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• W3000300599 abstract "With a worldwide prevalence of 15%, chronic constipation is one of the most frequent gastrointestinal diagnoses made in ambulatory medicine clinics, and is a common source cause for referrals to gastroenterologists and colorectal surgeons in the United States. Symptoms vary among patients; straining, incomplete evacuation, and a sense of anorectal blockage are just as important as decreased stool frequency. Chronic constipation is either a primary disorder (such as normal transit, slow transit, or defecatory disorders) or a secondary one (due to medications or, in rare cases, anatomic alterations). Colonic sensorimotor disturbances and pelvic floor dysfunction (such as defecatory disorders) are the most widely recognized pathogenic mechanisms. Guided by efficacy and cost, management of constipation should begin with dietary fiber supplementation and stimulant and/or osmotic laxatives, as appropriate, followed, if necessary, by intestinal secretagogues and/or prokinetic agents. Peripherally acting μ-opiate antagonists are another option for opioid-induced constipation. Anorectal tests to evaluate for defecatory disorders should be performed in patients who do not respond to over-the-counter agents. Colonic transit, followed if necessary with assessment of colonic motility with manometry and/or a barostat, can identify colonic dysmotility. Defecatory disorders often respond to biofeedback therapy. For specific patients, slow-transit constipation may necessitate a colectomy. No studies have compared inexpensive laxatives with newer drugs with different mechanisms. We review the mechanisms, evaluation, and management of chronic constipation. We discuss the importance of meticulous analyses of patient history and physical examination, advantages and disadvantages of diagnostic testing, guidance for individualized treatment, and management of medically refractory patients. With a worldwide prevalence of 15%, chronic constipation is one of the most frequent gastrointestinal diagnoses made in ambulatory medicine clinics, and is a common source cause for referrals to gastroenterologists and colorectal surgeons in the United States. Symptoms vary among patients; straining, incomplete evacuation, and a sense of anorectal blockage are just as important as decreased stool frequency. Chronic constipation is either a primary disorder (such as normal transit, slow transit, or defecatory disorders) or a secondary one (due to medications or, in rare cases, anatomic alterations). Colonic sensorimotor disturbances and pelvic floor dysfunction (such as defecatory disorders) are the most widely recognized pathogenic mechanisms. Guided by efficacy and cost, management of constipation should begin with dietary fiber supplementation and stimulant and/or osmotic laxatives, as appropriate, followed, if necessary, by intestinal secretagogues and/or prokinetic agents. Peripherally acting μ-opiate antagonists are another option for opioid-induced constipation. Anorectal tests to evaluate for defecatory disorders should be performed in patients who do not respond to over-the-counter agents. Colonic transit, followed if necessary with assessment of colonic motility with manometry and/or a barostat, can identify colonic dysmotility. Defecatory disorders often respond to biofeedback therapy. For specific patients, slow-transit constipation may necessitate a colectomy. No studies have compared inexpensive laxatives with newer drugs with different mechanisms. We review the mechanisms, evaluation, and management of chronic constipation. We discuss the importance of meticulous analyses of patient history and physical examination, advantages and disadvantages of diagnostic testing, guidance for individualized treatment, and management of medically refractory patients. The prevalence of chronic constipation (CC) among adults is approximately 15%, making it the sixth most common gastrointestinal symptom. CC often results in visits to ambulatory clinics and gastroenterology referrals.1Mugie S.M. Benninga M.A. Di Lorenzo C. Epidemiology of constipation in children and adults: a systematic review.Best Pract Res Clin Gastroenterol. 2011; 25: 3-18Crossref PubMed Scopus (398) Google Scholar, 2Lacy B.E. Levenick J.M. Epidemiology of constipation.in: Talley N.J. Locke G.R. Moayyedi P. GI Epidemiology: Diseases and Clinical Methodology. Blackwell, Hoboken, NJ2014: 235-248Crossref Scopus (0) Google Scholar, 3Peery A.F. Crockett S.D. Murphy C.C. et al.Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: update 2018.Gastroenterology. 