Promotility Agents Research Articles

Grade IV gastric ulceration, pyloric aplasia, and an ectopic duodenal papilla in a 13-year-old Quarter Horse gelding evaluated for recurrent colic.

The objective of this Case Report was to describe the clinical manifestation and postmortem findings of a horse evaluated for recurrent colic diagnosed with pyloric aplasia and an ectopic duodenal papilla. 13-year-old Quarter Horse gelding. The horse was presented to a referral center for signs of colic that were unresponsive to management on the farm. No abnormalities were noted on rectal palpation; however, upon passage of a nasogastric tube, 31 L of net gastric reflux was obtained. Gastroscopy noted grade IV squamous ulceration and moderate glandular ulceration, severe gastric dilatation, an abnormally positioned gastric outflow tract, and an ectopic duodenal papilla leaking bile-like fluid directly into the stomach. The horse was initially treated with gastroprotectants, promotility agents, and dietary modifications. Following treatment failure and repeated episodes of colic with increasing severity, the horse was euthanized and a necropsy performed. At necropsy, it was confirmed that the aboral aspect of the stomach formed a dilated pouch and continued directly into the proximal duodenum with no discernible pyloric sphincter. The area of the pylorus was delineated by a faint indentation. The ectopic duodenal papilla was traced to the liver. Congenital gastric abnormalities, even in adult horses, should be considered as differential diagnoses when investigating horses presenting with a history of chronic colic. Neither pyloric aplasia nor an ectopic duodenal papilla have been described in the equine literature, and this Case Report raises awareness of the presence of such malformations and their manifestations.

Leadership & professional development: Pro-motility agents: Mobilizing mentors to make progress.

Leadership & professional development: Pro-motility agents: Mobilizing mentors to make progress.

Hospital-Onset Clostridioides difficile infection in chronic kidney disease patients

Introduction: Hospital-onset Clostridioides difficile infection (HO-CDI), reported as laboratory-identified (LabID) event, is common in patients with chronic kidney disease (CKD), especially those with end-stage renal disease (ESRD), and is associated with prolonged length of hospitalization and more severe disease. CKD patients are at increased of developing CDI due to frequent antimicrobial and healthcare exposures. The objective of this study was to assess recent trends of HO-CDI in patients on a nephrology unit at our academic, tertiary care institution. Methods: Retrospective cross-sectional study of patients with HO-CDI who were hospitalized on a nephrology unit between January 2021 to December 2023. Collected variables included: demographic data, characterization of HO-CDI risk factors, infection and diagnosis (including prior history of CDI, toxin versus nucleic acid amplification test [NAAT] positivity, number of loose stools), CDI rate (defined as CDI count/patient days x1000), standardized antimicrobial administration ratio (SAAR) for high-risk for CDI antimicrobials (defined by the National Healthcare Safety Network), and infection prevention and control (IPC) practices, including hand hygiene audit rates. Results: A total of 30 HO-CDI infections were reported on the nephrology unit [Table], with 8 occurring in 2021, 5 in 2022, and 17 in 2023. The median age of patients was 70.8 (range: 37-96) years, and most patients (57%) were female. The majority of patients were admitted from home (73%), and two patients (7%) had a history of CDI in the last 6 months. Among the CDI cases, 60% were NAAT positive and toxin negative, and only 50% had >3 bowel movements (BM) within 24 hours prior to the positive test. Ten percent received promotility agents prior to testing. Most cases (77%) occurred when other CDI patients were on the unit. Hand hygiene compliance rates averaged 81% over the three-year period [Figure 1A]. Eight-four per cent of patients received antibiotics within 30 days of CDI diagnosis; SAAR was >1 for quarters 2 and 4 in 2022, and quarter 1 in 2023 [Figure 1B]. Conclusion: On our nephrology unit, patients often had < 3 BM within 24 hours of CDI diagnosis, and 60% of cases were toxin-negative, NAAT-positive, suggesting possible C. difficile colonization, rather than true infection. In addition, an elevated SAAR correlated with high CDI rates. Multicomponent interventions may be required to reduce the rates of HO-CDI in CKD patients. Opportunities include emphasis on diagnostic and antimicrobial stewardship, environmental cleaning and adherence to IPC practices, including hand hygiene.

