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Dysphagia is a common problem affecting all ages. It is increasing in frequency particularly among the younger population due to the rising incidence of eosinophilic oesophagitis, a condition which often leads to acute presentation to hospital for the first time with food bolus obstruction requiring endoscopic removal. Careful history taking remains the first and most important step in evaluating dysphagia, and it is especially important to distinguish an oropharyngeal versus oesophageal origin, which helps to guide further investigation and therapy. The three main investigations for dysphagia remain endoscopy, barium study and manometry, with endoscopy also offering therapeutic potential. Management is largely determined by the eventual diagnosis, often in a multi-disciplinary setting.

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.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.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.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.

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.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.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.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.

Introduction Night-time gastroesophageal reflux (nGER) symptoms are commonly associated with interrupted sleep. Most studies attempting to understand the relationship between sleep, arousal, and nGER events have been performed so using accelerometry; however, this technology is limited in its ability to precisely determine the temporal association between sleep and reflux events. We aimed to examine the temporal relationships between nGER events and arousal/awakening from sleep using high resolution, in-laboratory polysomnography (PSG). Methods Individuals between 18 and 70 years who had undergone a gastroscopy within 12 months underwent simultaneous 24-hour pH/impedance monitoring and in-laboratory PSG. The temporal relationship between each nGER event and sleep/arousals/awakenings was determined for each participant. Analyses were limited to the sleep period (between "lights out" and time of final waking). Results Analyses were conducted on the data from 25 individuals, 64% of whom had nGER episodes (5 ± 5 events per person, range 1-18) and 64% of whom had obstructive sleep apnea (OSA, mean apnea-hypopnea index 20 ± 11 events/hr, range 6-44). There were no differences in PSG-determined sleep duration, sleep efficiency, sleep architecture, arousals/awakenings, or sleep apnea severity between those with nGER and those without. Most nGER events (82%) occurred during a PSG epoch that had been classified as wake. Arousals/awakenings preceded almost all events (73/76), whereas fewer had an arousal/awakening after the event (15/76). Discussion As opposed to what is typically assumed, nGER does not seem to cause arousal from sleep, but rather arousal from sleep predisposes to nGER.

BACKGROUND: Treatment options for achalasia include endoscopic and surgical techniques that carry the risk of esophageal bleeding and perforation. The rare coexistence of esophageal varices has only been anecdotally described and treatment is presumed to carry additional risk. METHODS: Experience from physicians/surgeons treating this rare combination of disorders was sought through the International Manometry Working Group. RESULTS: Fourteen patients with achalasia and varices from seven international centers were collected (mean age 61 ± 9 years). Five patients were treated with botulinum toxin injections (BTI), four had dilation, three received peroral endoscopic myotomy (POEM), one had POEM then dilation, and one patient underwent BTI followed by Heller's myotomy. Variceal eradication preceded achalasia treatment in three patients. All patients experienced a significant symptomatic improvement (median Eckardt score 7 vs 1; p

Background Achalasia can be subdivided into manometric subtypes according to the Chicago classification. These subtypes are proposed to predict outcome after treatment. This hypothesis was tested using a database of patients who underwent laparoscopic Heller's cardiomyotomy with anterior fundoplication. Methods All patients who underwent Heller's cardiomyotomy for achalasia between June 1993 and March 2015 were identified from an institutional database. Manometry tracings were retrieved and re-reported according the Chicago classification. Outcome was assessed by a postal questionnaire, and designated a success if the modified Eckardt score was 3 or less, and the patient had not undergone subsequent surgery or pneumatic dilatation. Difference in outcome after cardiomyotomy was analysed with a mixed-effects logistic regression model. Results Sixty, 111 and 24 patients had type I, II and II achalasia respectively. Patients with type III achalasia were more likely to be older than those with type I or II (mean age 63 versus 50 and 49 years respectively; P = 0·001). Some 176 of 195 patients returned questionnaires after surgery. Type III achalasia was less likely to have a successful outcome than type II (odds ratio (OR) 0·38, 95 per cent c.i. 0·15 to 0·94; P = 0·035). There was no significant difference in outcome between types I and II achalasia (II versus I: OR 0·87, 0·47 to 1·60; P 0·663). The success rate at 3-year follow-up was 69 per cent (22 of 32) for type I, 66 per cent (33 of 50) for type II and 31 per cent (4 of 13) for type III. Conclusion Type III achalasia is a predictor of poor outcome after cardiomyotomy. There was no difference in outcome between types I and II achalasia.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

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. 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. 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.

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.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.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).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.

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 99mTc-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.

This item is under embargo for a period of 12 months from the date of publication, in accordance with the publisher's policy., At 14 years after randomization, this study demonstrated that acid, weakly acidic, liquid and mixed reflux episodes are more common after anterior 180˚ fundoplication compared to Nissen fundoplication, although gas reflux and gastric belching and patient satisfaction are similar for both procedures., Support by a University Medical Center Utrecht Alexandre Suerman MD/PhD grant (to J.A.B.). Support for the randomized controlled trial from which the patient cohort was obtained, has been provided by Research Project Grants from the National Health and Medical Research Council (NHMRC) of Australia (grant numbers – 157986 & 375111).

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.Prospective, observational study.Tertiary critical care unit.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).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.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%; p0.001) 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.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.

Scintigraphy is considered the most accurate technique for the measurement of gastric emptying (GE) but, for patients in the intensive care unit, it is technically demanding, involves radiation and can interfere with care. The (13)C-octanoate breath test ((13)C-OBT) is a simple, non-invasive technique that does not involve radiation exposure.To evaluate the performance of the (13)C-OBT in the assessment of GE in critically ill patients.The GE was assessed in 33 mechanically ventilated patients (23 M; 54.3 ± 3.0 yrs; APACHE II: 22.0 ± 1.1). Following test meal administration (100 ml Ensure(®)), concurrent scintigraphic measurement and breath samples ((13)C-OBT) were collected over 4 h. Scintigraphic meal retention was determined and the gastric emptying coefficient (GEC) and half emptying time [t50(BT)] were calculated for the (13)C-OBT. Delayed GE was defined as meal retention13 % at 180 min.Delayed GE was identified in 27/33 patients. Meal retention correlated modestly with t50(BT) (r = 0.55-0.66; P 0.001) and well with GEC (r = -0.63 to -0.74; P 0.0001). The strength of agreement between the two techniques was highest between GEC and retention at 120 min. The best cut-off GEC for defining delayed GE was 3.25 (AUC = 0.75; 95 % CI = 0.52-0.99; P = 0.05), with 89 % sensitivity and 67 % specificity to detect delayed GE. The GE was delayed in all (23/23) patients with feed intolerance (GRV250 ml) on scintigraphy and 91 % (21/23) patients on (13)C-OBT.In critical illness, there was a correlation between (13)C-OBT and gastric scintigraphy, with GEC performing as a better and more sensitive marker of detecting delayed GE than t50. However the relatively wide 95 % confidence intervals suggest that (13)C-OBT is more suitable as a technique to assess GE in a group setting for research studies rather than for individual patients in clinical practice.

