[ARDS Diagnostics and Treatment after the Coronavirus Pandemic - Everything as it was?] / ARDS-Diagnostik und -Therapie nach der Coronapandemie ­ alles beim Alten?

ARDS is a syndrome that can develop as a result of various underlying diseases. For a long time, the prevailing belief was that the course of the disease was comparable regardless of the underlying disease. However, even before the COVID-19 pandemic, it was suspected that there were different manifestations that could be treated more individually and thus reduce the high mortality rate of ARDS, which has remained unchanged for years. The various findings on the heterogeneity of the course of the disease in COVID-related ARDS appear to confirm these assumptions. It is therefore to be expected that the diagnosis and treatment of non-COVID-related ARDS will also have to be individualised according to such phenotypes in the future. However, as long as the effectiveness of such strategies has not been proven in clinical trials, the current recommendations for ARDS therapy will remain valid for the time being. However, the adjustments already formulated in this context to individual pathophysiological conditions with regard to respiratory mechanics, ventilation-perfusion distribution and possible cardiac dysfunction should be made more meticulously than has usually been the case to date.

Using Gated Recurrent Unit Networks for the Prediction of Hemodynamic and Pulmonary Decompensation.

This paper presents a new medical severity scoring system, used to assess the risk of hemodynamic and pulmonary decompensation for patients being treated in intensive care units. The score presented here includes drug circulatory support and ventilation mode data for the evaluation of the patient's biosignals and laboratory values. It is shown that Gated Recurrent Unit-based neural networks are able to predict the maximal severity class within a 24 hour prediction time-frame (hemodynamic: 0.85 AUROC / pulmonary: 0.9 AUROC), and can estimate the underlying decompensation score for prediction times of up to 24 hours with mean errors of 6.3% of the maximal possible pulmonary, and 9.6% of the hemodynamic score. These results are based on 60h observation period. Clinical Relevance- Hemodynamic and pulmonary decom-pensation are life threatening dynamic events that can lead to death of patients. Early detection of these incidents is essential in order to intervene therapeutically and to improve survival chances. In everyday intensive care physicians are confronted with a vast number of laboratory values and vital parameters. There is a risk that early stages of hemodynamic and pulmonary decompensation are misjudged. The implementation of robust warning systems could support physicians in detecting these critical events and initiate therapeutical intervention in time which would achieve significant reduction of patient mortality.

[Emergency Cricothyrotomy - step by step]. / Notfallkoniotomie ­ Schritt für Schritt.

Emergency cricothyrotomy is a live saving intervention to rapidly gain access to the airways in patients who cannot be intubated nor ventilated. Considering complications such as bleeding, thyroid and cricoid cartilage injury and creation of a false tract emergency cricothyrotomy should not be performed until non-invasive attempts including video laryngoscopy and the use of supraglottic airway devices have been exploited within a fixed difficult airway management algorithm. Methods of emergency cricothyrotomy can be differentiated in a catheter-over-needle, Seldinger-wire and surgical technique. However, success is less dependent from the choice of method but from individual experience and training. Despite a lack of evidence due to its infrequent use cricothyrotomy generally results in an acceptable success rate. In this review a selection of commercially available cricothyrotomy sets is presented, indications for their use are outlined and their handling is described.

Efficacy and safety of early target-controlled plasma volume replacement with a balanced gelatine solution versus a balanced electrolyte solution in patients with severe sepsis/septic shock: study protocol, design, and rationale of a prospective, randomized, controlled, double-blind, multicentric, international clinical trial : GENIUS-Gelatine use in ICU and sepsis.

