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Bei vielen intensivmedizinischen Erkrankungen tritt eine Storung der Mikrozirkulation auf, die bisher noch nicht routinemasig untersucht werden kann. Fur Therapieentscheidungen und Prognoseeinschatzung wurde eine Information uber die Mikrozirkulation bei kritisch kranken Patienten jedoch von grosem Interesse sein. Die optische Koharenztomographie-Angiographie (OCTA) ermoglicht es, nichtinvasiv, kontaktlos und schnell den Blutfluss in der Mikrozirkulation der Retina darzustellen und hat daher moglicherweise das Potenzial, Storungen der Mikrozirkulation bei kritisch kranken Patienten zu diagnostizieren. Folgende Fragestellungen werden betrachtet: Stellenwert der Mikrozirkulation in der Intensivmedizin, Gegenuberstellung der Methoden der Videomikroskopie und der OCTA, Analyse der praklinischen und klinischen Daten zum Einsatz der OCTA bei intensivmedizinischen Krankheitsbildern. Es erfolgte eine selektive Literaturrecherche und Analyse der Daten. Eine direkte Darstellung der Mikrozirkulation ist seit Jahren mithilfe der Videomikroskopie moglich, im klinischen Alltag aber aufgrund der Storanfalligkeit und zeitaufwendigen Auswertung nicht etabliert. Die OCTA ist ein nichtinvasives und kontaktloses Verfahren zur Darstellung des retinalen Blutflusses. Die OCTA als nichtinvasives Verfahren ist eine vielversprechende Messmethode, die eine bettseitige Analyse der Mikrozirkulation bei kritisch kranken Patienten zukunftig ermoglichen konnte. Hierzu sind allerdings noch einige technische Einschrankungen zu uberwinden.

INTRODUCTION The conjunctival region may serve as an alternative site for microcirculatory measurements. The present study was performed to investigate the correlation of sublingual and conjunctival microcirculation in ovine models of septic and hemorrhagic shock. METHODS Septic shock was induced in 10 sheep by inoculation of feces into the peritoneal cavity until mean arterial pressure (MAP) was

Microcirculatory disorders are crucial in pathophysiology of organ dysfunction in critical illness. Evaluation of sublingual microcirculation is not routinely conducted in daily practice due to time-consuming analysis and susceptibility to artifacts. We investigated the suitability of optical coherence tomography angiography (OCTA) for contactless evaluation of sublingual microcirculation. Sublingual microcirculation was imaged in 10 healthy volunteers, using an OCTA device and an incident dark field (IDF) illumination microscopy (current gold standard). OCTA images were analyzed with regard to flow density and perfused vessel density (PVDbyOCTA). IDF videos were analyzed following current recommendations. Flow density was automatically extracted from OCTA images (whole en face 48.9% [43.2; 54.5]; central ring 52.6% [43.6; 60.6]). PVDbyOCTA did not differ from the PVD calculated from IDF videos (PVDbyOCTA 18.6 mm/mm² [18.0; 21.7]) vs. PVDbyIDF 21.0 mm/mm² [17.5; 22.9]; p = 0.430). Analysis according to Bland-Altman revealed a mean bias of 0.95 mm/mm² (95% Confidence interval −1.34 to 3.25) between PVDbyOCTA and PVDbyIDF with limits of agreement of −5.34 to 7.24 mm/mm². This study is the first to demonstrate the suitability of OCTA for evaluating sublingual microcirculation. Comparison of the perfused vessel density between methods showed a plausible level of agreement.

Background To determine the distribution of vancomycin into the cerebrospinal fluid (CSF) in patients with external ventricular drain (EVD)-associated ventriculitis, the pharmacokinetics of vancomycin were evaluated, and covariate relationships explored. Methods For the population pharmacokinetic model patients were recruited in a neuro-critical care unit at the University Hospital of Muenster in the period between January 2014 and June 2015. All patients had a clinical evidence of (EVD)-associated ventriculitis. Population pharmacokinetic analysis of vancomycin was performed using NONMEM®. Results A total of 184 blood and 133 CSF samples were collected from 29 patients. The final population pharmacokinetic model is a three-compartment model with linear elimination. Creatinine clearance (ClCr ) and CSF-lactate were detected as significant covariates, showing that the total vancomycin plasma clearance (Cl) depends on ClCr and furthermore, the clearance (Cldif ) between the central and CSF compartment correlates with CSF lactate concentration. Based on the final model, the following values were estimated by NONMEM®: Cl = 5.15 L/h, Q (intercompartmental clearance) =3.31L/h, Cldif = 0.0031 L/h, Vcentral = 42.1 L, VCSF = 0.32 L and the value of Vperipheral was fixed to 86.2 L. With the developed pharmacokinetic model, AUC (area under the curve) values as well as CSF trough levels were simulated. Conclusion Based on our analysis, the dosing of vancomycin should be referred to the degree of inflammation (derived from the CSF lactate concentration) and renal function (derived from ClCr ).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

