Showing papers by "Gernot Marx published in 2016"

Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial.

Abstract: Importance High-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress. Procalcitonin-guided antimicrobial therapy may hasten the diagnosis of sepsis, but effect on outcome is unclear. Objective To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality. Design, Setting, and Participants The Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT), a multicenter, randomized, clinical, 2 × 2 factorial trial performed in 33 intensive care units in Germany, was conducted from November 6, 2009, to June 6, 2013, including a 90-day follow-up period. Interventions Patients were randomly assigned to receive an initial intravenous loading dose of sodium selenite, 1000 µg, followed by a continuous intravenous infusion of sodium selenite, 1000 µg, daily until discharge from the intensive care unit, but not longer than 21 days, or placebo. Patients also were randomized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance. Main Outcomes and Measures The primary end point was 28-day mortality. Secondary outcomes included 90-day all-cause mortality, intervention-free days, antimicrobial costs, antimicrobial-free days, and secondary infections. Results Of 8174 eligible patients, 1089 patients (13.3%) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite (543 patients [49.9%]) with placebo (546 [50.1%]) and procalcitonin guidance (552 [50.7%]) vs no procalcitonin guidance (537 [49.3%]). The 28-day mortality rate was 28.3% (95% CI, 24.5%-32.3%) in the sodium selenite group and 25.5% (95% CI, 21.8%-29.4%) ( P = .30) in the placebo group. There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance (25.6% [95% CI, 22.0%-29.5%]) vs no procalcitonin guidance (28.2% [95% CI, 24.4%-32.2%]) ( P = .34). Procalcitonin guidance did not affect frequency of diagnostic or therapeutic procedures but did result in a 4.5% reduction of antimicrobial exposure. Conclusions and Relevance Neither high-dose intravenous administration of sodium selenite nor anti-infectious therapy guided by a procalcitonin algorithm was associated with an improved outcome in patients with severe sepsis. These findings do not support administration of high-dose sodium selenite in these patients; the application of a procalcitonin-guided algorithm needs further evaluation. Trial Registration clinicaltrials.gov Identifier:NCT00832039

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis The HYPRESS Randomized Clinical Trial

Abstract: Importance Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial. Objective To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock. Design, Setting, and Participants Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock. Interventions Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190). Main Outcomes and Measures The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]). Results The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, −1.8%; 95% CI, −10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, −5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, −5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, −4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia. Conclusions and Relevance Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients. Trial Registration clinicaltrials.gov Identifier:NCT00670254

The Ribonuclease A Superfamily in Humans: Canonical RNases as the Buttress of Innate Immunity

Abstract: In humans, the ribonuclease A (RNase A) superfamily contains eight different members that have RNase activities, and all of these members are encoded on chromosome 14. The proteins are secreted by a large variety of different tissues and cells; however, a comprehensive understanding of these proteins’ physiological roles is lacking. Different biological effects can be attributed to each protein, including antiviral, antibacterial and antifungal activities as well as cytotoxic effects against host cells and parasites. Different immunomodulatory effects have also been demonstrated. This review summarizes the available data on the human RNase A superfamily and illustrates the significant role of the eight canonical RNases in inflammation and the host defence system against infections.

Intravascular Volume Therapy in Adults: Guidelines From the Association of the Scientific Medical Societies in Germany

Abstract: Index Table of contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489 List of abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489 A. Rationale and goals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490 A1: Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490 A2: Initial situation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490 A3: Guideline requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491 A4: Guideline objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491 A5: Target user group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491 B: Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491 B1: Literature search and selection of evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491 Use of existing guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491 Systematic literature search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491 Selection of literature identified . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 492 B2: Appraisal and extraction of evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493

Impact of age on the clinical outcomes of major trauma.