BACKGROUND: Sepsis is associated with capillary leakage and vasodilatation and leads to hypotension and tissue hypoperfusion. Early plasma volume replacement is required to achieve haemodynamic stability (HDS) and maintain adequate tissue oxygenation. The right choice of fluids to be used for plasma volume replacement (colloid or crystalloid solutions) is still a matter of debate, and large trials investigating the use of colloid solutions containing gelatine are missing. This study aims to investigate the efficacy and safety of plasma volume replacement using either a combined gelatine-crystalloid regime (1:1 ratio) or a pure crystalloid regime. METHODS: This is a prospective, controlled, randomized, double-blind, international, multicentric phase IV study with two parallel groups that is planned to be conducted at European intensive care units (ICUs) in a population of patients with hypovolaemia in severe sepsis/septic shock. A total of 608 eligible patients will be randomly assigned to receive either a gelatine-crystalloid regime (Gelaspan® 4% and Sterofundin® ISO, B. Braun Melsungen AG, in a 1:1 ratio) or a pure crystalloid regime (Sterofundin® ISO) for plasma volume replacement. The primary outcome is defined as the time needed to achieve HDS. Plasma volume replacement will be target-controlled, i.e. fluids will only be administered to volume-responsive patients. Volume responsiveness will be assessed through passive leg raising or fluid challenges. The safety and efficacy of both regimens will be assessed daily for 28 days or until ICU discharge (whichever occurs first) as the secondary outcomes of this study. Follow-up visits/calls will be scheduled on day 28 and day 90. DISCUSSION: This study aims to generate evidence regarding which regimen-a gelatine-crystalloid regimen or a pure crystalloid regimen-is more effective in achieving HDS in critically ill patients with hypovolaemia. Study participants in both groups will benefit from the increased safety of target-controlled plasma volume replacement, which prevents fluid administration to already haemodynamically stable patients and reduces the risk of harmful fluid overload. TRIAL REGISTRATION: The European clinical trial database EudraCT 2015-000057-20 and the ClinicalTrials.gov Protocol Registration and Results System ClinicalTrials.gov NCT02715466 . Registered on 17 March 2016.

Validation of RESP and PRESERVE score for ARDS patients with pumpless extracorporeal lung assist (pECLA).

BACKGROUND: RESP score and PRESERVE score have been validated for veno-venous Extracorporeal Membrane Oxygenation in severe ARDS to assume individual mortality risk. ARDS patients with low-flow Extracorporeal Carbon Dioxide Removal, especially pumpless Extracorporeal Lung Assist, have also a high mortality rate, but there are no validated specific or general outcome scores. This retrospective study tested whether these established specific risk scores can be validated for pumpless Extracorporeal Lung Assist in ARDS patients in comparison to a general organ dysfunction score, the SOFA score. METHODS: In a retrospective single center cohort study we calculated and evaluated RESP, PRESERVE, and SOFA score for 73 ARDS patients with pumpless Extracorporeal Lung Assist treated between 2002 and 2016 using the XENIOS iLA Membrane Ventilator. Six patients had a mild, 40 a moderate and 27 a severe ARDS according to the Berlin criteria. Demographic data and hospital mortality as well as ventilator settings, hemodynamic parameters, and blood gas measurement before and during extracorporeal therapy were recorded. RESULTS: Pumpless Extracorporeal Lung Assist of mechanical ventilated ARDS patients resulted in an optimized lung protective ventilation, significant reduction of PaCO2, and compensation of acidosis. Scoring showed a mean score of alive versus deceased patients of 3 ± 1 versus - 1 ± 1 for RESP (p < 0.01), 3 ± 0 versus 6 ± 0 for PRESERVE (p < 0.05) and 8 ± 1 versus 10 ± 1 for SOFA (p < 0.05). Using receiver operating characteristic curves, area under the curve (AUC) was 0.78 (95% confidence interval (CI) 0.67-0.89, p < 0.01) for RESP score, 0.80 (95% CI 0.70-0.90, p < 0.0001) for PRESERVE score and 0.66 (95% CI 0.53-0.79, p < 0.05) for SOFA score. CONCLUSIONS: RESP and PRESERVE scores were superior to SOFA, as non-specific critical care score. Although scores were developed for veno-venous ECMO, we could validate RESP and PRESERVE score for pumpless Extracorporeal Lung Assist. In conclusion, RESP and PRESERVE score are suitable to estimate mortality risk of ARDS patients with an arterio-venous pumpless Extracorporeal Carbon Dioxide Removal.

[The Laryngeal mask - step by step]. / Die Larynxmaske ­ Schritt für Schritt.