There is increasing evidence in the literature that preoperative treatment with levosimendan optimizes cardiopulmonary haemodynamics in patients scheduled for the implantation of a Left Ventricular Assist Device (LVAD). The present case report describes changes in sublingual microcirculation using incident dark field video microscopy in a patient, who received a continuous infusion of 0.5 mg/h levosimendan 12 h before LVAD implantation. Despite no evident macrohaemodynamic or metabolic changes, there was a dramatic reduction in total vessel density and perfused vessel density suggesting a deterioration of microcirculation according to the consensus conference criteria in vessels smaller than 20 μm in diameter. However, the microcirculation of all visible vessels (regardless of diameter) was maintained. This potential misinterpretation is explained by a levosimedan-induced vasodilation and the subsequent reduction of the percentage of vessels with a diameter smaller than 20 μm. Physicians should carefully consider this pitfall of applying the consensus conference criteria in vasodilator-treated patients.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Fluid resuscitation in hemorrhagic shock aims to restore hemodynamics and repair altered microcirculation. Hemodynamic coherence is the concordant performance of macro- and microcirculation. The present study on fluid therapy in hemorrhagic shock hypothesized that the choice of fluid (0.9% sodium chloride [saline group] or balanced 6% hydroxyethyl starch 130/0.4 [hydroxyethyl starch group]) impacts on hemodynamic coherence. Methods After instrumentation, 10 sheep were bled up to 30 ml/kg body weight of blood stopping at a mean arterial pressure of 30 mmHg to establish hemorrhagic shock. To reestablish baseline mean arterial pressure, they received either saline or hydroxyethyl starch (each n = 5). Hemodynamic coherence was assessed by comparison of changes in mean arterial pressure and both perfused vessel density and microvascular flow index. Results Bleeding of 23 ml/kg blood [21; 30] (median [25th; 75th percentile]) in the saline group and 24 ml/kg [22; 25] (P = 0.916) in the hydroxyethyl starch group led to hemorrhagic shock. Fluid resuscitation reestablished baseline mean arterial pressure in all sheep of the hydroxyethyl starch group and in one sheep of the saline group. In the saline group 4,980 ml [3,312; 5,700] and in the hydroxyethyl starch group 610 ml [489; 615] of fluid were needed (P = 0.009). In hemorrhagic shock perfused vessel density (saline from 100% to 83% [49; 86]; hydroxyethyl starch from 100% to 74% [61; 80]) and microvascular flow index (saline from 3.1 [2.5; 3.3] to 2.0 [1.6; 2.3]; hydroxyethyl starch from 2.9 [2.9; 3.1] to 2.5 [2.3; 2.7]) decreased in both groups. After resuscitation both variables improved in the hydroxyethyl starch group (perfused vessel density: 125% [120; 147]; microvascular flow index: 3.4 [3.2; 3.5]), whereas in the saline group perfused vessel density further decreased (64% [62; 79]) and microvascular flow index increased less than in the hydroxyethyl starch group (2.7 [2.4; 2.8]; both P < 0.001 for saline vs. hydroxyethyl starch). Conclusions Resuscitation with hydroxyethyl starch maintained coherence in hemorrhagic shock. In contrast, saline only improved macro- but not microcirculation. Hemodynamic coherence might be influenced by the choice of resuscitation fluid.

Many critically ill patients show a disturbance of the microcirculation, which is not yet regularly examined in the clinical routine; however, for treatment decisions and estimation of the prognosis it would be important to obtain detailed information about the microcirculation in critically ill patients. Optical coherence tomography angiography (OCTA) is a non-invasive, contact-free technique, which enables visualization of the blood flow in the retinal microcirculation within a few seconds. Therefore, it may have the potential to diagnose microcirculation disorders in critically ill patients.The aims of the study were to assess the importance of the microcirculation in intensive care medicine, a comparison of the methods of video microscopy and OCTA and analysis of preclinical and clinical data on the use of OCTA in intensive care medicine.A selective literature review and data analysis were carried out.A direct visualization of the microcirculation has been possible for many years with the technique of video microscopy but this has not become established in the clinical routine due to the susceptibility to interferences and a time-consuming manual analysis. The OCTA is a non-invasive and contact-free method for the visualization of retinal blood flow. First preclinical data in septic and hemorrhagic shock show good results of OCTA for analysis of the microcirculation.The non-invasive technique of OCTA is a promising measurement method to enable bedside analysis of the microcirculation in critically ill paients in the future; however, some technical limitations must still be overcome.

