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.

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.

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.

Biomechanical correlates of sequential drinking behavior in aging.

BACKGROUND: The timed water swallow test (TWST) is a test of sequential swallowing where a measured volume is ingested as quickly as comfortably possible. We undertook a study of the biomechanics underpinning the TWST in healthy young and older participants. METHODS: Thirty healthy volunteers underwent high-resolution impedance manometry (MMS; Unisensor, 2.7 mm diameter, 32 pressure sensors, 16 impedance segments). Participants were asked to drink 150 mL, 0.9% normal saline solution rapidly. Swallowing biomechanics and bolus flow characteristics were assessed using pressure-flow analysis and compared using t test and Fisher's exact test with significance as P < .05. KEY RESULTS: Older participants (n = 18; 76 ± 11 years) took longer to complete the TWST (21.2 ± 2.5 vs 9.2 ± 1.0 seconds; P < .001) and displayed reduced volume per swallow (16.6 ± 1.3 vs 27.8 ± 2.9 mL; P < .001) compared to younger participants (n = 12; 29 ± 5 years). Two distinctive pharyngeal swallowing patterns were observed: (a) a single rapid sequence of swallows with or without a clearing swallow (Pattern I) or (b) multiple, shorter sequences interrupted and/or interspersed with single swallows or breaks (Pattern II). Some older participants showed biomechanical evidence of upper esophageal sphincter restriction (n = 7) or impaired deglutitive inhibition (n = 7), associated with the more prolonged Pattern II (TWST duration 30.1 ± 1.5 vs Pattern I 11.9 ± 1.5 seconds; P < .001). CONCLUSIONS AND INFERENCES: Healthy older participants had an increased duration of TWST, suggesting a need to adapt normative values for this population. Rapid sequential swallowing was associated with evidence of UES restriction and impaired deglutitive inhibition in some older participants.

The effect of exogenous glucagon-like peptide-1 on the glycaemic response to small intestinal nutrient in the critically ill: a randomised double-blind placebo-controlled cross over study.

INTRODUCTION: Hyperglycaemia occurs frequently in the critically ill, affects outcome adversely, and is exacerbated by enteral feeding. Furthermore, treatment with insulin in this group is frequently complicated by hypoglycaemia. In healthy patients and those with type 2 diabetes, exogenous glucagon-like peptide-1 (GLP-1) decreases blood glucose by suppressing glucagon, stimulating insulin and slowing gastric emptying. Because the former effects are glucose-dependent, the use of GLP-1 is not associated with hypoglycaemia. The objective of this study was to establish if exogenous GLP-1 attenuates the glycaemic response to enteral nutrition in patients with critical illness induced hyperglycaemia. METHODS: Seven mechanically ventilated critically ill patients, not previously known to have diabetes, received two intravenous infusions of GLP-1 (1.2 pmol/kg/min) and placebo (4% albumin) over 270 minutes. Infusions were administered on consecutive days in a randomised, double-blind fashion. On both days a mixed nutrient liquid was infused, via a post-pyloric feeding catheter, at a rate of 1.5 kcal/min between 30 and 270 minutes. Blood glucose and plasma GLP-1, insulin and glucagon concentrations were measured. RESULTS: In all patients, exogenous GLP-1 infusion reduced the overall glycaemic response during enteral nutrient stimulation (AUC30-270 min GLP-1 (2077 +/- 144 mmol/l min) vs placebo (2568 +/- 208 mmol/l min); P = 0.02) and the peak blood glucose (GLP-1 (10.1 +/- 0.7 mmol/l) vs placebo (12.7 +/- 1.0 mmol/l); P < 0.01). The insulin/glucose ratio at 270 minutes was increased with GLP-1 infusion (GLP-1 (9.1 +/- 2.7) vs. placebo (5.8 +/- 1.8); P = 0.02) but there was no difference in absolute insulin concentrations. There was a transient, non-sustained, reduction in plasma glucagon concentrations during GLP-1 infusion (t = 30 minutes GLP-1 (90 +/- 12 pmol/ml) vs. placebo (104 +/- 10 pmol/ml); P < 0.01). CONCLUSIONS: Acute, exogenous GLP-1 infusion markedly attenuates the glycaemic response to enteral nutrition in the critically ill. These observations suggest that GLP-1 and/or its analogues have the potential to manage hyperglycaemia in the critically ill. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry number: ACTRN12609000093280.

