Cyclic Vomiting ED Protocol

Recently, I was reading information from the Cyclic Vomiting Syndrome Association (Winter 2020 issue). On page 12, there is a pretty good protocol for emergency department treatment with the caveat that this “represents a sample template and should be tailored based on individual needs.” In addition, this protocol was derived from an article by Venkatesan et al (Neurogastroenterology and Motility 2019; S2.https://doi.org/10.1111/nmo.13604 Full text: Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association)

Key points from guidelines article:

  • “The committee strongly recommends that adults with moderate‐to‐severe CVS receive a tricyclic antidepressant (TCA) such as amitriptyline, as a first‐line prophylactic medication. “
  • Topiramate, Aprepitant, “Zonisamide or levetiracetam and mitochondrial supplements (Coenzyme Q10, L‐carnitine, and riboflavin) are conditionally recommended as alternate prophylactic medications, either alone or concurrently with other prophylactic medications.”
  • “For acute attacks, the committee conditionally recommends using serotonin antagonists such as ondansetron, and/or triptans such as sumatriptan or newer agents such as aprepitant (NK1 receptor antagonist) to abort symptoms.”
  • Evidence, dosing regimens, and algorithms are detailed in article

Sample ED CVS Protocol (for Adults):

____[name]____________ has an established diagnosis of Cyclic Vomiting Syndrome
Operational definition
* A recurring pattern of discrete episodes of severe vomiting, accompanied by profound nausea and/or severe abdominal pain
* Patient returns to usual health status between episodes (may have inter‐episodic nausea and or dyspepsia)
* In some patients, CVS episodes resemble a migraine attack
* Patients may be restless, anxious, and distressed
* Patients are not customarily dehydrated until late in the episode
Therapeutic goal
Rapid recognition and intervention may decrease severity of the attack and promote prompt resolution of symptoms
ED management
1. Clinical assessment: Pulse/Temp/BP/Weight, consciousness, and hydration
2. Laboratories/evaluation:
CBC, urea, creatinine, LFT’s, lipase, glucose, and electrolytes
EKG
Urine analysis
Diagnostic imaging at discretion of attending physician
Treatment
1. Intravenous fluids
a. IV saline bolus if clinically dehydrated
b. IV D5NS at 100%‐150% maintenance (suggested rate is 200 cc/h for a 70 kg adult.)
2. For vomiting and nausea
a. IV ondansetron 8 mg IV × 1—may repeat q 4‐6 h if ondansetron is ineffective
b. Consider diphenhydramine 50 mg IV and metoclopramide 10 mg IV
c. Consider IV fosaprepitant 150 mg if available
3. For sedation
a. IV lorazepam 1‐2 mg and b. IV diphenhydramine 50 mg for additional sedation
4. For migraine‐like presentation
a. Sumatriptan nasal 20 mg (head forward technique) or
b. Sumatriptan subcutaneous injection 6 mg/0.5 mL
5. For pain
a. IV ketorolac 30 mg if > 60 minutes from onset; may repeat 15 mg q 6 h x 2 (maximum 60 mg/d)
b. Opioids may be considered as part of an ongoing treatment plan in refractory patientsa
Reassess
1. Treatment failure—intensify treatment as indicated above or admit patient
2. Positive treatment response—discharge
a. Continue ondansetron (soluble tablets) q 6‐8 h × 24‐48 h if initially effective
b. Continue lorazepam × 24‐48 h if initially effective
c. Continue NSAIDs for pain as needed

My take: This reference is very useful. The pediatric NASPGHAN guidelines (BUK Li et al. JPGN 2008; 47:379–393. Full text: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Consensus Statement on the Diagnosis and Management of Cyclic Vomiting Syndrome) probably need to be updated, especially as there are newer agents available (eg. aprepitant, fosaprepitant).

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Resources:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

Using FLIP

A recent review article (E Sararino et al. Am J Gastroenterol 2020; 115: 1786-06. Use of the Functional Lumen Imaging Probe in Clinical Esophagology) is a terrific article for understanding Functional Lumen Imaging Probe (FLIP) techonology and uses. Thanks to Ben Gold for this reference.

