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Background Galactomannan antigen (GM) testing is widely used in the diagnosis of invasive aspergillosis (IA). Digestive enzymes play an important role in enzyme substitution therapy in exocrine pancreatic insufficiency. As digestive enzymes of fungal origin like Nortase contain enzymes from Aspergillus, a false-positive result of the test might be possible because of cross-reacting antigens of the cell wall of the producing fungi. We, therefore, asked whether the administration of fungal enzymes is a relevant cause of false-positive GM antigen test results. Methods Patients with a positive GM antigen test between January 2016 and April 2020 were included in the evaluation and divided into two groups: group 1—Nortase-therapy, group 2—no Nortase-therapy. In addition, dissolved Nortase samples were analyzed in vitro for GM and β-1,3-D-glucan. For statistical analysis, the chi-squared and Mann‒Whitney U tests were used. Results Sixty-five patients were included in this evaluation (30 patients receiving Nortase and 35 patients not receiving Nortase). The overall false positivity rate of GM testing was 43.1%. Notably, false-positive results were detected significantly more often in the Nortase group (73.3%) than in the control group (17.1%, p Conclusions Our data demonstrate that the administration of digestive enzymes of fungal origin like Nortase leads to a significantly higher rate of false-positive GM test results compared to that in patients without digestive enzyme treatment.

Accumulating evidence suggests that a patient subgroup with severe COVID-19 develops a cytokine release syndrome leading to capillary leakage and organ injury. Recent publications addressing therapy of cytokine storms recommended new extracorporeal therapies such as hemoadsorption. This case report describes a 59-year-old SARS-CoV-2-positive patient with severe ARDS. Due to severe hyperinflammation with concomitant hemodynamic instability and progressive renal failure, combination of continuous renal replacement and CytoSorb® hemoadsorption therapy was initiated. Treatment resulted immediately in a control of the hyperinflammatory response. Simultaneously, lung function continued to improve accompanied by profound hemodynamic stabilization. We report the successful utilization of CytoSorb® hemoadsorption in the treatment of a patient with SARS-CoV-2-induced cytokine storm syndrome.

We read with interest the recently described affections of the GI system in coronavirus disease (COVID-19).1 2 In addition to the effects on the gut, mild abnormalities in liver aminotransferase levels have been observed.3 4 We here report a previously non-described severe liver failure in a patient with COVID-19. A 65-year-old man was admitted to our emergency department with fever up to 40°C, dry cough and dyspnoea. The chest CT scan showed typical features of COVID-19, such as ground-glass opacities and peripheral consolidations. A throat swab confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Aminotransferase concentrations were slightly increased (alanine aminotransferase (ALT) 69 U/L and aspartate aminotransferase (AST) 92 U/L; upper limit of normal (ULN) ≤49 U/L). He had been receiving long-term treatment with hydrochlorothiazide and ramipril for arterial hypertension as sole medications and had no history of liver disease. The patient was admitted to the isolation ward and was given supplementary oxygen. He received piperacillin/tazobactam and azithromycin according to hospital standards, as well as paracetamol (1 g, up to two times per day). …

(1) Background: Extracorporeal membrane oxygenation (ECMO) therapy in intensive care units (ICUs) remains the last treatment option for Coronavirus disease 2019 (COVID-19) patients with severely affected lungs but is highly resource demanding. Early risk stratification for the need of ECMO therapy upon admission to the hospital using artificial intelligence (AI)-based computed tomography (CT) assessment and clinical scores is beneficial for patient assessment and resource management, (2) Methods: Retrospective single-center study with 95 confirmed COVID-19 patients admitted to the participating ICUs. Patients requiring ECMO therapy (n = 14) during ICU stay versus patients without ECMO treatment (n = 81) were evaluated for discriminative clinical prediction parameters and AI-based CT imaging features and their diagnostic potential to predict ECMO therapy. Reported patient data include clinical scores, AI-based CT findings and patient outcomes, (3) Results: Patients subsequently allocated to ECMO therapy had significantly higher sequential organ failure (SOFA) scores (p &lt, 0.001) and significantly lower oxygenation indices on admission (p = 0.009) than patients with standard ICU therapy. The median time from hospital admission to ECMO placement was 1.4 days (IQR 0.2–4.0). The percentage of lung involvement on AI-based CT assessment on admission to the hospital was significantly higher in ECMO patients (p &lt, 0.001). In binary logistic regression analyses for ECMO prediction including age, sex, body mass index (BMI), SOFA score on admission, lactate on admission and percentage of lung involvement on admission CTs, only SOFA score (OR 1.32, 95% CI 1.08–1.62) and lung involvement (OR 1.06, 95% CI 1.01–1.11) were significantly associated with subsequent ECMO allocation. Receiver operating characteristic (ROC) curves showed an area under the curve (AUC) of 0.83 (95% CI 0.73–0.94) for lung involvement on admission CT and 0.82 (95% CI 0.72–0.91) for SOFA scores on ICU admission. A combined parameter of SOFA on ICU admission and lung involvement on admission CT yielded an AUC of 0.91 (0.84–0.97) with a sensitivity of 0.93 and a specificity of 0.84 for ECMO prediction, (4) Conclusions: AI-based assessment of lung involvement on CT scans on admission to the hospital and SOFA scoring, especially if combined, can be used as risk stratification tools for subsequent requirement for ECMO therapy in patients with severe COVID-19 disease to improve resource management in ICU settings.

