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ZusammenfassungDie Lärmbelastung auf der Intensivstation ist ein allgegenwärtiges, erhebliches Problem für Patienten und Personal. Viele maßgebliche Lärmquellen sind mitverantwortlich für die häufigen Schlafstörungen der Patienten, die das Auftreten eines Delirs begünstigen. Der Beitrag fasst die aktuelle Evidenz zur Entstehung lärmassoziierter Auswirkungen zusammen und zeigt Optionen zur Lärmreduktion und Verbesserung der Therapie von Intensivpatienten auf.

During sepsis, an initial prothrombotic shift takes place, in which coagulatory acute-phase proteins are increased, while anticoagulatory factors and platelet count decrease. Further on, the fibrinolytic system becomes impaired, which contributes to disease severity. At a later stage in sepsis, coagulation factors may become depleted, and sepsis patients may shift into a hypo-coagulable state with an increased bleeding risk. During the pro-coagulatory shift, critically ill patients have an increased thrombosis risk that ranges from developing micro-thromboses that impair organ function to life-threatening thromboembolic events. Here, thrombin plays a key role in coagulation as well as in inflammation. For thromboprophylaxis, low molecular weight heparins (LMWH) and unfractionated heparins (UFHs) are recommended. Nevertheless, there are conditions such as heparin resistance or heparin-induced thrombocytopenia (HIT), wherein heparin becomes ineffective or even puts the patient at an increased prothrombotic risk. In these cases, argatroban, a direct thrombin inhibitor (DTI), might be a potential alternative anticoagulatory strategy. Yet, caution is advised with regard to dosing of argatroban especially in sepsis. Therefore, the starting dose of argatroban is recommended to be low and should be titrated to the targeted anticoagulation level and be closely monitored in the further course of treatment. The authors of this review recommend using DTIs such as argatroban as an alternative anticoagulant in critically ill patients suffering from sepsis or COVID-19 with suspected or confirmed HIT, HIT-like conditions, impaired fibrinolysis, in patients on extracorporeal circuits and patients with heparin resistance, when closely monitored.

ZusammenfassungDas innerklinische Notfallmanagement ist ein zentraler Baustein für die Patientensicherheit im Krankenhaus. Durch Frühwarnsysteme und die Etablierung Medizinischer Einsatzteams (MET) können sich verschlechternde Patienten frühzeitig erkannt und vermeidbare Todesfälle verhindert werden. Dieser Beitrag stellt wesentliche Elemente eines modernen innerklinischen Notfallmanagements dar.

Extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome (ARDS) is used to achieve oxygenation and protect lung ventilation. Near infrared spectroscopy (NIRS) measures cerebral regional tissue oxygenation (rSO2) and may contribute to patient safety during interhospital transport under ECMO support. We evaluated 16 adult ARDS patients undergoing interhospital ECMO transport by measuring cerebral rSO2 before and after initiation of ECMO support and continuously during transport. To compare peripheral oxygen saturation (SpO2) measurement with rSO2, both parameters were analyzed. NIRS monitoring for initiation of ECMO and interhospital transport under ECMO support was feasible, and there was no significant difference in the percentage of achievable valid measurements over time between cerebral rSO2 (88.4% [95% confidence interval {CI}, 81.3-95.0%]) and standard SpO2 monitoring 91.7% (95% CI, 86.1-94.2%), p = 0.68. No change in cerebral rSO2 was observed before 77% (73.5-81%) (median [interquartile range {IQR}]) and after initiation of ECMO support 78% (75-81%), p = 0.2. NIRS for cerebral rSO2 measurement is feasible during ECMO initiation and interhospital transport. Achievement of valid measurements of cerebral rSO2 was not superior to SpO2. In distinct patients (e.g., shock), measurement of cerebral rSO2 may contribute to improvement of patient safety during interhospital ECMO transport.

