Prise en charge à long terme du grêle court : spécificités de l'enfant

Short bowel syndrome is defined as the malabsorptive state that follows massive resection of the small intestine (remaining intestinal length < 80 cm). This definition implies that a significant malabsorption of nutrients, water and electrolytes is present, leading to long-term dependence on parenteral nutrition. The management goals in short bowel syndrome are to maintain growth and development, promote intestinal adaptation, prevent complications, ensure a good quality of life, and establish enteral nutrition. Children treated with long-term parenteral nutrition require the expertise of a multi-disciplinary nutritional care team in order to reach the best balance between the constraints of parenteral nutrition and a normal social and familial lifestyle. All the aspects of the disease (medical, social, educational and psychological) have to be taken into account to achieve weaning from parenteral nutrition. Intestinal transplantation is indicated in patients who are likely to die because of irreversible TPN-induced liver disease (associated with liver transplantation), recurrent sepsis or difficult vascular access.     

Effect de l'hGH sur le métabolisme des protéines et des acides aminés chez l'homme

The increased availability of human Growth Hormone (rhGH) as a result of recombinant molecular biology has provided the opportunity to explore its actions and potential utility in humans. rhGH administration is associated with an increase in the resting energy expenditure of GH-deficient adults, but has little effect on the resting energy expenditure of GH-sufficient individuals. By mechanisms which remain to be elucidated, rhGH increases the oxidation of fat, decreases the oxidation of protein, and has little effect on the oxidation of carbohydrate. The net effect of these changes in substrate oxidation is a reduction in fat mass and an increase in muscle mass in GH-deficient adults, and increased linear growth in GH-deficient children. The primary mechanism of rhGH on whole body protein would appear to increase the whole body rate of protein synthesis with little effect on the rates of proteolysis in both the fasting and intracibal conditions. rhGH appears to increase acutely the rates of protein synthesis in forearm tissues, but has little effect on muscle mass or strength following 3 months of treatment in GH-sufficient adults. The effects of rhGH on two experimental models of protein catabolism in humans (caloric restriction and glucocorticosteroid treatment) are reviewed. Our knowledge of the actions and utility of rhGH as a therapeutic agent has increased tremendously over the last decade. However, a great deal remains to be discovered about the specific genes induced or suppressed as a result of rhGH treatment before we will be knowledgeable in all of its potential clinical applications.     

Le concept d'intestin dépassé

After extensive small bowel resection, some patients develop a massive diarrhoea (daily faecal weight above 2 kg). Such massive faecal losses demonstrate that the residual absorptive capacities of the short bowel are overwhelmed. There is in each individual with a short bowel syndrome a correlation between daily faecal losses and daily enteral caloric intake. One can separate two different groups of patients: those who have massive faecal losses even when the enteral load is moderate (obligatory overwhelmed intestine syndrome) and those who develop massive faecal losses only when the enteral load is exceeding (induced overwhelmed intestine syndrome). In the latter patients autonomy via the enteral route is usual, whereas the former patients require prolonged or definitive parenteral nutrition.     

Traitement diététique et médicamenteux du syndrome du grêle court

The principles of the dietary and drug treatment of short bowel syndrome depend mainly on the presence or absence of the colon in continuity. In patients with a jejunostomy, the major problem is sodium and magnesium losses with corresponding fluid depletion, and a high-energy diet with added salt as in the WHO solution, Vichy water or NaCl capsules must be advised. The drugs used to reduce jejunostomy output include loperamide and codeine, gastric anti-secretory (proton pump inhibitors) and somatostatin analogs. In patients with a colon in continuity, bacterial fermentation of unabsorbed carbohydrates in the colon results in energy salvage; these patients are advised to eat a high-energy diet rich in carbohydrates and low in oxalates and can benefit from cholestyramine. Lactose, notably as milk, must be restricted; a low-fiber regimen is not justified in most cases. Oral or parenteral supplements of liposoluble vitamins (vitamin B12) and trace-elements (zinc) are needed in a majority of patients. The correction of magnesium deficiency is sometimes difficult, even after prolonged weaning of parenteral nutrition, by the oral route. The efficacy of these various measures as well as the status in micronutrients must be reevaluated regularly.     

