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Chronic Constipation Barbara P. Yawn, MD MSc FAAFP Olmsted Medical Center Rochester, MN [email protected] Thank you to Louis Kuritzky, M.D. for some of the slides. 1 AFP/FPM Live learning objectives • Discuss the etiologies of chronic constipation • Identify treatment options for chronic constipation • Explain the importance and details of behavioral therapy for chronic constipation • Describe treatment options for constipationpredominant irritable bowel syndrome 2 Our discussion today • What is constipation? • How common is it? • Different types – Primary – Secondary • Treatment – OTC – Prescriptions – Unusual – What to avoid 3 “No true definition exists for Constipation.” Etzkorn KP, Rodriguez L. “Constipation” in Conn’s Current Therapy 2002, Rakel, Bope, eds. WB Saunders (Philadelphia) 4 What is constipation? • Unsatisfactory defecation – Infrequent stool – Difficult stool passage – Both – ? <3 stools/week Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7. 5 Chronic Constipation: Rome criteria • • • • • • For past 3 months, with onset > 6 months prior, 2 or more of the following: straining > 25% of time lumpy or hard > 25% of time sensation of incomplete evacuation > 25% of the time sensation of obstruction/blockage > 25% of the time manual maneuvers > 25% of time < 3 defecations/week Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7. 6 Practical Clinical Definition Any noteworthy departure from established • persistent stool frequency • stool hardness • straining at stool. 7 How common is it? • • • • 2.5 million annual US physician visits > $500 million annual US laxative sales Overall annual cost of $29 billion 30% seen by family physicians Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7. 8 Constipation: Geriatrics • Survey: persons > 65 yrs, Olmsted County, Minnesota (n=328) • Constipation = 23% [def: straining, hard stools, < 3 stools/week ] • 23.7% required digital self-facilitation Ehrenpreis ED “Definitions and epidemiology of constipation” Constipation Etiology Evaluation & Management. Wexner SD, Bartolo DCC, eds (Butterworth-Heinemann Ltd , Oxford) 1995:3-8 9 Secondary constipation Causes – Endocrine and metabolic disorders (Diabetes, hypothyroidism, hypercalcemia) – Neurological disorders (Neuropathies, multiple sclerosis) – Collagen-vascular diseases (Progressive systemic sclerosis) – Medications 10 Secondary constipation Causes (continued) • Medications – Metals: aluminum, barium or iron – Analgesics-NSAIDs, opiods – Anti-cholinergic: anti-Parkinsons, anti-depressants, atropine – Anticonvulsants – Antihistamines – Anti-hypertensives – Chemotherapy: vinca alkaloids 11 Secondary constipation: Causes Hirschsprung disease Chagas disease Intestinal pseudo-obstruction Autonomic neuropathy Neurofibromatosis MS Cord Lesions Parkinsons Nervi Erigentes Trauma Stroke DM Hypothyroidism Ca++ Pregnancy Hypopituitarism Systemic Sclerosis Amyloidosis Dermatomyositis Myotonic dystrophy Etzkorn KP, Rodriguez L. “Constipation” in Conn’s Current Therapy 2002. Rakel, Bope, eds. WB Saunders (Philadelphia). 12 Extra-colonic Causes You Will See • Diabetes – ± 20%; probably autonomic neuropathy • Hypothyroidism: – May be 1st indicator; Rx restores normal function • Medications: – CCB: verapamil = 7.5% – NSAIDS: ibuprofen, naproxen = 3%, sulindac = 9% – Opioids • Chronic stimulant (e.g. anthraquinone, bisacodyl) use • Pregnancy – Often starts long before uterus enlarges Castro DD, Cherry DA”Extracolonic causes of constipation” Constipation Etiology Evaluation & Management. Wexner SD, Bartolo DCC, eds (Butterworth-Heinemann Ltd , Oxford) 1995:23-30 13 Primary constipation • Normal transit constipation – 59% of all, often perception not reality • Dyssynergic defecation – 25%, failure of pelvic floor to relax • Slow-transit constipation – 13% of all, delayed emptying of proximal colon Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7. 