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Ogilvie syndrome and a Review of the Pharmacologic Treatment of Constipation
1. Ogilvie Syndrome
and
Review of the Pharmacologic
Treatment of Constipation
Matthew Fabiszak, D.O.
Internal Medicine Resident Physician - PGY3
2.
3. Presentation Flow
ā¢ Clinical case
ā¢ Ogilvie Syndrome
ā¢ Background
ā¢ Characteristics
ā¢ Pathophysiology
ā¢ Etiology
ā¢ Epidemiology
ā¢ Prognosis
ā¢ Complications
ā¢ Medical and Surgical Treatments
ā¢ Review of the Pharmacologic Treatment of Constipation
4. Clinical Case
ā¢ 63 year old male presented to MercyOne Des Moines Medical Center with
right hip pain after he slipped in mud and fell on his right side while
walking his dog on a trail near his house.
ā¢ Med: HCTZ, Atorvastatin
ā¢ All: None
ā¢ PMH: HTN, HLD
ā¢ PSH: Appendectomy
ā¢ FH: Dad ā heart disease
ā¢ SH: Retired postman, lives with wife and 3 year old dog. Former tobacco
use. Rare EtOH. No illicit drugs. Participates in daily walks with no anginal
symptoms.
5. Physical Exam
ā¢ Vitals: Temp 98.4, HR 88, 142/74, RR 16, 97% RA
ā¢ Gen: No acute distress, well nourished, lying fairly comfortably in bed
ā¢ HEENT: Normocephalic, atraumatic, pupils equal and pinpoint. EOMI
ā¢ CV: Reg rate, rhythm, no murmur/rub, JVD, or LE edema
ā¢ Pulm: Non labored breathing, symmetrical chest rise, no accessory muscle use, clear to
auscultation
ā¢ Abd: Non distended, non-tender without masses, no umbilical hernia observed, bowel sounds
present.
ā¢ Ext: No clubbing, cyanosis
ā¢ Neuro: no dysarthria, cranial nerves II-XII grossly intact, grossly nonfocal
ā¢ MSK: normal tone, bulk, shortened and externally rotated right lower extremity and pain with
ROM
ā¢ Skin: No abrasions, lacerations, or rashes; but he is quite muddy
ā¢ Psych: Normal mood, alert and oriented.
9. Clinical Course:
ā¢ POD 0: Successful open reduction internal fixation
ā¢ POD 1: Feeling generally well, not passing flatus or stool and
ambulation limited due to poorly controlled pain, minimal appetite
ā¢ Oxycodone continued and scheduled Tylenol added to regimen with
improvement in symptoms. Miralax added for bowel regimen.
ā¢ POD 2: Still not passing flatus and abdomen becoming distended with
some generalized non-specific tenderness, no appetite
ā¢ Abdominal XR obtained
15. Background
ā¢ First described by British surgeon, Sir
William Heneage Ogilvie (1948)
ā¢ Clinical appearance of mechanical
obstruction without evidence of an
obstruction
16. Characteristics
ā¢ Colonic pseudo-obstruction is
characterized by massive
dilation of the cecum, with
diameter greater than 10 cm,
and the right colon on
abdominal x-ray
ā¢ It is type of megacolon,
sometimes referred to as āacute
megacolonā to distinguish it
from toxic megacolon
17. Why is the cecum usually the most dilated?
ā¢ Laplace's law
ā¢ The tension on the wall of a sphere is the
product of the pressure times the radius of
the chamber and the tension is inversely
related to the thickness of the wall.
18. Pathophysiology
ā¢ Exact mechanism is unknown
ā¢ Current theories continue to suggest the idea of an imbalance in the
autonomic nervous system.
ā¢ Possibly due to ā sympathetic tone, ā parasympathetic tone, or both
19.
20. Pathophysiology
ā¢ Support for ā sympathetic tone:
ā¢ 1988 study by Lee et al, hypothesized that increased sympathetic
tone to the colon results in the inhibition of colonic motility.
