Simplified lung ultrasound protocol shows excellent prediction of extravascular lung water in ventilated intensive care patients.

INTRODUCTION: Ultrasound of the lung and quantification of B lines was recently introduced as a novel tool to detect overhydration. In the present study, we aimed to evaluate a four-region protocol of lung ultrasound to determine the pulmonary fluid status in ventilated patients in the intensive care unit. METHODS: Fifty patients underwent both lung ultrasound and transpulmonary thermodilution measurement with the PiCCO system. An ultrasound score based on number of single and confluent B lines per intercostal space was used to quantify pulmonary overhydration. To check for reproducibility, two different intensivists who were blinded as to the ultrasound pictures reassessed and classified them using the same scoring system. The results were compared with those obtained using other methods of evaluating hydration status, including extravascular lung water index (EVLWI) and intrathoracic blood volume index calculated with data from transpulmonary thermodilution measurements. Moreover, chest radiographs were assessed regarding signs of pulmonary overhydration and categorized based on a numeric rating scale. RESULTS: Lung water assessment by ultrasound using a simplified protocol showed excellent correlation with EVLWI over a broad range of lung hydration grades and ventilator settings. Correlation of chest radiography and EVLWI was less accurate. No correlation whatsoever was found with central venous pressure measurement. CONCLUSION: Lung ultrasound is a useful, non-invasive tool in predicting hydration status in mechanically ventilated patients. The four-region protocol that we used is time-saving, correlates well with transpulmonary thermodilution measurements and performs markedly better than chest radiography.

The effect of continuous versus intermittent renal replacement therapy on the outcome of critically ill patients with acute renal failure (CONVINT): a prospective randomized controlled trial.

INTRODUCTION: Acute renal failure (ARF) requiring renal replacement therapy (RRT) occurs frequently in ICU patients and significantly affects mortality rates. Previously, few large clinical trials investigated the impact of RRT modalities on patient outcomes. Here we investigated the effect of two major RRT strategies (intermittent hemodialysis (IHD) and continuous veno-venous hemofiltration (CVVH)) on mortality and renal-related outcome measures. METHODS: This single-center prospective randomized controlled trial ("CONVINT") included 252 critically ill patients (159 male; mean age, 61.5 ± 13.9 years; Acute Physiology and Chronic Health Evaluation (APACHE) II score, 28.6 ± 8.8) with dialysis-dependent ARF treated in the ICUs of a tertiary care academic center. Patients were randomized to receive either daily IHD or CVVH. The primary outcome measure was survival at 14 days after the end of RRT. Secondary outcome measures included 30-day-, intensive care unit-, and intrahospital mortality, as well as course of disease severity/biomarkers and need for organ-support therapy. RESULTS: At baseline, no differences in disease severity, distributions of age and gender, or suspected reasons for acute renal failure were observed. Survival rates at 14 days after RRT were 39.5% (IHD) versus 43.9% (CVVH) (odds ratio (OR), 0.84; 95% confidence interval (CI), 0.49 to 1.41; P = 0.50). 14-day-, 30-day, and all-cause intrahospital mortality rates were not different between the two groups (all P > 0.5). No differences were observed in days on RRT, vasopressor days, days on ventilator, or ICU-/intrahospital length of stay. CONCLUSIONS: In a monocentric RCT, we observed no statistically significant differences between the investigated treatment modalities regarding mortality, renal-related outcome measures, or survival at 14 days after RRT. Our findings add to mounting data demonstrating that intermittent and continuous RRTs may be considered equivalent approaches for critically ill patients with dialysis-dependent acute renal failure. TRIAL REGISTRATION: NCT01228123, clinicaltrials.gov.

Mild hypothermia treatment in patients resuscitated from non-shockable cardiac arrest.

