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Transcript
Grace Varas, DO
Wake Forest School of Medicine
Section on General Medicine
Palliative Medicine

The presenter has no relevant financial
relationships to disclose
Sensitive stomachs may churn,
Some from the material, others from the puns!




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
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
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
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


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
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)



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



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…….

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20-24 ft
Food moves via wave like
contractions
Transit 1-3 hours
The “stuff” is still liquid as it is
delivered to ….


Ileocecal valve to anal spincter: 4 feet
Roles:
To extract water
 To lubricate stool
 To pass waste to Rectum to be expelled
from body.


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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

Defecation is evacuation of fecal material from
rectum. Combination of voluntary and
involuntary actions.


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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

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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.

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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

Disorders of defecation:
 Constipation
 Diarrhea
 Obstruction
 Anal diseases





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

Untreated can lead to:




Illus from: Jacques Fabian Gautier D’Agoty, Anatomie Generale, 1752
Fecal Impaction
Obstruction (megacolon)
Volvulus (ischemia)
ALL of which are
painful and potentially
life shortening!


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;130:1480-1491.
<= “The mushy
banana” is the
ideal form

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
Colon cancer
(“Apple core lesion”)
Rectum
Prolapsed Internal
hemorrhoids


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

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!!!!!!!

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Analgesics
Anti-inflammatories
Anticholinergic Drugs (the hidden enemy,
Beers List)
Antidepressants (esp. SSRI)
Antipsychotics
Anti-Parkinsonian
Antihypertensive
Antihistamines

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
Anticonvulsants
Anti-cancer (vinca alkaloids)
Anti-cholesterol (cholestyramine)
Antimony Metal Ions and Minerals
Antacids
 Iron
 Calcium
 Lead, mercury, arsenic


Alternative medicines


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
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Chinese Green Tea
Glucosamine
Chondroitin
Gingko Biloba
Saw Palmetto
Just about ANY medication!



History of bowel movements
Drug list review
Physical exam of :
Mouth
 Abdomen
 Rectum


Look at environment and functional status for
clues

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
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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)
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

Nausea/vomiting
 Delirium
 Terminal
restlessness
 Urinary retention
 Diarrhea

Illus from: C.E. Bock, Atlas of the Human Body, 1879



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
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
Lubricants
 Mineral Oil
 Vaseline Balls (!)
 Lubricates passage
 1-3 days to work
 Risk of aspiration, malabsorption of fatsoluble vitamins
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
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
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 min3hrs (avg 1 hr)
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)
If no BM > 3-4 days, gotta go from below…
Suppositories
 Local stimulation
 Glycerin 38% success in 1 hour
 Bisacodyl (dulcolax)--induces peristalsis in
20-180 minutes, 66% success in 1 hour
 Avoid in neutropenic and
thrombocytopenic patients
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

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Methylnaltrexone (Relistor, naloxone
derivative) as opioid antagonist at bowel
receptors
Only peripheral reversal, no CNS
 SQ injection, fairly new, $$, no long-term data

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L-arginine reducing colonic slowing caused
by Morphine--releases nitric oxide which
works as neuromodulator in gut
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Prunes and coffee
Rhubarb
Cascara
Ginger root
Licorice root
Irish Moss
Cayenne
Dandelion root
Chamomile
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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)
Prophylaxis is KEY for OIC
“Colace (softener) without
Senna (stimulant) is just mush
without push”
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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



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.

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

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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



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.


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
James L. Hallenbeck, M.D. Palliative Care Perspectives © 2003 by Oxford University Press, Inc.

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Traditional "conservative" management, "drip and
suck" therapy (IVF w/ NGT => traditional perioperative 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)

Bowel obstruction is a very dynamic process,
frequently reverting from total to partial
obstruction and back in as many as 50% of
cases.

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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.

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
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.

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.
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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.
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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.

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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.

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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

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.

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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: 150-300 mcg/day, either in divided SQ q8
or in continuous drip

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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? $$$)

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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 (1200-1500 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

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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.

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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.

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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.

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
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.



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)


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.


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.



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.




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!

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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



NGT output initially was >1L in first 12 hours,
decreased to minimal over 24-36 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.



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”


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.”
http://www.eperc.mcw.edu/ 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
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: 306-311
Never kick a fresh turd on a hot
day.
- Harry S Truman
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