Als zentraler Venendruck (ZVD) wird der Druck in der oberen Hohlvene (V. cava superior) sowie im rechten Vorhof bezeichnet. Dieser entspricht annahernd dem Fullungsdruck des rechten Ventrikels. Der ZVDwird auf Intensivstationen in der Regel mit einem invasiven Messverfahren bestimmt. Wird der ZVD zur Beurteilung pathologischer Zustande herangezogen, muss bedacht werden, dass multiple Faktoren Einfluss auf ihn ausuben (z.B. Funktion des rechten Ventrikels, Flussigkeitshaushalt, intrathorakale Druckverhaltnisse und Venentonus) [1]. In den zuruckliegenden Jahren wurde eine teils emotionale Diskussion uber die Bedeutung des ZVD als Surrogatparameter der Vorlast oder zur Beurteilung der Volumenreagibilitat gefuhrt [2–4]. Diese Diskussion hat dazu gefuhrt, dass der Parameter ZVD selbst unter Druck geraten ist und sein Image gelitten hat. Vorausgesetzt der ZVD wird korrekt bestimmt, kann man durch die Messung des ZVD bzw. die Beurteilung der Druckkurve jedoch auch heute noch relevante Informationen uber den Patienten gewinnen, unabhangig von seiner Eignung als Parameter der Volumenreagibilitat. Die vorliegende Ubersichtsarbeit diskutiert anhand der aktuellen Evidenz den Stellenwert des ZVD in der Intensivmedizin. Die Bestimmung des zentralen Venendrucks

The decision of the European Medicines Agency (EMA) against the use of hydroxyethyl starch (HES)-based volume replacement solutions in critically ill patients has led to a general uncertainty when dealing with HES-based solutions, even though HES-containing solutions can still be used for the treatment of hypovolaemia caused by acute (sudden) blood loss. This review discusses current evidence of the intraoperative use of HES-based solutions.HES solutions are often criticized for possible side-effects on the kidney, the coagulation system or tissue storage. Relevant differences exist between modern 6% HES 130/0.4 and older generation of starches. Because of pathophysiological differences between elective surgery and critical illness, the evidence on renal injury and coagulation impairment with HES administration cannot be generalized. Current data suggest that there is no clinically relevant impact of 6% HES 130/0.4 administration on perioperative renal function and coagulation. Over-resuscitation is a frequent problem associated with adverse outcomes. Due to the higher volume effect, fluid overload with HES is probably more harmful than with crystalloids, whereas goal-directed use of HES may be able to reduce intraoperative fluid accumulation and overload.The use of 6% HES 130/0.4 in elective surgery patients is associated with reduced fluid accumulation and no clinically relevant difference in bleeding or the rate of acute kidney injury as compared with crystalloid use alone. Current data do not allow a conclusion on mortality. As they provide no benefit, older starch preparations should not be used.

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

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.

The international, multicentre, double-blinded, randomized, controlled ATHOS-3 trial by Khanna and colleagues (1) was conducted from May 2015 to January 2017 in nine countries across Europe, North America, and Australia. ATHOS-3 was designed to answer two primary endpoints within a study period of 48 h.

Background Life-threatening diseases of critically ill patients are known to derange microcirculation. Automatic analysis of microcirculation would provide a bedside diagnostic tool for microcirculatory disorders and allow immediate therapeutic decisions based upon microcirculation analysis. Methods After induction of general anaesthesia and instrumentation for haemodynamic monitoring, haemorrhagic shock was induced in ten female sheep by stepwise blood withdrawal of 3 × 10 mL per kilogram body weight. Before and after the induction of haemorrhagic shock, haemodynamic variables, samples for blood gas analysis, and videos of conjunctival microcirculation were obtained by incident dark field illumination microscopy. Microcirculatory videos were analysed (1) manually with AVA software version 3.2 by an experienced user and (2) automatically by AVA software version 4.2 for total vessel density (TVD), perfused vessel density (PVD) and proportion of perfused vessels (PPV). Correlation between the two analysis methods was examined by intraclass correlation coefficient and Bland-Altman analysis. Results The induction of haemorrhagic shock decreased the mean arterial pressure (from 87 ± 11 to 40 ± 7 mmHg; p