Showing papers by "Gernot Marx published in 2017"

The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial

Abstract: Objective We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. Methods This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. Results 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). Conclusions In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.

Role of nutrition support in adult cardiac surgery: a consensus statement from an International Multidisciplinary Expert Group on Nutrition in Cardiac Surgery

Abstract: Nutrition support is a necessary therapy for critically ill cardiac surgery patients. However, conclusive evidence for this population, consisting of well-conducted clinical trials is lacking. To clarify optimal strategies to improve outcomes, an international multidisciplinary group of 25 experts from different clinical specialties from Germany, Canada, Greece, USA and Russia discussed potential approaches to identify patients who may benefit from nutrition support, when best to initiate nutrition support, and the potential use of pharmaco-nutrition to modulate the inflammatory response to cardiopulmonary bypass. Despite conspicuous knowledge and evidence gaps, a rational nutritional support therapy is presented to benefit patients undergoing cardiac surgery.

Perioperative intravenous fluid therapy in children: guidelines from the Association of the Scientific Medical Societies in Germany

Abstract: This consensus- based S1 Guideline for perioperative infusion therapy in children is focused on safety and efficacy. The objective is to maintain or re-establish the child's normal physiological state (normovolemia, normal tissue perfusion, normal metabolic function, normal acid- base- electrolyte status). Therefore, the perioperative fasting times should be as short as possible to prevent patient discomfort, dehydration, and ketoacidosis. A physiologically composed balanced isotonic electrolyte solution (BS) with 1-2.5% glucose is recommended for the intraoperative background infusion to maintain normal glucose concentrations and to avoid hyponatremia, hyperchloremia, and lipolysis. Additional BS without glucose can be used in patients with circulatory instability until the desired effect is achieved. The additional use of colloids (albumin, gelatin, hydroxyethyl starch) is recommended to recover normovolemia and to avoid fluid overload when crystalloids alone are not sufficient and blood products are not indicated. Monitoring should be extended in cases with major surgery, and autotransfusion maneuvers should be performed to assess fluid responsiveness.

Quality indicators in intensive care medicine for Germany - third edition 2017.

Abstract: Quality improvement in medicine is depending on measurement of relevant quality indicators. The quality indicators for intensive care medicine of the German Interdisciplinary Society of Intensive Care Medicine (DIVI) from the year 2013 underwent a scheduled evaluation after three years. There were major changes in several indicators but also some indicators were changed only minimally. The focus on treatment processes like ward rounds, management of analgesia and sedation, mechanical ventilation and weaning, as well as the number of 10 indicators were not changed. Most topics remained except for early mobilization which was introduced instead of hypothermia following resuscitation. Infection prevention was added as an outcome indicator. These quality indicators are used in the peer review in intensive care, a method endorsed by the DIVI. A validity period of three years is planned for the quality indicators.

Persistent low serum zinc is associated with recurrent sepsis in critically ill patients - A pilot study.

Abstract: Zinc is an essential trace element for both pathogens and hosts. Hypozincemia is a well known phenomenon in sepsis patients and represents the innate immune systems attempt to deprive pathogens of zinc. However little is known about course, restitution and prognostic value of serum zinc levels in sepsis patients. We performed a prospective observational single-center study set in a tertiary care university hospital intensive care unit. Serum zinc levels were singularly measured of healthy controls and sequentially of surgical sepsis patients and surgical patients over a 8-day period. Throughout the study period, we report significantly decreased serum zinc levels in surgical and surgical sepsis patients compared to healthy controls. Lower serum zinc levels in surgical sepsis patients were associated with a higher susceptibility to a recurrent sepsis episode. Furthermore, surgical sepsis patients with a higher number of organ dysfunctions and increased in-hospital mortality at day 28 and 90 showed lower serum zinc levels at admission. We report serum zinc levels as a promising biomarker in the diagnosis and evaluation of sepsis patients. However, it is still unclear whether these findings are caused by an over-amplified redistribution of zinc during acute-phase response, or whether the critically ill patients were zinc deficient before sepsis.

