Prokinetic Research Articles

Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate.MethodsA library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone.ResultsAfter screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC.ConclusionCollectively, these findings suggest that domperidone serves as an effective “multi-target” inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC.

Safety of prolonged use of metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis

BackgroundMetoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and associated side effects of prolonged-use metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis (SSc). MethodsA quantitative observational survey was conducted by interview questionnaire in rheumatology outpatients at a tertiary teaching hospital in Riyadh, Saudi Arabia. The study included all patients aged 25–80 years diagnosed with SSc. All patients were on metoclopramide or domperidone for the treatment of chronic gastrointestinal dysmotility symptoms over at least 12 weeks. ResultsEighteen eligible patients were included. Most study participants were diagnosed with SSc complicated by interstitial lung disease (n = 13; 72.2 %). The most frequently reported side effect that occurred while taking prokinetic drugs was shortness of breath (n = 12; 66.7 %). None of the participants reported experiencing depression, galactorrhea, or syncope. CNS side effects were reported in 5.6 %. There were no differences in side effects based on the type and dosage of prokinetic drug used. ConclusionsUse of metoclopramide and domperidone for the treatment of chronic gastrointestinal dysmotility in SSc patients for 12 weeks or longer was not associated with any troublesome side effects. Further studies with more participants are needed to confirm our findings.

Dispepsia: etiopatogenia, manifestaciones clínicas, diagnóstico y tratamiento

Dyspepsia is a set of symptoms originating in the gastroduodenal region. The term is complex and difficult to define; some symptoms are confused or overlap with other diseases. The main symptoms are burning or pain in the epigastrium, postprandial fullness, and early satiety. It is classified as organic or functional according to the origin of the symptoms. The pathophysiology of the latter is multifactorial, involving multiple factors such as slowing of gastric emptying, visceral hypersensitivity, or gastric accommodation, among others. It is an important disease with a significant prevalence in the population (20%) that generates high costs and an impact on patients’ quality of life. In order to diagnose it, it is essential to rule out an organic nature in patients with alarm symptoms by means of an oral panendoscopy. In the absence of these symptoms, the first step is to detect and treat Helicobacter pylori infection. If symptoms persist afterwards, first-line treatment is acid suppressant medications followed by tricyclic antidepressants and prokinetic agents.

Clinical Trial: Efficacy of Mosapride Controlled-release and Nortriptyline in Patients With Functional Dyspepsia: A Multicenter, Double-placebo, Double-blinded, Randomized Controlled, Parallel Clinical Study.

Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment. Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life. One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline. Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.

Gastroesophageal Reflux Disease: Pathophysiology and New Treatment Trends.

Gastroesophageal reflux disease (GERD) is caused by the reflux of gastric contents into the esophagus due to a decline in esophageal clearance and anti-reflux barrier mechanisms. Mucosal injury is caused by a combination of gastric juice directly damaging the esophageal mucosa and the immune and inflammatory mechanism in which inflammatory cytokines released from the esophageal mucosal epithelium cause neutrophil migration, triggering inflammation. Gastric secretion inhibitors are the first-line treatment for GERD, but they can be combined with prokinetic agents and Chinese herbal remedies. However, pharmacotherapy cannot improve anatomical problems or prevent physical causes of GERD, such as reflux of non-acidic contents. Therefore, surgery can be warranted, depending on the pathology. Intraluminal endoscopic therapy, which is both less invasive and more effective than surgery, was recently developed and applied in Europe and the United States. In Japan, intraluminal endoscopic therapies, such as anti-reflux mucosectomy, anti-reflux mucosal ablation, and endoscopic submucosal dissection, for GERD have been independently developed.

Potassium-Competitive Acid Blocker Versus Proton Pump Inhibitor: A Pilot Study on Comparable Efficacy in the Treatment of Gastroesophageal Reflux-Related Cough.