ā¢ By using epidural anesthesia to block the splanchnic sympathetics, the
authors successfully treated several patients whose acute colonic psuedo-
obstruction did not respond to conservative management
ā¢ 2005 report supported this hypothesis and use of spinal anesthesia
Lee JT, Taylor BM, Singleton BC. Epidural anesthesia for acute pseudo-obstruction of the colon (Ogilvie's syndrome). Dis Colon Rectum.
1988 Sep. 31(9):686-91.
Mashour GA, Peterfreund RA. Spinal anesthesia and Ogilvie's syndrome. J Clin Anesth. 2005 Mar. 17(2):122-3.
21. Pathophysiology (Continued)
ā¢ Evidence for ā parasympathetic tone derives from nerve distribution
ā¢ Disruption of the sacral innervation may leave the distal colon atonic,
resulting in a functional obstruction
ā¢ This hypothesis is consistent with studies showing a transition between
dilated and collapsed bowel often at or near the splenic flexure
Bachulis BL, Smith PE. Pseudoobstruction of the colon. Am J Surg. 1978 Jul. 136(1):66-72.
Christensen J. Intestinal motor physiology. Sleisenger MH, Fordtran JS, eds. Gastrointestinal Disease: Pathophysiology, Diagnosis,
Management. 6th ed. Philadelphia: WB Saunders Co; 1998. 1437-50.
22. Pathophysiology (Continued)
ā¢ Evidence for dual sympathetic and parasympathetic dysfunction:
ā¢ In 1992, Hutchinson et al reported successfully treating 8 of 11
patients with acute colonic pseudo-obstruction by using the
sympathetic adrenergic blocker guanethidine, followed by the
cholinesterase inhibitor neostigmine.
Hutchinson R, Griffiths C. Acute colonic pseudo-obstruction: a pharmacological approach. Ann R Coll Surg Engl. 1992 Sep. 74(5):364-7.
24. Epidemiology
ā¢ In studies of 13,000 orthopedic and burn patients, prevalence was
0.29%
ā¢ Generally a disease of older patients (60-70 years old)
ā¢ Exception of younger patients with spinal cord or other neurologic disorders
ā¢ Slightly more prominent in males (M:F 2:1)
25. Prognosis
ā¢ Typically quite poor
ā¢ Mortality ranges from 15-50% in the literature
ā¢ Highest mortality with perforation of the cecum
ā¢ Drug-induced megacolon associated with mortality rate as high as 27.5%
26. Complications
ā¢ Acute megacolon can lead to ischemic necrosis in the massively
dilated intestinal segments
ā¢ Volvulus
ā¢ Perforation
27. Medical Treatment
ā¢ Conservative therapy:
ā¢ Nil per os
ā¢ Decompressive nasogastric tube
ā¢ Maintenance IV fluids
ā¢ Bowel regimen ā scheduled suppositories / enemas
ā¢ Discontinue offending agents
ā¢ Neostigmine
ā¢ In a 1999 Study by Ponec et al, 11 patients with acute colonic pseudo-obstruction
were randomly assigned to neostigmine group; 10 to placebo group (IV saline)
ā¢ 10/11 had prompt colonic decompression compared to 0/10
ā¢ 2 of the 10 that were responsive ultimately required colonoscopic decompression
ā¢ Median time to response of 4 minutes
ā¢ Side effects: Abdominal pain, excess salivation, vomiting, symptomatic bradycardia
Ponec et al. Neostigmine for the Treatment of Acute Colonic Pseudo-Obstruction. N Engl J Med 1999; 341:137-141
29. Review of the Pharmacologic
Treatment of Constipation
30. Presentation Flow
ā¢ Constipation Review
ā¢ Fiber
ā¢ Osmotic laxatives
ā¢ Stimulant laxatives
ā¢ Enemas and suppositories
ā¢ Other
31.