BACKGROUND: Criteria for transient lower esophageal sphincter relaxations (TLESRs) are well-defined for Dentsleeve manometry. As high-resolution manometry (HRM) is now the gold standard to assess esophageal motility, our aim was to propose a consensus definition of TLESRs using HRM. METHODS: Postprandial esophageal HRM combined with impedance was performed in 10 patients with gastroesophageal reflux disease. Transient lower esophageal sphincter relaxations identification was performed by 17 experts using a Delphi process. Four investigators then characterized TLESR candidates that achieved 100% agreement (TLESR events) and those that achieved less than 25% agreement (non-events) after the third round. Logistic regression and decision tree analysis were used to define optimal diagnostic criteria. KEY RESULTS: All diagnostic criteria were more frequently encountered in the 57 TLESR events than in the 52 non-events. Crural diaphragm (CD) inhibition and LES relaxation duration >10 seconds had the highest predictive value to identify TLESR. Based on decision tree analysis, reflux on impedance, esophageal shortening, common cavity, upper esophageal sphincter relaxation without swallow and secondary peristalsis were alternate diagnostic criteria. CONCLUSION & INFERENCES: Using HRM, TLESR might be defined as LES relaxation occurring in absence of swallowing, lasting more than 10 seconds and associated with CD inhibition.

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.Prospective, randomized study.Tertiary critical care unit.Studies were performed in 28 critically ill patients.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).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.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.

Context: Acute hyperglycemia slows gastric emptying, but its effects on small intestinal motor activity and glucose absorption are unknown. In type 2 diabetes, the postprandial secretion of glucose-dependent insulinotropic polypeptide (GIP) is preserved, but that of glucagon-like peptide-1 (GLP-1) ispossibly reduced; whether the latter is secondary to hyperglycemia or diabetes per se is unknown. Aim: The aim was to investigate the effects of acute hyperglycemia on duodenal motility and flowevents, glucose absorption, and incretin hormone secretion. Methods: Nine healthy volunteers were studied on two occasions. A combined manometry/impedance catheter was positioned in the duodenum. Blood glucose was clamped at either 9 mmol/liter (hyperglycemia) or 5 mmol/liter (euglycemia) throughout the study. Manometry and impedance recordings continued between T 10 min and T 180 min. Between T 0 and 60 min, an intraduodenal glucose infusion was given (3 kcal/min), together with 14C-labeled 3-O-methylglucose (3-OMG) to evaluate glucose absorption. Results: Hyperglycemia had no effect on duodenal pressure waves or flow events during the 60 min of intraduodenal glucose infusion, when compared to euglycemia. During hyperglycemia, there was an increase in plasma GIP (P 0.05) and 14C-3-OMG (P 0.05) but no effect on GLP-1 concentrations in response to the intraduodenal infusion, compared to euglycemia. Conclusion: Acute hyperglycemia in the physiological range has no effect on duodenal pressurewaves and flow events but is associated with increased GIP secretion and rate of glucose absorptionin response to intraduodenal glucose. Refereed/Peer-reviewed

To evaluate the effects of sedation with morphine and midazolam (MM) versus propofol on gastric emptying in critically ill patients.Descriptive study.Mixed medical and surgical intensive care unit.Thirty-six unselected, mechanically ventilated, critically ill patients.Gastric scintigraphic data were analysed retrospectively according to whether patients were receiving MM (n=20; 14M, 6F) or propofol (n=16; 7M, 9F). Measurements were performed over 4 h after administration of 100 ml of Ensure, labelled with 20 MBq Tc99m.Gastric half-emptying time (t1/2) and total and regional (proximal and distal stomach) meal retention (%) were assessed. The median t1/2 of patients receiving MM (153 (IQR: 72-434) min) was significantly longer than that of patients receiving propofol (58 (34-166) min, p=0.02). Total gastric retention was greater in patients receiving MM compared to those receiving propofol (p0.01). Proximal (p=0.02) but not distal (p=0.80) gastric retention was greater in patients who received MM. Patients who received MM were more likely to haveor=5% meal retention at 240 min than those treated with propofol (95% (19/20) vs. 56% (9/16); p=0.01). Changes in blood glucose concentrations during the study were similar in the two groups.In critical illness, patients receiving MM for sedation are more likely to have slow gastric emptying, and proximal meal retention than those receiving propofol. The apparent beneficial effects of propofol-based sedation need confirmation by a prospective randomised controlled study.

