Albumin and fibrinogen synthesis rates in advanced chronic liver disease.

Synthesis of plasma proteins is an important function of the liver that has sparsely been investigated by modern techniques in patients with advanced chronic liver disease (CLD). Twenty-eight well-characterized patients with CLD under evaluation for liver transplantation were included. Albumin and fibrinogen synthesis rates were measured by the flooding dose technique using stable isotope-labeled phenylalanine. Transcapillary escape rate of albumin and plasma volume were assessed by radioiodinated human serum albumin. The absolute albumin synthesis rates were low (65 mg/kg/day, range: 32-203) and were associated with impaired liver function, as reflected by the risk-scores Child-Pugh (P = 0.025) and model for end-stage liver disease (rs = -0.62, P = 0.0005). The fibrinogen synthesis rate (12.8 mg/kg/day, range: 2.4-52.9) was also negatively associated with liver function. The synthesis rates of albumin and fibrinogen were positively correlated. Plasma volume was high (51 ± 9 mL/kg body wt), which contributed to an almost normal intravascular albumin mass despite low plasma concentration. Autoimmune inflammatory etiologies to CLD were associated with higher fibrinogen synthesis. De novo synthesis rates of albumin and fibrinogen in advanced chronic liver failure were negatively correlated to prognostic scores of liver disease. Albumin synthesis rate was low and associated with both liver failure and autoimmune inflammation, whereas fibrinogen synthesis was often normal and positively associated with chronic inflammation. This is different from acute inflammatory states in which both albumin and fibrinogen synthesis rates are high.NEW & NOTEWORTHY Albumin and fibrinogen synthesis were positively correlated, but the high variation indicates that these are probably influenced by different mechanisms. There might be a limited metabolic reserve for the liver to increase both albumin and fibrinogen synthesis in response to longstanding inflammation in CLD and fibrinogen seems to be prioritized.

Plasma glutamine status at intensive care unit admission: an independent risk factor for mortality in critical illness.

BACKGROUND: A plasma glutamine concentration outside the normal range at Intensive Care Unit (ICU) admission has been reported to be associated with an increased mortality rate. Whereas hypoglutaminemia has been frequently reported, the number of patients with hyperglutaminemia has so far been quite few. Therefore, the association between hyperglutaminemia and mortality outcomes was studied in a prospective, observational study. PATIENTS AND METHODS: Consecutive admissions to a mixed general ICU were eligible. Exclusion criteria were < 18 years of age, readmissions, no informed consent, or a 'do not resuscitate' order at admission. A blood sample was saved within one hour from admission to be analysed by high-pressure liquid chromatography for glutamine concentration. Conventional risk scoring (Simplified Acute Physiology Score and Sequential Organ Failure Assessment) at admission, and mortality outcomes were recorded for all included patients. RESULTS: Out of 269 included patients, 26 were hyperglutaminemic (≥ 930 µmol/L) at admission. The six-month mortality rate for this subgroup was 46%, compared to 18% for patients with a plasma glutamine concentration < 930 µmol/L (P = 0.002). A regression analysis showed that hyperglutaminemia was an independent mortality predictor that added prediction value to conventional admission risk scoring and age. CONCLUSION: Hyperglutaminemia in critical illness at ICU admission was an independent mortality predictor, often but not always, associated with an acute liver condition. The mechanism behind a plasma glutamine concentration outside normal range, as well as the prognostic value of repeated measurements of plasma glutamine during ICU stay, remains to be investigated.

A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice.

The preferential use of the oral/enteral route in critically ill patients over gut rest is uniformly recommended and applied. This article provides practical guidance on enteral nutrition in compliance with recent American and European guidelines. Low-dose enteral nutrition can be safely started within 48 h after admission, even during treatment with small or moderate doses of vasopressor agents. A percutaneous access should be used when enteral nutrition is anticipated for ≥ 4 weeks. Energy delivery should not be calculated to match energy expenditure before day 4-7, and the use of energy-dense formulas can be restricted to cases of inability to tolerate full-volume isocaloric enteral nutrition or to patients who require fluid restriction. Low-dose protein (max 0.8 g/kg/day) can be provided during the early phase of critical illness, while a protein target of > 1.2 g/kg/day could be considered during the rehabilitation phase. The occurrence of refeeding syndrome should be assessed by daily measurement of plasma phosphate, and a phosphate drop of 30% should be managed by reduction of enteral feeding rate and high-dose thiamine. Vomiting and increased gastric residual volume may indicate gastric intolerance, while sudden abdominal pain, distension, gastrointestinal paralysis, or rising abdominal pressure may indicate lower gastrointestinal intolerance.