32. Constipation
ā¢ General Definition:
ā¢ Three or fewer bowel movements per week
ā¢ Public Definition:
ā¢ In a self-reported survey of 1,028 young adults
ā¢ 52 percent defined constipation as straining
ā¢ 44 percent as hard stools
ā¢ 32 percent as infrequent stools
ā¢ 20 percent as abdominal discomfort
36. Normal Transit Constipation
ā¢ Perception of constipation on patient self-report, but normal stool
movement throughout the colon
ā¢ Other symptoms may include abdominal pain and bloating
ā¢ Usually responsive to medical therapy
ā¢ i.e. fiber supplementation or laxatives
37. Slow Transit Constipation
ā¢ Defined as prolonged transit time through the colon.
ā¢ Can be confirmed with radiopaque markers that are delayed on motility study.
ā¢ A prolonged colonic transit time is defined as more than six markers still visible on a plain
abdominal radiograph taken 120 hours after ingestion of one Sitzmarks capsule containing 24
radiopaque markers.
ā¢ Patients with slow transit constipation have normal resting colonic motility, but
do not have the increase in peristaltic activity that should occur after meals.
ā¢ Administration of bisacodyl (Dulcolax) and cholinergic agents does not cause an
increase in peristaltic waves as it does in persons without constipation
ā¢ Tend not to respond to fiber supplementation or laxatives
ā¢ One clinical trial demonstrated a response to biofeedback
38.
39. Outlet Constipation (Pelvic Floor Dysfunction)
ā¢ Defined as incoordination of the muscles of the pelvic floor during attempted
evacuation
ā¢ Outlet constipation is not caused by muscle or neurologic pathology
ā¢ Most patients have normal colonic transit
ā¢ In patients with outlet constipation, stool is not expelled when it reaches the
rectum
ā¢ Common features include prolonged or excessive straining, soft stools that are
difficult to pass, and rectal discomfort.
ā¢ Requirements of manual aid to evacuate stool from the rectum is not uncommon
ā¢ The exact etiology of outlet constipation remains unclear
ā¢ Defecation disorders do not respond to traditional medical treatment, but may
respond to biofeedback and relaxation training
43. Medications
ā¢ Common
ā¢ Antacids, especially with calcium
ā¢ Iron supplements
ā¢ Opioids
ā¢ Less common
ā¢ Anticholinergic agents
ā¢ Antidiarrheal agents
ā¢ Antihistamines
ā¢ Antiparkinsonian agents
ā¢ Antipsychotics
ā¢ Calcium channel blockers
ā¢ Calcium supplements
ā¢ Diuretics
ā¢ Nonsteroidal anti-inflammatory drugs
ā¢ Sympathomimetics
ā¢ Tricyclic antidepressants
44. What tests should be performed in assessment of
medical causes of constipation?
ā¢ In the absence of other symptoms and signs, only a complete blood
cell count is necessary (strong recommendation, low-quality
evidence).
ā¢ Unless other clinical features warrant otherwise, metabolic tests
(glucose, calcium, sensitive thyroid-stimulating hormone) are not
recommended for chronic constipation (strong recommendation,
moderate-quality evidence).
ā¢ A colonoscopy should not be performed in patients without alarm
features (eg, blood in stools, anemia, weight loss) unless age-
appropriate colon cancer screening has not been performed (strong
recommendation, moderate-quality evidence).
American Gastroenterological Association Medical Position on Constipation (2013)
45. What tests should be performed in assessment of
medical causes of constipation?
ā¢ Anorectal manometry and a rectal balloon expulsion should be
performed in patients who fail to respond to laxatives (strong
recommendation, moderate-quality evidence).
ā¢ Defecography should be considered when results of anorectal
manometry and rectal balloon expulsion are inconclusive for
defecatory disorders (strong recommendation, low-quality evidence).
ā¢ Colonic transit should be evaluated if anorectal test results do not
show a defecatory disorder or if symptoms persist despite treatment
of a defecatory disorder (strong recommendation, low-quality
evidence).