Abstract: In view of demographic changes over the past few decades, the average age of trauma patients is progressively increasing. We therefore aimed to summarize the specific characteristics of geriatric trauma and to identify potential fields for further research to improve the care of elderly trauma patients. Review of the literature. Due to the diverse risk factors (e.g., pre-existing conditions, limited physiological reserve), geriatric patients are prone to developing severe complications, even after less severe trauma. Yet, age is not considered as the only predictor of worse outcomes, and it should not be considered the only criterion for limiting care in those patients. It is crucial that age-specific treatment guidelines are developed to optimize the outcomes for senior trauma patients. Based on the current literature, these guidelines should emphasize the importance of field triage directly to a trauma center, along with the activation of the trauma team. Furthermore, early intensive monitoring, aggressive resuscitation, and time of surgical intervention are of upmost importance to reduce mortality. The impact of several factors [age, premedical conditions (PMC), decreased physiological reserves, and impaired immune function] on the post-traumatic course of elderly trauma patients needs to be clarified in future experimental and clinical studies for the early identification of geriatric high-risk patients and for the development of age-adapted therapeutic strategies.

Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma

Abstract: Chest trauma has a significant relevance on outcome after severe trauma. Clinically, impaired lung function typically occurs within 72 hours after trauma. However, the underlying pathophysiological mechanisms are still not fully elucidated. Therefore, we aimed to establish an experimental long-term model to investigate physiological, morphologic and inflammatory changes, after severe trauma. Male pigs (sus scrofa) sustained severe trauma (including unilateral chest trauma, femur fracture, liver laceration and hemorrhagic shock). Additionally, non-injured animals served as sham controls. Chest trauma resulted in severe lung damage on both CT and histological analyses. Furthermore, severe inflammation with a systemic increase of IL-6 (p = 0.0305) and a local increase of IL-8 in BAL (p = 0.0009) was observed. The pO2/FiO2 ratio in trauma animals decreased over the observation period (p < 0.0001) but not in the sham group (p = 0.2967). Electrical Impedance Tomography (EIT) revealed differences between the traumatized and healthy lung (p < 0.0001). In conclusion, a clinically relevant, long-term model of blunt chest trauma with concomitant injuries has been developed. This reproducible model allows to examine local and systemic consequences of trauma and is valid for investigation of potential diagnostic or therapeutic options. In this context, EIT might represent a radiation-free method for bedside diagnostics.

miR-155 targets Caspase-3 mRNA in activated macrophages

Abstract: To secure the functionality of activated macrophages in the innate immune response, efficient life span control is required. Recognition of bacterial lipopolysaccharides (LPS) by toll-like receptor 4 (TLR4) induces downstream signaling pathways, which merge to induce the expression of cytokine genes and anti-apoptotic genes. MicroRNAs (miRNAs) have emerged as important inflammatory response modulators, but information about their functional impact on apoptosis is scarce. To identify miRNAs differentially expressed in response to LPS, cDNA libraries from untreated and LPS-activated murine macrophages were analyzed by deep sequencing and regulated miRNA expression was verified by Northern blotting and qPCR. Employing TargetScan(TM) we identified CASPASE-3 (CASP-3) mRNA that encodes a key player in apoptosis as potential target of LPS-induced miR-155. LPS-dependent primary macrophage activation revealed TLR4-mediated enhancement of miR-155 expression and CASP-3 mRNA reduction. Endogenous CASP-3 and cleaved CASP-3 protein declined in LPS-activated macrophages. Accumulation of miR-155 and CASP-3 mRNA in miRNA-induced silencing complexes (miRISC) was demonstrated by ARGONAUTE 2 (AGO2) immunoprecipitation. Importantly, specific antagomir transfection effectively reduced mature miR-155 and resulted in significantly elevated CASP-3 mRNA levels in activated macrophages. In vitro translation assays demonstrated that the target site in the CASP-3 mRNA 3'UTR mediates miR-155-dependent Luciferase reporter mRNA destabilization. Strikingly, Annexin V staining of macrophages transfected with antagomir-155 and stimulated with LPS prior to staurosporine (SSP) treatment implied that LPS-induced miR-155 prevents apoptosis through CASP-3 mRNA down-regulation. In conclusion, we report that miR-155-mediated CASP-3 mRNA destabilization in LPS-activated RAW 264.7 macrophages suppresses apoptosis, as a prerequisite to maintain their crucial function in inflammation.

