Proximal gastric response to small intestinal nutrients is abnormal in mechanically ventilated critically ill patients.

AIM: To determine the response of the proximal stomach to small intestinal nutrients in critically ill patients. METHODS: Proximal gastric motility was measured in 13 critically ill patients (49.3 +/- 4.7 years) and 12 healthy volunteers (27.7 +/- 2.9 years) using a barostat technique. Recordings were performed at baseline, during a 60-min intra-duodenal infusion of Ensure (2 kcal/min), and for 2 h following the infusion. Minimum distending pressure (MDP), intra-bag volume and fundic wave activity were determined. RESULTS: The MDP was higher in patients (11.7 +/- 1.1 vs 7.8 +/- 0.7 mmHg; P < 0.01). Baseline intra-bag volumes were similar in the 2 groups. In healthy subjects, a 'bimodal' proximal gastric volume response was observed. In patients, the initial increase in proximal gastric volume was small and delayed, but eventually reached a maximal volume similar to that of healthy subjects. In healthy subjects, the proximal gastric volume rapidly returned to baseline level after nutrient infusion (median 18 min). In contrast, the recovery of volume to baseline was delayed in critically ill patients (median 106 min). In 6 patients, the volume had not returned to baseline level 2 hours after nutrient infusion. In patients, fundic volume waves were less frequent (P < 0.05) and had lower amplitude (P < 0.001), compared to healthy subjects. CONCLUSION: In critical illness, proximal gastric motor responses to small intestinal nutrient stimulation are abnormal.

Distal small bowel motility and lipid absorption in patients following abdominal aortic aneurysm repair surgery.

AIM: To investigate distal small bowel motility and lipid absorption in patients following elective abdominal aortic aneurysm (AAA) repair surgery. METHODS: Nine patients (aged 35-78 years; body mass index (BMI) range: 23-36 kg/m(2)) post-surgery for AAA repair, and seven healthy control subjects (20-50 years; BMI range: 21-29 kg/m(2)) were studied. Continuous distal small bowel manometry was performed for up to 72 h, during periods of fasting and enteral feeding (Nutrison). Recordings were analyzed for the frequency, origin, length of migration, and direction of small intestinal burst activity. Lipid absorption was assessed on the first day and the third day post surgery in a subset of patients using the (13)C-triolein-breath test, and compared with healthy controls. Subjects received a 20-min intraduodenal infusion of 50 mL liquid feed mixed with 200 microL (13)C-triolein. End-expiratory breath samples were collected for 6 h and analyzed for (13)CO(2) concentration. RESULTS: The frequency of burst activity in the proximal and distal small intestine was higher in patients than in healthy subjects, under both fasting and fed conditions (P<0.005). In patients there was a higher proportion of abnormally propagated bursts (71% abnormal), which began to normalize by d 3 (25% abnormal) post-surgery. Lipid absorption data was available for seven patients on d 1 and four patients on d 3 post surgery. In patients, absorption on d 1 post-surgery was half that of healthy control subjects (AUC (13)CO(2) 1323+/-244 vs 2646+/-365; P<0.05, respectively), and was reduced to the one-fifth that of healthy controls by d 3 (AUC (13)CO(2) 470+/-832 vs 2646+/-365; P<0.05, respectively). CONCLUSION: Both proximal and distal small intestinal motor activity are transiently disrupted in critically ill patients immediately after major surgery, with abnormal motility patterns extending as far as the ileum. These motor disturbances may contribute to impaired absorption of enteral nutrition, especially when intraluminal processing is necessary for efficient digestion.

Glycemic, hormone, and appetite responses to monosaccharide ingestion in patients with type 2 diabetes.

To investigate the relative effects of fructose and glucose on blood glucose, plasma insulin and incretin (glucagon-like peptide-1 [GLP-1] and gastric inhibitory peptide [GIP]) concentrations, and acute food intake, 10 (6 men, 4 women) patients with diet-controlled type 2 diabetes (diabetic) (44 to 71 years) and 10 age and body mass index (BMI)-matched (6 men, 4 women) nondiabetic, control subjects with varying degrees of glucose tolerance (nondiabetic), were studied on 3 days. In random order, they drank equienergetic preloads of glucose (75 g) (GLUC), fructose (75 g) (FRUCT) or vehicle (300 mL water with noncaloric flavoring [VEH]) 3 hours before an ad libitum buffet lunch. Mean glucose concentrations were lower after FRUCT than GLUC in both type 2 diabetics (FRUCT v GLUC: 7.5 +/- 0.3 v 10.8 +/- 0.4 mmol/L, P <.001) and nondiabetics (FRUCT v GLUC: 5.9 +/- 0.2 v 7.2 +/- 0.3 mmol/L, P <.05). Mean insulin concentrations were approximately 50% higher after FRUCT in type 2 diabetics than in nondiabetics (diabetics v nondiabetics: 23.1 +/- 0.7 v 15.1 +/- 1.3 microU/mL; P <.0001). Plasma GLP-1 concentrations after fructose were not different between type 2 diabetics and nondiabetics (P >.05). Glucose, but not FRUC, increased GIP concentrations, which were not different between type 2 diabetics and nondiabetics (P >.05). Food intake was suppressed 14% by GLUC (P <.05 v CONT) and 14% by FRUC (P <.05 v CONT), with no difference between the amount of food consumed after GLUC and FRUC treatment in either type 2 diabetics or nondiabetics (P >.05). We have confirmed that oral fructose ingestion produces a lower postprandial blood glucose response than equienergetic glucose and demonstrated that (1) fructose produces greater increases in plasma insulin concentration in type 2 diabetics than nondiabetics, not apparently due to greater plasma incretin concentrations and (2) fructose and glucose have equivalent short-term satiating efficiency in both type 2 diabetics and nondiabetics. We conclude that on the basis of improved glycemic control, but not satiating efficiency, fructose may be useful as a replacement for glucose in the diet of obese patients with type 2 diabetes.

Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations.

OBJECTIVE: 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. DESIGN: Randomized, controlled trial. SETTING: Level 3, mixed medical and surgical intensive care unit. SUBJECTS: A total of 31 mechanically ventilated, critically ill patients (23 men, 51 +/- 3 yrs) and 28 healthy subjects (21 men, 43 +/- 2 yrs). INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Endogenous nitric oxide modulates small intestinal nutrient transit and activity in healthy adult humans.

OBJECTIVE: Nitric oxide (NO) mechanisms have been shown to modulate fasting small intestinal motility in humans, but a role in the regulation of human postprandial small intestinal motility has not been assessed. The aim of this study was to evaluate the effect of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on the regulation of small intestinal nutrient transit and postprandial small intestinal motility in healthy humans. MATERIAL AND METHODS: Seven healthy male volunteers (18-27 years) underwent antroduodenal manometry recordings for 4 h on 2 occasions after intraduodenal instillation of a 500 KJ [120 Kcal] test meal. The meal was administered 15 min after the commencement of a 60-min intravenous infusion of L-NMMA (4 mg kg-1 h-1) or saline (0.9%). Studies were separated, performed in randomized order and >3 days apart. The frequency and amplitude of duodenal pressure waves together with time to return of fasting motility (phase III) was determined. On each day, small intestinal transit was measured using a lactulose breath test. RESULTS: The test meal interrupted fasting small intestinal motility in all subjects. The time to recurrence of fasting motility following its postprandial disruption was similar (L-NMMA versus saline 1.6+/-0.2 h versus 1.9+/-0.1 h; p>0.05). Duodenocaecal transit was delayed by infusion of L-NMMA compared with saline (L-NMMA versus saline 92.1+/-3.9 min versus 66.4+/-6.4 min; p<0.005). Infusion of L-NMMA significantly increased the frequency (L-NMMA versus saline 50.4+/-6.6 versus 34.8+/-5.5 waves per 30 min; p<0.05) and amplitude (L-NMMA versus saline 20.4+/-1.5 versus 15.5+/-1.1 mmHg; p<0.01) of duodenal pressure waves. CONCLUSIONS: These data suggest that endogenous NO may play a role in the regulation of small intestinal nutrient transit by regulating small intestinal motility in healthy individuals.

Diet, food intake, and disturbed physiology in the pathogenesis of symptoms in functional dyspepsia.

Functional dyspepsia (FD) remains a relatively poorly characterized gastrointestinal disorder of unknown etiology that is frequently difficult to manage. A systematic review of the literature relating to food intake and FD is summarized here. Many patients with FD report symptoms after meal ingestion, including fullness, bloating, epigastric pain, nausea, and vomiting, and this has been interpreted as indicative of an underlying "motor disorder of the stomach or small intestine." Such hypotheses are, however, still largely unsubstantiated, and the data that do exist are inconclusive, particularly as few studies have directly examined the temporal relationships between dyspeptic symptoms, meal ingestion, and disordered gastric motility. Moreover, studies attempting to relate symptoms to specific disturbances in gastric motor function have, in most cases, not evaluated symptoms concurrently with the function test, and/or have used suboptimal symptom scoring to quantify symptoms. Furthermore, the term "early satiety" has been used loosely as a symptom, rather than a quantitative measure of food intake. Currently, the most widely accepted mechanism underlying FD is visceral hypersensitivity, which may contribute to both enhanced motor and symptomatic responses to food ingestion. However, the possible contribution of food and dietary habits to the induction and/or exacerbation of dyspeptic symptoms represents a relatively new area-despite frequent reports by patients that their symptoms are often related to food ingestion; this association has not been formally assessed. Dietary assessments have frequently implicated fatty foods in symptom induction, and these findings are supported by laboratory-based studies, particularly the demonstration that FD patients more often experience symptoms after intraduodenal infusions of fat, than glucose. Further studies into the potential role of dietary factors in the induction of dyspeptic symptom are required to establish whether dietary therapies have any place in the management of FD.

Similar effects of foods high in protein, carbohydrate and fat on subsequent spontaneous food intake in healthy individuals.

Pre-loads high in protein, as compared to carbohydrate and fat, produce greater satiety and reduce food intake after a fixed time interval. This study investigated the effect of macronutrient composition on spontaneous eating behaviour. On four separate occasions, 16 fasted, healthy, non-obese men, blinded to the true purpose of the study, consumed iso-energetic ( approximately 3MJ) yoghurt-based pre-loads of equivalent weight ( approximately 0.5 kg), high in fat (40%) [HF], carbohydrate (60%) [HC] or protein (29%) [HP], and no pre-load in a randomized, single-blind fashion. Subjects ate at will from a selection of food items for the remainder of the day (7 h) with the time of food requests (h) and energy content (kJ) and macronutrient distribution (%) of food eaten recorded. The three pre-loads delayed the first spontaneous request for food by 1.5-1.8 h relative to no pre-load. Total spontaneous food intake was suppressed 29% [HP], 20% [HF] and 17% [HC] by the pre-loads. Neither the amount of food eaten per spontaneous eating episode, nor the spontaneous eating frequency differed statistically following ingestion of the different pre-loads or no pre-load. In this study, in subjects who were free to choose when as well as how much they ate, a high-protein pre-load exerted similar effects on satiety as did iso-energetic high-fat and high-carbohydrate pre-loads.