Characteristics and progression of childhood-onset and adult-onset eosinophilic esophagitis.

BACKGROUND AND AIM: The prevalence and incidence of eosinophilic esophagitis (EoE) has been increasing over recent years. However, the natural history remains incompletely understood particularly the differences in disease characteristics and progression of childhood-onset and adult-onset EoE. The aim of this study was to evaluate the disease characteristics and progression of childhood-onset and adult-onset EoE. METHODS: A cross-sectional, questionnaire-based study, on 87 adults and 67 children from 2 major tertiary hospitals in South Australia was conducted. Data of those who were diagnosed with EoE between 1999 and 2018 were collected and correlated with medical records. RESULTS: Of the 87 adults with EoE, 34 (39%) were diagnosed at the age of < 18 years (childhood-onset EoE). Reflux symptoms were more common in childhood-onset EoE, whereas asthma was more common in adult-onset EoE. The median duration of symptoms prior to diagnosis of EoE was > 1-4 years in childhood-onset disease (44%) and ≥ 10 years in adult-onset disease (34%). Food impaction was significantly more common on initial presentation in those with adult-onset EoE, whereas weight loss was more common in childhood-onset EoE. At the time of questionnaire, regurgitation, abdominal pain, and bloating were more common in childhood-onset EoE. Those with childhood-onset EoE were more likely to have multiple symptoms at questionnaire when compared with their adult-onset counterparts. In both groups, 15% (5/34 childhood-onset EoE and 8/53 adult-onset EoE) were asymptomatic at the time of questionnaire. CONCLUSION: Childhood-onset EoE appears to be a progressive disease from childhood to adulthood, however with more inflammatory-type symptoms post transition compared to those with adult-onset EoE.

Distal esophageal wall thickness correlates with dysphagia in adult patients with eosinophilic esophagitis.

BACKGROUND: Thickening of the esophageal wall in patients with eosinophilic esophagitis (EoE) and gastro-esophageal reflux disease (GERD) has been shown in studies using endoscopic ultrasound (EUS). We hypothesise that transmural inflammation in EoE results in prominent esophageal wall thickening compared with the mucosal inflammation in GERD. The aim of this study was to compare the relationship among dysphagia, endoscopic appearance, wall thickness, histology, and motility in EoE and GORD. METHODS: EoE and GERD patients were prospectively studied between February 2012 and April 2021. Patients were studied on 2 separate occasions with endoscopy, EUS and mucosal biopsies, followed by high-resolution manometry. Epidemiology and dysphagia data were obtained. RESULTS: A total of 45 patients (31 EoE, 14 GERD) were included. There were no significant differences in age, sex, duration of disease and presence of esophageal motility disorders. EoE patients had a higher dysphagia score (P < 0.001), EREFS score (P < 0.001) and peak eosinophil count (P < 0.001) compared with GERD patients. Thickness of the submucosa in the distal esophagus in EoE was significantly higher than GERD (P = 0.003) and positively correlated with duration of disease (P = 0.01, R = 0.67). Positive correlation was also found between dysphagia score and distal total esophageal wall thickness (P = 0.03, R = 0.39) in EoE patients. No correlation was found between these variables in GERD patients. CONCLUSION: Distal esophageal wall thickness positively correlates with dysphagia score in EoE but not GERD. This appears to be related to the composition of the submucosa which can be identified using EUS.

Incidence of Achalasia in South Australia Based on Esophageal Manometry Findings.

BACKGROUND & AIMS: Achalasia is a disorder of esophageal motility with a reported incidence of 0.5 to 1.6 per 100,000 persons per year in Europe, Asia, Canada, and America. However, estimates of incidence values have been derived predominantly from retrospective searches of databases of hospital discharge codes and personal communications with gastroenterologists, and are likely to be incorrect. We performed a cohort study based on esophageal manometry findings to determine the incidence of achalasia in South Australia. METHODS: We collected data from the Australian Bureau of Statistics on the South Australian population. Cases of achalasia diagnosed by esophageal manometry were identified from the 3 adult manometry laboratory databases in South Australia. Endoscopy reports and case notes were reviewed for correlations with diagnoses. The annual incidence of achalasia in the South Australian population was calculated for the decade 2004 to 2013. Findings were standardized to those of the European Standard Population based on age. RESULTS: The annual incidence of achalasia in South Australia ranged from 2.3 to 2.8 per 100,000 persons. The mean age at diagnosis was 62.1 ± 18.1 years. The incidence of achalasia increased with age (Spearman rho, 0.95; P < .01). The age-standardized incidence ranged from 2.1 (95% CI, 1.8-2.3) to 2.5 (95% CI, 2.2-2.7). CONCLUSIONS: Based on a cohort study of esophageal manometry, we determined the incidence of achalasia in South Australia to be 2.3 to 2.8 per 100,000 persons and to increase with age. South Australia's relative geographic isolation and the population's access to manometry allowed for more accurate identification of cases than hospital code analyses, with a low probability of missed cases.

