SARS-CoV-2 rapid antigen test: Fast-safe or dangerous? An analysis in the emergency department of an university hospital.

The use of Antigen point of care tests (AgPOCT) might be an essential tool to fight the coronavirus disease 2019 (COVID-19) pandemic. Manufacturer information indicates a specificity of about 95% and there is a growing interest to use these tests area-wide. Therefore, it is necessary to clarify whether AgPOCT can be used safely for "rule-in" (detection of positive patients) and for "rule-out" (valid negative testing). Two thousand three hundred and seventy-five patients received polymerase chain reaction (PCR) testing and AgPOCT for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) regardless of symptoms. The positive predictive value of symptomatic and asymptomatic patients was compared with a cut-off threshold cycle (C t ) value of ≤30 and in total. Five hundrded and fifty-one patients tested positive for the SARS-CoV-2 virus by PCR, of whom 35.2% presented without symptoms. In all patients, regardless of their symptoms or C t values, a sensitivity of 68.9% and a specificity of 99.6% were calculated for AgPOCT. In patients with C t values ≤30, a sensitivity of 80.5% (95% confidence interval: ±1.62) and a specificity of 99.6% were shown for all tests (symptomatic/asymptomatic). Highly infectious patients (C t ≤ 20), regardless of symptoms, were reliably detected by the AgPOCT. In infectious patients with C t values ≤30, the test has a sensitivity of about 80% regardless of COVID-19 typical symptoms, which is apparently less than the 96.52% specificity indicated by the manufacturer. Relevant improvement in test sensitivity by querying the patients who are symptomatic and asymptomatic is also not feasible. We strongly suggest that we critically question the use of AgPOCT for "rule-out," as they only provide a supposed safety.

What about the others: differential diagnosis of COVID-19 in a German emergency department.

BACKGROUND: The ongoing COVID-19 pandemic remains a major challenge for worldwide health care systems and in particular emergency medicine. An early and safe triage in the emergency department (ED) is especially crucial for proper therapy. Clinical symptoms of COVID-19 comprise those of many common diseases; thus, differential diagnosis remains challenging. METHOD: We performed a retrospective study of 314 ED patients presenting with conceivable COVID-19 symptoms during the first wave in Germany. All were tested for COVID-19 with SARS-Cov-2-nasopharyngeal swabs. Forty-seven patients were positive. We analyzed the 267 COVID-19 negative patients for their main diagnosis and compared COVID-19 patients with COVID-19 negative respiratory infections for differences in laboratory parameters, symptoms, and vital signs. RESULTS: Among the 267 COVID-19 negative patients, 42.7% had respiratory, 14.2% had other infectious, and 11.2% had cardiovascular diseases. Further, 9.0% and 6.7% had oncological and gastroenterological diagnoses, respectively. Compared to COVID-19 negative airway infections, COVID-19 patients showed less dyspnea (OR 0.440; p = 0.024) but more dysgeusia (OR 7.631; p = 0.005). Their hospital stay was significantly longer (9.0 vs. 5.6 days; p = 0.014), and their mortality significantly higher (OR 3.979; p = 0.014). CONCLUSION: For many common ED diagnoses, COVID-19 should be considered a differential diagnosis. COVID-19 cannot be distinguished from COVID-19 negative respiratory infections by clinical signs, symptoms, or laboratory results. When hospitalization is necessary, the clinical course of COVID-19 airway infections seems to be more severe compared to other respiratory infections. TRIAL REGISTRATION: German Clinical Trial Registry DRKS, DRKS-ID of the study: DRKS00021675 date of registration: May 8th, 2020, retrospectively registered.

