Metabolic and hormonal changes during the refeeding period of prolonged fasting.

OBJECTIVE: The discovery of leptin, a hormone primarily involved in adaptation to fasting, led to an increased interest in appetite regulation and appetite-modulating hormones. Here, we present unique data from a case of extreme starvation and refeeding, showing changes in plasma concentrations of appetite-modulating and metabolic hormones as well as biochemical changes, and draw attention to the dangers of the refeeding syndrome. PATIENTS AND METHODS: We studied the refeeding period of a 44-day voluntary fast uncomplicated by underlying disease. Biochemical and hormonal variables were compared with 16 matched subjects such that the BMI range of the controls covered the entire spectrum for the index subject's recovering BMI. RESULTS: Lack of calorie intake with free access to water resulted in 25% loss of body weight. Haemoconcentration was observed and feeding was started with a low sodium, hypocaloric liquid formulation. During early refeeding, marked hypophosphataemia, haemodilution and slight oedema developed. Vitamins B1, B12 and B6 were depleted while serum free fatty acids, ketone bodies and zinc levels were abnormally high; abnormal liver function developed over the first week. The hormonal profile showed low IGF-I and insulin levels, and elevated IGF-binding protein-1 concentrations. Appetite-regulating hormones were either very low (leptin and ghrelin) or showed no marked difference from the control group (peptide YY, agouti-related peptide, alpha-melanocyte-stimulating hormone, neuropeptide Y and pro-opiomelanocortin). Appetite was low at the beginning of refeeding and a transient increase in orexin and resistin was observed coincidently with an increase in subjective hunger. CONCLUSIONS: Our study illustrates the potential dangers of refeeding and provides a comprehensive insight into the endocrinology of prolonged fasting and the refeeding process.

Novel substrates.

Enteral and parenteral feeds need at least to contain adequate amounts of water, energy, protein, electrolytes, vitamins and trace elements. Ready-manufactured parenteral feeds for example are incomplete because of shelf-life constraints and require the addition of vitamins (especially) and trace elements. Acute vitamin deficiencies, notably thiamine deficiency, can be precipitated if this is not adhered to. An increasing interest, however, exists in the use of feeds containing substrates, which are intended to improve patient outcome in particular clinical circumstances. The purpose of this article is to examine as to what is available and make recommendations on their use. It deals with artificial feeds only - disease-specific diets are outside our remit.

Longitudinal trends in quality of life after starting home parenteral nutrition: a randomised controlled study of telemedicine.

BACKGROUND AND AIMS: This study defines and quantifies longitudinal changes in quality of life (QoL) at the time of first discharge home on home parenteral nutrition (HPN) and over the first year. METHODS: Results were compared in patients in standard contact with a nutrition nurse specialist by telephone, with results of those in contact via telemedicine in a randomised controlled trial. Participants were recruited from nine UK HPN centres. Patients were randomised to receive telemedicine upon initial discharge or after 1 year. The SF36 was the principal instrument chosen to determine QoL throughout the year on three predetermined occasions. EQ5D and hospital anxiety and depression scores were also recorded. RESULTS: Thirty participants were recruited to the study from March 2001 to June 2003. In all domains, QoL scores were significantly lower than normative data at discharge. QoL scores significantly improved over the first 6 months in physical functioning, physical role (RP), vitality (VT), social functioning (SF), emotional-role (RE) domains, and mental component summary (MCS). At 6 months RE, mental health (MH) and MCS were no longer significantly lower than normative data. There was no significant change in bodily pain (BP), general health (GH), MH, and physical component summary (PCS). Opiate use significantly reduced SF36 domains RP, BP, VT, SF, MH, and MCS at 6 months and was associated with more subsequent inpatient episodes and central line reinsertions. Patients with an acute onset of intestinal failure had less pain and better GH scores at 6 months, and had less inpatient episodes after discharge than patients with a more chronic onset. Telemedicine had no impact on QoL or subsequent clinical outcome. CONCLUSIONS: Aspects of QoL improve over the first 6 months of HPN. Opiate use and chronic diagnosis have a negative impact on some elements of QoL and clinical outcome variables.

Measurements of gastric emptying during continuous nasogastric infusion of liquid feed: electric impedance tomography versus gamma scintigraphy.

