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The use of outpatient parenteral antimicrobial therapy (OPAT) for children has several advantages, including reduced length of hospital stay and costs. A reliable vascular access is key to delivering safe and effective pediatric OPAT. In recent years, midline catheters (MC) have been increasingly used for short-term intravenous antibiotic therapy in children. However, there are no studies investigating the use of MCs in the OPAT setting. The main aim of this paper was to evaluate the success and complications of using MCs for pediatric OPAT. This was a retrospective cohort study from a tertiary academic pediatric hospital. All MCs inserted at the hospital and used for OPAT were eligible for study inclusion. The primary objective was to describe the percentage of patients able to complete OPAT without the need for additional venous access. Forty-one MCs were included in the study. Patient mean (SD) age was 5.9 (4.9) years. In 31 cases (76%, 95% CI 62-86%), the iv therapy could be successfully completed using only the MC. Imbalances between the groups suggested unfavorable outcome for saphenous vein catheters as well as for shorter and smaller-sized catheters. Fourteen patients (34%) were subjected to a MC-related complication. Pain on injection in the MC was the most frequent complication (n = 10, 24%).    Conclusion: Midline catheters could be an alternative to central venous access for pediatric OPAT. Avoiding saphenous vein insertion and using longer and larger-sized catheters could increase MC success rate. No severe MC-related complication was found. Further randomized studies comparing different catheter types are needed. What is Known: • For selected patients, pediatric outpatient parenteral antimicrobial therapy (OPAT) is safe and provides health-economic, psychosocial, and medical advantages compared to in-hospital care. • A reliable venous access is one of the key factors to the success of OPAT, but this can be a challenge in children. What is New: • Using midline catheters, 76% of patients could complete their intended iv therapy without the need for additional venous access. Avoiding saphenous vein insertion and using longer and larger-sized catheters could increase the success rate. • Thirty-four percent of catheters were subject to some kind of complication, the most common being pain on injection in the catheter., (© 2024. The Author(s).)

Background: Midline catheters are peripheral intravenous (IV) catheters in which the tip of the catheter does not reach the central circulation. In children, the use of midline catheters could lead to decreased complications from central venous catheters. To validate the safety of midline catheter use in children, we aimed to describe the complications and dwell time of pediatric midline catheters. The primary outcome was the incidence of catheter-related venous thromboembolism (VTE)., Methods: We conducted an observational, prospective study including consecutive patients at a tertiary multidisciplinary pediatric hospital. One hundred pediatric midline catheters were followed for thrombotic, infectious, and mechanical complications. After catheter removal, Doppler ultrasonography was performed to detect asymptomatic VTE., Results: The mean age was 6.0 years (standard deviation [SD], 4.7), and median catheter dwell time was 6 (4-8) days. Most midline catheters were inserted in arm veins, most commonly in the basilic vein (56%). Catheter-related VTE was diagnosed in 30 (30%; 95% confidence interval [CI], 21%-40%) cases, corresponding to an incidence rate of 39 (95% CI, 26-55) cases per 1000 catheter days. Eight of 14 saphenous vein catheters were complicated by VTE compared to 22 of 86 arm vein catheters, suggesting an imbalance in favor of arm vein insertion site. Two patients needed anticoagulation therapy due to catheter-related VTE. Thirty (30%) catheters were removed unintentionally or due to complications, 22 of these needed additional IV access to complete the intended therapy. No catheter-related bloodstream infection (95% CI, 0%-4%) occurred. Mechanical complications occurred in 33 (33%; 95% CI, 24%-43%) midline catheters., Conclusions: In children, thrombotic and mechanical complications of midline catheters are common, but only few VTEs are severe enough to warrant anticoagulation therapy. Systemic infectious complications are rare. Seventy-eight percent of patients did not need additional venous access to complete short-term IV therapy. Considering the rate of clinically relevant complications and the catheter dwell time, pediatric midline catheters could be an alternative to central venous access for short-term (5-10 days) IV therapy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

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.