Functional assessment of the diaphragm by speckle tracking ultrasound during inspiratory loading

Abstract: Transdiaphragmatic pressure using esophageal and gastric balloons is the gold standard to assess diaphragm effort However, this technique is invasive and requires expertise, and the interpretation

Elevated Soluble Urokinase Plasminogen Activator Receptor and Proenkephalin Serum Levels Predict the Development of Acute Kidney Injury after Cardiac Surgery.

Abstract: Acute kidney injury (AKI) develops in up to 40% of patients after cardiac surgery. The soluble urokinase plasminogen activator receptor (suPAR) has been identified as a biomarker for incident chronic kidney disease (CKD). Proenkephalin (proENK) also has been shown to be a biomarker for renal dysfunction. We hypothesized that pre-surgery suPAR and proENK levels might predict AKI in patients undergoing cardiac surgery. Consecutive patients (n = 107) undergoing elective cardiac surgery were studied prospectively. Clinical data, laboratory parameters, suPAR and proENK serum levels were assessed before operation, after operation and days one and four post-operatively. A total of 21 (19.6%) patients developed AKI within the first four days after elective surgery. Serum levels of suPAR and proENK, but not of creatinine, were significantly higher before surgery in these patients compared to those patients without AKI. This difference remained significant for suPAR, if patients with or without AKI were matched for risk factors (hypertension, diabetes, CKD). If cardiac surgery patients with pre-existing CKD (n = 10) were excluded, only pre-operative suPAR but not proENK serum levels remained significantly elevated in patients with subsequent AKI. Thus, our findings indicate that suPAR may be a predictive biomarker for AKI in the context of cardiac surgery, even in patients without underlying CKD.

Electrical impedance tomography for predicting failure of spontaneous breathing trials in patients with prolonged weaning.

Abstract: Spontaneous breathing trials (SBTs) on a T-piece can be difficult in patients with prolonged weaning because of remaining de-recruitment phenomena and/or insufficient ventilation. There is no clinically established method existent other than experience for estimating whether an SBT is most probably beneficial. Electrical impedance tomography (EIT) is a clinical useful online monitoring technique during mechanical ventilation, particularly because it enables analysis of effects of regional ventilation distribution. The aim of our observational study was to examine if EIT can predict whether patients with prolonged weaning will benefit from a planned SBT. Thirty-one patients were examined. Blood gas analysis, vital parameter measurements, and EIT recordings were performed at three time points: (1) baseline with pressure support ventilation (PSV) (t0), (2) during a T-piece trial (t1), and (3) after resumption of PSV (t2). Calculation of EIT parameters was performed, including the impedance ratio (IR), the tidal variation of impedance (TIV), the changes in end-expiratory lung impedance (ΔEELI), the global inhomogeneity index (GI), and the regional ventilation delay (RVD) index with use of different thresholds of the percentage inspiration time (RVD40, RVD60, RVD80). The predictive power of the baseline GI with regard to clinical impairment of an SBT was analyzed by means of ROC curves. Clinical deterioration was assumed when tidal volume was decreased by at least 20 ml after the T-piece trial, measured at t2. Partial pressure of arterial oxygen significantly decreased at t1 (71 ± 15 mmHg) compared with t0 (85 ± 17 mmHg, p 40, sensitivity of 85% and specificity of 50% were reached for predicting an increased future tidal volume. EIT enables monitoring of regional ventilation distribution during SBTs and is suitable to estimate whether an SBT probably will be beneficial for an individual patient. Therefore, the application of EIT can support clinical decisions regarding patients in the phase of prolonged weaning.

Novel Synthetic, Host-defense Peptide Protects Against Organ Injury/Dysfunction in a Rat Model of Severe Hemorrhagic Shock.