American Gastroenterological Association Medical Position on Constipation (2013)
47. Fiber
ā¢ Draws water into stool (soluble) and adds bulk to fecal material
(insoluble)
ā¢ Used in normal-transit or slow-transit constipation (better for NT)
ā¢ Goal 20 ā 25 grams per day
ā¢ Try dietary intake first, then supplements if necessary
ā¢ Adverse reactions can lead to poor complianceātitration is key
ā¢ Potentially can bind to medications (e.g., thyroid products;
antibiotics)
48. Fiber Supplements
ā¢ Psyllium (Metamucil, Fiberall)
ā¢ Natural fiber, undergoes bacterial degradation ļ can lead to bloating and
flatulence
ā¢ Requires adequate water intake to avoid obstruction
ā¢ Methylcellulose (Citrucel)
ā¢ Semisynthetic cellulose fiber that is resistant to colonic bacterial degradation
ā¢ Fastest acting
ā¢ Polycarbophil (Fibercon)
ā¢ Synthetic fiber of polymer of acrylic acid
ā¢ Most resistant to bacterial degradation
49. Osmotic Laxatives
ā¢ Draws water into the intestine by creating an osmotic gradient
ā¢ Can take several days to work
ā¢ Two groups:
ā¢ Saline laxatives
ā¢ Sugar laxatives
50. Saline Laxatives
ā¢ Magnesium hydroxide (Phillipsā Milk of Magnesia)
ā¢ A small percentage of magnesium is actively absorbed in the small intestines
ā¢ Hypermagnesemia can occur in patients with renal failure and in children
ā¢ Magnesium citrate (Evac-Q-Mag)
ā¢ A small percentage of magnesium is actively absorbed in the small intestines
ā¢ Hypermagnesemia can occur in patients with renal failure and in children
ā¢ Sodium phosphate (Fleet Enema)
ā¢ Hyperphosphatemia can occur in renal insufficiency
ā¢ Previously commonly used for bowel preparation prior to colonoscopy
ā¢ Potential for acute phosphate nephropathy due to phosphate crystal deposition
51. Sugar Laxatives
ā¢ Lactulose
ā¢ Synthetic disaccharide consisting of galactose and fructose linked by bond resistant to
disaccharidases
ā¢ Not absorbed by small intestine
ā¢ Undergoes bacterial fermentation in the colon with formation of short-chain fatty acids
ā¢ Fermentation leads to common SE of gas and bloating
ā¢ Sorbitol, Mannitol
ā¢ Poor intestinal absorption
ā¢ Undergoes bacterial fermentation
ā¢ Polyethylene glycol and electrolytes (GoLYTLELY)
ā¢ Organic polymers that are poorly absorbed and not metabolized by colonic bacteria
ā¢ As such, may have less bloating and cramping
ā¢ Can be mixed with non-carbonated beverages
ā¢ Polyethylene glycol (Miralax)
ā¢ As above, but no electrolytes
52. Stimulant Laxatives
ā¢ Increase intestinal motility and secretions
ā¢ Work within hours and may cause abdominal cramps
ā¢ Historical theory of cathartic colon with use has not been proven
53. Stimulant Laxatives
ā¢ Senna
ā¢ Anthraquinone derivative and as such may cause melanosis coli
ā¢ Converted by colonic bacteria to active form
ā¢ Bisacodyl
ā¢ Hydrolyzed by endogenous esterases to active form ā impaired by increased stomach pH
ā¢ Leads to increased motility and secretions in the small intestine and colon through irritation
of smooth muscle
ā¢ Castor oil
ā¢ Hydrolyzed by lipase in the small intestine to ricinoleic acid, which inhibits intestinal water
absorption
ā¢ Increases mucosal permeability
ā¢ Stimulates motility through release of neurotransmitters from mucosal enterochromaffin