OBJECTIVE: Therapeutic hypothermia has proved effective in improving outcome in patients after cardiac arrest due to ventricular fibrillation (VF). The benefit in patients with non-VF cardiac arrest is still not defined. METHODS: This prospective observational study was conducted in a university hospital setting with historical controls. Between 2002 and 2010 387 consecutive patients have been admitted to the intensive care unit (ICU) after cardiac arrest (control n=186; hypothermia n=201). Of those, in 175 patients the initial rhythm was identified as non-shockable (asystole, pulseless electrical activity) rhythm (control n=88; hypothermia n=87). Neurological outcome was assessed at ICU discharge according to the Pittsburgh cerebral performance category (CPC). A follow-up was completed for all patients after 90 days, a Kaplan-Meier analysis and Cox regression was performed. RESULTS: Hypothermia treatment was not associated with significantly improved neurological outcome in patients resuscitated from non-VF cardiac arrest (CPC 1-2: hypothermia 27.59% vs control 18.20%, p=0.175). 90-Day Kaplan-Meier analysis revealed no significant benefit for the hypothermia group (log rank test p=0.82), and Cox regression showed no statistically significant improvement. CONCLUSIONS: In this cohort patients undergoing hypothermia treatment after non-shockable cardiac arrest do not benefit significantly concerning neurological outcome. Hypothermia treatment needs to be evaluated in a large multicentre trial of cardiac arrest patients found initially to be in non-shockable rhythms to clarify whether cooling may also be beneficial for other rhythms than VF.

New insights into the management of hepato-renal syndrome.

Hepato-renal syndrome (HRS) is a serious complication in patients with advanced liver disease indicating a very poor prognosis. Nevertheless, effective treatment strategies have been introduced into clinical practice over the last decade. The combined treatment with terlipressin/albumin has been proven to be effective in most published studies and should be regarded as the standard of care. Norepinephrine or midodrine are possible alternatives when terlipressin is not available. Although there is presently not enough evidence to recommend extracorporeal liver support therapy as a standard procedure in patients with HRS, these concepts constitute promising options that need to be studied in prospective clinical trials.

Mild therapeutic hypothermia alters neuron specific enolase as an outcome predictor after resuscitation: 97 prospective hypothermia patients compared to 133 historical non-hypothermia patients.

INTRODUCTION: Neuron specific enolase (NSE) has been proven effective in predicting neurological outcome after cardiac arrest with a current cut off recommendation of 33 microg/l. However, most of the corresponding studies were conducted before the introduction of mild therapeutic hypothermia (MTH). Therefore we conducted a study investigating the association between NSE and neurological outcome in patients treated with MTH. METHODS: In this prospective observational cohort study the data of patients after cardiac arrest receiving MTH (n = 97) were consecutively collected and compared with a retrospective non-hypothermia (NH) group (n = 133). Serum NSE was measured 72 hours after admission to ICU. Neurological outcome was classified according to the Pittsburgh cerebral performance category (CPC 1 to 5) at ICU discharge. RESULTS: NSE serum levels were significantly lower under MTH compared to NH in univariate analysis. However, in a linear regression model NSE was affected significantly by time to return of spontaneous circulation (ROSC) and ventricular fibrillation rhythm but not by MTH. The model for neurological outcome identified NSE, NSE*MTH (interaction) as well as time to ROSC as significant predictors. Receiver Operating Characteristic (ROC) analysis revealed a higher cutoff value for unfavourable outcome (CPC 3 to 5) with a specificity of 100% in the hypothermia group (78.9 microg/l) compared to the NH group (26.9 microg/l). CONCLUSIONS: Recommended cutoff levels for NSE 72 hours after ROSC do not reliably predict poor neurological outcome in cardiac arrest patients treated with MTH. Prospective multicentre trials are required to re-evaluate NSE cutoff values for the prediction of neurological outcome in patients treated with MTH.

Treatment with granulocyte-macrophage colony-stimulating factor is associated with reduced indoleamine 2,3-dioxygenase activity and kynurenine pathway catabolites in patients with severe sepsis and septic shock.

