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Curriculum Vitae Nama Tempat & Tanggal lahir Alamat : : : Pekerjaan : Riwayat pendidikan : Riwayat pekerjaan : Organisasi : Publikasi : Dr. dr. H. CHUDAHMAN MANAN SpPD-KGEH , FINASIM Jakarta, 1 Juni 1951 Jl. Taman Golf 6, BG 1, No. 7, Cipondoh Tangerang. (15515) Staf Senior Divisi Gastroenterologi, Dept. Ilmu .Penyakit .Dalam FKUI/RSUPNCM, Fakultas Kedokteran UI, tahun 1976 Spesialis Penyakit Dalam FKUI tahun 1986 JICA Program in Gastroenterology, Tokyo,1989 Konsultan Gastroentero-Hepatologi, th. 1996 S3 , Sains Veteriner, IPB 2012 Kepala Puskesmas Kota Agung, Lahat, Sum-Sel 1976-1980 Kepala RSUD Kabupaten Lahat, Sum-Sel 1980-1981. Pendidikan Spesialis Penyakit Dalam FKUI/RSCM, 1981-1986 Spesialis P.Dalam RS Sekupang Batam 1986 Koordinator Pelayanan Masyarakat, Bag.I.P.Dalam FKUI/RSCM 1998-2000 Ketua Divisi Gastroenterologi, Dept.I.P.Dalam FKUI/RSUPNCM 2001-2008 Anggota Ikatan Dokter Indonesia (IDI) Anggota Perhimpunan Ahli Penyakit Dalam Indonesia Advisory PB PGI/PEGI Anggota Perhimpunan Peneliti Hati Indonesia (PPHI) Anggota Perkumpulan Onkologi Indonesia Councillor Asian Pasific Association of Gastroenterology Councillor Asian Pacific Association of Digestive Endoscopy Member OMED (Word organization of Digestive Endoscopy) Dalam dan Luar Negeri Current management of chronic constipation Chudahman Manan Indonesian Society of Gastroenterology Epidemiology oConstipation problem most finding in western country. oIn USA constipation prevalence 2-27% with physician consultation about 2.5 million and hospitalized patients about 100.000 pts. oData from RSCM-Jakarta during 1998-2005, 2.397 colonoscopy exam , 216 (9%) indication for constipation oGender comparative women and men (4 : 1) Sumber: buku konsensus nasional penatalaksanaan konstipasi di Indonesia oleh PGI How Do We Define Constipation? o The American College of Gastroenterology (ACG) definition of constipation: o Unsatisfactory defecation characterized by infrequent stools, difficult stool passage, or both. Difficult stool passage includes straining, a sense of difficulty passing stool, incomplete evacuation, hard/lumpy stools, prolonged time to pass stool, or need for manual maneuvers to pass stool o The ACG Chronic Constipation Task Force also clarified what is meant by chronic: o Chronic constipation is defined as the presence of these symptoms for at least 3 months American College of Gastroenterology Chronic Constipation Task Force. Am J Gastroenterol. 2005;100(S1):1-4. Differentiating Between Occasional and Chronic Constipation Occasional Constipation Chronic Constipation Infrequent Present for at least 3 months and may persist for years Occasional or short-term condition that may temporarily interrupt usual routine Long-term condition that may dominate personal and work life May be brought on by patient’s behavior, change in diet, lack of exercise, illness, or medication Not only related to patient’s behavior, change in diet, lack of exercise, or medication May be relieved by diet, exercise, and over-the-counter (OTC) medication May need medical attention and prescription medication Overlap Between Common Disorders Bloating Belching Constipation Chronic Constipation Dyspepsia IBS Discomfort GERD Heartburn Brandt L, et al. Am J Gastroenterol. 2005;100(S1):5-22. Abdominal Pain Regurgitation Abdominal Pain: Salient Feature Absent in Chronic Constipation (-) Abdominal Pain Chronic constipation (+) Abdominal Pain IBS with constipation Presence or absence of abdominal pain is the major differentiating feature Brandt LJ, et al. Am J Gastroenterol. 