Background: Esophagectomy is a major surgical intervention and a cornerstone in the treatment of esophageal cancer. There is clinical experience that blood lactate concentration often is elevated in the period following esophagectomy, but the incidence and clinical consequences are sparsely studied., Methods: We extracted data from all patients undergoing esophagectomy at Karolinska University Hospital 2016-2018, n = 153. Most were performed with minimally invasive technique, n = 130. Blood lactate values directly after surgery, highest value during the first night, and morning level on postoperative day one were recorded. Primary outcome was hospital length of stay and secondary outcome was a composite of postoperative infection, additional surgery, or intensive care during the hospital stay. Development of anastomotic leak was analyzed separately., Results: Postoperative hyperlactatemia was common as 93% of patients had peak lactate concentration >1.6 mmol/L and 27% >3.5 mmol/L in the first night following operation. Median hospital length of stay was 14 days. Blood lactate showed a weak correlation to hospital stay and intensive care the morning following surgery, but not at arrival to postoperative ward. There were no statistical differences between those with and without anastomotic leak at any of the time points. Elevated lactate in the first 12-16 h postoperatively was related to surgical factors (open technique, surgery time, and perioperative bleeding) but not to patient related factors (ASA-class, Charlson comorbidity index, sex, age) or cumulative fluid balance., Conclusion: In conclusion, elevated blood lactate in the immediate time following esophagectomy showed a weak association to intensive care and length of stay but not anastomotic leak., (© 2022 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

The risk for venous thromboembolism (VTE) is considered to be low in the general paediatric intensive care unit (PICU) population, and pharmacological thromboprophylaxis is not routinely used. PICU patients considered at high-risk of VTE could possibly benefit from pharmacological thromboprophylaxis, but the incidence of VTE in this group of patients is unclear. This was an observational, prospective study at a tertiary multi-disciplinary paediatric hospital. We used comprehensive ultrasonography screening for VTE in critically ill children with multiple risk factors for VTE. Patients admitted to PICU ≥ 72 h and with ≥ two risk factors for VTE were included. Patients receiving pharmacological thromboprophylaxis during their entire PICU stay were excluded. The primary outcome of the study was VTEs not related to the use of a CVC. Ultrasonography screening of the great veins was performed at PICU discharge. Seventy patients with median (interquartile range) 3 (2-4) risk factors for VTE were evaluated. Median age was 0.3 years (0.03-4.3) and median PICU length of stay 9 days (5-17). Regarding the primary outcome, no symptomatic VTEs occurred and no asymptomatic VTEs were found on ultrasonography screening, resulting in an incidence of VTEs not related to a vascular catheter of 0% (95% CI: 0-5.1%)., Conclusion: Our results indicate that VTEs not related to a vascular catheter are a rare event even in a selected group of severely ill small children considered to be at high risk of VTE., What Is Known: • Children in the PICU often have several risk factors for venous thromboembolism (VTE). • The incidence of VTE in PICU patients is highly uncertain, and there are no evidence-based guidelines regarding VTE prophylaxis., What Is New: • This study found an incidence of VTEs not related to a vascular catheter of 0% (95% CI: 0-5.1%). • This indicates that such VTE events are rare even in PICU patients with multiple risk factors for VTE., (© 2022. The Author(s).)

Objectives: Pediatric venous thromboembolic events are commonly associated with in situ central venous catheters. The risk for severe venous thromboembolism increases if a larger portion of the vessel lumen is occupied by the central venous catheter. A functioning vascular catheter is required when the continuous renal replacement therapy is used in critically ill children. Due to the high blood flow required for continuous renal replacement therapy, the external diameter of the catheter needs to be larger than a conventional central venous catheter used for venous access, potentially increasing the risk of venous thromboembolism. However, children on continuous renal replacement therapy often receive systemic anticoagulation to prevent filter clotting, possibly also preventing venous thromboembolism. The frequency of catheter-related venous thromboembolic events in this setting has not been described. Our main objective was to determine the prevalence of catheter-related venous thromboembolism in pediatric continuous renal replacement therapy., Design: Retrospective cohort study., Setting: Tertiary multidisciplinary academic pediatric hospital., Patients: Patients 0-18 years old with a vascular catheter used for continuous renal replacement therapy., Interventions: None., Measurements and Main Results: In our series of 80 patients, we used 105 vascular catheters. The median age of the patients was 10 months and PICU mortality rate was 21%. Venous thromboembolic events were considered to be catheter related if located in the same vein as the vascular catheter and radiologically verified. Six (5.7%) catheter-related venous thromboembolic events were found. The clinically relevant complications of venous thromboembolism included superior vena cava syndrome and catheter dysfunction. In one patient, severe and life-threatening pulmonary embolism occurred. In comparison with patients without venous thromboembolism, venous thromboembolic events were associated with lower body weight (p = 0.03) and longer durations of continuous renal replacement therapy (p < 0.01), mechanical ventilation (p = 0.03), and PICU stay (p < 0.01). Five out of six venous thromboembolisms appeared in neonates., Conclusions: Catheter-related venous thromboembolism is a clinically relevant complication of pediatric continuous renal replacement therapy, with a prevalence of 5.7% in our cohort. Clinicians involved in pediatric continuous renal replacement therapy need to be vigilant for symptoms of venous thromboembolisms and initiate appropriate treatment as soon as possible., Competing Interests: Dr. Szeps disclosed that this study was funded through institutional funds only. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

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.