14 Mrs. J is 64 year old woman with multiple problems for which she takes 6 medications daily. She comes in complaining of constipation. Which of the following do you want to know by week’s end? – A. History of stooling – B. Types of medications – C. Whether she has seen blood in stools – D. The results of her barium enema. – E. All of the above. 15 Delayed Transit = Colonic Inertia Slowed Colonic Emptying Fluid Absorption Hard, Dry Stool 16 Delayed Transit = Colonic Inertia Slowed Colonic Emptying Rectal Stool Volume Delivery Insufficient Stool to Trigger Rectal Evacuation Mechanism Stool Interval 17 Active absorption 1000 mL fluid presented to colon daily NaCl Osmotic Effect ClFollows Electrical Gradient Na+ Electrical gradient 900 mL fluid absorption Guyton AC, Hall JE. Digestion and absorption in the GI tract. In: Textbook of Medical Physiology. 10th ed. Philadelphia, PA: WB Saunders Co 2000;754-763 18 Dyssynergic Defecation (Anismus) • Failure to coordinate pelvic floor anal sphincter • Aberrant manometry patterns on insertion of probe: – rectal pressure + paradoxic anal sphincter pressure – no rectal pressure + paradoxic anal contraction – Rectal pressure + incomplete/no anal sphincter relaxation Jancin B. “Biofeedback Often Effective in Chronic Constipation” Report on a presentation at 19 the ACG by SSC Rao, Fam Pract News 2001; page 17 Medical history • • • • • • Patient’s definition Describe onset Severity Duration Relationship to “normal” Usual behaviors – – – – Fluid and diet intake Activity Cognitive abilities Medications—OCT and prescribed Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7.. 20 Bristol scale • • • • • • • 1= hard lumps like nuts 2=sausage but not lumpy 3=sausage like with “cracks” 4=smooth, snake-like 5=soft blobs 6=fluffy pieces 7=watery, no form Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7.. 21 Physical examination • Digital rectal exam – Anal strictures – Masses – Sphincter tone – Puborectalis tenderness or spasm • Abdominal exam • Pelvic exam for women Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7. 22 Digital rectal examination should evaluate • Resting tone of the sphincter segment, and its augmentation by a squeezing effort. • The voluntary external anal sphincter will be tightened by squeezing; the internal sphincter will not. – Puborectalis muscle (above internal spincter) • Palpate during squeeze and compress between the examining finger and the thumb. Acute localized pain along the border of the muscle is a feature of the puborectalis spasm syndrome. – Ability to integrate the expulsionary forces by requesting that she/he "expel my finger". • http://www.guidelines.gov/summary/summary.aspx?doc_id=3061 &nbr=002287&string=Constipation 23 At the conclusion of initial evaluation, you can tentatively diagnose … • Irritable bowel syndrome when pain and the other features of irritable bowel syndrome are present; • Slow-transit constipation; • Rectal outlet obstruction; • A combination of slow-transit constipation and rectal outlet obstruction; • Organic constipation (mechanical obstruction or drug side effect) • Constipation due to systemic disease. (Level B) – http://www.guidelines.gov/summary/summary.aspx?doc_id=3061&nbr=00228 7&string=Constipation 24 Laboratory, imaging and other tests Not unless alarming signs – No evaluation – Try 2-4 weeks of empiric therapy Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7. 25 Alarming signs • Fever, nausea, vomiting, wt loss > 10 pounds • Blood in stool, anemia • Family history – Inflammatory bowel disease – Colon cancer • Onset after age 50 • Acute changes in “elderly” (age 60 and over) Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7. 