BACKGROUND & AIMS: Continuous nasogastric infusion is commonly used to deliver enteral feed but current methods used to assess tolerance based on aspiration and measurement of gastric residual volume have been criticised. Electric impedance tomography (EIT) measures gastric emptying by monitoring changes in epigastric impedance when a meal progressively empties from the stomach. AIMS: (1) to establish whether EIT was a valid method for measuring gastric emptying during continuous nasogastric infusion by comparing it with gamma scintigraphy (GS) and (2) to provide data on gastric emptying patterns during continuous nasogastric infusion. METHODS: Gastric emptying of 400 ml of enteral feed given over 200 min was measured simultaneously using EIT and GS in 10 healthy volunteers (five male and five female). RESULTS: Gastric emptying curves were obtained in 10 subjects by EIT but only eight by GS. Visual examination of the curves showed reasonable agreement. Patterns of emptying and filling during continuous nasogastric infusion were variable between individuals; the prevailing pattern was a trend towards a steady-state volume of approximately 50-125 ml. CONCLUSIONS: While EIT does not provide an accurate estimate of gastric volume during continuous infusion, it does show patterns of gastric emptying over time. With further development this could make it a useful tool for monitoring gastric emptying in patients at risk of gastroparesis.

Macro- and micronutrient losses and nutritional status resulting from 44 days of total fasting in a non-obese man.

OBJECTIVE: We wanted to establish and understand how the fractional losses of fat, fat-free tissues, and selected nutrients compare with that of body mass during a 44-d voluntary starvation (water only) and measurements of nutrient status. METHODS: We used anthropometry, sequential measurements of urinary substances during the fast, and blood analytes at the end of the fast. RESULTS: At the start of the fast, body weight was 96.0 kg (20% fat) and body mass index was 28.36 kg/m(2). The changes in body mass and arm anthropometry and in the pattern of urinary excretion of creatinine, ammonia, sodium, and ketone bodies during the study were consistent with starvation. At the end of the fast, body mass had decreased by 25.5%, of which a quarter to a third was due to loss of fat and the remainder to fat-free mass, predominantly muscle. There was an estimated loss of 20% of total body protein, 20-25% of fat-free mass, and a greater fractional loss of fat. Total energy expenditure was estimated to be 1638-2155 kcal/d of which 13.0-17.1% was from protein oxidation. Differential losses of minerals in urine ranged from 1.2% of estimated initial body content for manganese to 17.3% for selenium and 40.5% for zinc. At the end of the study, plasma concentrations of zinc and vitamin B12 were increased, those of copper, selenium, and manganese were normal, and there was biochemical evidence of deficiency in thiamine, riboflavin, and vitamin K (prothrombin time). CONCLUSION: The data confirm and extend the available information on prolonged fasting in lean individuals and have relevance to the understanding of the physiologic responses to starvation and the associated homeostatic mechanisms.

A comparison of mid upper arm circumference, body mass index and weight loss as indices of undernutrition in acutely hospitalized patients.

A nutritional supplementation trial (Vlaming et al., Clin Nutr 2001; 20: 517) enabled us to assess the nutrition of 1561 patients on emergency admission to hospital. Patients acutely admitted to the 15 relevant medical, surgical and orthopaedic wards were identified. Mid upper arm circumference (MUAC) measurements were obtained in 95% (848 m, 635f) patients. For clinical reasons, Body mass index (BMI) was assessable in only 44% patients (408 m, 285f). Data on three month weight loss were obtainable in 509 patients. These measurements combined to demonstrate that 18.3% of patients were undernourished (At least one of : BMI<20 kg/m(2) or MUAC<25 cm or loss of weight > or =10%). There was a close relationship between BMI and MUAC. Regression equations (excluding age)were for men : BMI=1.01 x MUAC-4.7, (R(2)=0.76), and for women BMI=1.10 x MUAC-6.7, (R(2)=0.76). After adjustment for age, weight loss > or =10% was the most significant of the three as a predictor of mortality. Among patients in whom weight loss was not recorded MUAC was a significant predictor of mortality either alone (P=0.002) or after adjustment for BMI (P=0.007), but BMI was not significant. All three measures, even when adjusted for age and sex, were poor predictors of hospital stay although MUAC was significant in the larger group with a MUAC measure (R(2)=0.7% P<0.001). MUAC correlates closely with BMI, is easier to measure and predicts poor outcome better.

ESPEN Guidelines on Parenteral Nutrition: gastroenterology.

Undernutrition as well as specific nutrient deficiencies has been described in patients with Crohn's disease (CD), ulcerative colitis (UC) and short bowel syndrome. In the latter, water and electrolytes disturbances may be a major problem. The present guidelines provide evidence-based recommendations for the indications, application and type of parenteral formula to be used in acute and chronic phases of illness. Parenteral nutrition is not recommended as a primary treatment in CD and UC. The use of parenteral nutrition is however reliable when oral/enteral feeding is not possible. There is a lack of data supporting specific nutrients in these conditions. Parenteral nutrition is mandatory in case of intestinal failure, at least in the acute period. In patients with short bowel, specific attention should be paid to water and electrolyte supplementation. Currently, the use of growth hormone, glutamine and GLP-2 cannot be recommended in patients with short bowel.

Nutritional interventions in critical illness.