Background and Aim: The pathophysiology of non-erosive reflux disease is poorly understood. Triggering of secondary peristalsis is impaired in patients with erosive esophagitis but data in patients with non-erosive reflux disease are lacking. The aim of this study was to evaluate the difference in esophageal motility between patients with non-erosive reflux disease and healthy subjects. Methods: Twenty patients with non-erosive reflux disease, with reflux symptoms occurring more than twice per week, and 20 healthy subjects of comparable age and sex underwent esophageal manometry. Primary peristalsis was tested with 10 swallows of a 5-mL water bolus. Secondary peristalsis was triggered by esophageal distention using a 20-mL air bolus, which was injected rapidly into the mid-esophagus. After 20 s, each stimulus was followed by a dry swallow to clear any residual air and then each stimulus was repeated five times. Results: Basal lower esophageal sphincter pressure, pressure wave amplitude in the upper, middle and lower esophagus, wave velocity and the rates of successful primary peristalsis were similar in non-erosive reflux disease patients and controls. The rate of triggering of secondary peristalsis in patients with non-erosive reflux disease (median 20%, interquartile range 0–40%) was significantly lower (P

Objective: To compare the efficacy of combination therapy, with erythromycin and metoclopramide, to erythromycin alone in the treatment of feed intolerance in critically ill patients. Design: Randomized, controlled, double-blind trial. Setting: Mixed medical and surgical intensive care unit. Patients: Seventy-five mechanically ventilated, medical patients with feed intolerance (gastric residual volume ≥250 mL). Interventions: Patients received either combination therapy (n = 37; 200 mg of intravenous erythromycin twice daily + 10 mg of intravenous metoclopramide four times daily) or erythromycin alone (n = 38; 200 mg of intravenous erythromycin twice daily) in a prospective, randomized fashion. Gastric feeding was re-commenced and 6-hourly gastric aspirates performed. Patients were studied for 7 days. Successful feeding was defined as a gastric residual volume

To assess the relationship between blood glucose concentrations (BSL) and intolerance to gastric feeding in critically ill patients. Prospective, case-controlled study. Two-hourly BSL and insulin requirements over the first 10 days after admission were assessed in 95 consecutive feed-intolerant (NG aspirate > 250 ml during feed) critically ill patients and 50 age-matched, feed-tolerant patients who received feeds for at least 3 days. Patients with diabetes mellitus were excluded. A standard insulin protocol was used to maintain BSL at 5.0–7.9 mmol. The peak BSLs were significantly higher before and during enteral feeding in feed-intolerant patients. The mean and trough BSLs were, however, similar between the two groups on admission, 24 h prior to feeding and for the first 4 days of feeding. The variations in BSLs over 24 h before and during enteral feeding were significantly greater in feed-intolerant patients. A BSL greater than 10 mmol/l was more prevalent in patients with feed intolerance during enteral feeding. The time taken to develop feed intolerance was inversely related to the admission BSL (r = –0.40). The amount of insulin administered before and during enteral feeding was similar between the two groups. Feed intolerance in critically ill patients is associated with a greater degree of glycaemic variation, with a greater number of patients with transient hyperglycaemia. These data suggest more intensive insulin therapy may be required to minimize feed intolerance, an issue that warrants further study.

A functional integration exists between proximal and distal gastric motor activity in dogs but has not been demonstrated in humans. To determine the relationship between proximal and distal gastric motor activity in humans. Concurrent proximal (barostat) and distal (antro-pyloro-duodenal (APD) manometry) gastric motility were recorded in 10 healthy volunteers (28 +/- 3 years) during (i) fasting and (ii) two 60-min duodenal infusions of Ensure((R)) (1 and 2 kcal min(-1)) in random order. Proximal and APD motor activity and the association between fundic and propagated antral waves (PAWs) were determined. During fasting, 32% of fundic waves (FWs) were followed by a PAW. In a dose-dependent fashion, duodenal nutrients (i) increased proximal gastric volume, (ii) reduced fundic and antral wave (total and propagated) activity, and (iii) increased pyloric contractions. The proportion of FWs followed by a distal PAW was similar between both infusions and did not differ from fasting. During nutrient infusion, nearly all PAWs were antegrade, propagated over a shorter distance and less likely to traverse the pylorus, compared with fasting. In humans, a functional association exists between proximal and distal gastric motility during fasting and duodenal nutrient stimulation. This may have a role in optimizing intra-gastric meal distribution.

This study aimed to a) compare the efficacy of metoclopramide and erythromycin in the treatment of feed intolerance in critical illness; and b) determine the effectiveness of "rescue" combination therapy in patients who fail monotherapy.Randomized controlled trial.Level III mixed medical and surgical intensive care unit.Ninety mechanically ventilated, medical patients with feed-intolerance (gastric residual volumeor=250 mL).Patients received either metoclopramide 10 mg intravenously four times daily (n=45) or erythromycin 200 mg intravenously twice a day (n=45) in a double-blind, randomized fashion. After the first dose, nasogastric feeding was commenced and 6-hourly nasogastric aspirates were performed. If a gastric residual volumeor=250 mL recurred on treatment, open-label, combination therapy was given. Patients were studied for 7 days. Successful feeding was defined as 6-hourly gastric residual volume250 mL with a feeding rateor=40 mL/hr.Demographic data, blood glucose levels, and use of inotropes, opioids, and benzodiazepines were similar between the two groups. After 24 hrs of treatment, both monotherapies reduced the mean gastric residual volume (metoclopramide, 830+/-32 mL to 435+/-30 mL, p.0001; erythromycin, 798+/-33 mL to 201+/-19 mL, p.0001) and improved the proportion of patients with successful feeding (metoclopramide=62% and erythromycin=87%). Treatment with erythromycin was more effective than metoclopramide, but the effectiveness of both treatments declined rapidly over time. In patients who failed monotherapy, rescue combination therapy was highly effective (day 1=92%) and maintained its effectiveness for the study duration (day 6=67%). High pretreatment gastric residual volume was associated with poor response to prokinetic therapy.In critical illness, erythromycin is more effective than metoclopramide in treating feed intolerance, but the rapid decline in effectiveness renders both treatments suboptimal. Rescue combination therapy is highly effective, and further study is required to examine its role as the first-line therapy.

Upper gastrointestinal motor function and incretin hormone secretion are major determinants of postprandial glycemia and insulinemia. However, the impact of small intestinal flow events on glucose absorption and incretin release is poorly defined. Intraluminal impedance monitoring is a novel technique that allows flow events to be quantified. Eight healthy volunteers were studied twice, in random order. A catheter incorporating six pairs of electrodes at 3-cm intervals, and six corresponding manometry sideholes, was positioned in the duodenum. Hyoscine butylbromide (20 mg) or saline was given as an intravenous bolus, followed by a continuous intravenous infusion of either hyoscine (20 mg/h) or saline over 60 min. Concurrently, glucose and 3- O-methylglucose (3-OMG) were infused into the proximal duodenum (3 kcal/min), with frequent blood sampling to measure glucose, 3-OMG, insulin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The frequency of duodenal pressure waves and propagated pressure wave sequences was reduced by hyoscine in the first 10 min ( P < 0.01 for both), but not after that time. In contrast, there were markedly fewer duodenal flow events throughout 60 min with hyoscine ( P < 0.005). Overall, blood glucose ( P < 0.01) and plasma 3-OMG concentrations ( P < 0.05) were lower during hyoscine than saline, whereas plasma insulin, GLP-1, and GIP concentrations were initially ( t = 20 min) lower during hyoscine ( P < 0.05). In conclusion, intraluminal impedance measurement may be more sensitive than manometry in demonstrating alterations in duodenal motor function. A reduction in the frequency of duodenal flow events is associated with a decreased rate of glucose absorption and incretin release in healthy subjects.

