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Background: This is Part 2 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy (EL) using an Enhanced Recovery After Surgery (ERAS) approach. This paper addresses intra- and postoperative aspects of care. Methods: Experts in aspects of management of high-risk and emergency general surgical patients were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and Medline database searches were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses, and large cohort studies and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. Some ERAS® components covered in other guideline papers are outlined only briefly, with the bulk of the text focusing on key areas pertaining specifically to EL. Results: Twenty-three components of intraoperative and postoperative care were defined. Consensus was reached after three rounds of a modified Delphi Process. Conclusions: These guidelines are based on best available evidence for an ERAS® approach to patients undergoing EL. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies. [ABSTRACT FROM AUTHOR]

Critically ill patients treated for multiple organ failure often develop muscle dysfunction. Here we test the hypothesis that mitochondrial and energy metabolism are deranged in leg and intercostal muscle of critically ill patients with sepsis-induced multiple organ failure. Ten critically ill patients suffering from sepsis-induced multiple organ failure and requiring mechanical ventilation were included in the study. A group (n = 10) of metabolically healthy age- and sex-matched patients undergoing elective surgery were used as controls. Muscle biopsies were obtained from the vastus lateralis (leg) and intercostal muscle. The activities of citrate synthase and mitochondrial respiratory chain complexes I and 1V and concentrations of ATP, creatine phosphate, and lactate were analyzed. Morphological evaluation of mitochondria was performed by electron microscopy. Activities of citrate synthase and complex I were 53 and 60% lower, respectively, in intercostal muscle of the patients but not in leg muscle compared with controls. The activity of complex IV was 30% lower in leg muscle but not in intercostal muscle. Concentrations of ATP and creatine phosphate were, respectively, 40 and 34% lower, and lactate concentrations were 43% higher in leg muscle but not in intercostal muscle. We conclude that both leg and intercostal muscle show a twofold decrease in mitochondrial content in intensive care unit patients with multiple organ failure, which is associated with lower concentrations of energy-rich phosphates and an increased anaerobic energy production in leg muscle but not in intercostal muscle. mitochondrial respiratory chain; energy-rich phosphates; skeletal muscle; intensive care unit; oxidative stress

The complex nature of pancreatic operation makes it a high-risk and technically demanding major abdominal procedure, resulting in early pathophysiological alterations. This study aims to observe changes in body composition, muscle function and biochemical values in patients during the early postoperative days (PODs) following pancreaticoduodenectomy or total pancreatectomy. Assessment of body composition by bioimpedance spectroscopy, muscle function by peak expiratory flow rate (PEFR) and maximum handgrip strength (HGS), and biochemical values were measured in patients the day before surgery and on PODs 3, 6 and 9. Significant changes occurred among 34 patients on POD 3 in body weight +2.3 (0.8–3.6) kg, total body water +2.8 (1.1–5.9) L, extracellular water +2.5 (1.2–3.7) L, intracellular water +1.1 (−0.4–1.9) L, phase angle −1.0 (−1.2 to −0.7)°, PEFR −250.0 (−407.5 to −125.0) L/m and HGS −4.8 (−7.3 to −3.0) kg, C-reactive protein +78.0 (41.0–102.8) mg/L, haemoglobin −34.5 (−45.8 to −26.0) g/L, albumin −12 (−16.5 to −10.0) g/L. Changes in water distribution, phase angle, initial reduced muscle function and altered biochemical values were observed during the first 9 PODs. [ABSTRACT FROM AUTHOR]