The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) controls tryptophan metabolism and is induced by pro-inflammatory stimuli. We investigated whether immunostimulatory treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) influences IDO activity and tryptophan metabolism in sepsis. Thirty-six patients with severe sepsis/septic shock and sepsis-associated immunosuppression (assessed using monocytic human leukocyte antigen-DR (mHLA-DR) expression) were assessed in a controlled trial of GM-CSF or placebo treatment for 8 days. Using tandem mass spectrometry, levels of tryptophan, kynurenine, kynurenic acid, quinolinic acid, 5-hydroxytryptophan, serotonin, and estimated IDO activity were determined in a blinded fashion over a 9-day interval. At baseline, tryptophan and metabolite levels did not differ between the study groups. Although tryptophan levels were unchanged in both groups over the treatment interval (all p>0.8), IDO activity was markedly reduced after GM-CSF treatment (35.4 +/- 21.0 vs 21.6 +/-9.9 (baseline vs day 9), p = 0.02). IDO activity differed significantly between the 2 groups after therapy (p = 0.03). Metabolites downstream of IDO (kynurenine, quinolinic acid, kynurenic acid) were all induced in sepsis and declined in the GM-CSF group, but not in controls. Serotonin pathway metabolites remained unchanged in both groups (all p>0.15). Moreover, IDO activity correlated with procalcitonin (p< 0.0001, r = 0.56) and mHLA-DR levels (p = 0.005, r = -0.28) in the overall samples group. Thus, GM-CSF therapy is associated with decreased IDO activity and reduced kynurenine pathway catabolites in sepsis. This may be due to an improved antibacterial defence.

Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial.

RATIONALE: Sustained sepsis-associated immunosuppression is associated with uncontrolled infection, multiple organ dysfunction, and death. OBJECTIVES: In the first controlled biomarker-guided immunostimulatory trial in sepsis, we tested whether granulocyte-macrophage colony-stimulating factor (GM-CSF) reverses monocyte deactivation, a hallmark of sepsis-associated immunosuppression (primary endpoint), and improves the immunological and clinical course of patients with sepsis. METHODS: In a prospective, randomized, double-blind, placebo-controlled, multicenter trial, 38 patients (19/group) with severe sepsis or septic shock and sepsis-associated immunosuppression (monocytic HLA-DR [mHLA-DR] <8,000 monoclonal antibodies (mAb) per cell for 2 d) were treated with GM-CSF (4 microg/kg/d) or placebo for 8 days. The patients' clinical and immunological course was followed up for 28 days. MEASUREMENTS AND MAIN RESULTS: Both groups showed comparable baseline mHLA-DR levels (5,609 +/- 3,628 vs. 5,659 +/- 3,332 mAb per cell), which significantly increased within 24 hours in the GM-CSF group. After GM-CSF treatment, mHLA-DR was normalized in 19/19 treated patients, whereas this occurred in 3/19 control subjects only (P < 0.001). GM-CSF also restored ex-vivo Toll-like receptor 2/4-induced proinflammatory monocytic cytokine production. In patients receiving GM-CSF, a shorter time of mechanical ventilation (148 +/- 103 vs. 207 +/- 58 h, P = 0.04), an improved Acute Physiology and Chronic Health Evaluation-II score (P = 0.02), and a shorter length of both intrahospital and intensive care unit stay was observed (59 +/- 33 vs. 69 +/- 46 and 41 +/- 26 vs. 52 +/- 39 d, respectively, both not significant). Side effects related to the intervention were not noted. CONCLUSIONS: Biomarker-guided GM-CSF therapy in sepsis is safe and effective for restoring monocytic immunocompetence. Use of GM-CSF may shorten the time of mechanical ventilation and hospital/intensive care unit stay. A multicenter trial powered for the improvement of clinical parameters and mortality as primary endpoints seems indicated. Clinical trial registered with www.clinicaltrials.gov (NCT00252915).

Inferior vena cava diameter correlates with invasive hemodynamic measures in mechanically ventilated intensive care unit patients with sepsis.

