Satish S. Rao

Efficacy and Safety of Traditional Medical Therapies for Chronic Constipation: Systematic Review

OBJECTIVES:Constipation is common, and its treatment is unsatisfactory. Although many agents have been tried, there are limited data to support their use. Our aim was to undertake a systematic review of the efficacy and safety of traditional medical therapies for chronic constipation and to make evidence-based recommendations.METHODS:We searched the English literature for drug trials evaluating treatment of constipation by using MEDLINE and PUBMED databases from 1966 to 2003. Only studies that were randomized, conducted on adult subjects, and published as full manuscripts were included. Studies were assigned a quality score based on published methodology. Standard forms were used to abstract data regarding study design, duration, outcome measures, and adverse events. By using the cumulative evidence of published data for each agent, recommendations were made regarding their use following the United States Preventive Services Task Force guidelines.RESULTS:Good evidence (Grade A) was found to support the use of polyethylene glycol (PEG) and tegaserod. Moderate evidence (Grade B) was found to support the use of psyllium, and lactulose. There was a paucity of quality data regarding many commonly used agents including milk of magnesia, senna, bisacodyl, and stool softeners.CONCLUSIONS:There is good evidence to support the use of PEG, tegaserod, lactulose, and psyllium. Surprisingly, there is a paucity of trials for many commonly used agents. These aspects should be considered when designing trials comparing new agents with traditional therapies because their use may not be well validated.

Functional disorders of the anus and rectum

In this report the functional anorectal disorders, the etiology of which is currently unknown or related to the abnormal functioning of normally innervated and structurally intact muscles, are discussed. These disorders include functional fecal incontinence, functional anorectal pain, including levator ani syndrome and proctalgia fugax, and pelvic floor dyssynergia. The epidemiology of each disorder is defined and discussed, their pathophysiology is summarized and diagnostic approaches and treatment are suggested. Some suggestions for the direction of future research on these disorders are also given.

Obstructive defecation : A failure of rectoanal coordination

Objective:The pathophysiology of obstructive defecation is unclear. We investigated whether impaired rectoanal coordination causes obstructive defecation and if this dysfunction can be corrected by biofeedback therapy.Methods:We prospectively studied 25 healthy subjects and 35 consecutive patients with constipation (>1 year) with anorectal manometry and balloon expulsion test. Symptoms were assessed from diary cards. Patients found to have obstructive defecation were offered biofeedback therapy. After treatment, their defecation dynamics and symptoms were reassessed.Results:Eighteen patients had obstructive defecation and 17 had normal defecation dynamics (nonobstructive). Five normals (20%) exhibited obstructive pattern but only one failed to expel balloon. In the obstructive group, during straining, the intrarectal pressure and defecation index were lower (p < 0.05), and anal residual pressure was higher (p < 0.01) when compared with the nonobstructive group or normals. After biofeedback therapy, the intrarectal pressure and defecation index increased (p < 0.02) and anal residual pressure decreased (p < 0.001); stool frequency, degree of straining, and bowel satisfaction scores improved (p < 0.05); 67% stopped laxatives and 11 patients discontinued stooling with digitation.Conclusion:Patients with obstructive defecation showed impaired rectal contraction, paradoxical anal contraction, or inadequate anal relaxation. These features suggest that rectoanal coordination was impaired. Biofeedback therapy rectified these pathophysiological disturbances and improved constipation.

Diagnosis and Management of Fecal Incontinence

Fecal incontinence is defined as either the involuntary passage or the inability to control the discharge of fecal matter through the anus. Clinically there are three subtypes (a) passive incontinence—the involuntary discharge of stool or gas without awareness; (b) urge incontinence—the discharge of fecal matter in spite of active attempts to retain bowel contents, and (c) fecal seepage—the leakage of stool following otherwise normal evacuation. The severity of incontinence can range from the unintentional elimination of flatus to the seepage of liquid fecal matter or sometimes the complete evacuation of bowel contents. Not surprisingly, these events cause considerable embarrassment, which in turn can lead to a loss of self-esteem, social isolation, and a diminished quality of life (1).

