[Relationship between body temperature, neuron-specific enolase, and clinical course in patients after out-of-hospital cardiac arrest]. / Zusammenhang zwischen Körpertemperatur, neurononspezifischer Enolase und klinischem Verlauf bei Patienten nach prähospitaler Reanimation.

BACKGROUND: According to ILCOR (International Liaison Committee on Resuscitation) recommendations (released in 2003), use of therapeutic hypothermia is recommended for unconscious adult patients who have survived a cardiac arrest regardless of the initial monitored cardiac rhythm. Thereby, the treatment goal is to achieve and maintain a body temperature of 32-34 °C for a period of 12-24 h. According to the October 2015 recommendations of the European Resuscitation Council (ERC), targeted temperature management (TTM) remains part of treatment, but, as an option, it is advised that the targeted body temperature be 36 °C rather than 32-34 °C. PATIENT POPULATION AND METHODS: For a non-randomized retrospective observational study, a total of 149 patients were treated with cardiopulmonary resuscitation (CPR) between May 1999 and September 2009. For the first 4 days after CPR, data associated with demography, resuscitation, therapy (temperature course, neuron-specific enolase [NSE]) and clinical-neurological development (Glasgow Outcome Scale [GOS]) were collected. In the study, patients receiving mild hyperthermia were compared with those who did not receive hypothermia. RESULTS: Of the 149 patients included, 90 were treated with mild hypothermia (as decided by the attending physician), while 59 received no hypothermia therapy. Assessment reveals that mild hypothermia positively influences clinical-neurological progression, but not survival. On day three and four, patients with an unfavorable neurological progression exhibited significantly increased serum levels of NSE (day 4: 108.7 ± 137.3 ng/ml versus 25.5 ± 15.4 ng/ml). Patients receiving hypothermia showed lower average NSE levels compared with persons not receiving hypothermia. Furthermore, during the first 4 days, their NSE values tended to increase slower (NSE value at day 4: 55.9 ± 64.9 ng/ml versus 129.9 ± 174.9 ng/ml). The best cut-off-value for an unfavorable neurological result was 74.2 ng/ml at day four (specificity 100%, sensitivity 48.6%). For the group of patients who received hypothermia, the best cut-off-value was 74.2 ng/ml at day four (specificity 100%, sensitivity 40.9%), and, for the comparison group, best cut-off-value was 25.5 ng/ml at day three (specificity 100%, sensitivity 88.2%). CONCLUSION: After out-of-hospital resuscitation, there is a trend for improved clinical-neurological progression with mild hypothermia but it does not influence the prognostic significance of serum NSE. After assessment of available data, it is not possible to recommend uniform cut-off values for patients who received mild therapeutic hypothermia and for those who did not receive hypothermia treatment.

[Prognostic relevance of tissue oxygen saturation in patients in the early stage of multiple organ dysfunction syndrome]. / Prognostische Relevanz der Gewebesauerstoffsättigung bei Patienten in der Frühphase eines Multiorgandysfunktionssyndroms.

BACKGROUND: Patients in circulatory shock exhibit insufficient peripheral perfusion to ensure adequate oxygenation of vital organs such as the heart and brain. Early detection of reduced tissue oxygen saturation (StO2) could be used for rapid therapeutic intervention and thus improve the prognosis of patients in the early stage of multiple organ dysfunction syndrome (MODS). MATERIALS AND METHODS: A total of 60 patients in the early stage of MODS (APACHE [Acute Physiology and Chronic Health Evaluation] II score ≥20) were investigated in a monocentric, prospective, randomized phase II study. StO2 was measured using the InSpectraTM StO2 system and compared with known indicators of hypoxia (peripheral oxygen saturation [SpO2], arterial oxygen saturation [SaO2], central venous oxygen saturation [ScvO2], pH, serum lactate). Clinical endpoints of the study were 28-day and 6­month mortality as well as the need for invasive mechanical ventilation and renal replacement therapy during the hospital stay, respectively. RESULTS: An increased 28-day and 6­month mortality is found for patients with StO2 <75% in contrast to patients with StO2 ≥75%. Correlations of StO2 with SpO2, ScvO2, and serum lactate are confirmed. Patients with reduced StO2 tend to show a higher disease severity as measured by APACHE II score. CONCLUSION: StO2 shows prognostic relevance in patients at the early stage of MODS. Thus, the rapid and noninvasive assessment of StO2 could be useful in risk stratification of these patients.