BACKGROUND Posaconazole and itraconazole are commonly used for systemic antifungal prophylaxis after lung transplantation. The aim of this study on critically ill lung transplant recipients was to assess the rate of adequate plasma concentrations and the frequency of fungal-induced transitions from antifungal prophylaxis to therapy after the administration of either posaconazole or itraconazole for systemic prophylaxis. METHODS Critically ill lung transplant recipients with postoperative posaconazole or itraconazole prophylaxis and therapeutic drug monitoring from February 2016 to November 2019 were retrospectively included in the study. Positive fungal cultures or Aspergillus antigen tests resulting in a transition from antifungal prophylaxis to therapy were analyzed from the first day of prophylaxis until 7 days after the last sample for each patient. Adequate plasma concentrations were defined as ≥500 µg/L for itraconazole and ≥700 µg/L for posaconazole. RESULTS Two hundred seventy-five samples from 73 patients were included in the analysis. Overall, 60% of the posaconazole and 55% of the itraconazole concentrations were subtherapeutic. Administration of posaconazole suspension resulted significantly (P

Purpose SARS-COV-2 infection can develop into a multi-organ disease. Although pathophysiological mechanisms of COVID-19-associated myocardial injury have been studied throughout the pandemic course in 2019, its morphological characterisation is still unclear. With this study, we aimed to characterise echocardiographic patterns of ventricular function in patients with COVID-19-associated myocardial injury. Methods We prospectively assessed 32 patients hospitalised with COVID-19 and presence or absence of elevated high sensitive troponin T (hsTNT+ vs. hsTNT-) by comprehensive three-dimensional (3D) and strain echocardiography. Results A minority (34.3%) of patients had normal ventricular function, whereas 65.7% had left and/or right ventricular dysfunction defined by impaired left and/or right ventricular ejection fraction and strain measurements. Concomitant biventricular dysfunction was common in hsTNT+ patients. We observed impaired left ventricular (LV) global longitudinal strain (GLS) in patients with myocardial injury (-13.9% vs. -17.7% for hsTNT+ vs. hsTNT-, p = 0.005) but preserved LV ejection fraction (52% vs. 59%, p = 0.074). Further, in these patients, right ventricular (RV) systolic function was impaired with lower RV ejection fraction (40% vs. 49%, p = 0.001) and reduced RV free wall strain (-18.5% vs. -28.3%, p = 0.003). Myocardial dysfunction partially recovered in hsTNT + patients after 52 days of follow-up. In particular, LV-GLS and RV-FWS significantly improved from baseline to follow-up (LV-GLS: -13.9% to -16.5%, p = 0.013; RV-FWS: -18.5% to -22.3%, p = 0.037). Conclusion In patients with COVID-19-associated myocardial injury, comprehensive 3D and strain echocardiography revealed LV dysfunction by GLS and RV dysfunction, which partially resolved at 2-month follow-up. Trial registration COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.

Background: Myocardial injury, defined by elevated troponin levels, is associated with adverse outcome in patients with coronavirus disease 2019 (COVID-19). The frequency of cardiac injury remains highly uncertain and confounded in current publications; myocarditis is one of several mechanisms that have been proposed. Methods: We prospectively assessed patients with myocardial injury hospitalized for COVID-19 using transthoracic echocardiography, cardiac magnetic resonance imaging, and endomyocardial biopsy. Results: Eighteen patients with COVID-19 and myocardial injury were included in this study. Echocardiography revealed normal to mildly reduced left ventricular ejection fraction of 52.5% (46.5%–60.5%) but moderately to severely reduced left ventricular global longitudinal strain of −11.2% (−7.6% to −15.1%). Cardiac magnetic resonance showed any myocardial tissue injury defined by elevated T1, extracellular volume, or late gadolinium enhancement with a nonischemic pattern in 16 patients (83.3%). Seven patients (38.9%) demonstrated myocardial edema in addition to tissue injury fulfilling the Lake-Louise criteria for myocarditis. Combining cardiac magnetic resonance with speckle tracking echocardiography demonstrated functional or morphological cardiac changes in 100% of investigated patients. Endomyocardial biopsy was conducted in 5 patients and revealed enhanced macrophage numbers in all 5 patients in addition to lymphocytic myocarditis in 1 patient. SARS-CoV-2 RNA was not detected in any biopsy by quantitative real-time polymerase chain reaction. Finally, follow-up measurements of left ventricular global longitudinal strain revealed significant improvement after a median of 52.0 days (−11.2% [−9.2% to −14.7%] versus −15.6% [−12.5% to −19.6%] at follow-up; P =0.041). Conclusions: In this small cohort of COVID-19 patients with elevated troponin levels, myocardial injury was evidenced by reduced echocardiographic left ventricular strain, myocarditis patterns on cardiac magnetic resonance, and enhanced macrophage numbers but not predominantly lymphocytic myocarditis in endomyocardial biopsies.

BACKGROUND In a pandemic situation the overall mortality rate is of considerable interest; however, these data must always be seen in relation to the given healthcare system and the availability of local level of care. A recently published German data evaluation of more than 10,000 COVID-19 patients treated in 920 hospitals showed a high mortality rate of 22% in hospitalized patients and of more than 50% in patients requiring invasive ventilation. Because of the high infection rates in Bavaria, a large number of COVID-19 patients with considerable severity of disease were treated at the intensive care units of the LMU hospital. The LMU hospital is a university hospital and a specialized referral center for the treatment of patients with acute respiratory distress syndrome (ARDS). OBJECTIVE Data of LMU intensive care unit (ICU) patients were systematically evaluated and compared with the recently published German data. METHODS Data of all COVID-19 patients with invasive and noninvasive ventilation and with completed admission at the ICU of the LMU hospital until 31 July 2020 were collected. Data were processed using descriptive statistics. RESULTS In total 70 critically ill patients were included in the data evaluation. The median SAPS II on admission to the ICU was 62~points. The median age was 66 years and 81% of the patients were male. More than 90% were diagnosed with ARDS and received invasive ventilation. Treatment with extracorporeal membrane oxygenation (ECMO) was necessary in 10% of the patients. The median duration of ventilation was 16 days, whereby 34.3% of patients required a tracheostomy. Of the patients 27.1% were transferred to the LMU hospital from external hospitals with reference to our ARDS/ECMO program. Patients from external hospitals had ARDS of higher severity than the total study population. In total, nine different substances were used for virus-specific treatment of COVID-19. The most frequently used substances were hydroxychloroquine and azithromycin. Immunomodulatory treatment, such as Cytosorb® (18.6%) and methylprednisolone (25.7%) were also frequently used. The overall in-hospital mortality rate of ICU patients requiring ventilation was 28.6%. The mortality rates of patients from external hospitals, patients with renal replacement therapy and patients with ECMO therapy were 47.4%, 56.7% and 85.7%, respectively. CONCLUSION The mortality rate in the ventilated COVID-19 intensive care patients was considerably different from the general rate in Germany. The data showed that treatment in an ARDS referral center could result in a lower mortality rate. Low-dose administration of steroids may be another factor to improve patient outcome in a preselected patient population. In the authors' opinion, critically ill COVID-19 patients should be treated in an ARDS center provided that sufficient resources are available.