2005;100(suppl 1):S5-S21. Prevalence of Functional Gastrointestinal Disorders 45 Population (%) 40 40 35 30 25 25-40 2-28 28 25 3-20 20 6-18 15 10 8 8 5 0 Chronic DyspepsiaFunctional GERD Heartburn Constipation IBS Wong WM, Fass R. Curr Treat Options Gastroenterol. 2004;7(4):273-278. Corazziari E. Best Pract Res Clin Gastroenterol. 2004;18(4):613-631. Higgins PD, Johanson JF. Am J Gastroenterol. 2004;99(4):750-759. Brandt L, et al. Am J Gastroenterol. 2002;97(suppl11):S7-26. Hyper- Migraine Asthma Diabetes tension Wolf-Maier K, et al. JAMA. 2003;289:2363-2369. Lawrence EC. South Med J. 2004 Nov;97(11):1069-1077. CDC. MMWR Morb Mortal Wkly Rep. 2004;53:145-148. CDC. MMWR Morb Mortal Wkly Rep. 2003;52:833-837. Constipation Increases With Age and Is More Common in Women 10 Harari, et al Population: NHIS 1989 Criteria: self-report 8 6 4 2 25 Prevalence of Constipation (%) Prevalence of Constipation (%) 12 Study 1 N = 42,375 0 Men 20 15 10 5 0 Study 2 N = 5,430 Drossman Age Group (years) NHIS = National Health Interview Survey Higgins PDR, et al. Am J Gastroenterol. 2004;99:750-759. Women Study 3 N = 1,149 Pare Sex Study 4 N = 10,018 Stewart Normal Physiology of Defecation o Increased abdominal pressure or propulsive colorectal contractions o Relaxation of internal anal sphincter (autonomic) o Relaxation of external anal sphincter (voluntary) o Straightening of pelvic musculature (levator ani, puborectalis) At rest Lembo A, Camilleri M. N Engl J Med. 2003;349:1360-1368. Muller-Lissner S. Best Pract Res Clin Gastroenterol. 2002;16:115-133. With straining Chronic Constipation Interferes with Daily Lives of the Aging Population Constipation No GI symptoms Mean MOS Score 100 8 0 6 0 4 0 2 0 0 Physical Role Functioning Functioning Social Functioning Mental Health Health Perception Bodily Pain MOS = medical outcomes survey • Impact of chronic constipation on quality of life in Olmsted County, MN, residents aged ≥ 65 years • Lower score indicates worse quality of life Adapted from Talley NJ. Rev Gastroenterol Disord. 2004;4(suppl 2):S3-S10. Primary Causes of Chronic constipation : o Normal-transit constipation o Slow-transit constipation o Defecatory dysfunction o IBS with constipation Bosshard W, et al. Drugs Aging. 2004;21:911-930. Hadley S.K, et al. Journal of Am Fam Physician. 2005;72:2501-2506. Stool Form Correlates With Intestinal Transit Time The Bristol Stool Form Scale Slow Transit Type 1 Separate hard lumps Type 2 Sausage-like but lumpy Type 4 Sausage-like but with cracks in the surface Smooth and soft Type 5 Soft blobs with clear-cut edges Type 3 Type 6 Fast Transit Type 7 O’Donnell LJD, et al. BMJ. 1990;300:439-440. Fluffy pieces with ragged edges, a mushy stool Watery, no solid pieces Primary Constipation • Slow-transit Constipation – – – – – – • Characterized by prolonged intestinal transit time Altered regulation of enteric nervous system Decreased nitric oxide production Impaired gastrocolic reflex Alteration of neuropeptides (VIP, substance P) Decreased number of interstitial cells of Cajal in the colon • Irritable Bowel Syndrome (IBS) with Constipation – Alterations in brain-gut axis – – – – Stress-related condition Visceral hypersensitivity Abnormal brain activation Altered gastrointestinal motility – Role for neurotransmitters, hormones – Presence of non-GI sympt Headache, back pain, fatigue, myalgia, dyspareunia, – urinary symptoms, dizziness Primary Constipation(1): • Normal-transit Constipation – Intestinal transit and stool frequency are within the normal range – Most frequent type of constipation Bosshard W, et al. Drugs Aging. 2004;21:911-930. Gallagher P, et al. Drugs Aging. 