1. The Scoop on Poop Grace Varas, DO Wake Forest School of Medicine
Section on General Medicine
Palliative Medicine

2. The presenter has no relevant financial relationships to disclose

3. Warning! Sensitive stomachs may churn,
Comment est-ce possible ?
Sensitive stomachs may churn,
Some from the material, others from the puns!

4. Objectives To understand physiology of waste elimination via bowels
To recognize disorders of waste elimination
To learn current recommendations for treatment and prophylaxis of constipation
To review the medical management of Malignant Bowel Obstructions

5. Mrs. O
67 yo woman
Ovarian cancer S/P multiple interventions, peritoneal mets, now with MBO
Admitted from acute care hospital in late October to inpatient hospice unit
Family told by previous physicians she only had “hours, maybe a day to live”
Patient delirious, in distress with abd pain and nausea

6. What’s It All About? The Gastrointestinal Tract:
Teeth to tail: 30 feet
Function: to take in food and liquids, extract useful nutrients, and expel waste
Many enzymes, proteins, hormones, organs, and muscles in an intricate dance
The GI tract communicates with other organs (including brain)

7. Let’s Start at the Very Beginning
Dentition: critical to tearing and grinding food.
Oropharynx: salivary glands produce digestive enzymes that begin digestive process
Esophagus: first of muscular tubular structures that propels food along gi tract. (esophagus about 1 foot) Transit time: 13 seconds

8. Next…..
Stomach: Acids to dissolve food and continue digestion--Strong muscular organ that mixes and threshes food. Time: 2-4 hours
Duodenal bulb next.(stomach through second portion of duodenum also 1 foot)
Food passes to…….

9. The small intestine 20-24 ft Food moves via wave like contractions
Transit 1-3 hours
The “stuff” is still liquid as it is delivered to ….

10. The large intestine Ileocecal valve to anal spincter: 4 feet Roles:
To extract water
To lubricate stool
To pass waste to Rectum to be expelled from body.

11. The colon continued…
Material is transported via segmenting contractions and propagating contractions
By 24 hours, stool has made it to transverse colon
By 48 hours, stool has made it to descending colon and sigmoid rectum

12. Rectum and Anus--The End!
Defecation is evacuation of fecal material from rectum. Combination of voluntary and involuntary actions.
Stool fills rectum, causing distension
Straightening of anorectal angle (90 deg)
Involuntary relaxation of Int Anal Sphincter
To pass stool, puborectalis muscle holds angle and Ext Anal Sphincter relax

13. What about Endangered Feces?
What composes feces?
Feces is composed primarily of water (75%)
Remainder: 1/3 dead bacteria, 1/3 residue (fiber), balance: sloughed cells from intestine, bilirubin, fats, salts
When people don’t eat, do they still make feces? YUP.

14. Don’t forget the other stuff!
Digestive enzymes from salivary glands, pancreas, gallbladder, small intestine
Amylase, proteases, lipase, disaccharidases
Hydrochloric acid
Bile (liver via GB)
Mucus
Hormones
Gastric secretions 2L/d

15. That was the “normal stuff”…
Disorders of defecation:
Constipation
Diarrhea
Obstruction
Anal diseases

16. Constipation Frequent problem INDEPENDENT of Palliative Medicine!
Over than 2.5 Million physician visits per year related to constipation
In elderly, over 50% using laxatives regularly
Laxative use in US: $400 Million
More commonly reported in women (21% vs. 8% men--NHANES 1989) and blacks

17. Constipation Untreated can lead to:
Fecal Impaction
Obstruction (megacolon)
Volvulus (ischemia)
ALL of which are painful and potentially life shortening!
Illus from: Jacques Fabian Gautier D’Agoty, Anatomie Generale, 1752

18. Rome III Criteria for Functional Constipation
Symptoms ≥3 mo; onset ≥6 mo prior to diagnosis
Must include ≥2 of the following:
– Straining*
– Lumpy or hard stools*
– Sensation of incomplete evacuation*
– Sensation of anorectal obstruction/blockage*
– Manual maneuvers to facilitate defecation (eg, digital evacuation, support of the pelvic floor)*
– <3 defecations/wk
Loose stool rarely present w/o use of laxatives
Insufficient criteria for IBS-C
Based on: Longstreth GF et al. Gastroenterology. 2006;130:

