported in over 75% of patients  Causes:  Reduction in amount of saliva produced  Poor quality of saliva  Drug therapy  XRT  Dehydration  And lots of others

53. Associated Problems  Chewing and swallowing impaired  Taste impaired  Difficulty speaking  Poor oral hygiene  Dental caries  Dentures problematic  Embarrassment  Oral candida  Other oral infection  General deterioration in health

54. Management of Dry Mouth  Review medication  Frequent sips of water  Mouth care  Debride tongue  Mouthwashes  Pineapple chunks  Sponge sticks  Lip salve

55. Management of Dry Mouth  Stimulate salivary flow  Chewing gum, boiled sweets, citric acid  Pilocarpine (Davies et al 1998)  Artificial saliva  Glandosane, Saliva Orthana, Oralbalance  Use PRN  Usually better than water

56. Oral Candidiasis  30% of terminally ill patients  Causes  Dry mouth  Dentures  Topical steroids  (oral corticosteroids, antibiotics)

57. Oral Candidiasis  Features:  May be asymptomatic  Symptoms may relate to underlying cause e.g. dry mouth  White plaques +/- smooth, red, painful tongue +/- angular stomatitis

58. Oral Candidiasis  Treatment  Good mouth care, including dentures  Treat underlying problem  Topical antifungal agents e.g. nystatin for 10 days (sometimes continuous)  Systemic antifungals e.g. fluconazole, ketoconazole  Significant resistance to systemic antifungals

59. Summary  Gastrointestinal symptoms are extremely common in all cancer patients  A thorough evaluation of the underlying cause of any symptom is vital  Treatment should be directed according to the underlying cause  Set achievable goals  Review the response to treatment regularly