2019; 156: 254-272.e11Abstract Full Text Full Text PDF PubMed Google Scholar Although the prevalence is greater in non-Caucasians than Caucasians, in women (median female to male ratio of 1.5:1), and in institutionalized rather than community-living elderly persons, symptoms can affect all ages, races, socioeconomic groups, and nationalities. Chronic constipation is either primary or secondary (attributed to another disease), determined from patient history and results from examinations and laboratory tests (Table 1).4Bharucha A.E. Pemberton J.H. Locke 3rd, G.R. American Gastroenterological Association technical review on constipation.Gastroenterology. 2013; 144: 218-238Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar The Rome IV criteria for primary constipation are based on results from anorectal tests and categorize patients as having functional constipation (FC), constipation-predominant irritable bowel syndrome (IBS-C), or defecatory disorders (DDs) (Supplementary Figure 1).5Mearin F. Lacy B.E. Chang L. et al.Bowel disorders.Gastroenterology. 2016; 18: 18Google Scholar FC and IBS-C are primarily defined by symptoms alone (Table 2). DDs are defined by symptoms (such as FC or IBS-C) and results from anorectal tests that indicate impaired rectal evacuation. Prior American Gastroenterological Association reviews and this update classify patients with constipation based on assessments of colonic transit and anorectal function; the classifications are normal transit constipation (NTC), slow transit constipation (STC), and pelvic floor dysfunction or DDs (Supplementary Figure 1).4Bharucha A.E. Pemberton J.H. Locke 3rd, G.R. American Gastroenterological Association technical review on constipation.Gastroenterology. 2013; 144: 218-238Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar,6Locke 3rd, G.R. Pemberton J.H. Phillips S.F. AGA technical review on constipation. American Gastroenterological Association.Gastroenterology. 2000; 119: 1766-1778Abstract Full Text Full Text PDF PubMed Google ScholarTable 1Common Medical Conditions Associated With ConstipationCauseCommentsDrug effectsSee Supplementary Table 1Mechanical obstruction: colon cancer, external compression from malignant lesion, strictures (diverticular or post ischemic), rectocele (if large), megacolon, anal fissureOften associated with alarm clinical features or laboratory tests, apparent on digital rectal examination (fissure) or x-ray image of the abdomen, or preceded by the primary event (diverticulitis)Metabolic conditions: diabetes mellitus, hypothyroidism, hypercalcemia, hypokalemia, hypomagnesemia, uremia, heavy metal poisoning, uremia, heavy metal poisoningAll are associated with/can be diagnosed by abnormal results from laboratory tests, which should be performed only when there is a high index of suspicion (such as in patients on diuretics)Myopathies: amyloidosis, sclerodermaTypically associated with other clinical features of these conditionsNeuropathies: Parkinson’s disease, spinal cord injury or tumor, cerebrovascular disease, and multiple sclerosisConstipation, either due to slow colon transit and/or DD, is common in patients with these disorders, which have many other featuresOther conditions: depression, degenerative joint disease, autonomic neuropathy, cognitive impairment, immobility, cardiac diseaseThe disorder and/or medications may contribute to constipation Open table in a new tab Table 2Definitions of ConstipationRome IV criteriaCriteria used in studies of pharmacologic agentsFCIBS-CFC169Lembo A.J. Kurtz C.B. MacDougall J.E. et al.Efficacy of linaclotide for patients with chronic constipation.Gastroenterology. 2010; 138: 886-895Abstract Full Text Full Text PDF PubMed Scopus (168) Google ScholarIBS-C170Rao S. Lembo A.J. Shiff S.J. et al.A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation.Am J Gastroenterol. 2012; 107 (quiz 1725): 1714-1724Crossref PubMed Scopus (0) Google ScholarSymptoms for ≥6 mo and 2 or more of the following symptoms for >25% of defecations during past 3 mo:○Straining○Lumpy or hard stools○Sensation of incomplete evacuation○Sensation of anorectal obstruction/blockade○Manual maneuvers to facilitate defecations;○<3 defecations/wk○Loose stools are not present, and there are insufficient criteria for IBSRecurrent abdominal pain at least 1 d/wk in the past 3 mo associated with 2 or more of the following:○Related to defecation○Onset associated with change in frequency of stool○Onset associated with change in form (appearance) of stool○>25% of bowel movements were hard and <25% were loose stools<3 SBMs/wk and 1 or more of the following symptoms for at least 12 wk during the preceding 12 