Serum IgG levels and mortality in patients with severe sepsis and septic shock : The SBITS data.

BACKGROUND: The role of intravenous immune globulin (Ig) therapy in patients with severe sepsis and septic shock is discussed controversially. Low initial IgG levels could help to identify those patients who might benefit from an adjunctive Ig treatment. OBJECTIVES: To investigate the effect of initial serum IgG levels on 28-day mortality in patients with severe sepsis and septic shock. MATERIALS AND METHODS: In this retrospective analysis of the SBITS trial data, 543 patients were allocated to four groups (quartiles) depending on their initial serum IgG levels (1: IgG ≤ 6.1 g/l; 2: IgG 6.2-8.4 g/l; 3: IgG 8.5-11.9 g/l; 4: IgG > 11.9 g/l). The third quartile was taken as the reference quartile. For the applied logistic regression model clinically relevant confounders were defined and integrated into further risk-adjusted calculations. RESULTS: Patients with the lowest IgG levels had a mortality rate similar to those patients with initial IgG levels in the second and third quartile, representing the physiological IgG range in healthy people. Surprisingly, patients with the highest IgG levels even showed a significantly higher mortality in a risk-adjusted calculation compared to the reference quartile (OR 1.69, CI 1.01-2.81, p = 0.05). Subgroup analyses revealed that initial IgG levels were of no prognostic value in patients presenting with vasopressor-dependent septic shock on admission as well as in patients with either gram-positive or gram-negative sepsis. CONCLUSIONS: Initially low IgG levels do not discriminate between survival and nonsurvival in patients with severe sepsis and septic shock. Therefore, low IgG cannot help to identify those patients who might benefit from an adjunctive IgG sepsis therapy. Whether a high initial IgG serum level is an independent mortality risk factor needs to be investigated prospectively.

Influence of the serum levels of immunoglobulins on clinical outcomes in medical intensive-care patients.

INTRODUCTION: Endogenous immunoglobulins (Igs) are of fundamental importance in the host defense after microbial infections. However, the therapeutic administration of intravenous IgG (IVIgG) has not yet been shown to improve clinical outcomes in patients suffering from sepsis, and in the case of IgM-containing preparations (IVIgGMA) the positive evidence is only weak. Recently published studies implicate that Ig levels on admission could have an impact on the patient's response to IVIg treatment and on outcomes of critically ill patients. METHODS: In this noninterventional study, the serum levels of IgG, IgM, and IgA were determined in 340 medical patients on ICU admission, and clinical outcomes were prospectively recorded (ICU mortality, need for renal replacement therapy (RRT), need for mechanical ventilation, substitution of coagulation factors, and amount of red cell transfusions). Patients were prospectively grouped according to their main reason for ICU admission (sepsis, respiratory failure, cardiovascular diseases, acute renal failure, postoperative condition, state after cardiopulmonal resuscitation, gastrointestinal diseases, and others). RESULTS AND DISCUSSION: There was no correlation between the Ig levels on admission and ICU mortality neither in the total cohort of medical ICU patients nor in any prespecified subgroup. However, in a logistic regression model that was adjusted for APACHE II score on admission, an increase in serum IgG was associated with a reduced need for mechanical ventilation in patients suffering from cardiovascular disease. On the other hand, in patients suffering from sepsis, an increased level of IgM was linked to an increased administration of coagulation factors. CONCLUSION: Our data do not support the hypothesis that serum levels of immunoglobulins are linked to mortality in medical ICU patients.

Lung protective ventilation and hospital survival of cardiac intensive care patients.

