#334 IBS, Functional Dyspepsia, and Cyclic Vomiting: Disorders of Gut Brain Interaction (DGBI)

May 9, 2022 | By Elena Gibson

Video

Understand the conditions, set goals, fear diagnosis no more!

Learn diagnostic and therapeutic management strategies for IBS, functional dyspepsia, and cyclic vomiting (aka disorders of gut brain interaction (DGBI))! It’s like three episodes in one as we run through how to individualize evaluation and management for patients with functional dyspepsia, IBS, and cyclic vomiting. Topics: scripts for counseling patients, the pathophysiology of DGBI, which diagnostic tests are necessary, pharmacologic and nonpharmacologic options, and even hypnotherapy?! We’re joined again by the great Dr. Xiao Jing (Iris) Wang, (@IrisWangMD, Mayo Clinic)

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Credits

• Producer: Elena Gibson MD
• Writer: Andréa Perdigão, Elena Gibson
• Show Notes and Infographics: Andréa Perdigão
• Cover Art: Kate Grant
• Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP   
• Associate Editor: Leah Witt
• Showrunner: Matthew Watto MD, FACP
• Production team: Pod Paste
• Guest: Dr. Xiao Jing (Iris) Wang MD

Sponsor: Ten Thousand

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Sponsor: Pattern

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Show Segments

• Intro, disclaimer, guest bio
• Guest one-liner, Picks of the Week*
• Case from Kashlak; Definitions (6:20) 
• Definition of Disorders of the Gut-Brain Interaction (7:30-11:00)
• Functional Dyspepsia: diagnostic criteria, definitions (15:30-24:30), and treatments  (24:30-36:00)
• Irritable bowel disease: diagnostics (41:00), testing algorithm, and treatments (55:00)
• Cyclic Vomiting Syndrome and Cannabis Hyperemesis Syndrome: definitions, diagnosis, and management (1:11)
• Take home points
• Outro

DGBI Pearls

1. DGBI are not psychosomatic conditions! Listen carefully to identify the patterns of the disorders. 
2. Give a positive diagnosis (don’t make DGBI a diagnosis of exclusion)! 
3. Always explain DGBI to the patient, the rationale for the work up, and the reason why you are prescribing medications.
4. DGBI conditions are heterogeneous, so the treatments won’t be one size fits all! Certain symptoms will respond to certain treatments better, so a good history is key to identify what is the most bothersome symptom. 
5. Cognitive Behavioral Therapy works for IBS treatment!
6. DGBI care should be multidisciplinary; you must involve different professionals to give a better treatment for your patient. 

Disorders of Gut Brain Interaction (DGBI)

Definition

Disorders of the Gut Brain Interaction (DGBI), formerly known as functional GI disorders, are conditions caused by interactions between the nervous systems in the gut and brain. DGBI are characterized by symptom clusters with limited findings or structural abnormalities on diagnostic testing. 

The pathophysiology of DGBI involves a combination of altered motility, visceral hypersensitivity, changes in the epithelial barrier of the gut, mucosal immune dysfunction, microbiome disturbance and gut central nervous system neural processing.

Dr. Wang explains DGBI to patients by describing the pathophysiology and focusing on DGBI as a positive diagnosis, not a diagnosis of exclusion. It’s important to talk about DGBI before testing, explaining that negative test results are evidence of DGBI. Reinforce the importance of ruling out potentially threatening structural etiologies and validate the patients’ symptoms and impact on quality of life (Keefer, 2021). 

Curing Hepatitis C – Notes

Difficult to manage? 

Patients with these disorders are often considered challenging to manage by health care providers because there is a lack of understanding and experience managing DGBI during professional training. Additionally, symptoms commonly overlap with multiple structural abnormalities of the GI system, making the diagnosis more difficult. To address these gaps in comfort, providers should establish a systematic diagnostic approach for DGBI (Keefer, 2021).

Functional Dyspepsia 

Definition and diagnostic criteria 

Satiation vs. Satiety

Early satiation = a smaller portion of food leads to feeling full 

• Early satiation correlates with insufficient accommodation (stretching and changes caused by food in the stomach) (Klaassen, 2021). 
• There are inadequate diagnostic studies for gastric accommodation. Studies have investigated the use of nuclear medicine imaging to evaluate postprandial gastric accommodation (Amiriani, 2015) but it is rarely done and further research into diagnostic testing is being needed.