Predictors for acute and chronic renal failure and survival in patients supported with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Renal failure is a common occurrence in patients with refractory cardiogenic shock including those supported with veno-arterial extracorporeal membrane oxygenation. Prevalence and outcome of acute and chronic kidney failure in extracorporeal membrane oxygenation patients have not been well documented. In this study, we investigated the occurrence of acute and chronic kidney failure in veno-arterial extracorporeal membrane oxygenation patients as well as predictors for survival. METHODS: This is a single center retrospective clinical study. We included adult patients with refractory cardiogenic shock who were supported by veno-arterial extracorporeal membrane oxygenation between 2008 and 2015. The primary endpoint of the study was acute kidney injury (KDIGO Stage 3) during extracorporeal membrane oxygenation and chronic kidney failure requiring renal replacement therapy, 30 and 90 days after extracorporeal membrane oxygenation. The secondary endpoint was in-hospital survival and 90-day survival. RESULTS: A total of 196 veno-arterial extracorporeal membrane oxygenation patients were investigated. In total, 41.8% (82/196) patients had acute renal failure requiring continuous renal replacement therapy during extracorporeal membrane oxygenation. The 30- and 90-day survival was 55.1% (108/196) and 48.5% (95/196), respectively; 21.3% (23/108) and 11.6% (11/95) patients needed renal replacement therapy after 30 and 90 days, respectively. Predictors for KDIGO Stage 3 renal failure during extracorporeal membrane oxygenation were lactate (p = 0.026) and the number of blood units transfused during extracorporeal membrane oxygenation support (p = 0.000). A predictor for renal replacement therapy after 30 and 90 days was an elevated plasma-free hemoglobin level. The in-hospital survival was 54.6% (107/196). Serum lactate of less than 4.3 mmol/L, lower age, plasma-free hemoglobin of ⩽62 mg/dL, low number of blood units transfused during extracorporeal membrane oxygenation, and the use of an intra-aortic balloon pump were predictors for in-hospital and 90-day survival.

Comparison of videolaryngoscopy and direct laryngoscopy by German paramedics during out-of-hospital cardiopulmonary resuscitation; an observational prospective study.

BACKGROUND: Videolaryngoscopy (VL) has become a popular method of intubation (ETI). Although VL may facilitate ETI in less-experienced rescuers there are limited data available concerning ETI performed by paramedics during CPR. The goal was to evaluate the impact VL compared with DL on intubation success and glottic view during CPR performed by German paramedics. We investigated in an observational prospective study the superiority of VL by paramedics during CPR compared with direct laryngoscopy (DL). METHODS: In a single Emergency Medical Service (EMS) in Germany with in total 32 ambulances paramedics underwent an initial instruction from in endotracheal intubation (ETI) with GlideScope® (GVL) during resuscitation. The primary endpoint was good visibility of the glottis (Cormack-Lehane grading 1/2), and the secondary endpoint was successful intubation comparing GVL and DL. RESULTS: In total n = 97 patients were included, n = 69 with DL (n = 85 intubation attempts) and n = 28 VL (n = 37 intubation attempts). Videolaryngoscopy resulted in a significantly improved visualization of the larynx compared with DL. In the group using GVL, 82% rated visualization of the glottis as CL 1&2 versus 55% in the DL group (p = 0.02). Despite better visualization of the larynx, there was no statistically significant difference in successful ETI between GVL and DL (GVL 75% vs. DL 68.1%, p = 0.63). CONCLUSIONS: We found no difference in Overall and First Pass Success (FPS) between GVL and DL during CPR by German paramedics despite better glottic visualization with GVL. Therefore, we conclude that education in VL should also focus on insertion of the endotracheal tube, considering the different procedures of GVL. TRIAL REGISTRATION: German Clinical Trial Register DRKS00020976, 27. February 2020 retrospectively registered.

Heparin-induced thrombocytopenia in patients on extracorporeal membrane oxygenation and the role of a heparin-bonded circuit.

BACKGROUND: In patients supported with extracorporeal membrane oxygenation, and who develop heparin-induced thrombocytopenia, there is no clear evidence to support changing to a non-heparin-coated extracorporeal membrane oxygenation circuit. Our goal was to evaluate clinical outcomes of patients who were continued on heparin-bonded circuits despite diagnosed heparin-induced thrombocytopenia. METHODS: We completed a single-center retrospective study of all patients who underwent extracorporeal membrane oxygenation support from July 2008 to July 2017 and were tested heparin-induced thrombocytopenia positive while on extracorporeal membrane oxygenation support. After diagnosis of heparin-induced thrombocytopenia, mean platelet count (k/µL) was measured on consecutive days for 14 days. RESULTS: Out of 455 patients, 14 (3.1%) had a diagnosis of heparin-induced thrombocytopenia by serotonin release assay and systemic heparin treatment was discontinued in every case. In total, 11 of the heparin-induced thrombocytopenia patients (78.6%) survived to discharge. The overall survival of all 455 extracorporeal membrane oxygenation patients was 54.1%. Platelets counts after discontinuation of systemic heparin in the heparin-induced thrombocytopenia patients increased from a mean of 59.8 k/µL at time of heparin-induced thrombocytopenia diagnosis to a mean of 280.2 k/µL at 14 days after discontinuation of heparin despite continuation of the heparin-bonded circuit. Platelet count increased in heparin-induced thrombocytopenia patients on extracorporeal membrane oxygenation support after discontinuation of systemic heparin even if maintained on the heparin-bonded circuit. CONCLUSION: Discontinuation of systemic heparin but continuation of heparin-coated extracorporeal membrane oxygenation circuits appeared to be an appropriate response for our extracorporeal membrane oxygenation-supported patients who developed heparin-induced thrombocytopenia. Survival in this group was not significantly different to those patients on extracorporeal membrane oxygenation without heparin-induced thrombocytopenia. Larger studies should evaluate the safety of heparin-bonded extracorporeal membrane oxygenation systems in heparin-induced thrombocytopenia patients.

