Background and aims: Glucagon-like peptide 2 (GLP-2) may improve intestinal absorption in short bowel syndrome (SBS) patients with an end jejunostomy. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant GLP-2 analogue, prolongs the intestinotrophic properties of GLP-2 in animal models. The safety and effect of teduglutide were investigated in SBS patients with and without a colon in continuity. Methods: Teduglutide was given subcutaneously for 21 days once or twice daily to 16 SBS patients in the per protocol investigational group, 10 with end jejunostomy (doses of 0.03 (n = 2), 0.10 (n = 5), or 0.15 (n = 3) mg/kg/day), one with ,50% colon in continuity (dose 0.03 mg/kg/day), and five with >50% colon in continuity (dose 0.10 mg/kg/day). Nutrient balance studies, D-xylose tests, and intestinal mucosa biopsies were performed at baseline, on the last three days of treatment, and after three weeks of follow up. Pre-study fasting native GLP-2 levels were determined for the five patients with >50% colon in continuity.Results: Pooled across groups and compared with baseline, teduglutide increased absolute (+743 (477) g/day; p,0.001) and relative (+22 (16)%; p,0.001) wet weight absorption, urine weight (+555 (485) g/day; p,0.001), and urine sodium excretion (+53 (40) mmol/day; p,0.001). Teduglutide decreased faecal wet weight (2711 (734) g/day; p = 0.001) and faecal energy excretion (2808 (1453) kJ/day (2193 (347) kcal/day); p = 0.040). In SBS patients with end jejunostomy, teduglutide significantly increased villus height (+38 (45)%; p = 0.030), crypt depth (+22 (18)%; p = 0.010), and mitotic index (+115 (108)%; p = 0.010). Crypt depth and mitotic index did not change in colonic biopsies from SBS patients with colon in continuity. The most common side effects were enlargement of the stoma nipple and mild lower leg oedema. The improvements in intestinal absorption and decreases in faecal excretion noted after treatment had reversed after the drug free follow up period. A controlled study with a more robust design is ongoing in order to determine the optimal dosage of teduglutide for SBS patients to achieve the maximal effect and utility of this drug in clinical practice. Conclusion: Teduglutide, at three dose levels for 21 days, was safe and well tolerated, intestinotrophic, and significantly increased intestinal wet weight absorption in SBS patients with an end jejunostomy or a colon in continuity.
Aspiration is the leading cause of pneumonia in the intensive care unit and the most serious complication of enteral tube feeding (ETF). Although aspiration is common, the clinical consequences are variable because of differences in nature of the aspirated material and individual host responses. A number of defense mechanisms normally present in the upper aerodigestive system that protect against aspiration become compromised by clinical events that occur frequently in the critical care setting, subjecting the patient to increased risk. The true incidence of aspiration has been difficult to determine in the past because of vague definitions, poor assessment monitors, and varying levels of clinical recognition. Standardization of terminology is an important step in helping to define the problem, design appropriate research studies, and develop strategies to reduce risk. Traditional clinical monitors of glucose oxidase strips and blue food coloring (BFC) should no longer be used. A modified approach to use of gastric residual volumes and identification of clinical factors that predispose to aspiration allow for risk stratification and an algorhythm approach to the management of the critically ill patient on ETF. Although the patient with confirmed aspiration should be monitored for clinical consequences and receive supportive pulmonary care, ETF may be continued when accompanied by appropriate steps to reduce risk of further aspiration. Management strategies for treating aspiration pneumonia are based on degree of diagnostic certainty, time of onset, and host factors.
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