Observational studies have shown an association between hyperglycaemia and increased complications in orthopaedic patients. The aim of the study was to investigate if impaired preoperative glycaemic control, reflected by elevated HbA1c, was associated with adverse postoperative events in hip fracture patients. 160 patients (116 women and 44 men; age 80 ± 10 and BMI 24 ± 4; mean ± SD) with hip fractures were included in a prospective observational cohort study. The patients were divided into two groups, normal glycaemic control (NGC) and impaired glycaemic control (IGC) HbA1c ≥ 42 mmol/mol. The patients were also characterized according to BMI and nutritional status using MNA-SF (Minimal Nutritional Assessment Short Form). Complications within 30 days of surgery were classified according to Clavien–Dindo and 1-year mortality was compared between the groups. Out of 160 patients, 18 had diabetes and 4 more had likely occult diabetes (HbA1c ≥ 48). Impaired glycaemic control (IGC) was seen in 29 patients (18.1%) and normal glycaemic control (NGC) in 131 (81.9%). In patients with NGC and IGC, no postoperative complications (Clavien–Dindo Grade 0) were seen in 64/131 vs. 14/29 (48.9 vs. 48.3%), Grade 1-3a in 54/131 vs. 14/29 (41.2 vs. 48.3%) and Grade 3b-5 in 13/131 vs. 1/29 (9.9 vs. 3.4%) respectively, p = NS. There were no differences in 30-day complications (p = 0.55) or 1-year mortality (p = 0.35) between the groups. Elevated HbA1c at admission is not associated with increased complications or mortality after hip fracture surgery. [ABSTRACT FROM AUTHOR]

Background and Aims: Indirect calorimetry (IC) is the gold standard for determining energy expenditure in patients requiring mechanical ventilation. Metabolic armbands using data derived from dermal measurements have been proposed as an alternative to IC in healthy subjects, but their utility during critical illness is unclear. The aim of this study was to determine the level of agreement between the SenseWear armband and the Deltatrac Metabolic Monitor in mechanically ventilated intensive care unit (ICU) patients.Methods: Adult ICU patients requiring invasive ventilator therapy were eligible for inclusion. Simultaneous measurements were performed with the SenseWear Armband and Deltatrac under stable conditions. Resting energy expenditure (REE) values were registered for both instruments and compared with Bland-Altman plots.Results: Forty-two measurements were performed in 30 patients. The SenseWear Armband measured significantly higher REE values as compared with IC (mean bias, 85 kcal/24 h; P = .027). Less variability was noted between individual SenseWear measurements and REE as predicted by the Harris-Benedict equation (2 SD, ±327 kcal/24 h) than when IC was compared with SenseWear and Harris-Benedict (2 SD, ±473 and ±543 kcal/24 h, respectively).Conclusions: The systematic bias and large variability of the SenseWear armband when compared with gas exchange measurements confer limited benefits over the Harris Benedict equation in determining caloric requirements of ICU patients. [ABSTRACT FROM AUTHOR]

Background. The aim of this population-based study was to describe characteristics of patients with liver cirrhosis undergoing cholecystectomy and evaluate the risk for perioperative and postoperative complications during the 30-day postoperative period. Method. All laparoscopic and open cholecystectomy procedures registered between 2006 and 2011 in the Swedish Registry for Gallstone Surgery and ERCP (GallRiks) were included. Patients with liver cirrhosis were identified by linking data to the Swedish National Patient Registry (NPR). Results. Of 62,488 patients undergoing cholecystectomy, 77 (0.12%) had cirrhosis, of which 29 patients (37.7%) had decompensated cirrhosis. Patients with cirrhosis were older and had more often gallstone complications at the time for surgery. Postoperative complications were registered in 13 (16.9%) patients with liver cirrhosis and in 5,738 (9.2%) patients in the noncirrhotic group (P<0.05). Univariable analysis showed that patients with liver cirrhosis are more likely to receive postoperative blood transfusion (OR = 4.4, CI 1.08–18.0, P<0.05) and antibiotic treatment >1 day (OR = 2.3, CI 1.11–4.84, P<0.05) than noncirrhotic patients. Conclusion. Patients with cirrhosis undergoing cholecystectomy have a higher incidence of postoperative complications than patients without cirrhosis. However, cholecystectomy is safe and if presented with adequate indication, surgery should not be delayed due to fears of surgical complications. [ABSTRACT FROM AUTHOR]