Link to patient explanation of EndoFLIP at Univ Michigan

The FLIP “measures luminal cross sectional area (CSA) and pressure in the esophagus using impedance planimetry and serves as an adjunct to existing esophageal investigative tests. A distensible balloon encasing a catheter with multiple pairs of impedance electrodes is used, and the balloon is distended with fluid of known conductivity and volume.”

FLIP can be done at time of endoscopy.

  • Distensibility index (DI). This is the ratio of EGJ cross sectional area to intraballoon pressure is generally considered the most useful FLIP metric. Normal DI values in adults range from 3.1 to 9.0 m3/mm Hg. Lower values indicated reduced EGJ opening.
  • FLIP can complement the diagnosis of achalasia when manometry and barium studies are inconclusive or negative in patients with typical symptoms.
  • FLIP can be used to assess fibrostenotic remodeling of the esophagus in eosinophilic esophagitis.
  • Lumen diameter measured using FLIP in complex strictures can potentially guide management.

This review has several helpful figures to illustrate the type of visual data available. It also provides a standard protocol for using FLIP. The current limitations for FLIP include the lack of real-time software analysis of the data which hinders reporting, and limited data supporting use.

Related blog post: #NAASPGHAN17 Eosinophilic Esophagitis Session

While this picture makes me look like a scofflaw, in fact one can sit on the sand below the median high tide mark. So there!

Budesonide for Maintaining EoE Remission

A Straumann et al. Gastroenterology 2020; Free Full Text Link: Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis

Methods: Two hundred and four adults with EoE in clinical and histologic remission, from 29 European study sites, were randomly assigned to groups given budesonide orodispersible tablet (BOT) 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks

Key Findings:

  • At end of treatment, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (P < .001 for both comparisons of BOT with placebo)
  • Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment

In the discussion, the authors state that “we recommend monitoring symptoms and signs of adrenal insufficiency when administrating topical-acting corticosteroids over prolonged time periods, in particular in children and when using higher dosages.”

My take (from discussion): “EoE requires a proper long-term anti-inflammatory therapy because, without active treatment, the vast majority of patients experience a relapse within the first 100 days after cessation of the medication.”

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“Best Practice Advice” for Small Intestinal Bacterial Overgrowth– ????

EMM Quigley, JA Murray, M Pimental. Gastroenterol 2020; 159: 1526-1532. Clinical Practice Guidelines. Full Free Text: AGA Clinical Practice Update on Small Intestinal Bacterial Overgrowth: Expert Review

This is a really lousy clinical practice guideline but a pretty good review of small intestinal bacterial overgrowth (SIBO). The reason why it is lousy: it provides virtually no recommendations on how to define/diagnose SIBO, does not recommend specific testing and equivocates on specific treatments.

Here are a few of the “best practice advice” as examples:

  • #1 The definition of SIBO as a clinical entity lacks precision and consistency; it is a term generally applied to a clinical disorder where symptoms, clinical signs, and/or laboratory abnormalities are attributed to changes in the numbers of bacteria or in the composition of the bacterial population in the small intestine
  • #5 A major impediment to our ability to accurately define SIBO is our limited understanding of normal small intestinal microbial populations
  • #6 Controversy remains concerning the role of SIBO in the pathogenesis of common functional symptoms, such as those regarded as components of irritable bowel syndrome
  • #9 There is a limited database to guide the clinician in developing antibiotic strategies for SIBO

While not providing ‘best practical advice,’ the article does provide details regarding limitations in testing, underlying pathogenesis, and potential treatment regimens for adults.

Table 3 -Provides Some Takeaway Points

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Potential Efficacy of Ondansetron for Irritable Bowel -More Studies Needed

A recent correspondence letter (CJ Black, AC Ford. AJG 2020; doi: 10.14309/ajg.0000000000000932. Full text: Efficacy of Ondansetron for Irritable Bowel Syndrome With Diarrhea) shows that ondansetron could be an effective option for irritable bowel syndrome with diarrhea. Thanks to Ben Gold for this reference.

