My alma mater, the University of Virginia, has a fair amount of useful GI educational material on their website.
Here are a few links:
Irritable Bowel Syndrome (IBS) diet
Short Bowel Syndrome Diet (Long Version)
Nutritional Considerations for Patients with Inflammatory Bowel Disease
A recent study shows that holding off on blood transfusions can improve survival with severe acute upper gastrointestingal bleeidng (NEJM 2013; 368: 11-21). This finding is not unexpected as this has been shown in observational studies. In addition, in critical care patients without acute GI bleeding, a restrictive approach to transfusions has also been beneficial.
This study which enrolled 921 patients (>18 years) assigned 461 to a restrictive transfusion strategy (transfusion if <7 g/dL or at discretion of physician) and 460 to a “liberal” strategy (transfusion if <9 g/dL).
In additon to fewer transfusions, the restrictive group had improved survival:
The reasons for bleeding in this study included peptic ulcers in about 50%, and varices in 24%. The other causes included Mallory-Weiss tears, erosisve gastritis/esophagitis, and neoplasms.
Why does giving less blood result in better outcomes?
Also (unrelated to this posting), a thoughtful comment to a recent post on FDA regulations was posted by Ben Gold (Can the FDA prohibit free speech? | gutsandgrowth).
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A useful review (Clin Gastroenterol Hepatol 2013; 11: 6-12) provides information on these clinical problems.
Belching or eructation can be divided into gastric belches which are normal and supragastric belching. Supragastric belching which is a behavior (not a reflex), is often provoked by stress. Air does not originate from the stomach or air swallowing (aerophagia). The most common mechanism: a contraction of the diaphragm causes negative pressure in the chest and allows air to be suctioned into the esophagus. It is expelled subsequently as a belch. In some instances, it can occur up to 20 times a minute. Supragastric belching does not occur during sleep and usually does not occur during speaking.
A clinical diagnosis usually is sufficient, though esophageal impedance can document these events as well.
Management:
Hiccups (singultus) are abnormal if lasting more than 48 hours.
Hiccups (at least in adults) have more likelihood of underlying pathology than belching. This review suggests workup including blood tests (CBC, CMP, Amylase/lipase, CRP, Cortisol) and consideration of EKG, CT of chest, Upper endoscopy, MRI of brainstem, and esophageal impedance.
Physical maneuvers have usually been tried and include the following: scaring the patient, rapid drinking, eyeball compression, holding breath, biting a lemon, swallowing sugar, and sniffing vinegar. A good differential diagnosis is given as well in this review -though many cases are idiopathic.
In the U.S. the only approved drug treatment is chlorpromazine. Typical starting dose for adults with this condition is 25 mg 3-4/day. Potential side effects include drowsiness and rarely tardive dyskinesia. Potential alternatives include baclofen and gabapentin. Numerous other agents and even surgical options are listed in this review that have been reported in case studies.
Aerophagia indicates excessive swallowing of air (capable of inducing symptoms like bloating or pain). No controlled studies have been completed. Expert opinion suggests using a nasogastric tube and sedatives like lorazepam in severe acute cases. In more typical chronic cases, advice includes restriction of carbonated beverages and possibly speech therapy. Agents like simethicone may be helpful. Laxatives may be helpful in some cases as well.
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This eponym is derived from E.C. Heyde, a general practitioner from Vancouver, Washington who observed in 1958 that patients with calcific aortic stenosis were prone to massive gastrointestinal bleeding. This clinical observation now has a molecular insight (NEJM 2012; 367: 1954-56).
Submucosal angiodysplasia was identified as the source of GI bleeding. This in turn was discovered to be related to an acquired von Willebrand’s syndrome. What’s happening is that elevated shear stress coverts the globular von Willebrand polymer into an elongated asymmetric protein. This conformational change exposes a site to the protease ADAMTS13 which binds and cleaves the protein, leaving a less competent smaller von Willebrand factor.
