27th ESPEN Congress

 

European Society of Clinical Nutrition and Metabolism

August 27 – August 30,2005

Brussels,Belgium

Glutathione metabolism in critical illness

F Hammarqvist,MD-Sweden

 

Glutathione (GSH) is the body's principal scavenger of reactive oxygen species (ROS) and used to reduce oxidative stress.GSH,a tripeptide of glutamate,cysteine and glycine,is found in the blood,muscle and liver,and in highest concentration in the duodenal mucosa.GSH acts with the enzyme glutathione peroxidase and the trace element selenium (Se) to neutralize ROS.Another enzyme,glutathione reductase,recycles the oxidized glutathione for further use.

Mitochondrial malfunction in critical illness was discussed throughout the congress,with a focus in this session on the inhibitory effects of ROS and the corresponding decrease in GSH production (Brealey D,et al.Lancet 2002;360:219-223).Lower GSH levels have also been measured in patients with malnutrition and Crohn's disease.A number of trials support the use of glutamine in attenuating post-traumatic GSH depletion.It was also noted that cysteine is a rate-limiting constituent of GSH.Compounds high in cysteine may enhance GSH synthesis and thereby decrease oxidative stress associated with cellular and organ damage.

 

Life saving effects of tight blood glucose control in the critically ill

G Van den Berghe,MD-Belgium

 

Dr Van den Berghe shared the results of her latest randomized controlled trial (RCT),which assessed blood glucose (BG) control in surgical and medical intensive care unit (ICU) patients (n=1,200).ICU and total hospital mortality rates were lower in patients with tight BG control (80-110 mg/dL) than those with poorer BG control (180-200 mg/dL).

A question was raised to ask whether the positive outcomes are due to decreased BG or increased insulin levels.Despite the contribution of both insulin and BG,it appears that the reduction in BG is the more important factor.

Discussion followed about animal studies that have shown lactic acidosis develops when insulin drives large amounts of glucose from the blood into cells.This observation may support a need to limit overall carbohydrate intake to control BG levels,and ultimately lowering insulin requirements.

 

The effects of severe chronic malnutrition and refeeding on metabolism,protein synthesis and digestive function

T Winter,MD-USA

 

Research has shown that secretion of gastric acid and pancreatic enzymes is impaired in the severely undernourished,as well as those with malnutrition secondary to Crohn's disease (Winter TA,et al .Inflamm Bowel Dis 2004;10:618-625;Winter TA,et al.Nutrition 2001;17:230-235).Severe chronic malnutrition also decreases gastrointestinal (GI) motility and increases intestinal permeability.In the severely malnourished,refeeding has a trophic effect on the gut and resolves pancreatic atrophy.Successful refeeding has been observed in patients given semi-elemental diets for 1-2 weeks,with subsequent transition to polymeric feeds.People with malnutrition secondary to anorexia are a notable exception,as it appears that protein synthesis and intestinal permeability are not impacted in these patients as is in severe chronic malnutrition.

 

Physiological response of the pancreas to enteral and parenteral nutrition

S.O'Keefe,MD-USA

 

Several studies in healthy volunteers examined the effect of different enteral formulations and TPN (total parenteral nutrition) on pancreatic secretion.TPN did not stimulate the pancreas,while elemental formula fed orally or duodenally decreased pancreatic secretion by 50% compared with a standard whole protein formula.An additional study in 8 healthy volunteers (Vu MK,et al.Eur J Clin Invest 1999;29:1053-1059) showed that placing the feeding tube 40 cm distal to the ligament of Treitz was most effective in avoiding pancreatic stimulation.Mid-distal jejunal feeding tube placement in severe acute pancreatitis is feasible,even in those with ileus (Kaushik N,et al.Pancreas 2005 [in press]).However,there are conflicting views as to the correct position of the tip of the feeding tube for patients with severe acute pancreatitis patients.Dr O'Keefe challenged a recent study in patients with pancreatitis (Eatock FC,et al.Am J Gastroenterol 2005;100:432-439) that found no difference between feeding via the nasogastric vs the nasojejunal route.Dr O'Keefe questioned the conclusions of the study,suggesting that the data reflects an inconsistent use of feeding tubes that are small enough to be placed jejunally.