Histologic Healing and IBD Outcomes

Several recent studies recently evaluated outcomes based on histologic healing compared to endoscopic remission.

RK Pai et al. Clin Gastroenterol Hepatol 2020; 18: 2510-2517. Full text link: Complete Resolution of Mucosal Neutrophils Associates With Improved Long-Term Clinical Outcomes of Patients With Ulcerative Colitis n=281.Key findings:

  • “We found histologic evidence of UC activity (Geboes score ≥ 2B.1) in biopsies from 182 patients (65%) and endoscopic evidence of UC activity in 149 patients (53%) (substantial agreement, κ = 0.60).”
  • “Histologic features of UC activity were associated with increased rates of systemic corticosteroid use, colectomy, and hospitalization in the entire cohort (P < .05 for all) and associated with increased rates of systemic corticosteroid use in an analysis limited to patients in endoscopic remission (P < .001).”

B Christensen et al. Clin Gastroenterol Hepatol 2020; 18: 2518-2525. Full text link: Histologic Healing Is More Strongly Associated with Clinical Outcomes in Ileal Crohn’s Disease than Endoscopic Healing This was a a retrospective study of 101 patients with CD (52% male) isolated to the terminal ileum. Key findings:

  • At ileo-colonoscopy, 63% of patients had endoscopic healing and 55% had histologic evidence of healing. The level of agreement between endoscopic and histologic activity was fair (62%, K = 0.2250, P = .0064)
  • On multivariate analysis, only histologic healing was associated with decreased risk of clinical relapse (hazard ratio [HR], 2.05; 95% CI, 1.07–3.94; P = .031), medication escalation (HR, 2.17; 95% CI, 1.2–3.96; P = .011), and corticosteroid use (HR, 2.44; 95% CI, 1.17–5.09; P = .018).
Kaplan-Meier analysis of effect of endoscopic and histologic activity on (A) clinical relapse-free survival versus histologic healing, (B) clinical relapse-free survival versus endoscopic healing

D Kevans et al. Inflamm Bowel Dis 2020; 26: 1722-1729. Histological Markers of Clinical Relapse in Endoscopically Quiescent Ulcerative Colitis Key finding: In endoscopically quiescent UC (n=76), active histological inflammation …[is] adjunctive histological marker associated with increased likelihood of disease relapse. The associated editorial (1730-32 by Asher Kornbluth) quotes Voltaire: “A wise Italian says that the best is the enemy of the good.” He notes that there is “a very real risk of abandoning an effective drug while chasing the goal of some yet to be universally defined histologic remission.” Currently organizational guidelines (ACG, AGA, ECCO, IOIBD) do NOT suggest the use of histologic normalization as an endpoint at this point.

My take: These studies show that histologic healing in ileal Crohn’s disease and in ulcerative colitis are associated with better outcomes that endoscopic appearance. However, there are a lot questions because many patients, possibly a majority, will not achieve histologic healing despite aggressive treatment. Related technical issues include how many biopsies are needed to assess histology and having a validated histologic assessment.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

New Treatment for Eosinophilic Gastritis and Duodenitis

ES Dellon et al. NEJM 2020; 383: 1624-1634. Anti–Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis

Background: AK002 (lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells.

Methods: In this phase 2 trial, the authors randomly assigned adults (n=65) who had symptomatic eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or placebo

Key findings:

  • The mean percentage change in gastrointestinal eosinophil count was −86% in the combined AK002 group, as compared with 9% in the placebo group
  • Treatment response  (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) occurred in 63% of the patients who received AK002 and in 5% of the patients who received placebo
  • The authors note that AK002 “also resulted in alleviation of dysphagia in patients with a history of concomitant eosinophilic esophagitis.”
  • Limitations: Small study and 10% developed antibodies to drug

My take: Larger phase 3 studies with AK002 are underway (NCT04322604 & NCT04322708). AK002 looks promising for eosinophilic gastrointestinal diseases.