Background: Glutamine plasma concentrations outside the normal range at intensive care unit (ICU) admission are associated with unfavorable outcomes. Based on the hypothesis that hypoglutaminemia in the ICU is the result of an increased utilization of glutamine which cannot be fully met by endogenous production, extra glutamine supplementation has been advocated to ICU patients with hypoglutaminemia. However, it is still unclear whether there is a causal relation between hypo- and hyperglutaminemia and outcomes. Present guidelines advise against supplementation, although there is no evidence available for patients with hypoglutaminemia. The pathophysiology of abnormal glutamine levels and whether glutamine production or glutamine utilization is compromised is largely unknown. Therefore, the aim of this study was to elucidate the relationship between plasma glutamine levels and the endogenous glutamine production in ICU patients., Method: In this observational study, a technique using a small bolus of intravenous glutamine with an isotopic label was used to measure glutamine production., Results: There was a statistically significant correlation between de novo endogenous production of glutamine (not emanating directly from protein breakdown) and plasma glutamine concentrations in the low and normal range in circulatory stabilized ICU patients (n = 19), R 2  = 0.35 (P ≤ 0.01)., Conclusion: The predictive value of a low plasma glutamine concentration at ICU admission on outcomes may thus be related to a low endogenous production, which may need to be supplemented in the best interest of this cohort of patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction:  Early differentiation between perforated and nonperforated acute appendicitis (AA) in children is of major benefit for the selection of proper treatment. Based on pilot study data, we hypothesized that plasma sodium concentration at hospital admission is a diagnostic marker for perforation in children with AA., Materials and Methods:  This was a prospective diagnostic accuracy study, including previously healthy children, 1 to 14 years of age, with AA. Blood sampling included plasma sodium concentration, plasma glucose, base excess, white blood cell count, plasma arginine vasopressin (AVP), and C-reactive protein., Results:  Eighty children with histopathologically confirmed AA were included in the study. Median plasma sodium concentration on admission in patients with perforated AA (134 mmol/L, [interquartile range 132-136]) was significantly lower than in children with nonperforated AA (139 mmol/L, [137-140]). The receiver operating characteristic curve of plasma sodium concentration identifying patients with perforated AA showed an area under the curve of 0.93 (95% confidence interval, 0.87-0.99), with a sensitivity and specificity of 0.82 (0.70-0.90) and 0.87 (0.60-0.98), respectively. Plasma sodium concentrations ≤136 mmol/L resulted in an odds ratio of 31.9 (6.3-161.9) for perforation. The association between low plasma sodium concentration and perforated AA was confirmed in a multivariate logistic regression analysis. Median plasma AVP on admission was higher in patients with perforated (8.6 pg/mL [5.0-14.6]) as compared with nonperforated AA (3.4 pg/mL [2.5-6.6])., Conclusion:  In children with AA, there is a strong association between low plasma sodium concentration and perforation, a novel and not previously described finding., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

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 13 C-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 (R a ) 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: R a 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.