Another observation is that the von Willebrand factor is essential for the role that platelets have in maintaining vascular integrity. Degradation of von Willebrand factor as in Heyde’s syndrome allows for the development of the angiodysplasia in these patients and it leads to an intrinsic vascular diathesis in young patients with hereditary von Willebrand’s disease.
It is pretty cool to see how the science explains the clinical picture.
A recent randomized, double-blind, placebo-controlled crossover functional dyspepsia (FD) trial showed that 4 weeks of treatment with buspirone (10 mg TID) improved overall symptom severity, including early satiety and bloating (Clin Gastroenterol Hepatol 2012; 10: 1239-45).
This study enrolled 17 patients (13 women) with a mean age of 38.5 years. There were two 2-week treatment periods and a 2-week washout in between. Patients filled out a dyspepsia symptom score before treatment and at the conclusion. In addition, patients underwent gastric emptying by using breath tests and barostat measurement.
Overall symptom score was improved with buspirone compared to placebo: 7.5 ± 1.3 vs. 11.5 ± 1.2. Symptoms of postprandial fullness, early satiety, and abdominal bloating all improved significantly.
Buspirone treatment increased gastric accommodation compared with placebo: 229 ± 28 vs. 141 ± 32 mL respectively. Overall, gastric emptying was not affected by buspirone treatment; however, delayed emptying of liquids was evident (half-life = 64 vs. 119 minutes respectively).
The effect of buspirone on FD appears to be primarily related to improvement in gastric accommodation. Impaired accommodation has been identified in about 40% of FD patients. Buspirone which is a 5-HT1A receptor agonist acts on cholinergic nerve endings and leads to relaxation of the proximal stomach.
Buspirone also is used for the treatment of anxiety. In the present study, baseline anxiety scores were not correlated to symptom improvement but these scores were not followed at the end of treatment.
In this small study, buspirone was well tolerated and had similar adverse events as placebo. In previous studies, it has been associated with light-headedness, dizziness, and nausea.
Given the small scale of the study, it would be premature to consider buspirone a proven treatment for FD; however, this study provides the framework for larger studies to determine more conclusively the role of buspirone for FD.
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Genovese syndrome is more commonly called the “bystander effect” (NEJM 2013; 368: 8-9).
“Genovese syndrome” was coined after the brutal stabbing of Catherine Genovese in Queens, NY on March 13, 1964. What was astonishing was that ~38 people either observed the attacks or heard the victim’s pleas for help and did nothing. This prompted a large amount of psychological research. The central factor identified as the reason for the bystander effect was the diffusion of responsibility.
Awareness of the bystander effect is increasingly important in medicine where large teams often are involved in the care of complex patients. Sometimes it is difficult even to answer “Who is my doctor?”
When many doctors are involved in the care of a patient, it is easy for a passive approach to patient care to develop. How can this be reversed?
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More data on teduglutide indicate its potential for short bowel syndrome (SBS) (Gastroenterol 2012; 143: 1473-81, editorial 1416-20). Treatments for SBS are needed. One year of parenteral nutrition often costs the health care system in excess of $100,000 per year. This cost does not account for laboratory studies, health care visits, complications, and hospitalizations. Treatment of intestinal failure with transplantation “may cost upwards of $1 million.”
In this study of adult patients with an average of 50 years, teduglutide was given in a prospective randomized double-blind study to 42 patients and another 43 patients received placebo. The dose of 0.05 mg/kg/day via subcutaneous injection was chosen based on a previous trial which showed that a higher dose was less effective. Among these patients, the most common reasons for SBS were vascular disease (34%), Crohn’s disease (21%), volvulus (11%), and injury ((9%).
Bottom line:
How does teduglutide work? Teduglutide is a much more stable analog of glucagon-like peptide-2 (GLP-2). The latter is released by the distal small bowel and colon. GLP-2 promotes intestinal epithelial growth and increases transit time.