Change in total symptom score over 14 weeks. “Shown is the least-squares mean percentage change from baseline in total symptom score over time.” The total symptom score ranges from 0 to 80, with higher scores indicating greater symptom severity. Each of eight symptoms are given a score of 0 to 10: abdominal pain, nausea, vomiting, early satiety, loss of appetite, abdominal cramping, bloating and diarrhea.

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45 Years –The New Recommendation for Colorectal Cancer Screening

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Update on Upper GI Bleeding Recommendations

DK Mullady et al. Gastroenterol 2020; 159: 1120-1128. AGA Clinical Practice Update on Endoscopic Therapies for Non-Variceal Upper Gastrointestinal Bleeding: Expert Review

Listed below are the 10 ‘Best Practice Advice’ recommendations. I think the acknowledgement that “hemostatic powder should be preferentially used as a rescue therapy and not for primary hemostasis, except in cases of malignant bleeding or massive bleeding with inability to perform thermal therapy or hemoclip placement” (#7) is very useful.

“Best Practice Advice:”
  • Endoscopic therapy should achieve hemostasis in the majority of patients with NVUGIB.
    • This may include clips, thermal (heater probes, bipolar/multipolar catheters, hemostatic forceps), diluted epinephrine injection, and hemostatic spray
  • Initial management of the patient with NVUGIB should focus on resuscitation, triage, and preparation for upper endoscopy. After stabilization, patients with NVUGIB should undergo endoscopy with endoscopic treatment of sites with active bleeding or high-risk stigmata for rebleeding.
  • Endoscopists should be familiar with the indications, efficacy, and limitations of currently available tools and techniques for endoscopic hemostasis, and be comfortable applying conventional thermal therapy and placing hemoclips.
  • Monopolar hemostatic forceps with low-voltage coagulation can be an effective alternative to other mechanical and thermal treatments for NVUGIB, particularly for ulcers in difficult locations or those with a rigid and fibrotic base.
  • Hemostasis using an over-the-scope clip should be considered in select patients with NVUGIB, in whom conventional electrosurgical coagulation and hemostatic clips are unsuccessful or predicted to be ineffective.
  • Hemostatic powders are a noncontact endoscopic option that may be considered in cases of massive bleeding with poor visualization, for salvage therapy, and for diffuse bleeding from malignancy.
  • Hemostatic powder should be preferentially used as a rescue therapy and not for primary hemostasis, except in cases of malignant bleeding or massive bleeding with inability to perform thermal therapy or hemoclip placement.
  • Endoscopists should understand the risk of bleeding from therapeutic endoscopic interventions (eg, endoluminal resection and endoscopic sphincterotomy) and be familiar with the endoscopic tools and techniques to treat intraprocedural bleeding and minimize the risk of delayed bleeding.
  • In patients with endoscopically refractory NVUGIB, the etiology of bleeding (peptic ulcer disease, unknown source, post surgical); patient factors (hemodynamic instability, coagulopathy, multi-organ failure, surgical history); risk of rebleeding; and potential adverse events should be taken into consideration when deciding on a case-by-case basis between transcatheter arterial embolization and surgery.
  • Prophylactic transcatheter arterial embolization of high-risk ulcers after successful endoscopic therapy is not encouraged.

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Small Study: Kiwi For Constipation

Healio Gastroenterology: Kiwi fruit effective, well tolerated in treating chronic constipation

From a randomized (Virtual) ACG 2020 study from Samuel W. Chey and colleagues (University of Michigan), n=79 adults:

  • “All three treatments improved complete spontaneous bowel movement (P .003). Prunes demonstrated the largest magnitude of response at 67% vs. 64% for psyllium vs. 45% for Kiwi fruit”
  • “The highest proportion of participants – 68% – reported treatment satisfaction with kiwifruit while similar proportions of those receiving prunes and psyllium – 48% – reported satisfaction”
  • “The kiwi group had the lowest proportion of participants reporting treatment dissatisfaction at 7%….Participants receiving prunes and psyllium were more likely to report abdominal pain and bloating than those receiving kiwi”