Background: Venous thrombosis (VT) in children is often associated with a central venous catheter (CVC). We aimed to determine the incidence of VT associated with percutaneous non-tunnelled CVCs in a general paediatric population, and to identify risk factors for VT in this cohort., Methods: Observational, prospective study enrolling consecutive patients at a tertiary multi-disciplinary paediatric hospital. A total of 211 percutaneous, non-tunnelled CVCs were analysed. Data regarding potential risk factors for CVC-related VT were collected. Compression ultrasonography with colour Doppler was used to diagnose VT., Results: Overall, 30.3% of children developed CVC-related VT, with an incidence rate of 29.6 (confidence interval, 22.5-36.9) cases/1000 CVC days. Upper body CVC location, multiple lumen CVCs, and male gender were independent risk factors for VT in multivariate analysis. All upper body VTs were in the internal jugular vein (IJV). The occurrence of CVC-related VT did not affect length of paediatric ICU or hospital stay. In patients with VT, femoral CVCs, young age, paediatric ICU admission, and a ratio of CVC/vein diameter >0.33 were associated with VT being symptomatic, occlusive, or both. IJV VT was often asymptomatic and non-occlusive., Conclusions: Paediatric non-tunnelled CVCs are frequently complicated by VT. Avoiding IJV CVCs and multiple lumen catheters could potentially reduce the overall risk of VT. However, IJV VT was more likely to be smaller and asymptomatic compared with femoral vein VT. More data are needed on the risk of complications from smaller, asymptomatic VT compared with the group of VT with symptoms or vein occlusion. Femoral vein CVCs and CVC/vein diameter >0.33 could be modifiable risk factors for VT with larger thrombotic mass., Clinical Trial Registration: ACTRN12615000442505., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with multiple organ failure (MOF) often receive large amounts of resuscitation fluid, making them at high risk of fluid overload (FO). Our main objective was to investigate if the ability to achieve a negative fluid balance during the first 3 continuous renal replacement therapy (CRRT) days was associated with mortality in children with MOF., Methods: Retrospective cohort study in a tertiary multidisciplinary academic paediatric hospital. The study included 63 patients (age 0-18 years) with 3 or more failing organs receiving CRRT due to acute kidney injury and/or fluid overload., Results: The median age was 4 months, and PICU mortality was 29%. Survivors had significantly lower degree of FO at CRRT initiation, (median 15% (Interquartile range 9-22)) than non-survivors (24% (17%-37%), P = 0.002). On PICU admission, PIM-3 score was significantly higher in non-survivors (P = 0.01), but at CRRT initiation there was no difference in PELOD-2 score (P = 0.98). Mortality in patients achieving a cumulative net negative fluid balance during the first 3 days after CRRT initiation was 12%, compared to 86% in those not achieving this (P < 0.0001). In multivariate analysis, the inability to achieve a net negative fluid balance during 3 days after CRRT initiation (P < 0.0001) and FO >20% at CRRT initiation (P = 0.0019) remained associated with mortality., Conclusion: Our results suggest that early fluid removal is associated with improved patient outcome in critically ill children receiving CRRT, and that prompt measures should be taken to prevent fluid overload in critical illness. These results need to be verified in further, prospective studies., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

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., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Ventilator associated pneumonia and sepsis are frequent complications in neonatal care. Bacterial colonization of medical devices and interfaces used for respiratory support may contribute by functioning as a bacterial reservoir seeding bacteria into airways. We have developed an antibacterial surface coating based on a cysteine ligand covalently coupled via a spacer to a carboxylic backbone layer on an acrylic acid grafted silicone surface. This coating was applied on a commercially available nasal prong and the antibacterial effect was evaluated both in vitro and in vivo in a first-in-human phase 1 trial. The coated nasal prongs had strong antibacterial activity against both Gram-negative and Gram-positive bacteria in vitro. In a randomized pre-clinical trial study of 24 + 24 healthy adult volunteers who carried coated or non-coated nasal prongs for 18 h, a 10 log difference in mean bacterial colonization of 5.82 (p < 0.0001) was observed. These results show that this coating technique can prevent colonization by the normal skin and mucosal flora, and thus represent a promising novel technology for reduction of medical device-associated hospital acquired infections., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background & Aims: Low concentration of serum selenium is associated with the inflammatory response and multiple organ failure in adult ICU-patients. Critically ill children are less well characterized. In this study, serum selenium concentration and its possible relation to multiple organ failure as well as glutathione status was investigated in pediatric intensive care (PICU) patients., Methods: A prospective consecutive cohort of critically ill children (n = 100) admitted to the PICU of a tertiary university hospital, and in addition an age stratified reference group of healthy children (n = 60) were studied. The concentrations of serum selenium and reduced and total glutathione were determined at admission and at day 5 for patients still in the PICU., Results: Low concentration of serum selenium as well as a high-reduced fraction of glutathione (GSH/tGSH) was associated with multiple organ failure (p < 0.001 and p < 0.01) respectively. A correlation between low serum selenium concentration and high-reduced fraction of glutathione (GSH/tGSH) was also seen (r = -0.19 and p = 0.03). The serum selenium concentrations in the pediatric reference group in a selenium poor area were age dependent with lower concentrations in infants as compared to older children (p < 0.001)., Conclusions: Both low serum selenium concentration and high reduced fraction of glutathione (GSH/tGSH) were associated with the development of multiple organ failure. The association between low serum selenium concentration and high fraction of reduced glutathione in whole blood favour the hypothesis that selenium is of critical importance for the scavenge capacity of glutathione peroxidase (GPX)., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

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.

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- 13 C]-phenylalanine was added to ongoing enteral nutrition to quantify the enteral uptake of amino acids. Primed intravenous infusions of [ring- 2 H 5 ]-phenylalanine and [3,3- 2 H 2 ]-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.