Prevalence and impact of chronic dysglycemia in intensive care unit patients-A retrospective cohort study.

BACKGROUND: The prevalence of chronic dysglycemia (diabetes and prediabetes) in patients admitted to Swedish intensive care units (ICUs) is unknown. We aimed to determine the prevalence of such chronic dysglycemia and asses its impact on blood glucose control and patient-centered outcomes in critically ill patients. METHODS: In this retrospective observational cohort study, we obtained glycated hemoglobin A1c (HbA1c) in patients admitted to four tertiary ICUs in Sweden between March and August 2016. Based on previous diabetes history and HbA1c we determined the prevalence of chronic dysglycemia. We used multivariable regression analyses to study the association of chronic dysglycemia with the time-weighted average blood glucose concentration, glycemic lability index (GLI), and development of hypoglycemia (co-primary outcomes), and with ICU length of stay, mechanical ventilation duration, renal replacement therapy (RRT) use, vasopressor use, ICU-acquired infections, and mortality (exploratory clinical outcomes). RESULTS: Of 943 patients, 312 (33%) had chronic dysglycemia. Of these 312 patients, 84 (27%) had prediabetes, 43 (14%) had undiagnosed diabetes and 185 (59%) had known diabetes. Chronic dysglycemia was independently associated with higher time-weighted average blood glucose concentration (P < .001), higher GLI (P < .001), and hypoglycemia (P < .001). Chronic dysglycemia was independently associated with RRT use (adjusted odds ratio 1.97, 95% CI 1.24-3.13, P = .004) but not with other exploratory clinical outcomes. CONCLUSIONS: In four tertiary Swedish ICUs, measurement of HbA1c showed that one-third of patients had chronic dysglycemia. Chronic dysglycemia was associated with marked derangements in glycemic control, and a greater need for renal replacement therapy.

Lactate kinetics in ICU patients using a bolus of 13C-labeled lactate.

BACKGROUND: Plasma lactate concentrations and their trends over time are used for clinical prognosis, and to guide treatment, in critically ill patients. Although heavily relied upon for clinical decision-making, lactate kinetics of these patients is sparsely studied. AIM: To establish and validate a feasible method to study lactate kinetics in critically ill patients. METHODS: Healthy volunteers (n = 6) received a bolus dose of 13C-labeled lactate (20 µmol/kg body weight), and 43 blood samples were drawn over 2 h to determine the decay in labeled lactate. Data was analyzed using non-compartmental modeling calculating rates of appearance (Ra) and clearance of lactate. The area under the curve (AUC) was calculated using a linear-up log-down trapezoidal approach with extrapolation beyond 120 min using the terminal slope to obtain the whole AUC. After evaluation, the same protocol was used in an unselected group of critically ill patients (n = 10). RESULTS: Ra for healthy volunteers and ICU patients were 12.8 ± 3.9 vs 22.7 ± 11.1 µmol/kg/min and metabolic clearance 1.56 ± 0.39 vs 1.12 ± 0.43 L/min, respectively. ICU patients with normal lactate concentrations showed kinetics very similar to healthy volunteers. Simulations showed that reducing the number of samples from 43 to 14 gave the same results. Our protocol yielded results on lactate kinetics very similar to previously published data using other techniques. CONCLUSION: This simple and user-friendly protocol using an isotopically labeled bolus dose of lactate was accurate and feasible for studying lactate kinetics in critically ill ICU patients. TRIAL REGISTRATION: ANZCTR, ACTRN12617000626369, registered 8 March 2017. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372507&isReview=true.

Gastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda proposed by the Section of Metabolism, Endocrinology and Nutrition of the European Society of Intensive Care Medicine.

BACKGROUND: Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. METHODS: This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. RESULTS: Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. CONCLUSIONS: Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.

Serum selenium in critically ill patients: Profile and supplementation in a depleted region.