Objectives Beta-lactam antibiotics are often subject to therapeutic drug monitoring, but breakpoints of target attainment are mostly based on expert opinions. Studies that show a correlation between target attainment and infection resolution are missing. This analysis investigated whether there is a difference in infection resolution based on two breakpoints of target attainment. Methods An outcome group out of 1392 critically ill patients treated with meropenem or piperacillin-tazobactam was formed due to different selection criteria. Afterwards, three groups were created: group 1=free drug concentration (f) was < 100% of the time (T) above the minimal inhibitory concentration (MIC) (< 100% fT >MIC), group 2=100% fT >MIC<4xMIC, and group 3=100% fT >4xMIC. Parameters for infection control, renal and liver function, and estimated and observed in-hospital mortality were compared between those groups. Statistical analysis was performed with one-way analysis of variance, Tukey post hoc test, U test, and bivariate logistic regression. Results The outcome group consisted of 55 patients (groups 1–3, 17, 24, and 14 patients, respectively). Patients allocated to group 2 or 3 had a significantly faster reduction of the C-reactive protein in contrast to patients allocated to group 1 (p = 0.033 and p = 0.026). Patients allocated to group 3 had a worse renal function, a higher Acute Physiology and Chronic Health Evaluation (APACHE II) score, were older, and had a significantly higher in-hospital mortality compared to group 1 (p = 0.017) and group 2 (p = 0.001). The higher mortality was significantly influenced by worse liver function, higher APACHE II, and higher Sequential Organ Failure Assessment (SOFA) score and norepinephrine therapy. Conclusion Achieving the target 100% fT >MIC leads to faster infection resolution in the critically ill. However, there was no benefit for patients who reached the highest target of 100% fT >4xMIC, although the mortality rate was higher possibly due to confounding effects. In conclusion, we recommend the target 100% fT >MIC<4xMIC for critically ill patients. Trial registration NCT03985605

Immunosuppression leaves transplanted patients at particular risk for severe acute respiratory syndrome 2 (SARS‐CoV‐2) infection. The specific features of coronavirus disease 2019 (COVID‐19) in immunosuppressed patients are largely unknown and therapeutic experience is lacking. Seven transplanted patients (two liver, three kidneys, one double lung, one heart) admitted to the Ludwig‐Maximilians‐University Munich because of COVID‐19 and tested positive for SARS‐CoV‐2 were included. The clinical course and the clinical findings were extracted from the medical record. The two liver transplant patients and the heart transplant patient had an uncomplicated course and were discharged after 14, 18 and 12 days, respectively. Two kidney transplant recipients were intubated within 48 hours. One kidney and the lung transplant recipients were required to intubate after ten and 15 days, respectively. Immunosuppression was adapted in five patients, but continued in all patients. Compared to non‐transplanted patients at the ICU (n=19) the inflammatory response was attenuated in transplanted patients, which was proven by decreased IL‐6 blood values. This analysis might provide evidence that continuous immunosuppression is safe and probably beneficial since there was no hyperinflammation evident. Although transplanted patients might be more susceptible to an infection with SARS‐CoV‐2, their clinical course seems to be similar to immunocompetent patients.

Various studies have reported insufficient beta-lactam concentrations in critically ill patients. The extent to which therapeutic drug monitoring (TDM) in clinical practice can reduce insufficient antibiotic concentrations is an ongoing matter of investigation. We retrospectively evaluated routine meropenem and piperacillin measurements in critically ill patients who received antibiotics as short infusions in the first year after initiating a beta-lactam TDM program. Total trough concentrations above 8.0 mg/L for meropenem and above 22.5 mg/L for piperacillin were defined as the breakpoints for target attainment. We included 1832 meropenem samples and 636 piperacillin samples. We found that 39.3% of meropenem and 33.6% of piperacillin samples did not reach the target concentrations. We observed a clear correlation between renal function and antibiotic concentration (meropenem, r = 0.53, piperacillin, r = 0.63). Patients with renal replacement therapy or creatinine clearance (CrCl) of &lt, 70 mL/min had high rates of target attainment with the standard dosing regimens. There was a low number of patients with a CrCl &gt, 100 mL/min that achieved the target concentrations with the maximum recommended dosage. Patients with impaired renal function only required TDM if toxic side effects were noted. In contrast, patients with normal renal function required different dosage regimens and TDM-guided therapy to reach the breakpoints of target attainment.