2008;25(10):807-821. Primary Constipation(2): • Slow-transit Constipation – Characterized by prolonged intestinal transit time – Altered regulation of enteric nervous system – Decreased nitric oxide production – Impaired gastrocolic reflex – Alteration of neuropeptides (VIP, substance P) – Decreased number of interstitial cells of Cajal in the colon Lembo A, Camilleri M. N Eng J Med. 2003;349:1360-1368. Primary Constipation(3): • Defecatory Dysfunction – More common in older women – childbirth trauma – Pelvic floor dyssynergia – Contributing factors include anal fissures, hemorrhoids, rectocele, rectal prolapse, posterior rectal herniation – Excessive perineal descent – Pathogenesis may be multifactorial – structural problem – Abnormal anorectal manometry and/or defecography Bosshard W, et al. Drugs Aging. 2004;21:911-930. Hadley S.K, et al. Journal of Am Fam Physician. 2005;72:2501-2506. Primary Constipation(4): • Irritable Bowel Syndrome (IBS) with Constipation – Alterations in brain-gut axis – Stress-related condition – Visceral hypersensitivity – Abnormal brain activation – Altered gastrointestinal motility – Role for neurotransmitters, hormones – Presence of non-GI symptoms Headache, back pain, fatigue, myalgia, dyspareunia, urinary symptoms, dizziness Videlock E, Chang L. Gastroenterol Clin N Am. 2007;36:665-685. Hadley SK, et al. Journal of Am Fam Physician. 2005;72:2501-2506. Rome III Criteria for IBS-C Recurrent abdominal pain or discomfort (an uncomfortable sensation not described as pain) at least 3 days per month in the last 3 months associated with 2 or more of the following: 1. Improvement with defecation 2. Onset associated with a change in frequency of stool 3. Onset associated with a change in form of stool Criteria must be fulfilled for the last 3 months, with symptom onset at least 6 months prior to diagnosis In pathophysiology research and clinical trials, a pain/discomfort frequency of at least 2 days a week during screening for patient eligibility Longstreth G, et al. Gastroenterology. 2006;130:1480-1491. Rome III Diagnostic Criteria* for Functional Constipation Chronic constipation must include 2 or more of the following: During at least 25% of defecations Straining Lumpy or hard stools Sensation of incomplete evacuation Sensation of anorectal obstruction/ blockage Manual maneuvers to facilitate defecations <3 defecations per week Loose stools are rarely present without the use of laxatives Insufficient criteria for irritable bowel syndrome *Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis Longstreth GF, et al. Gastroenterology. 2006;130:1480-1491. Patient Care : o Through patient history o Physical/abdominal/digital rectal exams o Evaluate symptoms in terms of diagnostic criteria Chronic constipation/IBS-C o Assessment for red flags/alarm features o Need for additional testing o Treatment/Management plan Ask the Right Questions o Define the meaning of “constipation” o How long have you experienced these symptoms? o Frequency of bowel movements? o Abdominal pain? o Other symptoms? o What is most distressing symptom? o Manual maneuvers to assist with defecation? o Any limitation of daily activities? o Are you taking any medications? o What treatment have you tried? o What investigations have been done? Locke GR III, et al. Gastroenterology. 2000;119:1761-1778. 90 Percent of Patients 80 Common Patient Descriptions of Constipation 81 72 70 60 Physicians think: < 3 BM per week 54 50 39 40 37 36 28 30 20 10 0 Straining Hard or Incomplete Stool Abdominal < 3 BM lumpy emptying per cannot fullness or stools bloating week be passed N = 1149 Pare P, et al. Am J Gastroenterol. 