19. <= “The mushy banana” is the ideal form

20. Constipation
Basic problems:
Slow transit time
Obstructed defecation

21. Obstructed defecation
Outlet obstruction:
cystocoele, rectocoele, anal stricture, tumor (anywhere along GI tract)
Pelvic floor dys-synergy
Muscular hypertonicity and spasm
Incomplete relaxation of pelvic floor
Paradoxical contractions
Think of these when patient needs to manually help or when laxatives are ineffective

22. Colon cancer
(“Apple core lesion”)

23. Rectum
Prolapsed Internal hemorrhoids

24. Anal Pathology Painful conditions!
Patients reluctant to pass stool, even if able
Hemorrhoids
Anal Fissures
Stercoral ulcers (pressure ulcers within the rectum from prolonged constipation)
Other anal lesions: H. zoster, tumors
Tenesmus

25. Constipation Delayed Transit time
Main causes: inactivity, spinal cord pathology, colonic myopathy
Metabolic causes: hypercalcemia, diabetes mellitus, hypothyroidism
Number one, two and three causes?
DRUGS, DRUGS, DRUGS!!!!!!!

26. Drugs: Our Friends, Our Foes
Analgesics
Anti-inflammatories
Anticholinergic Drugs (the hidden enemy, Beers List)
Antidepressants (esp. SSRI)
Antipsychotics
Anti-Parkinsonian
Antihypertensive
Antihistamines

27. Drugs: Our Friends, Our Foes
Anticonvulsants
Anti-cancer (vinca alkaloids)
Anti-cholesterol (cholestyramine)
Antimony Metal Ions and Minerals
Antacids
Iron
Calcium
Lead, mercury, arsenic

28. Drugs: Our Friends, Our Foes
Alternative medicines
Chinese Green Tea
Glucosamine
Chondroitin
Gingko Biloba
Saw Palmetto
Just about ANY medication!

29. Evaluation for Constipation
History of bowel movements
Drug list review
Physical exam of :
Mouth
Abdomen
Rectum
Look at environment and functional status for clues

30. Managing constipation
Increase fluids
Increased activity (even just getting upright)
Toileting strategies--take advantage of the gastro-colic reflex (within 20 minutes of eating)
Are there barriers to having a BM? (no assistance with ambulating/transferring to BSC, fear of soiled diaper or of pain)

31. Managing constipation
Attempt to select/substitute less constipating drugs (eg. d/c Calcium channel blockers for another class)
Consider lab work: calcium, TSH
Abdominal flat plate: Constipation score
0-3 in all 4 quadrants. More than a “7” calls for aggressive therapy

32. This guy is FOS!

33. Think of fecal impaction:
Nausea/vomiting
Delirium
Terminal restlessness
Urinary retention
Diarrhea
Illus from: C.E. Bock, Atlas of the Human Body, 1879

34. Drugs: Still Our Friends
Opiates are BIG culprits in constipation for palliative patients:
Tolerance develops to most other opioid s/e (sedation, nausea, itching), but NOT to slowing effect on transit time in the colon

35. Constipation Interventions
Fiber, which is helpful in the general population, may not be helpful & may actually *worsen* constipation if fluid intake is poor (<36 oz./day)
Start slowly; Increase water intake with increasing fiber doses
Age Recommendations for fiber:
MEN
WOMEN
<50 y.o.
38g
25g
>50 y.o.
30g
21g
Livestrong.com

36. Laxatives: Our Friends
Stool softeners
Dioctyl sodium sulfsuccinate “Docusate”
Decreases surface tension
Water enters stool more easily
Need increased fluid intake to work optimally
1-3 days to work
Indicated with anal pathology to reduce straining

37. Laxatives: Our Friends
Lubricants
Mineral Oil
Vaseline Balls (!)
Lubricates passage
1-3 days to work
Risk of aspiration, malabsorption of fat-soluble vitamins

38. Laxatives: Our Friends
Osmotic agents:
Lactulose, mannitol, sorbitol, Polyethylene glycol
Draw water into stools primarily in small intestine
PEG requires large volumes water
1-3 days to work
Risk of electrolyte shifts (i.e. cause pulmonary edema), hypomagnesemia, hyperkalemia, dehydration

39. Laxatives: Our Friends
Osmotic agents:
Magnesium and phosphate salts
Increase intestinal water secretion, stimulate peristalsis
1-6 hours
Not considered first line
Risk of electrolyte shifts, hypermagnesemia, hyperkalemia