Quality Indicator Development for the Approach to Ineffective Esophageal Motility: A Modified Delphi Study.

Develop quality indicators for ineffective esophageal motility (IEM). IEM is identified in up to 20% of patients undergoing esophageal high-resolution manometry (HRM) based on the Chicago Classification. The clinical significance of this pattern is not established and management remains challenging. Using RAND/University of California, Los Angeles Appropriateness Methods, we employed a modified-Delphi approach for quality indicator statement development. Quality indicators were proposed based on prior literature. Experts independently and blindly scored proposed quality statements on importance, scientific acceptability, usability, and feasibility in a 3-round iterative process. All 10 of the invited esophageal experts in the management of esophageal diseases invited to participate rated 12 proposed quality indicator statements. In round 1, 7 quality indicators were rated with mixed agreement, on the majority of categories. Statements were modified based on panel suggestion, modified further following round 2's virtual discussion, and in round 3 voting identified 2 quality indicators with comprehensive agreement, 4 with partial agreement, and 1 without any agreement. The panel agreed on the concept of determining if IEM is clinically relevant to the patient's presentation and managing gastroesophageal reflux disease rather than the IEM pattern; they disagreed in all 4 domains on the use of promotility agents in IEM; and had mixed agreement on the value of a finding of IEM during anti-reflux surgical planning. Using a robust methodology, 2 IEM quality indicators were identified. These quality indicators can track performance when physicians identify this manometric pattern on HRM. This study further highlights the challenges met with IEM and the need for additional research to better understand the clinical importance of this manometric pattern.

Surgical Treatment of Gastroparesis.

Gastroparesis and intestinal dysmotility are life-altering diagnoses with no cure. Lifestyle changes, pharmacological, and surgical interventions are combined in a multidisciplinary fashion to improve the quality of life in this patient population. Starting with lifestyle changes, adjustments are made to the types and amounts of food consumed, medical conditions are optimized, and the use of narcotic pain medications as well as smoking is discontinued. For many, these changes are not enough, and antiemetics and promotility agents are used to control symptoms. Finally, when these measures fail, patients turn to surgery, which can include surgical alterations to the stomach, implantation of a gastric stimulator, placement of drainage tubes, and possibly even the complete removal of different organs, including the stomach or gallbladder. In our clinic, patients not only see a surgeon but also a gastroenterologist, dietitian, and psychologist. We strongly believe in a multidisciplinary approach to this condition. The goal is to provide patients with hope and help them live fuller and happier lives. The study primarily addresses technical considerations and the surgical approach for patients diagnosed with gastroparesis. It outlines the entire process, starting from preparations before the surgery, encompassing the preoperative work-up, and detailing the steps involved in the surgical procedure. One of the key diagnostic challenges faced in treating gastroparesis patients is determining the underlying cause of the condition, as this information is critical for selecting the appropriate surgical intervention. Once the patient's condition has been categorized based on the cause, the medical team engages in a discussion with the patient regarding potential treatment options, which may include endoscopic procedures, minimally invasive techniques, or open surgery.

Effect of Glucagon-Like Peptide-1 Receptor Agonists on Bowel Preparation for Colonoscopy.

Inadequate bowel preparation can result in decreased diagnostic accuracy and therapeutic safety of colonoscopy for colon cancer screening. The Boston Bowel Preparation Scale (BBPS) has been used to assess the quality of bowel preparation. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are commonly used medications for diabetes mellitus and obesity that are known to delay gastrointestinal motility. We hypothesized that the use of GLP-1RA would be associated with decreased quality of bowel preparation. We performed a retrospective cohort study of patients who underwent screening or surveillance colonoscopy at a large academic medical center between December 2021 and December 2022. We included patients taking any GLP-1RA for diabetes or obesity during colonoscopy defined as our cases, and patients who were prescribed GLP-1RA at one point but not within 3 months of colonoscopy defined as our controls. We excluded patients on any promotility or antimotility agents and those without BBPS recorded on their procedure report. Independent t test assessed statistical differences in the case and control groups to compare the quality of bowel preparation for continuous variables, and the χ 2 test was used for categorical variables. Multivariate linear regression including diabetes as a covariate was also performed for continuous variables, and multivariate logistic regression was performed for categorical variables. A total of 446 patients were included in the study, comprising 265 (59%) cases and 181 controls (41%). There were no statistically significant differences between groups at baseline except for the diagnosis of diabetes ( P = 0.001) with a higher proportion of patients with diabetes in the cases. The mean BBPS was significantly higher in controls (7.0 ± 1.9 vs 7.5 ± 2.4, P = 0.046) when controlling for diabetes. The percentage of patients with a total BBPS score of <5 was significantly higher in cases (15.5% vs 6.6%, P = 0.01). The proportion of patients who required a repeat colonoscopy due to poor bowel preparation was also significantly higher in cases (18.9% vs 11.1%, P = 0.041). The use of GLP-1RA was associated with a statistically significantly lower quality of bowel preparation, with additional clinical significance given a notable difference in the need for a repeat colonoscopy. It will be essential to understand the cumulative effect of medications that may delay gastric emptying on the quality of bowel preparation to better understand the appropriate measures and counseling that need to be taken before undergoing outpatient colonoscopies.

