Abstract: ABSTRACT: BACKGROUND: Neuron specific enolase (NSE) has repeatedly been evaluated for neurological prognostication in patients after cardiac arrest. However, it is unclear whether current guidelines for NSE cutoff levels also apply to cardiac arrest patients treated with hypothermia. Thus, we investigated the prognostic significance of absolute NSE levels and NSE kinetics in cardiac arrest patients treated with hypothermia. METHODS: In a prospective study of 35 patients resuscitated from cardiac arrest, NSE was measured daily for four days following admission. Outcome was assessed at ICU discharge using the CPC score. All patients received hypothermia treatment for 24 hours at 33 degrees C with a surface cooling device according to current guidelines. RESULTS: The cutoff for absolute NSE levels in patients with unfavourable outcome (CPC 3-5) 72 hours after cardiac arrest was 57 ug/l with an area under the curve (AUC) of 0.82 (sensitivity 47%, specificity 100%). The cutoff level for NSE kinetics in patients with unfavourable outcome (CPC 3-5) was an absolute increase of 7.9 ug/l (AUC 0.78, sensitivity 63%, specificity 100%) and a relative increase of 33.1% (AUC 0.803, sensitivity 67%, specificity 100%) at 48 hours compared to admission. CONCLUSION: In cardiac arrest patients treated with hypothermia, prognostication of unfavourable outcome by NSE kinetics between admission and 48 hours after resuscitation may be superior to prognostication by absolute NSE levels.
Abstract: Prehospital induction of therapeutic hypothermia after cardiac arrest may require temperature monitoring in the field. Tympanic temperature is non-invasive and frequently used in clinical practice. Nevertheless, it has not yet been evaluated in patients undergoing mild therapeutic hypothermia (MTH). Therefore, a prospective observational study was conducted comparing three different sites of temperature monitoring during therapeutic hypothermia.
Abstract: 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.
Abstract: 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.
Abstract: Mild hypothermia treatment (32-34°C) in survivors after cardiac arrest (CA) is clearly recommended by the current guidelines. The effects of cooling procedure towards QT interval have not been evaluated so far outside of case series. In a prospective study 34 consecutive survivors after cardiac arrest were continuously monitored with Holter ECG over the first 48 h.
Abstract: 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.
Abstract: 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.
Abstract: Therapeutic hypothermia has been proven to be effective in improving neurological outcome in patients after cardiac arrest due to ventricular fibrillation (VF). Data concerning the effect of hypothermia treatment on long-term survival however is limited.
Abstract: 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.
Abstract: Bilateral absent N20 responses of median nerve somatosensory evoked potentials (SEPs) reliably predict poor prognosis after cardiac arrest. However, the studies supporting this fact were carried out before hypothermia was established as standard treatment. Recent evidence suggests that hypothermia treatment affects the predictive value of clinical findings in cardiac arrest patients, raising the question whether the predictive value of N20 responses has changed as well.
Abstract: 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.
Abstract: BACKGROUND: With the recent introduction of therapeutic hypothermia the application of sedation becomes necessary in cardiac arrest patients. We therefore analysed the usefulness of the Glasgow coma score (GCS) for outcome prediction in survivors of cardiac arrest treated with therapeutic hypothermia. PATIENTS AND METHODS: In a prospective observational study we identified 72 comatose patients admitted to our intensive care unit after cardiac arrest. All patients were treated with therapeutic hypothermia. After sedation stop the Glasgow coma scale (GCS) was recorded until day 4. Neurological outcome was assessed using the Pittsburgh cerebral performance category (CPC) score. RESULTS: Forty-four of 72 patients (61%) were discharged with a favourable neurological outcome (CPC 1+2). GCS was significantly higher in patients with good outcome compared to patients with unfavourable outcome at every point in time after sedation stop (p<0.001). The value for prediction of good outcome with the highest accuracy was a GCS>4 at the first day after sedation stop (sensitivity 61%, PPV 90% and AUC 0.808) and GCS>6 in the following days (sensitivity 84%, PPV 92.5% and AUC 0.921 at day 4). In particular a score of >3 on the motor component of the GCS predicted good outcome with a specificity of 100% (sensitivity 43%) at the first day. CONCLUSIONS: Our results indicate that monitoring of the GCS is a simple and reliable method for clinical outcome assessment in patients treated with therapeutic hypothermia. Thus, GCS monitoring remains a powerful tool to predict outcome of patients treated with therapeutic hypothermia.