In recent years, there has been mounting evidence on the clinical importance of body composition, particularly obesity and sarcopenia, in various patient populations. However, the relevance of these pathologic conditions remains controversial, especially in the field of traumatology. Computed tomography-based measurements allow clinicians to gain a prompt and thorough assessment of fat and muscle compartments in trauma patients. Our aim was to investigate whether CT-based anthropometric parameters of fat and muscle tissues show correlations with key elements of pre-hospital and clinical care in an adult population with multiple trauma. In this retrospective analysis we searched our institutional records of the German Trauma Registry (TraumaRegister DGU®) from January 2008 to May 2014. Included were 297 adult trauma patients with multiple trauma who underwent a whole-body CT-scan on admission and were treated in an ICU. We measured anthropometric determinants of abdominal core muscle and adipose tissue using the digital imaging software OsiriX™. Multivariate linear and logistic regression analyses were conducted to unveil potential correlations. None of the obesity-linked anthropometric parameters were associated with longer pre-hospital or initial ED treatment times. Obese patients were less frequently intubated at the site of the accident. Patients with increased abdominal fat tissue received on average lower volumes during fluid resuscitation in the pre-hospital phase but were not more often in shock on admission. During ED treatment, fluid resuscitation and transfusion volumes were not affected by abdominal fat tissue, although transfusion rates were higher in the obese. Furthermore, damage control surgeries took place less frequently in patients with increased abdominal fat tissue markers. Obesity parameters did not affect the prevalence of sepsis, although increased abdominal fat was associated with higher white blood cell counts on admission. Finally, there was no statistically significant correlation between sarcopenia or obesity markers and duration of mechanical ventilation, ICU length of stay or neurologic outcome. CT-based assessment of abdominal fat and muscle mass is a simple method in revealing pathologic body composition in trauma patients. Our study suggests that obesity influences pre-hospital and ED treatment and early immune response in multiple trauma. Nevertheless, we could not demonstrate any significant effect of abdominal fat and muscle tissue parameters on the course of treatment, in particular the duration of mechanical ventilation, ICU length of stay and neurologic outcome.

Obesity leads to better survival in critically ill patients. Although there are several studies confirming this thesis, the "obesity paradox" is still surprising from the clinician's perspective. One explanation for the "obesity paradox" is the fact that the body mass index (BMI), which is used in almost all clinical evaluations to determine weight categories, is not an appropriate measure of fat and skeletal muscle mass and its distribution in critically ill patients. In addition, height and weight are frequently estimated rather than measured. Central obesity has been identified in many disorders as an independent risk factor for an unfavourable outcome. The first clues are to be found in intensive care. Along with obesity, an individual's entire muscle mass is a variable that has an influence on outcome. Central obesity can be measured relatively easily with an abdominal calliper, but the calculation of muscle mass is more complex. A valid and detailed measurement of this can be obtained using computed tomography (CT) images, acquired during routine care. For future clinical observation or interventional studies, single cross-sectional CT is a more sophisticated tool for measuring patients' anthropometry than a measuring tape and callipers. Patients with sarcopenic obesity, for example, who may be at a particular risk, can only be identified using imaging procedures such as single cross-sectional CT. Thus, BMI should take a back seat as an anthropometric tool, both in the clinic and in research.

(1) Background: To assess the value of chest CT imaging features of COVID-19 disease upon hospital admission for risk stratification of invasive ventilation (IV) versus no or non-invasive ventilation (non-IV) during hospital stay. (2) Methods: A retrospective single-center study was conducted including all patients admitted during the first three months of the pandemic at our hospital with PCR-confirmed COVID-19 disease and admission chest CT scans (n = 69). Using clinical information and CT imaging features, a 10-point ordinal risk score was developed and its diagnostic potential to differentiate a severe (IV-group) from a more moderate course (non-IV-group) of the disease was tested. (3) Results: Frequent imaging findings of COVID-19 pneumonia in both groups were ground glass opacities (91.3%), consolidations (53.6%) and crazy paving patterns (31.9%). Characteristics of later stages such as subpleural bands were observed significantly more often in the IV-group (52.2% versus 26.1%, p = 0.032). Using information directly accessible during a radiologist’s reporting, a simple risk score proved to reliably differentiate between IV- and non-IV-groups (AUC: 0.89 (95% CI 0.81–0.96), p &lt, 0.001). (4) Conclusions: Information accessible from admission CT scans can effectively and reliably be used in a scoring model to support risk stratification of COVID-19 patients to improve resource and allocation management of hospitals.

Tobacco use after lung transplantation is associated with adverse outcome. Therefore, active smoking is regarded as a contraindication for lung transplantation and should be excluded prior to placement on the waiting list. The aim of the study was to compare self-reporting with a systematic cotinine based screening approach to identify patients with active nicotine abuse. Nicotine use was systematically assessed by interviews and cotinine test in all lung transplant candidates at every visit in our center. Patients were classified according to the stage prior to transplantation and cotinine test results were compared to self-reports and retrospectively analyzed until June 2019. Of 620 lung transplant candidates, 92 patients (14.8%) had at least one positive cotinine test. COPD as underlying disease (OR 2.102, CI 1.110-3.981; p = 0.023), number of pack years (OR 1.014, CI 1.000-1.028; p = 0.047) and a time of cessation less than one year (OR 2.413, CI 1.410-4.128; p = 0.001) were associated with a positive cotinine test in multivariable regression analysis. The majority of non-COPD patients (n = 13, 72.2%) with a positive test had a cessation time of less than one year. 78 patients (84.7%) falsely declared not consuming any nicotine-based products prior to the test. Finally, all never smokers were test negative. In conclusion, our data demonstrate that active nicotine use is prevalent in transplant candidates with a high prevalence of falsely declaring nicotine abstinence. COPD was the main diagnosis in affected patients. Short cessation time and a high number of pack years are risk factors for continued nicotine abuse.