Major Publications in the Critical Care Pharmacotherapy Literature: 2021.

PubMed/MEDLINE. Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critical care patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2021, and December 31, 2021. Candidate articles were organized by clinical domain based on the emerging themes from all studies. A modified Delphi process was applied to obtain consensus on the most impactful publication within each clinical domain based on overall contribution to scientific knowledge and novelty to the literature. The search revealed 830 articles, of which 766 were excluded leaving 64 candidate articles for the Delphi process. These 64 articles were organized by clinical domain including: emergency/neurology, cardiopulmonary, nephrology/fluids, infectious diseases, metabolic, immunomodulation, and nutrition/gastroenterology. Each domain required the a priori defined three Delphi rounds. The resultant most impactful articles from each domain included five randomized controlled trials and two systematic review/meta-analyses. Topics studied included sedation during mechanical ventilation, anticoagulation in COVID-19, extended infusion beta-lactams, interleukin-6 antagonists in COVID-19, balanced crystalloid resuscitation, vitamin C/thiamine/hydrocortisone in sepsis, and promotility agents during enteral feeding. This synoptic review provides a summary and perspective of the most impactful articles relevant to the pharmacotherapy of critically ill adults published in 2021.

Role of diagnostic stewardship in reducing healthcare facility-onset Clostridioides difficile infections

Background:Clostridioides difficile infection (CDI) is the most common healthcare-associated infection (HAI) in the United States. Healthcare facility-onset (HO) CDI reporting is a laboratory-identified (LabID) event and does not rely on symptoms. Inappropriate testing can lead to overdiagnosis in patients who are colonized, especially in those receiving promotility agents. Approximately 45% of HO-CDI cases at our institution occurred in the setting of laxative use in 2019. We assessed the effectiveness of an electronic medical record (EMR) “hard stop” in reducing inappropriate CDI testing and its impact on HO-CDI rates. Methods: We conducted a pre–post quasi-experimental retrospective study comparing test order rates per 1,000 patient days, CDI rate per 1,000 patient days, and standardized infection ratio (SIR) in the preintervention period (January 2018–December 2019) to the intervention period (April 2020–September 2021), at a 5-hospital healthcare system in southeastern Michigan. In February 2020, we implemented a hard stop in Epic that was triggered &gt;3 days after admission for the following criteria: patients &lt;1 year of age; repeated testing within 7 days, and receipt of promotility agents within 48 hours. After discontinuing the promotility agents for at least 48 hours, providers were allowed to place an order if diarrhea persisted. The medical director of infection prevention and control or designee had the ability to override the hard stop when deemed necessary after reviewing the case upon provider request. All orders expired after 24 hours if a specimen was not collected. We retrospectively reviewed the number of overrides after the intervention to determine the positivity rate. Results: Our CDI rates per 1,000 patient days were 3.21 in the preintervention period and 1.48 in the postintervention period, a 54% reduction (Fig. 1). The test order rates were 119.4 in the preintervention period and 87.7 in the postintervention period, a 26.5% reduction (Fig. 2). The SIR decreased from 0.542 in the preintervention period to 0.361 in the postintervention period, a 33% reduction (95% CI, 0.54–0.82; P = .0001). After the intervention, 299 patients had an override. Of these, samples from 218 patients (72.9%) were negative, 50 orders (16.7%) were cancelled, and 28 samples (9%) were positive. Conclusions: Diagnostic stewardship, utilizing an electronic hard stop, was effective in reducing inappropriate C. difficile testing in the setting of promotility agents without delaying diagnosis of HO-CDI. This strategy combined with standard best practices can significantly reduce HO-CDI rates.Funding: NoneDisclosures: None