Abstract: ABSTRACT: INTRODUCTION: A rare side effect of antipsychotic medication is neuroleptic malignant syndrome, mainly characterized by hyperthermia, altered mental state, haemodynamic dysregulation, elevated serum creatine kinase and rigor. There may be multi-organ dysfunction including renal and hepatic failure as well as serious rhabdomyolysis, acute respiratory distress syndrome and disseminated intravascular coagulation. The prevalence of neuroleptic malignant syndrome is between 0.02% and 2.44% for patients taking neuroleptics and it is not necessary to fulfil all cardinal features characterizing the syndrome to be diagnosed with neuroleptic malignant syndrome. Because of other different life-threatening diseases matching the various clinical findings, the correct diagnosis can sometimes be hard to make. A special problem of intensive care treatment is the management of severe hyperthermia. Lowering of body temperature, however, may be a major clinical problem because hyperthermia in neuroleptic malignant syndrome is typically unresponsive to antipyretic agents while manual cooling proves difficult due to peripheral vasoconstriction. CASE PRESENTATION: A 22-year-old Caucasian man was admitted unconscious with a body temperature of 42degreesC, elevated serum creatine phosphokinase, tachycardia and hypotonic blood pressure. In addition to intensive care standard therapy for coma and shock, a non-invasive cooling device (Arctic Sun 2000(R), Medivance Inc., USA), originally designed to induce mild therapeutic hypothermia in patients after cardiopulmonary resuscitation, was used to lower body temperature. After successful treatment it became possible to obtain information from the patient about his recent ambulant treatment with Olanzapin (Zyprexa(R)) for schizophrenia. CONCLUSION: Numerous case reports have been published about patients who developed neuroleptic malignant syndrome due to Olanzapin (Zyprexa(R)) medication. Frequently hyperthermia has been observed in these cases with varying outcomes. In our case the only residual impairment for the patient is dysarthria with corresponding symmetric cerebellar pyramidal cell destruction demonstrated by increased signal intensity in T2-weighted magnetic resonance imaging, most likely caused by the excessive hyperthermia.
Abstract: Abdominal infections are associated with significant morbidity and mortality. Nearly all bacteria causing abdominal infections are derived from the endogenous flora of the alimentary tract. The resulting infection is typically polymicrobial and comprised of both aerobic and anaerobic microbes. They can be classified by their severity as uncomplicated and complicated or by their origin as community or hospital acquired. Escherichia coli and Bacteroides fragilis are the most frequently isolated bacteria in community-acquired abdominal infections. Nosocomial infections typically involve a more resistant flora (e.g. Pseudomonas spp., Acinetobacter spp., Gram-negative bacilli producing extended-spectrum beta-lactamases [ESBL], vancomycin-resistant enterococci [VRE] and methicillin-resistant Staphylococcus aureus [MRSA]). Antimicrobial therapy should be guided by microbiological testing and frequently requires other interventions as well. In uncomplicated infections antimicrobial prophylaxis for < 24h may be considered. Patients with underlying or acquired immunodeficiency, i.e. organ transplant recipients and other patients on complex immunosuppressant regimens require special attention and antimicrobial coverage. We discuss the relevant microbiota, a rational diagnostic and therapeutic approach including strategies to handle challenging infections. The application of novel compounds and/or drug classes for abdominal infections such as glycylcyclines (i.e. tigecycline), glycopeptides (i.e. dalbavancin, telavancin, oritavancin), carbapenems (i.e. doripenem), and forth generation cephalosporins (i.e. ceftaroline, ceftobiprole) as well as patents on metalloproteinase and caspase inhibitors, interleukin antagonists, fusion proteins and nitric oxide donators is critically reviewed. The information is summarized in flow charts and algorithms for use in daily clinical practice and the review article also shows the useful information of the patents for the treatment of abdominal infections.
Abstract: 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).