Objective: To assess the incidence and significance of invasive fungal diseases (IFD) during veno-venous (VV) ECMO support for acute respiratory distress syndrome (ARDS). Methods: Retrospective analysis from January 2013 to April 2021 of all ECMO cases for ARDS at a German University Hospital. In patients with IFD (IFD patients), type of IFD, time of IFD, choice of antifungal agent, duration, and success of therapy were investigated. For comparison, patients without IFD (non-IFD patients) were selected by propensity score matching using treatment-independent variables (age, gender, height, weight, and the Sequential Organ Failure Assessment (SOFA) score at ICU admission). Demographics, hospital and ICU length of stay, duration of ECMO therapy, days on mechanical ventilation, prognostic scores (Charlson Comorbidity Index (CCI), Therapeutic Intervention Scoring System (TISS), and length of survival were assessed. Results: A total of 646 patients received ECMO, 368 patients received VV ECMO. The incidence of IFD on VV ECMO was 5.98%, with 5.43% for Candida bloodstream infections (CBSI) and 0.54% for invasive aspergillosis (IA). In IFD patients, in-hospital mortality was 81.8% versus 40.9% in non-IFD patients. The hazard ratio for death was 2.5 (CI 1.1–5.4; p: 0.023) with IFD. Conclusions: In patients on VV ECMO for ARDS, about one in 17 contracts an IFD, with a detrimental impact on prognosis. Further studies are needed to address challenges in the diagnosis and treatment of IFD in this population.

ObjectiveVeno-venous (V-V) extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe acute respiratory distress syndrome (ARDS). In case of additional cardio-circulatory failure, some experienced centers upgrade the V-V ECMO with an additional arterial return cannula (termed V-VA ECMO). Here we analyzed short- and long-term outcome together with potential predictors of mortality.DesignMulticenter, retrospective analysis between January 2008 and September 2021.SettingThree tertiary care ECMO centers in Germany (Hannover, Bonn) and Switzerland (Zurich).PatientsSeventy-three V-V ECMO patients with ARDS and additional acute cardio-circulatory deterioration required an upgrade to V-VA ECMO were included in this study.Measurements and main resultsFifty-three patients required an upgrade from V-V to V-VA and 20 patients were directly triple cannulated. Median (Interquartile Range) age was 49 (28–57) years and SOFA score was 14 (12–17) at V-VA ECMO upgrade. Vasoactive-inotropic score decreased from 53 (12–123) at V-VA ECMO upgrade to 9 (3–37) after 24 h of V-VA ECMO support. Weaning from V-VA and V-V ECMO was successful in 47 (64%) and 40 (55%) patients, respectively. Duration of ECMO support was 12 (6–22) days and ICU length of stay was 32 (16–46) days. Overall ICU mortality was 48% and hospital mortality 51%. Two additional patients died after hospital discharge while the remaining patients survived up to two years (with six patients being lost to follow-up). The vast majority of patients was free from higher degree persistent organ dysfunction at follow-up. A SOFA score > 14 and higher lactate concentrations at the day of V-VA upgrade were independent predictors of mortality in the multivariate regression analysis.ConclusionIn this analysis, the use of V-VA ECMO in patients with ARDS and concomitant cardiocirculatory failure was associated with a hospital survival of about 50%, and most of these patients survived up to 2 years. A SOFA score > 14 and elevated lactate levels at the day of V-VA upgrade predict unfavorable outcome.