Early optimization of fluid status is of central importance in the treatment of critically ill patients. This study aims to investigate whether inferior vena cava (IVC) diameters correlate with invasively assessed hemodynamic parameters and whether this approach may thus contribute to an early, non-invasive evaluation of fluid status. Thirty mechanically ventilated patients with severe sepsis or septic shock (age 60 +/- 15 years; APACHE-II score 31 +/- 8; 18 male) were included. IVC diameters were measured throughout the respiratory cycle using transabdominal ultrasonography. Consecutively, volume-based hemodynamic parameters were determined using the single-pass thermal transpulmonary dilution technique. This was a prospective study in a tertiary care academic center with a 24-bed medical intensive care unit (ICU) and a 14-bed anesthesiological ICU. We found a statistically significant correlation of both inspiratory and expiratory IVC diameter with central venous pressure (p = 0.004 and p = 0.001, respectively), extravascular lung water index (p = 0.001, p < 0.001, respectively), intrathoracic blood volume index (p = 0.026, p = 0.05, respectively), the intrathoracic thermal volume (both p < 0.001), and the PaO(2)/FiO(2) oxygenation index (p = 0.007 and p = 0.008, respectively). In this study, IVC diameters were found to correlate with central venous pressure, extravascular lung water index, intrathoracic blood volume index, the intrathoracic thermal volume, and the PaO(2)/FiO(2) oxygenation index. Therefore, sonographic determination of IVC diameter seems useful in the early assessment of fluid status in mechanically ventilated septic patients. At this point in time, however, IVC sonography should be used only in addition to other measures for the assessment of volume status in mechanically ventilated septic patients.

Establishment of an extracorporeal cardio-pulmonary resuscitation program in Berlin - outcomes of 254 patients with refractory circulatory arrest.

OBJECTIVE: Optimal management of out of hospital circulatory arrest (OHCA) remains challenging, in particular in patients who do not develop rapid return of spontaneous circulation (ROSC). Extracorporeal cardiopulmonary resuscitation (eCPR) can be a life-saving bridging procedure. However its requirements and feasibility of implementation in patients with OHCA, appropriate inclusion criteria and achievable outcomes remain poorly defined. DESIGN: Prospective cohort study. SETTING: Tertiary referral university hospital center. PATIENTS: Here we report on characteristics, course and outcomes on the first consecutive 254 patients admitted between August 2014 and December 2017. INTERVENTION: eCPR program for OHCA. MESUREMENTS AND MAIN RESULTS: A structured clinical pathway was designed and implemented as 24/7 eCPR service at the Charité in Berlin. In total, 254 patients were transferred with ongoing CPR, including automated chest compression, of which 30 showed or developed ROSC after admission. Following hospital admission predefined in- and exclusion criteria for eCPR were checked; in the remaining 224, 126 were considered as eligible for eCPR. State of the art postresuscitation therapy was applied and prognostication of neurological outcome was performed according to a standardized protocol. Eighteen patients survived, with a good neurological outcome (cerebral performance category (CPC) 1 or 2) in 15 patients. Compared to non-survivors survivors had significantly shorter time between collaps and start of eCPR (58 min (IQR 12-85) vs. 90 min (IQR 74-114), p = 0.01), lower lactate levels on admission (95 mg/dL (IQR 44-130) vs. 143 mg/dL (IQR 111-178), p <  0.05), and less severe acidosis on admission (pH 7.2 (IQR 7.15-7.4) vs. 7.0 (IQR6.9-7.2), p <  0.05). Binary logistic regression analysis identified latency to eCPR and low pH as independent predictors for mortality. CONCLUSION: An eCPR program can be life-saving for a subset of individuals with refractory circulatory arrest, with time to initiation of eCPR being a main determinant of survival.

Increased indoleamine 2,3-dioxygenase (IDO) activity and elevated serum levels of tryptophan catabolites in patients with chronic kidney disease: a possible link between chronic inflammation and uraemic symptoms.