Impedance-high resolution manometry analysis of patients with nonerosive reflux disease.

BACKGROUND & AIMS: Transient lower esophageal sphincter relaxations (TLESRs) contribute to episodes of reflux. Few studies have assessed the frequencies or compositions of TLESRs and reflux episodes in patients with reflux disease. We used combined high-resolution manometry and impedance monitoring to analyze reflux episodes and esophageal motility in these patients, compared with those of healthy individuals. METHODS: We evaluated the frequency of TLESRs and the relationship between the reflux pattern and esophageal pressures during TLESRs in 14 patients with nonerosive reflux disease (NERD) and 11 controls. Study participants underwent combined high-resolution manometry and impedance monitoring before and 60 minutes after a solid and liquid meal. The diagnosis of NERD was confirmed by a 24-hour pH impedance test. RESULTS: The frequency of TLESRs did not differ between patients with NERD and controls. In patients with NERD, TLESRs were associated more often with reflux episodes than in controls (93% ± 6% vs 66% ± 19%; P < .05). Patients with NERD had a higher percentage of pure liquid reflux episodes (33% ± 15% vs 10% ± 2%; P < .05), whereas controls had a higher percentage of mixed reflux episodes (45% ± 16% vs 67% ± 17% in patients with NERD; P < .05). Patients with NERD also had a higher percentage of reflux (liquid and mixed) associated with common cavities (74% ± 18% vs 50% ± 20% in controls; P < .05). CONCLUSIONS: In contrast to previous studies, we found that TLESRs are associated more often with reflux in patients with NERD than control subjects; this association increases when only liquid and mixed refluxes are considered. These findings indicate that factors involved in the occurrence of reflux in patients with NERD during TLESRs are different from those in healthy subjects.

Combined impedance-manometry for the evaluation of esophageal disorders.

PURPOSE OF REVIEW: Combined impedance-manometry was introduced just over 20 years ago for the assessment of esophageal motor function. Since then, technical developments have led to the introduction of high-resolution impedance-manometry (HRIM). However, analysis of the impedance and manometry recordings has remained separate and relatively unchanged since the introduction of HRIM, and it is unclear whether the addition of impedance has had a significant impact on the management of esophageal motor disorders. RECENT FINDINGS: The major technical advance over the past 12 months or so has been the development of automated impedance-manometry (AIM) analysis, in which the impedance and manometric data are analyzed together to assess the interactions between pressure and flow. This analysis has revealed subtle abnormalities in esophageal function in patients with nonobstructive dysphagia who have normal manometry and conventional impedance analyses. AIM analysis has also revealed preoperative characteristics in patients that may predict the occurrence of postfundoplication dysphagia. SUMMARY: Through ongoing technical development, impedance-manometry is becoming increasingly useful clinically to assess esophageal motility disorders as well as to provide further insights into esophageal physiology.

Complicated and uncomplicated peptic ulcer disease: altered symptom response to a nutrient challenge linked to gastric motor dysfunction.

BACKGROUND: Bleeding peptic ulcer (BPU) frequently occurs in the absence of preceding dyspeptic symptoms. We have observed that patients with BPU had a diminished symptom response to nutrient challenge test compared to uncomplicated peptic ulcer disease (uPUD). We postulated that more symptoms are manifest in patients with uPUD than BPU because there are greater derangements in gastric motor function. AIM: To assess gastric emptying in patients with BPU, uPUD and healthy controls (HC). METHODS: We studied 17 patients with BPU, 10 with uPUD, and 15 HC. After an 8-hour fast, subjects ingested 200 ml of an enteral feeding solution, containing 5 MBq (99m)Tc-rhenium sulphide colloid, every 5 min up to a cumulative volume of 800 ml. Gastric emptying was measured by scintigraphy for the total, proximal and distal stomach. RESULTS: Patients with uPUD had significantly higher gastric retention in the proximal and total stomach at 100 min than HC and BPU, while BPU had similar percent retention to HC. Patients with uPUD had significantly higher cumulative symptom response to the nutrient challenge than did HC and BPU, while BPU had similar symptom responses to HC. CONCLUSIONS: Patients with uPUD have significantly delayed gastric emptying compared to HC and BPU. Data suggest that in addition to alterations of visceral sensory function, altered gastric motor function occurs during a nutrient challenge in uPUD but not BPU. Gastric motor function may contribute to the manifestation of dyspeptic symptoms in PUD.