Elevated systemic pentraxin 3 (PTX3) levels appear to be a powerful marker of inflammatory status and a superior outcome predictor in patients with chronic kidney disease (CKD). As previous data imply that PTX3 is involved in vascular pathology and that adipose tissue mass may influence circulating PTX3 levels, we aimed to study the importance of adipose tissue expression of PTX3 in the uremic milieu and its relation to endothelial dysfunction parameters. Plasma PTX3 and abdominal subcutaneous adipose tissue (SAT) PTX3 mRNA levels were quantified in 56 stage 5 CKD patients (median age 57 [range 25–75] years, 30 males) and 40 age and gender matched controls (median age 58 [range 20–79] years, 27 males). Associations between PTX3 measures and an extensive panel of clinical parameters, including surrogate markers of endothelial function, were assessed. Functional ex vivo studies on endothelial status and immunohistochemical staining for PTX3 were conducted in resistance subcutaneous arteries isolated from SAT. SAT PTX3 mRNA expression correlated with plasma PTX3 concentrations (rho = 0.54, p = 0.0001) and was increased (3.7 [0.4–70.3] vs. 1.2 [0.2–49.3] RQ, p = 0.02) in CKD patients with cardiovascular disease (CVD), but was not significantly different between patients and controls. The association to CVD was lost after adjustments. SAT PTX3 mRNA levels were independently correlated to asymmetric dimethylarginine and basal resistance artery tone developed after inhibition with nitric oxide synthase and cyclooxygenase (rho = −0.58, p = 0.002). Apparent positive PTX3 immunoreactivity was observed in both patient and control arteries. In conclusion, fat PTX3 mRNA levels are associated with measures of endothelial cell function in patients with CKD. PTX3 may be involved in adipose tissue-orchestrated mechanisms that are restricted to the uremic milieu and modify inflammation and vascular complications in CKD patients. [ABSTRACT FROM AUTHOR]

The study focuses on the mechanisms of endothelial dysfunction in the uremic milieu. Subcutaneous resistance arteries from 35 end-stage renal disease (ESRD) patients and 28 matched controls were studied ex-vivo. Basal and receptor-dependent effects of endothelium-derived factors, expression of endothelial NO synthase (eNOS), prerequisites for myoendothelial gap junctions (MEGJ), and associations between endothelium-dependent responses and plasma levels of endothelial dysfunction markers were assessed. The contribution of endothelium-derived hyperpolarizing factor (EDHF) to endothelium-dependent relaxation was impaired in uremic arteries after stimulation with bradykinin, but not acetylcholine, reflecting the agonist-specific differences. Diminished vasodilator influences of the endothelium on basal tone and enhanced plasma levels of asymmetrical dimethyl L-arginine (ADMA) suggest impairment in NO-mediated regulation of uremic arteries. eNOS expression and contribution of MEGJs to EDHF type responses were unaltered. Plasma levels of ADMA were negatively associated with endothelium-dependent responses in uremic arteries. Preserved responses of smooth muscle to pinacidil and NO-donor indicate alterations within the endothelium and tolerance of vasodilator mechanisms to the uremic retention products at the level of smooth muscle. We conclude that both EDHF and NO pathways that control resistance artery tone are impaired in the uremic milieu. For the first time, we validate the alterations in EDHF type responses linked to kinin receptors in ESRD patients. The association between plasma ADMA concentrations and endothelial function in uremic resistance vasculature may have diagnostic and future therapeutic implications. [ABSTRACT FROM AUTHOR]