40. Laxatives: Our Friends
Stimulants
Phenolic: Bisacodyl
Hydrolyzed by intestinal enzymes
Acts on both the small and large bowel
Powerful propulsive motor activity within minutes. Risk of cramping.
PO 6-12 hours to work; suppository 20 min-3hrs (avg 1 hr)

41. Laxatives: Our Friends
Stimulants
Anthracene: Senna
Hydrolyzed by bacterial glycosidases in colon
Induce peristalsis, increase stool water, senna some softening effects
Risk of cramping
Senna alone continues to be the drug of choice for OIC prophylaxis in the literature (Twycross, et al. JPSM 2012)

42. Laxatives Orally Or? If no BM > 3-4 days, gotta go from below…
Suppositories
Local stimulation
Glycerin 38% success in 1 hour
Bisacodyl (dulcolax)--induces peristalsis in minutes, 66% success in 1 hour
Avoid in neutropenic and thrombocytopenic patients

43. Laxatives Orally Or? Enemas
Pure tap water--concern re: electrolyte shifts
Soap and water: irritates rectal mucosa and potential for hyperkalemia
Milk & Molasses enemas (1:1 mix)
paucity of literature, but little there is shows less s/e than others, especially of electrolyte shift
C/I if milk protein allergy
My favorite to order

44. Other Strategies?
Methylnaltrexone (Relistor, naloxone derivative) as opioid antagonist at bowel receptors
Only peripheral reversal, no CNS
SQ injection, fairly new, $$, no long-term data
L-arginine reducing colonic slowing caused by Morphine--releases nitric oxide which works as neuromodulator in gut

45. Alternative/Natural Medicines
Prunes and coffee
Rhubarb
Cascara
Ginger root
Licorice root
Irish Moss
Cayenne
Dandelion root
Chamomile

46. Selecting Laxatives
Suspected obstruction? NO BULK AGENTS! =>Softeners
Anal pathology: softener to reduce straining
Fecal impaction--may need disimpaction + fecal softening: glycerin, arachis, olive oil
Soft feces in rectum: stimulant
No feces in rectum: stimulant
Opioids: stimulant (NO tolerance shown to develop to this s/e of opioids)

47. Take Away
Prophylaxis is KEY for OIC
“Colace (softener) without Senna (stimulant) is just mush without push”

48. Anal Diseases
Stool softeners the primary strategy for hemorrhoids, anal fissures, and stercoral ulcers
Herpes of perineum may need aggressive treatment--aciclovir, famciclovir, but if resistant/unable po--cidofovir or foscarnet

49. Malignant Bowel Obstruction
Common and distressing outcome in patients with abdominal or pelvic cancer.
Any time in their clinical history
5.5 to 51% ovarian cancer
10% to 28% colorectal cancer
Other tumors: gastric, pancreatic, cervical, bladder, endometrial, mesothelial (of peritoneum), carcinoma, and melanoma

50. Malignant Bowel Obstruction
Causes: postoperative adhesions, a focal malignant or benign deposit, or relapse or diffuse carcinomatosis.
Classic symptoms: intestinal colic, continuous abdominal pain, nausea or vomiting.
Patients must be selected for surgery or medical treatment of their symptoms based on their clinical status.

51. Pathophysiology of Malignant Bowel Obstruction (MBO)
The goal of therapy is to normalize gut function proximal to the obstruction.
The physiologic changes that arise with obstruction would be adaptive to reversible forms of bowel obstruction that may have occurred for our ancient ancestors, but they are maladaptive for patients with cancer.
What "misunderstanding" arises in malignant bowel obstruction?
Similarly, kidneys demonstrate a maladaptive response to heart failure. Decreased renal perfusion is sensed as dehydration. Fluid is retained to compensate when, in fact, the patient is drowning. We adjust for this by "overruling" the kidneys, telling them to get rid of salt and water and not hold on to them. The kidneys can be mistaken.