Designing phase 3 sepsis trials: application of learned experiences from critical care trials in acute heart failure

Abstract: Substantial attention and resources have been directed to improving outcomes of patients with critical illnesses, in particular sepsis, but all recent clinical trials testing various interventions or strategies have failed to detect a robust benefit on mortality. Acute heart failure is also a critical illness, and although the underlying etiologies differ, acute heart failure and sepsis are critical care illnesses that have a high mortality in which clinical trials have been difficult to conduct and have not yielded effective treatments. Both conditions represent a syndrome that is often difficult to define with a wide variation in patient characteristics, presentation, and standard management across institutions. Referring to past experiences and lessons learned in acute heart failure may be informative and help frame research in the area of sepsis. Academic heart failure investigators and industry have worked closely with regulators for many years to transition acute heart failure trials away from relying on dyspnea assessments and all-cause mortality as the primary measures of efficacy, and recent trials have been designed to assess novel clinical composite endpoints assessing organ dysfunction and mortality while still assessing all-cause mortality as a separate measure of safety. Applying the lessons learned in acute heart failure trials to severe sepsis and septic shock trials might be useful to advance the field. Novel endpoints beyond all-cause mortality should be considered for future sepsis trials.

The synthetic antimicrobial peptide 19-2.5 attenuates septic cardiomyopathy and prevents down-regulation of SERCA2 in polymicrobial sepsis.

Abstract: An impairment of cardiac function is a key feature of the cardiovascular failure associated with sepsis. Although there is some evidence that suppression of sarcoplasmic reticulum Ca2+-ATP-ase (SERCA2) contributes to septic cardiomyopathy, it is not known whether prevention of the down-regulation of SERCA2 improves outcome in sepsis. Thus, we investigated whether the administration of the synthetic antimicrobial peptide Pep2.5 may attenuate the cardiac dysfunction in murine polymicrobial sepsis through regulating SERCA2 expression. We show here for the first time that the infusion of Pep2.5 reduces the impaired systolic and diastolic contractility and improves the survival time in polymicrobial sepsis. Preservation of cardiac function in sepsis by Pep2.5 is associated with prevention of the activation of NF-κB and activation of the Akt/eNOS survival pathways. Most notably, Pep2.5 prevented the down-regulation of SERCA2 expression in a) murine heart samples obtained from mice with sepsis and b) in cardiomyocytes exposed to serum from septic shock patients. Thus, we speculate that Pep2.5 may be able to prevent down-regulation of cardiac SERCA2 expression in patients with sepsis, which, in turn, may improve cardiac function and outcome in these patients.

The Human Host Defense Ribonucleases 1, 3 and 7 Are Elevated in Patients with Sepsis after Major Surgery--A Pilot Study.

Abstract: Sepsis is the most common cause of death in intensive care units and associated with widespread activation of host innate immunity responses. Ribonucleases (RNases) are important components of the innate immune system, however the role of RNases in sepsis has not been investigated. We evaluated serum levels of RNase 1, 3 and 7 in 20 surgical sepsis patients (Sepsis), nine surgical patients (Surgery) and 10 healthy controls (Healthy). RNase 1 and 3 were elevated in Sepsis compared to Surgery (2.2- and 3.1-fold, respectively; both p < 0.0001) or compared to Healthy (3.0- and 15.5-fold, respectively; both p < 0.0001). RNase 1 showed a high predictive value for the development of more than two organ failures (AUC 0.82, p = 0.01). Patients with renal dysfunction revealed higher RNase 1 levels than without renal dysfunction (p = 0.03). RNase 1 and 3 were higher in respiratory failure than without respiratory failure (p < 0.0001 and p = 0.02, respectively). RNase 7 was not detected in Healthy patients and only in two patients of Surgery, however RNase 7 was detected in 10 of 20 Sepsis patients. RNase 7 was higher in renal or metabolic failure than without failure (p = 0.04 and p = 0.02, respectively). In conclusion, RNase 1, 3 and 7 are secreted into serum under conditions with tissue injury, such as major surgery or sepsis. Thus, RNases might serve as laboratory parameters to diagnose and monitor organ failure in sepsis.

Psychoacoustic analysis of noise and the application of earplugs in an ICU: A randomised controlled clinical trial.