We investigated an effect of uraemia on structural and functional features of human resistance vasculature. Arteries (≈ 200 μm) isolated from subcutaneous fat biopsies obtained from 35 ESRD (end-stage renal disease) patients starting peritoneal dialysis and 30 matched controls were studied using isolated small artery bioassays. Flow-mediated dilatation was attenuated in ESRD patients compared with controls. NO (nitric oxide) contribution to flow was lacking in ESRD patients, but present in the controls. ADMA (asymmetrical dimethyl L-arginine) levels were higher in the ESRD group compared with the control group. Dilatation in response to acetylcholine was reduced in ESRD patients compared with controls, but response to NO donor was similar. Expression of nitrotyrosine and heat shock proteins 70 and 27, but not 90, was increased in arteries from ESRD patients compared with controls. Arterial remodelling was absent in ESRD patients. There was no difference between the groups in myogenic tone, vascular reactivity or sensitivity to several vasoconstrictors. Arterial distensibility, reflecting passive properties of the vascular wall, was reduced in ESRD patients compared with controls. Exclusion of ESRD patients with diabetes and/or cardiovascular disease from analyses had no influence on the main findings. Thus we propose that uraemia has a strong impact on endothelial function and passive properties of the arterial wall of human peripheral resistance vasculature. The reduced contribution of NO to flow stimulus via enhanced nitrosative stress and higher plasma concentrations of ADMA may suggest potential mechanisms behind endothelial dysfunction in the resistance peripheral circulation in ESRD. [ABSTRACT FROM AUTHOR]

This study explored if a combined supplementation of GH and IGF-1 had an additive effect on whole body nitrogen economy, energy, substrate and skeletal muscle metabolism following surgical trauma. Patients were randomized to controls (C; n = 10), to GH (0.15 IU/kg/injection) (GH; n = 7) or GH combined with IGF-1 (40 μg/kg/injection) subcutaneously twice a day (GH-IGF-1; n = 9) together with standardized parenteral nutrition. Muscle amino acids, glutathione and the ribosomal pattern reflecting protein synthesis, and nitrogen balance were measured. GH- and GH-IGF-1 groups showed lower urea and higher plasma glucose concentrations. Energy expenditure increased in the GH-group. GH-IGF-1 prevented a decrease in muscle polyribosomes indicating a preserved muscle protein synthesis. In the GH group unaltered BCAA and AAA levels were seen in muscle indicating an unchanged protein breakdown, while the other groups showed increased muscle concentrations postoperatively. Without statistically difference GH marginally improved the nitrogen balance, in terms of higher values, and growth factors improved the nitrogen balance when the shift in urea was taken into account. To conclude, growth factors influences urea metabolism, protein degradation and protein synthesis. There was no clearcut additional effect when combining GH and IGF-1 but the study was probably underpowered to outrule this and effects on nitrogen balance. [ABSTRACT FROM AUTHOR]

Muscle tissue serves as a protein reservoir which is mobilized to meet the specific metabolic needs associated with various catabolic conditions in human subjects, such as trauma and critical illness. Glutathione is one of the most abundant short-chain peptides and a major source of non-protein thiol in the body, and tissue glutathione concentration is related to its oxidative capacity. Skeletal muscle is relatively unique with respect to a variety of metabolic properties, such as oxidative potential, patterns of amino acid utilization, and antioxidant enzyme activity. The glutathione concentration is not influenced by food intake, or by food deprivation. Moreover, there is no diurnal variation on muscle glutathione levels. Following elective surgery the muscle concentration of GSH (the reduced form) decreases by 40 % 24 h post-operatively, while the concentration of GSSG (the oxidized form) remains unaltered. During critical illness a similar decrease in the GSH concentration is seen, but in addition a change in the redox status indicative of an elevated GSSG level occurs. Furthermore, correlations between the concentrations of glutamine as well as glutamate and GSH exist in these patients. From available evidence accumulated it is clear that glutathione plays a pivotal role in the maintenance of the intracellular redox status, the antioxidant vitamin levels, and the antioxidant enzyme functions under various metabolic conditions. The effectiveness of glutathione protection in the individual tissue depends on the tissue concentration of glutathione as well as the capacity of the tissue to import GSH and to export GSSG. The mechanisms by which catabolism regulates tissue glutathione levels and the enzyme activities associated with the γ-glutamyl cycle are not completely understood and further studies need to be conducted. [ABSTRACT FROM PUBLISHER]

Presents a study which examined the decrease of glutathione (GSH) synthetic capacity in human skeletal muscle tissue surgical trauma. Assessment of the postoperative skeletal muscle GSH metabolism; What the cellular GSH homeostasis depends on; Measurement of the total GSH and cysteine; Initiation of reaction.