 

Diet therapy and pharmacological therapy in chronic intestinal failure

B Messing,MD – France

 

Patients with intestinal failure may be classified into one of two groups:those with a jejunostomy and those with a preserved colon.Absorptive adaptation is more likely to occur in the latter group,although both are dependent upon the length of the remaining small intestine.Recommended nutritional intervention for both groups includes hyperphagia (>1.5 x resting energy expenditure [REE]) (Crenn P,et al.Gut 2004;53:1279-1286),a low oxalate diet,and the following dietary recommendations:

 

Jejunostomy	Jejuno-colon Anastomosis
Avoid hyperosmolar liquids	Avoid liquid intake outside of meal times
Fat not restricted	Restrict fat to <33% of total Kcal and utilize medium chain triglycerides (MCT)

 

A study done by Joly et al.compared a standard oral diet,tube feeding (TF) and a combination of TF and oral diet,which were given for 7 days.The combination of TF and oral diet resulted in a 20% increase in measured absorption (proteins and lipids,p <0.001) relative to oral diet alone.

Pharmacological interventions concentrate on supplementing hormonal peptides that regulate motility.After short bowel resection,physiological adaptive processes and pharmacological therapy can be optimized only in the absence of malnutrition.

 

Pre-and probiotics before and after liver transplantation

N Rayes MD-Germany

 

A recent prospective,randomized,double-blind trial (Rayes N,et al.Am J Transplant 2005;5:125-130) compared the effect of two enteral nutrition (EN) formulas on the incidence of post-operative bacterial infections after liver transplant (n=66).One group of patients received four lactic acid bacteria (LAB) in combination with four fibers (beta-glucan,inulin,pectin and resistant starch),while the second group received only the addition of supplemental fibers.Treatment was started the day before surgery and continued for 14 days.Thirty-day infection rate,length of stay (LOS),duration of antibiotic therapy,non-infectious complications and side effects of EN were recorded.The infection rates were markedly different between groups;the incidence was 48% in those receiving fibers alone compared with 3% in those receiving LABs and fibers.However,the infections were considered mainly mild or moderate across groups,with a large percentage of urinary tract infections (UTIs).The duration of antibiotic therapy was significantly shorter in the group receiving LABs and fibers.It was concluded that early EN combined with prebiotic fibers was associated with a low incidence of severe infections and may have a protective effect.Early EN with both LABs and fibers was found to reduce bacterial infection rates following liver transplantation.A possible mechanism for the protective effects of prebiotic fiber is the associated bifidogenic effect on healthy gut microbiota and supplemented probiotic bacteria.LABs are also known to induce heat-shock proteins (HSP).

The question of the safety of using probiotics in immunocompromised patients was raised.Dr Rayes noted 1 positive blood culture associated with the use of probiotics in the study,but it did not have clinical consequences for the patient.

 

Glutamine:role of heat shock protein expression

P.Wischmeyer MD – USA

 

HSPs are a family of highly conserved proteins that are present in all cells.HSPs are induced by a variety of stressors,and serve to stabilize cells and prevent cell death.Data was presented that showed pharmacological doses of alanyl-glutamine are associated with enhanced HSP expression in both cellular media and in animal models.Earlier induction of HSP may help to better attenuate end-organ injury related to trauma or stress.Enhanced pulmonary HSP expression is associated with a lessening of sepsis/systemic inflammatory response syndrome (SIRS) lung injury and intestinal epithelial cell injury.New data was presented from a 7-day study in critically ill patients given pharmacological doses of intravenous (IV) alanyl-glutamine that showed a 4-fold increase in HSP,and a decrease in LOS and time on the ventilator.

In the future,HSP may be a useful marker to study outcomes in critically ill patients.

 

 

 

 

 

 

 

 

 

Nestle Nutrition Institute Satellite Symposium:Wound Healing:Does Nutrition Make a Difference?

n Make a Difference?

Wound Physiology Overview

L.Teot MD,PhD-France

 

The complex aspects of the normal wound healing process were reviewed,with an emphasis on growth factors that spur the cascade of intracellular reactions that result in the synthesis of collagen.One such growth factor,nerve growth factor,is important in nerve development following angiogenesis that occurs with normal wound healing.A deficiency in this growth factor is considered one explanation for the impaired wound healing that occurs in patients with spinal cord injury.Under normal conditions,healing is promoted by neuropeptides that are released from newly generated nerve endings.