Objective: To assess the feasibility of extracorporeal membrane oxygenation (ECMO) or life support (ECLS) as last resort life support therapy in patients with acute pancreatitis and subsequent secondary acute respiratory distress syndrome (ARDS). Methods: Retrospective analysis from January 2013, to April 2020, of ECMO patients with pancreatitis-induced ARDS at a German University Hospital. Demographics, hospital and ICU length of stay, duration of ECMO therapy, days on mechanical ventilation, fluid balance, need for decompressive laparotomy, amount of blood products, prognostic scores (CCI (Charlson Comorbidity Index), SOFA (Sequential Organ Failure Assessment), RESP(Respiratory ECMO Survival Prediction), SAVE (Survival after Veno-Arterial ECMO)), and the total known length of survival were assessed. Results: A total of n = 495 patients underwent ECMO. Eight patients with acute pancreatitis received ECLS (seven veno-venous, one veno-arterial). Five (71%) required decompressive laparotomy as salvage therapy due to abdominal hypertension. Two patients with acute pancreatitis (25%) survived to hospital discharge. The overall median length of survival was 22 days. Survivors required less fluid in the first 72 h of ECMO support and showed lower values for all prognostic scores. Conclusion: ECLS can be performed as a rescue therapy in patients with pancreatitis and secondary ARDS, but nevertheless mortality remains still high. Thus, this last-resort therapy may be best suited for patients with fewer pre-existing comorbidities and no other organ failure.

IMPORTANCE: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. OBJECTIVE: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. DESIGN, SETTING, AND PARTICIPANTS: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. INTERVENTIONS: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. MAIN OUTCOMES AND MEASURES: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. RESULTS: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P

The current outbreak of coronavirus disease (COVID-19) has reached Germany The majority of people infected present with mild disease, but there are severe cases that need intensive care Unlike other acute infectious diseases progressing to sepsis, the severe courses of COVID19 seemingly show prolonged progression from onset of first symptoms to life-threatening deterioration of (primarily) lung function Diagnosis relies on PCR using specimens from the respiratory tract Severe ARDS reflects the hallmark of a critical course of the disease Preventing nosocomial infections (primarily by correct use of personal protective equipment) and maintenance of hospitals’ operational capability are of utmost importance Departments of Anaesthesia, Intensive Care and emergency medicine will envisage major challenges

The currently valid guidelines for resuscitation of the European Resuscitation Council (ERC) do not give any unambiguous recommendations for "transport with ongoing cardiopulmonary resuscitation". Furthermore, up to now there are no generally accepted criteria for terminating cardiopulmonary resuscitation, apart from certain signs of death. In spite of the generally poor outcome of patients being transported with ongoing cardiopulmonary resuscitation, there are a number of positive case reports and undisputable indications (e.g., in cases with a potentially reversible cause of cardiac arrest). The increase observed over the past few years in the number of patients being transported under cardiopulmonary resuscitation has as yet not been reflected in an improved prognosis for these patients. The use of mechanical chest compression devices with a better quality of chest compression, also under transport conditions, may have an influence on the number transports but this has not yet been evaluated sufficiently with regard to patient outcome. However, the decision to transport a patient resides with the responsible emergency physician who has to evaluate the prognosis for the patient on an individual basis.

Das Uberleben nach einem Herz-Kreislauf-Stillstand bleibt trotz erheblicher Bemuhungen zur Verbesserung der kardiopulmonalen Reanimation (CPR) gering. Die jungsten Anderungen der Internationalen Reanimationsrichtlinien 2005 betonen die Vermeidung von Unterbrechungen der Thoraxkompressionen. So wurden in der Vergangenheit auch verschiedene Reanimationsassistenzgerate mit dem Ziel entwickelt, effektive und kontinuierliche Thoraxkompressionen zu erreichen. Eine dieser Entwicklungen stellt das AutoPulse-System dar. Ausgehend von dem Fallbeispiel eines 66-jahrigen Patienten wird uber den mehr als 3-jahrigen Routineeinsatz des AutoPulse-Systems im Rettungsdienst der Stadt Bonn berichtet. Der AutoPulse stellt dieser Erfahrung nach eine sinnvolle Erweiterung und Bereicherung im Rahmen der Effektivitatsverbesserung der CPR dar.

