Survival in Immunocompromised Patients Ultimately Requiring Invasive Mechanical Ventilation: A Pooled Individual Patient Data Analysis.

Rationale: Acute respiratory failure (ARF) is associated with high mortality in immunocompromised patients, particularly when invasive mechanical ventilation is needed. Therefore, noninvasive oxygenation/ventilation strategies have been developed to avoid intubation, with uncertain impact on mortality, especially when intubation is delayed. Objectives: We sought to report trends of survival over time in immunocompromised patients receiving invasive mechanical ventilation. The impact of delayed intubation after failure of noninvasive strategies was also assessed. Methods: Systematic review and meta-analysis using individual patient data of studies that focused on immunocompromised adult patients with ARF requiring invasive mechanical ventilation. Studies published in English were identified through PubMed, Web of Science, and Cochrane Central (2008-2018). Individual patient data were requested from corresponding authors for all identified studies. We used mixed-effect models to estimate the effect of delayed intubation on hospital mortality and described mortality rates over time. Measurements and Main Results: A total of 11,087 patients were included (24 studies, three controlled trials, and 21 cohorts), of whom 7,736 (74%) were intubated within 24 hours of ICU admission (early intubation). The crude mortality rate was 53.2%. Adjusted survivals improved over time (from 1995 to 2017, odds ratio [OR] for hospital mortality per year, 0.96 [0.95-0.97]). For each elapsed day between ICU admission and intubation, mortality was higher (OR, 1.38 [1.26-1.52]; P < 0.001). Early intubation was significantly associated with lower mortality (OR, 0.83 [0.72-0.96]), regardless of initial oxygenation strategy. These results persisted after propensity score analysis (matched OR associated with delayed intubation, 1.56 [1.44-1.70]). Conclusions: In immunocompromised intubated patients, survival has improved over time. Time between ICU admission and intubation is a strong predictor of mortality, suggesting a detrimental effect of late initial oxygenation failure.

Characteristics and Outcome of Patients After Allogeneic Hematopoietic Stem Cell Transplantation Treated With Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

OBJECTIVES: The acute respiratory distress syndrome is a frequent condition following allogeneic hematopoietic stem cell transplantation. Extracorporeal membrane oxygenation may serve as rescue therapy in refractory acute respiratory distress syndrome but has not been assessed in allogeneic hematopoietic stem cell transplantation recipients. DESIGN: Multicenter, retrospective, observational study. SETTING: ICUs in 12 European tertiary care centers (Austria, Germany, France, and Belgium). PATIENTS: All allogeneic hematopoietic stem cell transplantation recipients treated with venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome between 2010 and 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-seven patients, nine of whom underwent noninvasive ventilation at the time of extracorporeal membrane oxygenation initiation, were analyzed. ICU admission occurred at a median of 146 (interquartile range, 27-321) days after allogeneic hematopoietic stem cell transplantation. The main reason for acute respiratory distress syndrome was pneumonia in 81% of patients. All but one patient undergoing noninvasive ventilation at extracorporeal membrane oxygenation initiation had to be intubated thereafter. Overall, seven patients (19%) survived to hospital discharge and were alive and in remission of their hematologic disease after a follow-up of 18 (range, 5-30) months. Only one of 24 patients (4%) initiated on extracorporeal membrane oxygenation within 240 days after allogeneic hematopoietic stem cell transplantation survived compared to six of 13 (46%) of those treated thereafter (p < 0.01). Fourteen patients (38%) experienced bleeding events, of which six (16%) were associated with fatal outcomes. CONCLUSIONS: Discouraging survival rates in patients treated early after allogeneic hematopoietic stem cell transplantation do not support the use of extracorporeal membrane oxygenation for acute respiratory distress syndrome in this group. On the contrary, long-term allogeneic hematopoietic stem cell transplantation recipients otherwise eligible for full-code ICU management may be potential candidates for extracorporeal membrane oxygenation therapy in case of severe acute respiratory distress syndrome failing conventional measures.

Thalamic involvement in patients with neurologic impairment due to Shiga toxin 2.