BACKGROUND: General selenium supplementation to intensive care unit (ICU) patients in regions with selenium-rich soil does not improve outcomes. Still selenium supplementation may reduce morbidity and mortality in patients with low-serum selenium concentration (S-Se) in selenium-poor areas who respond to treatment. The primary aim of this observational study was to investigate S-Se in a selenium-deficient region at time of intensive care admission, and in addition to monitor S-Se during high-dose selenium supplementation for safety. METHODS: We measured S-Se in 100 consecutive patients admitted to a tertiary general ICU. After initial sampling, high-dose intravenous (iv) selenium supplementation was administered up to 20 days. RESULTS: At admission, in 95% of the cases, S-Se was below the saturation level for selenoenzymes, in 91%, below the Swedish reference level, and in 71%, below the level where selenoenzyme function may be impaired. At day 5 of substitution, all patients still remaining in the ICU (n = 26) were within the range for enzyme function, 12% were below reference, and 24% did not reach full enzymatic saturation. At day 10 and forward, all patients were within target for treatment. No patients were at risk for toxic S-Se concentration. CONCLUSIONS: S-Se concentration was substantially lower compared to normal values at ICU admission in this cohort of unselected Swedish critical care patients. Selenium supplementation restituted S-Se to levels corresponding to enzymatic saturation and the Swedish reference interval for all subjects remaining in the ICU on day 5.

Metabolic support in the critically ill: a consensus of 19.

Metabolic alterations in the critically ill have been studied for more than a century, but the heterogeneity of the critically ill patient population, the varying duration and severity of the acute phase of illness, and the many confounding factors have hindered progress in the field. These factors may explain why management of metabolic alterations and related conditions in critically ill patients has for many years been guided by recommendations based essentially on expert opinion. Over the last decade, a number of randomized controlled trials have been conducted, providing us with important population-level evidence that refutes several longstanding paradigms. However, between-patient variation means there is still substantial uncertainty when translating population-level evidence to individuals. A cornerstone of metabolic care is nutrition, for which there is a multifold of published guidelines that agree on many issues but disagree on others. Using a series of nine questions, we provide a review of the latest data in this field and a background to promote efforts to address the need for international consistency in recommendations related to the metabolic care of the critically ill patient. Our purpose is not to replace existing guidelines, but to comment on differences and add perspective.

Optimal cut-off for hourly lactate reduction in ICU-treated patients with septic shock.

BACKGROUND: A decrease in lactate concentration over time during septic shock is associated with favourable outcomes. However, if this applies to hourly intervals during the initial time period in the ICU is unknown. The aim of this study was to investigate whether there is an early hourly reduction rate of lactate that is related to clinical outcome in septic shock patients treated in the ICU. METHODS: A cohort of adult septic shock patients admitted to the ICU with an initial lactate level >2 mmol/L and receiving vasopressor was retrospectively analysed. Mean hourly reduction rate of lactate (ΔLact/h) was calculated individually from all lactate concentrations measured from inclusion until normalization of lactate (≤1.5 mmol/L) within 24 hours. The mortality at 30 days following ICU admission was evaluated. RESULTS: Among 1405 ICU admissions during 2 years, 104 patients were eligible. Mortality rate at 30 days was 34%. The optimal cut-off values of baseline lactate and ΔLact/h for 30-day mortality were 4 mmol/L and 2.5%/h. When stratifying the patients by these cut-points, those with baseline lactate > 4 mmol/L and ΔLact/h < 2.5%/h had lowest probability of survival (27%). Multivariable logistic regression showed that ΔLact/h <2.5%/h, baseline lactate >4 mmol/L and high Simplified Acute Physiology Score III were independent risk factors of 30-day mortality. CONCLUSIONS: In this retrospective pilot cohort, a mean reduction rate of lactate <2.5%/h within the first 24 hours of ICU stay was associated with an increased risk of 30-day mortality in septic shock patients.

An attenuated rate of leg muscle protein depletion and leg free amino acid efflux over time is seen in ICU long-stayers.