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.

The effects of sedation on gastric emptying and intra-gastric meal distribution in critical illness.

OBJECTIVE: To evaluate the effects of sedation with morphine and midazolam (M&M) versus propofol on gastric emptying in critically ill patients. DESIGN: Descriptive study. SETTING: Mixed medical and surgical intensive care unit. PATIENTS: Thirty-six unselected, mechanically ventilated, critically ill patients. INTERVENTIONS: Gastric scintigraphic data were analysed retrospectively according to whether patients were receiving M&M (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. MEASUREMENTS AND RESULTS: 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 M&M (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 M&M compared to those receiving propofol (p<0.01). Proximal (p=0.02) but not distal (p=0.80) gastric retention was greater in patients who received M&M. Patients who received M&M were more likely to have >or=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. CONCLUSIONS: In critical illness, patients receiving M&M 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.

Mechanisms underlying feed intolerance in the critically ill: implications for treatment.

Malnutrition is associated with poor outcomes in critically ill patients. Although nutritional support is yet to be proven to improve mortality in non-malnourished critically ill patients, early enteral feeding is considered best practice. However, enteral feeding is often limited by delayed gastric emptying. The best method to clinically identify delayed gastric emptying and feed intolerance is unclear. Gastric residual volume (GRV) measured at the bedside is widely used as a surrogate marker for gastric emptying, but the value of GRV measurement has recently been disputed. While the mechanisms underlying delayed gastric emptying require further investigation, recent research has given a better appreciation of the pathophysiology. A number of pharmacological strategies are available to improve the success of feeding. Recent data suggest a combination of intravenous metoclopramide and erythromycin to be the most successful treatment, but novel drug therapies should be explored. Simpler methods to access the duodenum and more distal small bowel for feed delivery are also under investigation. This review summarises current understanding of the factors responsible for, and mechanisms underlying feed intolerance in critical illness, together with the evidence for current practices. Areas requiring further research are also highlighted.

Age-related impairment of esophagogastric junction relaxation and bolus flow time.

AIM: To investigate the functional effects of abnormal esophagogastric (EGJ) measurements in asymptomatic healthy volunteers over eighty years of age. METHODS: Data from 30 young controls (11 M, mean age 37 ± 11 years) and 15 aged subjects (9 M, 85 ± 4 years) were compared for novel metrics of EGJ-function: EGJ-contractile integral (EGJ-CI), "total" EGJ-CI and bolus flow time (BFT). Data were acquired using a 3.2 mm, 25 pressure (1 cm spacing) and 12 impedance segment (2 cm) solid-state catheter (Unisensor and MMS Solar GI system) across the EGJ. Five swallows each of 5 mL liquid (L) and viscous (V) bolus were analyzed. Mean values were compared using Student's t test for normally distributed data or Mann Whitney U-test when non-normally distributed. A P value < 0.05 was considered significant. RESULTS: EGJ-CI at rest was similar for older subjects compared to controls. "Total" EGJ-CI, measured during liquid swallowing, was increased in older individuals when compared to young controls (O 39 ± 7 mmHg.cm vs C 18 ± 3 mmHg.cm; P = 0.006). For both liquid and viscous bolus consistencies, IRP4 was increased (L: 11.9 ± 2.3 mmHg vs 5.9 ± 1.0 mmHg, P = 0.019 and V: 14.3 ± 2.4 mmHg vs 7.3 ± 0.8 mmHg; P = 0.02) and BFT was reduced (L: 1.7 ± 0.3 s vs 3.8 ± 0.2 s and V: 1.9 ± 0.3 s vs 3.8 ± 0.2 s; P < 0.001 for both) in older subjects, when compared to young. A matrix of bolus flow and presence above the EGJ indicated reductions in bolus flow at the EGJ occurred due to both impaired bolus transport through the esophageal body (i.e., the bolus never reached the EGJ) and increased flow resistance at the EGJ (i.e., the bolus retained just above the EGJ). CONCLUSION: Bolus flow through the EGJ is reduced in asymptomatic older individuals. Both ineffective esophageal bolus transport and increased EGJ resistance contribute to impaired bolus flow.

Effects of Fat and Protein Preloads on Pouch Emptying, Intestinal Transit, Glycaemia, Gut Hormones, Glucose Absorption, Blood Pressure and Gastrointestinal Symptoms After Roux-en-Y Gastric Bypass.