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.

The possibility of using two different isotopomers, for the incorporation of isotopically labeled amino acids, was explored to enable longitudinal studies of de novo synthesis of two export liver proteins, albumin and fibrinogen. The agreement of the synthesis rates between the two different labels was evaluated along with the reproducibility of repeated experiments using different time intervals. Healthy volunteers were studied in a standardized fed state. Protocol A (n = 10) involved two measurements 48 hours apart. Protocol B (n = 6) involved three measurements at baseline and five hours and then seven days after the initial measurement. De novo synthesis of albumin and fibrinogen by the incorporation of D5-phenylalanine or D8-phenylalanine were measured using the flooding dose technique. Albumin and fibrinogen were isolated from plasma using standard techniques. Fractional and absolute synthesis rates were calculated. Repeated measurements employing the two isotoptomers showed good agreement for albumin fractional synthesis rate after 48 hours (p = 0.92) and after 7 days (p = 0.99), with a coefficient of variation of 5.9% when using the same isotopic label. For fibrinogen, the coefficient of variation for the fractional synthesis rate employing the same isotopic label was 16.6%. Repeated measurements after 48 hours and seven days showed less agreement although there was no statistical difference (P = 0.32 and P = 0.30 respectively). Repeated measurement after five hours showed a statistical significant difference for the fractional synthesis rate of fibrinogen (p = 0.008) but not for albumin (p = 0.12). Repeated measurements of albumin de novo synthesis more than 48 hours apart show acceptable agreement using either one or two different isotopic labels. For fibrinogen the larger intra-individual scatter necessitates larger study groups to detect changes in longitudinal studies. Repeated measurements within 48 hours need to be validated further.

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 123 I-labeled and 125 I-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. 123 I-labeled and 125 I-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.

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.

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.

Background: Higher than normal plasma glutamine concentration at admission to an intensive care unit is associated with an unfavorable outcome. Very high plasma glutamine levels are sometimes seen in both acute and chronic liver failure. We aimed to systematically explore the relation between different types of liver failure and plasma glutamine concentrations., Methods: Four different groups of patients were studies; chronic liver failure (n = 40), acute on chronic liver failure (n = 20), acute fulminant liver failure (n = 20), and post-hepatectomy liver failure (n = 20). Child-Pugh and Model for End-stage Liver Disease (MELD) scores were assessed as indices of liver function. All groups except the chronic liver failure group were followed longitudinally during hospitalisation. Outcomes were recorded up to 48 months after study inclusion., Results: All groups had individuals with very high plasma glutamine concentrations. In the total group of patients (n = 100), severity of liver failure correlated significantly with plasma glutamine concentration, but the correlation was not strong., Conclusion: Liver failure, regardless of severity and course of illness, may be associated with a high plasma glutamine concentration. Further studies are needed to understand whether high glutamine levels should be regarded as a biomarker or as a contributor to symptomatology in liver failure.

Purpose of Review: Muscle wasting is dramatic in critically ill patients and related to worsened outcome. The question is whether this can be prevented or reduced by adequate protein feeding. Recommendations for protein requirements are different between different societies, because of limited and weak evidence. Most studies, on which these recommendations are based, use nitrogen balance as primary outcome. However, nitrogen balance to estimate protein needs over short periods, is not reliable., Recent Findings: Studies using tracer methodology to assess the effects of feeding on whole-body protein synthesis, breakdown and balance, show that both adult and pediatric critically ill patients can utilize parenterally and enterally given proteins or amino acids to build body protein, and that the extra amino acids are not oxidized., Summary: Recent studies show a positive correlation between protein intake and protein balance, with many patients reaching a positive protein balance. However, many questions remain. Especially whether adult patients should have a constant positive protein balance, whether the route of administration affects utilization, which proteins are synthesized and whether these are beneficial, is more protein better and what is the upper limit, and whether a positive protein balance affects clinical outcome?