A245 DETERMINING THE PREVALENCE OF DELAYED GASTRIC EMPTYING IN PEDIATRIC PATIENTS WITH CONSTIPATION USING NUCLEAR SCINTIGRAPHY

BackgroundGastrointestinal motility is coordinated by complex neurohormonal circuits existing between different segments of the gastrointestinal tract. It has been hypothesized that one of these pathways, the “cologastric brake,” acts as a negative feedback system to inhibit gastric motility when there is loading of stool within the colon in conditions such as constipation.AimsTo assess gastric emptying in pediatric patients presenting with constipation using whole-gut nuclear scintigraphy. We hypothesize that children with constipation are likely to exhibit delayed gastric emptying due to neurohormonal pathways such as the cologastric brake.MethodsA retrospective review of all patients under 18 years of age who underwent a whole-gut nuclear scintigraphy study for the work-up of constipation at The Hospital for Sick Children between January 2014 and May 2021 was completed. Demographic and clinical data at the time of presentation was summarized. The proportion of patients with delayed gastric emptying and delayed small and large bowel transit were calculated. Exploratory univariable analyses were performed to identify clinical predictors of delayed gastric emptying.ResultsThis study identified 140 patients meeting inclusion criteria of whom 72 were male (51.4%), (meanage = 10.04 ± 4.79). The prevalence of patients with delayed gastric emptying was 61.9% (n = 86). Despite this, only 5.0% (n = 7) and 21.8% (n = 29) had delayed small and large bowel transit respectively. Children with delayed gastric emptying were significantly younger (meanage = 9.15 ± 4.60) than those with normal gastric emptying (meanage = 11.53 ± 4.79), p = .01. A chi-square test of independence showed that there was no significant relationship between use of a promotility agent and delayed gastric emptying ( p = .48). There was also no significant association between the presence of upper gastrointestinal symptoms and delayed gastric emptying ( p = .79).ConclusionsWe found that children with constipation have a high prevalence of delayed gastric emptying. However, only a small proportion of these patients have delayed bowel transit. This supports the idea that delayed gastric emptying in children with constipation is likely not due to intrinsic neuromuscular defects of the gut but rather, secondary to a neurohormonal “cologastric brake.” This is important information for clinicians as it suggests that a key step in managing delayed gastric emptying in this scenario is to treat patients’ constipation as opposed to initiating therapies, such as prokinetic agents, which attempt to directly improve gastric emptying.Funding AgenciesNone

European Respiratory Society guidelines on the diagnosis and treatment of chronic cough in adults and children

These guidelines incorporate the recent advances in chronic cough pathophysiology, diagnosis and treatment. The concept of cough hypersensitivity has allowed an umbrella term that explains the exquisite sensitivity of patients to external stimuli such a cold air, perfumes, smoke and bleach. Thus, adults with chronic cough now have a firm physical explanation for their symptoms based on vagal afferent hypersensitivity. Different treatable traits exist with cough variant asthma (CVA)/eosinophilic bronchitis responding to anti-inflammatory treatment and non-acid reflux being treated with promotility agents rather the anti-acid drugs. An alternative antitussive strategy is to reduce hypersensitivity by neuromodulation. Low-dose morphine is highly effective in a subset of patients with cough resistant to other treatments. Gabapentin and pregabalin are also advocated, but in clinical experience they are limited by adverse events. Perhaps the most promising future developments in pharmacotherapy are drugs which tackle neuronal hypersensitivity by blocking excitability of afferent nerves by inhibiting targets such as the ATP receptor (P2X3). Finally, cough suppression therapy when performed by competent practitioners can be highly effective. Children are not small adults and a pursuit of an underlying cause for cough is advocated. Thus, in toddlers, inhalation of a foreign body is common. Persistent bacterial bronchitis is a common and previously unrecognised cause of wet cough in children. Antibiotics (drug, dose and duration need to be determined) can be curative. A paediatric-specific algorithm should be used.