BACKGROUND: The aim was to determine the effects of fat and protein preloads on pouch emptying (PE), caecal arrival time (CAT), glucose absorption, blood glucose (BSL), gut hormones, haemodynamics and gastrointestinal (GI) symptoms in subjects who had undergone Roux-en-Y gastric bypass (RYGB) >12 months previously. METHODS: Ten RYGB subjects were studied on three occasions, in randomised order, receiving 200-ml preloads of either water, fat (30 ml olive oil) or whey protein (55 g), 30 min before a mixed meal. PE, CAT, BSL, plasma 3-O-methyl-D-glucopyranose (3-OMG), insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and glucagon, blood pressure (BP), heart rate (HR) and GI symptoms were assessed over 270 min. RESULTS: Although fat and protein preloads did not alter PE of either solids or liquids, the CAT of solids, but not liquids, was longer than that after the water preload (fat 68 ± 5 min and protein 71 ± 6 min vs. water 46 ± 5 min; P = 0.02). BSL elevated promptly after the meal on all days (P < 0.001), but after protein, the magnitude and integrated increases in the first 75 min were less than fat and water preloads (area under the curve (AUC(0-75 min)), 18.7 ± 18.2 vs. 107.2 ± 30.4 and 76.1 ± 19.3 mmol/L/min; P < 0.05). Compared to water preload, the protein and fat preloads were associated with greater increases in plasma insulin, GLP-1 and glucagon concentrations, a reduction in BP, and greater increases in HR, fullness, bloating and nausea. Plasma 3-OMG levels were lower after the protein than after the water and fat preloads (P < 0.001). CONCLUSIONS: Given its effects to attenuate post-prandial glycaemia, reduce intestinal glucose absorption and potentiate the "incretin response", without inducing more adverse post-prandial GI symptom, protein preload may prove clinically useful in RYGB patients and warrant further evaluation, particularly in those with type 2 diabetes (T2DM) and/or dumping syndrome.

Effects of Posture and Meal Volume on Gastric Emptying, Intestinal Transit, Oral Glucose Tolerance, Blood Pressure and Gastrointestinal Symptoms After Roux-en-Y Gastric Bypass.

BACKGROUND: The purpose of this study is to determine the effects of posture and drink volume on gastric/pouch emptying (G/PE), intestinal transit, hormones, absorption, glycaemia, blood pressure and gastrointestinal (GI) symptoms after gastric bypass (Roux-en-Y gastric bypass (RYGB)). METHODS: Ten RYGB subjects were studied on four occasions in randomized order (sitting vs. supine posture; 50 vs. 150 ml of labelled water mixed with 3 g 3-O-methyl-D-glucose (3-OMG) and 50 g glucose). G/PE, caecal arrival time (CAT), blood glucose, plasma insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), 3-OMG, blood pressure, heart rate and GI symptoms were assessed over 240 min. Controls were ten volunteers with no medical condition or previous abdominal surgery, who were studied with the 150-ml drink in the sitting position. RESULTS: Compared to controls, PE (P < 0.001) and CAT (P < 0.001) were substantially more rapid in RYGB subjects. In RYGB, PE was more rapid in the sitting position (2.5 ± 0.7 vs. 16.6 ± 5.3 min, P = 0.02) and tends to be faster after 150 ml than the 50-ml drinks (9.5 ± 2.9 vs. 14.0 ± 3.5 min, P = 0.16). The sitting position and larger volume drinks were associated with greater releases of insulin, GLP-1 and PYY, as well as more hypotension (P < 0.01), tachycardia (P < 0.01) and postprandial symptoms (P < 0.001). CONCLUSIONS: Pouch emptying, blood pressure and GI symptoms after RYGB are dependent on both posture and meal volume.

Changes in esophageal and lower esophageal sphincter motility with healthy aging.