Abstract: Background Patients and medical staff are exposed to high noise levels in ICUs, which may have a negative impact on their health. Due to the diversity of noise sources present, including the operating noise of medical devices, staff conversations and the unwrapping of disposables, noise profiles are varied. Psychoacoustics deals with the analysis of sound, focusing on its effects on physiological perception and stress. Objectives The aim of our study was to examine and to classify noise and its psychoacoustic properties in different locations in our ICU at different times. The impact of noise on subjective parameters and stress-related physiological data was also assessed with and without interventional methods. Design A randomised, controlled, single-blinded clinical trial. Setting University Hospital, from November 2010 to May 2011. Patients One hundred and forty-four patients in the ICU. Interventions In the first part, multidisciplinary psychoacoustic measurement was performed on the patients in our ICU. In the subsequent clinical trial, patients were equipped with effective earplugs, less effective earplugs and no earplugs. Thereafter, active noise cancellation headphones with or without sound masking were employed on a third patient population. Main outcome measures Cortisol and α-amylase in saliva, skin conductance measures, vital signs, psychoacoustic analyses and two standardised questionnaires [State-Trait Anxiety Inventory (STAI) and Hospital Anxiety and Depression Scale (HADS)] were assessed. Results In the first part, the mean ± standard deviation (SD) subjective loudness was 9.2 ± 4.0 sone. Although absolute sound pressure level and loudness were lower during the night, the number of loud events increased significantly. Skin conductance in the earplug groups was significantly reduced in comparison to that in the control population but not the active noise reduction groups. Nevertheless, noise reduction was found to be comfortable for most patients. Conclusion Noise in the ICU is of high clinical relevance. Diverse noise reduction methods, such as earplugs and active noise cancellation, are available. The avoidance of unnecessary noise, however, should be the primary focus. Trial registration German Clinical Trials Register (DRKS00000534).

Evidence-based fluid management in the Icu

Abstract: Purpose of review Evidence-based fluid therapy is complicated by blurred boundaries toward other fields of therapy and the majority of trials not focusing on patient-relevant outcomes. Additionally, recent trials unsettled the faith in traditional concepts on fluid therapy. The article reviews the evidence on diagnosis and treatment of hypovolemia and discusses the use of balanced solutions and early goal-directed therapy (EGDT) in septic shock resuscitation. Recent findings Hypovolemia should be diagnosed and its treatment guided by a multifaceted approach, including medical history, physical examination, volume responsiveness, and technical parameters – dynamic indicators, volumetric indicators, sonography, and metabolic indicators. Central venous pressure and pulmonary artery occlusion pressure should be avoided. In ICU patients, balanced crystalloids should primarily be used, because unbalanced infusions (especially saline) cause hyperchloremic acidosis which is associated with renal impairment and infections. Colloids are beneficial to restore blood volume rapidly. Hydroxyethyl starch may be harmful although the validity of the respective recent studies is limited by methodological flaws. Early aggressive fluid therapy is still beneficial in septic shock resuscitation, despite recent trials challenging the EGDT concept. Today, 10 years after Rivers, ‘usual care’ includes aggressive fluid resuscitation that is as effective as formal EGDT. Summary Evidence-based fluid therapy includes a multifaceted diagnostic approach, the primary use of balanced crystalloids and early aggressive (septic) shock resuscitation.

Myocardial Ischemia Induces SDF-1α Release in Cardiac Surgery Patients.

Abstract: In the present observational study, we measured serum levels of the chemokine stromal cell-derived factor-1α (SDF-1α) in 100 patients undergoing cardiac surgery with cardiopulmonary bypass at seven distinct time points including preoperative values, myocardial ischemia, reperfusion, and the postoperative course. Myocardial ischemia triggered a marked increase of SDF-1α serum levels whereas cardiac reperfusion had no significant influence. Perioperative SDF-1α serum levels were influenced by patients' characteristics (e.g., age, gender, aspirin intake). In an explorative analysis, we observed an inverse association between SDF-1α serum levels and the incidence of organ dysfunction. In conclusion, time of myocardial ischemia was identified as the key stimulus for a significant upregulation of SDF-1α, indicating its role as a marker of myocardial injury. The inverse association between SDF-1α levels and organ dysfunction association encourages further studies to evaluate its organoprotective properties in cardiac surgery patients.