OBJECTIVE: To detect connections between parameters of ventilation and outcomes of cardiac intensive care patients. DESIGN AND SETTING: Noninterventional study. Between 05/11 and 05/12 all patients with acute heart failure and post cardiopulmonary resuscitation were registered. Lung protective ventilation was defined as peak inspiratory pressure (PIP) < 30 mmHg and tidal volume (Vt) < = 6 ml/kg. RESULTS: In total, 129 patients were included in the study, 68.2 % male, age 67.9 ± 13.4 years, weight 71.4 ± 37.2 kg, predictive body weight 66.9 ± 8.8 kg, mortality 47.3 %. Lung protective ventilated patients at day 1: 17.3 % with a significant difference between surviving and nonsurviving patients (24.1 % vs. 9.6 %; p < 0.05). Logistic regression models showed a strong connection between PIP and survival (odds ratio 1.13; p < 0.05). Vt showed no significant influence on survival. CONCLUSION: Our data recommends a strict observance of a low PIP for cardiac intensive care patients, whereas Vt seems to be of secondary importance.

Overexpression of protein phosphatase 2A in a murine model of chronic myocardial infarction leads to increased adverse remodeling but restores the regulation of ß-catenin by glycogen synthase kinase 3ß.

BACKGROUND/OBJECTIVES: Increased activity of cardiac protein phosphatases is an important feature in human heart failure. Several different protein phosphatases (PP) are involved in the regulation of excitation-contraction-coupling of the myocardium. Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase consisting of a dimeric core enzyme and tissue-specific subunits. In this study we used transgenic mice overexpressing PP2A to further investigate the role of PP2A in cardiac remodeling after myocardial infarction. METHODS AND RESULTS: Adult male CD-1 mice overexpressing the catalytic subunit α of PP2A (αMHC-PP2A; TG) underwent chronic LAD-ligation or sham surgery, respectively; wildtype littermates (WT) were used as controls. Cardiac function was determined by echocardiography before and 28 days after LAD-ligation. 28 days after MI, the animals were sacrificed and cardiac remodeling was analyzed in histological sections and by Western blots. PP2A overexpression leads to dilated cardiomyopathy in mice, and increased cardiomyocyte hypertrophy and fibrosis of the remote myocardium can be seen after myocardial infarction. However, we found an improved survival of TG in the subacute phase after MI in comparison to WT. On the molecular level, TG shows reduced expression of SERCA and CaMKII alpha both under basal condition as well 28 days after MI. Additionally, the regulation of the Akt/GSK3ß/ß-catenin pathway is severely disturbed in TG at baseline where a significant activation of Akt is found that coincides with the typical phosphorylation of GSK3ß. However, this does not lead to the accumulation of ß-catenin - on the contrary: phosphorylation-induced degradation of ß-catenin is significantly enhanced. CONCLUSION: Transgenic overexpression of myocardial PP2A causes adverse remodeling which coincides with a disruption of the classical Akt/GSK3/ß-catenin pathway under baseline conditions that is restored to normal values in chronic myocardial infarction. Even so overall survival of TG after myocardial infarction was not constrained and survival after day 2 post MI was improved.

[Indocyanine green elimination for the evaluation of liver function: prognostic value in patients with community-acquired sepsis]. / Indocyaningrün-Elimination als Maß der Leberfunktion : Prognostische Bedeutung bei Patienten mit ambulant erworbener Sepsis.