Predicting Survival in Patients Treated With Extracorporeal Membrane Oxygenation After Myocardial Infarction.

OBJECTIVES: Acute myocardial infarction is the most common cause of cardiogenic shock. Although the number of patients with acute myocardial infarction complicated by cardiogenic shock who were treated with venoarterial extracorporeal membrane oxygenation increased during the last decade, detailed data on survival are lacking. We sought to analyze covariates that were independently associated with survival in this patient population and to externally validate the newly developed prEdictioN of Cardiogenic shock OUtcome foR Acute myocardial infarction patients salvaGed by venoarterial Extracorporeal membrane oxygenation (ENCOURAGE) score. DESIGN: Retrospective clinical study. SETTING: A single academic teaching hospital. PATIENTS: Adult patients with acute myocardial infarction complicated by cardiogenic shock who were supported by venoarterial extracorporeal membrane oxygenation from June 2008 to September 2016. INTERVENTIONS: Fourteen individual variables were assessed for their association with the primary endpoint. These variables were prespecified by the study team as being the most likely to affect survival. A receiver operating characteristic analysis was also performed to test the ability of the ENCOURAGE score to predict survival in this patient cohort. MEASUREMENTS AND MAIN RESULTS: The primary endpoint of the study was in-hospital survival. A total of 61 patients were included in the analysis. Thirty-seven (60.7%) could be weaned from venoarterial extracorporeal membrane oxygenation and 36 (59.0%) survived. Survival was significantly higher in patients less than 65 years old (odds ratio, 14.6 [CI, 2.5-84.0]; p = 0.003), whose body mass index was less than 32 kg/m (odds ratio, 5.5 [CI, 1.2-25.4]; p = 0.029) and international normalized ratio was less than 2 (odds ratio, 7.3 [CI, 1.3-40.1]; p = 0.022). In patients where the first lactate drawn was less than 3 mmol/L, the survival was not significantly higher (odds ratio, 4.4 [CI, 0.6-32.6]; p = 0.147). The C-statistic for predicting survival using a modified version of the ENCOURAGE score, which replaced prothrombin activity less than 50% with an international normalized ratio greater than 2, was 0.74 (95% CI, 0.61-0.87). CONCLUSIONS: In this single-center study, several important covariates were associated with improved survival in patients with acute myocardial infarction complicated by cardiogenic shock who were supported by venoarterial extracorporeal membrane oxygenation and the ENCOURAGE score was found to be externally valid for predicting survival to hospital discharge.

Is pulseless electrical activity a reason to refuse cardiopulmonary resuscitation with ECMO support?

BACKGROUND: Cardiopulmonary resuscitation with ECMO support (ECPR) has shown to improve outcome in patients after cardiac arrest under resuscitation. Most current recommendations for ECPR do not include patients with a non-shockable rhythm such as PEA and asystole. AIM: The aim of this study was to investigate the outcome of 3 patient groups separated by initial rhythm at time of ECMO placement during CPR: asystole, PEA and shockable rhythm. METHODS: We made a retrospective single-center study of adults who underwent ECPR for in-hospital cardiac arrest between June 2008 and January 2017. Outcome and survival were identified in 3 groups of patients regarding to the heart rhythm at the time decision for ECMO support was made: 1. patients with asystole, 2. patients with pulseless electrical activity, 3. patients with a shockable rhythm. RESULT: 63 patients underwent ECPR in the mentioned time frame. Five patients were excluded due to incomplete data. Under the 58 included patients the number of cases for asystole, PEA, shockable rhythm was 7, 21 and 30 respectively. The means of CPR-time in these groups were 37, 41 and 37min. Survival to discharge was 0.0%, 23.8% and 40.0% respectively (p=0.09). All survivors to discharge had a good neurological outcome, defined as cerebral performance category 1or 2. CONCLUSION: Survival to discharge in patients with PEA as initial rhythm at the time of decision for ECPR is 23.8% while no patients with asystole as initial rhythm survived discharge. Patients with PEA should be carefully considered for ECPR.