Influence of weaning methods on the diaphragm after mechanical ventilation in a rat model

Abstract: Mechanical ventilation (MV) is associated with diaphragm weakness, a phenomenon termed ventilator-induced diaphragmatic dysfunction. Weaning should balance diaphragmatic loading as well as prevention of overload after MV. The weaning methods pressure support ventilation (PSV) and spontaneous breathing trials (SBT) lead to gradual or intermittent reloading of a weak diaphragm, respectively. This study investigated which weaning method allows more efficient restoration of diaphragm homeostasis. Rats (n = 8 per group) received 12 h of MV followed by either 12 h of pressure support ventilation (PSV) or intermittent spontaneous breathing trials (SBT) and were compared to rats euthanized after 12 h MV (CMV) and to acutely euthanized rats (CON). Force generation, activity of calpain-1 and caspase-3, oxidative stress, and markers of protein synthesis (phosphorylated AKT to total AKT) were measured in the diaphragm. Reduction of diaphragmatic force caused by CMV compared to CON was worsened with PSV and SBT (both p < 0.05 vs. CON and CMV). Both PSV and SBT reversed oxidative stress and calpain-1 activation caused by CMV. Reduced pAKT/AKT was observed after CMV and both weaning procedures. MV resulted in a loss of diaphragmatic contractility, which was aggravated in SBT and PSV despite reversal of oxidative stress and proteolysis.

Kinetics of ventilation-induced changes in diaphragmatic metabolism by bilateral phrenic pacing in a piglet model.

Abstract: Perioperative necessity of deep sedation is inevitably associated with diaphragmatic inactivation. This study investigated 1) the feasibility of a new phrenic nerve stimulation method allowing early diaphragmatic activation even in deep sedation and, 2) metabolic changes within the diaphragm during mechanical ventilation compared to artificial activity. 12 piglets were separated into 2 groups. One group was mechanically ventilated for 12 hrs (CMV) and in the second group both phrenic nerves were stimulated via pacer wires inserted near the phrenic nerves to mimic spontaneous breathing (STIM). Lactate, pyruvate and glucose levels were measured continuously using microdialysis. Oxygen delivery and blood gases were measured during both conditions. Diaphragmatic stimulation generated sufficient tidal volumes in all STIM animals. Diaphragm lactate release increased in CMV transiently whereas in STIM lactate dropped during this same time point (2.6 vs. 0.9 mmol L-1 after 5:20 hrs; p < 0.001). CMV increased diaphragmatic pyruvate (40 vs. 146 μmol L-1 after 5:20 hrs between CMV and STIM; p < 0.0001), but not the lactate/pyruvate ratio. Diaphragmatic stimulation via regular electrodes is feasible to generate sufficient ventilation, even in deep sedation. Mechanical ventilation alters the metabolic state of the diaphragm, which might be one pathophysiologic origin of ventilator-induced diaphragmatic dysfunction. Occurrence of hypoxia was unlikely.

Telemedizin in der Intensivmedizin – Möglichkeiten und Grenzen einer Innovation

Abstract: Die Intensivmedizin wird durch den demographischen Wandel und zunehmende Behandlungszahlen, bei gleichzeitig bestehendem Arztemangel, vor eine Herausforderung gestellt. Eine Moglichkeit, die Versorgung auch in Zukunft zu gewahrleisten, stellt die Teleintensivmedizin dar. In den USA hat sich durch den Mangel an Intensivmedizinern in den letzten Jahren bereits eine umfassende teleintensivmedizinische Zusatzversorgung entwickelt; mittlerweile sind 11 % aller Krankenhauser durch ein Telemedizinzentrum mitbetreut. Der positive Einfluss in Bezug auf Behandlungsqualitat, Patientensicherheit und okonomische Faktoren wurde in zahlreichen Multicenterstudien bestatigt. In der grosten Multicenterstudie von Lilly et al., mit 107.432 Patienten in der Interventionsgruppe, fuhrten telemedizinische Interventionen zu einer Reduktion der Krankenhaussterblichkeit sowie der Sterblichkeit auf der Intensivstation. Daruber hinaus konnte die Liegedauer im Krankenhaus und auf der Intensivstation gesenkt werden. Weitere in Metaanalysen ausgewertete Studien bestatigten diese Ergebnisse und untersuchten weitere Aspekte. Die Rate beatmungsassoziierter Pneumonien wie auch katheterassoziierter Infektionen konnte reduziert werden. Durch erhohte Leitlinienadharenz wurden die Patientensicherheit und das Behandlungsergebnis verbessert. Die Behandlungskosten konnten insgesamt gesenkt werden. Die positiven Ergebnisse liesen sich auch auf grosere und akademische Krankenhauser ubertragen, jedoch muss betont werden, dass eine ungeprufte Ubertragung auf andere Gesundheitssysteme aufgrund unterschiedlicher Ausgangsbedingungen nicht angenommen werden sollte. Letztendlich muss untersucht werden, inwiefern sich die Ergebnisse auch auf die Situation in Deutschland ubertragen lassen. Durch teleintensivmedizinische Zusatzversorgung kann eine relevante Verbesserung intensivmedizinischer Behandlungsergebnisse sowohl wahrend des Krankenhausaufenthalts als auch im Langzeitergebnis bis zur Entlassung ins hausliche Umfeld erreicht werden. Teleintensivmedizin ist weder ein Allheilmittel, noch ein Arzt-ersetzendes Verfahren, sondern eine neue Form arztlicher Kooperation zum Nutzen unserer schwerkranken Patientinnen und Patienten.