The oxidoreductase Macrophage Migration Inhibitory Factor (MIF) is discussed as a promising target for immunomodulatory therapy in patients with severe sepsis. Moreover, MIF expresses tautomerase as well as thiol-protein oxidoreductase activities and has a potential role in cellular redox homeostasis, apoptosis inhibition, endotoxin responsiveness as well as regulation of nuclear transcription factors. To further elucidate a potential role of intracellular MIF in severe sepsis, we assessed alterations of intracellular MIF content in peripheral blood leukocytes of patients with severe sepsis in comparison to healthy controls and non-septic patients after major surgery. Intracellular MIF was significantly elevated simultaneously in lymphocytes, B-cells, macrophages and granulocytes of patients with severe sepsis when compared to healthy control individuals (p0.05) and increased when compared to non-septic patients after major surgery. In parallel, plasma MIF levels were elevated in severe sepsis (p0.05). There was no difference of intracellular MIF in lymphocytes, B-cells, macrophages or granulocytes between surviving and non-surviving patients with severe sepsis (p0.05). However, in survivors LPS ex vivo stimulation increased MIF secretion but not in non-survivors of sepsis (p0.05). This finding underlines the role of intracellular MIF in inflammatory diseases. It suggests monitoring of intracellular MIF in further clinical and non-clinical research valuable.

During sepsis, a severe systemic disorder, micronutrients often are decreased. Apoptosis is regarded as an important mechanism in the development of often significant immunosuppression in the course of the disease. This study aimed to investigate alpha-tocopherol and selenium in reference to apoptosis in patients with sepsis. 16 patients were enrolled as soon as they fulfilled the criteria of severe sepsis. 10 intensive care patients without sepsis and 11 healthy volunteers served as controls. alpha-Tocopherol, selenium and nucleosomes were measured in serum. Phosphatidylserine externalization and Bcl-2 expression were analyzed in T-cells by flow cytometry. Serum alpha-tocopherol and selenium were decreased in severe sepsis but not in non-septic critically ill patients (p < 0.05). Conversely, markers of apoptosis were increased in sepsis but not in critically ill control patients: Nucleosomes were found to be elevated 3 fold in serum (p < 0.05) and phosphatidylserine was externalized on an expanded subpopulation of T-cells (p < 0.05) while Bcl-2 was expressed at lower levels (p < 0.05). The decrease of micronutrients correlated with markers of accelerated apoptosis. Accelerated apoptosis in sepsis is associated with low alpha-tocopherol and selenium. The results support the investigation of micronutrient supplementation strategies in severe sepsis.

Objective: Cardiac surgery causes induction and release of inflammatory mediators that may be regulated by genetic background. Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator that is known to be up-regulated in patients undergoing cardiac operations. Here we analyzed genotype distribution and allele frequency of the MIF-173*G/C single nucleotide polymorphism (SNP) and MIF plasma levels in patients undergoing surgical revascularization with (on-pump, n = 45) and without (off-pump, n = 34) cardiopulmonary bypass (CPB). Methods: Genotyping was performed using a real-time PCR-based system with a hybridization probe system specific for the MIF-173*G/C SNP. In on-pump patients, blood samples were drawn before start of CPB, after termination of CPB and 12 h postoperatively. In off-pump patients, blood samples were collected before stabilizer placement, after removal of the stabilizer and 12 h postoperatively. MIF levels were measured using ELISA technique. Results: Genotype distribution and allele frequencies were comparable between on-pump and off-pump patients. When comparing patients according to MIF genotype, a significant increase of MIF plasma levels after completed coronary bypass grafting using CPB was found in patients heterozygous for the MIF-173*G/C SNP (p < 0.05). Moreover, on-pump patients showed significantly decreased MIF plasma levels after 12 h postoperatively (p < 0.05). In off-pump patients, MIF plasma levels were not significantly different over the time-course and were independent of the genotype. Conclusions: Patients carrying the C-allele showed significantly increased levels of the proinflammatory cytokine MIF compared to G/G homozygous when revascularization was carried out using CPB. The G/C genotype may be associated with a severe inflammatory reaction and therefore preoperative screening could be beneficial for patients undergoing cardiac surgery using CPB.