Presents a study which examined the significance of surgical trauma in decreasing glutathione (GHS) synthetic capacity in human skeletal muscle tissue. Methodology; Characteristics of patients and the operative procedure; Measurement of activities of GHS-related enzymes; Experimental results.

G-protein-coupled estrogen receptors (GPERs) have been proposed to mediate estrogen-mediated vasodilation. The presence of GPER-dependent vasodilation in human resistance-sized arteries (HRAs) or its signal transduction pathways have not been investigated. HRAs in subcutaneous fat tissues (biopsies from postmenopausal women (PMW), age-matched men (M) and pregnant women (PGW)) were mounted for in vitro isometric force recording. Vasodilation induced by G-1 (selective GPER-agonist, 3μM) from HRAs pre-contracted with norepinephrine amounted to 40±5% in PMW, significantly larger than those obtained from M (20±5%) or PGW (20±5%). l-NAME (nitric oxide (NO) synthase inhibitor) abolished these relaxations in PGW, attenuated them in PMW and had no effect in M. Immunohistochemical analysis confirmed the presence of GPER in both smooth muscle and endothelial cells of HRA with maximum expression in PGW. In cultured human umbilical vein endothelial cells (HUVECs), G-1 increased NO-synthesis concentration-dependently through higher expressions of endothelial NO-synthase (eNOS) and through enhanced phosphorylation of eNOS on Ser1177. In conclusion, GPER vasodilates human resistance arteries through various activating mechanisms of the eNOS-signaling pathway. [ABSTRACT FROM AUTHOR]

Patients with septic shock have high plasma glutathione concentrations, whereas intracellular concentrations in erythrocytes and muscle are low. In the present study, we investigated the temporal pattern of glutathione status and glutathione kinetics in healthy volunteers during the initial phase of sepsis using a human endotoxin model. The present study was a descriptive pilot study in healthy male volunteers (n=8) before and after an endotoxin challenge. The glutathione status was determined in plasma and whole blood at baseline and hourly for 4 h after intravenous endotoxin injection and in skeletal muscle at baseline and at 2 and 4 h after endotoxin injection. In plasma, the concentration of total glutathione decreased 24% (P<0.05) at 3 h after endotoxin injection and 32% (P<0.001) at 4 h. In whole blood and skeletal muscle, the concentrations of both GSH and total glutathione as well as the redox status remained unaltered during the initial 4 h after the endotoxin challenge. The FSR (fractional synthesis rate) of glutathione in whole blood was 38+/-20%/day before and 59+/-22%/day 4 h after the endotoxin challenge (P=0.088) and in skeletal muscle this was 41+/-25 and 46+/-18%/day (P=0.68) respectively. During the initial phase of sepsis, as represented by an intravenous endotoxin challenge to healthy volunteers, plasma concentrations of total glutathione decreased, whereas glutathione status and synthesis rate in skeletal muscle and whole blood remained unaltered. However, due to the variation in the synthesis measurements, larger studies are needed to confirm these findings.

Glutathione is a major antioxidant, and, in the present study, we investigated whether a clinical model of short warm ischaemia and reperfusion of the human liver during surgery would influence glutathione and amino acid metabolism. Previous studies in humans have demonstrated that ischaemia and reperfusion in skeletal muscle for up to 120 min have no major effect on muscle glutathione concentrations. Liver ischaemia and reperfusion in animals have demonstrated diverging results concerning glutathione metabolism. In the present study, six patients with liver malignancies, undergoing liver resection during warm ischaemia, were included. Liver biopsies were obtained from healthy appearing liver tissue from both lobes before ischaemia and at maximal ischaemia, and from the remaining liver lobe after 5, 10, 15, 20, 25 and 30 min of reperfusion. The biopsies were analysed for glutathione, amino acids and lactate. Median ischaemia time was 28 (range, 15-36) min. Lactate increased 266% at maximal ischaemia (P<0.05). No alterations in glutathione concentrations or the redox status of glutathione (GSH/total glutathione) were observed. Glutamate decreased 22% (P<0.05) at maximal ischaemia and increased thereafter 72% at 30 min of reperfusion (P<0.05). Alanine increased 105% at maximal ischaemia (P<0.05) and was normalized during reperfusion. BCAAs (branched-chain amino acids) increased 67% at maximal ischaemia (P<0.05). In conclusion, short-time ischaemia and reperfusion in the human liver did not affect glutathione concentrations, whereas changes were observed in amino acid concentrations during both ischaemia and reperfusion.