Delayed gastric emptying and intolerance to gastric feeding occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Cholecystokinin (CCK) slows gastric emptying. The aim of this study was to determine plasma CCK concentrations during fasting and in response to small-intestine nutrient infusion in critically ill patients.Randomized, controlled trial.Level 3, mixed medical and surgical intensive care unit.A total of 31 mechanically ventilated, critically ill patients (23 men, 51 +/- 3 yrs) and 28 healthy subjects (21 men, 43 +/- 2 yrs).Subjects received two 60-min duodenal infusions of Ensure (complete balanced nutrition), at 1 and 2 kcal/min, in a randomized, single-blind fashion. The nutrient infusions were separated by a 2-hr "washout" period. Blood samples for measurement of plasma CCK concentrations were obtained immediately before and every 20 mins during nutrient infusion.Baseline and nutrient-stimulated plasma CCK concentrations were higher in critically ill patients compared with healthy subjects (p.001). The magnitude of the rise in plasma CCK in response to nutrients was also greater in the critically ill (p.01). Of the 23 patients who received enteral nutrition before the study, nine were intolerant of gastric feeding. In these patients, both the baseline plasma CCK concentration and the magnitude of CCK increase during nutrient infusions were greater than in patients with feed tolerance (p.002). Impaired renal function was associated with an increased baseline CCK concentration but had no effect on the CCK response to nutrients.Both fasting and nutrient-stimulated plasma CCK concentrations are increased in critically ill patients, particularly in those with feed intolerance. This may provide a humoral mechanism for delayed gastric emptying seen in critical illness.

AIM: To evaluate the practice of nutritional assessment and management of hospitalised patients with cirrhosis and the impact of malnutrition on their clinical outcome. METHODS: This was a retrospective cohort study on patients with liver cirrhosis consecutively admitted to the Department of Gastroenterology and Hepatology at the Royal Adelaide Hospital over 24 mo. Details were gathered related to the patients’ demographics, disease severity, nutritional status and assessment, biochemistry and clinical outcomes. Nutritional status was assessed by a dietician and determined by subjective global assessment. Estimated energy and protein requirements were calculated by Simple Ratio Method. Intake was estimated from dietary history and/or food charts, and represented as a percentage of estimated daily requirements. Median duration of follow up was 14.9 (0-41.4) mo. RESULTS: Of the 231 cirrhotic patients (167 male, age: 56.3 ± 0.9 years, 9% Child-Pugh A, 42% Child-Pugh B and 49% Child-Pugh C), 131 (57%) had formal nutritional assessment during their admission and 74 (56%) were judged to have malnutrition. In-hospital caloric (15.6 ± 1.2 kcal/kg vs 23.7 ± 2.3 kcal/kg, P = 0.0003) and protein intake (0.65 ± 0.06 g/kg vs 1.01 ± 0.07 g/kg, P = 0.0003) was significantly reduced in patients with malnutrition. Of the malnourished cohort, 12 (16%) received enteral nutrition during hospitalisation and only 6 (8%) received ongoing dietetic review and assessment following discharge from hospital. The overall mortality was 51%, and was higher in patients with malnutrition compared to those without (HR = 5.29, 95%CI: 2.31-12.1; P < 0.001). CONCLUSION: Malnutrition is common in hospitalised patients with cirrhosis and is associated with higher mortality. Formal nutritional assessment, however, is inadequate. This highlights the need for meticulous nutritional evaluation and management in these patients.

Achalasia is a motility disorder encountered by surgeons during the investigation and treatment of dysphagia. Recent advances in manometry technology, a widely accepted new classification system and a new treatment rapidly gaining international acceptance, have changed the working knowledge required to successfully manage patients with achalasia. We review the Chicago classification subtypes of achalasia with type II achalasia being a predictor of success and type III achalasia a predictor of treatment failure. We review per-oral endoscopic myotomy as an emerging treatment option and its potential for improving the treatment of type III achalasia.

OBJECTIVES: Esophageal wave amplitude is an important determinant of esophageal clearance. A threshold of 30 mmHg is widely accepted as the threshold for effective clearance in the distal esophagus. However, the precise relationship between wave amplitude and clearance has received relatively little attention. The aim of this study was to assess the impact of peristaltic wave amplitude on esophageal volume clearance using multiple intraluminal impedance (MII) measurement. METHODS: Concurrent manometry and MII were performed on 42 healthy asymptomatic volunteers and 13 patients with ineffective esophageal motility. Esophageal motility was measured at four sites 5-cm apart, starting 2 cm above the lower esophageal sphincter. MII was measured at corresponding sites with electrodes incorporated into the manometric assembly. Ten 5-mL liquid (saline) boluses and ten 5-mL low impedance viscous boluses were tested in each subject. Pressure wave amplitude was determined at each site as well as peristaltic success of the responses. Bolus clearance was measured from individual recording segment and from the esophagus as a whole. RESULTS: The proportion of liquid boluses cleared at each site was directly related to wave amplitude and did not increase significantly above a threshold of 25 mmHg in the proximal esophagus, 22 mmHg in the mid-esophagus, and 30 mmHg in the distal esophagus. Corresponding wave amplitudes for total esophageal clearance were 35-40 mmHg. There was a good correlation between the wave amplitude at one site of the esophagus and those of the rest of the esophagus. For both liquid and viscous boluses, the likelihood of impaired clearance was directly related to the number of segments with hypotensive pressure waves. CONCLUSION: The findings confirm the validity of the wave amplitude threshold required for effective liquid bolus clearance and have established the amplitude threshold for clearance of viscous boluses. However, the number of hypotensive pressure waves required for the definition of ineffective motility may be too low.