OBJECTIVE: The outbreak of hemolytic-uremic syndrome and diarrhea caused by Shiga toxin-producing Escherichia coli O104:H4 in Germany during May to July 2011 involved severe and characteristic neurologic manifestations with a strong female preponderance. Owing to these observations, we designed a series of experimental studies to evaluate the underlying mechanism of action of this clinical picture. METHODS: A magnetic resonance imaging and electroencephalographic study of patients was performed to evaluate the clinical picture in detail. Thereafter, combinations of different experimental settings, including electrophysiological and histological analyses, as well as calcium imaging in brain slices of rats, were conducted. RESULTS: We report on 7 female patients with neurologic symptoms and signs including bilateral thalamic lesions and encephalopathic changes indicative of a predominant involvement of the thalamus. Experimental studies in rats revealed an enhanced expression of the Shiga toxin receptor globotriaosylceramide on thalamic neurons in female rats as compared to other brain regions in the same rats and to male animals. Incubation of brain slices with Shiga toxin 2 evoked a strong membrane depolarization and intracellular calcium accumulation in neurons, associated with neuronal apoptosis, predominantly in the thalamic area. INTERPRETATION: These findings suggest that the direct cytotoxic effect of Shiga toxin 2 in the thalamus might contribute to the pathophysiology of neuronal complications in hemolytic-uremic syndrome.

Amiodarone-induced pulmonary toxicity--a fatal case report and literature review.

Amiodarone is a widely used and very potent antiarrhythmic substance. Among its adverse effects, pulmonary toxicity is the most dangerous without a causal treatment option. Due to a very long half-life, accumulation can only be prevented by strict adherence to certain dosage patterns. In this review, we outline different safe and proven dosing schemes of amiodarone and compare the incidence and description of pulmonary toxicity. Reason for this is a case of fatal pulmonary toxicity due to a subacute iatrogenic overdosing of amiodarone in a 74-year-old male patient with known severe coronary artery disease, congestive heart failure and ectopic atrial tachycardia with reduced function of kidneys and liver but without preexisting lung disease. Within 30 days, the patient received 32.2 g of amiodarone instead of 15.6 g as planned. Despite early corticosteroid treatment after fast exclusion of all other differential diagnoses, the patient died another month later in our intensive care unit from respiratory failure due to bipulmonal pneumonitis.

Influence of Red Blood Cell Storage Time on Clinical Course and Cytokine Profile in Septic Shock Patients.

BACKGROUND: Previous investigations have suggested beneficial effects of fresh versus stored red blood cell transfusion in critically ill patients. The present study investigates the effects of red blood cell storage time on the clinical course and hemodynamic and laboratory parameters in patients with septic shock. PATIENTS AND METHODS: 18 patients with septic shock received 2 erythrocyte units stored for ? 7 days (n = 8) or > 7 days (n = 10). The sequential organ failure assessment (SOFA) score was calculated for 7 days. Hemodynamic parameters (cardiac index, extravascular lung water) were determined using transpulmonary thermodilution. Laboratory parameters (lactate, base excess, C-reactive protein, procalcitonin, IL-1Β, IL-6, TNF-α, sVCAM-1, sICAM-1) were monitored before and 1, 3, 6, 12, 24, and 48 h after transfusion. The Mann-Whitney-U test and Neumann test were used for group comparison and trend assessment, respectively. RESULTS: We failed to observe significant differences with respect to SOFA scores between patients receiving fresh or stored erythrocytes. However, a significant trend towards an improvement in the SOFA score was found in the group receiving fresh erythrocytes (p < 0.01). No significant differences in hemodynamic or laboratory parameters were found between both groups. CONCLUSION: While the present findings do not provide clear-cut evidence supporting beneficial effects of fresh red blood cells in septic shock, they warrant larger randomized studies to confirm or refute such effects.

Veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe respiratory failure in adult cancer patients: a retrospective multicenter analysis.