Association between gastroprotective agents and risk of incident interstitial lung disease in systemic sclerosis

ObjectivesAlthough interstitial lung disease (ILD) occurs in over half of systemic sclerosis (SSc) patients and represents a leading cause of mortality, there are currently no preventative strategies. We evaluated if gastroprotective agents were associated with a lower incident risk of SSc-ILD. MethodsAn SSc cohort without clinically apparent ILD at baseline was constructed from the Canadian Scleroderma Research Group registry. The primary exposure was any use of gastroprotective agents. Treatment with promotility agents was assessed as a secondary exposure. Time to development of clinically apparent ILD was compared between exposed and unexposed person-time, using a multivariable marginal structural Cox model incorporating inverse probability of treatment weights to address time-varying confounding. ResultsIn total, 798 subjects met inclusion criteria. At cohort entry, median disease duration was 7.6 (IQR 3.9–15.6) years. During a median 4.4 (IQR 2.6–7.2) years of follow-up, 158 new ILD cases were diagnosed, for a crude incidence of 4.4 (95% CI 3.8–5.1) events per 100 person-years. Most (2085, 73.4%) person-visits were exposed to gastroprotective agents, 579 (20.4%) were exposed to promotility agents, and 554 (19.5%) were exposed to both agents. The marginal structural weighted hazard ratio (HR) for incident ILD related to gastroprotective agents was 0.86 (95% CI 0.52–1.41). When exposure was defined as treatment with promotility agents, the weighted adjusted HR was 0.79 (95% CI: 0.35–1.77). ConclusionIn this large retrospective cohort study, we were unable to demonstrate a protective role for gastroprotective and promotility agents in preventing clinically apparent SSc-ILD.

Gastroesophageal reflux disease: new approaches to optimizing pharmacotherapy

Proton pump inhibitors (PPIs) are baseline drugs for induction and maintenance of remission in gastroesophageal reflux disease (GERD). PPIs have proven to be highly effective in healing esophageal mucosal lesions and relieving the symptoms of the disease in most cases. However, according to the literature data, the incidence rate of clinical ineffectiveness of PPIs in the form of partial or complete persistence of current symptoms during administration of standard doses of PPIs ranges from 10 to 40%. Optimization of GERD therapy in PPI refractory patients is a significant challenge. In most cases, experts advise to increase a dose / dosage frequency of PPIs, switch to CYP2C19-independent PPIs (rabeprazole, esomeprazole, dexlansoprazole), add an esophagoprotective or promotility agents to therapy. At the same time, these recommendations have a limited effect in some patients, which opens up opportunities for looking for new solutions related to the optimization of GERD therapy. Today there is growing evidence of the relevance of the role of disruption of the cytoprotective and barrier properties of the esophageal mucosa in the genesis of GERD and the formation of refractoriness. Intercellular contacts ensure the integrity of the barrier function of the esophageal mucosa to protect it from various exogenous intraluminal substances with detergent properties. Acid-peptic attack in patients with GERD leads to alteration of the expression of some tight junction proteins in epithelial cells of the esophageal mucosa. The latter leads to increased mucosal permeability, which facilitates the penetration of hydrogen ions and other substances into the submucosal layer, where they stimulate the terminals of nerve fibers playing a role in the induction and persistence of the symptoms of the disease. The above evidence brought up to date the effectiveness study of the cytoprotective drugs with tropism to the gastrointestinal tract, as part of the combination therapy of GERD.