Abstract: Objective To evaluate (1) levels of the host-defense/antimicrobial peptide LL-37 in patients with trauma and hemorrhagic shock (HS) and (2) the effects of a synthetic host-defense peptide; Pep19-4LF on multiple organ failure (MOF) associated with HS. Background HS is a common cause of death in severely injured patients. There is no specific therapy that reduces HS-associated MOF. Methods (1) LL-37 was measured in 47 trauma/HS patients admitted to an urban major trauma center. (2) Male Wistar rats were submitted to HS (90 min, target mean arterial pressure: 27-32 mm Hg) or sham operation. Rats were treated with Pep19-4LF [66 (n = 8) or 333 μg/kg · h (n = 8)] or vehicle (n = 12) for 4 hours following resuscitation. Results Plasma LL-37 was 12-fold higher in patients with trauma/HS compared to healthy volunteers. HS rats treated with Pep19-4LF (high dose) had a higher mean arterial pressure at the end of the 4-hour resuscitation period (79 ± 4 vs 54 ± 5 mm Hg) and less renal dysfunction, liver injury, and lung inflammation than HS rats treated with vehicle. Pep19-4LF enhanced (kidney/liver) the phosphorylation of (1) protein kinase B and (2) endothelial nitric oxide synthase. Pep19-4LF attenuated the HS-induced (1) translocation of p65 from cytosol to nucleus, (2) phosphorylation of IκB kinase on Ser, and (3) phosphorylation of IκBα on Ser resulting in inhibition of nuclear factor kappa B and formation of proinflammatory cytokines. Pep19-4LF prevented the release of tumor necrosis factor alpha caused by heparan sulfate in human mononuclear cells by binding to this damage-associated molecular pattern. Conclusions Trauma-associated HS results in release of LL-37. The synthetic host-defense/antimicrobial peptide Pep19-4LF attenuates the organ injury/dysfunction associated with HS.

The β-d-Endoglucuronidase Heparanase Is a Danger Molecule That Drives Systemic Inflammation and Correlates with Clinical Course after Open and Endovascular Thoracoabdominal Aortic Aneurysm Repair: Lessons Learnt from Mice and Men.

Abstract: Thoracoabdominal aortic aneurysm (TAAA) is a highly lethal disorder requiring open or endovascular TAAA-repair, both of which are rare, but extensive and complex surgical procedures associated with a significant systemic inflammatory response and high post-operative morbidity and mortality. Heparanase is a β-D-endoglucuronidase that remodels the endothelial glycocalyx by degrading heparan sulfate in many diseases/conditions associated with systemic inflammation including sepsis, trauma and major surgery. We hypothesized that a) perioperative serum levels of heparanase and heparan sulfate are associated with the clinical course after open or endovascular TAAA-repair, and b) induce a systemic inflammatory response and renal injury/dysfunction in mice. Using a reverse-translational approach, we assessed a) the serum levels of heparanase, heparan sulfate and the heparan sulfate proteoglycan syndecan-1 preoperatively as well as 6 and 72 hours after intensive care unit (ICU)-admission in patients undergoing open or endovascular TAAA-repair and b) laboratory and clinical parameters and 90-day survival, and c) the systemic inflammatory response and renal injury/dysfunction induced by heparanase and heparan sulfate in mice. When compared to preoperative values, the serum levels of heparanase, heparan sulfate and syndecan-1 significantly transiently increased within 6 hours of ICU-admission and returned to normal within 72 hours after ICU-admission. The kinetics of any observed changes in heparanase, heparan sulfate or syndecan-1 levels, however, did not differ between open and endovascular TAAA–repair. Postoperative heparanase levels positively correlated with noradrenalin dose at 12 hours after ICU-admission and showed a high predictive value of vasopressor requirements within the first 24 hours. Postoperative heparan sulfate showed a strong positive correlation with interleukin-6 levels day 0, 1 and 2 post ICU-admission and a strong negative correlation with lactate clearance during the first 6 hours post ICU-admission. Moreover, systemic administration of heparanase and heparan sulfate induced an inflammatory response and a small degree of renal dysfunction in mice. In conclusion, these results suggest that heparanase and heparan sulfate exhibit a substantial role as clinically relevant danger molecules and may serve as both, promising biomarkers and therapeutic targets in patients undergoing open or endovascular TAAA-repair and, indeed, other conditions associated with significant systemic inflammation.