26 ASGE guideline on using endoscopy in managing constipation Colonoscopy is indicated in selected patients to exclude obstruction from cancer, stricture, and extrinsic compression. Patients with constipation should undergo colonoscopy if they have rectal bleeding, heme-positive stool, iron deficiency anemia, weight loss, obstructive symptoms, recent onset of constipation, rectal prolapse, or change in stool caliber. Colonoscopy should also be done before surgery for constipation. (Level C) http://www.guidelines.gov/summary/summary.aspx?doc_id=7780&nbr=004485 27 Older patients may need colonoscopy Patients older than 50 who have not had colorectal cancer screening should undergo colonoscopy. Chronic constipation associated with risk of colon cancer in two US population-based, retrospective studies (odds ratio 2.36: 95% CI 1.4, 3.93; relative risk 4.4 for severe constipation: 95% CI 2.1, 8.9) but not in a prospective study of women nurses. A retrospective study from Australia also reported increased cancer risk in patients with constipation, and a retrospective study from Japan found increased risk in frequent laxative users. (Level B) http://www.guidelines.gov/summary/summary.aspx?doc_id=7780&nbr=004485 28 What you might see on Barium Enema • • • • • Obstructing neoplasm Strictures Hirschsprung’s (megacolon) Spasm (suggests laxative abuse) Absent haustral markings (seen in chronic laxative use, atonic megacolon) Cheskin LJ. “Constipation and Diarrhea” in Principles of Ambulatory Medicine 5th Edition, 1999; Barker LR, Burton HR, Zieve PD, Eds Williams & Wilkins (Baltimore) 29 Diagnostic Studies 3 day colonic transit study (radio-opaque marker): presence > 70 hours = colonic inertia Etzkorn KP, Rodriguez L. “Constipation” in Conn’s Current Therapy 2002. Rakel, Bope, eds. WB Saunders (Philadelphia). 30 Mrs. J has long history of 2 stools per week. Since she added the NSAIDs and occasional opoids for her PHN to her medication for hypothyroidism, antihypertensive, statin, daily baby aspirin and calcium tablets, she is having much more straining at stool, sees occasional blood on tissue and has only 1 stool per week with manual help. You decide that … A. This is acute onset constipation. B. This is probably aggravation of existing constipation. C. This sounds like primary constipation. D. This sounds like secondary constipation. 31 Is it Constipation? Secondary? Evaluate, Diagnose, Treat Idiopathic? • • • • Provisional Rxs 2-4 weeks: Stool Hygiene Fiber/Hydration Osmotic Laxatives (PEG) Emollient Inadequate Response? ?Referral Saline Laxative Stimulant Alarm/Alerts? Late onset Sudden onset Blood Obstructive Sx Weight loss Fever Mass Further evaluation BE, endoscopy 32 Clinical:Scientific Discordance We don’t approach this commonplace and burdensome malady with the same scientific intellectual base that is accorded essentially all other equally consequential health issues. We do a rudimentary (read fair to poor) job of constipation management. 33 Patient with multiple morbidities OA DM DYSLIPDEMIA OBESITY HTN CONSTIPATION 34 Our Prioritization DYSLIPDEMIA DM HTN OA CONSTIPATION OBESITY 35 Which is the patient’s top priority? A. B. C. D. E. Diabetes Hyperlipidemia Obesity Constipation Pleasing you 36 Patient Priorities CONSTIPATION OA DM OBESITY HTN DYSLIPDEMIA 37 Constipation: Typical Scenario Pt (at end of visit, after HTN, DM, Obesity, yada yada, have been dealt with): “… and Doc, I have been having a bit of constipation lately.” MD: “More fiber and water.” Pt: OK Doc, we’ll give it a try. 38 Treatment types • Laxative: slower onset of action (1-3 days), lesser degree of bowel evacuation • Cathartic: more rapid onset of action (6-12 hours), greater degree of bowel evacuation Locke GR 3rd, Pemberton JH, Phillips SE. AGA technical review on constipation Gastroenterology. 2000;119:1766-1778 39 Primary constipation: • Normal transit constipation – 59% of all, often perception, not reality • Dyssynergic defecation – 25%, failure of pelvic floor to relax • Slow-transit constipation – 13% of all, delayed emptying of proximal colon Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7. 40 Secondary constipation Causes – Endocrine and metabolic disorders (Diabetes, hypothyroidism, hypercalcemia) – Neurological disorders (Neuropathies, multiple sclerosis) – Collagen-vascular diseases (Progressive systemic sclerosis) – Medications 41 Secondary constipation Causes (continued) • Medications – Metals: aluminum, barium or iron – Analgesics-NSAIDs, opiods – Anti-cholinergic: anti-Parkinsons, anti-depressants, atropine – Anticonvulsants – Antihistamines – Anti-hypertensives – Chemotherapy: vinca alkaloids 42 Rx Approach “After exclusion or appropriate Rx of medical problems, the therapy of constipation is empiric.” Jensen JE “Medical treatment of constipation” in Constipation Etiology Evaluation & Management. Wexner SD, Bartolo DCC, eds (Butterworth-Heinemann Ltd , Oxford) 1995:137-153. 