Laryngeal masks are supraglottic airway devices developed in the early 1980s. Today, they are frequently used in clinical routine to provide airway access for mechanical ventilation in patients undergoing surgery with a short duration. Moreover, the they have also become integral part of difficult airway management in patients who cannot be intubated by the use of conventional laryngoscopy.Relevant advances have been made to simplify their positioning and improve tightness with the aim to allow for the use of higher airway pressures during mechanical ventilation thereby reducing the risk of gastric insufflation and pulmonary aspiration. Focusing on this goal, several different prototypes have been developed and introduced in clinical practice until today. However, even these new developed laryngeal masks still do not provide reliable protection against pulmonary aspiration until today. Consequently, their use In critical care medicine is still limited to rescue situations with intubation failure.In this review some of the most popular lanryngeal masks are presented, indications for their use are outlined and their handling is described.

[ARDS - An Update - Part 2: Therapy and Outcome]. / ARDS ­ Ein Update ­ Teil 2: Therapie und Outcome.

The Acute Respiratory Distress Syndrome (ARDS) is defined by hypoxemic respiratory failure due to inflammatory response within the lung usually requiring invasive mechanical ventilation. Despite more than 50 years of scientific research numerous issues especially regarding mechanical ventilation as the most important treatment option remain unclear. Most important, adjustment of mechanical ventilation is challenging due to desirable beneficial effects on pulmonary gas exchange on the one hand and deleterious effects in terms of ventilator-associated lung injury on the other. Specifically, optimal settings of positive end-expiratory pressure and the role of spontaneous breathing activity are still controversial. Because no specific pharmacological therapy revealed beneficial effects until today, adjunctive treatment is actually limited to prone positioning and restrictive fluid balance. Long-term outcome of ARDS survivors is often affected by anxiety and mental health disorders.

[ARDS - An Update - Part 1: Epidemiology, Pathophysiology and Diagnosis]. / ARDS ­ Ein Update ­ Teil 1: Epidemiologie, Pathophysiologie und Diagnostik.

The Acute Respiratory Distress Syndrome (ARDS) is defined by hypoxemic respiratory failure caused by inflammatory response within the lung usually requiring invasive mechanical ventilation. Despite more than 50 years of research numerous issues regarding epidemiology, pathophysiology and diagnosis remain unclear until today: Due to rather unspecific clinical diagnostic criteria incidence of ARDS varies considerably in clinical trials with a range from 4 to 79 cases per 100 000 persons per year. Consequently, mortality is also highly variable from about 40 to 60% in severe ARDS. Pathophysiology is mainly characterized by granulocyte infiltration of the lung thereby inducing interstitial and intra-alveolar lung edema with surfactant depletion and atelectasis formation. However, it is unknown whether pulmonary and extrapulmonary causes and risk factors for ARDS are accompanied by different pathophysiologic processes due to primary endothelial and epithelial injury. Thus, possible benefits of corresponding biomarker panels for the differentiation of endothelial and epithelial lung injury are also speculative until today. Therefore, ARDS diagnosis is still based on clinical findings and radiological imaging.

[Management of a Port Catheter-Related Superior Vena Cava Thrombosis in the Setting of Active Crohn's Disease: A Case Report]. / Management einer portassoziierten Vena-cava-superior-Thrombose im Rahmen eines Crohn-Schubes.

History and clinical findings A 56 year-old woman was admitted to our hospital for treatment of a severe exacerbation of Crohn's disease. During the stay a port catheter was implanted, safeguarding nutrition. A few days later the patient developed symptoms of a severe superior vena cava (SVC) syndrome with dyspnea, cyanosis, headaches and swelling of face and upper extremities. Examination A CT scan showed port catheter-associated SVC thrombosis with complete occlusion of the SVC. Diagnosis There was a coexistence of a port catheter-associated SVC thrombosis with complete occlusion of the SVC and a severe exacerbation of Crohn's disease with haematochezia. Therapy and clinical course Local prolonged thrombolysis through the port catheter analogous to the regimen used in the 2012 CaVenT Study was started. Subsequently, symptoms of SVC obstruction as well as thrombus extent improved markedly, with only minor increase in gastrointestinal bleeding. Conclusion Local thrombolysis appears to be a safe and effective therapy for port catheter-associated thrombosis that may be considered in the setting of increased risk of hemorrhage.

Preserving spontaneous breathing during mechanical ventilatory support: an old yet fascinating story.