Macrophage Migration Inhibitory Factor Predicts Outcome in Complex Aortic Surgery

Abstract: The perioperative inflammatory response is associated with outcome after complex aortic repair. Macrophage migration inhibitory factor (MIF) shows protective effects in ischemia-reperfusion (IR), but also adverse pro-inflammatory effects in acute inflammation, potentially leading to adverse outcome, which should be investigated in this trial. This prospective study enrolled 52 patients, of whom 29 (55.7%) underwent open repair (OR) and 23 (44.3%) underwent endovascular repair (ER) between 2014 and 2015. MIF serum levels were measured until 72 h post-operatively. We used linear mixed models and ROC analysis to analyze the MIF time-course and its diagnostic ability. Compared to ER, OR induced higher MIF release perioperatively; at 12 h after ICU admission, MIF levels were similar between groups. MIF course was significantly influenced by baseline MIF level (P = 0.0016) and acute physiology and chronic health evaluation (APACHE) II score (P = 0.0005). MIF level at 24 h after ICU admission showed good diagnostic value regarding patient survival [sensitivity, 80.0% (28.4-99.5%); specificity, 51.2% (35.1-67.1%); AUC, 0.688 (0.534-0.816)] and discharge modality [sensitivity, 87.5% (47.3-99.7%); specificity, 73.7% (56.9-86.6%), AUC, 0.789 (0.644-0.896)]. Increased perioperative MIF-levels are related to an increased risk of adverse outcome in complex aortic surgery and may represent a biomarker for risk stratification in complex aortic surgery.

Isolation of Endothelial Progenitor Cells from Healthy Volunteers and Their Migratory Potential Influenced by Serum Samples After Cardiac Surgery

Abstract: Endothelial progenitor cells (EPCs) are recruited from the bone marrow under pathological conditions like hypoxia and are crucially involved in the neovascularization of ischemic tissues. The origin, classification and characterization of EPCs are complex; notwithstanding, two prominent sub-types of EPCs have been established: so-called "early" EPCs (subsequently referred to as early-EPCs) and late-outgrowth EPCs (late-EPCs). They can be classified by biological properties as well as by their appearance during in vitro culture. While "early" EPCs appear in less than a week after culture of peripheral blood-derived mononuclear cells in EC-specific media, late-outgrowth EPCs can be found after 2-3 weeks. Late-outgrowth EPCs have been recognized to be directly involved in neovascularization, mainly through their ability to differentiate into mature endothelial cells, whereas "early" EPCs express various angiogenic factors as endogenous cargo to promote angiogenesis in a paracrine manner. During myocardial ischemia/reperfusion (I/R), various factors control the homing of EPCs to regions of blood vessel formation. Macrophage migration inhibitory factor (MIF) is a chemokine-like pro-inflammatory and ubiquitously expressed cytokine and was recently described to function as key regulator of EPCs migration at physiological concentrations1. Interestingly, MIF is stored in intracellular pools and can rapidly be released into the blood stream after several stimuli (e.g. myocardial infarction). This protocol describes a method for the reliable isolation and culture of early-EPCs from adult human peripheral blood based on CD34-positive selection with subsequent culture in medium containing endothelial growth factors on fibronectin-coated plates for use in in vitro migration assays against serum samples of cardiac surgical patients. Furthermore, the migratory influence of MIF on chemotaxis of EPCs compared to other well-known angiogenesis-stimulating cytokines is demonstrated.

Enrichment of a diving computer with body sensor network data

Abstract: Decompression algorithms in hyperbaric applications currently usually base on information about the ambient pressure in a temporal course However, the impact of other factors like temperature or physical activity is well documented in literature Therefore, we elaborated a prototypic setup, which is not only able to enrich the decompression algorithms run on a diving computer by this data, but also store this information for successive data mining

Organ-specific effects on inflammation and apoptosis of recombinant human activated protein C in a murine model of sepsis:

Abstract: There is legitimate interest in the effects of recombinant human activated protein C (rhAPC) on various organs and individual patients, but the specific effects on organ tissues during early sepsis...