Delayed gastric emptying (GE) is common both in critical illness and in patients with diabetes mellitus (DM). The effect of DM on the incidence of slow GE in these patients is unknown. We evaluated the effect of DM on liquid GE in critically ill patients. Retrospective analysis of GE using a standard [13C]octanoic acid breath test in 12 type 2 DM patients compared with (a) 44 critically ill patients without DM, including (b) a subgroup of 15 age- and sex-matched patients and (c) 15 healthy volunteers. We determined the gastric emptying coefficient (GEC) and the gastric half-emptying time (t 50). Mean APACHE II scores, blood glucose levels and use of morphine were similar between patient groups. GE was faster in critically ill patients with DM (t 50 122 ± 11 min, GEC: 3.8 ± 0.3) than in patients without DM (t 50 168 ± 16 min, GEC 2.8 ± 0.1) and in age- and sex-matched controls (t 50 165 ± 13 min, GEC 2.7 ± 0.2) and was similar to that in healthy volunteers (t 50 148 ± 13 min, GEC 3.5 ± 0.1). The proportion of patients with slow emptying (GEC

BACKGROUND: Non-obstructive dysphagia (NOD) often poses diagnostic problems. The aim of this study was to evaluate the value of the addition of multichannel intraluminal impedance (MII) recording to esophageal manometry in the work-up of patients with NOD.METHODS: A total of 40 consecutive patients with NOD underwent combined esophageal MII recording and perfusion manometry. Ten liquid and 10 viscous boluses were tested in each patient. Values for bolus presence time (BPT) at each of the four recording sites and total bolus transit time (TBTT) were calculated. Bolus transit (BT) was considered to be normal when BPT at all sites and TBTT were within the normal limits defined in 42 healthy subjects. Patients were judged to have normal transit if >= 80% of liquid and >= 70% of viscous swallows showed normal transit.RESULTS: The following manometric diagnoses were made: normal motility (20), ineffective esophageal motility (IEM) (13), diffuse esophageal spasm (DES) (4), and achalasia (3). Abnormal transit for liquid and/or viscous boluses was found in 35.3% of patients with normal motility, in 66.7% of DES patients, and in 100% of achalasia patients. In patients with achalasia quantification of BT was often made impossible by low initial impedance baseline. Two IEM patients (15.4%) showed normal liquid and viscous transit. Swallows showing normal transit had significantly longer duration of LES relaxation in patients with normal manometry and IEM (p CONCLUSIONS: MII recording identifies esophageal function abnormalities in NOD patients with normal manometry, IEM, and DES. The MII technique seems to be less suitable for the most severe end of the dysphagia spectrum like achalasia.

Acupuncture has been shown to modulate visceral sensation and function. Traditionally, stimulation at the Neiguan (pericardial meridian) has been used to treat upper gastrointestinal symptoms. Some of the effects of acupuncture may be mediated through release of endogenous opioids and are reversed by naloxone. Gastric distension is the major trigger for transient lower esophageal sphincter (LES) relaxations (TLESRs). The aim of this study was to investigate the effect of electric stimulation at the Neiguan and naloxone on the TLESRs. In 14 healthy volunteers, electrical acupoint stimulation was applied at the Neiguan and a sham point on the hip in randomized order on the same day. In 12 healthy volunteers, the effects of naloxone (80 μg/kg iv bolus injection) and saline on electrical acupoint stimulation were compared on separate days at least 1 wk apart. Esophageal motility was measured during distension of the proximal stomach with 500 ml of air using a barostat balloon. Electric acupoint stimulation at the Neiguan decreased the rate of TLESRs by ∼40% from a median of 6/h to 3.5/h ( P < 0.02). Acupoint stimulation had no effect on basal LES pressure, the residual LES pressure during TLESRs, the duration of TLESRs, or gastrointestinal symptoms of fullness, bloating, discomfort, or nausea. The effect of acupoint stimulation was not inhibited by naloxone. Electric acupoint stimulation at the Neiguan significantly inhibits the frequency of TLESRs in response to gastric distention in healthy subjects. This effect does not appear to be mediated through μ-opioid receptors.

Wireless pH monitoring is a significant advance for intraluminal pH recording. It will provide more meaningful data for evaluation of patients and, hopefully, more discriminative diagnosis Since its introduction in 1974,1 ambulatory oesophageal pH monitoring has secured a valuable but complementary role in the diagnosis of gastro-oesophageal reflux disease. Monitoring of oesophageal pH allows not only the detection of excessive levels of acid exposure but also, and more importantly, assessment of the relationship between acid reflux and symptoms. It is especially useful for clarification of the diagnosis in patients with typical or atypical reflux symptoms who do not response to empirical therapy with a proton pump inhibitor, and for assessment of the level of acid suppression in patients with refractory symptoms or oesophagitis despite appropriate antisecretory therapy.2,3 The traditional method of pH monitoring uses a pH electrode mounted on a catheter that is passed transnasally into the oesophagus and positioned 5 cm above the manometrically defined upper border of the lower oesophageal sphincter. The catheter is connected to a portable data logger thereby allowing ambulatory recordings to be made. Ideally, the circumstances under which the pH recordings are made should reflect, as best as possible, the usual living conditions and physical activities normally undertaken by the patient. However, because the catheter is conspicuous and uncomfortable, most patients restrict their activities and dietary intake,4,5 which could potentially lead to false negative results. In addition, because the electrode is not fixed to the oesophageal wall but rather to the nose, it can become displaced, or transiently “migrate” into the stomach in patients with large mobile hiatus hernias, thereby altering the amount of reflux that is recorded6 and potentially leading to erroneous recordings.7 Recently, a new pH monitoring system has been developed that overcomes these limitations …