Speckle tracking echography allows sonographic assessment of diaphragmatic loading

Abstract: Introduction: Assessment of diaphragm function should ideally be assessed using magnetic twitch pressure or esophageal and gastric balloons. Conventional sonographic techniques as thickness and fractional thickening (FT), only provide limited insight in diaphragm function. Speckle tracking echocardiography allows reliable quantification of muscle function by tracking of grey patterns and their motion; strain as parameter of muscle deformation and strain rate as deformation velocity. Aim: To investigate whether speckle tracking can quantify loading of the diaphragm, superior to FT. Methods: 13 healthy volunteers underwent an inspiratory loading protocol with recording of transdiaphragmatic pressure (Pdi) and diaphragm electromyography (EMGdi). Inspiratory loading of 0 to 30% of maximal inspiratory pressure was applied in random order for 5 minutes per applied load. Diaphragmatic sonography was performed using a 2-4 MHz linear phased array transducer positioned at the right-lateral thoracic wall in the anterior axillary line longitudinal to the body axis. Ultrasound recordings of the diaphragm were made at the marked location during 10 seconds. Results: Increased inspiratory loading increased Pdi and EMGdi. Sonographic markers of contractility increased with incremental loading. Pdi correlated with strain (r=0.75; p=0.000) and strain rate (r=0.77; p=0.000). Contrarily, FT was not correlated with Pdi. Conclusion: Speckle tracking of the diaphragm can detect changes in diaphragmatic loading up to 30% of maximal inspiratory pressure. It might be a valuable tool to detect changes in loading in specific patient categories, including patients with acute respiratory failure and ventilated ICU patients.

Investigating colloids and crystalloids--everything clear?