BACKGROUND: Tryptophan (Trp) is catabolized by indoleamine 2,3-dioxygenase (IDO). Changes in Trp metabolism and IDO activity in chronic kidney disease (CKD) have not been widely studied, and the impact of haemodialysis is uncertain. Here we investigate Trp catabolism, IDO activity and the role of inflammation in moderate to very severe CKD and haemodialysis. METHODS: Eighty individuals were included in a prospective blinded endpoint analysis. Using tandem mass spectrometry, serum levels of Trp, kynurenine (Kyn), kynurenic-acid (Kyna), quinolinic-acid (Quin), 5-hydroxytryptophan (OH-Trp), serotonin (5-HT), estimated IDO activity and inflammatory markers were assessed in 40 CKD patients (age 57 +/- 14 years, 21 male, creatinine 4.5 +/- 2.7, n = 17 receiving haemodialysis), and in 40 healthy controls (age 34 +/- 9 years, 26 male). RESULTS: Trp levels were unchanged in CKD (P = 0.78 versus controls). Serum levels of Kyn, Kyna and Quin increased with CKD severity (stages 4, 5 versus controls all P < or = 0.01). IDO activity was significantly induced in CKD and correlated with disease severity (stages 3-5 versus controls, all P < or = 0.01) and inflammatory markers [high-sensitivity C-reactive protein (hsCRP), soluble TNF-receptor-1 (sTNFR-I); both P < or = 0.03]. IDO products (Kyn, Kyna, Quin) correlated also with hsCRP and sTNFR-I (all P < or = 0.04). Haemodialysis did not influence IDO activity (P = 0.26) and incompletely removed Kyn, Kyna, Quin, OH-Trp and 5-HT by 22, 26, 50, 44 and 34%, respectively. In multiple regression, IDO activity correlated with hsCRP and sTNFR-I (both P < or = 0.03) independent of serum creatinine, age and body weight. CONCLUSIONS: IDO activity and serum levels of tryptophan catabolites of the kynurenine pathway increase with CKD severity. In CKD, induction of IDO may primarily be a consequence of chronic inflammation.

Exercise capacity and body composition in living-donor renal transplant recipients over time.

BACKGROUND: Renal transplantation (RTx) restitutes the function of the failing organ and induces convalescence of the entire organism. Our study investigates whether this is accompanied by improvements in cardiovascular function and structural changes. METHODS: A total of 25 Caucasian patients (14 male, median age 44.2 +/- 9.2 years, BMI 23.7 +/- 4.0 kg/m(2)) were assessed in a prospective trial before, 1, 3 and 12 months after RTx from living donors by clinical examination, cardiopulmonary exercise testing, dual X-ray absorptiometry (DEXA) and analysis of plasma indices. RESULTS: Creatinine clearance improved from 8.0 +/- 3.1 to 60.9 +/- 18.1 mL/min at 1 month, but declined at 3 (51.6 +/- 16.3 mL/min) and 12 months (53.6 +/- 20.8 mL/min, P = 0.04 versus month 1). Body composition shifted from lean towards fat tissue (25.8 +/- 12.5-31.2 +/- 11.2% body fat content, P = 0.0001). Only baseline lean weight correlated with fat increase over time (r(2) = 0.28, P = 0.008). Patients with fat content above median (n = 13) had a 3-fold increased hazard ratio of infection (CI 1.04-9.41, P = 0.042) and overall hospitalization (hazard ratio 2.95, CI 1.10-7.93, P = 0.03). PeakVO(2) decreased over RTx (23.2 +/- 6.0- 17.6 +/- 5.1 mL/kg/min) and returned to baseline levels not until 1 year later (P < 0.001). After an initial decline, muscle oxidative capacity (peakVO(2)/lean mass) improved from 33.6 +/- 10.1 to 35.0 +/- 8.2 mL/kg/min at 12 months after RTx (P < 0.001). CONCLUSIONS: After RTx, body composition shifted continuously towards fat tissue, and baseline lean weight significantly correlated with fat increase over time. Both severe infections and hospitalizations are associated with a higher fat content before RTx. Exercise capacity (peakVO(2)) worsened after RTx and restitutes during follow-up, with muscle quality (peakVO(2)/lean) even exceeding baseline levels after 12 months.

Changes in serum creatinine in the first 24 hours after cardiac arrest indicate prognosis: an observational cohort study.