Effect of video laryngoscopy for non-trauma out-of-hospital cardiac arrest on clinical outcome: A registry-based analysis.

AIM: Videolaryngoscopy (VL) is a promising tool to provide a safe airway during cardiopulmonary resuscitation (CPR) and to ensure early reoxygenation. Using data from the German Resuscitation Registry, we investigated the outcome of non-traumatic out-of-hospital cardiac arrest (OHCA) patients treated with VL versus direct laryngoscopy (DL) for airway management. METHODS: We analysed retrospective data of 14,387 patients from 1 January 2018 until 31 December 2021 (VL group, n = 2201; DL group, n = 12186). Primary endpoint was discharge with cerebral performance categories one and two (CPC1/2). Secondary endpoints were the rate of return of spontaneous circulation (ROSC), hospital admission, hospital admission with ongoing cardiopulmonary resuscitation, 30-day survival/ hospital discharge and airway management complications. We used multivariate binary logistic regression analysis to identify the effects on outcome of known influencing variables and of VL vs DL. RESULTS: The multivariate regression model revealed that VL was an independent predictor of CPC1/2 survival (OR = 1.34, 95% CI = 1.12-1.61, p = 0.002) and of hospital discharge/30-day survival (OR = 1.26, 95% CI = 1.08-1.47, p = 0,004). CONCLUSION: VL for endotracheal intubation (ETI) at OHCA was associated with better neurological outcome in patients with ROSC. Therefore, the use of VL for OHCA offers a promising perspective. Further prospective studies are required.

[Risk management in the triage of emergency room patients to outpatient care : Manchester Triage System and CEReCo-blue as a tool for low-risk patient management in integrated emergency centers]. / Risikomanagement in der Triage ambulanter Notfallpatienten : Manchester Triage System und CEReCo-blue als Instrument zur risikoarmen Patientensteuerung in integrierten Notfallzentren.

BACKGROUND: So-called "integrated emergency centers (IEC)" are going to be implemented in German hospitals and will be the first contact point in the emergency care setting. For early decision-making whether outpatient care or inpatient admission in the emergency department is indicated, it would be helpful to have a system to identify patients for outpatient treatment. In this study, we investigated whether the Manchester Triage System (MTS) is suitable for identifying patients who can be safely referred to emergency room patients to outpatient care. METHODS: Patients in the emergency department of the "blue" MTS level were examined for the endpoint inpatient admission and were compared with the next higher MTS category "green". In a second step, the "blue" MTS category was examined for the most common criteria leading to inpatient admission. RESULTS: After excluding patients who were presented by the emergency medical services (EMS) or after prior medical consultation, the rate of inpatient admissions in the blue MTS category was significantly lower than in the green category (10.8% vs 29.0%). The rate could be reduced to 0.9% by establishing a subgroup with the additional exclusion criteria chronic disorder and readmission after prior inpatient treatment (CEReCo-blue group: Chronic Disorder (C), Emergency Medical Service (E), Readmission (R), Prior Medical Consultation (Co)). CONCLUSION: The blue MTS category does not appear to be suitable for the selection of patients with indication for outpatient treatment. We propose the introduction of a subgroup, the so-called CEReCo-blue group, which could be helpful for the selection of this patient group.

[Wave riding - 12 months of COVID-19 in a German tertiary care center]. / Wellenreiten ­ 12 Monate COVID-19 im Maximalversorger.