43 Steps in therapy • • • • • • Correct misconceptions Reassure Identify neurotic preoccupation Modify medication regimen Behavioral Rx Laxatives Cheskin LJ. “Constipation and Diarrhea” in Principles of Ambulatory Medicine 5th Edition, 1999; Barker LR, Burton HR, Zieve PD, Eds Williams & Wilkins (Baltimore) 44 Step 1 • • • • • • • Education High Fiber Diet Fiber Supplementation Exercise Evacuation Posture Dedicated Time for Evacuation Avoidance of Stimulant Laxatives Adapted from Jensen JE “Medical treatment of constipation” in Constipation Etiology Evaluation & Management. Wexner SD, Bartolo DCC, eds (Butterworth-Heinemann Ltd , Oxford) 1995:137-153. 45 Step 2 • • • • Stool softeners Hyperosmolar agents Glycerin suppositories Enemas – Tap water – Avoid soap suds • Intermittent sparing use of stimulants Adapted from Jensen JE “Medical treatment of constipation” in Constipation Etiology Evaluation & Management. Wexner SD, Bartolo DCC, eds (Butterworth-Heinemann Ltd , Oxford) 1995:137-153. 46 Behavioral therapy • Regular daily routine for BM • Preferred time = 5-10 minutes PP (uses gastrocolic reflex) • May initially induce timed stool – Enema (lukewarm tap water preferred) – Suppository (bisacodyl preferred) Cheskin LJ. “Constipation and Diarrhea” in Principles of Ambulatory Medicine 5th Edition, 1999; Barker LR, Burton HR, Zieve PD, Eds Williams & Wilkins (Baltimore) 47 Laxatives: Basic Issues • • • • Mechanisms poorly understood Potential for toxicity often underestimated Few head-to-head comparative data Rx choice most often motivated by personal preference rather than objective efficacy data Cheskin LJ. “Constipation and Diarrhea” in Principles of Ambulatory Medicine 5th Edition, 1999; Barker LR, Burton HR, Zieve PD, Eds Williams & Wilkins (Baltimore) 48 Laxatives: Classification (> 700 brands in US) • • • • • Bulk-forming Emollient Saline Stimulant Osmotic Etzkorn KP, Rodriguez L. “Constipation” in Conn’s Current Therapy 2002. Rakel, Bope, eds. WB Saunders (Philadelphia). 49 Bulk-forming Laxatives • Components: natural polysaccharides, synthetic polysaccharides, or cellulose derivatives • Best effects with increased fluid intake (use with caution in CHF) • Multiple formats: powder, biscuit, tablet • GI adverse effects • Tolerance Etzkorn KP, Rodriguez L. “Constipation” in Conn’s Current Therapy 2002. Rakel, Bope, eds. WB Saunders (Philadelphia). 50 Bulk Forming Laxatives: Mechanisms • Water Absorption • Fecal Mass • Metabolism by colonic flora osmotically active metabolites Cheskin LJ. “Constipation and Diarrhea” in Principles of Ambulatory Medicine 5th Edition, 1999; Barker LR, Burton HR, Zieve PD, Eds Williams & Wilkins (Baltimore) 51 Bulk Forming Laxatives: Use • Examples: Konsyl, Effersyllium, Perdiem, Metamucil, FiberCon • Initial use may cause bloating, but over time • May cause obstruction if strictures, atonic colon • Mean impact = 1.4 stools/week Cheskin LJ. “Constipation and Diarrhea” in Principles of Ambulatory Medicine 5th Edition, 1999; Barker LR, Burton HR, Zieve PD, Eds Williams & Wilkins (Baltimore) 52 Emollient Laxatives • Mineral oil – Can cause decreased vitamin A, D, E, K absorption – Administer between meals – Avoid if aspiration risk (can cause lipid pneumonia) • Docusate sodium (Colace) – Decreases stool surface tension, which increases aqueous/fat mixtures, thereby increasing water penetration into stool and producing softer stool – Increases colonic fluid and electrolyte secretion Etzkorn KP, Rodriguez L. “Constipation” in Conn’s Current Therapy 2002. Rakel, Bope, eds. WB Saunders (Philadelphia). 