52. MBO: Maladaptive coping mechanisms
Imagine that you have been very hungry. Your tribe finally hunts down a mastodon, and it is time for a feast. You gorge yourself, eating great chunks of meat and causing a temporary obstruction. Your body would respond in the following way:
Mechanoreceptors and chemoreceptors would be stimulated by the distention caused by the large build-up of food proximal to the blockage.
These receptors would tell your brain to stop eating.
James L. Hallenbeck, M.D. Palliative Care Perspectives © 2003 by Oxford University Press, Inc

53. MBO: Maladaptive coping mechanisms
The intestine proximal to the blockage would begin hypersecreting fluid, trying to flood the system and wash the intestinal contents downstream.
Intestinal motility would increase, further trying to push contents downstream and causing cramping.
With luck, you would live to hunt another day.
While this approach works well for ingested mastodons, it works poorly for malignant bowel obstruction.
James L. Hallenbeck, M.D. Palliative Care Perspectives © 2003 by Oxford University Press, Inc

54. Pathophysiology of Malignant Bowel Obstruction (MBO)
A delicate balance of fluid absorption and secretion from and into the lumen is normally maintained.
Studies have demonstrated that with MBO the balance is shifted strongly in favor of secretion.
Increased secretion of fluid results in further intestinal dilatation, cramping, and frank nausea and vomiting.

55. Pathophysiology of Malignant Bowel Obstruction (MBO)
A vicious cycle is entered wherein hypersecretion (associated with cramping in the early stage) is followed by dilatation and vomiting, followed by further secretion and vomiting.
Dehydration and electrolyte disturbances quickly result, leading to death (and misery) if an intervention is not made

56. James L. Hallenbeck, M.D. Palliative Care Perspectives © 2003 by Oxford University Press, Inc.

57. Traditional Medical Approaches
Traditional "conservative" management, "drip and suck" therapy (IVF w/ NGT => traditional peri-operative management for obstruction)
No data that supports this approach as a long-term therapy for malignant bowel obstruction.
Multiple studies have shown dismal outcomes with this approach alone.
Theoretically, IV hydration, in addition to restoring intravascular volume, also increases hydrostatic pressure in the villi and therefore could increase secretion into the lumen, contributing to the “vicious cycle” (distension-secretion)

58. The Dynamic MBO
Bowel obstruction is a very dynamic process, frequently reverting from total to partial obstruction and back in as many as 50% of cases.

59. Early Palliative Approaches
Early palliative approaches stressed symptomatic relief.
Assumed that the gut was nonfunctional, and therefore no attempt was made to normalize function.
Symptomatic relief sometimes put the gut to sleep.
Anticholinergic drugs both decreased secretion into the gut and decreased motility, thereby alleviating cramping.
Opioids were also stressed, both to reduce motility and treat pain directly.
These approaches are still used when normalization of gut function is impossible, as it often is in very proximal gut obstruction.

60. Early Palliative Approaches
Steroids have been used in the hope of relieving obstruction by reducing swelling around obstructing growths, although their efficacy in this regard is debatable.
Only one controlled study of the use of steroids in bowel obstruction has been done. It showed no evidence that steroids were helpful in reducing the degree of obstruction. A major problem in this study was the very high rate of spontaneous conversion from total to partial obstruction.
Steroids may nevertheless be useful in bowel obstruction by decreasing bowel and peritoneal inflammation and by acting as appetite stimulants.

61. Recent Approaches
Recent approaches have tried to normalize gut function to the extent possible in addition to palliating symptoms directly.
The ability to normalize and use the proximal gut is highly dependent on the level of obstruction.
Many cases of malignant obstruction have multiple sites of obstruction, most frequently in the jejunum or ileum.

62. Recent Approaches
It is not uncommon to have many feet of potentially functional intestine proximal to the rate-limiting site of obstruction.
Very proximal obstructions prohibit normalization.
However, very proximal and very distal obstructions may be amenable to stent placement that results in significant palliation by forcing open the gut lumen using an expandable wire mesh stent.

63. Surgical Intervention
Surgical evaluation should be considered on all patients with MBO, though not all patients are candidates for surgery.
Surgery carries a high perioperative mortality rate (10%–20%), high complication rate (20%–40%), and the potential for re-obstruction.
Poor prognostic factors include recent laparotomy, carcinomatosis, and massive ascites.

64. Surgical Intervention
Relative contraindications are widespread tumor, advanced age, extra-abdominal symptomatic metastases, poor nutritional status, and previous radiotherapy.
Stents can be useful for lower bowel obstruction but not for the more common higher obstructions except very proximally.
A venting gastrostomy may be helpful for long-term decompression

65. Octreotide
An analogue of the hormone somatostatin, it significantly reduces secretion into the gut.
Study by Mangili, 13 patients with ovarian cancer-related obstruction had NG aspirate volumes measured. Mean drainage decreased from 1687 ml/day to < 50 ml/day. Similar significant results been repeated in studies by Mercadante and Shima.
Somatostatin inhibits secretion of GH, TSH, ACTH and prolactin and decreases the release of gastrin, CCK, insulin, glucagon, gastric acid and pancreatic enzymes.
It also inhibits neurotransmission in peripheral nerves of the GI tract leading to decreased peristalsis and a decrease in splanchnic blood flow.
The most important drug in the therapy of MBO is octreotide.