Abstract: BACKGROUND: The aim of the study was to report the impact of our hypothermia protocol on survival and neurological outcome. Furthermore, we were interested in the risk of bleeding complications in patients with acute myocardial infarction (AMI) being treated with percutaneous coronary revascularisation (PCI) and therapeutic hypothermia. METHODS AND RESULTS: In a prospective observational study we identified 31 comatose patients (25 male, age 65+/-13 years) admitted to our intensive care unit with out-of-hospital cardiac arrest due to AMI who were treated with hypothermia. They were compared to 31 historical age- and gender-matched controls (25 male, age 65+/-12 years) admitted after out-of-hospital cardiac arrest due to AMI in the era prior to hypothermia treatment. Peak creatinine kinase-MB was 118 U/L (94-248) in the hypothermia group and 131 U/L (98-257) in controls (p=0.51). In the hypothermia group, 19 patients were discharged with a favourable neurological outcome, whereas in controls, such outcome was observed in only six patients (p=0.002). In both groups, haemoglobin values and platelet counts declined during the first 48 h (all p<0.001). No differences regarding bleeding complications (p=1.0), transfusion requirements (p=1.0), and the number of transfusions (p=0.9) were observed between the groups. CONCLUSIONS: A major improvement in neurological outcome was observed in patients treated with hypothermia. Our results indicate that the combination of reperfusion strategies and the application of hypothermia do not carry an excessive risk of bleeding complications. Patients with AMI and out-of-hospital cardiac arrest should receive the optimal therapy for both conditions, that is, either thrombolysis or PCI and therapeutic hypothermia.
Abstract: 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.
Abstract: 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.
Abstract: A rare side effect of antipsychotic medication is neuroleptic malignant syndrome, mainly characterized by hyperthermia, altered mental state, haemodynamic dysregulation, elevated serum creatine kinase and rigor. There may be multi-organ dysfunction including renal and hepatic failure as well as serious rhabdomyolysis, acute respiratory distress syndrome and disseminated intravascular coagulation. The prevalence of neuroleptic malignant syndrome is between 0.02% and 2.44% for patients taking neuroleptics and it is not necessary to fulfil all cardinal features characterizing the syndrome to be diagnosed with neuroleptic malignant syndrome. Because of other different life-threatening diseases matching the various clinical findings, the correct diagnosis can sometimes be hard to make. A special problem of intensive care treatment is the management of severe hyperthermia. Lowering of body temperature, however, may be a major clinical problem because hyperthermia in neuroleptic malignant syndrome is typically unresponsive to antipyretic agents while manual cooling proves difficult due to peripheral vasoconstriction.
Abstract: 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.
Abstract: OBJECTIVES: Interleukin-6 (IL-6) is involved in inflammatory diseases, provides prognostical information, and allows the early identification and monitoring of septic patients. We investigated whether IL-6 can be assessed using a new densitometric point-of-care (POC) bedside assay. DESIGN AND METHODS: 392 samples were prospectively collected from 57 intensive care unit patients (38 male, age: 45.2 +/- 16.9years, APACHE II score: 25.4 +/- 4.8). Blinded IL-6 measurements were performed using conventional semiautomatic enzyme-linked immunosorbent assays (ELISA) and the POC test. RESULTS: Mean IL-6 levels were 102.9 +/- 388.6pg/mL (ELISA) and 97.0 +/- 535.5 (POC). A significant correlation was found (p < 0.0001, r = 0.92). The sensitivity/specificity for sepsis was 82.6%/86.5% (ELISA, AUC: 0.881), and 76.4%/95.0% (POC, AUC: 0.868). CONCLUSIONS: Here we demonstrate significant correlations of IL-6 levels determined using a POC test and semiautomatic ELISA. ROC analyses revealed no significant differences between the two tests. With a turn-around time of 20min, the bedside IL-6 test is a new tool that may help to initiate early goal-directed therapy.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: BACKGROUND: Animal studies suggest that the induction of therapeutic hypothermia in patients after cardiac arrest should be initiated as soon as possible after ROSC to achieve optimal neuroprotective benefit. A "gold standard" for the method of inducing hypothermia quickly and safely has not yet been established. In order to evaluate the feasibility of a hypothermia cap we conducted a study for the prehospital setting. METHODS AND RESULTS: The hypothermia cap was applied to 20 patients after out-of-hospital cardiac arrest with a median of 10 min after ROSC (25/75 IQR 8-15 min). The median time interval between initiation of cooling and hospital admission was 28 min (19-40 min). The median tympanic temperature before application of the hypothermia cap was 35.5 degrees C (34.8-36.3). Until hospital admission we observed a drop of tympanic temperature to a median of 34.4 degrees C (33.6-35.4). This difference was statistically significant (P < 0.001). We could not observe any side effects related to the hypothermia cap. 25 patients who had not received prehospital cooling procedures served as a control group. Temperature at hospital admission was 35.9 degrees C (35.3-36.4). This was statistically significant different compared to patients treated with the hypothermia cap (P < 0.001). CONCLUSIONS: In summary we demonstrated that the prehospital use of hypothermia caps is a safe and effective procedure to start therapeutic hypothermia after cardiac arrest. This approach is rapidly available, inexpensive, non-invasive, easy to learn and applicable in almost any situation.