In addition to malnutrition,a number of other barriers to normal wound healing that may be present in patients were described:

• Necrotic tissue

• Infection

• Age,neurological status and general physical condition

• Pressure as a causal factor

• Local treatment,ie,type of dressings

While evidence-based medicine is ideal,RCTs in this field are prohibitively expensive,and would require too large a number of patients to be conducted within Western Europe.Thus nutritional guidelines,based on smaller studies and meta-analyses,were discussed as a compromise to scientifically support the role of nutrition in wound healing and determine the most appropriate practice.

 

The Role of Nutrition in Wound Healing

C.Collins,SRD – United Kingdom

 

Independent risk factors for impaired wound healing include presence of infection,inadequate tissue perfusion,older age,poor glycemic control and suboptimal nutrition.The National Pressure Ulcer Long-Term Care Study (Horn SD,et al.J Am Geriatr Soc 2004;53:359-367) retrospectively evaluated 1,524 nursing home residents and found that the incidence of pressure ulcer (PU) was 29%.Furthermore,the risk of PU was increased by 74% and 42% in those with involuntary weight loss and dehydration,respectively.Disease-specific and high protein/energy TF,as well as oral nutritional supplements (ONS),statistically significantly lowered the risk of PU.

A range of nutrients can help to improve wound healing,and data was presented on the role of supplemental vitamin C.While a RCT (ter Riet G,et al.J Clin Epidemiol 1995;48:1453-1460) demonstrated no difference in pressure sore wound healing between patients receiving vitamin C supplements of 1,000 mg or 20 mg,the results have more recently been disputed because the wound dressings used in this study disrupted the granulation process,making any differences in healing unobservable.

The need to critically review research on micronutrient supplementation and wound healing was emphasized.Studies show that healing is impaired in patients with micronutrient deficiencies,but limited data is available supporting the benefit of supplementation beyond 100% of normal requirements.In practical terms,the challenge is to determine which patients are most at risk of deficiency and then implement supplementation as early as possible within current guidelines.

 

Pressure Ulcers:How big is the problem?

Mike Clark,PhD – United Kingdom

 

A recent pilot study from the European Pressure Ulcer Advisory panel (EPUAP) looked at PU prevalence in hospitals across five European countries and found that 20% of patients may experience some form of pressure lesion or injury.

Data on cost is difficult to obtain,as there is little data outside the acute sector.Within the acute sector,Stage I PUs are not always recorded.An ongoing study of the EPUAP may concentrate on identifying Stage II,III and IV PU,all of which involve a wound with broken skin.Stage I does not involve broken skin and,thus,would be excluded.

Cost data from the United Kingdom (UK) in 2004 predicts the cost of treatment for each Stage IV PU to be ?10,551 (US $19,427) and data from Allman RM and colleagues ( Adv Wound Care 1999;12:22-30) showed large increases in cost associated with a longer LOS for patients with PU.In general,up to 4% of Western healthcare budgets are currently spent on the treatment and complications of PU.

 

 

Can enteral nutrition prevent and treat pressure ulcers?

RJ Stratton,PhD – United Kingdom

 

A recent meta-analysis (Stratton RJ,et al.Ageing Res Rev 2005;4:422-450) of 15 studies involving patients on TF,ONS or a combination of the two (n=3,216) considered two questions:

• Can EN decrease the incidence of PU?

• Can EN improve healing of PU?

It was concluded that high protein EN could reduce the risk of developing PU by 25% in those at high risk compared with those with routine care (odds ratio 0.75,95% confidence interval [CI].62-0.89).Proposed mechanisms for the role of improved nutrition in preventing PU include:

• Increased soft tissue padding

• Increased well being and energy

• Improved skin condition from increased blood flow associated with the use of arginine

• Decrease in other treatments needed

EN may also improve PU healing (Benati G,et al.Arch Gerontol Geriatr Suppl 2001;7:43-47).As,the number of RCTs on this subject is presently inadequate;the current meta-analysis could not definitively address this question.

 

Is there evidence for enteral nutrition in cancer patients?