53 Saline Laxatives • Examples: Milk of Magnesia, Fleets Phosphosoda • Mg++ or Na+ salts • Mechanisms: – Poorly absorbed hyperosmolar solution water entry into colonic lumen – Stimulate cholecsytokinin release • Adverse effects: hypermagnesemia, hypocalcemia (PO4 OD), Na+ overload) • Avoid in renal disease or CHF • Not for chronic use Cheskin LJ. “Constipation and Diarrhea” in Principles of Ambulatory Medicine 5th Edition, 1999; Barker LR, Burton HR, Zieve PD, Eds Williams & Wilkins (Baltimore) 54 Osmotic Laxatives: Lactulose • Unmetabolizable semisynthetic disaccharide – osmotic effect of undigested sugar – conversion by colonic bacteria organic acids altered electrolyte transport colonic motility – 24-48 hrs to achieve effect Cheskin LJ. “Constipation and Diarrhea” in Principles of Ambulatory Medicine 5th Edition, 1999; Barker LR, Burton HR, Zieve PD, Eds Williams & Wilkins (Baltimore) 55 Hyperosmolar Agents: PEG, lactulose, sorbitol • Can be used chronically • May use PEG-ELS (e.g, GoLytely, NuLytely) reduced dose daily: 250-500 mL • PEG (Miralax) Etzkorn KP, Rodriguez L. “Constipation” in Conn’s Current Therapy 2002. Rakel, Bope, eds. WB Saunders (Philadelphia). 56 Stimulant Laxatives • Examples: – cascara sagrada (Peri-Colase) – bisacodyl (Dulcolax) – senna (Senokot, ExLax) • Mechanism: – altered mucosal electrolyte transport colonic motor activity – Chronic use can dependency Etzkorn KP, Rodriguez L. “Constipation” in Conn’s Current Therapy 2002. Rakel, Bope, eds. WB Saunders (Philadelphia). 57 Stimulant Laxatives: side effects • Phenolphthalein severe allergic dermatitis, Stevens-Johnson syndrome • Anthraquinones (e.g., Senna, cascara, danthron): chronic use can myenteric plexus damage impaired bowel motility Etzkorn KP, Rodriguez L. “Constipation” in Conn’s Current Therapy 2002. Rakel, Bope, eds. WB Saunders (Philadelphia). 58 Serotonin Modulation: Tegaserod • Study: Randomized, double-blind, controlled trial (n=1,348) adults with chronic idiopathic constipation • Rx: tegaserod 2mg b.i.d. (n=450), tegaserod 6 mg b.i.d. (n=451), or placebo (n=447) • Primary outcome: – ≥ 1 BM/week during weeks 1-4 • Secondary outcome: – ≥ 1 BM/week during weeks 1-12 Johanson JF, Wald A, Tougas G, et al. “Effect of tegaserod in chronic contstipation: a randomized, double-blind, controlled trial.” Clin Gastroenterol Hepatol. 2004;2:706-805. 59 Tegaserod status • Removed from market March 30, 20071 • Can be used in new drug (IND) protocol to treat irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in women younger than 55 who meet specific guidelines2 • Increased risk of cardiovascular events – 13 events in 11,614 on Tegaserod (0.11%) – 1 event in 7,031 on placebo (0.01%) • Talk to your physician • Seek immediate care if symptoms • Transition to other meds 1. Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7. 2. www.FDA.gov/bbs/topics/NEWS/2007/NEW01673.html. 60 Refractory Constipation: Misoprostol • STUDY: 9 pts severe chronic constipation • Rx: misoprostol 1200 mcg/d vs placebo X 3 wks • RESULTS: – misoprostol #BM / week ( 2.2 6.2) – Abdominal pain: Rx = placebo – Contra-indicated in pregnancy Soffer, EE Misoprostol is effective treatment for patients with severe chronic constipation. Dig Dis Sci 1994.39:929-933. 61 Chronic Constipation: Biofeedback • • • • May help with functional obstruction First long-term trial (1 yr) STUDY: chronic constipation (n=80) INTERVENTION: diaphragmatic breathing exercises, then biofeedback Q wk • RESULTS (at 6 wks, 6 months, &1 year): stool frequency 4.2/wk 7.2/wk Lembo A. Chronic constipation. N Eng J Med. 2003:349:1360-1368 62 Colchicine • • • • Diarrhea is known side effect Increases stool frequency Reduces need for laxative in 10% of CC Uncommon treatment due to side effects Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7. 63 Lubiprostone • • • • • • Bicyclic fatty acid Locally activates CL channels in membranes Increases intestinal fluid secretions Improved stool frequency Decreased straining at stool Side effects – – – – 31% nausea 13% diarrhea 13% headache 13% abdominal distention Cash BD et al. J Fam Pract. 2007; June supplement:S1-S7. 64 Summary • • • • Common but commonly mislabeled Must rule out secondary constipation Ask about patient’s priorities Primary constipation treated empirically first – Assessment of life style and self therapy – Fluid, diet and activity – Better toileting habits – Laxatives • Bulk • Stimulants • Unusual types 65