mo○Straining in >25% of defecations○Lumpy or hard stools in >25% of defecations○Sensation of incomplete evacuation in >25% of defecations○No loose or watery SBMs (Bristol Stool Form Scale scores of 6 or 7)Abdominal pain associated with 2 or more of the following:○Related to defecation○Onset associated with change in frequency of stool○Onset associated with change in form and (appearance) of stool○<3 SBMs and <3 CSBMs/wk; and at least 1 additional symptom○Straining in ≥25% of defecations○Lumpy or hard stools in ≥25% of defecations○Sensation of incomplete evacuation in ≥25% of defecationsCSBM, complete spontaneous bowel movements; SBM, spontaneous bowel movement. Open table in a new tab CSBM, complete spontaneous bowel movements; SBM, spontaneous bowel movement. Patients with constipation have infrequent stools (fewer than 3 bowel movements per week) and, more importantly, straining at stool, a feeling of incomplete evacuation, a need for digital assistance to evacuate stool, bloating, and hard or lumpy stools.7Pare P. Ferrazzi S. Thompson W.G. et al.An epidemiological survey of constipation in canada: definitions, rates, demographics, and predictors of health care seeking.Am J Gastroenterol. 2001; 96: 3130-3137Crossref PubMed Google Scholar The Rome IV criteria are predominantly symptom-based and as such require that patients with a diagnosis of FC have 2 or more of these symptoms, which affect >25% of bowel movements for at least 6 months and active symptoms for the past 3 months (Table 1). By contrast, IBS-C is defined by abdominal pain that is associated with 2 of 3 features: altered stool form, altered stool frequency, or relief of abdominal pain with defecation. Although patients with CC also have abdominal pain, the pain is not, in contrast to the definition for IBS-C, associated with the symptoms mentioned. In (real-world) clinical practice, it is more useful to conceptualize FC and IBS-C along a spectrum; it is sometimes difficult to distinguish FC from IBS-C and to determine which patients are true medication responders using the definitions used in clinical trials (see Table 2). IBS-C patients are more likely to predominantly have abdominal pain, heightened rectal sensation,8Whitehead W.E. Palsson O.S. Simren M. Biomarkers to distinguish functional constipation from irritable bowel syndrome with constipation.Neurogastroenterol Motil. 2016; 28: 783-792Crossref PubMed Scopus (0) Google Scholar upper gastrointestinal symptoms (eg, heartburn, dyspepsia), anxiety and depression, and urinary symptoms.9Bharucha A.E. Sharma M. Painful and painless constipation: all roads lead to (a change in) Rome.Dig Dis Sci. 2018; 63: 1671-1674Crossref PubMed Scopus (0) Google Scholar,10Bouchoucha M. Devroede G. Mary F. et al.Painful or mild-pain constipation? A clinically useful alternative to classification as irritable bowel syndrome with constipation versus functional constipation.Dig Dis Sci. 2018; 63: 1763-1773Crossref PubMed Scopus (13) Google Scholar However, blurring the distinction between FC and IBS-C, 1 study found that approximately 90% of patients with IBS-C also met criteria for FC and 44% of the FC patients also met criteria for IBS-C.11Wong R.K. Palsson O.S. Turner M.J. et al.Inability of the Rome III criteria to distinguish functional constipation from constipation-subtype irritable bowel syndrome.Am J Gastroenterol. 2010; 105: 2228-2234Crossref PubMed Scopus (140) Google Scholar In approximately one-third of patients, symptoms shift over time between FC and IBS-C.11Wong R.K. Palsson O.S. Turner M.J. et al.Inability of the Rome III criteria to distinguish functional constipation from constipation-subtype irritable bowel syndrome.Am J Gastroenterol. 2010; 105: 2228-2234Crossref PubMed Scopus (140) Google Scholar In individual patients, a diagnosis of either FC or IBS-C is possible only because the Rome criteria specify that patients with symptoms of IBS-C and FC be designated as IBS-C not FC. This limitation can be overcome by classifying constipated patients, based on the presence or absence of moderate to severe abdominal pain, into 1 of 2 categories, such as painful or painless constipation (Supplementary Figure 2).9Bharucha A.E. Sharma M. Painful and painless constipation: all roads lead to (a change in) Rome.Dig Dis Sci. 2018; 63: 1671-1674Crossref PubMed Scopus (0) Google Scholar,10Bouchoucha M. Devroede G. Mary F. et al.Painful or mild-pain constipation? A clinically useful alternative to classification as irritable bowel syndrome with constipation versus functional constipation.Dig Dis Sci. 2018; 63: 1763-1773Crossref PubMed Scopus (13) Google Scholar In contrast to the Rome