Acid inhibitors have been considered in treating gastroesophageal reflux-related cough (GERC). Compared to proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs) have more potent and durable effects on anti-acid secretion. However, whether vonoprazan and esomeprazole have different therapeutic effects on GERC remains unknown. Patients diagnosed with GERC were enrolled in our study and randomly treated with vonoprazan (20 mg, once daily, P-CAB) or esomeprazole (20 mg, twice daily, PPI) for two months. A prokinetic agent was also administered. Patients were followed up once a month. Cough severity visual analogue scale (VAS) was measured as the primary outcome, while cough symptom score (CSS) and scores for cough-related quality-of-life or reflux-related symptoms were the secondary endpoints. A total of 50 patients completed the study, with 25 patients in each group. P-CAB and PPI groups showed similar decreases in cough severity VAS and CSS scores after the 2-month treatment (all P < 0.001). For quality-of-life, the Leicester Cough Questionnaire (LCQ) score increased significantly from baseline in both groups, but the P-CAB group had greater improvement and a higher LCQ score in month 2 (all P ≤ 0.05). For reflux-related symptoms, the Hull Airway Reflux Questionnaire (HARQ) score declined substantially over time in the P-CAB group, while the reflux symptom index (RSI) score decreased in both groups. The P-CAB group tended to have a lower HARQ (P = 0.051) and RSI (P = 0.069) scores in month 2. In conclusion, vonoprazan may be comparable to esomeprazole in cough symptom relief in GERC during the 2-month treatment period, but possibly provides better gains on classic reflux symptoms and quality-of-life. The long-term efficacy of P-CABs on GERC may be worth further exploration. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200067089.

Efficacy of Pistacia lentiscus Plant (Rumi Mastagi) in Comparison to Levosulpiride in Patients with Diabetic Gastroparesis: A Double-Blind Non-Inferior Randomised Control Trial Study.

Gastrointestinal neuropathies are frequently found in diabetic patients. The pathogenesis of diabetic gastroparesis (DG) is multifactorial. The usual treatment for DG includes dietary modifications, prokinetic and antiemetic agents. There is increasing demand for more effective medicines to treat DG. The current study was conducted on the Pistacia lentiscus stem extract to add to the armamentarium of DG treatment and to find the efficacy of P. lentiscus plant extract (mastic gum) in comparison to levosulpiride in DG for improvement in gastroparesis symptoms and gastric emptying scintigraphy (GES) in a single centric double-blind non-inferiority randomised control trial. Thirty-eight individuals were recruited and equally randomised into two study groups based on Gastroparesis Cardinal Symptom Index (GCSI) score and TC99 Radionuclide GES, mastic gum group and levosulpiride group. Both pre and post-intervention (8 weeks) GCSI scores were calculated, GES was performed to quantify the improvement in gastric emptying. Power analysis was performed using G*POWER software version 3.1.9.7 and data analysis using SPSS 23.0, variables measured in mean ± standard deviation (SD). Various statistical tests were used such as independent t-test, Chi-square test or Fisher's exact test, Wilcox Mann-Whitney test, analysis of variance (ANOVA) test, and posthoc pairwise tests. The mastic gum is found effective in the improvement of 4 h gastric emptying percentage from the mean (SD) 76.60 (± 9.96) to mean (SD) 97.20 (2.17)% (P < 0.001). Mastic gum has the property of HbA1c reduction, which is more significant than that of levosulpiride (P = 0.044). Mastic gum also had significant Low density lipoprotein (LDL) (mg/dL) levels reduction, (P < 0.001), compared to levosupiride. An absolute increase was observed in haemoglobin (HB) level in mastic gum at a 2-month mean (SD) of 1.03 (0.77) (g/dL) (P-value <0.001). To our knowledge, this is the first study to compare the effect of levosulpiride with mastic gum concerning improvement in diabetic gastroparesis (DG) using GES. In the study, mastic gum was found to have great properties to improve DG with many important pleiotropic effects.