Acute changes in blood glucose concentration have major effects on gastrointestinal motor function. Patients with diabetes mellitus have an increased prevalence of gastroesophageal reflux. Transient lower esophageal sphincter (LES) relaxation (TLESR) is the most common sphincter mechanism underlying reflux. The aim of this study was to investigate the effect of acute hyperglycemia on triggering TLESRs evoked by gastric distension in healthy volunteers. TLESRs were stimulated by pressure-controlled and volume-controlled (500 ml) gastric distension using an electronic barostat and performed on separate days. On each day, esophageal manometry was performed in the sitting position during gastric distension for 1 h under euglycemia (5 mM), and either marked hyperglycemia (15 mM) or physiological hyperglycemia (8 mM) in randomized order was maintained by a glucose clamp. Marked hyperglycemia doubled the rate of TLESRs in response to both pressure-controlled [5 (3–10.5, median or interquartile range) to 10 (9.5–14.5) per hour, P < 0.02] and volume-controlled [4 (2.5–7.5) to 10.5 (7–12.5) per hour, P < 0.02] gastric distension but had no effect on basal LES pressure. Physiological hyperglycemia had no effect on the triggering of TLESRs or basal LES pressure. In healthy human subjects, marked hyperglycemia increases the rate of TLESRs. Increase in the rate of TLESRs is independent of proximal gastric wall tension. Mechanisms underlying the effect remain to be determined. Hyperglycemia may be an important factor contributing to the increased esophageal acid exposure in patients with diabetes mellitus.

Plication of the gastroesophageal junction by endoscopic suturing has been reported to improve symptoms and reduce acid exposure in patients with gastroesophageal reflux disease (GERD). The mechanisms underlying these effects are not well defined. The aims of our study were to determine the impact of endoscopic suturing of the gastroesophageal junction on lower esophageal sphincter (LES) function in patients with GERD.In 15 patients (7 males) with GERD (heartburn, % time esophageal pH4 greater than 4%, +/- history of erosive esophagitis within 6 months), two plications were performed circumferentially 1 cm below the gastroesophageal junction. Endoscopy and combined postprandial esophageal manometry and pH monitoring were performed before and 6 months after treatment; 24-h ambulatory pH monitoring and symptom assessment were also performed before, and at 6 and 12 months after treatment.Six months after treatment, the rate of transient LES relaxations (tLESRs) was decreased by 37% (p0.05) and basal LES pressure had increased from 4.3 +/- 2.2 mmHg to 6.2 +/- 2.1 mmHg (p0.05). The rate of postprandial reflux events and acid exposure time were not altered. Endoscopic suturing significantly reduced 24-h esophageal acid exposure from 9.6% (9.0-12.1) to 7.4% (3.9-10.1) at 6 months, due predominantly to a reduction in upright acid exposure. The reduction in total 24-h acid exposure was sustained to 12 months. At repeat endoscopy, only one plication was evident in 6 patients (40%) at 6 months. Seven patients (47%) remained off medications at 6 and 12 months follow-up.In patients with GERD, endoscopic suturing of the gastroesophageal junction results in a reduction in the rate of tLESRs, and an increase in basal LES pressure. These changes in LES function result in only a modest reduction in gastroesophageal reflux.

With proton pump inhibitors and current sophisticated endoscopic techniques, the number of patients requiring surgical intervention for upper gastrointestinal bleeding has decreased considerably while trans-arterial embolization is being used more often. There are few direct comparisons between the effectiveness of surgery and embolization.A retrospective study of patients from two Australian teaching hospitals who had surgery or trans-arterial embolization (n = 103) for severe upper gastrointestinal haemorrhage between 2004 and 2012 was carried out. Patient demographics, co-morbidities, disease pathology, length of stay, complications, and overall clinical outcome and mortality were compared.There were 65 men and 38 women. The median age was 70 (range 36-95) years. Patients requiring emergency surgical intervention (n = 79) or trans-arterial embolization (n = 24) were compared. The rate of re-bleeding after embolization (42%) was significantly higher compared with the surgery group (19%) (P = 0.02). The requirement for further intervention (either surgery or embolization) was also higher in the embolization group (33%) compared with the surgery group (13%) (P = 0.03). There was no statistical difference in mortality between the embolization group (5/24, 20.8%) and the surgical group (13/79, 16.5%) (P = 0.75).Emergency surgery and embolization are required in 2.6% of patients with upper gastrointestinal bleeding. Both techniques have high mortalities reflecting the age, co-morbidities and severity of bleeding in this patient group.

Meals increase the rate of transient lower esophageal sphincter (LES) relaxations, in part by gastric distension. The 5HT1 agonist sumatriptan reduces fasting fundic tone, prolongs the meal-induced fundic relaxation, and delays gastric emptying. We therefore hypothesized that sumatriptan might have a significant effect on the rate of postprandial transient LES relaxations and gastroesophageal reflux. We aimed to study the effect of sumatriptan on postprandial transient LES relaxations and reflux in healthy subjects.Esophageal manometry and pH monitoring were performed in 13 healthy volunteers for 30 min before and 90 min after a semiliquid meal (790 kcal). Sumatriptan 6 mg subcutaneous (s.c.) or s.c. placebo were administered on separate days 30 min after the meal.Sumatriptan significantly increased postprandial LES pressure from 11.0 +/- 1.2 mm Hg to 17.6 +/- 1.2 mm Hg (p0.05). However, reflux events were not diminished. In the contrary, reflux was more frequent after sumatriptan than after placebo (3 [1.5-4.5]/30 min vs 2 [0-3]/30 min, p0.05). Transient LES relaxations were more frequent after sumatriptan, particularly in the second 30-min period after drug administration (3 [2.5-5]/30 min vs 2 [1.5-2]/30 min, p0.05).Sumatriptan prevents the natural decay in rate of transient LES relaxations that occurs after a meal and favors the occurrence of gastroesophageal reflux despite increasing LES pressure. The sustained postprandial high rate of transient LES relaxations after sumatriptan may be a consequence of a prolonged fundus relaxation and retention of meal in the proximal stomach.

