BACKGROUND Prone positioning has become a standard therapy in acute respiratory distress syndrome to improve oxygenation and decrease mortality. However, little is known about prone positioning in lung transplant recipients. This large, singe-center analysis investigated whether prone positioning improves gas exchange after lung transplantation. METHODS Clinical data of 583 patients were analyzed. Prone position was considered in case of impaired gas exchange Pa O2 /fraction of oxygen in inhaled air (<250), signs of edema after lung transplantation, and/or evidence of reperfusion injury. Patients with hemodynamic instability or active bleeding were not proned. Impact of prone positioning (n = 165) on gas exchange, early outcome and survival were determined and compared with patients in supine positioning (n = 418). RESULTS Patients in prone position were younger, more likely to have interstitial lung disease, and had a higher lung allocation score. Patients were proned fora median of 19 hours (interquartile range,15-26) hours). They had significantly lower Pa O2 /fraction of oxygen in inhaled air (227 +/- 96 vs 303 +/- 127 mm Hg, P = .004), and lower lung compliance (24.8 +/- 9.1 mL/mbar vs 29.8 +/- 9.7 mL/mbar, P < .001) immediately after lung transplantation. Both values significantly improved after prone positioning for 24 hours (Pa O2 /fraction of oxygen ratio: 331 +/- 91 mm Hg; lung compliance: 31.7 +/- 20.2 mL/ mbar). Survival at 90 days was similar between the 2 groups (93% vs 96%, P = .105). CONCLUSIONS Prone positioning led to a significant improvement in lung compliance and oxygenation after lung transplantation. Prospective studies are needed to confirm the benefit of prone positioning in lung transplantation. (Ann Thorac Surg 2024;117:1045-52) (c) 2024 The Authors. Published by Elsevier Inc. on behalf of The Society of Thoracic Surgeons. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

This article is intended to provide clinically working anesthesiologists with a practice-oriented overview of selected important current guidelines and recommendations pertaining to intraoperative prevention of infection. The contents of this article are based on the guidelines or recommendation of the World Health Organization (WHO) and the Association of the Scientific Medical Societies in Germany (AWMF) as well as the Commission for Hospital Hygiene and Infection Prevention (KRINKO) at the Robert Koch Institute (RKI). The authors' objective is to foster and support the standard of infection prevention and control in the operating theater by optimizing the standard of hygiene in daily practice to reduce the number of perioperative infections.

Hasibeder, Walter; Markstaller, Klaus; Schaden, Eva; Kietaibl, Sibylle Author Information

Background Duration of invasive mechanical ventilation (IMV) prior to extracorporeal membrane oxygenation (ECMO) affects outcome in acute respiratory distress syndrome (ARDS). In coronavirus disease 2019 (COVID-19) related ARDS, the role of pre-ECMO IMV duration is unclear. This single-centre, retrospective study included critically ill adults treated with ECMO due to severe COVID-19-related ARDS between 01/2020 and 05/2021. The primary objective was to determine whether duration of IMV prior to ECMO cannulation influenced ICU mortality. Results During the study period, 101 patients (mean age 56 [SD ± 10] years; 70 [69%] men; median RESP score 2 [IQR 1–4]) were treated with ECMO for COVID-19. Sixty patients (59%) survived to ICU discharge. Median ICU length of stay was 31 [IQR 20.7–51] days, median ECMO duration was 16.4 [IQR 8.7–27.7] days, and median time from intubation to ECMO start was 7.7 [IQR 3.6–12.5] days. Fifty-three (52%) patients had a pre-ECMO IMV duration of > 7 days. Pre-ECMO IMV duration had no effect on survival ( p = 0.95). No significant difference in survival was found when patients with a pre-ECMO IMV duration of < 7 days (< 10 days) were compared to ≥ 7 days (≥ 10 days) ( p = 0.59 and p = 1.0). Conclusions The role of prolonged pre-ECMO IMV duration as a contraindication for ECMO in patients with COVID-19-related ARDS should be scrutinised. Evaluation for ECMO should be assessed on an individual and patient-centred basis.

BACKGROUND: Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown. METHODS: This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis. RESULTS: A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the 'SSC' group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of 'SSC' patients was severely impaired compared to 'no SSC' patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004). CONCLUSIONS: SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing. (C) 2022 The Author(s). Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.