cells
ā¢ Severe cramping and diarrhea are common
55. Stimulant Laxatives (Cont.)
ā¢ Docusate
ā¢ Ionic detergents soften stool by allowing water to interact more effectively
with solid stool
ā¢ Efficacy for treatment is not well established
ā¢ Mineral oil
ā¢ Provides stool lubrication through emollient action
ā¢ Long term can lead to fat-soluble vitamin malabsorption and anal seepage
ā¢ Risk of lipoid pneumonia in patients predisposed to aspiration
56. Enemas and Suppositories
ā¢ Initiates evacuation by:
ā¢ Distend the rectum
ā¢ Softening hard stools
ā¢ Topically stimulating the colonic muscle to contract
57. Enemas and Suppositories
ā¢ Phosphate (Fleet enema)
ā¢ Risk of hyperphosphatemia
ā¢ Contraindicated in heart failure
ā¢ Small volume
ā¢ Tap-water enema
ā¢ Risk of hyponatremia and fluid overload with repeat use
ā¢ Soapsuds enema
ā¢ Risk of mucosal irritation
ā¢ Glycerin suppository
ā¢ Lubricant effects eases stool passing
ā¢ Risk of irritation
ā¢ Bisacodyl suppository
ā¢ Directly irritates mucosa ļ peristalsis
58. Other Therapies
ā¢ Lubiprostone (Amitiza)
ā¢ Activates chloride channels to increase intestinal fluid secretion
ā¢ Can be used in opiate induced constipation
ā¢ Contraindicated in mechanical obstructions
ā¢ SE of dyspnea, nausea, and hypotension
ā¢ Linaclotide (Linzess)
ā¢ Increases cGMP concentrations ļ increased chloride and bicarbonate in intestinal lumen ļ increasing fluid
ā¢ Risk off diarrhea, worsened by taking with high-fat meal
ā¢ Contraindicated in pediatrics, avoid if under 18
ā¢ Naloxegol (Movantik)
ā¢ Peripherally blocks mu-opioid receptors to decrease opiod induced constipation
ā¢ Typically should stop maintenance laxatives prior to starting
ā¢ May restart after 3 days
ā¢ Methlynaltrexone (Relistor)
ā¢ As above but available as SC injection kit
59. With so many options, what is the typical
medical management?
ā¢ Increase fiber intake (diet and as supplements) and/or start an
inexpensive osmotic agent
ā¢ Supplement osmotic agent with stimulant laxative
ā¢ Administered 30 minutes after a meal to synergize the pharmacologic agent
with the gastrocolonic response
ā¢ Lubiprostone and Linaclotide are second line
ā¢ Biofeedback therapy improves symptoms in more than 70% of
patients with defecatory disorders.
American Gastroenterological Association Medical Position on Constipation (2013)
62. Clinical Course:
ā¢ POD 2: Opiates discontinued with scheduled Tylenol in its place. NG
tube was placed. IV fluids initiated. Electrolytes repleted. Surgery and
Gastroenterology consulted.
ā¢ No planned intervention at this time, if no bowel movement by early morning
then plan for either Neostigmine or colonic decompression
ā¢ Meanwhile, add Q4H Glycerin suppository, Tap-water enema BID, and Movantik
(Naloxegol)
ā¢ POD 3: Overnight, the patient began stooling. Abdomen was less
tender. He was up ambulating the halls. Starting to get some appetite.
Requests we slow down on the suppositories. ļ
ā¢ POD 4: Symptoms much better and tolerating oral feeds.
Editor's Notes
https://xkcd.com/1053/
Postoperative appendectomy course ā really bad constipation
intertrochanteric fracture with displacement
https://radiopaedia.org/images/2865598
3, 6, 9 rule
Large bowel Obstruction vs psuedoobstruction?
3, 6, 9 rule (small, large, cecum)
Large bowel Obstruction vs psuedoobstruction?
Ogilvie described 2 patients with metastatic cancer and retroperitoneal spread to the celiac plexus they clinically appeared to have mechanical obstruction, but were without obstruction
Wall tension of the colon increases ļ ischemia with longitudinal splitting of the serosa, herniation of the muscularis propria, mucosa ļ perforation
(including iatrogenic perforation during open or laparoscopic procedures) can occur.