BACKGROUND: The aim of our clinical study was to correlate liver function measured by indocyanine green (ICG) elimination and clinical outcomes in patients with an early stage of community-acquired sepsis (CAS). MATERIALS AND METHODS: A total of 341 patients (≥ 18 years) presenting with suspicion of CAS or evidence of an infection and fulfillment of ≥ 2 systemic inflammatory response syndrome (SIRS) criteria were included in the observational study"Prognosis of early sepsis 2" (Prognose der frühen Sepsis 2, ProFS 2). Patients who had been hospitalized within the last 7 days were excluded. In a subgroup of these patients (n = 72) who were transferred to an intensive or intermediate care unit according to the clinical judgment of the treating physicians, ICG elimination (plasma disappearance rate, ICG-PDR; 15 min retention rate, ICG-R15) was assessed by using a noninvasive monitoring system (LiMON, PULSION Medical Systems, Germany). ICG-PDR and -R15 were determined on the day of admission (n = 72) and after 96 h (n = 34). The primary end point of the study was defined as death within 30 days. Secondary endpoints were need for renal replacement therapy, requirement for invasive mechanical ventilation, and length of stay in an intermediate or intensive care unit. RESULTS AND CONCLUSION: In contrast to patients with sepsis or severe sepsis, ICG elimination was found to be significantly impaired in patients with septic shock. Furthermore, a significant predictive value of ICG-PDR and -R15 on the day of admission for the need for subsequent renal replacement therapy (n = 12) was observed. In addition, reduced ICG elimination was associated with a longer stay in an intermediate or intensive care unit. However, ICG elimination on admission could not predict 30-day mortality (n = 14) or requirement of mechanical ventilation (n = 20).

Outcome prediction using clinical scores and biomarkers in patients with presumed severe infection in the emergency department.

BACKGROUND: Severe infections play an important role in the emergency department (ED) and early risk stratification is essential. We compared the prognostic value of APACHE II, SOFA, and MEDS scores, and the biomarkers C-reactive protein (CRP), procalcitonin (PCT), and interleukin 6 (IL-6). METHODS: We performed a prospective observational study. Patients aged 18 years or older with a severe infection, from whom blood cultures were taken, were included. RESULTS: Two hundred and eleven patients were included. The 30-day mortality rate was 8.5%. All scores and biomarkers showed significant area under the curve (AUC) values of receiver operating characteristic curve analysis for death within 30 days: 0.801 for APACHE II, 0.785 for MEDS, 0.708 for SOFA, 0.693 for CRP, 0.651 for PCT, and 0.716 for IL-6. For treatment in an ICU and need for mechanical ventilation, these parameters had significant AUC values, too. For renal replacement therapy, only APACHE II, SOFA, and PCT showed significant AUC values. According to the trend observed, the AUC values were highest for the APACHE II score. CONCLUSIONS: All investigated parameters have a predictive value in patients with an infection in the ED. According to the trend observed, the APACHE II score seems to have the best discriminative power. Use of the APACHE II score already at the time of admission to the ED may be useful for stratifying patients at risk for ICU treatment, thereby using the same score in the ED and the ICU.

[Septic shock and septic cardiomyopathy]. / Septischer Kreislaufschock und septische Kardiomyopathie.

Patients suffering from septic shock often present with not only severe reduction of afterload induced by vasodilation but are also affected by sepsis-induced cardiac dysfunction. Elevated troponin levels, which are typically not caused by coronary ischemia, may indicate septic cardiomyopathy which is characterized both by altered systolic function as well as by disturbances in the regulation of heart rate and heart rate variability. The latter findings are based not only on the dysfunction of the autonomous nervous system but are also the result of the direct interaction of endotoxins with cardiac pacemaker cells. In order to quantify the extent of septic cardiomyopathy, cardiac output has to be considered in the light of the existing afterload, i.e., by the parameter 'afterload-related cardiac performance' (ACP). Therapy of septic shock (and thereby septic cardiomyopathy) is based on the well-known causative, supportive, and adjunctive strategies. Stabilization of cardiac function is assured by volume resuscitation (including blood transfusion) and inotropic support (dobutamine). Further specific therapeutic approaches have not yet been established.

Microbial diagnostics in patients with presumed severe infection in the emergency department.