INTRODUCTION: With more than 1400 COVID-19 inpatients, the university hospital of Essen is the main regional caregiver during COVID-19 pandemic. We present outcome data of our inpatients during the first 12 months of pandemic and our derived clinical care concepts. METHODS: Retrospective analysis of all 1396 COVID-19 inpatients presenting between March, 1st of 2020 and February, 28th of 2021 for comorbidities, survival and complications. Group comparison between patients receiving standard care and those requiring intermediate/ intensive care. RESULTS: Mortality rate of all inpatients was 19,8 % (277/ 1396), whereas 10.6 % (93/877) of the patients with standard care and 35.5 % (184/519) of those with intermediate/intensive care died during hospital stay. Age above 60 years, obesity, need for mechanical ventilation, nitric oxide therapy, ECMO and acute renal failure as well as stroke during the clinical course were independent predictors of mortality. CONCLUSIONS: The mortality of both patient groups ranges within the numbers published by other international groups. The vast impact of usual comorbidities could be observed as well as the high rate of complications in serious ill COVID-19 patients. The mean age of both patient groups was lower than expected (60 years standard care versus 63 years intermediate/ intensive care). A maximum of patient and staff protection measures, a fast and efficient testing strategy during primary triage, standardized concepts from emergency department to intensive care units and dynamic adjustment of resources to daily changing needs can ensure a high quality of care even during peak of pandemic.

Evaluation of a new COVID-19 triage algorithm in the emergency department including combined antigen and PCR-testing: A case-control study.

The coronavirus disease 2019 (COVID-19) pandemic is a major challenge for global healthcare systems. Early and safe triage in the emergency department (ED) is crucial for proper therapy. However, differential diagnosis remains challenging. Rapid antigen testing (RAT) may help to improve early triage and patient safety. We performed a retrospective study of 234 consecutive patients with suspected COVID-19 who presented to our ED in November 2020. All underwent SARS-CoV-2-nasopharyngeal swab testing using both RAT and reverse transcription polymerase chain reaction (RT-PCR). The inpatient treatment was established according to an empirically developed triage algorithm. The accuracy of the suggested algorithm was analyzed based on the rate of outpatients returning within 7 days and inpatients staying for less than 48 hours. COVID-19 inpatients and outpatients were compared for symptoms, vital signs, and C-reactive protein levels. Of the 221 included patients with suspected COVID-19 infection, the diagnosis could be confirmed in 120 patients (54.3%) by a positive RT-PCR result, whereas only 72% of those had a positive antigen test. Of the 56 COVID-19 outpatients, three returned within 7 days with the need for hospital treatment due to clinical deterioration. Among the 64 COVID-19 inpatients, 4 were discharged within 48 hours, whereas 60 stayed longer (mean duration 10.2 days). The suggested triage algorithm was safe and efficient in the first 234 consecutive patients. RAT can confirm a diagnosis in 72% of PCR proven COVID-19 patients and allows early cohort isolation as an important way to save hospital capacity.

Separating the wheat from the chaff-COVID-19 in a German emergency department: a case-control study.

BACKGROUND: COVID-19 pandemia is a major challenge to worldwide health care systems. Whereas the majority of disease presents with mild symptoms that can be treated as outpatients, severely ill COVID-19 patients and patients presenting with similar symptoms cross their ways in the emergency department. Especially, the variety of symptoms is challenging with primary triage. Are there parameters to distinguish between proven COVID-19 and without before? How can a safe and efficient management of these inpatients be achieved? METHODS: We conducted a retrospective analysis of 314 consecutive inpatient patients who presented with possible symptoms of COVID-19 in a German emergency department between March and April 2020 and were tested with a SARS-Cov-2 nasopharyngeal swab. Clinical parameters, Manchester Triage System categories, and lab results were compared between patients with positive and negative test results for SARS-Cov-2. Furthermore, we present the existing COVID-19 workflow model of the university hospital in Essen which proved to be efficient during pandemia. RESULTS: Forty-three of the 314 patients (13.7%) were tested positive for COVID-19 by SARS-Cov-2 nasopharyngeal swab. We did not find any laboratory parameter to distinguish safely between patients with COVID-19 and those with similar symptoms. Dysgeusia was the only clinical symptom that was significantly more frequent among COVID-19 patients. CONCLUSION: Dysgeusia seems to be a typical symptom for COVID-19, which occurred in 14% of our COVID-19 patients. However, no valid parameters could be found to distinguish clinically between COVID-19 and other diseases with similar symptoms. Therefore, early testing, a strict isolation policy, and proper personal protection are crucial to maintain workflow and safety of patients and ED staff for the months to come. TRIAL REGISTRATION: German Clinical Trials registry, DRKS00021675.