Background Although the number of lung transplantations (LTx) performed worldwide for coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS) is still low, there is general agreement that this treatment can save a subgroup of the most severely ill patients with irreversible lung damage. However, the true proportion of patients eligible for LTx, the overall outcome and the impact of LTx on the pandemic are unknown. Methods A retrospective analysis was performed using a nationwide registry of hospitalised patients with confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection admitted between 1 January 2020 and 30 May 2021 in Austria. Patients referred to one of the two Austrian LTx centres were analysed, and grouped into patients accepted and rejected for LTx. Detailed outcome analysis was performed for all patients who received a LTx for post-COVID-19 ARDS and compared with patients who underwent LTx for other indications. Results Between 1 January 2020 and 30 May 2021, 39 485 patients were hospitalised for COVID-19 in Austria. 2323 required mechanical ventilation and 183 received extracorporeal membrane oxygenation (ECMO) support. 106 patients with severe COVID-19 ARDS were referred for LTx. Of these, 19 (18%) underwent LTx. 30-day mortality after LTx was 0% for COVID-19 ARDS transplant recipients. At a median follow-up of 134 (47–450) days, 14 out of 19 patients were alive. Conclusions Early referral of ECMO patients to a LTx centre is pivotal in order to select patients eligible for LTx. Transplantation offers excellent midterm outcomes and should be incorporated in the treatment algorithm of post-COVID-19 ARDS.

Patients presenting with insufficient tissue oxygenation and impaired lung function as in acute respiratory distress syndrome (ARDS) frequently require mechanical ventilation with supplemental oxygen. Despite the lung being used to experiencing the highest partial pressure of oxygen during healthy breathing, the organ is susceptible to oxygen-induced injury at supraphysiological concentrations. Hyperoxia-induced lung injury (HALI) has been regarded as a second hit to pre-existing lung injury and ventilator-induced lung injury (VILI) attributed to oxidative stress. The injured lung has a tendency to form atelectasis, a cyclic collapse and reopening of alveoli. The affected lung areas experience oxygen conditions that oscillate between hyperoxia and hypoxia rather than remaining in a constant hyperoxic state. Mechanisms of HALI have been investigated in many animal models previously. These studies provided insights into the effects of hyperoxia on the whole organism. However, cell type-specific responses have not been dissected in detail, but are necessary for a complete mechanistic understanding of ongoing pathological processes. In our study, we investigated the effects of constant and intermittent hyperoxia on the lung endothelium from a mouse by an in vitro proteomic approach. We demonstrate that these oxygen conditions have characteristic effects on the pulmonary endothelial proteome that underlie the physiological (patho)mechanisms.

A multiplex polymerase chain reaction (PCR) procedure to amplify 18S rRNA gene fragments has been developed. Amplified DNA fragments of the expected size were obtained which were specific for Cryptosporidium parvum and Cryptosporidium wrairi (422 bp), Cryptosporidium baileyi (11106 bp) and Cryptosporidium muris (1346 bp). Criptosporidium parvum and C. wrairi can be distinguished using a PCR/restriction fragment length polymorphism (RFLP) analysis of the Cryptosporidium outer wall protein (COWP) gene, and these two techniques were applied to DNA extracted from whole faeces using a simple and rapid procedure. Cryptosporidium parvum DNA was detected in the faeces of 72 humans and 24 calves where cryptosporidial oocysts were demonstrated using conventional light microscopy. The specific DNA fragments were not amplified using extracts of material containing other lower eukaryotic parasites.

ZusammenfassungDer vorliegende Artikel soll klinisch tätigen AnästhesistInnen einen praxisorientierten Überblick zu ausgewählten, wichtigen Empfehlungen der Hygiene im OP-Bereich vermitteln. Die Inhalte des Artikels basieren auf den Leitlinien oder Empfehlungen der World Health Organisation (WHO), der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) sowie der Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) am Robert Koch-Institut (RKI). Die Zielsetzung der Autoren ist es, den Hygienestandard in der täglichen Praxis zu optimieren, um die Zahl perioperativer Infektionen zu reduzieren.