Comment réaliser et surveiller une nutrition postopératoire ?

Nutritional supply is necessary in post operative patients who can not assure a normal oral feeding, equivalent to 60 % of their needs, in the 9 days following surgical procedure. In a normal well-feed population, nutritional supply in a shorter post-operative period is whithout influence on mortality and morbidity. On the other hand in undernourished patients nutritional support seems to decrease morbidity. However, the definition of this group using simple means remains difficult. After elective surgery, comparison between total parenteral nutrition and enteral nutrition does not show any important difference. However in the case of post tranmatic surgery, infectious morbidity and intensive care and hospital stays are lower when enteral nutrition is used. The lack of difference following elective surgery is likely due to a small number of patients and the low rate of complications. Enteral nutritional support must be chosen when ever possible. Currently, it is not possible to affirm the porportion of each nutrient when nutrition is performed at the post-operative phase. Optimal glucose supply is around 4 to 6 mg/kg/min and the calorie to nitrogen ratio from 200 to 150/1. Some specific nutrient seem to be of interest especially alpha keto glutarate which can be theoretically employed as a substitute for glutamine. This substrate seems to decrease septic complications and delay of wound healing.Nutritional assessment and effectiveness of feeding regimen is very difficult during the post-operative phase. Only, the confrontation of several methods allows to have a good approach of the nutritional status. Among visceral proteins, transthyretin has the highest sensitivity and predictive specificity during a stable inflammatory process. Muscle strength and bio electrical impedance measurements seem of interest but need further studies. Subjective assessment at the preoperative period remains the best method of nutritional assessment but requires trained observers.     

L'intestin du patient agressé

Multiple organ failure syndrome often complicates the course of critically ill patients. In various experimental models, several features of gut dysfunction have been incriminated in the pathogenesis of this syndrome. This work aims at reviewing the clinical data on gut dysfunction recorded in critically ill patients. An increase in gut permeability and an alteration in intestinal motility have been clearly demonstrated, while bacterial translocation, an immune dysfunction and mucosal hypoperfusion are suggested by indirect arguments. The respective roles of these alterations in the pathogenesis of multiple organ failure syndrome remain to be clarified by further investigations.     

Facteurs trophiques : perspectives thérapeutiques de l'utilisation des facteurs de croissance et pharmaconutriments dans l'insuffisance intestinale

During intestinal insufficiency, improving intestinal functions may limit the needs for prolonged parenteral nutrition. Gut trophicity is supported by the intake of nutrients, polyamines, and nitrogenous pharmaconutrients such as glutamine, arginine and ornithine oxoglurate, but also growth factors acting as hormones or locally. Intestinal cell proliferation is stimulated by growth hormone and glucagonlike peptide-2, as well as by the insulin growth factor, epidermal growth factor, transforming growth factor-alpha, while it is inhibited by transforming growth factor-beta. The evaluation of combined therapies with glutamine, growth hormone and a specialized diet in short bowel patients has yielded conflicting results. The clinical use of GLP-2, alone or in combination, looks promising but need to be evaluated. The knowledge about intestinal growth factors and pharmaconutrients is increasing rapidly and should lead to innovative therapeutic strategies of intestinal insufficiency.     

Insulin-like Growth Factor-I et dénutrition aiguë ou chronique

Malnutrition is a common problem affecting many patients with both acute and chronic illnesses. Nutrient delivery via parenteral or enteral routes has alleviated some of the problems that arise from well defined nutritional deficiencies. However, it has made a much smaller impact on wasting associated with illness. Modulation of metabolism with exogenous agents is attractive as a means to improve outcomes in patients that are susceptible to wasting. Insulin-like Growth Factor-I (IGF-I) and Growth Hormone (GH) are hormones that can be used for this purpose, and may have widespread clinical utility to improve wound healing, maintain lean body mass, and preserve organ function. Studies are ongoing to elucidate the possible benefits of these agents.     