Background: AZD3043 is a positive allosteric modulator of the γ-aminobutyric acid type A receptor that is rapidly metabolized to an inactive metabolite by esterases present in blood and liver. Preclinical results suggest that AZD3043 has the potential as a short-acting IV sedative/anesthetic drug with rapid and predictable recovery characteristics and a favorable safety and tolerability profile., Methods: Our primary objective in this phase 1, single-center, open-label study was to evaluate the safety and tolerability of AZD3043 after IV infusion and to estimate the maximal tolerated dose. Secondary objectives included the evaluation of AZD3043 pharmacokinetics, pharmacodynamics, and efficacy. Sequential ascending-dose cohorts of 5 or 6 healthy male volunteers aged 18 to 45 years received a single 30-minute IV infusion of AZD3043. Assessments included adverse events, vital signs, blood gases, laboratory values, clinical signs of sedation/anesthesia, and bispectral index., Results: Fifty-three subjects received AZD3043 in infusion rate cohorts of 1, 3, 6, 12, 18, 27, 36, 54, and 81 mg/kg/h. There were no discontinuations, and dose escalation was stopped on reaching the predefined exposure limit. Adverse events occurring in >1 subject were headache (n = 4), erythema (n = 3), chest discomfort (n = 2), nausea (n = 2), and dyspnea (n = 2). The frequency and character of adverse events appeared unrelated to dose. There were no spontaneous reports of pain on injection and no clinically relevant changes in respiratory rate or arterial blood pressure. However, heart rate increased dose-dependently at infusion rates >18 mg/kg/h. Occurrence of sedation/anesthesia corresponded with dose; the lowest applied infusion rate to induce anesthesia according to clinical signs of sedation/anesthesia at predefined time points was 12 mg/kg/h (1 of 6 subjects anesthetized), and all subjects in the 3 highest dose groups were anesthetized. The onset of anesthesia ranged from 4 minutes in the highest infusion rate group to 29 minutes in the 12-mg/kg/h infusion rate group. Return of response to oral command occurred at 3 minutes after the end of infusion in the single subject who was anesthetized in the 12-mg/kg/h group and median 25 minutes in the 81-mg/kg/h group. Involuntary movements ranging from minor twitches to extensive movements were accompanied by increased muscle tone., Conclusions: AZD3043 was well tolerated in this first human study and seems to exhibit rapid onset and recovery, indicating potential use as a short-acting drug for anesthesia and sedation.

Background: AZD3043 is a positive allosteric modulator of the γ-aminobutyric acid type A receptor, with sedative and anesthetic properties. We describe a population pharmacokinetic (PK) model of arterial and venous concentrations of AZD3043 and the pharmacodynamic effects on bispectral index (BIS) in healthy volunteers., Methods: Arterial and venous plasma concentrations of AZD3043 and BIS were measured in 2 clinical studies in 125 healthy volunteers, where AZD3043 was given as a 1-minute bolus (1-6 mg/kg), a 30-minute infusion (1-81 mg/kg/h), or 0.8 + 10, 1 + 15, 3 + 30, and 4 + 40 (mg/kg bolus + mg/kg/h infusion for 30 minutes). Population PK/pharmacodynamic analysis was performed with NONMEM., Results: A recirculatory model, comprising a series of 5 compartments for the transit of drug between venous and arterial plasma, 2 peripheral distribution compartments, and 1 compartment for the nondistributive transit of drug from arterial to venous plasma, described the PK of AZD3043. Systemic clearance was high (2.2 L/min; 95% confidence interval, 2.12-2.25), and apparent volumes of distribution were low, leading to a short elimination half-life. The apparent volumes of distribution of the arterial and peripheral compartments increased with increasing administered dose, giving a total apparent volume of distribution of 15 L after the lowest dose and 37 L after the greatest dose. A sigmoid maximum effect (Emax) model with an EC50 of 15.6 µg/mL and a γ of 1.7 described the relationship between AZD3043 effect-site concentrations and BIS. The between-subject variability in EC50 was 37%. An effect compartment model, with a half-life of the equilibration rate constant ke0 of 1.1 min, described the delay in effect in relation to the arterial plasma concentrations., Conclusions: AZD3043 had a high clearance and a low apparent volume of distribution, leading to a short half-life. However, the apparent volume of distribution was dose dependent (P < 0.001), leading to an increased half-life with increasing dose. The distribution to the effect site was fast and together with the short plasma half-life led to a fast onset and offset of effects.