Per Oral Pyloromyotomy for Treatment of Gastroparesis in a Pediatric Patient

Per Oral Pyloromyotomy for Treatment of Gastroparesis in a Pediatric Patient

Linaclotide for the treatment of refractory lower bowel manifestations of systemic sclerosis

BackgroundLower gastrointestinal (GI) tract involvement can affect up to 50% of systemic sclerosis (SSc) patients, and may result in malabsorption, pseudo-obstruction, hospitalization, and death. We report our experience with linaclotide, a selective agonist of guanylate cyclase C (GC-C), for SSc patients with refractory lower GI disease.MethodsWe performed an analysis of patients seen at the Johns Hopkins Scleroderma Center and identified patients prescribed linaclotide for refractory lower GI manifestations. Patients had clinical data collected in our longitudinal database. Linaclotide responders were on medication for at least 12 months with documented effectiveness by the treating physician.ResultsThirty-one patients with SSc were treated with linaclotide. At the time of linaclotide initiation, 23 of these patients (74%) were classified as having severe GI disease, as defined by recurrent pseudo-obstruction, malabsorption, and/or need for artificial nutrition (Medsger GI severity score ≥ 3). The majority of patients (90.3%; 28/31) had a treatment response, while only three patients (9.7%) reported ineffectiveness or intolerable side effects. Low-dose linaclotide (≤ 145 mcg daily) was used in 18 patients and was effective in 94%. High-dose therapy (> 145 mcg daily) was effective in 11 of 13 patients (85%). Common side effects were diarrhea, cramping, or bloating (11/31, 35%). Ineffectiveness, cost, and abdominal pain were complaints cited among those who discontinued therapy.ConclusionLinaclotide is a well-tolerated and efficacious pro-secretory and pro-motility agent that can be used to manage refractory lower GI manifestations in SSc. We found that low-dose linaclotide is an effective option and may be better tolerated, though a subset of patients may require high dose regimens.

Early Intervention and Resolution of Pediatric Intestinal Pseudo-Obstruction in Systemic Lupus Erythematosus: A Pediatric Case Report

Early Intervention and Resolution of Pediatric Intestinal Pseudo-Obstruction in Systemic Lupus Erythematosus: A Pediatric Case Report

RIOCIGUAT AND GASTROPARESIS: A NOVEL ADVERSE EFFECT

SESSION TITLE: Fellows Pulmonary Vascular Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Riociguat is a novel agent for the treatment of pulmonary arterial hypertension (PAH) with known gastrointestinal side effects of nausea, vomiting, and diarrhea. We present a patient initiated on riociguat leading to severe gastroparesis, an adverse effect not previously described. CASE PRESENTATION: KB is a 53-year-old female with a history of rheumatoid arthritis (RA) and scleroderma who developed rapidly progressive dyspnea over 2 months. An echo demonstrated right heart strain, a comprehensive PH workup ensued and right heart catheterization (RHC) confirmed PAH.(Hemodynamics attached) She was initiated on combination therapy, riociguat and macitentan, with rapid clinical improvement. Three weeks later, she was admitted with nausea, vomiting, and newly elevated transaminases. Macitentan was held due to hepatotoxicity concerns without resolution of gastrointestinal symptoms. Esophagogastroduodenoscopy and abdominal CT scan were unrevealing. A gastric function study revealed pronounced dysmotility with 11% gastric emptying at 90 minutes. Promotility agents were added without benefit. We attributed her gastroparesis to scleroderma, continued riociguat and discharged her with modest improvement in GI symptoms. She was readmitted within a week with ongoing nausea and vomiting. We suspected drug involvement, stopped riociguat and observed marked improvement in 72 hours with complete resolution of GI symptoms at one month. DISCUSSION: KB is the first reported case of riociguat-induced gastroparesis. Onset of symptoms were approximately three weeks after starting riociguat. Initially assumed secondary to scleroderma, gastroparetic symptoms abated only after complete withdrawal of drug. Riociguat stimulates vascular smooth muscle via the nitric oxide-soluble guanyl cyclase-cyclic GMP (NO-sGC-cGMP) pathway. All three medications for pulmonary arterial hypertension targeting the NO pathway have been linked to gastrointestinal (GI) side effects, but a disproportionately high frequency of GI effects are associated with riociguat(1). The effect may be due to the high expression of sGC in the GI tract, including smooth muscle cells, interstitial cells of Cajal, and fibroblast-like cells(2). CONCLUSIONS: Nausea and vomiting are well-described side effects of riociguat that typically improve with anti-emetic therapy and time. We report a novel case of gastroparesis attributable to riociguat that failed to respond to usual therapies. Subjects predisposed to gastroparesis due to underlying connective tissue disease may be at additive risk. Reference #1: Khouri C, Lepelley M, Roustit M et al. Comparative safety of drugs targeting the nitric oxide pathway in pulmonary hypertension. Chest 2018; 154 (1):136-147. Reference #2: Lies B, Groneberg D, Friebe A. Toward a better understanding of gastrointestinal nitrergic neuromuscular transmission. Neurogastroenterol Motil 2014 Jul;26(7):901-12. DISCLOSURES: No relevant relationships by John Kingrey, source=Web Response No relevant relationships by Ami Perry, source=Web Response