66. Octreotide
Octreotide may prevent the pathologic alterations of bowel obstruction in cancer patients by inhibiting the release of vasointestinal peptide, reducing gastrointestinal secretion and motility, decreasing splanchnic flow, and increasing the absorption of water and salts.
Octreotide is generally well tolerated. It appears to have minimal effects on motility.
Dose: mcg/day, either in divided SQ q8 or in continuous drip
The most important drug in the therapy of MBO is octreotide.

67. Octreotide
Octreotide can result in significant improvements in nausea and vomiting; this appears to be due to decreased secretion of fluid into the gut.
Improvement often occurs in 24 to 48 hours.
A long-acting depo version of octreotide has been developed. (Role in chronic intermittant/MBO? $$$)
The most important drug in the therapy of MBO is octreotide.

68. One aggressive approach
Patients received a drug combination composed of metoclopramide 60 mg/day, octreotide 0.3 mg/day (100mcg TID), and dexamethasone 12 mg daily. with hydration ( ml/d) and morphine or transdermal fentanyl
Study of 29 consecutive patients with inoperable MBO, this combination produced a 90% recovery rate.
The treatment not only reduced gastrointestinal symptoms (vomiting) but also allowed for the restoration of intestinal transit and re-initiation of oral feeding.
Maintenance of this treatment prevented further episodes. Upon discontinuation of treatment, symptoms recurred. Patients maintained on the combination had survival prolonged from 75 days (with placebo) to 187 days.
Mercadante S et al. J Pain Symptom Mgmt 2004;28:412–416

69. Promotility agents
Promotility agents can be used if cramping is not present and if the intention is to normalize and use the proximal gut.
Clinicians have believed that promotility agents are contraindicated in bowel obstruction traditionally because increased motility could worsen cramping and theoretically result in gut perforation.
Reports of the beneficial effects of promotility drugs are beginning to appear in the literature.
Care should be used with metoclopramide in the presence of renal failure, as it is renally excreted, and in patients with Parkinson's disease because of dopamine receptor blockade Experts in the field have warned that promotility drugs should not be used in complete bowel obstruction, although the evidence base for this seems weak.
Since in practice it is not always easy to distinguish total from partial obstruction. Frequently, obstruction progresses from partial to total and back again, making the advice not to use promotility drugs in total obstruction easier to give in principle than to follow in practice.

70. Promotility agents
Metoclopramide is the drug of choice for this purpose. Metoclopramide works by binding 5HT4 receptors and releasing acetylcholine, which in turn binds cholinergic receptors and results in increased motility.
Concomitant use of drugs with anticholinergic effects, such as scopolamine, promethazine, or amitriptyline, may antagonize this action and reduce efficacy.
Dosing is usually begun at 5-10 mg TID AC PO and gradually increased.
For large bowel dysmotility a combination of metoclopramide with a large bowel stimulant, such as senna, will probably have to suffice until new motility agents are identified.
Care should be used with metoclopramide in the presence of renal failure, as it is renally excreted, and in patients with Parkinson's disease because of dopamine receptor blockade Experts in the field have warned that promotility drugs should not be used in complete bowel obstruction, although the evidence base for this seems weak.
Since in practice it is not always easy to distinguish total from partial obstruction. Frequently, obstruction progresses from partial to total and back again, making the advice not to use promotility drugs in total obstruction easier to give in principle than to follow in practice.

71. Direct antiemetics
If cramping/colic is present or if the intent is to rest the bowel, as with patients no longer capable of eating or drinking, anticholinergic and antihistaminic antiemetics such as promethazine may be used. Glycopyrrolate, a more locally acting anticholinergic drug, can be given orally or parenterally. It can reduce cramping, intestinal secretion, and nausea.
If the goal is to normalize gut function, anticholinergic agents should be avoided, because they both inhibit motility and block the use of metoclopramide.
5HT3 antagonists, such as ondansetron, may be the agents of choice for nausea, based on the limited data presented above suggesting 5HT3-mediated nausea and the fact that they have limited effects on motility.