Improvement of esophageal acid clearance appears to be an important effect of cisapride in the treatment of reflux disease. The mechanism underlying this effect is not clear. Esophageal peristalsis is a major component of the acid clearance process. In normal subjects secondary peristalsis is an important mechanism of esophageal acid clearance during sleep, and this response appears to be impaired in patients with reflux esophagitis. The effects of cisapride on secondary peristalsis are not known. The aim of this study was to investigate the effects of cisapride on the triggering and characteristics of secondary peristalsis in patients with reflux esophagitis.In 17 patients with reflux esophagitis and impaired secondary peristalsis cisapride, 10 mg q.i.d., or placebo were administered in a randomized double blind, crossover design for 4 days separated by a 4-7 day washout period. On the fourth day of treatment, primary peristalsis and secondary peristalsis in response to 10- and 20-ml air boluses were assessed.Secondary peristaltic success and amplitude were greater with the 20-ml bolus than with the 10-ml bolus. However, cisapride had no effect on either secondary peristaltic success or amplitude. Cisapride also had no effect on primary peristalsis or basal LES pressure.The improvement in esophageal acid clearance by cisapride is not explainable by improvement in secondary peristalsis.

Slow gastric emptying and intolerance to nasogastric feeds occurs in up to 40–50% of critically ill patients [1, 2]. Not only does this result in inadequate nutritional support, but it is also a major risk factor for gastro-oesophageal reflux and aspiration, with potential adverse affects on both morbidity and mortality [2, 3]. The currently available therapeutic options for managing delayed gastric emptying and feed intolerance in critically ill patients are: total parenteral nutrient therapy, prokinetic therapy and postpyloric feeding [4, 5]. Of these, treatment with prokinetic agents is efficacious and frequently used as the first-line therapy to avoid the septic complications associated with total parenteral nutrient therapy and the technical demand of postpyloric feeding [4, 5]. Low-dose erythromycin (1–3 mg kg−1), a motilin agonist, is a widely used prokinetic agent in critically ill patients. However, erythromycin has recently been reported to effect human haemodynamics adversely, with a fall in systolic blood pressure (SBP) of 10 ± 9 mmHg 1.5–2.5 h after an oral dose of 300 mg [6]. The mechanism responsible for the hypotension following erythromycin remains unclear. In animals, infusion of motilin was found to induce endothelial-dependent vasodilation and a transient reduction in blood pressure (BP) [7]. As erythromycin leads to an increase in plasma motilin concentrations in humans, it is conceivable that the hypotension associated the drug is related to the endothelium-mediated vasodilation exerted by motilin [8]. Although erythromycin is frequently used in critically ill patients, its haemodynamic effects in this group are unknown. A reduction of 10 mmHg in SBP after erythromycin may not be important in healthy subjects but may be clinically relevant in patients with potential cardiovascular compromise such as the critically ill [6]. This study therefore aimed to examine the acute effects of a single intravenous prokinetic dose of erythromycin on BP) and heart rate (HR) in critically ill patients, who were intolerant to nasogastric feeds and were not on inotropic supportive therapy. Nineteen mechanically ventilated, critically ill patients (age 52 ± 18 years, M:F 10 : 9, Acute Physiology and Chronic Health Evaluation II score 21 ± 6, length of Intensive Care Unit stay 10 ± 9 days) were randomized to either erythromycin (i.v. 200 mg) or placebo (i.v. normal saline) in a cross-over study, 12 h apart. Intolerance to intragastric feeding was defined as vomiting or regurgitation during feeding, or a 6-hourly gastric aspirate > 250 ml [9]. The cut-off gastric aspirate > 250 ml used in this study is a previously published clinical marker of feed intolerance [9, 10]. The majority of patients were sedated with morphine and midazolam and only two patients received propofol alone. Five patients received nasogastric antihypertensive medications (ACE inhibitors n = 3, β-blockers n = 1 and calcium channel blockers n = 1). Continuous lying BP (systolic, diastolic and mean) and HR were measured via an arterial line at 15-min intervals for 60 min before and 180 min after the administration of prokinetic therapy by using an automatic device (TRAM-RAC 4A; General Electric, Milwaukee, WI, USA). A reduction in SBP of >10% from baseline was defined as a clinically significant change. The study was approved by the Local Research Ethics Committee. Each subject gave written informed consent prior to the study. The effects of erythromycin on BP and HR were analysed using a linear mixed effects model fitted to the data. In this model, group status (erythromycin or placebo) and time were treated as fixed effects, while subject was treated as a random effect. Data are expressed as mean ± SD, except in Figure 1, where the error bars represent 95% confidence intervals. A P-value

Esophageal manometry has long been the gold standard for assessment of esophageal motility. Recently, high-frequency intraluminal ultrasonography (HFIUS) has been introduced to measure esophageal contractility and the thickness of esophageal muscle. Greater esophageal muscle thickness has been reported in patients with achalasia, diffuse spasm, and hypertensive peristalsis. In this issue of the Journal, Mittal and colleagues report additional observations in patients with esophageal symptoms referred for esophageal manometry. Their findings confirm earlier observations in patients with spastic motor disorders and report new findings of greater muscle thickness in patients with nonspecific motor disorders as well as normal manometry. Greater muscle thickness was associated with a greater prevalence of dysphagia suggesting the possibility that symptoms may be related, at least in part, to alterations in the biomechanics of the esophagus. The place of HFIUS in the assessment of esophageal function remains to be determined, but it offers the possibility of greater insights into esophageal physiology as well as clinical esophageal motor disorders.

BACKGROUND/AIMS A marked elevation in the blood glucose concentration (approximately 15 mmol L-1) slows oesophageal peristalsis. Recent studies indicate that changes in blood glucose within the normal postprandial range affect gastric motility and emptying. The aim of this study was to investigate whether such alterations in blood glucose also affect oesophageal motility. METHODS In eight healthy subjects oesophageal motility and sensation to balloon distension were measured on two separate days while blood glucose concentrations were stabilized with an insulin-glucose clamp at 4 mmol L-1 and 8 mmol L-1. RESULTS Peristaltic velocity in the proximal oesophagus and over the oesophagus as a whole was faster at a plasma glucose concentration of 8 mmol L-1 compared with those at 4 mmol L-1 (proximal 3.3 +/- 0.3 cm s-1 vs 2.6 +/- 0.2 cm s-1, P < 0.05, total 3.1 +/- 0.2 cm s-1 vs 2.7 +/- 0.2 cm s-1, P < 0.005) but there were no differences in wave amplitude or duration, or basal lower oesophageal sphincter pressure (LOSP). The threshold for initial perception of oesophageal distension was lower at a plasma glucose of 8 mmol L-1 (2.9 +/- 0.5 mL vs 4.9 +/- 1.0 mL, P < 0.05). CONCLUSIONS physiological variations in plasma glucose concentration influence oesophageal motility and sensation. These observations suggest that in order to minimize effects of varying plasma glucose levels on oesophageal motility, manometry should be performed under the same fasting or fed conditions when oesophageal motor function is evaluated.