Background: AZD3043 (THRX-918661) is an investigational phenylpropanoid sedative/anesthetic that is rapidly metabolized by esterases in blood and liver. In the first-in-man study, a 30-minute constant IV infusion of AZD3043 induced anesthesia without major safety or tolerability concerns and with rapid recovery characteristics., Methods: The primary objective of this phase 1, single-center, open-label study (clinicaltrials.gov NCT00984880) was to evaluate the safety and tolerability of AZD3043 administered as a single IV bolus and as a bolus followed by infusion. Secondary objectives included evaluation of AZD3043 pharmacodynamics and efficacy. Sequential ascending dose cohorts of 8 healthy volunteers aged 18 to 65 years received either a single 1-minute bolus IV infusion (part A) or a 1-minute bolus followed by a 30-minute infusion (part B). Assessments included adverse events, vital signs, blood gases, laboratory values, clinical signs of sedation/anesthesia, and bispectral index score., Results: Seventy-two subjects (8 females, 64 males) received AZD3043 doses of 1, 1.5, 2, 4, and 6 mg/kg bolus over 1 minute (part A) or 0.8 + 10, 1 + 15, 3 + 30, and 4 + 40 mg/kg bolus + mg/kg/h infusion for 30 minutes (part B). There were no discontinuations. Adverse events occurring in >1 subject were headache (n = 15; 21%), nausea (n = 7; 10%), vomiting (n = 3; 4%), and fatigue (n = 2; 3%). Twenty-one subjects experienced at least 1 adverse event. There seemed to be no dose relationship associated with any adverse event. Ventilation was maintained, but there was a dose-dependent increase in heart rate. There were no spontaneous reports of pain on injection. Thirty-two subjects were anesthetized, including all subjects in the highest dose group in part A and all subjects in the 2 highest dose groups in part B. Recovery from anesthesia was rapid, with swift return of orientation and proprioception. All subjects were able to walk 10 m without support at their first assessment, 30 minutes after end of dosing, except for 1 subject in each of the 2 mg/kg bolus (part A) and 4 mg/kg bolus + 40 mg/kg/h 30-minute infusion (part B) dose groups, who passed this test at the subsequent assessment, 45 minutes after the end of dosing. Involuntary movements were observed at higher doses, accompanied by increased muscle tone., Conclusions: AZD3043 provided rapid recovery from anesthesia with maintained ventilation. Further studies are warranted in a clinical setting.

Background: The drop in plasma albumin concentration following surgical trauma is well known, but the temporal pattern of the detailed mechanisms behind are less well described. The aim of this explorative study was to assess changes in albumin synthesis and transcapillary escape rate (TER) following major surgical trauma, at the time of peak elevations in two well-recognized markers of inflammation., Methods: This was a clinical trial of radiolabeled human serum albumin for the study of TER and plasma volume. Ten patients were studied immediately preoperatively and on the 2nd postoperative day after major pancreatic surgery. Albumin synthesis rate was measured by the flooding dose technique employing incorporation of isotopically labelled phenylalanine., Results: Fractional synthesis rate of albumin increased from 11.7 (95% CI: 8.9, 14.5) to 15.0 (11.7, 18.4) %/day (p = 0.027), whereas the corresponding absolute synthesis rate was unchanged, 175 (138, 212) versus 150 (107, 192) mg/kg/day (p = 0.21). TER was unchanged, 4.9 (3.1, 6.8) %/hour versus 5.5 (3.9, 7.2) (p = 0.63). Plasma volume was unchanged but plasma albumin decreased from 33.5 (30.9, 36.2) to 22.1 (19.8, 24.3) g/L. (p<0.001)., Conclusion: Two days after major abdominal surgery, at the time-point when two biomarkers of generalised inflammation were at their peak and the plasma albumin concentration had decreased by 33%, we were unable to show any difference in the absolute synthesis rate of albumin, TER and plasma volume as compared with values obtained immediately pre-operatively. This suggests that capillary leakage, if elevated postoperatively, had ceased at that time-point. The temporal relations between albumin kinetics, capillary leakage and generalised inflammation need to be further explored., Trial Registration: clinicaltrialsregister.eu: EudraCT 2010-08529-21 ClinicalTrials.gov NCT01194492.