CURRENT PHARMACOLOGICAL MANAGEMENT IN UPPER GASTROINTESTINAL BLEEDING

Upper gastrointestinal bleeding is a common reason for presentation to the hospital. Appropriate resuscitation followed by endoscopic assessment and endotherapy for high-risk lesions (active bleeding or non-bleeding with visible vessels) forms the cornerstone of management. Pharmacological therapies are utilised at each stage of management in both variceal and non-variceal bleeding. Proton pump inhibitors and prokinetic agents can be administered pre-endoscopically with vasoactive medication and antibiotics utilised in suspected variceal bleeding. Epinephrine may be used as a temporising measure to improve visualisation during endoscopy but should not applied as a single agent. Topical endoscopic therapies have also shown promise in achieving haemostasis. Following endoscopy, a high dose of proton pump inhibitor should be given to patients who require endotherapy and vasoactive medications, and antibiotics continued in confirmed variceal bleeds. The timing of resumption of antithrombotic medication is dependent on the agent utilised and underlying thrombotic risk.

Hyperprolactinemia in Functional Dyspepsia: The Entangled Domperidone Link.

The commonest medications prescribed in functional dyspepsia are prokinetic agents, specifically domperidone. However, its administration at times elevates serum prolactin levels, which can lead to pathological hyperprolactinemia. The present study investigated the effect of 28 days of 30 mg domperidone therapy on prolactinemia in functional dyspepsia patients. We recruited 97 patients (60 men and 37 women, aged18-80 years) who had functional dyspepsia diagnosed as per the Rome IV criteria. After taking a preliminary clinical history, we measured and compared serum prolactin levels at day 'zero' and day 'twenty-eight'. We found increased prolactin levels from day '0' to day '28' after treatment with domperidone in functional dyspepsia patients, specifically in male participants aged less than 40 years, who are married and belong to middle socioeconomic status. The most common functional dyspepsia symptom found was pain in the epigastric region. To conclude, our pragmatic domperidone-induced-hyperprolactinemia link warrants this side effect to be robustly taken into account while treating functional dyspepsia patients with domperidone.

1659. Prokinetic Antibiotic Agents in the Neonatal Intensive Care Unit: Ripe for Antibiotic Stewardship Efforts!

Abstract Background Intolerance to enteral nutrition among infants in the neonatal intensive care unit (NICU) may lead to the use of prokinetic agents to improve gastric emptying and feeding tolerance. Two such oral prokinetic agents are erythromycin and amoxicillin-clavulanate that have been used in cases of dysmotility due to intestinal failure. However, dosing strategies vary and the recommended duration of therapy has not been determined. Moreover, the use of these oral antibiotics in the NICU may fall under the radar of neonatal antimicrobial stewardship programs. Our objective was to quantify their use in the Level 4 outborn NICU at Nationwide Children’s Hospital, Columbus, OH in order to inform antibiotic stewardship efforts. Methods This was a retrospective cohort study of all infants who received enteral erythromycin or amoxicillin-clavulanate in the NICU. The number of doses of each antibiotic was obtained from the Nationwide Children’s Hospital Pharmacy database. Pertinent clinical, laboratory, and outcome data were obtained. Results From January 1, 2022 to April 30, 2023, 15 infants in the NICU received ≥1 dose of erythromycin ethylsuccinate and 19 infants received ≥1 dose of amoxicillin-clavulanate enterally. Erythromycin was always used to improve motility while amoxicillin-clavulanate served as a prokinetic agent in 53% of infants in whom it was prescribed. Demographics and reason for initiation are provided in Table 1. The median (IQR) doses per patient for erythromycin was 64 (28, 125; dosing interval varied from every 6 to every 8 hours) and for amoxicillin-clavulanate was 50 (9, 105) doses per patient (majority of doses were given on a BID schedule). Characteristics of infants who received prokinetic agents in the NICU Conclusion Enteral erythromycin and amoxicillin-clavulanate have not been the target of antimicrobial stewardship programs. These antibiotics may contribute to dysbiosis and adverse events in NICU infants. An automatic stop time with a time-out when ordered in the electronic health record may be a viable strategy to reduce overutilization of these antibiotics. Disclosures Pavel Prusakov, PharmD, Merck &amp; Co: Grant/Research Support|Merck &amp; Co: Employee Michael Storey, PharmD, MS, CSL Behring: Advisor/Consultant|Sarepta Therapeutics: Advisor/Consultant