2001;96:3130-3137. Need to press on anus Supportive exam : Colonoscopy Sumber: konsensus nasional penatalaksanaan konstipasi di Indonesia oleh PGI Any Alarm Symptoms? Are Diagnostic Tests Needed? Hematochezia Family history of colon cancer Family history of inflammatory bowel disease Anemia Positive fecal occult blood test “Unexplained” weight loss ≥ 10 pounds Severe, persistent constipation that is unresponsive to treatment o New-onset constipation in an elderly patient o o o o o o o Locke GR III, et al. Gastroenterology. 2000;119:1761-1778. Brandt LJ, et al. Am J Gastroenterol. 2005;100(suppl 1):S5-S21. Mediators of Gl Function Motility Visceral Sensitivity Serotonin Acetylcholine Nitric oxide Substance P Vasoactive intestinal peptide Cholecystokinin Corticotropin releasing factor Serotonin Tachykinins Calcitonin gene-related peptide Neurokinin A Enkephalins Corticotropin releasing factor Secretion Serotonin Acetylcholine Kim DY, Camilleri M. Am J Gastroenterol. 2000;95(10):2698-2709. Combined Risk Factors for Constipation in the Elderly Population Reduced fiber intake Reduced liquid intake Reduced mobility associated with functional decline Decreased functional independence Pelvic floor dysfunction Chronic conditions – Parkinson’s disease – Dementia – Diabetes mellitus – Depression o Polypharmacy (both over the counter and prescription medications, such as NSAIDs, antacids, antihistamines, iron supplements, anticholinergics, opiates, Ca channel blockers, diuretics, antipsychotics, anxiolytics, antidepressants) o o o o o o Common Changes with Aging that Increase the Risk for Constipation o o o o o o o Decreased total body water Decreased colonic motility* Deterioration of nerve function Increased pelvic floor descent Decreased rectal compliance Decreased rectal sensation Age-related changes to the internal and external anal sphincter *Demonstrated in some, but not all studies Gallagher P, et al. Drugs Aging. 2008;25(10):807-821. Schiller L. Gastroenterol Clin N Am. 2001;30:497-515. Consider Secondary Causes Psychological Depression Eating disorders Surgical Abdominal/pelvic surgery Colonic/anorectal surgery Lifestyle Inadequate fiber/fluid Inactivity Metabolic/ Endocrine Hypercalcemia Hyperparathyroidism Diabetes mellitus Hypothyroidism Hypokalemia Uremia Addison’s Porphyria Drugs Opiates Antidepressants Anticholinergics Antipsychotics Antacids (Al, Ca) Ca channel blockers Iron supplements Constipation Gastrointestinal Neurological Parkinson’s Multiple sclerosis Autonomic neuropathy Aganglionosis (Hirschsprung’s, Chagas) Spinal lesions Cerebrovascular disease Candelli M, et al. Hepatogastroenterology. 2001;48:1050-1057. Locke GR, et al. Gastroenterology. 2000;119:1761-1766. Systemic Amyloidosis Scleroderma Polymyositis Pregnancy Colorectal: neoplasm, ischemia, volvulus, megacolon, diverticular disease Anorectal: prolapse, rectocele, stenosis, megarectum Chronic Constipation Secondary to Diabetes Special Considerations o Constipation occurs in 20% of patients with diabetes o Related to duration of diabetes > 10 years o Diabetic autonomic neuropathy o Gastrocolic reflex may be absent, delayed, blunted o Constipation may be severe and can lead to megacolon Treatment Strategy* 1. Optimize diabetes care 2. Stepwise pharmacologic therapy – Exclude slow transit – Bulking agents, osmotic laxatives, Cl channel activators, stimulant laxatives *Treatment strategy based on clinical experience Verne GN, et al. Gastroenterol Clin North Am. 1998;27:861-874. Myths and Misconceptions About Chronic Constipation Misconception Reality Diseases arise from autointoxication by retained stools • No evidence to support this theory Fluctuations in hormones contribute to constipation • Fluctuations in sex hormones during