Avec quoi nourrir l''intestin agressé ?

The intestinal mucosa plays a key role in the barrier function against systemic diffusion of intraluminal endotoxins and bacteria. In a state of aggression, its anatomical and functional integrity is altered, allowing bacterial translocation and thus multivisceral failure syndrome. Among the different mechanisms responsible for the alteration of the intestinal barrier, a significant part is played by the nutritional deficits, both in quantity and quality, which are constant in aggression states. Their correction by a specific enteral nutrition given early should be able to minimise the intestinal barrier's deterioration. Several substances have been tested in animal and man in this indication. Glutamine for the enterocyte and short-chain fatty acids for the colonocyte are the most promising. Arginine has both local and systemic immunological properties that may be of interest. This amino acid should be used cautiously in the septic patient because of its strong implication in nitric oxide (NO) metabolism. Ornithine, ornithine alpha-ketoglutarate, nucleotides, short-chain fatty acids and polyunsaturated fatty acids theoretically have beneficial effects on the structure and/or function of the injured intestine, but this has still to be confirmed by clinical studies. In order to reduce the incidence of bacterial translocation, nutritional mixtures combining the prebiotic effects of dietary fibres with the effects of probiotic bacteria such as lactobacillus have recently been proposed. Other substances such as polyphenols, natural constituents of the diet, are likely to protect the injured intestinal mucosa but still have to undergo clinical trials. In situations where the intestinal barrier function is compromised, the optimal protective effects of a nutritional supplementation could be obtained by a combination of several specific substrates.     

IGF-I : métabolisme et action physiologique

Insulin-like growth factor-I (IGF-I) was discovered on the basis of its ability to stimulate cartilage sulfation and to substitute for GH as determined using in vivo and in vitro systems. Now, IGF-I is considered as mediating the large majority of the effects of GH by both endocrine and autocrine/paracrine mechanisms. IGF-I can be produced by a wide variety of cell types but hepatic production is responsible for % 50 of circulating IGF-I. The IFG-I gene expression is controleed mainly by GH; but other hormones such as estradiol, andogrens and cortisol are involved in its modulation as well as nutritional status. IGF-I, a 70 amino acid polypeptide sharing % 40 of homology with proinsulin, is present in the circulation and throughout the extracellular space almost entirely (% 95 of circulating IGF-I) bound to members of a family of high affinity insulin-like growth factor binding proteins (IGFBSs), six of which have been cloned and sequenced. IGFBPs have been proposed to play several major functions that are essential to co-ordinate and regulate bioavailability and biological activities of IGF-I. Most of the cellular effects of IGF-I are mediated by binding to the IGF-I receptor whose structure is very close to that of insulin receptor. The effects of IGF-I in vitro are either acute anabolic effects on protein and carbohydrate metabolism or longer term mitogenic effects. IGF-I stimulates DNA synthesis, cell replication and cell proliferation ; it is also a potent inducer of several specific cell differenciation and has been described as an inhibitor of apoptosis. In vivo, mitogenic effect of IGF-I results in its role in postnatal growth and most of the promoting activity of GH are mediated by IGF-I. Metabolic effects of IGF-I are similar to that of insulin but the presence of IGFBPs, which prolong IGF actions, buffers the acute hypoglycaemic effects of IGF-I.     

Quand et comment nourrir l'intestin agressé ?