Abstract: Intensive care medicine must take into account disturbed physiological variables. Treatment should be aimed at restoring normal values of these variables, or at least at preventing further deterioration. Shoemaker and colleagues demonstrated that organ failure occurs in high-risk surgical patients when they experience an oxygen deficit, especially intra-operatively and in the early postoperative period. The use of dobutamine to simply increase oxygen delivery (DO2) did not result in increased survival or decreased organ failure. But treatment of postoperative hypovolaemia should aim to compensate the potential shortage in DO2. In this regard, the investigation by Skytte and colleagues provides valuable new evidence on the choice of volume resuscitation in postoperative care in a sophisticated fashion. They found that a bolus administration of crystalloid solution compared with hydroxyethyl starch (HES) after cardiac surgery results in a decrease in renal vein oxygen saturation and an increase in renal oxygen extraction. Skytte and colleagues identified repeated boluses of crystalloid solution as a potential harm for renal oxygenation. This may be of special interest in patients with hypovolaemia when the renal DO2 is impaired. Since DO2 is improved by enhancing blood flow, the investigation by Skytte and colleagues is even more interesting because renal blood flow and cardiac output were increased by both crystalloids and colloids, but the ratio between renal blood flow and cardiac output decreased solely with crystalloids. The major limitation, as already mentioned by Skytte and colleagues, is that they included patientswhowere considered already haemodynamically stable. This is amajor weakness in all trials investigating fluid resuscitation in critically ill patients apart from the CRISTAL trial. In contrast to the investigation by Skytte and colleagues, a former investigation assessing the influence of crystalloid or HES in patients with colorectal surgery could not detect any benefit or harmwith respect to the presence of gastrointestinal (GI)morbidity within the first week after surgery. Other authors could not detect differences in cerebral oxygen extraction when comparing HES with a lactated Ringer’s solution. Yet, a major study leading to the ban of HES in intensive care is in line with the results of Skytte and colleagues. A higher proportion of Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) risk and injury in saline-treated patients compared with HES [3.3% increase (P=0.007) and 3.4% increase (P=0.005), respectively] was detected, but no difference was detectable in the RIFLE failure group. The decision for renal replacement therapy (RRT) was not controlled by the study protocol. Others who compared HES with crystalloids found higher rates of RRT and also exhibited a lack of a protocol for initiation of RRT. To overcome the uncertainty on the appropriate choice and guidance of volume therapy and resuscitation, an evidencedbased guideline on volume therapy in adults was generated by the Association of the Scientific Medical Societies in Germany [Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. (AWMF)]. AWMF represents Germany in the Council for International Organizations of Medical Sciences (CIOMS). This association affiliates 173 scientific societies from all specialties of medicine in Germany and has generated very high quality and methodological standards, leading to very robust and useful recommendations and guidelines. A guideline on volume therapy was generated on the highest evidence level possible (S3). Following this guideline, estimating the need for volume resuscitation by using central venous pressure (CVP) is not appropriate, as shown in numerous studies in anaesthesia and critical care settings. Thus, this level of evidence led to the recommendation that CVP should not be used for resuscitation guidance; the passive leg raise (PLR) or flow-based parameters should be used instead. The reliability of the PLR to detect changes in cardiac preload was described previously. Furthermore, the National Institute for Health and Care Excellence (NICE) guideline (CG174) on fluid therapy in adults recommends the PLR test for initial assessment of fluid responsiveness. The application of adequate volume resuscitation is more complex than in past decades. An important step is the consideration of fluids as a drug with special indications and contraindications. In this regard, the guidance of fluid therapy during four

Advanced hemodynamic monitoring in the critically ill patient : Nice to have or need to treat?

Abstract: The outcome of critically ill patients is still unacceptable high. Recently, an epidemiological investigation demonstrated that the incidence of severe sepsis and septic shock in Germany remains 11 % and that the mortality of septic shock is currently more than 40 %. Thus, every effort to improve diagnosis or treatment for critically ill patients is urgently needed. The value of hemodynamic monitoring has been under intensified discussion since the study of Connors et al. on the value of pulmonary artery catheter published exactly 20 years ago [1]. Since this time, we have learnt many lessons. Firstly, using a diagnostic tool per se cannot improve the outcome of critically ill patients. This is true for pulse oximetry, direct measurement of the arterial pressure as well as advanced hemodynamic monitoring variables. Monitoring of static variables such as central venous pressure (CVP) cannot be used for the assessment of volume status [2, 3]. Instead flow based hemodynamic variables seem to be more useful. There is evidence that the use of e.g. stroke volume or cardiac output measurement in combination with a passive leg raising test as an internal fluid challenge is a valuable tool to diagnose hypovolemia as well as to assess the volume responsiveness of a critically ill patient [4]. In this issue of the JCMC Perel and colleagues report on the value of advanced hemodynamic monitoring (transpulmonary thermodilution) for the therapeutic management of critically ill patients [5]. They performed a pre and post questionnaire study on the ability of intensivists to estimate the hemodynamic condition of critically ill patients and the impact on the decision making process. The authors revealed that unfortunately we are not as good as we think we are. The percentage error of the difference between estimated and measured thermodilution-derived variables ranged between 66 and 95 %. Only in 36 % of the cases the estimated cardiac output was within a range of ±20 % of the measured value, and in more than half of the cases intensivists underestimated the actual cardiac output by more than 20 %. Of note, these results were independent of the physician’s experience. Remarkably, in around 20 % therapeutic decisions on hemodynamic management including fluids, catecholamine or diuretics were changed according to the measured values of the advanced hemodynamic monitoring. Obviously, our patients deserve correct and rapid measurement using all possible resources and data to find out the correct diagnosis and best treatment. Furthermore, our patients cannot afford being exposed to erroneous decisions of their attending physicians, as these are frequently associated with detrimental consequences. The presented data strongly support the use of advanced hemodynamic monitoring regardless of the individual doctor’s experience to sharpen the diagnosis and focus consecutive therapeutic decisions. While there seems to be consensus on the kind of advanced monitoring to be used [6], the criteria for the use of such monitoring devices remain to be determined. This is important in view of both treatment quality and cost implications. In agreement with recommendations of the consensus group [6] the use of advanced hemodynamic monitoring should be initiated in: & G. Marx gmarx@ukaachen.de; http://www.operative-intensivmedizin.de

