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Background: Long-term outcome of lung transplantation (LTx) recipients is limited by chronic lung allograft dysfunction (CLAD). In this setting of new onset respiratory failure, the amount of oxygenated hemoglobin (OxyHem; hemoglobin (Hb) concentration × fractional oxygen saturation) may provide valuable information. Objective: We hypothesized that OxyHem predicts survival of LTx recipients at the onset of CLAD. Methods: Data from 292 LTx recipients with CLAD were analyzed. After excluding patients with missing data or supplemental oxygen, the final population comprised 218 patients. The relationship between survival upon CLAD and OxyHem was analyzed by Cox regression analyses and ROC curves. Results: Among the 218 patients (102 males, 116 females), 128 (58.7%) died, median survival time after CLAD onset being 1,156 days. Survival was significantly associated with type of transplantation, time to CLAD, CLAD stage at onset, and OxyHem, which was superior to Hb or oxygen saturation. The risk for death after CLAD increased by 14% per reduction of OxyHem by 1 g/dL, and values below 11 g/dL corresponded to an 80% increase in mortality risk. Conclusion: Thus, OxyHem was identified as an independent predictor of mortality after CLAD onset. Whether it is useful in supporting therapeutic decisions and potentially home monitoring in the surveillance of lung transplant recipients has to be studied further.

There are different methods of artificial liver support for patients with acute liver dysfunction (ALD). However, CytoSorb (CS) might be a new approved option for those patients. Question of interest is whether the elimination performance of CS was comparable to that of advanced organ support (ADVOS). Patients, treated with CS (integrated into high-flux dialysis) or ADVOS and a total bilirubin > 10 mg/dl were included. Laboratory parameters were evaluated before starting therapy (d0) and 12–24 h thereafter (d1). The Wilcoxon-test with associated samples was used for statistical analysis. Thirty-nine patients (33 CS, 6 ADVOS) were included. The median bilirubin at d0 was 16.9 and 17.7 mg/dl and at d1 was 13.2 and 15.9 mg/dl, in the CS and ADVOS group, respectively. There was a significant bilirubin reduction as well in the CS group (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.

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.

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.

Oxygen-derived free radicals (ROS) have been identified to contribute significantly to ischemia-reperfusion (I/R) injury by initiating chain reactions with polyunsaturated membrane lipids (lipid peroxidation, LPO) resulting in the generation of several aldehydes and ketones. Due to their volatile nature these LPO products can be measured noninvasively in breath. We hypothesized that one of these markers, namely propionaldehyde, will be increased in lung and heart-lung transplant patients where severe oxidative stress due to I/R injury with early graft dysfunction represents one of the major postoperative complications resulting in prolonged ventilation and increased in-hospital morbidity and mortality. Expiratory air measurements for acetone, isoprene, and propionaldehyde were performed in seven patients after lung (n = 5) or heart-lung (n = 2) transplantation, ventilated patients (n = 12), and healthy volunteers (n = 17) using online ion-molecule reaction mass spectrometry. Increased concentrations of acetone (transplanted: 3812 [2347-12498]; ventilated: 1255 [276-1959]; healthy: 631 [520-784] ppbv; P.001) and propionaldehyde (transplanted: 270 [70-424]; ventilated: 82 [41.8-142]; healthy: 1.7 [0.1-11.8] ppbv; P.001) were found in expiratory air of transplanted and ventilated patients. Propionaldehyde resulting from spontaneous fragmentation of peroxides due to free radical-induced LPO after I/R injury in patients after lung or heart-lung transplantation can be quantified in expired breath.

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.

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.

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

In patients with acute respiratory failure and life-threatening impairment of pulmonary gas exchange, venovenous extracorporeal membrane oxygenation offers further therapeutic options. During extracorporeal membrane oxygenation treatment, systemic anticoagulation is usually achieved by heparin administration, which exposes patients to the risk of heparin-induced thrombocytopenia type II. We present a patient with acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation who experienced heparin-induced thrombocytopenia type II and in whom anticoagulation was continued with argatroban. Because respiratory failure did not resolve, the patient was bridged to lung transplant with extracorporeal membrane oxygenation. Argatroban anticoagulation was safely used until lung transplant (on day 114 after extracorporeal membrane oxygenation initiation) and after transplant in the presence of hepatic failure.

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.