The temporal pattern of metabolic alterations in muscle tissue during total ischaemia and reperfusion are not well-characterized in humans with respect to glutathione, amino acids and energy-rich compounds. In the present study, knee replacement surgery was used as a clinical model to elucidate this pattern of metabolic alterations. Patients (n=15) undergoing elective knee replacement surgery employing tourniquet ischaemia were studied. Muscle biopsies were taken from the quadriceps femoris muscle on the operated side preoperatively, at maximal ischaemia and after 24 h of reperfusion. The biopsies were analysed for glutathione, amino acids and energy-rich compounds. In addition the patients were randomized to receive either glucose or a mannitol infusion in the 24 h following tourniquet ischaemia. During ischaemia, muscle lactate increased by 400% (P<0.05) and phosphocreatine decreased by 70% (P<0.05). During the subsequent 24 h of reperfusion, muscle-reduced glutathione and total glutathione decreased by 27% and 22% (P<0.05) respectively. The muscle amino acid pattern changed during ischaemia with an increase in alanine by 65% (P<0.001) and a decrease in glutamate by 29% (P<0.001). During the reperfusion part of the study, no differences attributable to the infusion of mannitol or glucose were observed. During tourniquet ischaemia and subsequent reperfusion, changes in glutathione metabolism developed, indicating oxidative stress. Knee replacement surgery as a clinical model was useful during the ischaemia period, whereas the reperfusion period was dominated by the general changes seen postoperatively.

Patients with sepsis in the ICU (intensive care unit) are characterized by skeletal muscle wasting. This leads to muscle dysfunction that also influences the respiratory capacity, resulting in prolonged mechanical ventilation. Catabolic conditions are associated with a general activation of the ubiquitin-proteasome pathway in skeletal muscle. The aim of the present study was to measure the proteasome proteolytic activity in both respiratory and leg muscles from ICU patients with sepsis and, in addition, to assess the variation of proteasome activity between individuals and between duplicate leg muscle biopsy specimens. When compared with a control group (n=10), patients with sepsis (n=10) had a 30% (P<0.05) and 45% (P<0.05) higher proteasome activity in the respiratory and leg muscles respectively. In a second experiment, ICU patients with sepsis (n=17) had a 55% (P<0.01) higher proteasome activity in the leg muscle compared with a control group (n=10). The inter-individual scatter of proteasome activity was larger between the patients with sepsis than the controls. We also observed a substantial intra-individual difference in activity between duplicate biopsies in several of the subjects. In conclusion, the proteolytic activity of the proteasome was higher in skeletal muscle from patients with sepsis and multiple organ failure compared with healthy controls. It was shown for the first time that respiratory and leg muscles were affected similarly. Furthermore, the variation in proteasome activity between individuals was more pronounced in the ICU patients for both muscle types, whereas the intra-individual variation between biopsies was similar for ICU patients and controls.

