Critical Care 2017, 21(Suppl 1):P349 Introduction Imbalance in cellular energetics has been suggested to be an important mechanism for organ failure in sepsis and septic shock. We hypothesized that such energy imbalance would either be caused by metabolic changes leading to decreased energy production or by increased energy consumption. Thus, we set out to investigate if mitochondrial dysfunction or decreased energy consumption alters cellular metabolism in muscle tissue in experimental sepsis. Methods We submitted anesthetized piglets to sepsis (n = 12) or placebo (n = 4) and monitored them for 3 hours. Plasma lactate and markers of organ failure were measured hourly, as was muscle metabolism by microdialysis. Energy consumption was intervened locally by infusing ouabain through one microdialysis catheter to block major energy expenditure of the cells, by inhibiting the major energy consuming enzyme, N+/K + -ATPase. Similarly, energy production was blocked infusing sodium cyanide (NaCN), in a different region, to block the cytochrome oxidase in muscle tissue mitochondria. Results All animals submitted to sepsis fulfilled sepsis criteria as defined in Sepsis-3, whereas no animals in the placebo group did. Muscle glucose decreased during sepsis independently of N+/K + -ATPase or cytochrome oxidase blockade. Muscle lactate did not increase during sepsis in naïve metabolism. However, during cytochrome oxidase blockade, there was an increase in muscle lactate that was further accentuated during sepsis. Muscle pyruvate did not decrease during sepsis in naïve metabolism. During cytochrome oxidase blockade, there was a decrease in muscle pyruvate, independently of sepsis. Lactate to pyruvate ratio increased during sepsis and was further accentuated during cytochrome oxidase blockade. Muscle glycerol increased during sepsis and decreased slightly without sepsis regardless of N+/K + -ATPase or cytochrome oxidase blocking. There were no significant changes in muscle glutamate or urea during sepsis in absence/presence of N+/K + -ATPase or cytochrome oxidase blockade. ConclusionsThese results indicate increased metabolism of energy substrates in muscle tissue in experimental sepsis. Our results do not indicate presence of energy depletion or mitochondrial dysfunction in muscle and should similar physiologic situation be present in other tissues, other mechanisms of organ failure must be considered. , and long-term follow up has shown increased fracture risk [2]. It is unclear if these changes are a consequence of acute critical illness, or reduced activity afterwards. Bone health assessment during critical illness is challenging, and direct bone strength measurement is not possible. We used a rodent sepsis model to test the hypothesis that critical illness causes early reduction in bone strength and changes in bone architecture. Methods 20 Sprague-Dawley rats (350 ± 15.8g) were anesthetised and randomised to receive cecal ligation and puncture (CLP) (50% cecum length, 18G needle single pass through anterior and posterior wa...

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days of PN. The intervention and comparator are low versus high parenteral leucine intakes expressed as either the percentage leucine content of the AA solution (%) or absolute leucine intake (mg/kg/d). The outcome measured was plasma leucine concentration (micromoles/L). All study designs were eligible for inclusion, except for review articles. Only articles which reported the actual parenteral AA intake and measured plasma leucine concentration after day 3 (72 hours) of PN were eligible. The data were obtained using a data extraction form designed for this review. Quality assessments using a custom-designed tool and the GRADE framework were performed.Results Twelve articles met the inclusion criteria, which collectively studied 650 VPNs. The dose-concentration relationships of leucine content (%) and absolute leucine intake (g/kg/d) with plasma leucine concentration (micromoles/L) both showed significant, moderately positive correlations (p < 0.05), as shown in figure 1. Regression analysis indicated that absolute leucine intake was the stronger predictor of outcome. Subgroup analysis indicated that neither the overall study design nor the analytical method used for AA analysis affected the plasma leucine level. Abstract 782 Figure 1 Dose concentration relationship graph of absolute leucine intake with plasma leucine concentration Abstract 782 Figure 2 Dose concentration relationship graph of percentage leucine content with plasma leucine concentrationConclusion There is a linear relationship between plasma leucine concentration and both percentage leucine content and leucine intake (mg/kg/day) in VPNs. This work indicates that the leucine content of future neonatal PN solutions should be reduced to 8-9g/100g AA to achieve plasma AA concentrations within the reference range. This methodology can be applied to all essential AA.