IV criteria for IBS-C, these definitions do not specify the temporal relationship, or lack thereof, between abdominal pain and bowel habits. Similar to the differences for FC and IBS-C, compared to mild pain constipation, patients with painful constipation have more prominent bowel, upper gastrointestinal (such as dyspepsia), anorectal, urinary and sexual symptoms, anxiety and depression, and slower rectosigmoid transit. The widespread symptoms in painful constipation could partly reflect increased perception of visceral sensations. Symptom-based criteria for discriminating between painful and mild-pain constipation have been proposed but require finalization. The right colon is a reservoir that mixes and stores contents.12Bharucha A.E. Camilleri M. Physiology of the colon and its measurement.in: Yeo C.J. DeMeester S.R. McFadden D.W. Shackelford’s Surgery of the Alimentary Tract. Volume 2, The Colon. 8th ed. Elsevier, Philadelphia2018: 1728-1739Google Scholar, 13Corsetti M. Costa M. Bassotti G. et al.First “translational” consensus on terminology and definition of colonic motility as studied in humans and animals by means of manometric and non-manometric techniques.Nat Clin Pract Gastroenterol Hepatol. 2019; 16: 559-579Crossref Scopus (4) Google Scholar, 14Palit S. Thin N. Knowles C.H. et al.Diagnostic disagreement between tests of evacuatory function: a prospective study of 100 constipated patients.Neurogastroenterol Motil. 2016; 28: 1589-1598Crossref PubMed Scopus (38) Google Scholar The left colon functions primarily as a conduit. The rectum and anal canal enable defecation and maintain fecal continence. Our understanding of motor activity, which is derived mostly from studies with non–high-resolution manometry catheters in which sensors were separated by 7.5 cm or more,13Corsetti M. Costa M. Bassotti G. et al.First “translational” consensus on terminology and definition of colonic motility as studied in humans and animals by means of manometric and non-manometric techniques.Nat Clin Pract Gastroenterol Hepatol. 2019; 16: 559-579Crossref Scopus (4) Google Scholar suggest that most colonic motor activity is irregular and nonpropagated and serves to segment and mix intraluminal contents. By comparison, newer high-resolution catheters have sensors separated by 1–2.5 cm and are more accurate for detecting propagated motor events (Supplementary Figure 3).15Dinning P.G. Wiklendt L. Gibbins I. et al.Low-resolution colonic manometry leads to a gross misinterpretation of the frequency and polarity of propagating sequences: initial results from fiber-optic high-resolution manometry studies.Neurogastroenterol Motil. 2013; 25: e640-e649PubMed Google Scholar Colonic motor patterns are diverse, and include individual or rhythmic events, which may be simultaneous or propagated (antegrade or retrograde), and have low or high amplitude.13Corsetti M. Costa M. Bassotti G. et al.First “translational” consensus on terminology and definition of colonic motility as studied in humans and animals by means of manometric and non-manometric techniques.Nat Clin Pract Gastroenterol Hepatol. 2019; 16: 559-579Crossref Scopus (4) Google Scholar Of these patterns, the gastrocolonic response to a meal and high-amplitude propagated contractions are arguably the most physiologically important. The gastrocolonic response begins shortly, often within a few seconds, after eating and may last for up to 2½ hours.16Narducci F. Bassotti G. Granata M.T. et al.Colonic motility and gastric emptying in patients with irritable bowel syndrome. Effect of pretreatment with octylonium bromide.Dig Dis Sci. 1986; 31: 241-246Crossref PubMed Scopus (0) Google Scholar Although a 1000-kcal meal invariably elicits a response, 600 kcal is probably equivalent.17Scott S.M. Manometric techniques for the evaluation of colonic motor activity: current status.Neurogastroenterol Motil. 2003; 15: 483-513Crossref PubMed Scopus (0) Google Scholar Propagated contractions, categorized as low (5–40 mmHg) or high-amplitude propagated contractions (HAPCs, >75 mmHg), occur an average of 6 times per day, originate predominantly in the cecum or ascending colon, cause mass movement of colon contents, and often precede defecation.18Bharucha A.E. High amplitude propagated contractions.Neurogastroenterol Motil. 