Abstract: 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.
Abstract: Severe liver dysfunction may lead to impairment of renal function without an underlying renal pathology. This phenomenon is called hepatorenal syndrome (HRS), which is associated with a poor prognosis showing a median survival of less than 2 months if renal replacement therapy is necessary. Liver transplantation is the best therapeutic option to regain renal function, but because of poor survival, these patients often die before transplantation. Herein we report a 37-year-old patient with ethyl-toxic liver cirrhosis who underwent hemodialysis due to HRS type I for more than 8 months. After living donor liver transplantation, diuresis immediately resumed, renal function soon recovered, and intermittent hemodialysis was stopped at 18 days after transplantation. Renal function was stable with a serum creatinine <2 mg/dL during the last 5 years posttransplantation. As far as we know, only a few cases of an anuric patient suffering from HRS have been reported with a survival beyond 8 months and full recovery of renal function after liver transplantation. This underlined that renal replacement therapy in HRS should be considered as a possible bridging method to liver transplantation even for longer periods.
Abstract: ABSTRACT: We report a case of fulminant multiple organ failure including the Acute Respiratory Distress Syndrome (ARDS), haemodynamic, and renal failure due to community-acquired methicillin-sensitive Panton Valentine Leukocidin (PVL) positive spa-type 284 (ST121) Staphylococcus aureus septic shock. The patient's first clinical symptom was necrotizing pneumonia. Despite organism-sensitive triple antibiotic therapy with linezolid, imipenem and clindamycin from the first day of treatment, progressive abscess formation in multiple skeletal muscles was observed. As a result, repeated surgical interventions became necessary. Due to progressive soft tissue infection, the anti-microbial therapy was changed to a combination of clindamycin and daptomycin. Continued surgical and antimicrobial therapy finally led to a stabilisation of the patients' condition. The clinical course of our patient underlines the existence of a "PVL-syndrome" which is independent of in vitro Staphylococcus aureus susceptibility. The PVL-syndrome should not only be considered in patients with soft tissue or bone infection, but also in patients with pneumonia. Such a condition, which may easily be mistaken for uncomplicated pneumonia, should be treated early, aggressively and over a long period of time in order to avoid relapsing infection.
Abstract: We describe a case of a 41-year-old female patient who was admitted with typical signs of thrombotic-thrombocytopenic purpura. Markers of myocardial ischemia (Troponin T, CK, CK-MB) were even present at admission without symptoms of angina pectoris. Only a few hours after admission the patient developed all signs of cardiogenic shock with subsequently cardiac arrest. Postmortal coronary angiographies showed occlusions in all coronary arteries with significant myocardial necrosis. We are unaware of any report that describes macrovascular occlusions in thrombotic-thrombocytopenic purpura.
Abstract: Group A streptococcal necrotizing fasciitis is a rare disease associated with high mortality. Since severe toxic shock syndrome is a common complication, only immediate and aggressive surgical intervention, adequate antimicrobial therapy and supportive intensive care can be life-saving. We report about successful treatment of a 60-year old patient with necrotizing fasciitis and multiple organ failure.
Abstract: AIMS: We hypothesized that chronic heart failure as a model of systemic hypoxia may result in systemic inflammation. The signs of a systemic inflammatory response should disappear after successful mechanical circulatory support using biventricular assist device systems. METHODS AND RESULTS: Plasma levels of cytokines (IL-6, IL-8, TNF-alpha) and soluble adhesion molecules (sVCAM, sE-, sL-, sP-Selectin) were determined in samples obtained from patients with chronic heart failure NYHA classes II-III, patients with overt cardiogenic shock before and after implantation of a mechanical assist-device system ('Berlin Heart') and in patients with coronary artery disease as a control. Elevated levels of cytokines and soluble adhesion molecules could be observed in patients with cardiogenic shock, although slightly decreased levels of soluble adhesion molecules were also detectable in patients with chronic heart failure NYHA classes II-III. The signs of systemic inflammation disappeared following successful mechanical circulatory support, but persisted in patients who developed infectious complications. CONCLUSIONS: Our data suggest that a systemic hypoxic and inflammatory syndrome is manifested during end-stage heart failure, such as in patients with sepsis or who have suffered non-infectious insults. During mechanical circulatory support, elevated levels of inflammatory mediators may be indicative of persistent peripheral hypoxia associated with a high risk for infection or sepsis. Therefore, the monitoring of inflammatory mediators should be evaluated as markers of the effectiveness of this therapy.