Background: Recent scientific work proved that knowledge about body composition beyond the body mass index is essential. Both adipose tissue and muscular status are determining risk factors of morbidity and mortality. Analysis of single cross-sectional computed tomography (CT) images, acquired during routine care only to prevent additional radiation exposure, provide a detailed insight into the body composition of chronically and critically ill patients. Methods: This retrospective study included 490 trauma patients of whom a whole-body multiple detector CT scan was acquired at admission. From a single cross-sectional CT, we compared eight diametric and planimetric techniques for the assessment of core muscle mass as well as visceral and subcutaneous adipose tissue. Furthermore, we derived formulas for converting the measurement results of various techniques into each other. Results: For intra- and interobserver reliability, we obtained intraclass correlation coefficients (ICCs) ranging from 0.947 to 0.997 (intraobserver reliability) and from 0.850 to 0.998 (interobserver reliability) for planimetric measurements. Diametric techniques conferred lower ICCs with 0.851–0.995 and 0.833–0.971, respectively. Overall, area-based measurements of abdominal adipose tissue yielded highly correlated results with diametric measures of obesity. For example, the Pearson correlation of visceral adipose tissue and sagittal abdominal diameter was 0.87 for male and 0.82 for female patients. Planimetric and diametric muscle measurements correlated best for lean psoas area and bilateral diametric measurement of the psoas with a Pearson correlation of 0.90 and 0.93 for male and female patients, respectively. Conclusion: Planimetric measurements should remain the gold standard to describe fat and muscle compartments. Diametric measurements could however serve as a surrogate if planimetric techniques are not readily available or feasible as for example in large registries.

Background Careful patient selection is the prerequisite to raise transplant benefit. In lung transplant (LT) candidates, the effect of body mass index (BMI) on postoperative outcome remains controversial, possibly due to the inaccuracy of BMI in discriminating between fat and muscle mass. We therefore hypothesized that assessment of body composition by muscle mass measures is more accurate than by BMI regarding postoperative outcome. Methods All LT recipients from 2011 to 2014 were included and retrospectively analyzed. Lean psoas area (LPA) was assessed from pretransplant computed tomography scans, and associations with postoperative outcomes were investigated. Results Included were 103 consecutive LT recipients with a mean pre-LT BMI of 22.0 ± 4.0 kg/m 2 and a mean LPA of 22.3 ± 8.3 cm 2 . LPA was inversely associated with length of mechanical ventilation ( p = 0.03), requirement of tracheostomy ( p = 0.035), and length of stay in the intensive care unit ( p = 0.02), while controlling for underlying disease, BMI, sex, age, and procedure; in contrast, BMI was not ( p = 0.25, p = 0.54, and p = 0.42, respectively.). Multiple regression analysis revealed that the 6-minute walk distance at the end of pulmonary rehabilitation was significantly associated with LPA ( p = 0.02). Conclusions LPA can easily be assessed in LT candidates as part of pretransplant evaluation and was significantly associated with short-term outcome, whereas BMI was not. Assessment of LPA may provide additional information on body composition beyond BMI. However, the clinical utility has to be further evaluated.

Acute pulmonary hypertension with life-threatening right heart failure may complicate the postoperative course following cardiothoracic surgery. Both inhaled nitric oxide and inhaled iloprost, a stable analogue of prostacyclin, have been used frequently for this purpose in acute pulmonary hypertension of various origins. We present a case of a patient with acute pulmonary hypertension and severely impaired gas exchange following pulmonary thrombo-endarterectomy. Therapy with one inhaled vasodilator alone did not satisfactorily abort a postoperative pulmonary hypertensive crisis and low-output syndrome due to right heart failure. Combined inhaled nitric oxide and inhaled iloprost, however, showed additive effects. Hence, the combination of both drugs may be reasonable in cases where the standard therapy fails. The effect has been demonstrated by means of continuous blood gas monitoring.

Objectives: Vasopressor-induced vasoconstriction may compromise renal and splanchnic blood flow in patients with septic shock, resulting in secondary organ failures. The authors compared the effects of the vasodilatatory agent dopexamine against renal-dose dopamine and placebo in patients with norepinephrine therapy and septic shock, using 24-hour serum creatinine clearance (C crea ) as a major endpoint. The primary hypothesis to be tested was that dopexamine is more effective than dopamine and that dopamine shows better effects than placebo regarding organ failures and C crea . Design: A prospective, randomized, controlled, double-blinded study. Setting: Intensive care unit in a tertiary care university hospital. Participants: Sixty-one patients with septic shock defined according to established criteria. Interventions: Patients received either dopexamine (2 μg/kg/min, n = 20), dopamine (3 μg/kg/min, n = 21), or placebo (n = 20). Results: The trial groups were similar in terms of baseline characteristics. The authors found no significant differences among the dopexamine, dopamine, and placebo groups with regard to a comprehensive number of renal function parameters including C crea and organ-failure scores. There was a significant increase in heart rate after dopexamine infusion; other hemodynamic parameters remained unchanged in the dopexamine group. In a post hoc analysis that included only patients with renal impairment at study inclusion (n = 28), patients who received dopamine showed significant improvements in C crea when compared with placebo. Dopexamine was not effective in this subgroup. Conclusions: Dopexamine is no more effective than dopamine or placebo regarding renal function in patients with septic shock requiring norepinephrine. Both therapies do not influence organ-failure scores.

In acute respiratory distress syndrome (ARDS) with severe hypoxemia or respiratory acidosis, veno-venous extracorporeal membrane oxygenation (VV-ECMO) ensures oxygenation and decarboxylation. Commonly, simultaneous cannulation of jugular and femoral veins is used for VV-ECMO. A recently introduced dual-lumen cannula for VV-ECMO promises single vessel access through the right internal jugular vein and patient ambulation. However, correct direction of the reinfusion jet toward the tricuspid valve during ECMO treatment requires more demanding cannula placement control. We present a new ultrasound-guided technique for the placement of a dual-lumen VV-ECMO cannula in a patient with ARDS and extreme obesity.