Early satiety = feeling full for a longer period of time

• Early satiety can be caused by delayed gastric emptying (ie gastroparesis). 
• A gastric emptying study and a gastric accommodation study should be considered to differentiate between early satiation and early satiety, but testing for accommodation is not widely available.  

Functional dyspepsia is diagnosed by the Rome-IV criteria:

• >1 the following symptoms: postprandial fullness, early satiation, epigastric pain, or epigastric burning
• Duration: >3 months with 
• Onset: >6months
• No evidence of structural disease to explain the symptoms (Ford, 2020).

Functional dyspepsia has two subgroups (Ford, 2020):

1. Postprandial Distress Syndrome: postprandial fullness and/or early satiation severe enough to affect daily activities or prevent finishing a regular size meal at least 3 days per week. Symptoms include postprandial epigastric pain or burning, epigastric bloating, excessive belching, nausea, vomiting.

2. Epigastric Pain Syndrome: epigastric pain and/or epigastric burning severe enough to affect usual activity and no clear relationship to eating.

Recommended testing 

The American College of Gastroenterology (ACG) and the Canadian Association of Gastroenterology (CAG) provide guidance for the evaluation of dyspepsia in a consensus statement (Moayyedi, 2017). Younger patients should be evaluated for H pylori by noninvasive testing such as stool antigen or urea breath test.  If any alarm features or age >55 years old, upper endoscopy is recommended to evaluate for H pylori and malignancy (Ford, 2020).  

Dr. Wang recommends a gastric emptying study in patients with significant vomiting, regurgitation or nausea to evaluate for delayed gastric emptying and gastroparesis. Ford et al describe how up to one quarter of patients with functional dyspepsia present with delayed gastric emptying pointing to potential overlap between these two conditions.

Treatment

The first step in functional dyspepsia management is explaining the disease pathophysiology to the patient. Next, you should discuss treatments directed toward specific symptoms. Pharmacologic and nonpharmacologic treatments should be considered depending on the patient’s preferences and comorbidities. It is important to reinforce that you believe the patient’s symptoms are real and will target the most bothersome symptoms first with the treatment options available (Keefer, 2021). 

Pharmacologic (consider for all patients with functional dyspepsia)

1. Treat H pylori infection if present
2. Proton Pump Inhibitors (PPIs) are the first-line, and Dr. Wang recommends a 4-week trial. In patients with functional dyspepsia, there is evidence of impaired duodenal clearance of gastric acid and duodenal hypersensitivity to gastric acid (Ford, 2020). 
3. Histamine-2 receptor blockers may be trialed nightly for the hypersensitivity component (Expert Opinion). 

“Next Step” options (Postprandial Distress Syndrome vs. Epigastric Pain Syndrome) 

Postprandial Distress Syndrome treatments target early satiation

1. Buspirone: a 5-HT receptor agonist that leads to smooth muscle relaxation & improves gastric stretching (Ford, 2020). Dr. Wang starts with 5mg of buspirone at night, increasing up to 15mg three times daily before meals. 

Epigastric Pain Syndrome treatments target visceral hypersensitivity

1. Tricyclic antidepressants (TCAs): good efficacy for pain control in DGBI. Amitriptyline and imipramine have been shown to improve epigastric pain, postprandial fullness and early satiety. (Ford, 2020). 
2. Selective serotonin reuptake inhibitors (SSRI) & serotonin-norepinephrine reuptake inhibitors (SNRI):  data is controversial but can be helpful (Ford, 2020).

New pharmacologic options

Acotiamide is an acetylcholinesterase inhibitor that relaxes the gastric fundus, but the exact mechanism of action is still not completely understood and the medication is not available in the US (Matsueda, 2012). Potassium competitive acid blockers, like Vonoprazan, might be a good choice for patients that do not metabolize PPIs well (Asaoka, 2017).