Objective outcomes 14 years after laparoscopic anterior 180-degree partial versus nissen fundoplication: results from a randomized trial.

OBJECTIVE: To investigate late objective outcomes 14 years after laparoscopic anterior 180-degree partial versus Nissen fundoplication. BACKGROUND: Clinical outcomes from randomized clinical trials suggest good outcomes for anterior 180-degree partial fundoplication, with similar control of reflux symptoms and less side effects, compared with Nissen fundoplication. However, objective outcomes at late follow-up have not been reported. METHODS: A subset of participants from a randomized trial of anterior 180-degree versus Nissen fundoplication underwent stationary esophageal high-resolution manometry and ambulatory 24-hour impedance-pH monitoring at 14 years' follow-up. The subset and other patients in the trial also completed a standardized clinical questionnaire to ensure that they were representative of the overall trial. RESULTS: Eighteen patients (8 anterior, 10 Nissen) underwent objective testing and had a symptom profile similar to those who did not (n = 59) have testing. Total esophageal acid exposure time and the total number of acid and weakly acidic reflux episodes per 24 hours were higher after anterior fundoplication than after Nissen fundoplication. Proximal, midesophageal and distal reflux were proportionately increased after anterior 180-degree fundoplication. The number of liquid and mixed reflux episodes was also higher after anterior fundoplication, which was accompanied by higher clinical heartburn scores. There were no differences in gas reflux, gastric belches, and supragastric belches, which is in line with the observation that gas-related symptoms were similar for both groups. Mean LES resting and relaxation nadir pressure were lower after anterior fundoplication, which was reflected by lower dysphagia scores. Patient satisfaction was similar after both procedures. CONCLUSIONS: At 14 years after randomization, this study demonstrated that acid, weakly acidic, liquid and mixed reflux episodes are more common after anterior 180-degree fundoplication than after Nissen fundoplication. On the contrary, gas reflux and gastric belching and patient satisfaction are similar for both procedures. Mean LES resting and relaxation nadir pressure are lower after anterior fundoplication. Overall, these findings suggest less effective reflux control after anterior 180-degree partial fundoplication, offset by less dysphagia, leading to a clinical outcome that is equivalent to Nissen fundoplication at late follow-up.

Sucrose malabsorption and impaired mucosal integrity in enterally fed critically ill patients: a prospective cohort observational study.

OBJECTIVE: Inadequate nutrition is common in critical illness due in part to gastric stasis. However, recent data suggest that altered small intestinal mucosal function may be a contributing factor. The aim of this study was to examine the effects of critical illness on sucrose absorption, permeability, and mucosal morphology. DESIGN: Prospective, observational study. SETTING: Tertiary critical care unit. SUBJECTS: Twenty mechanically ventilated patients (19 men; 52.2 ± 20.5 yr; 9 feed intolerant; Acute Physiology and Chronic Health Evaluation II score 16.2 ± 6.0) and 20 healthy subjects (14 men; 51.6 ± 21.5 yr). INTERVENTIONS: Following a 4-hr fast, a "meal" (100 kcal Ensure, 20-g enriched C-sucrose, 1.1 g rhamnose, 7.5 mL lactulose) was administered into the small intestine. Sucrose absorption was evaluated by analyzing 13CO2 concentration (cumulative percent of administered 13C dose recovered) in expiratory breath samples taken at timed intervals. At 90 minutes, a plasma lactulose/rhamnose concentration was also measured, with lactulose/rhamnose ratio, a marker of small intestinal mucosal permeability. When possible duodenal biopsies were taken in critically ill patients on insertion of the small intestinal feeding catheter and examined for disaccharidase levels and histology. Data are mean ± SD. RESULTS: When compared with healthy subjects, critically ill patients had significantly reduced cumulative CO2 recovery (90 min: 1.78% ± 1.98% vs. 8.04% ± 2.55%; p < 0.001) and increased lactulose/rhamnose ratio (2.77 ± 4.24 vs.1.10 ± 0.98; p = 0.03). The lactulose/rhamnose ratio was greater in feed-intolerant patients (4.06 ± 5.38; p = 0.003). In five patients, duodenal mucosal biopsy showed mild to moderate epithelial injury. Sucrase levels were normal in all patients. CONCLUSIONS: Sucrose absorption is reduced and intestinal permeability increased in critically ill patients, possibly indicating an impairment of small intestinal mucosal function. These results, however, are discordant with duodenal mucosal histology and sucrase levels. This may reflect an inactivation of sucrase in vivo or inadequate nutrient exposure to the brush border due to small intestinal dysmotility.