G Nitenberg,MD-France

 

A recent meta-analysis of 62 studies involving the use of EN or PN in cancer patients addressed two questions:

• Is EN better than PN in cancer patients?

• Does supplementation with eicosapentaenoic acid (EPA) show benefit?

Studies were categorized into 3 patient groups:

• Radiation/chemotherapy/bone marrow transplant (BMT)

• Cancer surgery

• Palliative care

No studies utilizing IEDs (immune-enhancing diets) were included.Although there were no significant differences in survival,it was concluded that EN vs PN in cancer surgery patients was associated with:

• Decreased hospital LOS by 1.72 days (95% CI 0.9–2.8)

• Reduced incidence of infectious complications

• Lower sepsis scores

There was some discussion about the comparative PN studies being dated and perhaps reflective of practice that is now classified as overfeeding.

Analysis of 3 RCTs in radiation/

chemotherapy/BMT patients showed an improvement in energy intake (381 Kcal/d) with the use of ONS.Conclusions could not be drawn on the use of EN vs PN in either this or the palliative care population,as insufficient RCTs exist.The same was true regarding EPA supplementation in cancer patients.It was noted that certain patient populations,often those of greatest concern,are often excluded from studies and that data from RCTs is only one component of the relevant information that must be evaluated to determine appropriate management in these patients.

 

 

 

 

 

 

 

 

 

Scientific Abstracts

 

Systematic review and meta-analysis of the effects of standard versus diabetes-specific enteral formulae for patients with diabetes mellitus?

Stratton RJ,Ceriello A,Laube H et al.

United Kingdom

 

A systematic review was undertaken to investigate the effects of standard enteral formulas compared with diabetes-specific enteral formulas given orally or via TF in patients with type I or II diabetes.The review identified 20 studies (n=744) of which 14 (n=437) compared ONS and 6 (n=307) compared enteral TF formulas.Meta-analyses were performed,where possible,to measure the following outcomes:BG,blood lipids,medication requirements and complications.

Diabetes-specific formulas significantly reduced post-prandial rise in BG,peak BG concentration and glucose area under the curve compared with standard formulas.No significant differences were noted in fasting glucose,high-density lipoprotein (HDL),low-density lipoprotein (LDL),total cholesterol or triglyceride concentrations.

The use of diabetic-specific enteral oral supplements and TF can improve glycemic control compared with standard supplements and TF.Accordingly,diabetic-specific enteral oral supplements and TF may assist management and improve outcomes in patients with diabetes.

 

If the gut works,use it! But how well does it work? A study on malabsorption in the ICU

Wierdsma NJ,Van Heijningen EB,De Groot SDW et al.The Netherlands

 

This pilot study evaluated energy loss via feces collected from stable,fully enterally-fed ICU patients (n=13) with loose stools.Stools were collected for 3 days;the energy value was determined using bomb calorimetry and fecal fat content was also analyzed.The total amount of TF during the 3-day collection period was recorded,and energy expenditure was measured by indirect calorimetry.Malabsorption was arbitrarily defined as an energy absorption capacity of 85% or less.

Mean energy absorption capacity was found to be 84 ± 14%.Forty six per cent of subjects met the criteria to be considered malabsorbers.Mean fecal fat loss was 8.0 ± 8.3 g/d,resulting in a mean fat absorption capacity of 90 ± 16%.A daily fecal output of >250g was a good predictor of malabsorption.

Malabsorption contributed to negative energy balances in 30% of patients,and is a previously unrecognized,but significant,problem in ICU patients with loose stools.

Selenium supplements reduce the incidence of nosocomial pneumonia after major burns.

Berger MM,Eggimann P,Revelly JP et al.

Switzerland

 

A previous trial in 20 patients found that the incidence of pneumonia was lower when Se,copper (Cu) and zinc (Zn) supplements were provided for 8 days after major burns.The present study examined the same outcome,but in a larger patient population (n=41,Body Surface Area Burn [BSAB]=46 ± 19%).Two consecutive prospective,randomized,placebo-controlled trials delivered Cu 59 µmol,Se 4.8 µmol (370 mg) and Zn 574 µmol,or placebo IV for 8-21 days depending on burn size.