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.Prospective randomized study.Three tertiary endoscopic centers.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 (MF; n = 126, 72 men, 54.9 ± 1.1 years old) during colonoscopy.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.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 MF: 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 MF.Inhaled Penthrox is not yet available in the United States and Europe.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.

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.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.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] [P0.001]) and an increase in the prevalence of EoE (from 0% [1996-2000] to 35% [2006-2010], P0.001). 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], P0.01). 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.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.

RAVINDER K. MITTAL,* RICHARD H. HOLLOWAY,* ROBERTO PENAGINI, § L. ASHLEY BLACKSHAW, t and JOHN DENT* *Department of Internal Medicine, University of Virginia, Charlottesville, Virginia; *Gastrointestinal Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia; and §Cattedra di Gastroenterologia, Istituto di Scienze Mediche, University of Milan, IRCCS Ospedale Maggiore, Milan, Italy

Purpose To characterize the prevalence, pathophysiology, and natural history of chronic radiation proctitis 5 years following radiation therapy (RT) for localized carcinoma of the prostate. Methods and Materials Studies were performed in 34 patients (median age 68 years; range 54-79) previously randomly assigned to either 64 Gy in 32 fractions over 6.4 weeks or 55 Gy in 20 fractions over 4 weeks RT schedule using 2- and later 3-dimensional treatment technique for localized prostate carcinoma. Each patient underwent evaluations of ( 1 ) gastrointestinal (GI) symptoms (Modified Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scales including effect on activities of daily living [ADLs]); ( 2 ) anorectal motor and sensory function (manometry and graded balloon distension); and ( 3 ) anal sphincteric morphology (endoanal ultrasound) before RT, at 1 month, and annually for 5 years after its completion. Results Total GI symptom scores increased after RT and remained above baseline levels at 5 years and were associated with reductions in ( 1 ) basal anal pressures, ( 2 ) responses to squeeze and increased intra-abdominal pressure, ( 3 ) rectal compliance and ( 4 ) rectal volumes of sensory perception. Anal sphincter morphology was unchanged. At 5 years, 44% and 21% of patients reported urgency of defecation and rectal bleeding, respectively, and 48% impairment of ADLs. GI symptom scores and parameters of anorectal function and anal sphincter morphology did not differ between the 2 RT schedules or treatment techniques. Conclusions Five years after RT for prostate carcinoma, anorectal symptoms continue to have a significant impact on ADLs of almost 50% of patients. These symptoms are associated with anorectal dysfunction independent of the RT schedules or treatment techniques reported here.

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.

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.

Background and study aims: To determine the utility of narrow-band imaging with optical magnification (NBI-Z) in the evaluation of villous morphology. Patients and methods: Patients considered at risk of having celiac disease were invited. After standard endoscopy, they underwent further evaluation with NBI-Z which was digitally recorded. Targeted biopsies of each area videoed with NBI-Z were performed and tissue sent for histopathological analysis. Two expert endoscopists then selected the best representative videos (developmental phase). Next, 41 representative images of these videos were classified as follows: villous patterns present (N) or absent (A). Images showing absence of villi were then classified as cerebriform (C) or flat (F), corresponding to partial or total villous atrophy respectively. Three NBI-Z-naive endoscopists then graded the videos. They underwent an interactive training session (learning phase) with video and images from a digital library before embarking on the actual assessment. To test for reproducibility, all videos were randomly reordered and graded again after a week. Results: Forty-one videos (10 celiac disease, 31 normal) from 21 patients (3 celiac disease, 18 normal) were analyzed. The overall sensitivity and specificity in correctly distinguishing the presence or absence of villi were 93.3 % and 97.8 % respectively, with interobserver and intraobserver agreement (kappa, K ) at 0.82 and 0.86. The sensitivity and specificity in differentiating partial from total villous atrophy were 83.3 % and 100 %, κ at 0.73 and 0.68 respectively. Conclusions: Using a simplified classification, we demonstrated the feasibility of using NBI-Z to detect villous atrophy in patients presenting with suspected celiac disease.

Symptoms are the main cause of morbidity and a significant impairment of quality of life in reflux disease. The majority of patients report their symptoms to primary care physicians, and do not have objective evidence of reflux oesophagitis. Thus symptom evaluation is the primary method of diagnosis, assessment of severity, and determining the choice of therapy. Symptoms are not currently judged to cause reflux disease until they occur on at least two days a week; at this level, they lead to significant impairment of quality of life. Heartburn and regurgitation and general considered to be the cardinal symptoms of reflux. However, these often occur in the setting of other upper gastrointestinal symptoms, particularly epigastric pain, which patients often have difficulty in distinguishing from heartburn. Questionnaires have been developed in order to standardise and improve symptom-based diagnosis, and perform as well as primary care clinicians. These have yet to become mainstream practise but offer great potential.

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.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).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, P0.0001). 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, P0.0001).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.

Small intestinal (SI) motor patterns are often disrupted after major non-gastrointestinal (non-GI) surgery, but the impact on luminal flow and nutrient absorption is unclear. This study examines interactions between SI motility, flow and absorption in the first 3 days after surgical repair of abdominal aortic aneurysm (AAA). Concurrent assessments of SI motility (manometry), flow (impedancometry) and lipid (13C-triolein) and glucose [plasma 3-O-methyl-glucose (3-OMG)] absorption were performed in 13 patients (12 male; 77 ± 2 years) on days 1 and 3 post surgery during 3-h intra-duodenal nutrient infusion (Ensure® with 200 μl 13C-triolein, 3 g 3-OMG). Data, presented as mean ± standard error of mean (SEM), are compared with 10 healthy volunteers (9 male; 57 ± 4 years). On day 1 post surgery, there were more motility bursts, fewer impedance events and reduced absorption of 13C-triolein [cumulative percent dose recovery (cPDR) 22.9 ± 2.4% versus 31.2 ± 4.2%; P