Facilitation of early spontaneous breathing activity is the most important measure to shorten weaning and avoid ventilator-induced lung injury and diaphragmatic injury in mechanically ventilated patients. However, the optimal degree of spontaneous muscle activity and ventilator support remains to be determined. Furthermore, effectiveness in relation to the pathophysiology of respiratory failure is unclear. In this regard the experimental study by Saddy and colleagues reveals interesting insights into the pathophysiology of ventilator-induced injury. More important, their results raise important questions that should be evaluated in further studies.

[Surgical therapy and critical care medicine in severely burned patients - Part 2: the basics in definite care]. / Operative Therapie und Intensivmedizin bei Schwerbrandverletzten - Teil 2: Grundzüge der Weiterversorgung.

Critical care medicine in severely burned patients should be adapted to the different pathophysiological phases. Accordingly, surgical and non-surgical therapy must be coordinated adequately. Initial stabilization of the burn victim during the first 24 hours (Surgical therapy and critical care medicine in severely burned patients - Part 1: the first 24 ours, AINS 9/12) is followed by a long lasting reconstructive period. During this time calculated fluid replacement to compensate evaporative losses by large bourn wounds is as essential as reconstruction of the integrity of the skin and the modulation of metabolic consequences following severe burn injury. Special attention has to be paid to local and systemic infections.

Lower tidal volume strategy (≈3 ml/kg) combined with extracorporeal CO2 removal versus 'conventional' protective ventilation (6 ml/kg) in severe ARDS: the prospective randomized Xtravent-study.

BACKGROUND: Acute respiratory distress syndrome is characterized by damage to the lung caused by various insults, including ventilation itself, and tidal hyperinflation can lead to ventilator induced lung injury (VILI). We investigated the effects of a low tidal volume (V(T)) strategy (V(T) ≈ 3 ml/kg/predicted body weight [PBW]) using pumpless extracorporeal lung assist in established ARDS. METHODS: Seventy-nine patients were enrolled after a 'stabilization period' (24 h with optimized therapy and high PEEP). They were randomly assigned to receive a low V(T) ventilation (≈3 ml/kg) combined with extracorporeal CO2 elimination, or to a ARDSNet strategy (≈6 ml/kg) without the extracorporeal device. The primary outcome was the 28-days and 60-days ventilator-free days (VFD). Secondary outcome parameters were respiratory mechanics, gas exchange, analgesic/sedation use, complications and hospital mortality. RESULTS: Ventilation with very low V(T)'s was easy to implement with extracorporeal CO2-removal. VFD's within 60 days were not different between the study group (33.2 ± 20) and the control group (29.2 ± 21, p = 0.469), but in more hypoxemic patients (PaO2/FIO2 ≤150) a post hoc analysis demonstrated significant improved VFD-60 in study patients (40.9 ± 12.8) compared to control (28.2 ± 16.4, p = 0.033). The mortality rate was low (16.5%) and did not differ between groups. CONCLUSIONS: The use of very low V(T) combined with extracorporeal CO2 removal has the potential to further reduce VILI compared with a 'normal' lung protective management. Whether this strategy will improve survival in ARDS patients remains to be determined (Clinical trials NCT 00538928).

[Surgical therapy and critical care medicine in severely burned patients - Part 1: the first 24 ours]. / Operative Therapie und Intensivmedizin bei Schwerbrandverletzten - Teil 1: die ersten 24 Stunden.

Critical care medicine in severely burned patients should be adapted to the different pathophysiological phases. Accordingly, surgical and non-surgical therapy must be coordinated adequately. Initial wound care comprises topical treatment of less severely injured skin and surgical debridement of severely burned areas. The first 24 hours of intensive care are focused on calculated fluid delivery to provide stable hemodynamics and avoid progression of local edema formation. In the further course wound treatment with split-thickness skin grafts is the major aim of surgical therapy. Critical care is focused on the avoidance of complications like infections and ventilator associated lung injury. Therefore, lung-protective ventilation strategies, weaning and sedation protocols, and early enteral nutrition are important cornerstones of the treatment.

Analysis of regional compliance in a porcine model of acute lung injury.