Non-pharmacologic options 

1. Peppermint oil and Caraway oil have antispasmodic and prokinetic effects while decreasing hypersensitivity. Both oils synergistically attenuate postinflammatory visceral hyperalgesia (Li, 2019). A study of 95 patients with FD found the combination of both oils in a duodenal release formulation improved postprandial symptoms in some (Chey, 2019). Peppermint oil has Ca²⁺ channel blocking properties and contributes to gastrointestinal smooth muscle relaxation. Enteric coating should be used to avoid relaxation of the gastroesophageal junction which can worsen reflux (Lacy 2021). Peppermint options include FDguard, IBguard, and enteric coated peppermint,. Caraway oil options include FDguard, IBguard, and caraway tea. 

2. Dietary changes are an option, but there is limited evidence (Ford, 2020). Patients with early satiation should consider small, frequent meals. Avoiding high fat or fiber foods can also accelerate gastric emptying. Dr. Wang recommends clarifying with patients that DGBI are functional impairments of the stomach and intestines, not a problem caused by oral intake. Elimination diets excessively restricted diets– remind patients that the problem is the vessel not the food.

Irritable Bowel Disease 

Diagnostic Criteria 

Irritable Bowel Syndrome (IBS) is diagnosed based on symptoms including recurrent abdominal pain associated with alteration of either stool frequency or consistency at least 1 day per week for > 3 months, with symptom onset >6 months prior. IBS can be classified as IBS with constipation (IBS-C) >¼ bowel movements are types 1 or 2 on the Bristol Stool Scale; IBS with diarrhea (IBS-D) >¼ of stools are types 6 or 7; IBS with mixed pattern, >¼ of stools are type 1 and 2 and >¼ are types 6 or 7. Unclassified meets the criteria for IBS but doesn’t fall in any of those categories (Ford, 2020). Dr. Wang recommends explaining when the diagnosis of IBS is very likely according to symptoms and testing is done to rule out other conditions that could mimic IBS. This will ensure appropriate treatment is started early. 

Testing Algorithm 

Note: Figures that can help diagnose and workup common GI symptoms from prior episodes: Constipation, Diarrhea Part I and Part II.  

IBS-D

Celiac disease, inflammatory Bowel Disease (IBD), Microscopic Colitis and Colorectal Cancer are on the differential diagnosis, and patient factors should guide how far you workup these diagnoses. For PCPs, Dr. Wang recommends celiac serology testing to rule out celiac disease and fecal calprotectin or lactoferrin for IBD (Ford, 2020). Testing for infectious causes is generally not recommended unless there are risk factors (eg, post-infectious IBS-D or possible exposures to Clostridium difficile and/or giardia. If Microscopic Colitis is a consideration, GI specialists will pursue flexible sigmoidoscopy with random biopsy to evaluate. Bile acid diarrhea should be considered for patients with abnormal bile acid circulation, like Crohn’s disease, iliac resection, extensive appendectomy, persistent GI symptoms after cholecystectomy. Bile acid diarrhea is investigated with 48 hour fecal bile acid excretion testing (Ford, 2020). Small intestinal bacterial overgrowth (SIBO) should be considered in patients with risk factors such as previous gastric or intestinal surgery or predisposition to bacteriostasis including Roux-en-Y bypass, small intestine diverticulosis, and dysmotility of the small bowel. 

IBS-C

Evalute for pelvic floor dysfunction with a digital rectum exam or anal rectal manometry. If >45 years old, colonoscopy should be performed for screening of colorectal cancer, not as a workup for constipation (Ford, 2020). 

 Treatment: pharmacological and nonpharmacological  

IBS management should start with a thorough explanation of the disease, symptoms, pathophysiology and natural history. Treatment aims to decrease the most bothersome symptom and should include a realistic discussion about the limitation of treatments available. 

Non-pharmacological 

• Cognitive Behavioral Therapy (CBT): good option for IBS treatment. CBT should be performed with a gastrointestinal specialized psychotherapist and focus on the management and treatment of the IBS symptoms. Treatment usually takes 8-12 weeks and trials have shown efficacy similar to TCAs (Black, 2020; Surdea-Blaga, 2016). 
• Hypnotherapy: usually a seven-session protocol over 12 weeks, about 30 minutes per session, with minimal side effects. Utilization is limited by availability of providers (Black, 2020; Surdea-Blaga, 2016). 
• Low-FODMAP diet: limited 6 week trial with nutritionist, ensure early food reintroduction to avoid micronutrient deficiency diet and persistent food intolerance/avoidance.
• Peppermint oil: 200mg 3 times a day, might also be used for IBS because of its alleviative effect on hyperalgesia (Weerts, 2021; Ford,, 2020). 

