Home parenteral nutrition (HPN) in patients with post-bariatric surgery complications.

BACKGROUND & AIMS: Obesity is a worldwide health problem. Bariatric surgery (BS) is becoming one of the most commonly used methods for fighting obesity and its associated comorbidities. However, current BS techniques can be associated with early or late complications that may require nutritional support. The aim of this retrospective observational study was to determine the indications and outcomes for patients on Home parenteral nutrition (HPN) due to post-bariatric surgery complications. METHODS: A specific questionnaire was designed by the ESPEN HAN/CIF working group and submitted to HPN centers. This questionnaire included: patient demographics, type of surgery, BMI before surgery and at start of HPN, indications for HPN including technical and nutritional complications (early within 2 months after surgery or late), outcome, PN regimen, and HPN complications. Patients were retrospectively included from January 2008 to June 2014. RESULTS: Eighteen HPN centers responded to the survey. A total of 2880 HPN patients were treated during the study period, 77 of whom had BS (65 females; mean age 51 ± 7 years); gastric bypass was performed in 69% of the patients; mean BMI was 44.4 before surgery and 23.2 at the start of HPN. Indications for HPN were early complications in 17 cases and late complications in 60 cases. Early complications were mostly anastomotic leakage/fistula; late complications were hypoalbuminemia, and vitamin and trace element deficiencies. Out of 77 patients, 16 needed a surgical re-intervention, 29 were weaned off HPN, and 6 died (no HPN-related deaths). During the HPN period, 58% of the patients were re-hospitalized and central venous complications were observed in 41%. Diabetes mellitus was described in 17/77 patients. HPN was supportive in 60 patients and exclusive in 17 patients (mean caloric intake: 23 ± 6 kcal/k BW/day and 1.2 g/kBW/day). Only 7/77 patients resumed their professional activities on HPN. CONCLUSIONS: This is the largest observational multicenter study describing the use of HPN in patients with post-BS complications. Severe hypoalbuminemia is a major late complication. Rates of re-hospitalization and CVC infection were high. HPN may be a "bridge therapy" before surgical revision after BS. The high mortality rate reflects the complexity of these cases.

Acute effects of continuous infusions of glucagon-like peptide (GLP)-1, GLP-2 and the combination (GLP-1+GLP-2) on intestinal absorption in short bowel syndrome (SBS) patients. A placebo-controlled study.

BACKGROUND AND AIMS: The ileocolonic brake is impaired in short bowel syndrome (SBS) patients with distal bowel resections. An attenuated meal-stimulated hormone secretion may cause gastric hypersecretion, rapid gastric and intestinal transit and a poor adaptation. Attempting to restore this ileocolonic brake, this study evaluated the acute effects of continuous intravenous administration of glucagon-like peptide (GLP) 1 and 2, alone or in combination, on gastrointestinal function in SBS patients. METHODS: SBS patients were admitted 4 times for identical 72-h balance studies, where infusions (1 pmol/kg/min) of GLP-1, placebo (saline), GLP-2 and GLP-1+2 (1 pmol/kg/min of each), were provided. Patients filled out a VAS questionnaire regarding subjective symptoms during treatments. Bone mineral content, body-weight and -composition were measured using DEXA scans. Blood glucose, insulin, pro insulin C-peptide and GLP concentrations were measured in relation to a standardized breakfast. RESULTS: Nine SBS patients (5 women/4 men, aged 52±11) were enrolled and completed the study; 7 had end-jejunostomies, 2 had 50% of colon-in-continuity. All treatments significantly reduced the fecal wet weight, energy, nitrogen, sodium and potassium losses compared to placebo. However, only GLP-2 containing treatments increased absolute absorption of wet weight and sodium. Only GLP-1+2 improved the hydrational status evaluated by DEXA increases in the fat mass and calculated total body weight. GLP-1 and GLP-1+2 reduced the post-prandial blood glucose levels. A tendency of nausea and reduced appetite was seen in relation to GLP-1 treatment, but this was ameliorated by the co-administration of GLP-2. CONCLUSION: GLP-1 decreased diarrhea and fecal excretions in SBS patients, but it seems less potent than GLP-2. The combination of GLP-1+2 numerically provided additive effects on intestinal absorption compared to either peptide given alone. Larger, long-term studies should further assess the potential of the glucagon-like peptides or analogs, alone or in combination, in the treatment of SBS patients.

A dose-equivalent comparison of the effects of continuous subcutaneous glucagon-like peptide 2 (GLP-2) infusions versus meal related GLP-2 injections in the treatment of short bowel syndrome (SBS) patients.