Performance of the Glasgow-Blatchford score in predicting clinical outcomes and intervention in hospitalized patients with upper GI bleeding.

BACKGROUND: Data regarding the utility of the Glasgow-Blatchford bleeding score (GBS) in hospitalized patients with upper GI hemorrhage are limited. OBJECTIVE: To evaluate the performance of the GBS in predicting clinical outcomes and the need for interventions in patients with upper GI hemorrhage. DESIGN: Prospective observational study. SETTING: Single, tertiary-care endoscopic center. PATIENTS: Between July 2010 and July 2012, 888 consecutive hospitalized patients managed for upper GI hemorrhage were entered into the study. INTERVENTION: GBS and Rockall scores. MAIN OUTCOME MEASUREMENTS: GBS and Rockall scores were prospectively calculated. The performance of these scores to predict the need for interventions and outcomes was assessed by using a receiver operating characteristic curve. RESULTS: Endoscopy was performed in 708 patients (80%). A total of 286 patients (40.3%) required endoscopic therapy, and 29 patients (3.8%) underwent surgery. GBS and post-endoscopy Rockall scores (post-E RS) were superior to pre-endoscopy Rockall scores in predicting the need for endoscopic therapy (area under the curve [AUC] 0.76 vs 0.76 vs 0.66, respectively) and rebleeding (AUC 0.71 vs 0.64 vs 0.57). The GBS was superior to Rockall scores in predicting the need for blood transfusion (AUC 0.81 vs 0.70 vs 0.68) and surgery (AUC 0.71 vs 0.64 vs 0.51). Patients with GBS scores ≤ 3 did not require intervention. LIMITATIONS: Subjective decision making as to need for endoscopic therapy and blood transfusion. CONCLUSION: Compared with post-E RS, the GBS was superior in predicting the need for blood transfusion and surgery in hospitalized patients with upper GI hemorrhage and was equivalent in predicting the need for endoscopic therapy, rebleeding, and death. There are potential cutoff GBS scores that allow risk stratification for upper GI hemorrhage, which warrant further evaluation.

Patient-controlled analgesia with inhaled methoxyflurane versus conventional endoscopist-provided sedation for colonoscopy: a randomized multicenter trial.

OBJECTIVE: Inhaled methoxyflurane (Penthrox, Medical Device International, Melbourne, Australia) has been used extensively in Australasia (Australia and New Zealand) to manage trauma-related pain. The aim is to evaluate the efficacy, safety, and outcome of Penthrox for colonoscopy. DESIGN: Prospective randomized study. SETTING: Three tertiary endoscopic centers. PATIENTS: Two hundred fifty-one patients were randomized to receive either Penthrox (n = 125, 70 men, 51.4 ± 1.1 years old) or intravenous midazolam and fentanyl (M&F; n = 126, 72 men, 54.9 ± 1.1 years old) during colonoscopy. MAIN OUTCOME MEASUREMENT: Discomfort (visual analogue scale [VAS] pain score), anxiety (State-Trait Anxiety Inventory Form Y [STAI-Y] anxiety score), colonoscopy performance, adverse events, and recovery time. RESULTS: Precolonoscopy VAS pain and STAI-Y scores were comparable between the 2 groups. There were no differences between groups in (1) pain VAS or STAI Y-1 anxiety scores during or immediately after colonoscopy, (2) procedural success rate (Penthrox: 121/125 vs M&F: 124/126), (3) hypotension during colonoscopy (7/125 vs 8/126), (4) tachycardia (5/125 vs 3/126), (5) cecal arrival time (8 ± 1 vs 8 ± 1 minutes), or (6) polyp detection rate (30/125 vs 43/126). Additional intravenous sedation was required in 10 patients (8%) who received Penthrox. Patients receiving Penthrox alone had no desaturation (oxygen saturation [SaO(2)] < 90%) events (0/115 vs 5/126; P = .03), awoke quicker (3 ± 0 vs 19 ± 1 minutes; P < .001) and were ready for discharge earlier (37 ± 1 vs 66 ± 2 minutes; P < .001) than those receiving intravenous M&F. LIMITATIONS: Inhaled Penthrox is not yet available in the United States and Europe. CONCLUSIONS: Patient-controlled analgesia with inhaled Penthrox is feasible and as effective as conventional sedation for colonoscopy with shorter recovery time, is not associated with respiratory depression, and does not influence the procedural success and polyp detection.