Patients with terminal lung failure may be bridged to lung transplantation (LTX) by extracorporeal membrane oxygenation (ECMO). With the present shortage of donor organs and the high level of invasiveness of ECMO treatment, appropriate selection criteria for bridge to transplant need to be defined. We report retrospective data from 26 patients on ECMO listed for LTX. Seven patients were successfully transplanted (LTX-s). Six patients survived until transplantation, but died intra- or post-operatively (LTX-ns). Thirteen patients died before transplantation (Fail). There was no difference between LTX-s and the 19 overall non-survivors (NS) prior to ECMO initiation with regard to demographic data or ventilator parameters except for higher PaO2 /FiO2 in the LTX-s. Time on ECMO pre-LTX did not differ in the LTX-s and LTX-ns groups. SOFA score was lower in LTX-s when compared to LTX-ns before ECMO (p = 0.0155), during bridging (p = 0.028), and right before transplantation (p = 0.0038). Maximal bilirubin during bridging and bilirubin prior to transplantation was markedly elevated in the LTX-ns group [4.2 (2.4-4.7) vs. 1.1 (0.8-2.0) mg/dL; p = 0.0266 and 1.6 (1.2-3.0) vs. 0.5 (0.5-0.5) mg/dL; p = 0.0047). Bridging to LTX is a challenging but viable option for selected patients. Special consideration should be given to hepatic function.

It was the aim of the present study to examine the influence of alpha-and beta-receptor stimulation on the function of the right (RV) and left (LV) ventricle of streptozotocin-diabetic rats (STZ; 60 mg.kg-1; n = 14). Phenylephrine (PE; 3 mg.kg-1.h-1) or isoproterenol (ISO; 24 micrograms.kg-1.h-1) were infused intravenously for 20 min 4 weeks after STZ injection. The hemodynamic parameters were measured on intact, anaesthetized animals with special Millar ultraminiature tipcatheter manometers. In the non-diabetic animals (n = 15), PE caused a significant elevation of left ventricular systolic pressure (LVSP) from 138.5 +/- 3.2 to 205.4 +/- 7.5 mmHg and raised heart rate (HR) from 362 +/- 12.6 to 399 +/- 17.2 beats.min-1 (mean +/- S.E.M.; P < 0.05). LVSP and HR were significantly lower in the diabetic animals under control conditions (110.5 +/- 6.4 mmHg and 273 +/- 16.0 beats.min-1, respectively) and not affected by PE. ISO induced a significant and comparable decrease in diastolic aortic pressure (DAP) and an increase in HR in both the non-diabetic and diabetic group. The PE-induced enhancements of LV dP/dtmax and RV dP/dtmax from 10533 +/- 805 to 21533 +/- 1386 and from 2044 +/- 262 to 3867 +/- 733 mmHg.s-1 were significant in the control animals. In the diabetic rats, LV dP/dtmax was lower (5971 +/- 901 mmHg.s-1) and was increased by PE to the range of control rats (11171 +/- 1591 mmHg.s-1). The PE-induced elevation of RV dP/dtmax from 2028 +/- 284 to 2771 +/- 391 mmHg.s-1 was less pronounced in the diabetic rats than in the controls. Under the influence of ISO, the increase of dP/dtmax in both ventricles was comparable to the effect of PE and fully preserved in the diabetic animals. Right ventricular systolic pressure (RVSP) was increased under PE and ISO in both groups to comparable values. These results demonstrate that the in vivo response to beta-adrenoceptor stimulation is well preserved in the diabetic rat, while the effects of alpha-stimulation are markedly reduced, especially in the left ventricle and systemic circulation.

The in vivo hemodynamic and morphologic responses of the rat left (LV) and right (RV) ventricle to continuous long-term i.v. infusion of norepinephrine (NE) at different dosages and for different durations of infusion were studied. Female Sprague-Dawley rats received continuous intravenous infusion of norepinephrine from infors syringe pumps for 24, 48 and 72 h at a dose of 200 mu g center dot kg-1 x h-1. Furthermore, NE was infused for 72 h at dosages of 50, 100 and 200 mu g center dot kg-1 x h-1. The beta-adrenergic blocker and vasodilator with alpha1-blocking activity carvedilol (0.5 mg x kg-1 x h-1) was coinfused with NE for 72 h. The hemodynamic effects were measured on intact, anesthetized rats with special Millar ultraminiature pressure tip catheters, and the weights of the left and right ventricles were measured. NE increased heart rate at any time or dose, whereas cardiac output and total peripheral resistance remained unchanged. LV and RV dP/dtmax were nearly doubled as compared to control values and RVSP was elevated by more than 100%. The effect of NE on LVSP was much less pronounced (< 20%) and only significant at 50 mu g x kg-1 x h-1 for 72 h. Neither LV nor RV end-diastolic pressures were elevated, indicating that cardiac failure had not occurred. The LV developed hypertrophy with an increase of the ventricular weight/body weight ratio (LVW/BW) of 22% even after only 2 days of NE (200 mu g x kg-1 center dot h-1). The RV showed no hypertrophy at any time of the experiments. The NE-induced changes in HR, dP/dtmax, RVSP and LVW/BW were completely prevented by the coinfusion of carvedilol. These studies show that the hemodynamic responses to continuous infusion of NE are more pronounced in the RV than in the LV. Conversely, NE induced hypertrophy only in the LV, not in the RV. The hemodynamic effects of chronic NE infusion did not change significantly between 1 and 3 days of infusion. The in vivo responses to exogenous NE therefore were unaffected by adaptive effects such as downregulation of adrenergic receptors.