PURPOSE: The question of whether cancer patients with severe respiratory failure benefit from veno-venous extracorporeal membrane oxygenation (vv-ECMO) remains unanswered. We, therefore, analyzed clinical characteristics and outcomes of a large cohort of cancer patients treated with vv-ECMO with the aim to identify prognostic factors. METHODS: 297 cancer patients from 19 German and Austrian hospitals who underwent vv-ECMO between 2009 and 2019 were retrospectively analyzed. A multivariable cox proportional hazards analysis for overall survival was performed. In addition, a propensity score-matched analysis and a latent class analysis were conducted. RESULTS: Patients had a median age of 56 (IQR 44-65) years and 214 (72%) were males. 159 (54%) had a solid tumor and 138 (47%) a hematologic malignancy. The 60-day overall survival rate was 26.8% (95% CI 22.1-32.4%). Low platelet count (HR 0.997, 95% CI 0.996-0.999; p = 0.0001 per 1000 platelets/µl), elevated lactate levels (HR 1.048, 95% CI 1.012-1.084; p = 0.0077), and disease status (progressive disease [HR 1.871, 95% CI 1.081-3.238; p = 0.0253], newly diagnosed [HR 1.571, 95% CI 1.044-2.364; p = 0.0304]) were independent adverse prognostic factors for overall survival. A propensity score-matched analysis with patients who did not receive ECMO treatment showed no significant survival advantage for treatment with ECMO. CONCLUSION: The overall survival of cancer patients who require vv-ECMO is poor. This study shows that the value of vv-ECMO in cancer patients with respiratory failure is still unclear and further research is needed. The risk factors identified in the present analysis may help to better select patients who may benefit from vv-ECMO.

Extracorporeal life support after failure of thrombolysis in pulmonary embolism.

INTRODUCTION: Fulminant pulmonary embolism (PE) may lead to cardiogenic shock or cardiac arrest with high mortality rates (65%) despite treatment with thrombolysis. Patients not responding to this therapy might benefit from extracorporeal life support (ECLS). Only occasional case reports of ECLS in PE patients are available. We studied the use of ECLS after thrombolysis in patients suffering from refractory cardiogenic shock due to PE. MATERIAL AND METHODS: Patients who were admitted to our university intensive care unit (ICU) with PE, not responding to throm-bolysis, and who received subsequent ECLS treatment were studied. RESULTS: 12 patients with severe PE were included. 6 patients were admitted by emergency medical services, 5 patients were transferred to the ICU from other hospitals and one patient presented at the emergency department by herself. 11 of 12 patients suffered from cardiac arrest and needed cardiopulmonary resuscitation (CPR) before ECLS implantation. Three ECLS were im-planted during CPR and nine ECLS were implanted during emergency conditions in patients with cardiogenic shock. All patients received thrombolysis before implementation of ECLS. Mean duration of ICU treatment was 22.4 ± 23.0 days. Mean duration of ECLS therapy was 5.6 ± 6.5 days. Bleeding complications occurred in four patients. Complications directly related to the ECLS system occurred in two patients (overall complication rate 42%). Overall, 6 of 12 patients (50%) survived. CONCLUSIONS: ECLS may be considered as abailout therapy in PE patients not responding to prior definitive treatment such as thrombolysis. ECLS therapy seems to be feasible with an acceptable complication rate even after thrombolysis.

Correction: Patients with Acute Myeloid Leukemia Admitted to Intensive Care Units: Outcome Analysis and Risk Prediction.

[This corrects the article DOI: 10.1371/journal.pone.0160871.].

Preterm birth but not mode of delivery is associated with an increased risk of developing inflammatory bowel disease later in life.

BACKGROUND: Exposure to bacterial antigens and other environmental factors in combination with a genetic susceptibility have been implicated in the etiology of inflammatory bowel disease (IBD). As certain perinatal circumstances, e.g., delivery by cesarean section, predispose to a different intestinal colonizations the aim of this analysis was to define a potential influence on the development of IBD in later life. METHODS: In a case-control study design, birth data were recorded from patients diagnosed with IBD (Crohn's disease [CD], n = 1,096; ulcerative colitis [UC], n = 763) and healthy controls ([C], n = 878) by a self-administered questionnaire. RESULTS: Preterm birth (CD: odds ratio [OR] 1.5 [95% confidence interval 1.1-2.0], UC: OR 1.3 [0.9-1.9]), mother's disease during pregnancy (CD: OR 1.9 [1.3-2.9], UC: OR 1.6 [1.0-2.4]), and disease in the first year of life (CD: OR 2.2 [1.6-2.9], UC: OR 1.7 [1.3-2.3]) are associated with the development of IBD in later life. No significant associations were found for the mode of delivery and breast feeding. In a logistic regression analysis female sex, smoking, appendectomy, maternal IBD, and disease in the first year of life were independently associated with CD. Female sex, appendectomy, and disease in the first year of life were independently associated with UC. CONCLUSIONS: Preterm birth and other perinatal circumstances are associated with the development of IBD, of which disease in the first year of life is an independent risk factor in multivariate analysis.

