Grace Varas, DOWake Forest School of Medicine

Section on General MedicinePalliative 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

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

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…….

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 waterTo lubricate stool To pass waste to Rectum to be

expelled from body.

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. 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

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.

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

Illus from: Jacques Fabian Gautier D’Agoty, Anatomie Generale, 1752

Untreated can lead to: 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-CBased 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-synergyMuscular hypertonicity and spasmIncomplete relaxation of pelvic floorParadoxical 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!!!!!!!

Analgesics Anti-inflammatories Anticholinergic Drugs (the hidden

enemy, Beers List) Antidepressants (esp. SSRI) Antipsychotics Anti-Parkinsonian Antihypertensive Antihistamines

Anticonvulsants Anti-cancer (vinca alkaloids) Anti-cholesterol (cholestyramine) Antimony Metal Ions and Minerals

Antacids Iron Calcium Lead, mercury, arsenic

Alternative medicines 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

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

Illus from: C.E. Bock, Atlas of the Human Body, 1879

Nausea/vomiting Delirium Terminal

restlessness Urinary

retention Diarrhea

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

fat-soluble 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

min-3hrs (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

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

Prunes and coffee Rhubarb Cascara Ginger root Licorice root Irish Moss Cayenne Dandelion root Chamomile

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”

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

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.

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)

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

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.

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.

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.

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.

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.

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.

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

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? $$$)

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;28:412–416Mercadante S et al. J Pain Symptom Mgmt 2004;28:412–416

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.

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.

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.

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!

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