A new complimentary web-based tool for manual analysis of microcirculation videos: validation of the capillary mapper against the current gold standard AVA 3.2

OBJECTIVE: The aim of the current study was to compare a newly developed web-based freely accessible software program for manual analysis of the microcirculation, the Capillary Mapper (CM), with AVA 3.2 software (AVA; MicroVision Medical B.V., Amsterdam, The Netherlands), which is the current gold standard for analysis of microcirculation videos. METHODS: A web-based software program was developed, which enables manual analysis of videos of the microcirculation to be carried out according to recommendations of the 2018 consensus conference. A set of 50 high quality microcirculation videos was analyzed with AVA and CM with respect to total vessel density, perfused vessel density, proportion of perfused vessels, and the microvascular flow index. RESULTS: Comparison of the mean values derived from manual analysis with CM and AVA revealed no significant differences in microcirculatory variables. Analysis according to Bland and Altman revealed an acceptable bias between manual analysis with the CM and AVA for all variables tested with sufficient limits of agreement. The analysis of intraclass correlation showed "excellent" agreement for all microcirculatory variables analyzed. CONCLUSIONS: The newly developed CM was successfully validated for manual analyses of microcirculation videos against the current gold standard, the software AVA 3.2

Auswirkungen einer balancierten Kristalloid- versus einer balancierten Hydroxyethylstärkelösung (6% HES 130/0.4) auf die Nierenfunktion und Tubulusschädigung endotoxämischer Schafe

Die vorliegende Arbeit untersuchte die Auswirkungen balancierter Kristalloide vs. balancierter Kolloide auf die Nierenfunktion und Tubulusschädigung endotoxämischer Schafe. Dafür wurden 28 gesunde Tiere nach einem etablierten Endotoxin-Modell instrumentiert. Nach einem definierten Schockzeitpunkt erfolgte die Randomisierung in 3 Gruppen (Kolloid, Kristalloid, Kontrolle). Die Tiere erhielten eine Volumentherapie nach den aktuellen Leitlinien mit Durchführung stündlicher Messungen. Nach 12-stündiger Untersuchungsdauer erfolgte die Tötung der Tiere sowie die Organentnahme. Es zeigte sich ein signifikanter Anstieg der Retentionsparameter Harnstoff und Kreatinin ohne Unterschied der Kreatinin-Clearance sowie ein signifikant geringerer ultrastruktureller Nierenschaden in der Kolloidgruppe. Es konnte kein negativer Effekt der Kolloidtherapie auf die Nierenfunktion nachgewiesen werden, der fehlende Kreatininanstieg der Kristalloidgruppe kann auf einem erhöhten Verteilungsvolumen beruhen

Sole causal therapy worsens outcome as compared to no therapy and combined causal and goal-directed supportive therapy in ovine septic shock

Background: There is dear evidence that early causal therapy improves outcome in sepsis and septic shock, whereas recent studies on supportive hemodynamic therapy have produced very conflictive results. The objective of the present study was to determine whether a supportive hemodvnamic therapy guided by clinically relevant invasive monitoring improves survival and organ function in a high-lethality model of septic shock in sheep as compared to sole causal therapy including surgical and antimicrobial treatment. Methods: Twenty healthy ewes were anaesthetized and instrumented for hemodynamic surveillance. After laparotomy and fecal withdrawal from the caecum, animals were randomly assigned to one of four groups: sham, control, causal and combined therapy. In all groups but the sham group, feces were injected into the peritoneal cavity. Septic shock was defined as mean arterial pressure (MAP) = 1.8 mmol(.)L(-1). Animals of the control group received no therapy, while the causal group received broad-spectrum antibiotic therapy and peritoneal lavage. The combined therapy group received causal therapy plus supportive hemodynamic therapy. Results: The sham animals showed no signs of systemic infection, while all other animals developed septic shock with arterial hypotension and lactic acidosis within 4.0 (4.0-6.8) hours. Induction of causal therapy did not impact on haemodynamics as compared to the control group. Notably, 50% of the control animals and none of the causal therapy animals survived the study. Combined therapy stabilized haemodynamics and improved organ function and survival as compared to control and causal therapy groups. Conclusions: The present data suggest that sole causal sepsis therapy without hemodynamic support worsens outcome even more than natural evolution of sepsis and combined causal and supportive therapy. This underlines the importance of early hemodynamic stabilization in parallel with antibiotic and surgical treatment of the sepsis focus

Impact of human albumin infusion on organ function in orthotopic liver transplantation - a retrospective matched-pair analysis

