Effect of Critical Illness on Triglyceride Absorption.

BACKGROUND: Adequate nutrition support for critically ill patients optimizes outcome, and enteral feeding is the preferred route of nutrition. Small intestinal glucose absorption is frequently impaired in critical illness. Despite lipid being a major constituent of liquid nutrient administered, there is little information about lipid absorption during critical illness. OBJECTIVES: To determine small intestinal lipid, as well as glucose, absorption in critical illness compared with health. MATERIALS AND METHODS: Twenty-nine mechanically ventilated critically ill patients and 16 healthy volunteers were studied. Liquid nutrient (60 mL, 1 kcal/mL), containing 200 µL (13)C-triolein and 3 g 3-O-methyl-glucose (3-OMG), was infused directly into the duodenum at a rate of 2 kcal/min. Exhaled (13)CO2 and serum 3-OMG concentrations were measured at timed intervals over 360 minutes. Lipid absorption was measured as the cumulative percentage dose (cPDR) of (13)CO2 recovered at 360 minutes. Glucose absorption was measured as the area under the 3-OMG concentration curve. Data are median (range) and analyzed using the Mann-Whitney U and Pearson correlation tests. RESULTS: Lipid absorption was markedly less in the critically ill (cPDR(13)CO2: patients, 22.6% [0%-100%] vs healthy participants, 40.7% [5.3%-84.7%]; P = .018). While glucose absorption was less at 60 minutes in the critically ill (3-OMG60: 13.2 [3.5-29.5] vs 21.1 [9.3-31.9] mmol/L·min; P = .003), this was not apparent at 360 minutes (3-OMG360: 92.7 [54.5-147.9] vs 107.9 [64.0-168.7] mmol/L·min; P = .126). There was no relationship between lipid and glucose absorption. CONCLUSION: Small intestinal absorption of lipid is diminished during critical illness.

The effects of critical illness on intestinal glucose sensing, transporters, and absorption.

OBJECTIVES: Providing effective enteral nutrition is important during critical illness. In health, glucose is absorbed from the small intestine via sodium-dependent glucose transporter-1 and glucose transporter-2, which may both be regulated by intestinal sweet taste receptors. We evaluated the effect of critical illness on glucose absorption and expression of intestinal sodium-dependent glucose transporter-1, glucose transporter-2, and sweet taste receptors in humans and mice. DESIGN: Prospective observational study in humans and mice. SETTING: ICU and university-affiliated research laboratory. SUBJECTS: Human subjects were 12 critically ill patients and 12 healthy controls. In the laboratory 16-week-old mice were studied. INTERVENTIONS: Human subjects underwent endoscopy. Glucose (30 g) and 3-O-methylglucose (3 g), used to estimate glucose absorption, were infused intraduodenally over 30 minutes. Duodenal mucosa was biopsied before and after infusion. Mice were randomized to cecal ligation and puncture to model critical illness (n = 16) or sham laparotomy (control) (n = 8). At day 5, mice received glucose (100 mg) and 3-O-methylglucose (10 mg) infused intraduodenally prior to mucosal tissue collection. MEASUREMENTS AND MAIN RESULTS: Quantitative polymerase chain reaction was performed to measure absolute (human) and relative levels of sodium-dependent glucose transporter-1, glucose transporter-2, and taste receptor type 1 member 2 (T1R2) transcripts. Blood samples were assayed for 3-O-methylglucose to estimate glucose absorption. Glucose absorption was three-fold lower in critically ill humans than in controls (p = 0.002) and reduced by a similar proportion in cecal ligation and puncture mice (p = 0.004). In critically ill patients, duodenal levels of sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2 transcript were reduced 49% (p < 0.001), 50% (p = 0.009), and 85% (p = 0.007), whereas in the jejunum of cecal ligation and puncture mice sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2 transcripts were reduced by 55% (p < 0.001), 50% (p = 0.002), and 69% (p = 0.004). CONCLUSIONS: Critical illness is characterized by markedly diminished glucose absorption, associated with reduced intestinal expression of glucose transporters (sodium-dependent glucose transporter-1 and glucose transporter-2) and sweet taste receptor transcripts. These changes are paralleled in cecal ligation and puncture mice.

Mesenteric blood flow, glucose absorption and blood pressure responses to small intestinal glucose in critically ill patients older than 65 years.