2012; 24: 977-982Crossref PubMed Scopus (0) Google Scholar HAPCs occur more frequently after awakening and after meals and can account for the urge to defecate in healthy subjects and in patients with IBS. HAPCs occur spontaneously, occasionally in response to luminal distention, or can be induced by glycerol, bisacodyl, oleic acid, and the cholinesterase inhibitor neostigmine. Colonic sensorimotor disturbances and pelvic floor dysfunction are the most widely recognized causes. Other factors, such as reduced caloric intake, disturbances of the microbiome, anatomical issues, or medications, can also contribute. Isolated slow-transit constipation (eg, no DD) is used as a marker of colonic motor dysfunction(s), perhaps due to reductions in colonic intrinsic nerves and interstitial cells of Cajal.19He C.L. Burgart L. Wang L. et al.Decreased interstitial cell of cajal volume in patients with slow-transit constipation.Gastroenterology. 2000; 118: 14-21Abstract Full Text Full Text PDF PubMed Google Scholar,20Farrugia G. Interstitial cells of Cajal in health and disease.Neurogastroenterol Motil. 2008; 20: 54-63Crossref PubMed Scopus (238) Google Scholar Manometry can reveal colonic motor disturbances, such as reduced propagated and nonpropagated activity and reduced phasic contractile responses to a meal and/or to bisacodyl or neostigmine, in patients with STC.21Camilleri M. Bharucha A.E. di Lorenzo C. et al.American Neurogastroenterology and Motility Society consensus statement on intraluminal measurement of gastrointestinal and colonic motility in clinical practice.Neurogastroenterol Motil. 2008; 20: 1269-1282Crossref PubMed Scopus (0) Google Scholar, 22Dinning P.G. Smith T.K. Scott S.M. Pathophysiology of colonic causes of chronic constipation.Neurogastroenterol Motil. 2009; 21: 20-30Crossref PubMed Scopus (46) Google Scholar, 23Ravi K. Bharucha A.E. Camilleri M. et al.Phenotypic variation of colonic motor functions in chronic constipation.Gastroenterology. 2010; 138: 89-97Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar Manometry catheters only measure phasic pressure activity. A barostat balloon device also records colonic tone; fasting tone and tonic contractile responses to a meal and/or neostigmine are reduced in STC (Figure 1).21Camilleri M. Bharucha A.E. di Lorenzo C. et al.American Neurogastroenterology and Motility Society consensus statement on intraluminal measurement of gastrointestinal and colonic motility in clinical practice.Neurogastroenterol Motil. 2008; 20: 1269-1282Crossref PubMed Scopus (0) Google Scholar, 22Dinning P.G. Smith T.K. Scott S.M. Pathophysiology of colonic causes of chronic constipation.Neurogastroenterol Motil. 2009; 21: 20-30Crossref PubMed Scopus (46) Google Scholar, 23Ravi K. Bharucha A.E. Camilleri M. et al.Phenotypic variation of colonic motor functions in chronic constipation.Gastroenterology. 2010; 138: 89-97Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar Colonic inertia, which represents profound motor dysfunction, can only be identified by manometry or a barostat and is defined by reduced or absent contractile response to a meal and to pharmacologic stimuli (such as bisacodyl or neostigmine).23Ravi K. Bharucha A.E. Camilleri M. et al.Phenotypic variation of colonic motor functions in chronic constipation.Gastroenterology. 2010; 138: 89-97Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar,24Bassotti G. If it is inert, why does it move?.Neurogastroenterol Motil. 2004; 16: 395-396Crossref PubMed Scopus (0) Google Scholar Unfortunately, NTC and STC are imperfect markers of normal and impaired colonic motor function, respectively. For example, fasting and/or postprandial colonic tone and/or compliance were reduced in 40% of patients with NTC, 47% in patients with STC, 53% in patients with DD and normal transit, and 42% in patients with DD and slow transit.23Ravi K. Bharucha A.E. Camilleri M. et al.Phenotypic variation of colonic motor functions in chronic constipation.Gastroenterology. 2010; 138: 89-97Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar Similarly, 43% of patients with STC had normal fasting colonic motility and motor responses to a meal and bisacodyl.25Herve S. Savoye G. Behbahani A. et al.Results of 24-h manometric recording of colonic motor activity with endoluminal instillation of bisacodyl in patients with severe chronic slow transit constipation. [see comment].Neurogastroenterol Motil. 2004; 16: 397-402Crossref PubMed Scopus (0) Google Scholar Patients with NTC might have symptoms of FC or IBS-C; 23% of patients with FC or IBS-C had delayed colonic transit.26Manabe N. 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• W3000300599 created "2020-01-23" @default.
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• W3000300599 date "2020-04-01" @default.
• W3000300599 modified "2023-10-16" @default.
• W3000300599 title "Mechanisms, Evaluation, and Management of Chronic Constipation" @default.
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