Apoptosis as a therapeutic tool in IBD?

Defective apoptosis of mucosal cell populations seems to be a relevant pathogenetic mechanism in inflammatory bowel disease (IBD). It has been suggested that the induction of apoptosis in various effector cells may be a relevant therapeutic mechanism in IBD. Indeed, it was shown that different drugs used for treatment of IBD have the capacity to induce apoptosis in T cells or monocytes in vitro and in vivo. However, it remains unclear whether these observations are related to clinical efficacy of these agents. TNF-alpha is one of the most relevant proinflammatory mediators in IBD and anti-TNF treatment has been shown to be of particular benefit for patients with IBD. It could subsequently be shown that various anti-TNF-alpha agents, such as infliximab and adalimumab, can induce apoptosis in activated monocytes and lymphocytes in vitro and in vivo. This mechanism requires reverse signaling via transmembranous TNF, thereby eliciting a signal transduction cascade that results in programmed cell death. Although other mechanisms might also contribute to the clinical effect of anti-TNF-alpha, current data suggest that apoptosis is a relevant mechanism that is associated with clinical efficacy of anti-TNF agents. Induction of apoptosis in activated monocytes or T cells may be regarded as therapeutic tool not only for anti-TNF agents, but also for other drugs used in IBD. Future strategies should focus on identification of mechanisms that prevent apoptosis in the mucosa of patients with IBD and in targeting apoptotic pathways as a therapeutic strategy in IBD.

Management of obese patients with respiratory failure - A practical approach to a health care issue of increasing significance.

In the general population, prevalence of obesity is increasing continuously. Concomitantly, a growing number of obese patients with severe illnesses presents at intensive care units (ICU). Particularly respiratory management of this patient group poses a challenge to intensive care physicians because of differences in respiratory anatomy and physiology in obese compared to non-obese individuals. Aim of this review is to present treatment options for critically ill obese patients requiring mechanical ventilation based on current studies concerning patient positioning, ventilatory regimen as well as extended therapy with veno-venous extracorporeal membrane oxygenation (ECMO). The ideal concept for respiratory management depends on multiple aspects and has to be determined individually. Knowledge of altered respiratory anatomy and physiology in obese patients and possible treatment options may facilitate respiratory management in this patient group.

Successful Use of Early Percutaneous Dilatational Tracheotomy and the No Sedation Concept in Respiratory Failure in Critically Ill Obese Subjects.

BACKGROUND: The prevalence of obesity in developed countries is rising. Currently, Europe has a prevalence of 9-30% with significant impact on public health systems. Obese patients in ICUs require special management and treatment. Altered anatomy in obese patients complicates procedures such as mechanical ventilation. Obesity affects cardiopulmonary physiology and requires elevated ventilation pressures. In our retrospective study, we determined the effect of early percutaneous dilatational tracheotomy (PDT) and cessation of sedation on respiratory parameters in severely obese subjects. METHODS: From June 2010 to July 2014, we included all subjects with a body weight of >130 kg (body mass index >35 kg/m(2)) and respiratory failure who were admitted to the medical ICU of the University Hospital of Münster. All subjects were treated with early PDT and immediate cessation of sedative drugs. We compared ventilator parameters and blood gas analysis before and after PDT. Parameters were recorded on days 0, 1, 3, and 5. Day 0 represents values during ventilation via an endotracheal tube, and days 1, 3, 5 represent values during ventilation via a tracheotomy tube. PDT was performed on day 0 after recording values during ventilation via an endotracheal tube. RESULTS: We included 23 subjects with a mean body mass index of 53.1 kg/m(2) and respiratory failure. After PDT and cessation of sedation, the required ventilation pressures and FIO2 could be rapidly reduced (P < .001), whereas blood gas parameters significantly improved. We observed no severe PDT-associated complications in our cohort. CONCLUSIONS: In severe obesity, respiratory failure might be increased by problems in mechanical ventilation due to required high pressures and obesity-induced pulmonary restriction. Rapid tracheotomy with reduction of dead-space ventilation and airway resistance as well as cessation of sedation to enable spontaneous breathing might be a key factor in the therapy of respiratory failure.