Nutritional support with enteral nutrition in intensive care patients is highly desirable for many reasons, but it is often difficult to realise. Critically ill patients suffer pylorus closure and reduced peristaltism due to mechanical ventilation and use of drugs like opiates, sedatives and catecholamines. Feeding through nasogastric tubes is the simplest technique. In case of failure, defined as persistent gastric residues > 300 mL or negative energy balances (delivering less than 75% of energy target for > 3 days), postpyloric feeding should be introduced. Daily energy delivery should be closely monitored to avoid progressive large negative energy balances: indeed, enteral nutrition is frequently interrupted in ICU patients for various therapeutic and diagnostic procedures. Combined enteral and parenteral nutrition can avoid the dire consequence of deficient energy intakes. Enteral nutrition may be initiated early in most categories of medical and surgical patients: the clinical benefits of this approach have been demonstrated in trauma and burn patients, but not yet in other diagnostic categories. In most patients, especially in the more stable patients, nutritional support may be introduced between 3 and 5 days post-admission. In the ICU, delivery is best performed with the continuous pump-controlled infusion technique. To be successful, nutrition must become a routine, supported by structured protocols.     

Prise en charge à long terme du grêle court (adulte)

Short bowel is the main cause for chronic intestinal failure. The small bowel is considered to be “short” when the length of the remaining gut is less than 2 meters; the anatomy of the residual intestine may influence the adaptative capacities of the gut. Almost half of the patients with a “short bowel” need a long-term parenteral support. The amount of parenteral lipids must be ranged between 1 g/kg body weight/week and 1 g/kg body weight/day in order to prevent essential fatty acids deficiency and, on the other hand, to limit the risk of lipid-related hepatopathy. Vitamins and trace-elements must be regularly provided; there is a risk of brain toxicity due to excessive iv administration of manganese. Advantages of glutamine or growth hormones are still debated.     

Audit de l’équilibre glycémique de patients diabétiques sous analogues de l’insuline : à propos de 2915 assurés de la CNAM (Tunisie)

Background: Insulin analogues are increasingly prescribed in Tunisia. These molecules, covered by the National Health Insurance Fund (CNAM) in Tunisia under certain conditions, have an important and constantly increasing cost. Aim: To audit the diabetes control among insured in the Northern district of the CNAM (Tunisia), treated with insulin analogues in 2019 and to assess factors associated with good glycemic control. Methods: Retrospective observational study including patients with diabetes who applied for renewal of insulin analogues between March and April 2019 in the northern district of the CNAM. Results: Our study included 2915 diabetic insured. The sex ratio was 1.08. The mean age was 56.5 ±18.56 years. More than half of the diabetic insured were followed by a specialist physician (44% by endocrinologists, 7% by internists, 6% by nutritionists and 4% by other specialists). The average duration of treatment with insulin analogues was 5 years ± 1.41. Almost three quarters (74%) of the diabetic insured were type 2 diabetics. The mean daily dose of rapid-acting, short-acting and premixed insulin analogues were 30±15.49 IU/d, 38±18.36 IU/d and 65±19.38 IU/d respectively. HbA1c targets were achieved in 8% of the diabetic insured. In univariate analysis, the variables significantly associated with diabetes balance were follow-up by a physician specializing in endocrinology (OR=3.14, 95% CI [0.98-10.08]), internal medicine (OR=5.06, 95% CI [1.49-17.21]) or nutrition (OR=2.06, 95% CI [0.54-7.77]), type 1 diabetes (OR=1.67, 95% CI [1.26-2.22]) and basal insulin therapy regimen (OR=1.88, 95% CI [1.39-2.54]). In multivariate analysis, the independent and significant factors associated with glycemic control were type 1 diabetes (ORa=1.81, 95% CI [1.37-2.39]) and basal insulin therapy regimen (ORa= 1.77, 95% CI [1.30-2.40]). Conclusion: This study showed that the majority of diabetic insured on insulin analogues had a poor controlled diabetes. Type 1 diabetes and basal insulin therapy regimen were the two factors associated with good glycemic control after multivariate analysis. A review of criteria for reimbursement of insulin analogues by the National Health Insurance Fund is necessary in order to rationalize the expenses related to these molecules.