Data was collected over 30 days and showed plasma Se and glutathione peroxidase concentrations were significantly higher in the supplemented group (TE) after day 5.The total number of infectious complications was lower in the TE group (2.0 vs 3.5 episodes,p=0.0002) as were the number of cases of pneumonia (0.6 vs 1.7 episodes,p=0.0005).Trace element supplementation was associated with a 30% risk of developing nosocomial pneumonia over a 30-day period compared with a risk of 80% in the placebo group.The length of ICU stay per % BSAB was also shorter in the TE group (0.64 vs 1.03 days/%,p=0.008).

Trace element supplements,including Se,were associated with a significant reduction in the incidence of nosocomial pneumonia and in length of ICU stay.The authors concluded that a possible mechanism is the reinforcement of antioxidant defenses by the trace elements.

 

Plasma amino acid profiles in critically ill children:Relationship with underlying disorder and severity of inflammation

Waardenburg DA,Luiking YC,Deutz NEP et al.

The Netherlands

 

This study aimed to investigate changes in arterial amino acid (AA) profiles in children (age 3 months to 16 years,n=60) admitted to the pediatric ICU with a variety of acute conditions:sepsis,trauma,major surgery and viral airway disease.Plasma AA levels were studied in the fasted state and within 24 hours of admission.

Glutamine,arginine and citrulline levels were lower while phenylalanine levels were higher in children with sepsis and trauma compared with those with viral disease.C-reactive protein (CRP) levels were significantly negatively correlated with total AA levels,plasma glutamine (p <0.001),citrulline (p <0.001) and arginine (p <0.001).

It was concluded that critical illness in children is associated with low arterial AA concentrations.The severity of inflammation,as defined by CRP and underlying acute illness,rather than severity of illness per se was correlated with alterations in plasma glutamine,arginine,citrulline and phenylalanine levels.

 

Continuous L-arginine infusion does not deteriorate the hemodynamic condition in patients with severe sepsis

Luiking YC,Poeze M,Hendrikx M et al.

The Netherlands

 

Arginine is the precursor of nitric oxide,a known vasodilator.Although patients with sepsis have reduced plasma arginine levels,use of arginine in this population has been of concern because of the vasodilatory properties of nitric oxide.This study was performed to measure the dose-response of continuous intravenous arginine supplementation in patients with severe sepsis.

Eight ICU patients who had severe sepsis/septic shock (APACHE II scores 27-43) for less than 48 hours were studied.Norepinephrine dose ranged between 0.05 and 0.8 µg/kg/min.Arginine levels were measured at baseline and every 2 hours as the dose of IV arginine was increased in a step-wise fashion (0.6,1.2 and 1.8 µmol/kg/min).Hemodynamics were recorded at 30-minute intervals.

No significant changes in systemic blood pressure were observed,while arginine levels were found to be significantly lower (p <0.05) than those of healthy age-matched controls.Heart rate decreased and stroke volume increased during arginine supplementation.

The authors concluded that arginine infusion does not affect blood pressure,but increases cardiac stroke volume.Continuous IV arginine supplementation was not associated with deterioration in hemodynamics in patients with severe sepsis,despite its vasodilatory effect.

 

Reduced circulating TNF receptor 75 after enriching enteral nutrition with glutamine and antioxidants following major upper GI surgery

Boelens PG,Melis GC,Diks J et al.

The Netherlands

 

This study evaluated the effect of EN enriched with glutamine and antioxidants on inflammatory markers following major upper GI surgery (n=20).All patients had undergone surgery for at least 3 hours and were fed postoperatively via jejunostomy with either standard EN (Sondalis ISO) or EN enriched with glutamine,cysteine,Zn,Se,?-tocopherol,?-carotene and Vitamin C.CRP,interleukin (IL)-6,IL-1,IL-8 and soluble tumor necrosis factor (TNF) receptor p75 were measured before surgery and postoperatively on days 1,3,5 and 7.CRP levels were lower in the first 5 and 7 days in patients receiving enriched EN (p=0.084).Soluble TNF receptor p75 decreased significantly in the first 3 days (p <0.05),with a trend for a reduction in the first 5 days (p=0.072).IL-1 and IL-6 levels were not significantly different between groups.

EN enriched with glutamine and antioxidants blunted the inflammatory response in patients after major GI surgery.