Pharmacologic 

IBS-D

• Antispasmodics: only if significant abdominal cramping—guidelines do not recommended for global symptom relief
• Scheduled loperamide, since it is widely available. Bismuth can also be used, especially for Microscopic Colitis (Senderovich, 2021). 
• Rifaximin: 550 mg three times a day is effective for treatment of IBS-C, but Dr. Wang reminds us it is infrequently covered by insurance and it might contribute to dysbiosis. She limits its use to patients with probable small intestinal bacterial overgrowth (SIBO), as they need a treatment that can limit their microbiota (expert opinion).
• Serotonin receptor (5-HT3) antagonists: slow gastrointestinal transit and decrease visceral hypersensitivity. Benefit of alosetron (0·5–1·0 mg twice a day) has been demonstrated for female patients with IBS  (Mangel, 1999).  Eluxadoline (100mg twice a day) may also be used, but its use is contraindicated in patients with prior cholecystectomy. Side effects include acute pancreatitis and sphincter of Oddi spasm (Ford, 2018).

IBS-C

• Prescription laxatives 
• Secretagogues, such as Lubiprostone (8 μg twice a day), Linaclotide (290 μg once a day) (Ford, 2020). Even though trials failed to show improvement of pain, the improvement of bowel movements might prevent hypersensitivity. Unfortunately, use of secretagogues might be limited by the insurance coverage (expert opinion). 

Both

• Tricyclic antidepressants (TCAs): good evidence for treating global IBS symptoms, but caution is imperative as TCAs have many potential interactions and side effects. Amitriptyline (10–30 mg at night) might be constipating, so Dr. Wang prefers nortriptyline (25-75mg at night) or desipramine (50mg at night) (Ford, 2018). It is important to exercise caution when considering antispasmodics and TCAs for older adult (geriatric) patients due to igh anticholinergic, sedative, and orthostatic hypotensive effects (American Geriatrics Society 2019 Updated Beers Criteria). 

• Microbiome treatment: Dr. Wang explains to patients that, to preserve the “good” bacteria living in the gut, people should avoid unnecessary antibiotics and eat a variety of foods. Evidence for probiotics is limited by heterogeneity of products (Ford, 2018). Therefore, Dr. Wang does not recommend starting probiotics, but if patients prefer using them she recommends VSL-3 or natural probiotics (yogurts, kombucha) (Connell, 2018).  Stool transplantation is an invasive procedure with risk for complications, and it is not a first line choice for IBS treatment (Ianiro, 2019). 

Cyclic Vomiting and Cannabinoid Hyperemesis Syndrome

Diagnostic Criteria 

Cyclic vomiting Syndrome (CVS) is a syndrome with episodes of uncontrollable vomiting, separated by periods of relative wellness/absence of vomiting. Episodes are often associated with nausea, abdominal pain, headache, photo- and phonophobia, and autonomic symptoms. 

Rome IV criteria: vomiting <1 week occurring at least 1 week apart with at least two acute-onset episodes in the past 6 months. Emesis is absent between episodes, but other symptoms might persist. CVS is associated with a family or personal history of migraines and abdominal migraines (Hasler, 2019; Hayes, 2018). 

Cannabinoid Hyperemesis Syndrome (CHS) is characterized by stereotypical episodic vomiting in the setting of chronic, daily cannabis use, and the relief of episodic vomiting with cessation of cannabis use. It is frequently associated with epigastric abdominal pain. There are periods of remission lasting from days to weeks between episodes, and episodes tend to coalesce over time if cannabis use continues (Gajendran, 2020). 