BACKGROUND: There is extensive documentation on skeletal muscle protein depletion during the initial phase of critical illness. However, for intensive care unit (ICU) long-stayers, objective data are very limited. In this study, we examined skeletal muscle protein and amino acid turnover in patients with a prolonged ICU stay. METHODS: Patients (n = 20) were studied serially every 8-12 days between days 10 and 40 of their ICU stay as long as patients stayed in the ICU. Leg muscle protein turnover was assessed by measurements of phenylalanine kinetics, for which we employed a stable isotope-labeled phenylalanine together with two-pool and three-pool models for calculations, and results were expressed per 100 ml of leg volume. In addition, leg muscle amino acid flux was studied. RESULTS: The negative leg muscle protein net balance seen on days 10-20 of the ICU stay disappeared by days 30-40 (p = 0.012). This was attributable mainly to an increase in the de novo protein synthesis rate (p = 0.007). It was accompanied by an attenuated efflux of free amino acids from the leg. Leg muscle protein breakdown rates stayed unaltered (p = 0.48), as did the efflux of 3-methylhistidine. The arterial plasma concentrations of free amino acids did not change over the course of the study. CONCLUSIONS: In critically ill patients with sustained organ failure and in need of a prolonged ICU stay, the initial high rate of skeletal muscle protein depletion was attenuated over time. The distinction between the acute phase and a more prolonged and more stable phase concerning skeletal muscle protein turnover must be considered in study protocols as well as in clinical practice. TRIAL REGISTRATION: Australian New Zealand Trial Registry, ACTRN12616001012460 . Retrospectively registered on 1 August 2016.

Albumin mass balance and kinetics in liver transplantation.

BACKGROUND: In major abdominal surgery albumin is shifted from the circulation, presumably leaking into the interstitial space, contributing to a 30-40% decrease in plasma albumin concentration. During and after liver transplantation exogenous albumin is infused for volume substitution and to maintain plasma albumin concentration. Here we used liver transplantation as a model procedure for the study of albumin mass balance and kinetics during major abdominal surgery with albumin substitution. METHODS: Patients were studied during liver transplantation (n = 16), and until postoperative day 3 (POD 3) (n = 11). Cumulative perioperative albumin shift was assessed by mass balance of albumin and hemoglobin. Synthesis rates of albumin and fibrinogen were estimated by the flooding technique using deuterium-labeled phenylalanine. Albumin distribution was assessed by radioiodinated human serum albumin. RESULTS: At the end of surgery, 37 ± 17 g of albumin (p < 0.0001) had shifted from plasma, and this amount was stable until POD 3 (48 ± 33 g, p = 0.0017 versus baseline). There was 91 ± 37 g exogenous albumin infused peroperatively and another 47 ± 35 g was infused postoperatively until POD 3. Absolute synthesis rates of albumin and fibrinogen on POD 3 were 239 ± 84 mg/kg body weight/day and 33 mg/kg body weight/day (range 5-161), respectively. CONCLUSIONS: Albumin net leakage from plasma progressed until the end of surgery, and was then unaltered until POD 3. This is in contrast with the normalization of the cumulative albumin shift identified at day 3 after non-transplant major abdominal surgery. Liver synthesis of export proteins was high compared to reference values at the third postoperative day, suggesting rapid recovery of synthesis capacity. TRIAL REGISTRATION: Swedish Medical Product Agency, EudraCT 2015-002568-18. Registered on 15 July 2015.

Lower versus higher hemoglobin threshold for transfusion in septic shock.

BACKGROUND: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. METHODS: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay. The primary outcome measure was death by 90 days after randomization. RESULTS: We analyzed data from 998 of 1005 patients (99.3%) who underwent randomization. The two intervention groups had similar baseline characteristics. In the ICU, the lower-threshold group received a median of 1 unit of blood (interquartile range, 0 to 3) and the higher-threshold group received a median of 4 units (interquartile range, 2 to 7). At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P=0.44). The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations. The numbers of patients who had ischemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups. CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. (Funded by the Danish Strategic Research Council and others; TRISS ClinicalTrials.gov number, NCT01485315.).

High protein intake without concerns?

The high fashion in nutrition for the critically ill is to recommend a high protein intake. Several opinion leaders are surfing on this wave, expanding the suggested protein allowance upwards. At the same time, there is no new evidence supporting this change in recommendations. Observational data show that in clinical practice protein intake is most often far below current ESPEN recommendations of 1.2-1.5 g/kg/day. Therefore, it may be in the best interests of our patients just to adhere to that guideline, and not to stretch them upwards for protein intake? Here we give arguments to stay conservative.

A supplemental intravenous amino acid infusion sustains a positive protein balance for 24 hours in critically ill patients.