[COVID-19 Triage: Who is an inpatient? The Essen triage model]. / COVID-19-Triage: Wer bleibt stationär? Das Modell Essen.

INTRODUCTION: Data about optimal initial assessment in patients with suspicion for COVID19-infection or already confirmed infection are sparse. Especially, in preparation for expected mass casualty incident it is necessary to distinguish early and efficiently between outpatient and inpatient treatment including the need for intensive care therapy. METHODS: We present a model for a safe and efficient triage, which is established and used in the university hospital of Essen, Germany. It is intended for a non-disaster situation. This model is a combination of clinical assessment by using vital parameters and Manchester triage scale (MTS). Possible additional parameters are POCT (point-of-care-testing) values, electrocardiogram, CT pulmonary angiography, SARS-Cov2-PCR as well as detailed diagnostic of laboratory values. The model was validated by 100 consecutive patients. We demonstrate three patients to illustrate this model. RESULTS: During the first two weeks after implementing this model in our normal operation at the emergency department, we had an efficient selectivity between need for inpatient and outpatient treatment. 16 patients were classified as "inpatients" according to initial assessment. Among 84 patients who were initially classified as "outpatients", 7 patients returned to our emergency department within 14 days. Three of these patients returned due to complaints other than COVID19. One female patient had to be admitted due to progressive dyspnea. CONCLUSIONS: This introduced triage-model seems to be an efficient concept. Adjustment might be necessary after further experience and after a growing number of patients.

Mitral valve repair complicated by left circumflex coronary artery occlusion: An under-recognized but potentially deadly complication.

Mitral valve repair is becoming an increasingly frequent surgery for patients with mitral valve regurgitation. Iatrogenic coronary artery injury and ischemic myocardial compromise have been previously reported in the literature as a rare but serious complication of surgical mitral valve repair. This potentially life-threatening complication should be considered and quickly recognized during perioperative mitral valve repair or replacement to prevent morbidity and mortality. To increase awareness and to prevent this complication from being missed in the future, we present a case report of iatrogenic left circumflex artery dynamic occlusion and subsequent myocardial infarction from mitral valve annuloplasty resulting in severe peri-operative heart failure and death.

Predictors of Survival for Nonhighly Selected Patients Undergoing Resuscitation With Extracorporeal Membrane Oxygenation After Cardiac Arrest.

In several case reports and case series, extracorporeal membrane oxygenation during chest compression (CPR) has been shown to be a reasonable tool to improve outcome of patients under resuscitation. Although recommendations for extracorporeal cardiopulmonary resuscitation (ECPR) include younger patients with shockable rhythm and short previous CPR-time, it remains unclear if nonhighly selected patients have a similar outcome. Aim of this study was to determine outcome in our nonhighly selected patient population treated with ECPR and investigate possible predictors of survival. We made a retrospective single-center study of adults who underwent ECPR for in-hospital cardiac arrest between June 2008 and September 2016. Outcome and predictors of survival were identified. In this period of time, 59 patients underwent ECPR due to cardiac arrest. Fifteen patients (25.4%) survived discharge of which all had a good neurological outcome (cerebral performance category ≤ 2). Survival to discharge of patients with shockable rhythm (ventricular fibrillation or ventricular tachycardia) was 40.7%. Serum lactate ≥ 8, pulseless electrical activity (PEA) or asystole and male gender could be identified as predictors for low survival rate. Age, body mass index, renal replacement-dependent kidney injury had no significant influence on survival outcome. Mean CPR-time was 41.1 minutes (interquartile range, ±29.25 minutes). Extracorporeal membrane oxygenation seems to be a useful tool to improve the outcome of CPR also in nonhighly selected patients when compared with CPR alone and could be considered in patients with refractory cardiac arrest also after longer previous CPR-time. Serum lactate and heart rhythm should be taken into account for patient selection.

Influence of tacrolimus metabolism rate on BKV infection after kidney transplantation.