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

OBJECTIVES:Linaclotide is a minimally absorbed guanylate cyclase-C agonist. The objective of this trial was to determine the efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C).METHODS:This phase 3, double-blind, parallel-group, placebo-controlled trial randomized IBS-C patients to placebo or 290 μg oral linaclotide once daily in a 12-week treatment period, followed by a 4-week randomized withdrawal (RW) period. There were four primary end points, the Food and Drug Administrations (FDAs) primary end point for IBS-C (responder: improvement of ≥30% in average daily worst abdominal pain score and increase by ≥1 complete spontaneous bowel movement (CSBM) from baseline (same week) for at least 50% of weeks assessed) and three other primary end points, based on improvements in abdominal pain and CSBMs for 9/12 weeks. Adverse events (AEs) were monitored.RESULTS:The trial evaluated 800 patients (mean age=43.5 years, female=90.5%, white=76.9%). The FDA end point was met by 136/405 linaclotide-treated patients (33.6%), compared with 83/395 placebo-treated patients (21.0%) (P<0.0001) (number needed to treat: 8.0, 95% confidence interval: 5.4, 15.5). A greater percentage of linaclotide patients, compared with placebo patients, reported for at least 6/12 treatment period weeks, a reduction of ≥30% in abdominal pain (50.1 vs. 37.5%, P=0.0003) and an increase of ≥1 CSBM from baseline (48.6 vs. 29.6%, P<0.0001). A greater percentage of linaclotide patients vs. placebo patients were also responders for the other three primary end points (P<0.05). Significantly greater improvements were seen in linaclotide vs. placebo patients for all secondary end points (P<0.001). During the RW period, patients remaining on linaclotide showed sustained improvement; patients re-randomized from linaclotide to placebo showed return of symptoms, but without worsening of symptoms relative to baseline. Diarrhea, the most common AE, resulted in discontinuation of 5.7% of linaclotide and 0.3% of placebo patients.CONCLUSIONS:Linaclotide significantly improved abdominal pain and bowel symptoms associated with IBS-C for at least 12 weeks; there was no worsening of symptoms compared with baseline following cessation of linaclotide during the RW period.

Minimum standards of anorectal manometry

Functional disorders of the anus and rectum affect 10–20% of the population. Tests of anorectal function can provide useful information regarding the pathophysiology of disorders that affect continence and defecation or those that cause anorectal pain. Currently, several tests are available for evaluating anorectal function (Table 1). Often, they complement each other, but among the various tests that are available, the two most commonly performed tests are: (i) anorectal manometry and (ii) the balloon expulsion test. Recent studies suggest that manometric tests can be useful in the management of defecation disorders. The diagnostic potential and yield of these tests have been described previously. However, there is lack of uniformity with regard to the methods of performance and interpretation of the tests. There is also a relative lack of normative data stratified for age and gender. Individual laboratories are therefore encouraged to either consult published data or establish their own normative data. Purpose

Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies

Background  Disorders of gastrointestinal (GI) transit and motility are common, and cause either delayed or accelerated transit through the stomach, small intestine or colon, and affect one or more regions. Assessment of regional and/or whole gut transit times can provide direct measurements and diagnostic information to explain the cause of symptoms, and plan therapy.