A Comprehensive Review of Gastroesophageal Reflux Disease (GERD) Treatment and its Clinical Perspectives

Gastroesophageal reflux disease (GERD) occurs by regurgitation of food in the stomach. Aggressive factors increase GERD whereas defensive factors decrease GERD progression. GERD if mild can be put under control by lifestyle modification and giving non-pharmacological treatment methods to patients however if the disease progresses non-pharmacological methods are ineffective. Drugs reduce GERD progression and also maintain the pH of the stomach to a normal level and prevent abnormal acid exposure to the oesophagus. Antacids and alginate protect oesophagus by reducing acidity and increasing viscosity. Proton pump inhibitors and histamine 2 receptor antagonists reduce acid secretion by inhibiting its secretion. Prokinetic agents increase the motility of the stomach and reduce obesity. Metabotropic glutamate receptors, gamma-aminobutyric acid receptor agonists, and cannabinoid receptors are receptor-specific drugs that act on receptors underlying the gastrointestinal tract and alter the function of receptors which increases reflux disease. Combination of antacid and alginate, domperidone and omeprazole, omeprazole and baclofen, aluminum hydroxide, magnesium, and simethicone are frequently given in GERD to expedite the healing rate and reduce acid secretion. Combinations of suitable medications reduce the adverse effects of a single medication and also make it therapeutically more effective than using monotherapy drugs. The pharmacological method is safe and effective and treats GERD completely.

Impact of Erythromycin as a Prokinetic on the Gut Microbiome in Children with Feeding Intolerance-A Pilot Study.

Studies have demonstrated that the gut microbiome changes upon exposure to systemic antibiotics. There is a paucity of literature regarding impact on the gut microbiome by long-term usage of erythromycin ethyl succinate (EES) when utilized as a prokinetic. Stool samples from pediatric patients with feeding intolerance who received EES (N = 8) as a prokinetic were analyzed for both bacteriome and mycobiome. Age-matched children with similar clinical characteristics but without EES therapy were included as controls (N = 20). In both groups, Proteobacteria, Firmicutes, and Bacteroidetes were the most abundant bacterial phyla. Ascomycota was the most abundant fungal phyla, followed by Basidiomycota. There were no significant differences in richness between the groups for both bacterial and fungal microbiome. Alpha diversity (at genus and species levels) and beta diversity (at the genus level) were not significantly different between the groups for both bacterial and fungal microbiome. At the species level, there was a significant difference between the groups for fungal microbiota, with a p-value of 0.029. We also noted that many fungal microorganisms had significantly higher p-values in the EES group than controls at both genera and species levels. In this observational case-control study, the prokinetic use of EES was associated with changes in beta diversity between the groups for mycobiome at the species level. Many fungal microorganisms were significantly higher in the EES group when compared to the controls. Confirmation of these results in larger trials will provide further evidence regarding the impact of EES on gut microbiota when utilized as a prokinetic agent.

Prokinetics for the treatment of functional dyspepsia: an updated systematic review and network meta-analysis

BackgroundSince the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD.MethodsAn updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software.ResultsA total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70–7.47), domperidone (OR: 2.29, 95%CI: 1.16–4.63), itopride(OR: 2.77, 95%CI: 1.41–5.59), acotiamide(OR: 2.63, OR: 1.33–5.36), and placebo(OR: 5.68, 95%CI: 2.98–11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75–3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16–4.14) and placebo (OR: 3.52, 95%CI: 2.01–6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics.ConclusionsMetoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.