Immunosuppression is the major risk factor for BK virus nephropathy (BKVN) after renal transplantation (RTx). As the individual tacrolimus (Tac) metabolism rate correlates with Tac side effects, we hypothesized that Tac metabolism might also influence the BKV infection risk. In this case-control study RTx patients with BK viremia within 4 years after RTx (BKV group) were compared with a BKV negative control group. The Tac metabolism rate expressed as the blood concentration normalized by the daily dose (C/D ratio) was applied to assess the Tac metabolism rate. BK viremia was detected in 86 patients after a median time of 6 (0-36) months after RTx. BKV positive patients showed lower Tac C/D ratios at 1, 3 and 6 months after RTx and were classified as fast Tac metabolizers. 8 of 86 patients with BK viremia had histologically proven BKN and a higher median maximum viral load than BKV patients without BKN (441,000 vs. 18,572 copies/mL). We conclude from our data that fast Tac metabolism (C/D ratio <1.05) is associated with BK viremia after RTx. Calculation of the Tac C/D ratio early after RTx, may assist transplant clinicians to identify patients at risk and to choose the optimal immunosuppressive regimen.

The tacrolimus metabolism rate influences renal function after kidney transplantation.

The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient's risk management strategies.

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.

Non-invasive ventilation in immunosuppressed patients with pneumonia and extrapulmonary sepsis.

PURPOSE: International guidelines recommend the use of noninvasive ventilation in immunocompromised patients with acute respiratory failure (ARF). We analyzed failure rates and risk factors for NIV failure in immunocompromised patients. METHODS: We retrospectively analyzed 120 immunodeficient patients treated with NIV in our medical ICU from 2005 to 2011. We compared the clinical course and NIV failure rates. Furthermore, we compared patients with secondary respiratory failure due to those with Systemic Inflammatory Response Syndrome (SIRS) of other than pulmonary origin to those with primary pulmonary infiltrations. RESULTS: Regression analyses revealed high APACHE II score (p < 0.01), need for catecholamines (p < 0.05) and low paO(2)/FIO(2) ratio (p < 0.05) as risk factors for NIV failure. Regarding the underlying diseases, we could not find differences in NIV duration (p = 0.07) and outcome (p = 0.44). 59.2% suffered from ARF due to lung infiltrations whereas 40.8% had secondary ARF caused by sepsis of extrapulmonary origin. Patients with lung infiltrations had a longer stay on ICU (16.3 vs 13.2 days; p = 0.047) and showed a trend toward longer NIV duration (87 ± 102 h vs 65.6 ± 97.8 h; p = 0.056). The SIRS patients compared to pneumonia patients showed a trend toward higher serum creatinine (1.63 mg/dL to 1.51 mg/dL; p = 0.059), a higher rate of renal failure (p < 0.01), higher APACHE II score (30.6-25.7, p < 0.01) and more frequently needed catecholamines (p < 0.01). NIV failure rate (overall 55%) was not different. CONCLUSIONS: Almost 50% of the immunocompromised patients treated with NIV did not require intubation independent of the etiology of ARF. High APACHE II scores and severity of oxygenation failure were associated with NIV failure.

Acute Respiratory Distress Syndrome as a presenting manifestation in young patients infected with H1N1 influenza virus.

INTRODUCTION: The new strain of influenza A (H1N1) 2009, often referred to colloquially as "swine flu", which was first detected in April 2009, raised to a pandemic of which the impact was not completely predictable. As reported, numerous cases with severe respiratory failure were also seen among young previously healthy people. PATIENTS: In the present study, we report eight cases of influenza A (H1N1) 2009 admitted to our medical intensive care with severe respiratory failure between November and December 2009 and in January 2011. All patients were older than 30 but younger than 50 years, had clinical and radiological evidence of an Acute Respiratory Distress Syndrome (ARDS) and needed invasive ventilatory support. RESULTS: Six of the eight patients had no relevant underlying disease; one had a pre-existing idiopathic lung fibrosis and another had a chronic obstructive pulmonary disease (COPD), an abuse of alcohol and an adiposities grade 3. Four patients needed an extracorporeal membrane oxygenation (ECMO) due to severe respiratory failure with global respiratory insufficiency that could not be treated by conservative ventilatory support. The one patient with a pre-existing lung fibrosis died shortly after lung transplantation despite use of an extracorporeal membrane oxygenation. One other patient died due to a subarachnoidal bleeding under the anticoagulatory regime during ECMO therapy. The adipose COPD-patient died due to septic shock with multiple organ failure without possibility for ECMO support. CONCLUSIONS: The clinical course of severe cases of influenza A (H1N1) 2009-infection is markedly different from the disease pattern seen during epidemics of seasonal influenza. Most of the patients admitted to our intensive care unit due to influenza A (H1N1) 2009 associated ARDS were previously healthy young people.