Lung protective ventilation in acute lung injury (ALI) focuses on using low tidal volumes and adequate levels of positive end-expiratory pressure (PEEP). Identifying optimal pressure is difficult because pressure-volume (PV) relations differ regionally. Precise analysis demands local measurements of pressures and related alveolar morphologies. In a porcine model of surfactant depletion (n=24), we combined measuring static pressures with endoscopic microscopy and electrical impedance tomography (EIT) to examine regional PV loops and morphologic heterogeneities between healthy (control group; CON) and ALI lungs ventilated with low (LVT) or high tidal volumes (HVT). Quantification included indices for microscopy (Volume Air Index (VAI), Heterogeneity and Circularity Index), EIT analysis and calculation of regional compliances due to generated PV loops. We found that: (1) VAI decreased in lower lobe after ALI, (2) electrical impedance decreased in dorsal regions and (3) PV loops differed regionally. Further studies should prove the potentials of these techniques on individual respiratory settings and clinical outcome.

Simvastatin reduces endotoxin-induced acute lung injury by decreasing neutrophil recruitment and radical formation.

INTRODUCTION: Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. As simvastatin exerts protective effects in inflammatory diseases we explored its effects on development of ALI and due to the importance of neutrophils in ALI also on neutrophil effector functions. METHODS: C57Bl/6 mice were exposed to aerosolized LPS (500 µg/ml) for 30 min. The count of alveolar, interstitial, and intravasal neutrophils were assessed 4 h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and albumin content in the BAL fluid. In vitro, we analyzed the effect of simvastatin on neutrophil adhesion, degranulation, apoptosis, and formation of reactive oxygen species. To monitor effects of simvastatin on bacterial clearance we performed phagocytosis and bacterial killing studies in vitro as well as sepsis experiments in mice. RESULTS: Simvastatin treatment before and after onset of ALI reduces neutrophil influx into the lung as well as lung permeability indicating the protective role of simvastatin in ALI. Moreover, simvastatin reduces the formation of ROS species and adhesion of neutrophils without affecting apoptosis, bacterial phagocytosis and bacterial clearance. CONCLUSION: Simvastatin reduces recruitment and activation of neutrophils hereby protecting from LPS-induced ALI. Our results imply a potential role for statins in the management of ALI.

Treatment of burns in the first 24 hours: simple and practical guide by answering 10 questions in a step-by-step form.

Residents in training, medical students and other staff in surgical sector, emergency room (ER) and intensive care unit (ICU) or Burn Unit face a multitude of questions regarding burn care. Treatment of burns is not always straightforward. Furthermore, National and International guidelines differ from one region to another. On one hand, it is important to understand pathophysiology, classification of burns, surgical treatment, and the latest updates in burn science. On the other hand, the clinical situation for treating these cases needs clear guidelines to cover every single aspect during the treatment procedure. Thus, 10 questions have been organised and discussed in a step-by-step form in order to achieve the excellence of education and the optimal treatment of burn injuries in the first 24 hours. These 10 questions will clearly discuss referral criteria to the burn unit, primary and secondary survey, estimation of the total burned surface area (%TBSA) and the degree of burns as well as resuscitation process, routine interventions, laboratory tests, indications of Bronchoscopy and special considerations for Inhalation trauma, immediate consultations and referrals, emergency surgery and admission orders. Understanding and answering the 10 questions will not only cover the management process of Burns during the first 24 hours but also seems to be an interactive clear guide for education purpose.

Neurological outcome after experimental lung injury.

We examined the influences of acute lung injury and hypoxia on neurological outcome. Functional performance was assessed using a neurocognitive test and a neurologic deficit score (NDS) five days before. On experimental day, mechanically ventilated pigs were randomized to hypoxia only (HO group, n=5) or to acute lung injury (ALI group, n=5). Hemodynamics, respiratory mechanics, systemic cytokines and further physiologic variables were obtained at baseline, at the time of ALI, 2, 4 and 8h thereafter. Subsequently, injured lungs were recruited and animals weaned from the ventilator. Neurocognitive testing was re-examined for five days. Then, brains were harvested for neurohistopathology. After the experiment, neurocognitive performance was significantly worsened and the NDS increased in the ALI group. Histopathology revealed no significant differences. Oxygenation was comparable between groups although significantly higher inspiratory pressures occured after ALI. Cytokines showed a trend towards higher levels after ALI. Neurocognitive compromise after ALI seems due to a more pronounced inflammatory response and complex mechanical ventilation.