Changing epidemiology of food bolus impaction: is eosinophilic esophagitis to blame?

BACKGROUND AND AIM: Data on the relationship between epidemiological changes in food bolus impaction (FBI) and its relationship to eosinophilic esophagitis (EoE) are limited. The aim of this study was to evaluate changes in the prevalence and etiology of FBI at the Royal Adelaide Hospital over 15 years. METHODS: Details of all patients who presented with FBI to Royal Adelaide Hospital (1996-2010) were reviewed from a prospective database. Detailed endoscopic and histological findings were examined for patients admitted under the Gastroenterology team. RESULTS: From 1996-2010, 539 patients were admitted. Prevalence of FBI increased overtime, with a male preponderance. The age at presentation was significantly lower in 2006-2010 (56.2 ± 1.6 years) compared with 2001-2005 (61.6 ± 1.9 years, P=0.03). There was a reduction in the proportion of patients with peptic-related stricture (from 75% [1996-2000] to 41% [2006-2010] [P<0.001]) and an increase in the prevalence of EoE (from 0% [1996-2000] to 35% [2006-2010], P<0.001). The proportion of patients who had esophageal biopsies taken at the index endoscopy also increased (8% [1996-2000] vs 28% [2001-2005] and 61% [2006-2010], P<0.01). There were no significant changes in rate of malignancy or post-surgical strictures. Endoscopic removal of food bolus was required in 86% of cases and, of these, 98% were successful with no complication or death. CONCLUSIONS: The prevalence of FBI has increased over the last 15 years. This was associated with an increased prevalence of EoE and a reduction in age of presentation and peptic-related strictures. These findings suggest that EoE is an important cause of FBI and that esophageal mucosal biopsy should be performed in all cases of FBI.

Increase in distal esophageal wall thickness with time in adult patients with eosinophilic esophagitis.

Background and Aim: Eosinophilic esophagitis (EoE) is a chronic disease which may progress to a fibro-stenotic phenotype due to esophageal sub-epithelial fibrosis. Esophageal wall thickening in patients with EoE has been demonstrated in a few studies using endoscopic ultrasound (EUS). The aim of this study was to longitudinally assess the endoscopic appearance, wall thickness, histology, and dysphagia score of EoE patients. Methods: Patients with EoE were recruited and studied between February 2012 and April 2021. Patients were evaluated on two separate occasions at least 12 months apart with endoscopy, EUS, and esophageal mucosal biopsies. The dysphagia score and epidemiology data were also assessed. Results: A total of 16 EoE patients were included with a mean follow-up duration of 2.2 ± 1.2 years. In 14/16 (88%) patients, the total wall thickness of the distal esophagus significantly increased (P = 0.0012) as a result of thickening of the muscularis propria (P = 0.0218). However, only 1/14 (7%) patient had an increase in the dysphagia score, while 8/14 (57%) and 5/14 (36%) had a stable and reduced dysphagia score, respectively. No differences were found in the total thickness of other esophageal regions, dysphagia score, endoscopic appearance, and eosinophil count over time. Conclusion: Distal esophageal wall thickness increases with time in EoE patients, independent of the dysphagia score and eosinophil count.

Delayed enteral feeding impairs intestinal carbohydrate absorption in critically ill patients.