Pierre-Simon, marquis de Laplace
French scholar and physicist (1749-1827)
https://en.wikipedia.org/wiki/Pierre-Simon_Laplace
https://posterng.netkey.at/esr/viewing/index.php?module=viewimage&task=&mediafile_id=402956&201201291740.gif
Ogilvie hypothesized that the etiology of their conditions was an imbalance in the autonomic nervous system with sympathetic deprivation to the colon, leading to unopposed parasympathetic tone and regional contraction, with resulting functional obstruction
Vagus nerve supplies the parasympathetic tone from the upper gastrointestinal (GI) tract to the splenic flexure
Sacral parasympathetic nerves (S2 to S5) supply the left colon, sigmoid, and rectum.
Sympathetic stimuli result in the inhibition of bowel motility and the contraction of sphincters.
Right colon: lower 6 thoracic segments
Left colon: lumbar segments 1-3
https://grossessequebec.files.wordpress.com/2015/10/the-autonomic-nervous-system.jpg
True prevalence is largely unknown as the disease may be self remitting
Neostigmine (acetylcholinesterase inhibitor)
Keep atropine on hand for bronchospasm / bradyarrhythmia
https://www.aafp.org/afp/2011/0801/p299.html
The Rome criteria are developed through a collaboration of researchers, physicians and other health professionals from around the world.
The Rome III criteria reflect the third revision of the functional gastrointestinal disorder diagnostic criteria and were published in 2006.
Note: Criteria must be fulfilled for the past three months with symptoms onset at least six months before diagnosis
Hypercalcemia depresses the autonomic nervous system and resulting smooth-muscle hypotonicity.
NSAID - decreased prostaglandin synthesis ļ constipation
Attempt to treat with laxatives, if no benefit, not normal transit constipation
Check manometry and balloon expulsion, if negative, not obstructive
Next, rule out slow transit
Balloon expulsion is a simple, office-based screening test for defecatory disorders.
After insertion of the latex balloon into the rectum, 50 ml of water or air is instilled into the balloon, and the patient is asked to expel the balloon into a toilet.
Inability to expel the balloon within two minutes suggests a defecatory disorder.
Defecography is performed by instilling thickened barium into the rectum.
With the patient sitting on a radiolucent commode, radiographic films or videos are taken during fluoroscopy while the patient is resting, contracting the anal sphincter, and straining to defecate.
This procedure is used to determine whether complete emptying of the rectum has been achieved, to measure the anorectal angle and perineal descent, and to detect structural abnormalities that may impede defecation, such as a rectocele, internal mucosal prolapse, or intussusception
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MRI shows minimal firing of his amygdala
Soluble fiber is "soluble" in water.Ā When mixed with water it forms a gel-like substance and swells.Ā Soluble fiber has many benefits, including moderating blood glucose levels and lowering cholesterol.
Insoluble fiber does not absorb or dissolve in water.Ā It passes through our digestive system in close to its original form.Ā Adds bulk to the stool which increases colonic residue and stimulates peristalsis.
Cathartic colon - Loss of haustration and dilatation of the colon
Melanosis coli, a brownāblack pigmentation of the colonic mucosa, may develop in patients who take stimulant laxatives containing anthraquinones.
Benign condition ā resolves in about 12 months
The pigmentation is due to the accumulation of apoptotic epithelial cells in the colon that have been phagocytosed by macrophages
Melanosis coli, a brownāblack pigmentation of the colonic mucosa, may develop in patients who take stimulant laxatives containing anthraquinones.
The pigmentation is due to the accumulation of apoptotic epithelial cells in the colon that have been phagocytosed by macrophages
https://shareitsfunny.com/stool-softener/
Linzess ā fatalities in juvenile mice; absolute contraindication < 6 yo. 6-18 somewhat relative, but just avoid it.
Inexpensive osmotic agent ā MoM or Miralax
Stimulant laxatives ā suppository may be best (eg, bisacodyl or glycerol suppositories)
$1 or less per day with the above. Compared to $7-10 per day with Linzess or Amitiza
https://www.gastrojournal.org/article/S0016-5085(12)01545-4/fulltext#sec4.1
3, 6, 9 rule
Large bowel Obstruction vs psuedoobstruction?