BACKGROUND: Providing supplemental amino acids to ICU patients during a 3-h period results in improved whole-body net protein balance, without an increase in amino acid oxidation. The primary objective was to investigate if a 24-h intravenous amino acid infusion in critically ill patients has a sustained effect on whole-body protein balance as was seen after 3 h. Secondary objectives were monitoring of amino acid oxidation rate, urea and free amino acid plasma concentrations. METHODS: An infusion of [1-13C]-phenylalanine was added to ongoing enteral nutrition to quantify the enteral uptake of amino acids. Primed intravenous infusions of [ring-2H5]-phenylalanine and [3,3-2H2]-tyrosine were used to assess whole-body protein synthesis and breakdown, to calculate net protein balance and to assess amino acid oxidation at baseline and at 3 and 24 hours. An intravenous amino acid infusion was added to nutrition at a rate of 1 g/kg/day and continued for 24 h. RESULTS: Eight patients were studied. The amino acid infusion resulted in improved net protein balance over time, from -1.6 ± 7.9 µmol phe/kg/h at 0 h to 6.0 ± 8.8 at 3 h and 7.5 ± 5.1 at 24 h (p = 0.0016). The sum of free amino acids in plasma increased from 3.1 ± 0.6 mmol/L at 0 h to 3.2 ± 0.3 at 3 h and 3.6 ± 0.5 at 24 h (p = 0.038). Amino acid oxidation and plasma urea were not altered significantly. CONCLUSION: We demonstrated that the improvement in whole-body net protein balance from a supplemental intravenous amino acid infusion seen after 3 h was sustained after 24 h in critically ill patients. TRIAL REGISTRATION: This trial was prospectively registered at Australian New Zealand Clinical Trials Registry. ACTRN, 12615001314516 . Registered on 1 December 2015.

Continuous glucose monitoring in the ICU: clinical considerations and consensus.

Glucose management in intensive care unit (ICU) patients has been a matter of debate for almost two decades. Compared to intermittent monitoring systems, continuous glucose monitoring (CGM) can offer benefit in the prevention of severe hyperglycemia and hypoglycemia by enabling insulin infusions to be adjusted more rapidly and potentially more accurately because trends in glucose concentrations can be more readily identified. Increasingly, it is apparent that a single glucose target/range may not be optimal for all patients at all times and, as with many other aspects of critical care patient management, a personalized approach to glucose control may be more appropriate. Here we consider some of the evidence supporting different glucose targets in various groups of patients, focusing on those with and without diabetes and neurological ICU patients. We also discuss some of the reasons why, despite evidence of benefit, CGM devices are still not widely employed in the ICU and propose areas of research needed to help move CGM from the research arena to routine clinical use.

Nutritional needs for the critically ill in relation to inflammation.

PURPOSE OF REVIEW: This review focuses on nutritional needs in critically ill patients. The inflammation corresponding to acute stress is highlighted. Simultaneously, we try to avoid limiting the perspective to only the acute phase. RECENT FINDINGS: During the last year, a number of important studies on nutritional needs in the critically ill have been published, including large randomized controlled trials. In particular studies addressing the needs for energy and proteins in the critically ill have imparted new knowledge in this field. However, there are few studies concerning the rehabilitation phase after critical illness. SUMMARY: Although the recent findings and publications contribute to a more nuanced understanding of nutrition during critical illness, the implications for clinical practice are not in discord with the current recommendations of guidelines.

Is the glutamine story over?

Glutamine has been launched as a conditionally indispensible amino acid for the critically ill. Supplementation has been recommended in guidelines from international societies. Although data have been presented pointing out that glutamine supplementation may not be for everybody, recommendations for treatments and design of study protocols have included all critically ill patients. Results from more recent studies and meta-analyses indicate that indiscriminate use of glutamine supplementation in critically ill patients may actually cause harm rather than beneficial effects. This viewpoint sorts out arguments of controversy in the glutamine story.

Leakage of albumin in major abdominal surgery.