BACKGROUND AND AIMS: Swallowing difficulties become increasingly prevalent in older age. Differences exist in lower esophageal sphincter (LES) function between older and younger patients with dysphagia, but the contribution of aging per se to these is unclear. METHODS: Esophageal motor function was measured using high resolution manometry in older (aged 81+/-1.7 yrs) and younger (23+/-1.7 yrs) asymptomatic healthy adults. After baseline recording, motility was assessed by swallowing boluses of liquid (right lateral and upright postures) and solids. Basal LES pressure, integrated relaxation pressure, distal esophageal peristaltic amplitude, distal contractile integral and velocity were measured. Data are presented as mean +/- SEM. RESULTS: Despite a trend for lower basal LES pressure (15.8+/-2.9 mmHg vs. 21.0+/-0.2 mmHg; P=0.08), completeness of LES relaxation was reduced in older subjects (liquid RL: P=0.003; UR: P=0.007; solid: P=0.03), with higher integrated relaxation pressure when upright (liquid: 6.9+/-1.1 vs. 3.1+/-0.4 mmHg; P=0.01; solids: 8.1+/-1.1 vs. 3.6+/-0.3 mmHg; P=0.001) and a longer time to recovery after liquid boluses (right lateral: P=0.01; upright: P=0.04). In young, but not older adults, esophageal peristaltic velocity was increased when upright (3.6+/-0.2 cm/sec; P=0.04) and reduced with solids (3.0+/-0.1 cm-s; P=0.03). Distal contraction amplitude was higher with solid cf. liquid in the younger individuals (51.8+/-7.9 mmHg vs. 41.4+/-6.2 mmHg; P=0.03). In elderly subjects, the distal contractile integral was higher with liquid swallows in the upright posture (P=0.006). CONCLUSION: There are subtle changes in LES function even in asymptomatic older individuals. These age-related changes may contribute to the development of dysphagia.

Modulation of individual components of gastric motor response to duodenal glucose.

AIM: To evaluate individual components of the antro-pyloro-duodenal (APD) motor response to graded small intestinal glucose infusions in healthy humans. METHODS: APD manometry was performed in 15 healthy subjects (12 male; 40 ± 5 years, body mass index 26.5 ± 1.6 kg/m(2)) during four 20-min intraduodenal infusions of glucose at 0, 0.5, 1.0 and 1.5 kcal/min, in a randomised double-blinded fashion. Glucose solutions were infused at a rate of 1 mL/min and separated by 40-min "wash-out" period. Data are mean ± SE. Inferential analyses are repeated measure analysis of variance with Bonferroni post-hoc testing. RESULTS: At 0 kcal/min frequency of pressure waves were: antrum (7.5 ± 1.8 waves/20 min) and isolated pyloric pressure waves (IPPWs) (8.0 ± 2.3 waves/20 min) with pyloric tone (0.0 ± 0.9 mmHg). Intraduodenal glucose infusion acutely increased IPPW frequency (P < 0.001) and pyloric tone (P = 0.015), and decreased antral wave frequency (P = 0.007) in a dose-dependent fashion. A threshold for stimulation was observed at 1.0 kcal/min for pyloric phasic pressure waves (P = 0.002) and 1.5 kcal/min for pyloric tone and antral contractility. CONCLUSION: There is hierarchy for the activation of gastrointestinal motor responses to duodenal glucose infusion. An increase in IPPWs is the first response observed.

Outcomes of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding.

AIM: To evaluate weight loss and surgical outcomes of Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric band (LAGB). METHODS: Data relating to changes in body mass index (BMI) and procedural complications after RYGB (1995-2009; n = 609; 116M: 493F; 42.4 ± 0.4 years) or LAGB (2004-2009; n = 686; 131M: 555F; 37.2 ± 0.4 years) were extracted from prospective databases. RESULTS: Pre-operative BMI was higher in RYGB than LAGB patients (46.8 ± 7.1 kg/m² vs 40.4 ± 4.2 kg/m², P < 001); more patients with BMI < 35 kg/m² underwent LAGB than RYGB (17.1% vs 4.1%, P < 0.0001). BMI decrease was greater after RYGB. There were direct relationships between weight loss and pre-operative BMI (P < 0.001). Although there was no difference in weight loss between genders during the first 3-year post-surgery, male LAGB patients had greater BMI reduction than females (-8.2 ± 4.3 kg/m² vs -3.9 ± 1.9 kg/m², P = 0.02). Peri-operative complications occurred more frequently following RYGB than LAGB (8.0% vs 0.5%, P < 0.001); majority related to wound infection. LAGB had more long-term complications requiring corrective procedures than RYGB (8.9% vs 2.1%, P < 0.001). Conversion to RYGB resulted in greater BMI reduction (-9.5 ± 3.8 kg/m²) compared to removal and replacement of the band (-6.0 ± 3.0 kg/m²). Twelve months post-surgery, fasting glucose, total cholesterol and low density lipoprotein levels were significantly lower with the magnitude of reduction greater in RYGB patients. CONCLUSION: RYGB produces substantially greater weight loss than LAGB. Whilst peri-operative complications are greater after RYGB, long-term complication rate is higher following LAGB.