What are the adverse effects of teduglutide? First, there is a concern that teduglutide could promote colonic adenomas based on studies in mice. GLP-2 receptors are present in the lung, and brain (including hypothalamus); its effects in these areas is poorly understood. In addition, abdominal pain, distention, nausea, peripheral edema, and nasopharyngitis were more common in the treatment group. The long-term consequences of teduglutide therapy are not known.
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No medical therapy has been shown to alter the natural history of irritable bowel syndrome (IBS). A number of therapies have been used to improve the symptoms. More data has been published on whether acupuncture is an effective therapy (Am J Gastroenterol 2012; 107: 835-47)
A number of treatment approaches have shown that several medical treatments are more effective than placebo, including soluble fiber, some antispasmotics, peppermint oil, antidepressants, and agents that act on the 5-HT receptor. In addition, cognitive-behavioral therapy and hypnotherapy seem to be more effective than placebo. Dietary therapies (see blog links below) are helpful in some patients. However, many patients have a poor response to all of these approaches.
To examine whether acupuncture may be effective for IBS, the authors of the current study reviewed 1421 citations and identified 17 eligible randomized controlled trials (RCTs) with >1800 patients. Only trials that used accepted traditional Chinese medicine methods of acupuncture were included.
Key findings:
This study should reduce the stress of practitioners of acupuncture. Whether they apply true acupuncture or sham acupuncture, the results may be equivalent. In these studies, sham acupuncture did have a high “placebo effect.” At the same time, this study indicates that the comparison medical treatments (most in these RCTs are not used in Western medicine) were less effective than acupuncture. So where does that leave us?
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Identifying patients gastroesophageal reflux with a so-called ‘PPI test’ is not effective (Clin Gastroenterol Hepatol 2012; 10: 1360-66).
This study examined data from the previous Diamond study (Gut 2010; 59: 714-21).
In short, among 308 patients who were evaluated by endoscopy and pH probe, 197 had GERD identified by the presence of reflux esophagitis, pH <4 for 5.5% or positive symptom association monitoring. Then all patients were given esomeprazole 40 mg once a day for two weeks.
A positive response to PPI Rx was observed in 69% of those with GERD and in 51% of those without GERD. If response was defined as ‘the absence of the most bothersome symptom in the last 3 days of treatment,’ then GERD patients had a 54% response compared to 35% of Non-GERD patients.
While the PPI test is a failure, in many clinical situations, symptom response to therapy may be more important than the reason for the symptoms. The attached link provides a nice synopsis: Study Finds ‘PPI Test’ a Poor Predictor of GERD : Internal Medicine …
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At least 50% of patients with long-term infliximab therapy require dose escalation. However, dose escalation can mean doubling the dose or shortening the infusion interval. So which strategy is best? A recent article provides some insight into this question (Inflamm Bowel Dis 2012; 18: 2026-33).
In this multicenter retrospective study of 168 Crohn’s disease (CD) patients, the outcome of patients who had dose-doubling (n=112) to 10 mg/kg/dose/8 weeks was compared with patients whose infusion intervals were halved to 5 mg/kg/dose/4 weeks (n=56). The entire cohort had a mean age of 25 years and a mean disease duration of 12 years. 39% had a history of previous intestinal surgery. Concurrent use of thiopurines was noted in 68% and concurrent use of methotrexate in 4%.
Sustained response at 1 year to dose-doubling strategy was 50% compared with 39% in the interval-halving group. Favorable factors included nonsmoking status, normal C-reactive protein, and CD diagnosis between 16-40 years of age.
It is noted that a subsequent dose escalation was experienced by 28 of the 87 patients who had loss of response after first dose escalation. Regained response occurred in 9 (32%) of this cohort.
The authors indicate that increasing the dose to 10 mg/kg/8 weeks is likely preferable due to convenience and cost. At the same time, it is apparent that shortening the infusion interval is not likely to be more effective than dose doubling.
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