INTRODUCTION: As patients after cardiac arrest suffer from the consequences of global ischemia reperfusion, we aimed to establish the incidence of acute kidney injury (AKI) in these patients, and to investigate its possible association to severe hypoxic brain damage. METHODS: One hundred and seventy-one patients (135 male, mean age 61.6 +/- 15.0 years) after cardiac arrest were included in an observational cohort study. Serum creatinine was determined at admission and 24, 48 and 72 hours thereafter. Serum levels of neuron-specific enolase (NSE) were measured 72 hours after admission as a marker of hypoxic brain damage. Clinical outcome was assessed at intensive care unit (ICU) discharge using the Pittsburgh cerebral performance category (CPC). RESULTS: AKI as defined by AKI Network criteria occurred in 49% of the study patients. Patients with an unfavourable prognosis (CPC 3-5) were affected significantly more frequently (P = 0.013). Whilst serum creatinine levels decreased in patients with good neurological outcome (CPC 1 or 2) over the ensuing 48 hours, it increased in patients with unfavourable outcome (CPC 3-5). ROC analysis identified DeltaCrea24 <-0.19 mg/dl as the value for prediction with the highest accuracy. The odds ratio for an unfavourable outcome was 3.81 (95% CI 1.98-7.33, P = 0.0001) in cases of unchanged or increased creatinine levels after 24 hours compared to those whose creatinine levels decreased during the first 24 hours. NSE levels were found to correlate with the change in serum creatinine in the first 24 hours both in simple and multivariate regression (both r = 0.24, P = 0.002). CONCLUSIONS: In this large cohort of patient after cardiac arrest, we found that AKI occurs in nearly 50% of patients when the new criteria are applied. Patients with unfavourable neurological outcome are affected more frequently. A significant association between the development of AKI and NSE levels indicating hypoxic brain damage was observed. Our data show that changes in serum creatinine may contribute to the prediction of outcome in patients with cardiac arrest. Whereas a decline in serum creatinine (> 0.2 mg/dL) in the first 24 hours after cardiac arrest indicates good prognosis, the risk of unfavourable outcome is markedly elevated in patients with constant or increasing serum creatinine.

Organ crosstalk in critically ill patients: hemofiltration and immunomodulation in sepsis.

Despite substantial advances in our understanding of the pathogenesis of sepsis, the mortality of patients with severe sepsis/septic shock is unacceptably high. The potential role of extracorporeal therapies in the adjunctive treatment of sepsis is highly controversial. The present article reviews the current status of clinical research in this area. Conventional 'renal dose' continuous and discontinuous renal replacement technologies fail to achieve a biologically relevant reduction of target molecules. This may be accomplished by modified approaches, e.g. using high-dose protocols, high cut-off membranes, or (selective or unselective) adsorption techniques; however, their clinical value remains to be established by prospective studies using clinical end points.

Mild therapeutic hypothermia shortens intensive care unit stay of survivors after out-of-hospital cardiac arrest compared to historical controls.

INTRODUCTION: Persistent coma is a common finding after cardiac arrest and has profound ethical and economic implications. Evidence suggests that therapeutic hypothermia improves neurological outcome in these patients. In this analysis, we investigate whether therapeutic hypothermia influences the length of intensive care unit (ICU) stay and ventilator time in patients surviving out-of-hospital cardiac arrest. METHODS: A prospective observational study with historical controls was conducted at our medical ICU. Fifty-two consecutive patients (median age 62.6 years, 43 males, 34 ventricular fibrillation) submitted to therapeutic hypothermia after out-of-hospital cardiac arrest were included. They were compared with a historical cohort (n = 74, median age 63.8 years, 53 males, 43 ventricular fibrillation) treated in the era prior to hypothermia treatment. All patients received the same standard of care. Neurological outcome was assessed using the Pittsburgh cerebral performance category (CPC) score. Univariate analyses and multiple regression models were used. RESULTS: In survivors, therapeutic hypothermia and baseline disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] score) were both found to significantly influence ICU stay and ventilator time (all P < 0.01). ICU stay was shorter in survivors receiving therapeutic hypothermia (median 14 days [interquartile range (IQR) 8 to 26] versus 21 days [IQR 15 to 30] in the control group; P = 0.017). ICU length of stay and time on ventilator were prolonged in patients with CPC 3 or 4 compared with patients with CPC 1 or 2 (P = 0.003 and P = 0.034, respectively). Kaplan-Meier analysis showed improved probability for 1-year survival in the hypothermia group compared with the controls (log-rank test P = 0.013). CONCLUSION: Therapeutic hypothermia was found to significantly shorten ICU stay and time of mechanical ventilation in survivors after out-of-hospital cardiac arrest. Moreover, profound improvements in both neurological outcome and 1-year survival were observed.

Sepsis: time has come to focus on the later stages.