Clinical utility of diagnostic tests for constipation in adults: a systematic review

BACKGROUND AND AIMS:Because symptoms alone do not identify pathophysiology or differentiate subgroups of constipation, diagnostic tests are generally recommended. However, their utility is not known. We performed a systematic review of diagnostic tests commonly used in constipation.METHODS:We searched the English literature using MEDLINE and PUBMED databases from 1966 to 2004 for studies in adults published as full manuscripts whose methodological quality was above a minimum score.RESULTS:No studies assessed the routine use of blood tests or abdominal x-ray. One retrospective endoscopic study showed that cancer and polyp detection rate was comparable to historical controls. Two studies of barium enema were unhelpful in diagnosis of constipation. Physiological studies showed differences in study population, methodology, and interpretation, and there was no gold standard. Ten colonic transit studies showed prevalence of 38–80% in support of slow transit constipation. Nine anorectal manometry studies showed prevalence of 20–75% for detecting dyssynergia. Nine studies of balloon expulsion showed impaired expulsion of 23–67%. Among 10 defecography studies, abnormalities were reported in 25–90% and dyssynergia in 13–37%.CONCLUSIONS:Evidence to support the use of blood tests, radiography, or endoscopy in the routine work up of patients with constipation without alarm features is lacking. Colonic transit, anorectal manometry, and balloon expulsion tests reveal physiologic abnormalities in many selected patients with constipation, but no single test adequately defines pathophysiology. Large, well-designed, prospective studies are required to examine the utility of these tests.

Investigation of the utility of colorectal function tests and Rome II criteria in dyssynergic defecation (Anismus)

Although 30–50% of constipated patients exhibit dyssynergia, an optimal method of diagnosis is unclear. Recently, consensus criteria have been proposed but their utility is unknown. To examine the diagnostic yield of colorectal tests, reproducibility of manometry and utility of Rome II criteria. A total of 100 patients with difficult defecation were prospectively evaluated with anorectal manometry, balloon expulsion, colonic transit and defecography. Fifty‐three patients had repeat manometry. During attempted defecation, 30 showed normal and 70 one of three abnormal manometric patterns. Forty‐six patients fulfilled Rome criteria and showed paradoxical anal contraction (type I) or impaired anal relaxation (type III) with adequate propulsion. However, 24 (34%) showed impaired propulsion (type II). Forty‐five (64%) had slow transit, 42 (60%) impaired balloon expulsion and 26 (37%) abnormal defecography. Defecography provided no additional discriminant utility. Evidence of dyssynergia was reproducible in 51 of 53 patients. Symptoms alone could not differentiate dyssynergic subtypes or patients. Dyssynergic patients exhibited three patterns that were reproducible: paradoxical contraction, impaired propulsion and impaired relaxation. Although useful, Rome II criteria may be insufficient to identify or subclassify dyssynergic defecation. Symptoms together with abnormal manometry, abnormal balloon expulsion or colonic marker retention are necessary to optimally identify patients with difficult defecation.

American Neurogastroenterology and Motility Society consensus statement on intraluminal measurement of gastrointestinal and colonic motility in clinical practice

Abstract  Tests of gastric, small intestinal and colonic motor function provide relevant physiological information and are useful for diagnosing and guiding the management of dysmotilities. Intraluminal pressure measurements may include concurrent measurements of transit or intraluminal pH. A consensus statement was developed and based on reports in the literature, experience of the authors, and discussions conducted under the auspices of the American Neurogastroenterology and Motility Society in 2008. The article reviews the indications, methods, performance characteristics, and clinical utility of intraluminal measurements of pressure activity and tone in the stomach, small bowel and colon in humans. Gastric and small bowel motor function can be measured by intraluminal manometry, which may identify patterns suggestive of myopathy, neuropathy, or obstruction. Manometry may be most helpful when it is normal. Combined wireless pressure and pH capsules provide information on the amplitude of contractions as they traverse the stomach and small intestine. In the colon, manometry assesses colonic phasic pressure activity while a barostat assesses tone, compliance, and phasic pressure activity. The utility of colonic pressure measurements by a single sensor in wireless pressure/pH capsules is not established. In children with intractable constipation, colonic phasic pressure measurements can identify patterns suggestive of neuropathy and predict success of antegrade enemas via cecostomy. In adults, these assessments may be used to document severe motor dysfunction (colonic inertia) prior to colectomy. Thus, intraluminal pressure measurements may contribute to the management of patients with disorders of gastrointestinal and colonic motility.