Prediction of prokinetic agents in critically ill patients with feeding intolerance: a prospective observational clinical study.

Prokinetic agents are currently considered the first-line therapy to improve gastric emptying when feeding intolerance occurred in critically ill adults. In this study, we developed a technique to assess the feasibility of predicting prokinetic agent efficacy in critically ill patients. The first images of each patient were obtained after EFI had occurred but before the first dose of prokinetic agents was administered and additional images were obtained every morning until the seventh day. The gastric antrum echodensity was recorded based on grayscale values (50th percentile, ED50; 85th percentile, ED85; mean, EDmean) and daily energy and protein intake was collected as the judgment for effective and ineffective group. A receiver operating characteristic curve was analyzed to distinguish the thresholds between the two groups and thus determine the ability of the gastric antrum echodensity to predict the efficacy of prokinetic agents. In total, 83 patients were analyzed. Patients in the ineffective group had a higher ED50 (58.13 ± 14.48 vs. 49.88 ± 13.78, p < 0.001, difference 95% CI: 5.68, 10.82), ED85 (74.81 ± 16.41 vs. 65.70 ± 16.05, p < 0.001, difference 95% CI:6.16, 12.05), and EDmean (60.18 ± 14.31 vs. 51.76 ± 14.08, p < 0.001, difference 95% CI: 5.85, 11.00) than those in the effective group. Patients in the effective group more easily reached the target energy 16.21 ± 7.98 kcal/kg vs. 9.17 ± 6.43 kcal/kg (p < 0.001), 0.72 ± 0.38 g/kg vs. 0.42 ± 0.31 g/kg (p < 0.001) than in the ineffective group intake by day. The gastric antrum echodensity might serve as a tool for judging the efficacy of prokinetic agents, helping clinicians to decide whether to use prokinetic agents or place a post-pyloric tube when feeding intolerance occurs in critically ill patients.Clinical trial registration:http://www.chictr.org.cn/addproject2.aspx, ChiCTR2200058373. Registered 7 April 2022.

Pharmacomagnetography assessment of the prokinetic effect on metronidazole absorption.

This study aimed to evaluate the effects of prucalopride, a prokinetic agent that acts as a potent serotonin agonist of 5-HT4 receptors, on gastric emptying and small bowel transit and assess its impact on the absorption of metronidazole. Six healthy volunteers, three men and three women, aged between 20 and 27 years, with a body weight ranging from 50 to 80 kg, were enrolled in this study. The pharmacokinetics and gastrointestinal transit parameters were evaluated simultaneously through pharmacomagnetography assessment, combining alternating current biosusceptometry and blood analysis. The results showed that prucalopride enhances gastric emptying and small bowel transit when administered orally and significantly impacts the rate of metronidazole absorption, leading to enhanced bioavailability and rapid therapeutic response. Pharmacomagnetography assessment allows simultaneous tracking of transit by images and is a valuable method for analysing drug absorption using multiple instruments.

What Is the Optimal Bowel Preparation for Capsule Colonoscopy and Pan-intestinal Capsule Endoscopy? A Systematic Review and Meta-Analysis