INTRODUCTION: Sepsis in the early stage is a common disease in emergency medicine, and rapid diagnosis is essential. Our aim was to compare pathogen diagnosis using blood cultures (BC) and the multiplex polymerase chain reaction (PCR) test.Methods. At total of 211 patients admitted to the multidisciplinary emergency department of our university hospital between 2006 and 2009 with suspected severe infection from any origin were studied. Blood samples for BC (aerobic and anaerobic) and multiplex PCR were taken for identification of infectious microorganisms immediately after hospital admission. Results of the BC and PCR correlated with procalcitonin concentration (PCT) and clinical diagnosis of sepsis (≥2 positive SIRS criteria) as well as with severity of disease at admission and with clinical outcome measures. RESULTS: Results of the BC were available in 200 patients (94.8%) and PCR were available in 119 patients (56.3%), respectively. In total, 87 BC (43.5%) were positive and identified 94 pathogens. In 45 positive PCRs, 47 pathogens (37.8%) were found. Identical results were obtained in 81.4%. In addition, BC identified 9 Gram-positive and 3 Gram-negative bacteria, while PCR added 5 Gram-negative pathogens. Coagulase-negative staphylococci were detected in blood cultures only (n=20, 21.3%), whereas PCR identified significantly more Gram-negative bacteria than BC. In patients with positive PCR results, the PCT level was significantly higher than in patients with negative PCR (15.0±23.3 vs. 8.8±32.8 ng/ml, p<0.001). This difference was not observed for BC (10.6±25.7 vs. 11.6±44.9 ng/ml, p=0.075). The APACHE II score correlated with PCR (19.2±9.1 vs. 15.8±8.9, p<0.05) and was also higher in positive BC (18.7±8.7 vs. 14.4±8.0, p<0.01). Positive PCR and BC were correlated with negative clinical outcomes (e.g., transfer to ICU, mechanical ventilation, renal replacement therapy, death). CONCLUSION: In patients admitted with suspected severe infection, a high percentage of positive BC and PCR were observed. Positive findings in the PCR correlate with elevated levels of PCT and high APACHE II scores.

[Shock, hemoconcentration, and generalized edema in a 47-year-old man]. / Schock, Hämokonzentration und generalisierte Ödeme bei 47-jährigem Patienten.

We report the case of a 47-year-old man who was admitted because of syncope. Upon hospital admission, he rapidly developed circulatory shock with generalized edema and a severe hemoconcentration with a hematocrit of 70%. The condition was stabilized with infusion of 17 l of cristalloid fluids over a period of 24 h. After ruling out possible secondary causes, the diagnosis of a systemic capillary leak syndrome--a severe transient endothelial barrier dysfunction of unknown origin--was made. A triad of hypotension, hemoconcentration (hematocrit >60%) and macromolecular extravasation is the typical finding; furthermore, a strong association with monoclonal gammopathy of unknown significance (MGUS) is described.

[Unexplained fever and B-symptoms in a young male Black African]. / Unklares Fieber und B-Symptome bei einem jungen Schwarzafrikaner.

An immunocompetent Nigerian developed a fulminant hemophagocytic lymphohistiocytosis due to Epstein-Barr virus reactivation. The patient initially presented with fever, hepatosplenomegaly and pancytopenia. The clinical status of our patient deteriorated quickly despite treatment with corticoids. Escalation of immunosuppressive treatment was not possible. He died of lung, liver and circulatory failure in our intensive care unit.Hemophagocytic lymphohistiocytosis is a rare disease characterized by inflammation due to prolonged and excessive activation of antigen-presenting cells. High plasma ferritin levels and phagocytosis of hematopoetic cells in bone marrow, spleen and liver lead to the diagnosis. Hemophagocytic lymphohistiocytosis should therefore be included in the differential diagnosis in patients with persistent fever, hepatosplenomegaly and cytopenia.

[Cardiac biomarkers in perioperative medicine : significance for noncardiac surgery patients]. / Kardiale Biomarker in der perioperativen Medizin : Stellenwert bei nichtherzchirurgischen Patienten.

Perioperative detection of cardiac biomarkers may help to identify patients at risk. Whether detection of these markers will be recommended in the preoperative setting for patients with cardiac diseases in the future has to be discussed as large prospective trials on this topic are missing. For preoperative evaluation of cardiac insufficiency quantification of brain natriuretic peptide (BNP) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) are useful markers. Troponin is the marker of choice for detection of myocardial ischemia/infarction in the postoperative setting. In unstable patients coronary angiography and/or percutaneous coronary intervention (PCI) are indicated. However, in stable patients the decision for coronary angiography and/or PCI has to be made in each patient individually after interdisciplinary discussion between anesthesiologists, cardiologists and surgeons.