Background & Aims: To evaluate the effect of nutrition therapy on protein turnover in critically ill patients isotopically labeled amino acids can be used. Here parallel measurements using (13)C-leucine and (2)H5-phenylalanine were performed to evaluate if one tracer was to be preferred., Methods: As a reference group, healthy volunteers (n = 8) were studied in the postabsorptive state and during parenteral nutrition delivery. ICU patients with multiple organ failure (n = 8) were studied during parenteral nutrition delivery only., Results: For the volunteers, the net protein balances changed from negative to positive during parenteral nutrition delivery (compared to the postabsorptive state) when evaluated with leucine and phenylalanine (P < 0.0001). For phenylalanine this change was attributable to an increased protein synthesis (P < 0.0001), while for leucine the change was attributable to a decreased protein degradation (P < 0.0001). For the patients, only measured during parenteral nutrition delivery, the estimates by the two amino acid tracers agreed, showing a protein balance not statistically significantly different from zero. The whole body protein turnover was higher than that of the healthy volunteers during parenteral nutrition delivery. In the patients, the net protein balance correlated positively to the amount of amino acids given., Conclusions: Critically ill patients with multiple organ failure have an increased protein turnover. The findings in the healthy volunteers indicate that the use of the two different amino acid tracers in parallel in future studies should be considered., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction: Low plasma glutamine concentration at ICU admission is associated with unfavorable outcomes. The prediction of plasma glutamine concentration after ICU discharge on outcomes has not been characterized. In the recent Scandinavian Glutamine Trial, a survival advantage was seen with glutamine supplementation as long as patients stayed in the ICU. It was therefore hypothesized that the glutamine level may drop at ICU discharge, indicative of a sustained glutamine deficiency, which may be related to outcome., Methods: Fully fed ICU patients intravenously supplemented with glutamine for >3 days were studied at ICU discharge and post ICU. In study A, plasma glutamine level was followed every 5 to 7 days post ICU of the remaining hospital stay and compared to the level on the day of ICU discharge (n=63). In study B, plasma glutamine level 24 to 72 hours after ICU discharge was related to 12-month all-cause mortality (n=100)., Results: Post-ICU plasma glutamine levels were within normal range and were not found to be predictive for mortality outcome. Plasma glutamine level at discharge, on the other hand, was within normal limits but higher in nonsurvivors. In addition, it was adding prediction value to discharge SOFA scores for post-ICU mortality., Conclusions: Post-ICU glutamine levels are not indicative of glutamine depletion. The relation between plasma glutamine concentration and glutamine availability during critical illness is not well understood, and needs to be studied further to define the possible role for glutamine supplementation.

Glutamine depletion is demonstrated to be an independent predictor of hospital mortality in ICU (intensive care unit) patients. Today glutamine supplementation is recommended to ICU patients on parenteral nutrition. In addition to glutamine, glutathione may be a limiting factor in ICU patients with MOF (multiple organ failure). To study the prevalence of glutamine and glutathione depletion an observational study was performed. The results were analysed in relation to mortality and the conventional predictors of mortality outcome, APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sequential Organ Failure Assessment). Consecutive patients admitted to the ICU at Karolinska University Hospital Huddinge were studied. Patient admission scoring of APACHE II and SOFA were registered as well as mortality up to 6 months. Plasma glutamine concentration and whole blood glutathione status at admittance were analysed. The admission plasma glutamine concentrations were totally independent of the conventional risk scoring at admittance, and a subnormal concentration was an independent predictor of mortality. In addition, glutathione redox status was also an independent mortality predictor, but here a normal ratio was the risk factor. In both cases the mortality risk was mainly confined to the post-ICU period. A low plasma concentration of glutamine at ICU admission is an independent risk factor for post-ICU mortality. The possible benefit of extending glutamine supplementation post-ICU should be evaluated prospectively.

Introduction: Pain is the most common symptom following laparoscopic cholecystectomy (LC) and might delay discharge from hospital after day surgery. A patient's ability to manage stressful situations can be assessed by the sense of coherence (SOC) and has been proposed to predict health. The aim of this study was to investigate predictors of average pain the first postoperative week after LC, and predictors of changes in perceived health, with special reference to individual coping resources measured by the Sense of Coherence Scale. Furthermore, a test-re-test was performed on SOC to evaluate the stability in the context of LC surgery., Method: Seventy-three patients completed questionnaires about SOC, health status, pain, anxiety, symptom occurrence and symptom distress preoperatively, postoperative day 1-7 and after 1 and 6 months following LC., Results: By multiple regression, 23% of the variability in pain intensity could be explained by the variables age, SOC and education. Age was the strongest predictor. Further, 19% of the change in health between day 7 and 1 month could be explained by the two variables symptom distress the first postoperative day and SOC. The test-re-test of SOC had a correlation coefficient (r) of 0.55. Forty-six patients (63%) remained within ±10% of their preoperative SOC score at 6 months, 11 patients (15%) decreased and 16 patients (22%) increased their SOC values., Conclusion: SOC was found to be a significant but weak predictor of pain intensity the first week after LC. Furthermore, patients scoring low SOC values experienced a delay in their health improvement. SOC was more unstable over time than previously suggested. Further, interventional studies are needed to clarify if SOC might be a clinically useful measure to identify vulnerable patients undergoing LC surgery., (© 2010 The Authors. Scandinavian Journal of Caring Sciences © 2010 Nordic College of Caring Science.)