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Die Sepsis gehort nach wie vor zu den haufigsten Todesursachen bei Intensivpatienten. Der Pathogenese der Erkrankung liegt ein komplexes Immungeschehen zugrunde. Neueste Erkenntnisse zeigen, dass Zellen des Abwehrsystems bei der Sepsis im Rahmen der Immunantwort haufig eine Signalkaskade aktivieren, die zum programmierten Zelltod, der sog. Apoptose, fuhrt. Apoptose von Leukozyten wurde sowohl im Tiermodell als auch bei Patienten mit Sepsis beobachtet. Bei der Regulation der Apoptose spielen das mitochondriale Protein Bcl-2 und die zytoplasmatische Enzymkaskade der Kaspasen eine wesentliche Rolle. Durch Uberexprimierung von Bcl-2 oder Hemmung der Kaspasen konnte im Tiermodell der Sepsis ein deutlicher Uberlebensvorteil demonstriert werden. Erste Arbeiten zeigten auch die Relevanz der Apoptose bei Patienten mit schwerer Sepsis. Ziel aktueller Forschung auf diesem Gebiet ist es, durch gezielte Beeinflussung der Apoptose neue molekulare Ansatze zur Therapie der Sepsis zu finden.

Background Heparin-induced thrombocytopenia (HIT) causes thromboembolic complications which threaten life and limb. Heparin is administered to virtually every critically ill patient as a protective measure against thromboembolism. Argatroban is a promising alternative anticoagulant agent. However, a safe dose which still provides effective thromboembolic prophylaxis without major bleeding still needs to be identified. Methods Critically ill patients (n = 42) diagnosed with HIT at a tertiary medical center intensive care unit from 2005 to 2010 were included in this retrospective analysis. Patient records were perused for preexisting history of HIT, heparin dosage before HIT, argatroban dosage, number of transfusions required, thromboembolic complications and length of ICU stay (ICU LOS). Patients were allocated to Simplified Acute Physiology Scores above and below 30 (SAPS >30, SAPS 0.05) to achieve effective anticoagulation. No thromboembolic complications were encountered. Argatroban had to be discontinued temporarily in 16 patients for a total of 57 times due to diagnostic or surgical procedures, supratherapeutic aPTT and bleeding without increasing the number of transfusions. A history of HIT was associated with a shorter ICU LOS and significantly reduced transfusion need when compared to patients with no history of HIT. Cost calculation favour argatroban due to increased transfusion needs during heparin administration and increase ICU LOS. Conclusion Argatroban can be used at doses

Background Macrophage migration inhibitory factor (MIF) plays an important regulatory role in sepsis. In the promoter region a C/G single nucleotide polymorphism (SNP) at position -173 (rs755622) and a CATT5-8 microsatellite at position -794 are related to modified promoter activity. The purpose of the study was to analyze their association with the incidence and outcome of severe sepsis. Methods Genotype distributions and allele frequencies in 169 patients with severe sepsis, 94 healthy blood donors and 183 postoperative patients without signs of infection or inflammation were analyzed by real time PCR and Sequence analysis. All included individuals were Caucasians. Results Genotype distribution and allele frequencies of severe sepsis patients were comparable to both control groups. However, the genotype and allele frequencies of both polymorphisms were associated significantly with the outcome of severe sepsis. The highest risk of dying from severe sepsis was detectable in patients carrying a haplotype with the alleles -173 C and CATT7 (p = 0.0005, fisher exact test, RR = 1,806, CI: 1.337 to 2.439). Conclusion The haplotype with the combination of the -173 C allele and the -794 CATT7 allele may not serve as a marker for susceptibility to sepsis, but may help identify septic patients at risk of dying.