BackgroundThe rate of adequate cleansing (ACR) and complete examinations (CR) are key quality indicators in capsule colonoscopy (CC) and pan-intestinal capsule endoscopy (PCE).AimsTo evaluate the efficacy of bowel preparation protocols regarding ACR and CR.MethodsWe conducted a systematic review and meta-analysis, search terms regarding colon capsule preparation, publication date from 2006/01, and date of search 2021/12, in six bibliographic databases. Multiple steps of the cleansing protocol were assessed: diet, adjunctive laxatives, purgative solution, use of prokinetic agents, and “booster”. The meta-analytical frequency of ACR and CR was estimated, and subgroup analyses performed. Strategies associated with higher ACR and CR were explored using meta-analytical univariable and multivariable regression models.ResultsTwenty-six observational studies and five RCTs included (n = 4072 patients). The pooled rate of ACR was 72.5% (95% C.I. 67.8–77.5%; I2 = 92.4%), and the pooled rate of CR was 83.0% (95% C.I. 78.7–87.7%; I2 = 96.5%). The highest ACR were obtained using a low-fibre diet [78.5% (95% C.I. 72.0–85.6%); I2 = 57.0%], adjunctive laxatives [74.7% (95% C.I. 69.8–80.1%); I2 = 85.3%], and split dose < 4L polyethylene glycol (PEG) as purgative [77.5% (95% C.I. 68.4–87.8%); I2 = 47.3%]. The highest CR were observed using routine prokinetics prior to capsule ingestion [84.4% (95% C.I. 79.9–89.2%); I2 = 89.8%], and sodium phosphate (NaP) as “booster” [86.2% (95% C.I. 82.3–90.2%); I2 = 86.8%]. In univariable models, adjunctive laxatives were associated with higher ACR [OR 1.81 (95% C.I. 1.13; 2.90); p = 0.014]. CR was higher with routine prokinetics [OR 1.86 (95% C.I. 1.13; 3.05); p = 0.015] and split-dose PEG purgative [OR 2.03 (95% C.I. 1.01; 4.09), p = 0.048].ConclusionsMain quality outcomes (ACR, CR) remain suboptimal for CC and PCE. Despite considerable heterogeneity, our results support low-fibre diet, use of adjunctive sennosides, split dose < 4L PEG, and routine prokinetics, while NaP remains the most consistent option as booster.

Effects of defoliant exposure and medication use on the development of Parkinson's disease in veterans.

Vietnam-era veterans were exposed to Agent Orange (AO), which is associated with a high prevalence of Parkinson's disease (PD). However, little is known about the development of PD-like symptoms caused by drug-induced parkinsonism (DIP) in such populations. This study aimed to investigate PD incidence and PD risk following exposure to AO or DIP-risk drugs in veterans. A retrospective cohort study was conducted using 12years (2009-2020) of electronic medical records of the Veterans Health Service Medical Center, the largest Veterans Affairs hospital in South Korea (n = 37,246; 100% male; age, 65.57 ± 8.12years). Exposure to AO or DIP-risk drugs, including antipsychotic, prokinetic, anti-epileptic, dopamine-depleting and anti-anginal agents, was assessed in veterans with PD, operationally defined as having a PD diagnosis and one or more prescriptions for PD treatment. The PD risk was calculated using multiple logistic regression analysis adjusted for age and comorbidities. The rates of DIP-risk drug use and AO exposure were 37.92% and 62.62%, respectively. The PD incidence from 2010 to 2020 was 3.08%; 1.30% with neither exposure, 1.63% with AO exposure, 4.38% with DIP-risk drug use, and 6.33% with both. Combined exposure to AO and DIP-risk drugs increased the PD risk (adjusted odds ratio = 1.68, 95% confidence interval, 1.36-2.08, P < 0.001). The PD incidence was 1.31 times higher with AO exposure alone and 1.68 times higher with AO exposure and DIP-risk drug use. The results suggest the necessity for careful monitoring and DIP-risk drug prescription in patients with AO exposure.