the menstrual cycle have minimal impact on constipation, but are associated with changes in other GI symptoms • Changes in hormones during pregnancy may play a role in slowing gut transit A diet poor in fiber causes constipation • A low fiber diet may be a contributory factor in a subgroup of patients with constipation • Some patients may be helped by an increase in dietary fiber, others with more severe constipation may get worse symptoms with increased dietary fiber intake Increasing fluid intake is a successful treatment for constipation • No evidence that constipation can be treated successfully by increasing fluid intake unless there is evidence of dehydration Muller-Lissner S, et al. Am J Gastroenterol. 2005;100:232-242. Heitkemper M, et al. Am J Gastroenterol. 2003;98(2):420-430. More Misconceptions About Chronic Constipation Misconception Reality Stimulant laxatives damage the enteric nervous system and increase the risk of cancer • Unlikely that stimulant laxatives at recommended doses are harmful to the colon • No data support the idea that stimulant laxatives are an independent risk factor for colorectal cancer Laxatives cause electrolyte disturbances • Laxatives can cause electrolyte disturbances, but appropriate drug and dose selection can minimize such effects Laxatives induce tolerance • Tolerance is uncommon in most laxative users, however tolerance to stimulant laxatives can occur in patients with severe constipation and slow colonic transit Laxatives are addictive • No potential for addiction to laxatives, but laxatives may be misused Muller-Lissner S, et al. Am J Gastroenterol. 2005;100:232-242. Lifestyle Modifications Modification Targeted Mechanism Efficacy Increase fluid intake Increase stool volume by augmenting luminal fluid Limited; majority of fluid is absorbed before reaching the colon and is expelled via urine Increase exercise Improve motility by decreasing transit time through the GI tract Moderate; some evidence suggests this is beneficial; however, not sufficient to treat Increase dietary fiber Increase water and bulk stool volume Limited benefit compared with placebo Chung BD, et al. J Clin Gastroenterol. 1999;28:29-32. Dukas L, et al. Am J Gastroenterol. 2003;98:1790-1796. ACG Chronic Constipation Task Force. Am J Gastroenterol. 2005;100(suppl 1):S1-S4. Are Patients Satisfied With Laxatives and Fiber? Dissatisfied Patients (%) 100 OTC laxatives (n = 146) Prescription laxatives (n = 42) 80 66 71 75 Fiber (n = 268) 80 79 67 60 60 50 50 52 50 44 40 20 0 Ineffective Relief Ineffective Relief of of Constipation Multiple Symptoms Lack of Predictability Johanson JF and Kralstein J. Aliment Pharmacol Ther. 2007;25:599-608. Ineffective Relief of Bloating Treating Constipation With Laxatives Laxative Description Bulking Agents Absorbs liquids in the intestines and swells to form a soft, bulky stool; the increase in fecal bulk is associated with accelerated luminal propulsion Osmotic Laxatives Draws water into the bowel from surrounding body tissues providing a soft stool mass and improved propulsion [saline, poorly absorbed mono- and disaccharides, polyethylene glycol] Stimulant Laxatives Cause rhythmic muscle contractions in the intestines, increase intestinal motility and secretions Lubricants Coats the bowel and the stool mass with a waterproof film; stool remains soft and its passage is made easier Stool Softeners Helps liquids mix into the stool and prevent dry, hard stool masses; has been said not to cause a bowel movement but instead allows the patient to have a bowel movement without straining Combinations Combinations containing more than 1 type of laxative; for example, a product may contain both a stool softener and a stimulant laxative Gallagher P, et al. Drugs Aging. 