Background Acute respiratory distress syndrome (ARDS) is a complex clinical diagnosis with various possible etiologies. One common feature, however, is pulmonary permeability edema, which leads to an increased alveolar diffusion pathway and, subsequently, impaired oxygenation and decarboxylation. A novel inhaled peptide agent (AP301, solnatide) was shown to markedly reduce pulmonary edema in animal models of ARDS and to be safe to administer to healthy humans in a Phase I clinical trial. Here, we present the protocol for a Phase IIB clinical trial investigating the safety and possible future efficacy endpoints in ARDS patients. Methods This is a randomized, placebo-controlled, double-blind intervention study. Patients with moderate to severe ARDS in need of mechanical ventilation will be randomized to parallel groups receiving escalating doses of solnatide or placebo, respectively. Before advancing to a higher dose, a data safety monitoring board will investigate the data from previous patients for any indication of patient safety violations. The intervention (application of the investigational drug) takes places twice daily over the course of 7 days, ensued by a follow-up period of another 21 days. Discussion The patients to be included in this trial will be severely sick and in need of mechanical ventilation. The amount of data to be collected upon screening and during the course of the intervention phase is substantial and the potential timeframe for inclusion of any given patient is short. However, when prepared properly, adherence to this protocol will make for the acquisition of reliable data. Particular diligence needs to be exercised with respect to informed consent, because eligible patients will most likely be comatose and/or deeply sedated at the time of inclusion. Trial registration This trial was prospectively registered with the EU Clinical trials register (clinicaltrialsregister.eu). EudraCT Number: 2017-003855-47 .

Supplemental oxygen is frequently used together with mechanical ventilation to achieve sufficient blood oxygenation. Despite the undoubted benefits, it is vigorously debated whether too much oxygen can also have unpredicted side-effects. Uncertainty is also due to the fact that the molecular mechanisms are still insufficiently understood. The lung endothelium is covered with an exceptionally broad glycocalyx, carrying N- and O-glycans, proteoglycans, glycolipids and glycosaminoglycans. Glycan structures are not genetically determined but depend on the metabolic state and the expression level and activity of biosynthetic and glycan remodeling enzymes, which can be influenced by oxygen and the redox status of the cell. Altered glycan structures can affect cell interactions and signaling. In this study, we investigated the effect of different oxygen conditions on aspects of the glycobiology of the pulmonary endothelium with an emphasis on N-glycans and terminal sialylation using an in vitro cell culture system. We combined a proteomic approach with N-glycan structure analysis by LC-MS, qRT-PCR, sialic acid analysis and lectin binding to show that constant and intermittent hyperoxia induced time dependent changes in global and surface glycosylation. An siRNA approach identified St6gal1 as being primarily responsible for the early transient increase of α2-6 sialylated structures in response to hyperoxia.

The pulmonary endothelium is an immediate recipient of high oxygen concentrations upon oxygen therapy and mediates down-stream responses. Cyclic collapse and reopening of atelectatic lung areas during mechanical ventilation with high fractions of inspired oxygen result in the propagation of oxygen oscillations in the hypoxic/hyperoxic range. We used primary murine lung endothelial cell cultures to investigate cell responses to constant and oscillating oxygen conditions in the hypoxic to hyperoxic range. Severe constant hyperoxia had pro-inflammatory and cytotoxic effects including an increase in expression of ICAM1, E-selectin, and RAGE at 24 hr exposure. The coagulative/fibrinolytic system responded by upregulation of uPA, tPA, and vWF and PAI1 under constant severe hyperoxia. Among antioxidant enzymes, the upregulation of SOD2, TXN1, TXNRD3, GPX1, and Gstp1 at 24 hr, but downregulation of SOD3 at 72 hr constant hyperoxia was evident. Hypoxic/hyperoxic oscillating oxygen conditions induced pro-inflammatory cytokine release to a lesser extent and later than constant hyperoxia. Gene expression analyses showed upregulation of NFKB p65 mRNA at 72 hr. More evident was a biphasic response of NOS3 and ACE1 gene expression (downregulation until 24 hr and upregulation at 72 hr). ACE2 mRNA was upregulated until 72 hr, but shedding of the mature protein from the cell surface favored ACE1. Oscillations resulted in severe production of peroxynitrite, but apart from upregulation of Gstp1 at 24 hr responses of antioxidative proteins were less pronounced than under constant hyperoxia. Oscillating oxygen in the hypoxic/hyperoxic range has a characteristical impact on vasoactive mediators like NOS3 and on the activation of the renin-angiotensin system in the lung endothelium.