OBJECTIVES: Delay in initiating enteral nutrition has been reported to disrupt intestinal mucosal integrity in animals and to prolong the duration of mechanical ventilation in humans. However, its impact on intestinal absorptive function in critically ill patients is unknown. The aim of this study was to examine the impact of delayed enteral nutrition on small intestinal absorption of 3-O-methyl-glucose. DESIGN: Prospective, randomized study. SETTING: Tertiary critical care unit. PATIENTS: Studies were performed in 28 critically ill patients. INTERVENTIONS: Patients were randomized to either enteral nutrition within 24 hrs of admission (14 "early feeding": 8 males, 6 females, age 54.9 ± 3.3 yrs) or no enteral nutrition during the first 4 days of admission (14 "delayed feeding": 10 males, 4 females, age 56.1 ± 4.2 yrs). MEASUREMENTS AND MAIN RESULTS: Gastric emptying (scintigraphy, 100 mL of Ensure (Abbott Australia, Kurnell, Australia) with 20 MBq Tc-suphur colloid), intestinal absorption of glucose (3 g of 3-O-methyl-glucose), and clinical outcomes were assessed 4 days after intensive care unit admission. Although there was no difference in gastric emptying, plasma 3-O-methyl-glucose concentrations were less in the patients with delayed feeding compared to those who were fed earlier (peak: 0.24 ± 0.04 mmol/L vs. 0.37 ± 0.04 mmol/L, p < .02) and integrated (area under the curve at 240 mins: 38.5 ± 7.0 mmol/min/L vs. 63.4 ± 8.3 mmol/min/L, p < .04). There was an inverse correlation between integrated plasma concentrations of 3-O-methyl-glucose (area under the curve at 240 mins) and the duration of ventilation (r = -.51; p = .006). In the delayed feeding group, both the duration of mechanical ventilation (13.7 ± 1.9 days vs. 9.2 ± 0.9 days; p = .049) and length of stay in the intensive care unit (15.9 ± 1.9 days vs. 11.3 ± 0.8 days; p = .048) were greater. CONCLUSIONS: In critical illness, delaying enteral feeding is associated with a reduction in small intestinal glucose absorption, consistent with the reduction in mucosal integrity after nutrient deprivation evident in animal models. The duration of both mechanical ventilation and length of stay in the intensive care unit are prolonged. These observations support recommendations for "early" enteral nutrition in critically ill patients.

Current and future techniques in the evaluation of dysphagia.

Dysphagia is common in the general population, and is generally due to either mechanical obstruction or dysmotility. Patient demographics and symptom evaluation are often useful in determining the likely cause, and guide subsequent investigation and management. Oropharyngeal dysphagia is usually caused by neurological conditions where treatment options are limited. Conversely, many of the esophageal causes of dysphagia are amenable to therapy. Gastroscopy is often the first test of choice, given its diagnostic and therapeutic potential, especially when mechanical causes are concerned. Esophageal motor function can be assessed by a variety of techniques, ranging from radiology such as barium swallow, to dedicated motility tests such as manometry and impedance monitoring. The choice of test relies on the clinical indication and the results should be interpreted in conjunction with the patients' symptoms. High-resolution manometry with topography is now the new benchmark for motility studies. Several new techniques for motility testing have also become available, such as esophageal ultrasound and functional lumen imaging probe, but are currently limited to the research setting.

Plasma erythromycin concentrations predict feeding outcomes in critically ill patients with feed intolerance.

OBJECTIVE: Motilin receptors are rapidly down-regulated by exposure to erythromycin, and its progressive loss of clinical prokinetic effect may relate to higher plasma drug concentrations. This study aimed to evaluate the relationship between plasma erythromycin concentrations and feeding outcomes in critically ill patients. DESIGN: Observational comparative study. SETTING: Tertiary critical care unit. PATIENTS: Twenty-nine feed-intolerant (gastric residual volume >250 mL) mechanically ventilated, medical critically ill patients. INTERVENTIONS: Patients received intravenous erythromycin 200 mg twice daily for feed intolerance. MEASUREMENTS: Plasma erythromycin concentrations were measured 1 and 7 hrs after drug administration on day 1. Success of enteral feeding, defined as 6-hourly gastric residual volume of ≤ 250 mL with a feeding rate ≥ 40 mL/h, was recorded over 7 days. RESULTS: At day 7, 38% (11 of 29) of patients were feed tolerant. Age, Acute Physiology and Chronic Health Evaluation scores, serum glucose concentrations, and creatinine clearance were comparable between successful and failed feeders. Both plasma erythromycin concentrations at 1 and 7 hrs after drug administration were significantly lower in successfully treated patients compared to treatment failures (1 hr: 3.7 ± 0.8 mg/L vs. 7.0 ± 1.0 mg/L, p = .02; and 7 hr: 0.7 ± 0.3 mg/L vs. 2.8 ± 0.6 mg/L, p = .01). There was a negative correlation between the number of days to failure of feeding and both the 1-hr (r = -.47, p = .049) and 7-hr (r = -.47, p = .050) plasma erythromycin concentrations. A 1-hr plasma concentration of >4.6 mg/L had 72% sensitivity and 72% specificity, and a 7-hr concentration of ≥ 0.5 mg/L had 83% sensitivity and 72% specificity in predicting loss of response to erythromycin. CONCLUSIONS: In critically ill feed-intolerant patients, there is an inverse relationship between plasma erythromycin concentrations and the time to loss of clinical motor effect. This suggests that erythromycin binding to motilin receptors contributes to variations in the duration of prokinetic response. The use of lower doses of erythromycin and tailoring the dose of erythromycin according to plasma concentrations may be useful strategies to reduce erythromycin tachyphylaxis.