BACKGROUND: The time course of plasma albumin concentration (P-alb) and cumulative perioperative albumin shift as a measure of albumin extravasation in major abdominal surgery is not well described. Knowledge of these indices of the vascular barrier and vascular content are important for our understanding of fluid physiology during surgery and anesthesia. METHODS: Patients (n = 10) were studied during esophageal or pancreatic surgery. P-alb was repeatedly measured over 72 h, and the mass balance of albumin and hemoglobin were obtained from measures of P-alb, blood hemoglobin and hematocrit. RESULTS: P-alb decreased rapidly from baseline (32.8 ± 4.8 g/L) until the start of surgical reconstruction (18.7 ± 4.8 g/L; p < 0.001), and was thereafter stable until postoperative day 3. Cumulative perioperative albumin shift increased until 1 h after the end of surgery, when 24 ± 17 g (p < 0.001) had been lost from the circulation. CONCLUSIONS: The rapid fall in P-alb of more than 40 % consistently occurred during the first part of the surgical procedure, but albumin leakage progressed until 1 h after the end of surgery. After the initial drop, P-alb was stable for 72 h.

Simultaneous assessment of the synthesis rate and transcapillary escape rate of albumin in inflammation and surgery.

BACKGROUND: Better knowledge of albumin kinetics is needed to define the indications for albumin use in clinical practice. This study involved two approaches: the synthesis rate and transcapillary escape rate of albumin were measured simultaneously at different levels of plasma albumin concentration in relation to acute inflammation and surgery; and two different tracers were compared to determine plasma volume and the transcapillary escape rate. METHODS: Healthy volunteers (n = 10), patients with acute inflammatory abdominal disease (n = 10), and patients undergoing elective pancreatic resection (n = 10) were studied. The albumin synthesis rate was measured by the incorporation of deuterium-labeled phenylalanine. Plasma volume and the transcapillary escape rate were assessed using 123I-labeled and 125I-labeled albumin. RESULTS: A 50 % elevated de-novo albumin synthesis rate was seen in patients with acute inflammation and marked hypoalbuminemia, while patients with marginal hypoalbuminemia before the start of surgery had a normal albumin synthesis rate. The transcapillary escape rate was elevated intraoperatively during the reconstructive phase of pancreatic surgery, when plasma albumin was decreased but stable. In acute inflammation with marked hypoalbuminemia, the transcapillary escape rate was no different from normal. 123I-labeled and 125I-labeled albumin were found exchangeable for plasma volume determinations, but could be used only in groups of patients for the transcapillary escape rate. CONCLUSIONS: This observational study illustrates the limited information contained in albumin plasma concentrations to reflect albumin kinetics. On the contrary, single measurements of the synthesis rate and/or transcapillary escape rate of albumin obviously cannot explain the plasma level of albumin or the changes seen in plasma albumin concentration. TRIAL REGISTRATION: www.clinicaltrials.gov , study number NCT01686776 . Registered 13 September 2012.

Measuring energy expenditure in the intensive care unit: a comparison of indirect calorimetry by E-sCOVX and Quark RMR with Deltatrac II in mechanically ventilated critically ill patients.

BACKGROUND: Indirect calorimetry allows the determination of energy expenditure in critically ill patients by measuring oxygen consumption (VO2) and carbon dioxide production (VCO2). Recent studies have demonstrated variable performance of "breath-by-breath" instruments compared to mixing chamber technology. The aim of this study was to validate two modern devices (E-sCOVX and Quark RMR) against a reference method (Deltatrac II). METHOD: Measurements of VO2/VCO2 with the test and reference devices were performed simultaneously over a 20-min period in mechanically ventilated adult intensive care unit patients. Accuracy and precision of instruments were analyzed using Bland-Altman plots. RESULTS: Forty-eight measurements in 22 patients were included for analysis. Both E-sCOVX and Quark RMR overestimated VO2 and VCO2 compared to Deltatrac II, corresponding to a 10% higher mean resting energy expenditure. Limits of agreement of resting energy expenditure within ± 2 standard deviations were ± 461 kcal/24 h (± 21% expressed as percentage error) for ΔE-sCOVX-Deltatrac II and ± 465 kcal/24 h (± 22%) for ΔQuark RMR-Deltatrac II. CONCLUSION: Both test devices overestimate VO2 and VCO2 compared to Deltatrac II. The observed limits of agreement are comparable to those commonly accepted in evaluations of circulatory monitoring, and significantly less than results from predictive equations. We hypothesize that the discrepancy between methods is due to patient/ventilator-related factors that affect the synchronization of gas and spirometry waveforms. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, Trial ID ACTRN12615000205538. Date registered 3 March 2015.