Despite numerous advances in intensive care medicine, sepsis remains a deadly disease. Today, conventional therapeutic approaches and mainstream scientific research mostly focus on symptomatic early goal directed organ support therapy. This includes fluid resuscitation, choice and timing of antibiotics and vasopressors, mechanical ventilation, and renal replacement strategies. Furthermore, great effort has been undertaken to investigate whether tightly controlled blood glucose levels, the application of corticosteroids, and early medication using activated protein C improves survival. However, most of these mainstream approaches have recently been shown unsuccessful in large-scale clinical trials. Current data now suggest that besides giving fluids, antibiotics, and symptomatic organ support, little - if at all - can be done to improve mortality from sepsis. This might be due to the fact that in the presence of modern intensive care medicine, most patients with severe sepsis or septic shock will survive the early "shock phase" of the disease. Mounting evidence suggests that in the course of the disease, most septic patients are then subjected to a secondary phase, which is characterised by a failure of cell-mediated immunity. This leads to repeated and uncontrolled infections, "chronic" multiple organ failure, and death in a large number of cases. Here we hypotheses that in order to profoundly influence survival from sepsis, future therapeutic efforts in the field should concentrate on this later "hypo-immune" stage of sepsis, associated immune phenomena, and novel immunomodulatory strategies. This may lead to the development of advanced immunomodulatory therapies available for widespread clinical use. Today, in the era of antibiotics and advanced organ system support therapy, it is not the bug that kills you- survival has become a matter of whether your cellular immune system can cope.

[Acute renal failure - how and when to treat?]. / Wann und wie behandeln? Therapiestrategien im Uberblick.

Acute renal failure is a common condition in intensive care units. The negative impact of acute renal failure on mortality has been demonstrated in recent studies. All critically ill patients should be regarded as a high risk population for renal failure. The optimization of intravasal fluid status and mean arterial pressure are preventive strategies in these patients. The use of nephrotoxic drugs (including radiocontrast media) should be avoided if possible. In cases of established acute renal failure today therapeutic strategies are still limited to best supportive care. The use of diuretics can facilitate fluid balance, however they seem to have an adverse effect on excretional renal function. A number of patients with acute renal failure need extracorporal renal support. Overload of potassium or fluids, severe acidosis, uremic pericarditis or uremic encephalopathy are urgent indications for the start of renal replacement therapy. Small randomized trials give some evidence that an early start of renal replacement therapy may be beneficial in critically ill patients. In this patient group renal replacement therapy should be considered when serum urea concentrations exceed 100mg/dl and/or when early signs of indications mentioned above are present. Large randomized multicenter trials have shown that a favourable effect on mortality can only be achieved when renal replacement therapy is supplied with a sufficient dose. Daily hemodialysis or continuous hemofiltration with a filtrate volume of 35ml/kg/h is regarded as a standard of care. There is still controversy whether continuous hemofiltration is superior to intermittent hemodialysis. Large meta-analyses could not show a difference in mortality with either one of the two therapy options.

[Prehospital management of geriatric patients]. / Der geriatrische Patient im Rettungsdienst - Besonderheiten der notärztlichen Versorgung.

The prehospital management of geriatric patients involves an understanding of the physiology of aging and necessitates the special acknowledgement of diagnosis and treatment of emergencies in the elderly. It is essential to keep in mind the prevention of an underestimation of the severity of disease and the necessity of an adequate therapy. The prehospital management of moribund patients gains special importance.

Visuo-spatial memory deficits following medial temporal lobe damage: A comparison of three patient groups.

The contributions of the hippocampal formation and adjacent regions of the medial temporal lobe (MTL) to memory are still a matter of debate. It is currently unclear, to what extent discrepancies between previous human lesion studies may have been caused by the choice of distinct patient models of MTL dysfunction, as disorders affecting this region differ in selectivity, laterality and mechanisms of post-lesional compensation. Here, we investigated the performance of three distinct patient groups with lesions to the MTL with a battery of visuo-spatial short-term memory tasks. Thirty-one subjects with either unilateral damage to the MTL (postsurgical lesions following resection of a benign brain tumor, 6 right-sided lesions, 5 left) or bilateral damage (10 post-encephalitic lesions, 10 post-anoxic lesions) performed a series of tasks requiring short-term memory of colors, locations or color-location associations. We have shown previously that performance in the association task critically depends on hippocampal integrity. Patients with postsurgical damage of the MTL showed deficient performance in the association task, but performed normally in color and location tasks. Patients with left-sided lesions were almost as impaired as patients with right-sided lesions. Patients with bilateral post-encephalitic lesions showed comparable damage to MTL sub-regions and performed similarly to patients with postsurgical lesions in the association task. However, post-encephalitic patients showed additional impairments in the non-associative color and location tasks. A strikingly similar pattern of deficits was observed in post-anoxic patients. These results suggest a distinct cerebral organization of associative and non-associative short-term memory that was differentially affected in the three patient groups. Thus, while all patient groups may provide appropriate models of medial temporal lobe dysfunction in associative visuo-spatial short-term memory, additional deficits in non-associative memory tasks likely reflect damage of regions outside the MTL. Importantly, the choice of a patient model in human lesion studies of the MTL significantly influences overall performance patterns in visuo-spatial memory tasks.