Effects of metoclopramide on duodenal motility and flow events, glucose absorption, and incretin hormone release in response to intraduodenal glucose infusion.

The contribution of small intestinal motor activity to nutrient absorption is poorly defined. A reduction in duodenal flow events after hyoscine butylbromide, despite no change in pressure waves, was associated with reduced secretion of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and a delay in glucose absorption. The aim of this study was to investigate the effect of metoclopramide on duodenal motility and flow events, incretin hormone secretion, and glucose absorption. Eight healthy volunteers (7 males and 1 female; age 29.8 ± 4.6 yr; body mass index 24.5 ± 0.9 kg/m²) were studied two times in randomized order. A combined manometry and impedance catheter was used to measure pressure waves and flow events in the same region of the duodenum simultaneously. Metoclopramide (10 mg) or control was administered intravenously as a bolus, followed by an intraduodenal glucose infusion for 60 min (3 kcal/min) incorporating the ¹4C-labeled glucose analog 3-O-methylglucose (3-OMG). We found that metoclopramide was associated with more duodenal pressure waves and propagated pressure sequences than control (P < 0.05 for both) during intraduodenal glucose infusion. However, the number of duodenal flow events, blood glucose concentration, and plasma 3-[¹4C]OMG activity did not differ between the two study days. Metoclopramide was associated with increased plasma concentrations of GLP-1 (P < 0.05) and GIP (P = 0.07) but lower plasma insulin concentrations (P < 0.05). We concluded that metoclopramide was associated with increased frequency of duodenal pressure waves but no change in duodenal flow events and glucose absorption. Furthermore, GLP-1 and GIP release increased with metoclopramide, but insulin release paradoxically decreased.

Association between clinical manifestations of complicated and uncomplicated peptic ulcer and visceral sensory dysfunction.

BACKGROUND AND AIMS: Peptic ulcer disease (PUD) usually manifests as either dyspepsia or less commonly with complications such as bleeding. Patients with bleeding ulcers are often asymptomatic until the bleeding occurs. A lack of dyspeptic symptoms might be explained by impaired visceral sensory function. The aim of this study was to assess symptom profiles and compare visceral sensory thresholds in patients with bleeding peptic ulcer (BPU) and uncomplicated PUD. METHODS: A total of 30 patients with BPU, 25 with uncomplicated PUD and 32 healthy controls (HC) without dyspeptic symptoms were recruited. In ulcer patients after at least 8 weeks of ulcer treatment and an 8-hr fast, visceral sensitivity was tested using a standardized nutrient challenge with an enteral feeding solution. Five key symptoms (fullness, abdominal pain, retrosternal/abdominal burning, nausea, and regurgitation) were assessed using visual analog scales (0-100). RESULTS: Twenty-five of the 30 (83%, 95% confidence interval 65-94%) patients with BPU had no dyspeptic symptoms compared with none of the 25 uncomplicated PUD patients. Patients with BPU and HC had significantly lower symptom responses (BPU 127.6 +/- 24.6, HC 89.8 +/- 13.9) to the nutrient challenge than uncomplicated PUD patients (338.4 +/- 56.2, P < 0.0001). Patients with dyspeptic symptoms (30/55) had significantly higher symptom responses (327.3 +/- 47.8) than the 25/55 patients without symptoms (98.9 +/- 23.4, P < 0.0001). CONCLUSION: Most patients with BPU present without dyspeptic symptoms. Even after healing of the ulcer, patients with uncomplicated PUD have a significantly augmented symptom response to a standardized nutrient challenge compared to patients with complicated ulcers and HC. Differences in the processing of upper gastrointestinal visceral afferents may play a major role in the clinical presentation (complicated vs uncomplicated) of PUD.

Beyond acid suppression: new pharmacologic approaches for treatment of GERD.