Gastric emptying measurement of liquid nutrients using the (13)C-octanoate breath test in critically ill patients: a comparison with scintigraphy.

PURPOSE: 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. AIM: To evaluate the performance of the (13)C-OBT in the assessment of GE in critically ill patients. METHODS: 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 retention >13 % at 180 min. RESULTS: 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 (GRV > 250 ml) on scintigraphy and 91 % (21/23) patients on (13)C-OBT. CONCLUSION: 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.

Lower esophageal sphincter relaxation is impaired in older patients with dysphagia.

AIM: To characterize the effects of age on the mechanisms underlying the common condition of esophageal dysphagia in older patients, using detailed manometric analysis. METHODS: A retrospective case-control audit was performed on 19 patients aged ≥ 80 years (mean age 85 ± 0.7 year) who underwent a manometric study for dysphagia (2004-2009). Data were compared with 19 younger dysphagic patients (32 ± 1.7 years). Detailed manometric analysis performed prospectively included basal lower esophageal sphincter pressure (BLESP), pre-swallow and nadir LESP, esophageal body pressures and peristaltic duration, during water swallows (5 mL) in right lateral (RL) and upright (UR) postures and with solids. Data are mean ± SE; a P-value < 0.05 was considered significant. RESULTS: Elderly dysphagic patients had higher BLESP than younger patients (23.4 ± 3.8 vs 14.9 ± 1.2 mmHg; P < 0.05). Pre-swallow LESP was elevated in the elderly in both postures (RL: 1 and 4 s P = 0.019 and P = 0.05; UR: P < 0.05 and P = 0.05) and solids (P < 0.01). In older patients, LES nadir pressure was higher with liquids (RL: 2.3 ± 0.6 mmHg vs 0.7 ± 0.6 mmHg, P < 0.05; UR: 3.5 ± 0.9 mmHg vs 1.6 ± 0.5 mmHg, P = 0.01) with shorter relaxation after solids (7.9 ± 1.5 s vs 9.7 ± 0.4 s, P = 0.05). No age-related differences were seen in esophageal body pressures or peristalsis duration. CONCLUSION: Basal LES pressure is elevated and swallow-induced relaxation impaired in elderly dysphagic patients. Its contribution to dysphagia and the effects of healthy ageing require further investigation.

Relationship between altered small intestinal motility and absorption after abdominal aortic aneurysm repair.

PURPOSE: 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). METHODS: 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). RESULTS: 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 < 0.001] and 3-OMG, compared with health. By day 3, total number of bursts and flow events were similar between groups, with fewer retrograde and more antegrade flow episodes. ¹³C-triolein absorption remained low in patients on day 3 (26.7 ± 2.2%, P < 0.05), correlating positively with total number of flow events (r = 0.49; P < 0.01), but negatively with prolonged events (r = -0.37; P = 0.03). In patients, 3-OMG absorption increased from day 1 to 3 to a level comparable to health. CONCLUSIONS: Whilst disruption in SI motility and flow (impedance) events was associated with reduced absorption of both lipid and carbohydrate, lipid malabsorption was more prolonged. This may reflect inadequate mixing of chyme from altered motility, so varying the nutrient composition of enteral feed may improve absorption in these patients.

Impact of bolus volume on small intestinal intra-luminal impedance in healthy subjects.

AIM: To assess the impact of bolus volume on the characteristics of small intestinal (SI) impedance signals. METHODS: Concurrent SI manometry-impedance measurements were performed on 12 healthy volunteers to assess the pattern of proximal jejunal fluid bolus movement over a 14 cm-segment. Each subject was given 34 boluses of normal saline (volume from 1 to 30 mL) via the feeding tube placed immediately above the proximal margin of the studied segment. A bolus-induced impedance event occurred if there was > 12% impedance drop from baseline, over > or = 3 consecutive segments within 10 s of bolus injection. A minor or major impedance event was defined as a duration of impedance drop < 60 s or > or = 60 s, respectively. RESULTS: The minimum volume required for a detectable SI impedance event was 2 mL. A direct linear relationship between the SI bolus volume and the occurrence of impedance events was noted until SI bolus volume reached 10 mL, a volume which always produced an impedance flow event. There was a moderate correlation between the bolus volume and the duration of impedance drop (r = 0.63, P < 0.0001) and the number of propagated channels (r = 0.50, P < 0.0001). High volume boluses were associated with more major impedance events (> or = 10 mL boluses = 63%, 3 mL boluses = 17%, and < 3 mL boluses = 0%, P = 0.02). CONCLUSION: Bolus volume had an impact on the type and length of propagation of SI impedance events and a threshold of 2 mL is required to produce an event.