Generalizable items and modular structure for computerised physician staffing calculation on intensive care units

Abstract: Generalizable items and modular structure for computerised physician staffing calculation on intensive care units

Intensive care medicine in 2017: urgent need and existing chances to improve outcome.

Abstract: Head of Department, Department of Intensive and Intermediate Care, Uniklinik RWTH Aachen, Aachen, Germany Caring for the critically ill patient in the ICU is a continuous challenge. There is always a potential for improvement of care/medicine, but in ICU there is an urgent need! In a recent prospective study, more than 12 000 ICU patients were prospectively included to investigate the incidence and mortality of sepsis in Germany [1]. According to the traditional definitions, the incidence of severe sepsis and septic shock was 11.6% and the ICU mortality of septic shock was 37.3%. Hospital mortality was as high as 43.3%. Analyzing the data according to the new sepsis-3 definition, the mortality of septic shock was even higher: 44.3% in the ICU and 50.9% in the hospital! These data are very important because they are demonstrating real-life prospective evidence. Indeed, the mortality is a lot higher compared to the retrospective analysis of large data bases or mortality rates of control groups in randomized control trials (RCT). Therefore, sepsis and critical illness in 2017 remain very frequent and extremely dangerous. Hence, there is a clear need for us to improve our care. We know from many RCTs that the treatment of patients in the control group according to protocols results in a better outcome associated with a mortality of around 30%. We know also from many guidelines how to do it. A recent important guideline example for changing our practice according to evidence is the diagnosis of hypovolemia and monitoring of fluid therapy [2]. This methodologically very robust guideline from the Association of the Scientific Medical Societies in Germany: ‘Intravascular Volume Therapy in Adults’ resulted in a high degree of consensus obtained among both the delegates and boards of the 14 participating medical societies. Two strong recommendations with a grade of recommendation A focused on the use of the central venous pressure:

Reply to: volume therapy in obstetrics.

Abstract: References 1 Marx G, Schindler AW, Mosch C, et al. Intravascular volume therapy in adults: guidelines from the Association of the Scientific Medical Societies in Germany. Eur J Anaesthesiol 2016; 33:488–521. 2 De Robertis E, Afshari A, Longrois D. The quest for the holy volume therapy. Eur J Anaesthesiol 2016; 33:483–487. 3 Cyna AM, Andrew M, Emmett RS, et al. Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Cochrane Database Syst Rev (3):2002;CD002251. 4 Mercier FJ, Diemunsch P, Ducloy-Bouthors AS, et al. 6% Hydroxyethyl starch (130/0.4) vs Ringer’s lactate preloading before spinal anaesthesia for caesarean delivery: the randomized, double-blind, multicentre CAESAR trial. Br J Anaesth 2014; 113:459–467. 5 Teoh WH, Westphal M, Kampmeier TG. Update on volume therapy in obstetrics. Best Pract Res Clin Anaesthesiol 2014; 28:297–303. 6 Ripollés Melchor J, Espinosa Á, Martı́nez Hurtado E, et al. Colloids versus crystalloids in the prevention of hypotension induced by spinal anesthesia in elective cesarean section. A systematic review and meta-analysis. Minerva Anestesiol 2015; 81:1019–1030. 7 Sümpelmann R, Kretz FJ, Luntzer R, et al. Hydroxyethyl starch 130/0.42/6:1 for perioperative plasma volume replacement in 1130 children: results of an European prospective multicenter observational postauthorization safety study (PASS). Paediatr Anaesth 2012; 22:371–378. 8 Van der Linden P, Dumoulin M, Van Lerberghe C, et al. Efficacy and safety of 6% hydroxyethyl starch 130/0.4 (Voluven) for perioperative volume replacement in children undergoing cardiac surgery: a propensity-matched analysis. Crit Care 2015; 19:87.