BACKGROUND: The purpose of this study was to retrospectively analyze the impact of human albumin (HA) substitution on organ function in patients undergoing orthotopic liver transplantation (OLT). METHODS: We retrospectively analyzed chart data of 15 hypoalbuminemic patients who received continuous infusion of HA (100 g/d) for seven d following OLT and matched them with 15 control patients for severity scores at admission. Primary endpoint was a difference in mean "sequential organ failure assessment" (SOFA) score during 14 d following OLT. Secondary endpoints included SOFA subscores, length of intensive care unit (ICU) stay, ICU mortality, one-yr mortality, fluid balance, colloid osmotic pressure (COP), serum albumin, and total protein concentrations. RESULTS: Substitution of HA was associated with a lower mean SOFA score as compared to control (11.0 ± 3.6 vs. 13.4 ± 3.7; p < 0.001). Patients treated with HA also exhibited lower cardiovascular SOFA subscore and higher COP, serum albumin, and total protein concentrations. There were no significant differences in fluid balance, length of ICU stay, ICU mortality, or one-yr mortality. CONCLUSIONS: The present data suggest that continuous infusion of HA may preserve cumulative organ function (as measured by SOFA score) with emphasis on cardiovascular function in patients following OL

Differential Effects of Selective and Nonselective Potassium Channel Inhibitors in Ovine Endotoxemic Shock (Macrocirculation) and in a Rat Model of Septic Shock (Microcirculation)

BACKGROUND: Potassium-(K)-channel inhibitors may increase systemic vascular resistance in vasodilatory shock states. OBJECTIVE: The purpose of the present study was to compare the macro- and microvascular effects of the adenosine triphosphate-sensitive K-channel-(KATP)-inhibitor glipizide and the nonselective K-channel inhibitor tetraethylammonium (TEA) in ovine endotoxemic shock and septic shock in rats. DESIGN: Two randomized, controlled laboratory studies. ANIMALS: Thirty female sheep and 40 male Sprague Dawley rats. SETTING: Animal research facility INTERVENTION:: Systemic hemodynamics were analyzed in ovine endotoxemic shock with guideline-oriented supportive therapy. Sheep were allocated to three treatment groups for 12 h: glipizide 10 mg kg·h, TEA 8 mg kg·h, or 0.9% saline. The microvascular effects of each drug were evaluated in septic rats (cecal ligation and puncture model) receiving a 2-h infusion of each study drug: glipizide 20 mg kg·h; TEA 50 mg kg·h, or 0.9% saline, respectively, followed by intravital microscopy of villi microcirculation. RESULTS: Compared with the control group, glipizide infusion increased systemic vascular resistance index and decreased cardiac index and heart rate (HR) in sheep (P < 0.05), whereas TEA infusion decreased HR and resulted in a decreased survival time (P = 0.001). In rats, glipizide infusion resulted in an increase in mean arterial pressure and a decrease in HR compared with baseline measurement (P < 0.05) without relevant effects on the villi microcirculation. TEA decreased HR and decreased capillary perfusion of the villi microcirculation compared with the sham group (P = 0.002). CONCLUSIONS: Selective inhibition of KATP-channels in ovine endotoxemic shock with glipizide partially restored vasomotor tone without exerting harmful effects on intestinal microcirculation in septic shock in rats. On the contrary, nonselective K-channel inhibition with TEA showed deleterious effects in both models, including impaired microcirculation and decreased survival time. Future research on glipizide in vasodilatory shock may be warranted

Comparison of first-line and second-line terlipressin versus sole norepinephrine in fulminant ovine septic shock

The Surviving Sepsis Guidelines suggest the use of vasopressin in case of catecholamine-refractory septic shock. Terlipressin (TP) as a V1-selective AVP analogue is a potential alternative, though data regarding the first-line administration in septic shock are scarce. The present study explored and compared the effects of first-line vs. second-line infusion of TP or sole norepinephrine regarding organ function, fluid and norepinephrine requirements and survival in fulminant ovine septic shock. Peritoneal sepsis was induced in 23 ewes after laparotomy and faecal withdrawal from the caecum. After onset of shock, causal and supportive sepsis therapy (antibiotics, peritoneal lavage, fluids and open-label norepinephrine) was performed in all animals. Concurrently, animals were randomized to receive 0.9% sodium chloride (control group) or TP (2 µg∙kg−1∙h−1, first-line group) after shock onset. In the second-line TP group, TP (2 µg∙kg−1∙h−1) was started once norepinephrine requirements exceeded 0.5 µg∙kg−1∙min−1. No significant differences were found between groups regarding survival, haemodynamics as well as fluid- and catecholamine-requirements. Kidney function and electron microscopic kidney injury were comparable between groups. In the present model of fulminant ovine septic shock, first-line TP infusion had no significant effect on fluid and norepinephrine requirements or organ dysfunction as compared to second-line TP infusion or placebo

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A model of porcine polymicrobial septic shock

Abstract Background Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs. Materials and methods The literature search was performed using the keywords “pig”, “sepsis” and “septic shock”. For the establishment of septic shock in n = 10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3 g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA. Results Published porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8 ± 0.29 h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54 ± 1 mmHg) and significant hyperlactatemia (3.76 ± 0.65 mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred. Conclusions We here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs

Additional file 3: of Feasibility of optical coherence tomography angiography to assess changes in retinal microcirculation in ovine haemorrhagic shock

Video of conjunctival microcirculation in haemorrhagic shock. Conjunctival microcirculation in haemorrhagic shock measured with incident dark-field (IDF) video microscope. (MP4 4106 kb