2008;25:807-821. Laxatives Laxative Type Bulk-forming Lubricating Stool Softeners Saline Stimulant Osmotic Generic Name Brand Name(s) Methylcellulose Citrucel® Polycarbophil FiberCon®, Fiber-Lax® Psyllium Metamucil®, Konsyl® Glycerin Glycerin suppository (generic) Mineral oil Mineral oil (generic) Magnesium hydroxide (milk of magnesia) and mineral oil Phillips’® M-O Docusate sodium Colace®, Dulcolax® Stool Softener, Phillips’ Liqui-Gels® Magnesium hydroxide (milk of magnesia) Ex-Lax® Milk of Magnesia Laxative/Antacid Phillips’® Chewable Tablets Phillips’® Milk of Magnesia Bisacodyl Ex-Lax Ultra, Dulcolax Bowel Prep Kit Sodium bicarbonate and potassium bitartrate Ceo-Two Evacuant® Sennosides Ex-Lax® Laxative Pills Castor oil Purge® Senna Senokot® Polyethylene glycol 3350 GlycoLax®, MiraLAX Lactulose Kristalose® Aim of bisacodyl study: oTo observe Complete Spontaneous Bowel Movements (CSBM) every week during 4 weeks treatment oTwo condition related to bowel movement : Spontaneous Bowel Movement (SBM): spontaneous defecation Complete Spontaneous Bowel Movement (CSBM): spontanneous defecation with good sensation Material & Method : o Adult patients total 368 pts o Diagnosis chronic constipation o Bisacodyl tab (Dulcolax)R vs. placebo; during 4 weeks o Center of study Germany & UK Study result: Complete Spontaneous bowel movement at first day & 4 weeks after treatment : Placebo Bisacodyl Total patients 117 239 First step evaluation 1.1 1.1 4 weeks evaluation 2.0 5.2 Different result between bisacodyl & placebo 3.3 95% Confidence interval (2.6 , 4.0) p-value <0.0001 Significant difference the end result from 2 groups , bisacodyl more superior than placebo Result : Complete spontaneous bowel movement after 4 weeks ** ** ** ** Significant diff in CSBM between Bisacodyl mand placebo Result : Avarage Spontaneous Bowel Movement after 4 weeks ** ** ** ** Significant diff between Bisacodyl & plasebo to increase SBM Patients self assesment for quality of life (QOL) Percentageof patients 60 50 40 PBO BIS 30 20 10 0 Good Satisfactory Not satisfactory Bad Bisacodyl increase QOL from patients with constipation recovery bowel habit every day . 80% patients have satisfied with Bisacodyl. Patients symptoms improvement after bisacodyl treatment o Regular bowel habit everyday o Decreased constipation symptoms o Decreased bloating symptoms o Decreased abdominal discomfort Bisacodyl relief clinical symptoms due to constipation Suggested Management Algorithm for Chronic Constipation Bleeding, anemia, weight loss, sudden change in stool caliber, abdominal pain Alarm Symptoms No Alarm Symptoms Lifestyle, OTC, stimulant laxative Directed testing Refer to a specialist as needed + Response Continue regimen No response OTC = over-the-counter therapies (probiotics, herbal medications, stool softeners [docusate sodium], psyllium, methylcellulose, calcium polycarbophil, bisacodyl, senna) Summary o Chronic constipation is a common condition mostly in the elderly o Quality of life pts with constipation especialy in elderly patients is negatively affected by the symptoms of chronic constipation o Identify risk factors and secondary causes for constipation o Be vigilant for red flags or alarm symptoms; directed tested may be necessary Summary cont’d o Main objective of treatment for chronic constipation is to improve patients’ symptoms, restore normal bowel function (≥ 3 bowel movements per week), improve quality of life o Bisacodyl have good therapeutic effect and minimal side effect with good safety profile Thank you very much for your kind attention