OBJECTIVE: Glucagon-like peptide 2 (GLP-2), secreted endogenously from L-cells in the distal bowel in relation to meals, modulates intestinal absorption by adjusting gastric emptying and secretion and intestinal growth. Short bowel syndrome (SBS) patients with distal intestinal resections have attenuated endogenous GLP-2 secretion, which may contribute to their rapid gastric emptying, gastric hypersecretion and poor intestinal adaptation, whereas SBS patients with preserved terminal ileum and colon, who have a constantly elevated GLP-2 secretion, seem to do better in these respects. This study compared effects of continuous, subcutaneous (s.c.), exogenous GLP-2 infusion (CONT-GLP-2) versus three daily s.c. GLP-2 injections (TID-GLP-2) on intestinal absorption in SBS patients. DESIGN: Eight SBS patients (5 F, 3 M; 60±7 years; remnant small bowel 111±62 cm; 1 with 50% colon) were studied. In an open-label, sequential study, the 72-hour baseline admission was followed by two dose-equivalent, 21-day, dosing regimens; CONT-GLP-2, providing 1.0mg/day by a MiniMed insulin pump and TID-GLP-2, providing 0.33 mg injections in relation to three meals, separated by a washout period of at least 3 weeks. During admissions, the intestinal absorption was evaluated by analysing a double portion of the diet, faecal and urinary excretions. Post-absorptive plasma citrulline, reflecting enterocyte mass, was measured by HPLC. RESULTS: Compared to baseline, both GLP-2 dosing regimens reduced diarrhoea (CONT-GLP-2: 749±815 g/d and TID-GLP-2: 877±1004 g/d, p=0.01) and increased wet weight absorption (CONT-GLP-2: 19±19% and TID-GLP-2: 25±21%, p=0.003). Significant increases in plasma citrulline (CONT-GLP-2: 7.5±7 µmol/L and TID-GLP-2, 12.7±8 µmol/L; p=0.001) suggesting intestinotrophic effects in relation to GLP-2 treatment, are followed by increases in relative absorption of energy, carbohydrate and fat. No significant difference was seen on any of the absorptive parameters measured between the two dosing regimens. CONCLUSION: Both GLP-2 regimens significantly reduced diarrhoea in SBS patients, but a significant difference between continuous GLP-2 administration and TID injections could not be detected in a study of this size.

Glucagon-like peptide-2 stimulates mucosal microcirculation measured by laser Doppler flowmetry in end-jejunostomy short bowel syndrome patients.

BACKGROUND: In animal and human studies glucagon-like peptide-2 (GLP-2) has been shown to increase blood flow in the superior mesenteric artery and the portal vein. This study describes the effect of GLP-2 measured directly on the intestinal mucosal blood flow by laser Doppler flowmetry (LDF) in end-jejunostomy short bowel syndrome (SBS) patients. METHODS: In five SBS patients with end-jejunostomy a specially designed laser Doppler probe was inserted into the stoma nipple, and blood flow measured directly on the jejunal mucosa for 105 min in relation to no treatment, systemic saline infusion, topical adrenaline application and a subcutaneous injection of 800 µg native GLP-2. RESULTS: The GLP-2 injection increased jejunal mucosal blood flow by 79±37% compared to conditions, where no treatment was given (p<0.001). The significant effect was present at least 105 min. Systemic saline infusion and topical, mucosal adrenaline application did not affect mucosal microcirculation. CONCLUSIONS: GLP-2 raises jejunal microcirculation in SBS patients with end-jejunostomy. This may explain the redness and increase in the end-jejunostomy nipple size imminently after commencing GLP-2 injections. The potential beneficial effects of this GLP-2-mediated increase of blood flow in the mesenteric bed should be investigated in clinical conditions other than the short bowel syndrome.

Irreversibility of kindled alcohol-withdrawal behaviour in rats.

In order to investigate whether alcohol-withdrawal kindling is an irreversible process, male Wistar rats were exposed to 12 episodes, each consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal. Spontaneous withdrawal seizures were found in 15% of the animals during episodes 10-12. After an alcohol-free period of 26 days, the animals were subjected to three more episodes of alcohol dependence (i.e. episodes 13-15) in which 12% of the animals developed spontaneous withdrawal seizures. Based on several statistical tests, we concluded that there was no true difference between the seizure activity in episodes 10-12 and episodes 13-15, indicating that alcohol-withdrawal kindling is a long-lasting and perhaps irreversible process. In a second experiment, an alcohol-withdrawal kindled group was first exposed to seven episodes of alcohol dependence. A diazepam group went through the same alcohol regimen, but each withdrawal reaction was blocked by diazepam treatment. Finally, a single episode group was included which was fed isocalorically with the kindled animals. After an alcohol-free period of 11 days, all three groups were subjected to 4 days of severe alcohol intoxication. During the subsequent withdrawal reaction seizures were observed in 22-26% of the animals with no significant differences across the groups. These results call for a modification of the kindling hypothesis of alcohol withdrawal and suggest that kindling-induced alterations may be overlooked if convulsive behaviour is tested during a relatively strong withdrawal reaction.