The metabolism of critical illness is characterised by a combination of starvation and stress. There is increased production of cortisol, catecholamines, glucagon and growth hormone and increased insulin-like growth factor-binding protein-1. Phagocytic, epithelial and endothelial cells elaborate reactive oxygen and nitrogen species, chemokines, pro-inflammatory cytokines and lipid mediators, and antioxidant depletion ensues. There is hyperglycaemia, hyperinsulinaemia, hyperlactataemia, increased gluconeogenesis and decreased glycogen production. Insulin resistance, particularly in relation to the liver, is marked. The purpose of nutritional support is primarily to save life and secondarily to speed recovery by reducing neuropathy and maintaining muscle mass and function. There is debate about the optimal timing of nutritional support for the patient in the intensive care unit. It is generally agreed that the enteral route is preferable if possible, but the dangers of the parenteral route, a route of feeding that remains important in the context of critical illness, may have been over-emphasised. Control of hyperglycaemia is beneficial, and avoidance of overfeeding is emphasised. Growth hormone is harmful. The refeeding syndrome needs to be considered, although it has been little studied in the context of critical illness. Achieving energy balance may not be necessary in the early stages of critical illness, particularly in patients who are overweight or obese. Protein turnover is increased and N balance is often negative in the face of normal nutrient intake; optimal N intakes are the subject of some debate. Supplementation of particular amino acids able to support or regulate the immune response, such as glutamine, may have a role not only for their potential metabolic effect but also for their potential antioxidant role. Doubt remains in relation to arginine supplementation. High-dose mineral and vitamin antioxidant therapy may have a place.

Determinants of quality of life in home parenteral nutrition.

PURPOSE OF REVIEW: To highlight the most important and salient articles regarding home parenteral nutrition and quality of life published within the last 3 years. RECENT FINDINGS: In recent years, quality of life research in home parenteral nutrition has highlighted the need for a therapy-specific validated questionnaire. Several papers suggest a greater psychological input is required to better understand and evaluate this patient population. Issues surrounding the use of home parenteral nutrition in malignancy have arisen, prompting discussion on ideal timing and candidacy for home parenteral nutrition. Intestinal transplantation is evolving and improving, making it a possible alternative to home parenteral nutrition. Earlier referral is suggested as late referral can result in poorer outcome. SUMMARY: Home parenteral nutrition is a life-sustaining therapy for individuals with intestinal failure. There is now a relatively large amount of research into the quality of life in this population, but more focused measurements (in the form of validated therapy-specific questionnaires) are required to answer questions relating to cancer and intestinal transplantation.

Selenium in critical illness.

PURPOSE OF REVIEW: Selenium is a trace element essential to human health. Critical illness is associated with the generation of oxygen free radicals resulting in a condition of oxidative stress. Supplementing critically ill patients with antioxidant nutrients may improve survival. Selenium levels can be low due to redistribution to high-priority organs and dilution associated with aggressive resuscitation of the patient. The purpose of this review is to investigate the benefit of selenium supplementation in critically ill patients. RECENT FINDINGS: Most of the selenium-supplementation trials were performed in relatively small patient populations presenting with trauma, sepsis, burns and adult respiratory distress syndrome. Widely varying doses of selenium of between 200 and 1000 microg were used, either alone or in combination with other antioxidants. Significant improvements have been demonstrated in length of hospital stay, rate of infection and need for haemodialysis in these patients. However, no trial has demonstrated a statistically significant improvement in mortality. Two recent meta-analyses suggest a trend towards reduced mortality with selenium supplementation. SUMMARY: Selenium, by supporting antioxidant function, may be associated with a reduction in mortality. To demonstrate this large, well-designed randomized trials are required.

The management of short-term intestinal failure in obese patients.

The prevalence of obesity in the general population is high and it is inevitable that artificial feeding will be needed from time to time in the obese patient, particularly in the critical care setting. Against a background of generous endogenous stores of energy as adipose tissue and the ability of obese individuals to survive starvation longer than non-obese individuals, emphasis is placed on preserving lean body mass and optimizing physiological function. Insulin resistance is typical of the obese individual and is exacerbated by stress; overfeeding is dangerous, particularly if it results in hyperglycaemia. Refeeding syndrome also has to be avoided. Weight may be difficult to measure and lean body mass difficult to assess. Calculation of energy requirements is therefore problematic in practice in the obese individual and there is substantial evidence from controlled clinical trials of the safety of feeding at or below resting energy expenditure. If this approach is taken it is wise to provide a more generous than normal protein intake and to beware of patients with a very high baseline urinary N excretion.

Artificial nutrition: principles and practice of enteral feeding.

Enteral feeding is a commonly used form of nutritional supplementation for patients with intestinal failure, both in hospitals and in the community. This article concentrates on the basic principles of enteral feeding, including the physiological effects of feeding into the intestinal tract. It covers the indications for enteral feeding, the different methods of supplying enteral feeds to the gastrointestinal tract, and the potential complications. There is also a discussion of the indications for and practice of home enteral nutrition.