How rapid is rapid? Exemplary results of real-life rapid rule-out troponin timing in troponin-positive acute coronary syndromes without persistent ST-segment elevation in two contrasting German chest pain unit facilities.

AIM: To analyse the timing of cardiac troponin (cTn) measurements in high-risk and cTn-positive acute coronary syndromes without persistent ST-segment elevation (NSTE-ACS) in two structurally different German chest pain units (CPUs), contrasting an urban university maximum care and a rural regional primary care facility. METHODS: All patients encoded as NSTEMI during the year 2013 were retrospectively enrolled in two centres: site (I)--centre of maximum care in an urban university setting and site (II)--centre of primary care in a rural regional care setting. Data acquisition included time intervals from admission to baseline cTn and first and second cTn control as well as type and timing of invasive management. RESULTS: The median times (site I vs. site II) from admission to cTn result announcement were 26.5 vs. 33.0 min (p = 0.02) for baseline, 4 vs. 4 h (p = 0.43) for the first and 11.0 vs. 16.5 h (p = 0.03) for the second control. Timely announcement, as recommended by guidelines, was available in 86.9% at baseline, 59.4% for the first or 41.1% for the second cTn control. Rates and timing of invasive management were independent from the time point of positive cTn announcement (p = 0.51 and p = 0.68, respectively). CONCLUSIONS: German CPUs provide timely identification of cTn-positive patients in a narrow and guideline-adherent time frame using a rapid rule-out protocol. Especially, baseline and early cTn timing was comparable between the urban university maximum care and the rural regional primary care facility without relevant impact on guideline-conforming invasive management, underlining the high standard of care in those highly professional institutions.

Automated assessment of early hypoxic brain edema in non-enhanced CT predicts outcome in patients after cardiac arrest.

INTRODUCTION: Early prediction of potential neurological recovery in patients after cardiac arrest is challenging. Recent studies suggest that the densitrometic gray-white matter ratio (GWR) determined from cranial computed tomography (CT) scans may be a reliable predictor of poor outcome. We evaluated an automated, rater independent method to determine GWR in CT as an early objective imaging predictor of clinical outcome. METHODS: We analyzed imaging data of 84 patients after cardiac arrest that underwent noncontrast CT within 24h after arrest. To determine GWR in CT we applied two methods using a recently published automated probabilistic gray-white matter segmentation algorithm (GWR_aut) and conventional manual measurements within gray-white regions of interest (GWR_man). Neurological outcome was graded by the cerebral performance category (CPC). As part of standard routine CPC was assessed by the treating physician in the intensive care unit at admission and at discharge to normal ward. The performance of GWR measures (automated and manual) to predict the binary clinical endpoints of poor (CPC3-5) and good outcome (CPC1-2) was assessed by ROC analysis with increasing discrimination thresholds. Results of GWR_aut were compared to GWR_man of two raters. RESULTS: Of 84 patients, 55 (65%) showed a poor outcome. ROC curve analysis revealed reliable outcome prediction of GWR_aut (AUC 0.860) and GWR_man (AUC 0.707 and 0.699, respectively). Predictive power of GWR_aut was higher than GWR_man by each rater (p=0.019 and p=0.021, respectively) at an optimal cut-off of 1.084 to predict poor outcome (optimal criterion with 92.7% sensitivity, 72.4% specificity). Interrater reliability of GWR_man by intra-class correlation coefficient (ICC) was moderate (0.551). CONCLUSION: Automated quantification of GWR in CT may be used as an objective observer-independent imaging marker for outcome in patients after cardiac arrest.