 

Protein undernutrition in quiescent Crohn's disease:An unrecognized problem?

Suibhne Nic T,O'Morain C,O'Sullivan M et al.

Ireland

 

Undernutrition may be well studied in active Crohn's disease (CD),but the problem is poorly defined in patients who are in remission.This study examined the nature and prevalence of malnutrition in non-hospitalized CD patients (n=70) vs healthy controls (n=23).Protein stores were measured by midarm muscle circumference (MAMC) and grip strength (GS),and fat stores by triceps skin fold thickness (TSF).Undernutrition was defined as MAMC and TSF <15 th centile,GS <population standard and BMI (body mass index) <20 kg/m 2.Remission was defined as a Crohn's Disease Activity Index (CDAI) <150.

Low MAMC and GS values were significantly more prevalent in CD compared with controls.Additional study of the CD participants with factors suggestive of muscle depletion found the majority had normal BMI,serum albumin and fat stores.Data suggests a 47% prevalence of undetected muscle protein depletion among CD patients in remission with normal BMI.

 

High prevalence of sarcopenia in patients with Crohn's disease:Association with osteopenia

Al-Jaouni R,Filippi J,Wiroth J,,et al.-France

 

The presence of sarcopenia and an association between sarcopenia and osteopenia were examined in adult patients (37 ± 13 years) with CD in remission (n=67) and healthy volunteers (n=39).CD patients had a CDAI <150 and CRP <10 mg/L.Appendicular muscle mass (AMM) and bone mineral density (BMD) were measured using DEXA (Hologic) and osteopenia assessed according to the World Health Organization (WHO) classification.AMM was lower in CD patients than controls (p=0.02) and a positive correlation was found between AMM and BMD (r=0.50;p=0.0001).The prevalence of sarcopenia was 61% in patients and 20% in controls (p <0.001),while prevalence of osteopenia was 30% in patients and 5% in controls.Further,the prevalence of osteopenia was 43% in patients with sarcopenia,and 8% in patients without sarcopenia (p <0.001).Sarcopenia is strongly associated with osteopenia and the prevalence of sarcopenia is high in patients with CD.These two phenomena may have synergistic deleterious effects and may share similar mechanisms.Findings suggest the routine determination of BMD and AMM may be helpful in CD patients.

Mini Nutritional Assessment (MNA a ):Preferable nutritional assessment tool

Hengstermann S,Nagel A,Azzaro M et al.

Germany

 

In this study three established assessment tools (MNA a ,subjective global assessment [SGA] and the malnutrition universal screening tool [MUST]) were compared in geriatric patients with multiple comorbidities (n=520) to assess their accuracy in identifying malnutrition.The most efficient assessment tool was found to be the MNA a ,which was subsequently modified and termed the M-MNA.The MNA a was comparable with the M-MNA and identified 11% of patients as well nourished,76% with a risk of malnutrition and 13% malnourished.In comparison,the SGA found 42% well nourished and 5% malnourished while the MUST indicated the highest portion of malnutrition (43%).The MNA a was found to be the most sensitive parameter to identify malnutrition due questions about diet mobility and dementia.

 

A cost-benefit analysis of oral nutritional supplements in preventing pressure ulcers in hospital

Elia M,Stratton RJ – United Kingdom

 

A systematic review of 4 RCTs examining the effect of liquid ONS (200-400 mL/d;1-1.5 Kcal/mL,2-26 weeks) on the incidence of PUs in high-risk hospitalized elderly patients was performed to conduct a cost-benefit analysis.A 25% increase in PU incidence was found in controls (39%;n=712) compared with ONS patients (32%;n=613).However,information on the stage of PU was lacking,and the cost analysis used full hospital costs for each PU stage from the UK (?1,064,?4,402,?7,313 and ?10,551 for Stages I,II,III and IV,respectively.) The ONS cost was also based on UK hospital practice (?0.20/200 mL).A net cost saving in favor of ONS was observed for all stages of PU;however,these cost savings were only statistically significant for Stage III (p=0.04) and IV (p=0.04) PU.This corresponds to a net cost saving of ?5 (Stage I) to ?460 (Stage IV) per patient,suggesting that use of ONS in older patients at high risk of PU produces a net cost-benefit,the magnitude of which depends on the stage of ulcer.