Die Pulskonturanalyse ist ein einfach anzuwendendes Verfahren zur kontinuierlichen Bestimmung des Herzzeitvolumens (PCCO) bei kritisch kranken Patienten. Die Berechnung des Schlagvolumens erfolgt uber die Analyse der arteriellen Pulsdruckkurve zusammen mit einem fur jeden Patienten mittels Referenzverfahren individuell zu bestimmenden Kalibrationsfaktor. PCCO wurde an 20 Intensivpatienten uber eine Gesamtzeit von 110 h gemessen und mit Thermodilutionswerten (TDCO) verglichen. Die relative Abweichung (±2 SD) von PCCO gegenuber TDCO wurde ermittelt: (1) unter hamodynamisch stabilen Bedingungen, und (2) unter Bedingungen von verandertem Vasotonus und Hamodynamik bei Dosisanderungen vasoaktiver Substanzen. Insgesamt wurden an 165 Meszeitpunkten TDCO-Messungen durchgefuhrt und die korrespondierenden PCCO-Werte registriert. Die relative Abweichung von PCCO gegenuber TDCO betrug ±23,9% (SD=0,85 l·min −1 ), wenn die PCCO-Methode einmalig bei jedem Patienten vor Beginn der Messerien kalibriert wurde. Die Differenz der Mittelwerte der Herzzeitvolumina (CO) beider Methoden (Bias) war dabei −0,09 l·min −1 . Durch zusatzliche Kalibrationen konnte die relative Abweichung (±2 SD) auf ±15,7% verbessert werden (SD= 0,56 l·min −1 ; Bias 0,003 l·min −1 ). Anderungen in der Dosierung vasoaktiver Substanzen in klinisch ublichen Grosenordnungen hatten keinen Einflus auf die Mesgenauigkeit von PCCO. Es konnte gezeigt werden, das die Pulskonturanalyse ein leicht anzuwendendes und klinisch ausreichend genaues Verfahren zur kontinuierlichen Messung des CO darstellt.

Background Secondary sclerosing cholangitis is a severe disease of the biliary tract. Over the last decade, several cases of sclerosing cholangitis in critically ill patients (SC-CIP) were reported. Reports in the literature so far are characterized by a wide variety of underlying causes of critical illness, thereby hindering a risk-factor analysis. We report on a homogenous cohort of critically ill patients with influenza A (H1N1) pneumonia and severe acute respiratory distress syndrome (ARDS), of whom a subgroup developed sclerosing cholangitis, allowing for probing of risk factors associated with SC-CIP. Methods Twenty-one patients (5 female, 16 male, 46.3 ± 10.8 years) with severe ARDS due to H1N1 pneumonia were retrospectively divided into two groups, characterized by the presence (n = 5) and absence of SC-CIP (n = 16). A large array of clinical data, laboratory parameters, and multi-detector computed tomography-derived measures were compared. Results Both patient groups showed severe pulmonary impairment. Severity of disease on admission day and during the first 14 days of treatment showed no difference. The patients developing SC-CIP had a higher body mass index (BMI) (37.4 ± 6.0 kg/m2 vs. 29.3 ± 6.8 kg/m2; P = 0.029) and a higher volume of intraperitoneal fat (8273 ± 3659 cm3 vs. 5131 ± 2268 cm3; P = 0.033) and spent a longer cumulative period in the prone position during the first 14 days (165 ± 117 h vs. 78 ± 61 h; P = 0.038). Conclusion Our results suggest that obesity, intraperitoneal fat volume, and a longer cumulative duration spent in the prone position may put patients with ARDS at risk of developing SC-CIP. These results lead us to propose that the prone position should be carefully deployed, particularly in abdominally obese patients, and that frequent checks be made for early hepatic dysfunction.

at a cut-off value of 1.5. Cardiac functions were stable with absence of cardiac arrhythmia despite intermittent atrial fibrillation until the patient suddenly died from acute heart failure. The autopsy findings are shown in figure 1 . Prevalence rates of 4.5% of invasive aspergillosis after lung transplantation in non-cystic fibrosis patients have been reported. Mortality rates of invasive pulmonary aspergillosis in lung transplant recipients are as high as 81.9% [1] . A 64-year-old man with a history of pulmonary fibrosis and right-sided single lung transplantation was admitted for left-sided pulmonary aspergillosis. Leftsided pneumonectomy was performed. A bronchopleural fistula developed and persisted despite prolonged combined antimycotic therapy, left-sided thoracoplasty and reduction of immunosuppressant therapy. Blood ELISA detected Aspergillus galactomannan antigen in 2 out of 27 measurements at a cut-off value of 0.5 Optical Density Index (ODI) and 0 out of 27 measurements Published online: November 13, 2012

An interventional lung assist membrane ventilator (iLA) for arteriovenous extracorporeal CO2 removal was connected to a small-diameter femoral artery by use of a chimney graft in an underweight patient with acute respiratory failure and a previous history of heart-lung transplantation. This concept offers additional therapeutic options in underweight patients requiring extracorporeal CO2 removal with arterial vessels that are too small for percutaneous arterial cannulation with standard-sized percutaneous insertable iLA cannulae.

To evaluate the feasibility of dual-energy CT (DECT) ventilation imaging in combination with DE perfusion mapping for a comprehensive assessment of ventilation, perfusion, morphology and structure of the pulmonary parenchyma. Two dual-energy CT acquisitions for xenon-enhanced ventilation and iodine-enhanced perfusion mapping were performed in patients under artificial respiration. Parenchymal xenon and iodine distribution were mapped and correlated with structural or vascular abnormalities. In all datasets, image quality was sufficient for a comprehensive image reading of the pulmonary CTA images, lung window images and pulmonary functional parameter maps and led to expedient results in each patient. With dual-source CT systems, DECT of the lung with iodine or xenon administration is technically feasible and makes it possible to depict the regional iodine or xenon distribution representing the local perfusion and ventilation.