Endogenous glucagon-like peptide-1 slows gastric emptying in healthy subjects, attenuating postprandial glycemia.

INTRODUCTION: The role of glucagon-like peptide-1 (GLP-1) in the regulation of gastric emptying is uncertain. The aim of this study was to determine the effects of endogenous GLP-1 on gastric emptying, glucose absorption, and glycemia in health. METHODS: Ten healthy fasted subjects (eight males, two females; 48 +/- 7 yr) received the specific GLP-1 antagonist, exendin(9-39) amide [ex(9-39)NH(2)] (300 pmol/kg x min iv), or placebo, between -30 and 180 min in a randomized, double-blind, crossover fashion. At 0 min, a mashed potato meal ( approximately 2600 kJ) containing 3 g 3-ortho-methyl-D-glucose (3-OMG) and labeled with 20 MBq (99m)Technetium-sulphur colloid was eaten. Gastric emptying, including the time taken for 50% of the meal to empty from the stomach (T50), blood glucose, plasma 3-OMG, and plasma insulin were measured. RESULTS: Ex(9-39)NH(2) accelerated gastric emptying [T50 ex(9-39)NH(2), 68 +/- 8 min, vs. placebo, 83 +/- 7 min; P < 0.001] and increased the overall glycemic response to the meal [area under the curve (0-180 min) ex(9-39)NH(2), 1540 +/- 106 mmol/liter x min, vs. placebo, 1388 +/- 90 mmol/liter x min; P < 0.02]. At 60 min, ex(9-39)NH(2) increased the rise in glycemia [ex(9-39)NH(2), 9.9 +/- 0.5 mmol/liter, vs. placebo, 8.4 +/- 0.5 mmol/liter; P < 0.01], plasma 3-OMG [ex(9-39)NH(2), 0.25 +/- 0.01 mmol/liter, vs. placebo, 0.21 +/- 0.01 mmol/liter; P < 0.05], and plasma insulin [ex(9-39)NH(2), 82 +/- 13 mU/liter, vs. placebo, 59 +/- 9 mU/liter; P < 0.05] concentrations. There was a close within-subject correlation between glycemia and gastric emptying [e.g. at 60 min, the increment in blood glucose and gastric emptying (T50); r = -0.89; P < 0.001]. CONCLUSION: GLP-1 plays a physiological role to slow gastric emptying in health, which impacts on glucose absorption and, hence, postprandial glycemia.

Prokinetic therapy for feed intolerance in critical illness: one drug or two?

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 > or =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 <250 mL with the feeding rate > or =40 mL/hr, over 7 days. Secondary outcomes included daily caloric intake, vomiting, postpyloric feeding, length of stay, and mortality. MEASUREMENTS AND MAIN RESULTS: Demographic data; use of inotropes, opioids, or benzodiazepines; and pretreatment gastric residual volume were similar between the two groups. The gastric residual volume was significantly lower after 24 hrs of treatment with combination therapy, compared with erythromycin alone (136 +/- 23 mL vs. 293 +/- 45 mL, p = .04). Over the 7 days, patients treated with combination therapy had greater feeding success, received more daily calories, and had a lower requirement for postpyloric feeding, compared with erythromycin alone. Tachyphylaxis occurred in both groups but was less with combination therapy. Sedation, higher pretreatment gastric residual volume, and hypoalbuminemia were significantly associated with a poor response. There was no difference in the length of hospital stay or mortality rate between the groups. Watery diarrhea was more common with combination therapy (20 of 37 vs. 10 of 38, p = .01) but was not associated with enteric infections, including Clostridium difficile. CONCLUSIONS: In critically ill patients with feed intolerance, combination therapy with erythromycin and metoclopramide is more effective than erythromycin alone in improving the delivery of nasogastric nutrition and should be considered as the first-line treatment.