Findings in CVS and CHS overlap, requiring a detailed history to differentiate the two, particularly when CVS patients use cannabis for anti-nausea effects. If nausea/emesis was present prior to cannabis use, CVS is more likely (Matheson, 2020; Venkatesan, 2019). Both CVS and CHS can be alleviated by hot showers. Remember to discuss with patients how the effects of cannabis on symptoms can vary with time, so even if cannabis use previously helped nausea/emesis, it can worsen symptoms now.

The Phases of CVS & CHS

Dr. Wang reminds us that CVS and CHS have phases. 

CVS: Phase 1: feeling fine; Phase 2: prod of nausea/emesis; Phase 3: hyperemesis with intractable nausea/emesis; Phase 4: recovery 

CHS: Phase 1: Prod phase – nausea, fear of vomiting, anorexia and abdominal discomfort; Phase 2: Hyperemesis phase – intractable vomiting and sympathetic overactivity; Phase 3: Recovery phase – patient returns to baseline without symptoms (Gajendran, 2020; Hayes, 2018).

Management 

Cannabis Use

Focus on treatment of nausea and emesis during the acute hyperemesis phase. Following resolution of the acute phase, cannabis cessation counseling should be provided while acknowledging cessation can be very difficult (Gajendran, 2020; Venkatesan, 2019; Hayes, 2018). There are no guidelines about how long patients must stop using cannabis to see improvement in symptoms, but it is usually at least several months. Dr. Wang reminds us it is important to ally with patients, making it clear that you are not just blaming cannabis use, but you are trying to treat the symptoms. 

Action Plans 

For CVS and CHS, action plans are recommended to help patients understand the disease and plan for management according to their current phase. During the wellness phase, the goal is to prevent an episode; treatment is similar to migraine prevention with efficacy for prevention found with amitriptyline, propranolol, and cyproheptadine. In the prodromal phase, the goal is preventing episodes from starting; benzodiazepines, analgesics, or triptans may be used. During the hyperemesis phase, many antiemetics do not have good efficacy, but IV or sublingual ondansetron, lorazepam, chlorpromazine, diphenhydramine can be more helpful. Consider haloperidol as second-line treatment (Gajendran, 2020; Venkatesan, 2019; Hayes, 2018). Medications such as aprepitant, commonly approved for chemotherapy-induced nausea, can be used orally (Venkatesan, 2019). An action plan and therapeutic relationship with outpatient providers can help patients manage crises and ask for treatments that work for them during hyperemesis episodes in the ED.

Links*

1. Flo Rida – Club Can’t Handle Me 
2. Bon Jovi – Wanted Dead or Alive 
3. Searching for Sugar Man
4. Johnny Rodrigues’ Albums 
5. It takes two -Two Player game 
6. Thelma and Louise 
7. Curbsiders’ episode: Constipation
8. Curbsiders’ episode: Diarrhea Part 1 and Part 2  
9.  Foundation – GastroPsych
10. Brain-Gut Psychotherapy – Referral Guide
11. The  Foundation Hypnosis Techniques Training for Health Psychologists working in Disorders of Gut Brain Interactions (DGBIs)
12. American Society of Clinical Hypnotherapy – Certification Program 

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on our Amazon.com links and buy something we earn a (very) small commission, yet you don’t pay any extra.

Goal

Listeners will develop a framework to diagnose and manage DGBI, and learn to make an action plan that will treat patients based on their most bothersome symptoms. 

Learning objectives

After listening to this episode listeners will…  

1. Define disorders of the gut brain interaction (DGBI) 
2. Identify diagnostic criteria for functional dyspepsia,  irritable bowel syndrome (IBS), cyclic vomiting syndrome, and cannabis hyperemesis syndrome. 
3. Develop a framework for collaborative treatment of symptoms related to DGBI.
4. Review nonpharmacologic and pharmacologic treatment options for DGBI.
5. Identify the differences and overlap between cyclic vomiting syndrome and cannabis hyperemesis syndrome.

Disclosures

Dr. Xiao Jing (Iris) Wang reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.

Citation

Gibson E, Perdigão AG, Wang XJ, Williams PN, Watto MF. “#333 IBS, Functional Dyspepsia and, Cyclic Vomiting: Disorders of Gut Brain Interaction (DGBI)”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Final publishing date, 2021.