Background: The aim of this proof of concept, prospective, randomized pilot trial was to investigate the effects of extracorporeal cytokine removal (CytoSorb®) applied as a standalone treatment in patients with septic shock. Methods: 20 patients with early (b24 h) onset of septic shock of medical origin, on mechanical ventilation, norepinephrineN10 μg/min, procalcitonin (PCT) N 3 ng/mL without the need for renal replacement therapy were randomized into CytoSorb (n = 10) and Control groups (n = 10). CytoSorb therapy lasted for 24 h. Clinical and laboratory data were recorded at baseline (T 0), T 12 , T 24 , and T 48 hours. Results: Overall SOFA scores did not differ between the groups. In the CytoSorb-group norepinephrine requirements and PCT concentration decreased significantly

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...

BackgroundFluid resuscitation remains a cornerstone in the management of acute bleeding. According to Starling's “Three-compartment model”, four-times more crystalloids have the same volume effect as colloids. However, this volume-replacement ratio remains a controversial issue as it may be affected by the degradation of the endothelial glycocalyx layer, a situation often found in the critically ill. Our aim was to compare colloid and crystalloid based fluid resuscitation during an experimental stroke volume index (SVI) guided hemorrhage and resuscitation animal model.MethodsAnesthetized and mechanically ventilated pigs were randomized to receive a colloid (Voluven®,HES, n=15) or crystalloid (Ringerfundin®,RF, n=15) infusion. Animals were bled till baseline SVI (Tbsl) dropped by 50% (T0), followed by resuscitation until initial SVI was reached (T4) in four steps. Invasive hemodynamic measurements, blood gas analyses and laboratory tests were performed at each assessment points. Glycocalyx degradation markers (Syndecan-1/hematocrit ratio, Glypican/hematocrit ratio) were determined at Tbsl, T0 and T4.ResultsSimilar amounts of blood were shed in both groups (HES group: 506±159 mls blood, RF group: 470±127 mls blood). Hemodynamic changes followed the same pattern without significant difference between the groups. Animals received significantly less resuscitation fluid in the HES compared to the RF-group: 425 [320-665], vs 1390 [884-1585] mls, p <0.001. The volume replacement ratio was 0.92 [0.79-1.54] for HES; and 3.03 [2.00-4.23] for the RF-group (p <0.001). There was no significant difference between the groups in the glycocalyx degradation markers.ConclusionIn this moderate bleeding-resuscitation animal model the volume-replacement ratio for crystalloids and colloids followed similar patterns as predicted by Starling's principle, and the glycocalyx remained intact. This indicates that in acute bleeding events, such as trauma or during surgery, colloids may be beneficial as hemodynamic stability may be achieved more rapidly than with crystalloids.

Invasive fungal infections have become a serious problem in the critically ill. One of the main reasons is the development of an immunocompromised condition. The most frequently found pathogens are Candida species. In order to provide adequate treatment, understanding this potentially life-threatening infection is mandatory. The aim of this summary is to view Candida infections from a different perspective and to give an overview on epidemiology, the range of pathophysiology from colonization to the invasive infections, and its impact on mortality. New therapeutic options will also be discussed and how these relate to current guidelines. Finally, the key issue of the choice of anti-fungal agents will be evaluated.

BACKGROUND Macro, and microcirculatory effects of crystalloids and colloids are difficult to compare, because interventions to achieve haemodynamic stability seldom follow similar criteria. OBJECTIVES Our aim was to compare the effects of crystalloids and colloids on the microcirculation during free flap surgery when management was guided by detailed haemodynamic assessment. DESIGN A randomised, controlled clinical trial. SETTINGS The investigation was performed at the University of Szeged, Hungary. PATIENTS Patients undergoing maxillofacial tumour resection and free flap reconstruction were randomised into groups treated with either intra-operative crystalloid (Ringerfundin, n ¼ 15) or colloid (6% hydroxyethyl starch, HES, n ¼ 15) solutions. INTERVENTIONS Macrohaemodynamics were monitored by a noncalibrated device (PulsioFlex-PULSION). Central venous oxygen saturation, venous-to-arterial PCO 2-gap, lactate levels and urine output were measured hourly. Maintenance fluid was Ringerfundin (1 ml kg À1 h À1), and a multimodal, individualised, approach-based algorithm was applied to guide haemodynamic support. Hypovolaemia was treated with Ringerfundin or HES fluid boluses, respectively. The microcirculatory effects were assessed by laser-Doppler flowmetry (PeriFlux 5000 LDPM), with the probe placed on the flap and on a control area. Measurements were performed after the flap was prepared, then 1 and 12 h later. MAIN OUTCOME MEASURES The primary end-point was microcirculatory perfusion as determined by laser-Doppler flowmetry. RESULTS There was no difference between the groups regarding patient characteristics. Both groups remained haemodynamically stable throughout due to the use of approximately a 1.5 times higher total fluid volume in the Ringerfundin group than in the HES group: mean AE SD: 2581 AE 986 and 1803 AE 497) ml, respectively, (P ¼ 0.011). There was no significant difference in the microcirculatory blood flow between the groups. CONCLUSION Our results showed that when fluid management was guided by detailed haemodynamic assessment, more crystalloid than colloid was needed to maintain haemodynamic stability, but there was no difference between the effects of crystalloids and colloids on the microcirculation. TRIAL REGISTRATION ClinicalTrials.gov NCT03288051.