Weak diagnostic performance of troponin, creatine kinase and creatine kinase-MB to diagnose or exclude myocardial infarction after successful resuscitation.

BACKGROUND: The aim of this study is to evaluate the diagnostic accuracy of the cardiac injury markers troponin (TNT), creatine kinase (CK) and creatine kinase-MB (CK-MB) to diagnose or exclude acute myocardial infarction after cardiac arrest. METHODS: 226 patients who underwent diagnostic coronary angiography after sudden cardiac arrest were analyzed retrospectively. Levels of TNT, CK and CK-MB on admission and 6h, 24h and 36 h later were retrieved from the files and compared with the results of coronary angiography. RESULTS: Acute myocardial infarction (AMI) as well as non-AMI patients showed increasing levels of TNT and CK after resuscitation, although the AMI group showed significantly higher TNT and CK levels. Receiver operator curves were calculated to determine the diagnostic precision of TNT, CK and CK-MB to differentiate AMI and non-AMI patients. All analyzed markers yielded mediocre diagnostic precision with an area under the ROC curve of 0.7020, 0.6802 and 0.6508 for 6h TNT, CK and CK-MB, respectively. Applying a modified cut-off of 1 µg/l the 6h TNT measurement had a sensitivity of 70.9% and specificity of 61.2% to diagnose AMI after cardiac arrest. Using CK 800 U/l as cut-off level resulted in a sensitivity of 62.5% and specificity of 73.7%, CK-MB levels higher than 100 U/l yielded a sensitivity of 58.8% and specificity of 72.7%. CONCLUSION: Cardiac injury markers cannot be used to reliably diagnose or rule out AMI after resuscitation. Consequently we propose that indication for coronary angiography should be extended to all patients without a certain alternative diagnosis explaining the occurrence of cardiac arrest.

Duplex sonography of cerebral blood flow after cardiac arrest--a prospective observational study.

AIM: Despite successful resuscitation, cardiac arrest (CA) often has a poor clinical prognosis. Different diagnostic tools have been established to predict patients' outcome. However, their sensitivity remains low. Assessment of cerebral perfusion by duplex ultrasound might provide additional information regarding the extent of neuronal damage. The aim of the present study was to analyse the changes of global cerebral blood flow (CBF) and intracranial blood flow parameters in the acute stage after CA and its correlation with patients' outcome. METHODS: We investigated 54 patients (17-85 years, mean age: 63±17 years) after CA with return of spontaneous circulation on an intensive care unit. All patients received therapeutic hypothermia (TH) for 24 h after CA and reanimation. Serial measurements of CBF as well as intracranial blood flow velocities and pulsatility indices of the middle cerebral artery and the basal vein of Rosenthal were performed within the first 10 days using duplex ultrasound. Clinical outcome was measured using the Cerebral Performance Category. RESULTS: Measurements were successful in 53 patients. CBF values differed between 210 and 1100 ml/min. 24 patients (45%) attained a good outcome. No correlation between CBF or intracranial blood flow characteristics and outcome was found. Neither cerebral hypo- nor hyperperfusion was associated with a fatal outcome. CONCLUSION: Cerebral perfusion varies widely after CA. Neither hypo- nor hyperperfusion seems to be an independent risk factor for poor outcome. Duplex ultrasound of cerebral haemodynamics after CA is suitable but probably of limited prognostic value.