The general perception that catabolism and inflammation are associated with a high synthesis rate of total liver protein and a low albumin synthesis rate has been challenged in recent years by several studies in man, indicating that the synthesis rate of albumin in response to a catabolic insult is increased rather than decreased. Thus changes in liver protein synthesis rates in conjunction with catabolism and acute inflammation in man need to be characterized better. The aim of the present study was to measure protein synthesis rates of total liver protein and albumin during a state of acute inflammation. Patients (n = 10) undergoing acute laparoscopic cholecystectomy due to acute cholecystitis were investigated. FSRs (fractional synthesis rates) of total liver protein (liver biopsy specimens) and albumin (plasma samples) were investigated as early as possible during the surgical procedure, using a flooding dose of L-[2H5]phenylalanine. The results were compared with a reference group of patients without cholecystitis undergoing elective laparoscopic cholecystectomy (n = 17). FSR of total liver protein was 60% higher (P < 0.001) and the FSR of albumin was 45% higher (P < 0.01) in the cholecystitis patients compared with the control group. In conclusion, the synthesis rates of total liver protein and albumin are both increased in patients with an acute general inflammatory reaction undergoing laparoscopic cholecystectomy.

Aim: The effects of short-term starvation and refeeding on the free amino acids and glutathione in skeletal muscle in healthy man are not known. This is necessary baseline knowledge when studying the effects of nutrition, trauma and sepsis on protein, amino acid and glutathione metabolism., Methods: Concentrations of free amino acids and glutathione in muscle and plasma from young healthy male volunteers (n = 8) were measured before and after a 3-day fast and then again after 2 days refeeding. Nitrogen balance was determined during the study period., Results: The cumulated nitrogen loss was 36.9+/-5.4 g during the fasting period indicating a condition of protein catabolism. During the fasting period decreases were seen in muscle glutamate by 48 +/- 20% and in glutamine by 38 +/- 12%. These changes were returned back to normal levels during the refeeding period. The changes seen in other muscle amino acids during the study period were reflected by similar changes in plasma amino acids, again with normalisation after the refeeding period. Muscle glutathione concentration and the redox status of glutathione remained unaffected of short-term starvation and refeeding., Conclusion: A short-term fasting followed by a refeeding period induced changes in the concentrations of concentrations of glutamate, glutamine, branched chained and basic amino acids in muscle and plasma. Despite this, no changes were seen regarding the glutathione levels in muscle and plasma or its redox status, indicating that the glutathione system is of priority.

Background & Aims: Muscle wasting during critical illness is generally believed to be an increase in muscle protein degradation mediated by the proteasome proteolytic pathway. Polyubiquinated proteins are recognised and degraded by the 26S multicatalytic proteasome complex. Animal models for various catabolic conditions have shown increased expression of mRNA:s for several enzymes and subunits in the ubiquitin-proteasome pathway as well as an increase in proteasome activity. The aim of this study was to measure the proteolytic activity of the proteasome in human skeletal muscle. We investigated the proteasome activity in leg muscle biopsies from 7 critically ill patients and from a reference group of 7 age and sex matched patients by a method that could also be suitable for repetitive measurements of intensive care unit patients in future studies., Methods: Proteasomes were isolated by ultracentrifugation and the fractions containing cytosolic soluble and membrane-bound proteasomes were, respectively, incubated with a fluorogenic peptide substrate to assess the chymotrypsin-like peptidase activity., Results: In the critically ill the proteasome activity in the membrane-bound fraction of proteasomes was 30% higher compared to the reference group (P<0.02), whereas no difference was seen regarding the soluble fraction., Conclusion: The results indicate that there is an altered distribution of proteasome activity at the subcellular level in skeletal muscle of critically ill intensive care unit patients.

The development of nutrition and the knowledge of metabolism has increased exponentially during the last decades since the start of ESPEN. This article, based on the Arvid Wretlind lecture 2003 in Cannes, describes important historical and modern landmarks in the field. The presentation also highlights the important contributions made by Arvid Wretlind regarding the development of lipid emulsions and amino acid solutions. The last 25 years of nutritional development is very much linked to the modern history of ESPEN. The fruitful balance between research, industry and education is recognised.