Nutritional management of a malnourished cancer patient with high output ileostomy

High output stoma is a complication that may follow ileostomy formation, with an incidence of 23%. There is no general consensus on the limit of ileostomy production to be defined as high output. However, output of more than 2000 mL/day, can cause fluid and electrolyte imbalance, also malnutrition due to reduced nutrient absorption. Delay in recognition and treatment, especially in cancer patient with high risk of malnutrition, can further deteriorate patient’s nutritional status. A 43-year-old malnourished female with ascending colon cancer underwent tumor resection and ileocolostomy surgery. Starting from the third postoperative day, ileostomy effluent drastically increased to 2700 mL/day, causing severe hyponatremia, hypokalemia, and hypomagnesemia. Risk factors of high output stoma identified were routine prokinetic medication use and unresolved malignancy-related retroperitoneal abscess. Moreover, increment of food intake in the first days after surgery, specifically food high in insoluble fiber, was one of the contributing factors. High output stoma was then resolved by abscess drainage, discontinuation of prokinetic agent, and administration of antimotility agent. Hyponatremia and hypomagnesemia improved with correction, whereas hypokalemia needed longer time to resolve. Enteral nutrition was maintained and increased gradually to prevent further malnutrition. Oral hypotonic fluid intake was limited to 1000 mL/day and isotonic solution consumption was advised. High stoma production due to hypersecretory phase after ileostomy was expected, but thorough management would prevent patient’s deterioration that was caused by the fluid, electrolyte, and nutritional imbalances.

913 Role of Botulinum Toxin in the Medical Management of Respiratory Distress Secondary to Suspected Intraabdominal Hypertension After Abdominal Wall Reconstruction

Abstract Introduction Botulinum toxin (BTX) is a neurotoxin which causes functional denervation of muscles. Botulinum toxin type A (BTX) has been approved for a wide range of clinical applications. In addition, off-label preoperative injection of BTX is increasingly used for chemical component relaxation of the lateral abdominal wall muscles prior to abdominal wall reconstruction. Rationale Postoperative intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) with consequent organ dysfunction can be a potential complication after abdominal wall reconstruction. The IAH and ACS clinical practice guidelines suggest improving abdominal wall compliance in their medical management algorithm including neuromuscular blockade. Method Following an open retrorectus mesh repair with left component separation via transversus abdominis release of a midline incisional hernia, we report a case of postoperative respiratory distress and acute kidney injury suspected secondary to increasing intraabdominal hypertension due to ileus unresponsive to standard conservative measures including nasogastric tube insertion, use of prokinetic agents and judicious fluid management. We performed Botox A injection under ultrasound guidance to the lateral abdominal wall musculature. This resulted in improved abdominal wall compliance, consequent resolution of respiratory symptoms and reversal of acute renal injury with eventual resolution of ileus and a good post operative outcome. There was an increase in length of stay by 2 days compared to our average. The patient remains well at 3 months post operatively. Conclusions Botulinum Toxin A injection can be considered as adjunct in the medical management of IAH and ACS if it has not been used in the pre-operative setting.

Domperidone-associated Ventricular Arrhythmia and Sudden Cardiac Death: A Descriptive Literature Review

Background: Domperidone is an antiemetic and prokinetic agent that is widely used to treat nausea and vomiting, gastroparesis, and as a galactagogue. Objective: This review article focuses on QT prolongation, torsades de pointes, severe ventricular arrhythmia, and sudden cardiac death associated with the use of domperidone or domperidone-containing products. Methods: The online databases, such as Medline/Pubmed/PMC, Google Scholar, Science Direct, Ebsco, Scopus, Web of Science, Embase, and reference lists, were searched using keywords like Domperidone, Cardiotoxicity, QT prolongation, Cardiac arrhythmia, Torsades de pointes, Ventricular arrhythmia, and Sudden Cardiac Death, to identify published articles relevant to domperidone-associated cardiotoxicity. Results: Domperidone has been linked to an increased risk of QT prolongation, torsades de pointes, severe ventricular arrhythmia, and sudden cardiac death, according to a number of epidemiological studies and meta-analyses. Conclusion: Domperidone can only be used to treat nausea and vomiting in patients between the ages of 12 and 60, and a maximum daily dose of 30 mg has been set by a number of regulatory bodies. The risk of severe ventricular arrhythmia and sudden cardiac death caused by domperidone should be made clear to clinicians along with the recommendations from regulatory bodies to avoid any potential complications.