Soon after its discovery in the 18th century, oxygen was applied as a therapeutic agent to treat severely ill patients. Lack of oxygen, commonly termed as hypoxia, is frequently encountered in different disease states and is detrimental to human life. However, at the end of the 19th century, Paul Bert and James Lorrain Smith identified what is known as oxygen toxicity. The molecular basis of this phenomenon is oxygen's readiness to accept electrons and to form different variants of aggressive radicals that interfere with normal cell functions. The human body has evolved to maintain oxygen homeostasis by different molecular systems that are either activated in the case of oxygen under-supply, or to scavenge and to transform oxygen radicals when excess amounts are encountered. Research has provided insights into cellular mechanisms of oxygen homeostasis and is still called upon in order to better understand related diseases. Oxygen therapy is one of the prime clinical interventions, as it is life saving, readily available, easy to apply and economically affordable. However, the current state of research also implicates a reconsidering of the liberal application of oxygen causing hyperoxia. Increasing evidence from preclinical and clinical studies suggest detrimental outcomes as a consequence of liberal oxygen therapy. In this review, we summarize concepts of cellular mechanisms regarding different forms of disturbed cellular oxygen homeostasis that may help to better define safe clinical application of oxygen therapy.

Coronavirus disease 2019 (COVID-19) progresses mildly in most of the cases; however, about 5% of the patients develop a severe acute respiratory distress syndrome (ARDS). Of all COVID-19 patients 3% need intensive care treatment, which becomes a great challenge for anesthesiology and intensive care medicine, medically, hygienically and for technical safety requirements. For these reasons, only experienced medical and nursing staff in the smallest grouping possible should be assigned. For these team members, a consistent use of personal protective equipment (PPE) is essential.Due to the immense medical challenges, the following treatment guidelines were developed by the ÖGARI (Österreichische Gesellschaft für Anästhesiologie, Reanimation und Intensivmedizin), FASIM (Federation of Austrian Societies of Intensive Care Medicine) and ÖGIAIN (Österreichische Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin).The recommendations given in this article are to be understood as short snapshots of the moment; all basic guidelines are works in progress and will be regularly updated as evidence levels, new study results and additional experience are gathered.

Summary The pandemic from the SARS-CoV‑2 virus is currently challenging healthcare systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe working environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develop respiratory or circulatory failure that is refractory to conventional treatment, it is of utmost importance to clearly define criteria for the use of ECMO in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.

The pandemic from the SARS-CoV­2 Virus is currently challenging health care systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe work environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develops respiratory or circulatory failure that is refractory to conventional therapies, it is of utmost importance to clearly define criteria for the use of ECMOs in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.

Zusammenfassung Die aktuelle COVID-19-Pandemie, die durch das SARS-CoV‑2 ausgelöst wird, hat bereits in vielen betroffenen Ländern zu gravierenden Ressourcenengpässen der jeweiligen Gesundheitssysteme geführt. Obwohl sehr viele COVID-19-Patienten nur moderate Symptome zeigen, entwickelt eine Subgruppe ein schweres respiratorisches oder auch kardiales Versagen. Die extrakorporale Membranoxygenierung (ECMO) stellt eine wertvolle Therapieoption für Patienten mit therapierefraktärem Lungen- oder Herzversagen dar. Es bedarf klarer Empfehlungen, die den ECMO-Einsatz in dieser zahlenmäßig stetig steigenden Patientenpopulation regeln. Die ECMO-Arbeitsgruppe der Medizinischen Universität Wien hat daher die folgenden Empfehlungen für eine ECMO-Unterstützung bei COVID-19-Patienten formuliert.

Importance:An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain.Objective:To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP.Design, Setting, and Participants:Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018.Interventions:Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight.Main Outcomes and Measures:The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute).Results:Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P = .23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P < .001).Conclusions and Relevance:Among obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications.Trial Registration:ClinicalTrials.gov Identifier: NCT02148692.