PURPOSE: To compare nutrient-stimulated changes in superior mesenteric artery (SMA) blood flow, glucose absorption and glycaemia in individuals older than 65 years with, and without, critical illness. METHODS: Following a 1-h 'observation' period (t (0)-t (60)), 0.9 % saline and glucose (1 kcal/ml) were infused directly into the small intestine at 2 ml/min between t (60)-t (120), and t (120)-t (180), respectively. SMA blood flow was measured using Doppler ultrasonography at t (60) (fasting), t (90) and t (150) and is presented as raw values and nutrient-stimulated increment from baseline (Δ). Glucose absorption was evaluated using serum 3-O-methylglucose (3-OMG) concentrations during, and for 1 h after, the glucose infusion (i.e. t (120)-t (180) and t (120)-t (240)). Mean arterial pressure was recorded between t (60)-t (240). Data are presented as median (25th, 75th percentile). RESULTS: Eleven mechanically ventilated critically ill patients [age 75 (69, 79) years] and nine healthy volunteers [70 (68, 77) years] were studied. The magnitude of the nutrient-stimulated increase in SMA flow was markedly less in the critically ill when compared with healthy subjects [Δt (150): patients 115 (-138, 367) versus health 836 (618, 1,054) ml/min; P = 0.001]. In patients, glucose absorption was reduced during, and for 1 h after, the glucose infusion when compared with health [AUC(120-180): 4.571 (2.591, 6.551) versus 11.307 (8.447, 14.167) mmol/l min; P < 0.001 and AUC(120-240): 26.5 (17.7, 35.3) versus 40.6 (31.7, 49.4) mmol/l min; P = 0.031]. A close relationship between the nutrient-stimulated increment in SMA flow and glucose absorption was evident (3-OMG AUC(120-180) and ∆SMA flow at t (150): r (2) = 0.29; P < 0.05). CONCLUSIONS: In critically ill patients aged >65 years, stimulation of SMA flow by small intestinal glucose infusion may be attenuated, which could account for the reduction in glucose absorption.

Randomized double-blind crossover study to determine the effects of erythromycin on small intestinal nutrient absorption and transit in the critically ill.

BACKGROUND: The gastrokinetic drug erythromycin is commonly administered to critically ill patients during intragastric feeding to augment small intestinal nutrient delivery. However, erythromycin has been reported to increase the prevalence of diarrhea, which may reflect reduced absorption and/or accelerated small intestinal transit. OBJECTIVE: The objective was to evaluate the effects of intravenous erythromycin on small intestinal nutrient absorption and transit in the critically ill. DESIGN: On consecutive days, erythromycin (200 mg in 20 mL 0.9% saline) or placebo (20 mL 0.9% saline) were infused intravenously between -20 and 0 min in a randomized, blinded, crossover fashion. Between 0 and 30 min, a liquid nutrient containing 3-O-methylglucose (3-OMG), [13C]triolein, and [(99m)Tc]sulfur colloid was administered directly into the small intestine at 2 kcal/min. Serum 3-OMG concentrations and exhaled (13)CO2 (indices of glucose and lipid absorption, respectively) were measured. Cecal arrival of the infused nutrient was determined by scintigraphy. Data are medians (ranges) and were analyzed by using Wilcoxon's signed-rank test. RESULTS: Thirty-two mechanically ventilated patients were studied. Erythromycin increased small intestinal glucose absorption [3-OMG AUC360: 105.2 (28.9-157.0) for erythromycin compared with 91.8 (51.4-147.9) mmol/L · min for placebo; P = 0.029] but tended to reduce lipid absorption [cumulative percentage dose (13)CO2 recovered: 10.4 (0-90.6) compared with 22.6 (0-100) %; P = 0.06]. A trend to slower transit was observed after erythromycin [300 (39-360) compared with 228 (33-360) min; P = 0.07]. CONCLUSIONS: Acute administration of erythromycin increases small intestinal glucose absorption in the critically ill, but there was a tendency for the drug to reduce small intestinal lipid absorption and slow transit. These observations have implications for the use of erythromycin as a gastrokinetic drug in the critically ill. This trial was registered in the Australian New Zealand Clinical Trials Registry as ACTRN 12610000615088.