IntroductionFluid resuscitation is the cornerstone of treatment in hemorrhagic shock. Despite increasing doubts, several guidelines recommend to maintain mean arterial pressure (MAP) >65 mmHg as the most frequent indication of fluid therapy. Our aim was to investigate the effects of a MAP-guided management in a bleeding-resuscitation animal experiment.Materials and methodsAfter anesthesia and instrumentation (tbsl) animals were bled till the initial stroke volume index dropped by 50% (t0). Fluid replacement was performed in 4 equivalent steps (t1-4) with balanced crystalloid solution to reach the baseline values of MAP. Invasive hemodynamic measurements and blood gas analyses were performed after each step.ResultsMean arterial pressure dropped from tbsl to t0 (114±11 vs 76.9±16.9 mmHg, p<0.001) and returned to baseline by t4 (101.4±14.4 mmHg). From tbsl-t0 stroke volume index (SVI), cardiac index (CI) decreased (SVI: 40±8.6 vs 19.3±3.6 ml/m2, p<0.001; CI: 3.4±0.3 vs 1.9±0.3 l/min/m2, p<0.001), pulse pressure variation (PPV) increased (13.2±4.3 vs 22.1±4.3%, p<0.001). There was a decrease in oxygen delivery (464±45 vs 246±26.9 ml/min, p<0.001), central venous oxygen saturation (82.8±5.4 vs 53.6±12.1%, p<0.001) and increase in lactate levels (1.6±0.4 vs 3.5±1.6 mmol/l, p<0.005). SVI, CI and PPV returned to their initial values by t2. To normalize MAP fluid therapy had to be continued till t4, with the total infused volume of 4.5±0.8 l.ConclusionIn the current experiment bleeding led to hemorrhagic shock, while MAP remained higher than 65 mmHg. Furthermore, MAP was unable to indicate the normalization of SVI, CI and PPV that resulted in unnecessary fluid administration. Our data give further evidence that MAP may be an inappropriate parameter to follow during fluid resuscitation.

No abstract

The current protocol is a bleeding-resuscitation model intended to imitate the effects of severe blood loss and subsequent fluid resuscitation. The experimental subjects were Vietnamese pot-bellied pigs of both sexes weighing 33±4 kg. The animals underwent a 12-hours fasting pre-operatively but had free access to water. Anesthesia was induced by intramuscular injection of a mixture of ketamine (20 mg/kg) and xylazine (2 mg/kg) and maintained with a continuous iv. infusion of Propofol (50 µL/min/kg IV; 6 mg/kg/hr), while analgesia was maintained with intermittent nalbuphine (0.1 mg/kg). After endotracheal intubation, the animals were mechanically ventilated with a Hamilton C1 respirator (Hamilton Medical AG, USA). The tidal volume was set to 10 ml/kg, and the respiratory rate was adjusted to maintain the end-tidal carbon dioxide and partial pressure of arterial carbon dioxide within the range of 35–45 mmHg and the arterial pH between 7.35 and 7.45. The depth of anaesthesia was assessed by checking jaw tone. After induction of anaesthesia, catheters were inserted into the left jugular vein, left external carotid artery and the left femoral artery. For invasive hemodynamic monitoring, a transpulmonary thermodilution catheter (PiCCO, PULSION Medical Systems SE, Munich, Germany) was used. The femoral artery served as the site for arterial blood gas sampling, the central venous line was used for taking central venous blood gas samples and for the injection of cold saline boluses for the thermodilution measurements, whilst the carotid arterial catheter was used for draining blood. A transpubic catheter was placed into the urinary bladder for monitoring renal function. Animals were covered in scrubs and an external heating device was used to maintain physiological body temperature.