Proton pump inhibitors are highly successful in treating gastroesophageal reflux disease, but a significant proportion of patients have persistent symptoms from weakly or nonacidic reflux. Transient lower esophageal sphincter relaxation (TLESR) represents the dominant mechanism of gastroesophageal reflux and has therefore become the most intensely investigated therapeutic target. The triggering of TLESR involve the vagal pathways and the gamma-aminobutyric type B (GABA(B)) and metabotropic glutamate type 5 (mGluR5) receptors. Baclofen is a GABA(B) receptor agonist that is effective in inhibiting TLESR and reducing the number of reflux episodes, but is associated with significant central nervous system (CNS) side effects. The newer GABA(B) agonists, such as AZD9343 and AZD3355, and mGluR5 antagonists, such as 2-methyl-6-(phenylethynyl)-pyridine (MPEP), have been shown in small, randomized, controlled trials to have comparable efficacy to baclofen, but possibly a more favorable CNS side effect profile. Cannibinoid agonists, such as Delta(9)-THC, have also been demonstrated to reduce TLESRs and reflux events respectively. Macrolide antibiotics (eg, erythromycin) show early promise in a select group of patients with possible reflux associated post-lung transplant problems.

The impact of delaying enteral feeding on gastric emptying, plasma cholecystokinin, and peptide YY concentrations in critically ill patients.

BACKGROUND: Enteral nutrient (EN) deprivation slows gastric emptying (GE) and increases plasma cholecystokinin (CCK) concentrations in healthy humans and may potentially contribute to the delayed GE in the critically ill. This study examined the impact of delayed feeding on GE, plasma CCK, and peptide YY (PYY) concentrations in the critically ill. DESIGN: Randomized controlled trial. SETTING: Mixed medical and surgical intensive care unit (ICU). INTERVENTIONS: Twenty-eight critically ill patients were randomized to receive EN either within 24 hrs of admission ("early feeding": 54.9 +/- 3.3 yrs; Acute Physiology and Chronic Health Evaluation (APACHE) II = 23.0 +/- 1.8) or on day 4 of admission after GE assessment ("delayed feeding": 56.1 +/- 4.2 yrs, APACHE II = 21.7 +/- 1.8). GE of 100 ml of Ensure was measured using scintigraphy on day 4 of admission. Blood was sampled for measurement of plasma CCK, PYY, and glucose concentrations. RESULTS: Demographics, APACHE II score, use of inotrope and morphine sedation were similar between the groups. The mean administered/prescribed caloric ratio in the "early feeding" group was 72 +/- 4%. There were no differences in the retention of meal, intragastric meal distribution, proportion of patients with delayed GE (9/14 vs. 9/14), and plasma CCK and PYY concentrations during fasting and postprandially between the two groups. There was no relationship between the number of calories received and percentage of meal retention at 240 min (p > .05). However, delayed feeding was associated with longer duration of mechanical ventilations (13.7 +/- 1.9 vs. 9.2 +/- .9 days, p = .049) and length of stay in ICU (15.9 +/- 1.9 vs. 11.3 +/- 0.8 days, p = .048), but no difference in mortality. CONCLUSIONS: In critical illness, delayed enteral feeding appears to have little impact on either GE or the enterogastric feedback hormones. However, the association between delayed feeding and increased duration of ventilation and length of stay in the ICU supports the current recommendation that enteral nutrition should be commenced early.

Diminished functional association between proximal and distal gastric motility in critically ill patients.

OBJECTIVE: This study examined the effects of critical illness on the relationship between proximal and distal gastric motor activity during fasting and duodenal nutrient stimulation. DESIGN: Prospective, case-controlled study. PATIENTS AND PARTICIPANTS: Ten critically ill patients and ten healthy volunteers. INTERVENTIONS: Concurrent proximal gastric (barostat) and antro-pyloro-duodenal (manometry) motility were recorded during fasting and during two 60-min duodenal nutrient infusions (Ensure at 1 kcal/min and 2 kcal/min) in random order, separated by a 2-h wash-out period. RESULTS: Baseline proximal gastric volumes were similar between the two groups. At 10 min nutrient-induced fundic relaxation was lower in patients than healthy subjects (45 +/- 26 vs. 196 +/- 29 ml). In patients the frequency and volume amplitude of fundic waves were also lower. There were fewer propagated antral waves in patients than in healthy subjects during both fasting and nutrient infusion. These were more retrograde, shorter in length and associated with a pyloric contraction. The proportion of fundic waves followed by a distally propagated antral wave was significantly less in patients (0%, 0-8%) than controls 36% (11-44%). CONCLUSIONS: In critical illness, in addition to impairment of proximal and distal gastric motor activity, the association between the two gastric regions is abnormal. This disturbance may interfere with meal distribution and further contribute to slow gastric emptying in these patients.