[Septic shock in a renal transplanted patient after consumption of uncooked pork meat]. / Septischer Schock bei einem nierentransplantierten Patienten nach Genuss von rohem Schweinefleisch.

Salmonellosis caused by Salmonella enteritidis is an acute and in most cases zoonotic disease, but chronic human carriers are also known. Mostly, affected persons recover without treatment, but severe complications occur occasionally. For the first time we report a case of probably food-borne invasive Salmonella enteritidis infection with septic shock in a patient with Tacrolimus treatment, 13 years after renal transplantation, probably acquired by uncooked ground pork meat.

[Sepsis and heart]. / Sepsis und Herz.

In patients suffering from severe sepsis an impairment of cardiac function is seen constantly. Patients with septic shock often show a transient reduction of cardiac ejection fraction. Besides, a tremendous impairment of heart rate variability corresponding to a poor prognosis is often found. Endotoxin might play a pivotal role in the conjunction of inflammation and the disturbance of heart rate regulation. Experimental studies show that the complex interactions of endotoxin, the cardiac pacemaker current I (f), and the autonomous nervous system lead to an increase of resting heart rate and in parallel to a decrease of heart rate variability - as typically seen in patients with severe sepsis. The method of choice to quantify the degree of septic cardiomyopathy at the intensive care unit certainly is to determine cardiac output in relation to systemic vascular resistance. Unfortunately, clinical trials aiming to influence the causal pathogenesis of septic cardiomyopathy (inhibition of excess formation of nitric oxide, suppression of cytokine release etc.) were rather disappointing so far. Positive effects might be assumed for the administration of activated protein C thereby underlining the role of microcirculatory alterations in the development of septic cardiomyopathy.

[Septic circulatory shock and septic cardiomyopathy]. / Septischer Kreislaufschock und septische Kardiomyopathie.

Septic shock is not only a circulatory shock but is also a cardiac shock, the consequence of a potentially reversible heart impairment known as septic cardiomyopathy. Disturbances of macrocirculation as well as microcirculation, an individually heterogeneous reduction of cardiac function, and an extensive impairment of demand-oriented regulation of heart function characterize the septic shock state. Bacterial toxins, inflammatory mediators, and a disseminated intravasal coagulopathy are responsible for these disturbances; for the impairment of cardiac regulation, the interaction of endotoxin with the cardiac pacemaker current I(f) also plays a role. Circulatory shock as well as septic cardiomyopathy should be quantified: The lowering of systemic vascular resistance characterizes the extent of circulatory shock, and the reduction of relative cardiac output in relation to afterload characterizes the extent of septic cardiomyopathy. The intensity of circulatory as well as of cardiac impairment correlates with an unfavorable prognosis. Treatment of septic circulatory shock and of septic cardiomyopathy is predominantly symptomatic; first causal approaches are under investigation.

[Specific aspects in septic patients: initial phase in the emergency department, age, sex and post-ICU-care]. / Spezielle Aspekte bei Sepsispatienten : Initiale Phase auf der Notaufnahme, Lebensalter, Geschlecht, Postintensivphase.

This article deals with specific aspects of the patient with sepsis and his treatment. With adequate therapy (antibiotics started within the first hour, early goal-directed therapy) initiated as early as possible, the patient with community-aquired severe sepsis in the emergency department has a considerable better chance to survive than the patient with prolonged severe sepsis in the ICU. The average age of patients with severe sepsis and septic shock treated at the ICU is rising, with consequences like oligosymptomatic presentation, altered pharmakokinetics according to older-age-induced reduced organ functions and prolonged stay at the ICU due to comorbidity. Due to sexual dimorphisms of the immune system, women have a better prognosis in sepsis than men. In an animal sepsis model activation of the estrogen receptor beta improves prognosis. Within six months after having survived severe sepsis, morbidity and mortality is still increased. Taking care for the patient in a post-ICU outpatient department during this time will help to recognize these problems and to effectively treat the patient as soon as possible.