S3596 Chronic Abdominal Pain After Gastrojejunostomy: An Unexpected Outcome

INTRODUCTION: Gastroparesis is a neuromuscular disorder of the upper gastrointestinal (UGI) tract. Diabetes is the most common known etiology, accounting for 20–30% of cases. Other major causes include medication adverse effects, neuromuscular disease, idiopathic, and post-surgical gastroparesis (PSG), which has a prevalence of 0.4-5%. We present a case of PSG treated with botulinum toxin (Botox). CASE DESCRIPTION/METHODS: A 56-year-old man with uncontrolled diabetes (HbA1c 14.2), hypertension, and small bowel perforation status post gastrojejunostomy in 2014 presented with nausea, vomiting, and diffuse postprandial abdominal pain. Initial medical management with pro-motility agents: erythromycin and metoclopramide were unsuccessful. CT scan abdomen was negative for acute pathology. EGD revealed a patent gastrojejunostomy with normal pyloric contractions. No retained food, ulcer, or gastritis was found. A gastric emptying study was negative for gastroparesis, showing a functional gastrojejunostomy. The patient underwent EGD with Botox injection into the pylorus and gastrojejunal anastomosis (Figures 1 and 2). He was also started on low dose nortriptyline. He remained symptoms free at 2 months follow up. DISCUSSION: PSG is thought to have a multifactorial etiology including dysfunction of the parasympathetic system after vagotomy and lack of duodenal motilin release after duodenal resection. After one year, a significant percentage of patients develop compensatory neurostimulation to adapt to their new anatomy. Gastrojejunostomy predisposes to slow emptying from the gastric remnant and delayed transit in the denervated efferent limb. Therefore, less than 25 cm resection is often recommended to avoid stasis. Botox injection for refractory PSG has some evidence of efficacy. One trial showed an average response rate of 43% for 5 months, with a target on quality of life. Whereas another demonstrated a 55% improvement at 6 weeks post-procedure with positive outcomes in the motility of solid food. Additionally, non-selective serotoninergic inhibitors (NSRI) such as nortriptyline (with the least anticholinergic effect) have shown promising effects at low doses for patients with refractory gastroparesis. Our patient likely had a combination of diabetic gastroparesis and PSG, which did not respond to medical therapy. We demonstrate the effective use of botulinum injection in combination with NSRI.Figure 1.: Pylorus, blood is seen post Botox injection.Figure 2.: Patent gastrojejunostomy and antrum.

Gabapentin versus baclofen for treatment of refractory gastroesophageal reflux-induced chronic cough

Refractory gastroesophageal reflux-induced chronic cough (GERC) is a special type of gastroesophageal reflux disease (GERD) with predominant cough resistant to pragmatic standard anti-reflux therapy including antisecretory agents alone or in combination with promotility agents but with a favorable response to intensified anti-reflux treatment. The condition is not rare and is difficult to treat. Neuromodulators such as baclofen and gabapentin are considered potential therapeutic options for refractory GERC. Limited data indicate that gabapentin and baclofen could attenuate the cough symptom in patients with refractory GERC by blockade of gastroesophageal reflux or by direct antitussive effects. However, no study has compared the efficacy of these two drugs in treatment of refractory GERC. In an open-labeled randomized clinical study, we demonstrated that, as add-on therapy, gabapentin and baclofen had a similar prevalence of therapeutic success for suspected refractory GERC but gabapentin may be more preferable because of its fewer central side effects. The efficacy of baclofen and gabapentin was suboptimal, so further studies are needed to select the patients with refractory GERC suitable for precise treatment using these two neuromodulators.