Differences between prolonged weaning patients from medical and surgical intensive care units.

Abstract: Background It is not clear whether patients entering a specialized, interdisciplinary weaning unit from surgical or medical intensive care units (ICU) distinguish substantially. The purpose of the present study was to assess differences in patients with prolonged weaning being referred from surgical and medical ICU. Methods Data collected from April 2013 to April 2014 was conducted for retrospective analysis. Mortality rates, demographic data, clinical, and microbial differences in 150 patients with prolonged weaning were assessed (80 surgical and 70 medical). Results Surgical ICU referrals tended to be older (70.7 ± 11.3 vs. 67.3 ± 12.3, P = 0.051) and had fewer underlying pulmonary diseases (45% vs. 60%, P = 0.067). Sodium values at the time of referral to the weaning unit were significantly higher in surgical (147.1 ± 9.6) vs. medical (141.3 ± 6.7 mmol/l) patients (P < 0.001). Each 10-unit increase in sodium at the time of referral to the weaning unit was associated with a 2.5-day (95% CI −0.4, 5.4; P = 0.09) prolongation of stay in the weaning unit. Although significant differences in microbiological agents from tracheal aspiration were seen, the infection rate on the weaning unit was similar in both groups. There was no difference in weaning unit mortality between surgical and medical ICU patients (18% vs. 23%; P = 0.41). Conclusion Few differences were found between patients being referred to a specialized weaning unit from surgical vs. medical ICUs. Besides differences in microbiological characteristics of tracheal secretions, there were also differences in sodium levels, which appear to influence on treatment duration.

Intensive care medicine: new insights to improve care.

Abstract: DOI:10.1097/ACO.0000000000000315 Intensive care medicine is not only a fascinating, but also a challenging area of our specialty. Until today and despite all scientific and clinical efforts, critical illnesses such as sepsis or multiple organ dysfunction and failure are associated with an unacceptable high mortality rate in our patients [1]. Interestingly, there are differences in the development of epidemiology between Australia and the USA and Europe. Although in Australia and the USA there is a decrease in mortality in sepsis [2,3], recent data from Spain show a high incidence of severe sepsis associated with a mortality rate of more than 40% [4]. Unfavorable outcome is among others especially associated with age and organ dysfunction. Understanding the underlying problems and pathophysiology is essential for improving diagnostic tools and therapeutic interventions. Being confronted with life-threatening complex situations obviously induces a high innovative drive for evolving the area. There have been numerous experimental and clinical investigations including many large randomized control trials in the last decades. Over time, we had to learn many lessons. Compared with other specialties and fields such as cardiology or hemato-oncology, intensivists are dealing rather with syndromes than with clearly defined diseases and additionally dealing with a patient population that is very heterogeneous. Thus, it is not easy to create robust scientific evidence. Another hurdle is the primary outcome parameter 28-day mortality. To be able to achieve this primary study goal in the intensive care area, there is the sole option to perform large-scale randomized controlled trials with a couple of thousand patients. To include many patients in an acceptable time period, the protocols cannot be very specific resulting in a heterogeneous patient population. In contrast, smaller trials with difficult protocols are rarely able to provide the necessary power to produce outcome-relevant evidence. To overcome this obstacle, there is the option to discuss within the scientific community whether resolution of organ dysfunction might be a useful alternative as an outcome parameter in clinical trials. Furthermore, time between onset of diagnosis and enrollment and study-related measures is a