Objective: To evaluate the magnitude and cause of metabolic acidosis after infusion of 7.5% sodium chloride 6% dextran 70. Design: Randomized, prospective clinical study. Setting: University hospital. Patients: Two groups of 14 patients each, undergoing repair of abdominal aortic aneurysm. Interventions: Patients were randomly assigned to receive either 250 mL of hypertonic saline dextran (HSD) or a conventional fluid regimen with 250 mL of hydroxyethyl starch in normal saline solution (H-NS) during the period of aortic clamping. Additionally, normal saline was used in both groups to reach a target pulmonary artery occlusion pressure of 15–18 mmHg. pH, Paco2, and serum concentrations of sodium, potassium, magnesium, calcium, chloride, lactate, albumin, and phosphate were measured. Strong ion difference was calculated as (sodium + potassium + magnesium + calcium) − (chloride + lactate). The amount of weak plasma acid was calculated. Measurements and Main Results: The infusion of HSD resulted in an immediate large increase in serum sodium (19 mmol/L) and chloride (22 mmol/L), whereas the infusion of H-NS led only to mild increases in serum sodium (3 mmol/L) and chloride (6 mmol/L). Both HSD and H-NS caused concomitant and equal decreases in the amount of weak plasma acid, strong ion difference, and pH (7.28–7.30). The reduction of bicarbonate was also identical and proportional to the extent of dilution due to infusion of HSD and H-NS. This induced metabolic acidosis was corrected spontaneously in both groups 24 hrs after surgery. Conclusion: Both the intravenous administration of 7.5% sodium chloride and the conventional fluid regimen with saline-based 6% hydroxyethyl starch solution resulted in a metabolic acidosis of equal extent. This suggests dilution of plasma buffers or a decrease in strong ion difference to be the primary cause of metabolic acidosis.

The effects of the angiotensin II receptor type 1 (AT 1 ) antagonist losartan on pressure overload-induced left ventricular (LV) hypertrophy were studied in female Sprague–Dawley rats. Starting on the day of surgery, losartan (L, 12 mg/kg/day) was administered as continuous intraperitoneal infusion for 2 weeks by using alzet mini-osmotic-pumps (model 2002). This dose of losartan shifted the in vivo dose–response curve of the angiotensin II-induced elevation of left ventricular systolic pressure (LVSP) to the right. Pressure overload was achieved by placing a band around the aortic arch. This caused an aortic stenosis (AS) with an outer diameter of 1.0 mm. The hemodynamic effects were measured in the intact, anesthetized rats ( n =15). The hearts were excised, and the weights of the left (LV) and right ventricle (RV) were determined. Some of these hearts ( n =7) were perfused with collagenase to obtain isolated cardiac myocytes for the measurement of cell volume. Other hearts ( n =8) were examined for morphological changes. In the animals with AS, LVSP was markedly elevated. Furthermore, LV weight and LV myocyte cell volume were increased in this group, while RV weight and RV myocyte cell volume remained stable in all the groups. L had no significant effect on the AS-induced increase in LVSP and cell size parameters, nor on the weight gain of the LV. Histological analysis revealed that the AS-induced enlargement of the mean myocyte diameter was not affected by L. The interstitial collagen fraction was increased in the AS rats and became normalized by L. These data suggest that the renin–angiotensin system might not be involved in the development of pressure-induced cardiac hypertropy within the time-frame of these experiments, but that it does play a major role in the genesis of the interstitial fibrosis which is a typical feature of this pathophysiological condition.

We developed a method for measuring left ventricular maximal isovolumetric pressure (LVMIP) in intact rats and applied it in the presence of acutely administered antihypertensive drugs and in experimental diabetes mellitus. The combination of a 2 French Fogarty arterial embolectomy balloon catheter with a new ultra-thin shaft (0.25 mm diameter) Millar ultra-miniature pressure tip catheter was used. Closed-chest, thiopental anaesthetized female Sprague-Dawley rats received the beta-adrenoceptor blocker metoprolol (1 mg/kg/h), the alpha-adrenoceptor blocker prazosin (0.1 mg/kg/h), and the calcium antagonist nifedipine (0.5 mg/kg/h). They were applied as continuous i.v. infusion for 30 minutes. The angiotensin II type 1 (AT1) receptor antagonist losartan (3 mg/kg) was applied as bolus i.v. injection. Diabetes mellitus was induced by a single tail vein injection of streptozotocin (60 mg/kg) five weeks prior to hemodynamic measurements. Under control conditions, left ventricular systolic pressure (LVSP) was 136.5 +/- 3.7 mmHg and increased to 263 +/- 5.4 mmHg when the balloon was inflated (LVMIP). LVSP was significantly lower in the presence of prazosin, metoprolol, nifedipine, and in diabetic rats. However, LVMIP was significantly reduced only in the metoprolol-treated and diabetic rats. Both LVSP and LVMIP did not change significantly in losartan-treated rats. The degree of the increase in left ventricular maximal isovolumetric pressure during balloon inflation (LVMIP-LVSP) was not significantly different in any experimental condition. These results suggest that the mechanism for evoking LVMIP is not dependent on the acute stimulation of cardiac alpha- and beta-adrenergic receptors, on calcium channels, nor on the AT1 receptors. In addition, the intrinsic mechanism for the generation of LVMIP seems not to be influenced in the diabetic state.

Comparison of the results of three experimental models of cardiac hypertrophy in rats reveals that angiotensin-converting enzyme (ACE) inhibition and angiotensin (Ang) II receptor blockade have different effects. In the model of pressure-induced left ventricular (LV) overload induced by constriction of the aortic arch, ACE inhibition with ramipril had no effect whatsoever on the development of cardiac hypertrophy both at the gross and the cellular morphological level. This may be because in this particular model, ACE inhibition was prevented from having an effect on blood pressure since the site of aortic constriction was quite near to the left ventricle. It may therefore be hypothezised that the clinical effects of this treatment may be related to the blood pressure-lowering effect. The local renin-angiotensin system (RAS) seems not to play a major role in this experimental model for the hypertrophy process. This is somewhat different in the model of right ventricular (RV) pressure overload induced by pulmonary artery stenosis. The development of RV hypertrophy was not influenced by treatment with ramipril; however, the cell morphology revealed a reduction in cell volume and cross-sectional area. Thus, the typical morphological feature of concentric hypertrophy was attenuated.