Abstract: Persistently elevated levels of cytokines (IL-6, IL-8) during the course of mechanical circulatory support correlated well with fatal outcome. To determine the influence of blood/artificial surface interaction on the chronic inflammatory process, we studied the biocompatibility of silicone and polyurethane membranes in vitro. Cultures of isolated mononuclear cells or whole blood were incubated for 24 hours in tubes coated with silicone or polyurethane, both used in the construction of ventricular assist systems. Concentrations of several inflammatory mediators were measured in the supernatant. Our results can be summarized as follows: a) Monocytes were stimulated to release inflammatory cytokines like IL-8 and MIP-1 alpha, particularly when silicone was involved; b) Both silicone and polyurethane stimulated thrombocytes thus resulting in the release of P-Selectin and PDGF-AB, although polyurethane was a stronger stimulus; c) Moderate complement activation was triggered by contact with either of the artificial surfaces. However, the prevention of most of these effects by coating the artificial surface with protein and the lack of correlation between in vitro data and serum levels of IL-6 and IL-8 during the course of circulatory support suggest that the persistence of inflammatory cytokines during BVAD support is not caused by blood/surface interaction.
Abstract: We studied the plasma levels of TNF-alpha, IL-6, IL-8 and soluble adhesion molecules (sE-Selectin, sL-Selectin, sVCAM-1) immediately before and during mechanical circulatory support with a Biventricular Assist Device System (BVAD-"Berlin Heart") in comparison to patients with chronic heart failure (NYHA classes II/III) and patients with coronary artery disease with normal ventricular function. Additionally, the biocompatibility of the membranes used in the "Berlin Heart" was tested in vitro. IL-6 and IL-8 but not TNF-alpha could only be detected in patients with cardiogenic shock immediately before starting circulatory support. Furthermore, plasma concentrations of soluble adhesion molecules were statistically significantly elevated in patients with cardiogenic shock compared to patients with coronary artery disease. This picture of a systemic inflammatory response syndrome without significant level of TNF-alpha looks quite similar to that seen in patients following trauma and severe operations. During mechanical circulatory support plasma levels of cytokines and soluble adhesion molecules dropped to low levels in patients, who were successfully maintained on BVAD. By contrast, we have found persistently elevated levels of these mediators in patients with fatal outcome. This seems not to be the result of individual distinct response of blood cells to contact with the artificial surfaces of the device. In summary, our data suggest the development of a systemic inflammatory response syndrome may be due to hypoxia during cardiogenic shock. Persistence of systemic inflammation suggests failing of the mechanical support. Therefore, the monitoring of inflammatory mediators may be relevant as a prognostic marker in these patients (disappearance of peripheral hypoxia).
Abstract: OBJECTIVE: To determine whether the serum concentrations of some circulating cytokines (as highly sensitive markers of inflammation) are of value in predicting the outcome of patients with cardiogenic shock and end-stage heart disease, who undergo ventricular assist device implantation until heart transplantation. DESIGN: Cohort study. SETTING: University teaching hospitals. PATIENTS: Twenty patients with cardiogenic shock or end-stage heart disease were consecutively selected for this study, if assist device implantation was performed as a bridge to heart transplantation. MEASUREMENTS AND MAIN RESULTS: The circulating concentrations of the cytokines interleukin (IL)-1 beta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha were monitored from the beginning to the end of assist device support two to three times a week, using commercial enzyme-linked immunosorbent assays (ELISA). In all patients, circulating IL-6 and IL-8 values were increased shortly after assist device implantation. In patients with uncomplicated courses, IL-6 and IL-8 concentrations decreased after an initial increase and were low at the time of transplantation, whereas serum cytokine concentrations increased and remained increased in the nonsurvivors (survivors vs. nonsurvivors, p < .001). Circulating IL-1 beta and TNF-alpha concentrations were rarely detectable. CONCLUSIONS: Monitoring of IL-6 and IL-8 values during ventricular assist device support provides a means of early identification of high-risk patients that may allow optimization of antimicrobial therapy and selection of the appropriate time for transplantation.