Metoclopramide Reduces Fluoroscopy and Procedure Time during Gastrojejunostomy Tube Placement: A Placebo-Controlled Trial

PurposeTo determine whether a single 10-mg intravenous dose of the promotility agent metoclopramide reduces the fluoroscopy time, radiation dose, and procedure time required for gastrojejunostomy (GJ) tube placement. MethodsThis prospective, randomized, double-blind, placebo-controlled trial enrolled consecutive patients who underwent primary GJ tube placement at a single institution from April 10, 2018, to October 3, 2019. Exclusion criteria included age less than 18 years, inability to obtain consent, metoclopramide allergy or contraindication, and altered pyloric anatomy. Average fluoroscopy times, radiation doses, and procedure times were compared using t-tests. The full study protocol can be found at www.clinicaltrials.gov (NCT03331965). ResultsOf 110 participants randomized 1:1, 45 received metoclopramide and 51 received placebo and underwent GJ tube placement (38 females and 58 males; mean age, 55 ± 18 years). Demographics of the metoclopramide and placebo groups were similar. The fluoroscopy time required to advance a guide wire through the pylorus averaged 1.6 minutes (range, 0.3–10.1 minutes) in the metoclopramide group versus 4.1 minutes (range, 0.2–27.3 minutes) in the placebo group (P = .002). Total procedure fluoroscopy time averaged 5.8 minutes (range, 1.5–16.2 minutes) for the metoclopramide group versus 8.8 minutes (range, 2.8–29.7 minutes) for the placebo group (P = .002). Air kerma averaged 91 mGy (range, 13–354 mGy) for the metoclopramide group versus 130 mGy (range, 24–525 mGy) for the placebo group (P = .04). Total procedure time averaged 16.4 minutes (range, 8–51 minutes) for the metoclopramide group versus 19.9 minutes (range, 6–53 minutes) for the placebo group (P = .04). There were no drug-related adverse events and no significant differences in procedure-related complications. ConclusionsA single dose of metoclopramide reduced fluoroscopy time by 34%, radiation dose by 30%, and procedure time by 17% during GJ tube placement.

3:18 PM Abstract No. 220 A randomized controlled trial of metoclopramide versus placebo to reduce fluoroscopy time during gastrojejunostomy tube placement

Gastrojejunostomy (GJ) tube placement is a common procedure performed to provide post pyloric nutritional support, but advancing a guidewire and the tube through the pylorus can be a tedious and time consuming step. The purpose of this study was to determine whether a single dose of the gastric promotility agent metoclopramide prior to GJ tube placement facilitates passage of the guidewire through the pylorus thus reducing fluoroscopy time. In this single-institution, randomized, double-blind, placebo-controlled trial, consecutive patients over 18 undergoing GJ tube placement were enrolled from April 9, 2018, to September 4, 2019. Patients unable to provide written consent or with metoclopramide allergy, altered pyloric anatomy (e.g., prior Whipple), long QT, extrapyramidal symptoms or seizure disorders were excluded. 51 patients were randomized to a single dose of metoclopramide 10 mg IV and 51 patients were randomized to placebo immediately prior to GJ tube placement. Balloon retained GJ tubes were placed using standard push technique. Fluoroscopy time, air kerma, and total procedure time were recorded. Groups were compared using t-tests and Fisher’s exact test. 43 of 51 patients (n = 33 males, mean age = 57) randomized to metoclopramide and 48 of 51 (n = 27 males, mean age = 54) randomized to placebo underwent GJ placement (P = 0.20). Mean fluoroscopy time to advance the guidewire from the stomach through the pylorus was 1.6 minutes (range, 0.3-10.1) in the metoclopramide group versus 4.2 minutes (range, 0.2-27.3) for placebo (P = 0.003). Mean total procedure fluoroscopy time was 5.8 minutes (range, 1.5-16.2) versus 8.7 minutes (range, 2.8-29.7) (P = 0.004). Mean air kerma was 90 mGy (range, 13-354) versus 124 mGy (range, 24-525) (P = 0.08). Mean total procedure time was 16.5 minutes (range, 8-51) versus 19.7 minutes (range, 6-53) (P = 0.07). There was no significant difference in the 30 day major complication rate (n = 1 in each group; P = 1.0). There were no drug related adverse events. A single dose of 10 mg metoclopramide immediately prior to GJ tube placement leads to a statistically significant reduction in fluoroscopy time by a factor of one third.