Patients with Acute Myeloid Leukemia Admitted to Intensive Care Units: Outcome Analysis and Risk Prediction.

BACKGROUND: This retrospective, multicenter study aimed to reveal risk predictors for mortality in the intensive care unit (ICU) as well as survival after ICU discharge in patients with acute myeloid leukemia (AML) requiring treatment in the ICU. METHODS AND RESULTS: Multivariate analysis of data for 187 adults with AML treated in the ICU in one institution revealed the following as independent prognostic factors for death in the ICU: arterial oxygen partial pressure below 72 mmHg, active AML and systemic inflammatory response syndrome upon ICU admission, and need for hemodialysis and mechanical ventilation in the ICU. Based on these variables, we developed an ICU mortality score and validated the score in an independent cohort of 264 patients treated in the ICU in three additional tertiary hospitals. Compared with the Simplified Acute Physiology Score (SAPS) II, the Logistic Organ Dysfunction (LOD) score, and the Sequential Organ Failure Assessment (SOFA) score, our score yielded a better prediction of ICU mortality in the receiver operator characteristics (ROC) analysis (AUC = 0.913 vs. AUC = 0.710 [SAPS II], AUC = 0.708 [LOD], and 0.770 [SOFA] in the training cohort; AUC = 0.841 for the developed score vs. AUC = 0.730 [SAPSII], AUC = 0.773 [LOD], and 0.783 [SOFA] in the validation cohort). Factors predicting decreased survival after ICU discharge were as follows: relapse or refractory disease, previous allogeneic stem cell transplantation, time between hospital admission and ICU admission, time spent in ICU, impaired diuresis, Glasgow Coma Scale <8 and hematocrit of ≥25% at ICU admission. Based on these factors, an ICU survival score was created and used for risk stratification into three risk groups. This stratification discriminated distinct survival rates after ICU discharge. CONCLUSIONS: Our data emphasize that although individual risks differ widely depending on the patient and disease status, a substantial portion of critically ill patients with AML benefit from intensive care.

Impact of d-Dimers on the Differential Diagnosis of Acute Chest Pain: Current Aspects Besides the Widely Known.

d-dimers are cleavage products of fibrin that occur during plasmin-mediated fibrinolysis of blood clots. In the emergency department, d-dimer measurement represents a valuable and cost-effective tool in the differential diagnosis of acute chest pain including the main life-threatening entities: acute coronary syndrome, pulmonary embolism, and acute aortic syndrome. Whereas the diagnostic and prognostic values of d-dimer testing in acute coronary syndrome is of less priority, increases of d-dimers are frequently found in venous thromboembolism and acute aortic syndromes, especially acute aortic dissection. As to the high negative predictive value of d-dimer in those disorders, patients with low to intermediate pretest probability may profit in terms of less necessity of further non-invasive or even invasive imaging, simultaneously reducing potential complications and healthcare-related costs. However, because of the low specificity of the different d-dimer tests in contrast to its frequent usage, adequate interpretation is required. Age-related adjustment of d-dimer levels may be used to increase its diagnostic power.

Impact of preexisting chronic kidney disease on acute and long-term outcome of critically ill patients on a medical intensive care unit.

BACKGROUND: Chronic kidney disease (CKD) increases acute and long-term mortality of many diseases. Limited data are available, in how far a preexisting non-dialysis dependent CKD affects the outcome of critically ill patients treated for non-renal causes. METHODS: In a retrospective study, we assessed the outcome of 524 patients with need for mechanical ventilation at our medical intensive care unit between 2002 and 2007. Patients were divided into 5 CKD stages depending on their calculated glomerular filtration rate at hospital admission excluding patients with pre-existing end-stage renal failure. In-hospital and long-term outcome up to 5 years were assessed. RESULTS: Advanced stages of CKD at admission were associated with higher age (p < 0.001) and diabetes (p = 0.003). Patients with higher CKD stages suffered more often from acute renal failure (p < 0.001), required longer renal replacement therapy (p < 0.001) and more often in-hospital resuscitation (p = 0.019). 405 patients died during follow-up (226 in-hospital). Multivariate Cox regression analysis identified eGFR as independent predictor of 30-day- (HRR 0.994, 95 % CI 0.990-0.998) and 1-year-mortality (HRR 0.996, 95 % CI 0.993-1.000). Long-term survival decreased significantly with increasing CKD stages (p = 0.004) and occurrence of acute renal failure (p < 0.001). CONCLUSIONS: In critically ill patients requiring mechanical ventilation, preexisting non-dialysis dependent CKD has marked impact on occurrence of acute renal failure, 30-day- and 1-year-mortality.