72. NG/venting gastrostomies
NG tube placement can be very helpful for initial gut decompression.
Venting gastrostomies have been used as a long-term alternative to NG tubes for decompression.
No studies have compared venting gastrostomies to long-term octreotide therapy.
A consensus panel of the European Association of Palliative Care recommended that venting gastrostomies be used only if medications fail to control nausea.

73. Low-fiber diet
Most patients with bowel obstruction who are able to eat should be on a low-fiber/low-residue diet.
This is essential if they are trying to eat with a total obstruction (as is, in fact, sometimes possible).
Patients with complete obstruction who do eat often vomit or regurgitate every few days.

74. Opioids
Opioids are very effective in dealing with the cramping of bowel obstruction and are usually needed for pain management associated with advanced malignant disease.
However, they can have undesirable effects on motility if one is trying to normalize gut function.
As a general rule, pain management trumps motility management (but patient goals should be addressed)

75. Opioids
The fentanyl patch may have a lesser effect on GI motility than do other agents. It is often preferred, as well, because the oral route is generally unreliable in bowel obstruction.
Methadone is also a less constipating opioid and can be administered rectally if necessary.

76. Psychosocial support
Patients with distal obstruction often become distended, which alters body image and can be distressing.
While most patients hate NG tubes, they can also become dependent on them and may resist suggestions to discontinue them.
This may be because when they were initially placed they did provide relief. Such patients also probably fear possible tube replacement.
NG Tubes, although discouraged as long-term therapy, may also represent medical caring, and thus patients and families may view suggestions to discontinue them as potential abandonment.

77. Psychosocial support
The rationale for discontinuation of any therapy must be carefully explained.
The inability to eat or drink normally causes an intense grief reaction in patients and families.
Adjusting the diet to a low-fiber/low-residue liquid-based one, may allow nurturing to continue even in the presence of complete bowel obstruction.

78. Back to Mrs. O
67 yo woman
Ovarian cancer S/P multiple interventions, peritoneal mets with MBO
Admitted from acute care hospital (without a PC team) in late October after a prolonged stay to inpatient hospice unit on my call
Patient was delirious, in distress with abd pain and intractable nausea/vomiting. Family also in distress!

79. What I did then… Octreotide 100 mcg SQ q8 hours Placed NGT to LIWS
Haloperidol for nausea & delirium
Dexamethasone 12 mg IV qam
NS IVF (50 cc/hr)
Morphine scheduled & prn
Reassured family we would aggresively treat her for comfort

80. What happened next…
NGT output initially was >1L in first 12 hours, decreased to minimal over hours
Patient awoke, comfortable, pain controlled with prn meds
On day 4, had a small BM (to the shock of family), and wanted to start drinking fluids, which I agreed to.

81. What happened next…
Family asked about prognosis. I told them, “Well, I don’t know if I can guarantee New Years, but certainly seems like she’ll have a place at the Thanksgiving table.”
Multiple jaws hit the floor.
Family told by previous physicians prior to discharge she only had “hours, maybe a day to live without surgery”

82. What happened next…
Patient did go on to live through Halloween, Thanksgiving, Christmas, New Years, and Valentines Day. She did require 2 short stays for recurrent MBO mgmt during this 5 month period at the inpt hospice unit. She died shortly before Easter, again under my watch.
More importantly, her QOL was restored: she went on motorcycle trips with her husband, returned to a careful diet, and was pain-free most of the time. She called this her “bonus life on hospice care.”

83. References
End of life/Palliative Education Resource Center Hallenbeck, James L. Palliative Care Perspectives © 2003 by Oxford University Press, Inc. Mercadante, S., Ripamonti, C. “How to Use Octreotide for Malignant Bowel Obstruction” J Support Oncology 2004;2:357–364 Storey, P. UNIPAC Four: Management of Selected Non-Pain Symptoms in the Terminally Ill New York: Mary Ann Liebert, Inc. 3rd edition, 2008

84. References
Sykes, N. Constipation and diarrhoea. In Doyle D, Hanks G, Cherney N, Calman K Oxford Textbook of Palliative Medicine NewYork: Oxford University Press 4th edition, 2009 Twycross, R., Sykes, N., Mihalyo, M., Wilcock, A.,“Therapeutic Reviews: Stimulant Laxatives and Opioid-Induced Constipation” Journal of Pain and Symptom Management Vol. 43 No. 2 February 2012:

85. Never kick a fresh turd on a hot day.
Memorable Sayings
Never kick a fresh turd on a hot day.
- Harry S Truman