Background & Aims: Postoperative metabolism is characterised by insulin resistance and a negative whole-body nitrogen balance. Preoperative carbohydrate treatment reduces insulin resistance in the first day after surgery. We hypothesised that preoperative oral carbohydrate treatment attenuates insulin resistance and improves whole-body nitrogen balance 3 days after surgery., Methods: Fourteen patients undergoing total hip replacement were double-blindly randomised to preoperative oral carbohydrate treatment (12.5%, 800 + 400 ml, n = 8) or placebo (n = 6). Glucose kinetics (6,6-D2-glucose), substrate utilisation (indirect calorimetry) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) were measured preoperatively and on the third day after surgery. Nitrogen losses were monitored for 3 days after surgery. Values are mean (SEM). Analysis of variance (ANOVA) statistics were used., Results: Endogenous glucose release during insulin infusion increased after surgery in the placebo group. Preoperative carbohydrate treatment, as compared to placebo, significantly attenuated postoperative endogenous glucose release (0.69 (0.07) vs. 1.21 (0.13)mg kg(-1) x min(-1), P < 0.01), while whole-body glucose disposal and nitrogen balance were similar between groups., Conclusions: While insulin resistance in the first day after surgery has previously been characterised by reduced glucose disposal, enhanced endogenous glucose release was the main component of postoperative insulin resistance on the third postoperative day. Preoperative carbohydrate treatment attenuated endogenous glucose release on the third postoperative day., (Copyright 2004 Elsevier Ltd.)

Purpose of Review: During recent years techniques and metabolic considerations have been discussed intensively. One contributing reason is that results have not always been easy to interpret and introduce into clinical practice. Nutrition through the enteral and parenteral route has classically been compared, and this is the topic of this review., Recent Findings: During the past 2 years a growing number of studies have focused on the amount and type of nutrition that is possible to give by enteral nutrition to intensive care unit patients. How to handle the clinical problem with paralysis and gastroparesis has also been studied. Basic research has shown a link between the gastrointestinal tract, immunocompetence and nutritional status. More evidence now exists that this is also clinically valid., Summary: Recent research has shown that enteral nutrition alone does not cover the total nutritional needs of intensive care unit patients. Enteral nutrition given early in a high dose is associated with a higher risk of complications. Metabolism in intensive care unit patients is different from the perioperative condition, which has been highlighted in recent studies with important clinical implications. The final solution has not been found yet, if it exists at all, and research in this field will continue. As the situation in biology and in real intensive care unit life is neither black nor white, it would be most beneficial for the intensive care unit patient if enteral nutrition and parenteral nutrition joined together in a good balance in order to avoid underload and overload.

Unlabelled: The thermic effect of amino acids is augmented under general anesthesia and counteracts hypothermia. Mild hypothermia may increase surgical bleeding. We studied whether amino acids also induce thermogenesis under spinal anesthesia and whether this endogenous heat production reduces bleeding during hip arthroplasty. Rectal temperature, oxygen uptake, and perioperative bleeding were measured in 22 patients receiving an IV amino acid mixture (Vamin 18), 240 kJ/h) for 1 h before and then during spinal anesthesia and in 24 control patients receiving acetated Ringer's solution. Blood loss was calculated after surgery by weighing the swabs and the content of the suction tubes after subtraction of the saline used. After surgery, the closed drains were weighed after 24 h. In the amino acid group, the preanesthesia temperature increased by 0.4 degrees C +/- 0.2 degrees C (P < 0.01) and was unchanged in controls. At end of surgery, core temperature had decreased by 0.9 degrees C +/- 0.4 degrees C in controls and by 0.4 degrees C +/- 0.3 degrees C in the amino acid patients (P < 0.01). Oxygen uptake increased by 26 +/- 7 mL/min, or 16% +/- 5% (P < 0.05), from baseline in the amino acid patients, whereas it was unchanged in the controls. Blood loss during surgery was significantly larger in the control patients (702 +/- 344 mL) than in the amino acid patients (516 +/- 272 mL) (P < 0.05). After surgery, there were no significant differences in shed blood volume. In conclusion, amino acid infusion also induced a thermogenic response under spinal anesthesia. In addition, the prevention of temperature decrease during spinal anesthesia seemed to have a positive effect on intraoperative blood loss., Implications: Infusion of a balanced mixture of amino acids during spinal anesthesia prevented core body temperature decrease. Bleeding was also less pronounced.