Predictors and outcome of early-onset pneumonia after out-of-hospital cardiac arrest.

BACKGROUND: Early-onset pneumonia (EOP) after out-of-hospital cardiac arrest is frequently observed. Causative factors are loss of airway protection during cardiac arrest, pulmonary contusion, and emergency airway management. We assessed the incidence, risk factors, and clinical course of EOP, and evaluated the impact of an early exchange of the prehospitally inserted endotracheal tube (ETT). METHODS: In our retrospective analysis we included 104 consecutive subjects admitted to our ICU after out-of-hospital cardiac arrest between 2007 and 2012. All subjects underwent therapeutic hypothermia. We analyzed clinical course, inflammation indicators, Clinical Pulmonary Infection Score, occurrence of EOP, duration of ventilatory support, microbiological findings, and short-term outcome. RESULTS: Of the 104 subjects, 46.2% received an exchange of ETT directly after hospital admission. Neither ETT exchange nor observed aspiration were associated with elevated CPIS or EOP, nor with proof of microorganisms in respiratory secretions. We found no differences in duration of ventilatory support, P(aO2)/F(IO2), ICU days, or outcome. C-reactive protein was significantly higher in subjects with aspiration (P = .046). Sex, age, smoking status, aspiration, cause of cardiac arrest, first detected heart rhythm, and use of supraglottic airways devices were not associated with EOP. Subjects with EOP had a longer need for ventilatory support (P = .005), higher tracheotomy rate (P = .03), longer ICU stay (P = .005), higher C-reactive protein (P < .001), higher body temperature (P = .003), higher Clinical Pulmonary Infection Score (P < .001), and lower P(aO2)/F(IO2) (P = .008). CONCLUSIONS: The rate of EOP was not significantly influenced by the exchange of the preclinically inserted ETT, but was associated with longer need for mechanical ventilation and ICU stay.

Impact of copeptin on diagnosis, risk stratification, and intermediate-term prognosis of acute coronary syndromes.

BACKGROUND: The aim of the current study was to evaluate the diagnostic and intermediate-term prognostic impact of C-terminal portion of provasopressin (copeptin) in combination with troponin I. METHODS: In this prospective single-center study we recruited a total of 230 unselected patients with suspected recent acute coronary syndrome (ACS) presenting consecutively at our chest pain unit. Troponin I and copeptin levels were determined at presentation and after 3-6 h. Follow-up was performed after 180 days. RESULTS: Acute myocardial infarction (AMI) was the final diagnosis in 107 patients (STEMI: 24, NSTEMI: 83). The median copeptin level was significantly higher in patients having AMI than in those without (20.83 vs. 12.2 pmol/L, p < 0.0001). A troponin I level <0.04 ng/mL in combination with copeptin <14 pmol/L at admission ruled out AMI with an negative predictive value (NPV) of 97.3 %. p = 0.0045 for the added value of copeptin to troponin I. Kaplan-Meier analysis showed that copeptin levels above the diagnostic cut-off were associated with an elevated intermediate-term (180 days) mortality (p = 0.019), while no patient with copeptin values below the cut-off died. Univariate Cox regression analysis identified copeptin as strong predictor of intermediate-term mortality (HR 4.28, 95 % CI 1.58-11.6, p = 0.004). The predictive performance for prediction of 180-day mortality was significantly better if copeptin was included (C-index of 0.80) compared with that of troponin alone (C-index 0.78, p = 0.01 for the added value of copeptin to troponin I). CONCLUSIONS: Additional assessment of copeptin allows a rapid and reliable exclusion of AMI and improves diagnostic accuracy in myocardial ischemia. This study showed for the first time that copeptin provides valuable predictive information for risk stratification and intermediate-term outcome in ACS patients.