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BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation.METHODS: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing.FINDINGS: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms.INTERPRETATION: Patient's age, timing of cannulation (FUNDING: None.

The optimal management of respiratory failure related to SARS-CoV-2 infection is a subject of heated debates in the scientific community. The lack of solid scientific evidence, combined with the unclear pathophysiology of COVID-19 pneumonia, means that the modalities and duration of ventilator assistance often rely on subjective assessments of the doctor on call. In establishing a suitable respiratory support, it is essential to evaluate the degree of activation of the respiratory muscles as objectively as possible. Among the various methods of evaluating the inspiratory effort, measurement of the phasic variations of esophageal pressure (intended as a surrogate of pleural pressure) represents the gold standard. Esophageal pressure measurement can be implemented in a minimally invasive way in every patient category, does not require sophisticated devices, and provides objective data about respiratory muscle activity. In patients with ongoing COVID-19-related respiratory failure, esophageal pressure monitoring allows i) optimizing the type and settings of noninvasive ventilation, ii) providing objective support in the delicate choice of establishing invasive ventilation in cases in which such an indication is unclear, and iii) monitoring the clinical evolution of COVID-19 pneumonia to allow early interception of cases with progressive worsening of lung function. Esophageal manometry provides a complete and objective assessment of respiratory muscle activity. Its clinical use in patients with respiratory failure in the course of COVID-19 would allow clarifying some pathophysiological aspects of the disease and customizing ventilatory support according to the needs of specific patients.

The introduction of pathways to enrol deceased donors after cardio-circulatory confirmation of death (donation after circulatory death, DCD) is expanding in many countries to face the shortage of organs for transplantation. The implementation of normothermic regional reperfusion (NRP) with warm oxygenated blood is a strategy to manage in-situ the organs of DCD donors. This approach, an alternative to in-situ cold preservation, and followed by prompt retrieval and cold static storage and/or ex-vivo machine perfusion (EVMP), could be limited to abdominal organs (A-NRP) or extended to the thorax (thoraco-abdominal, TA-NRP. NRP is also referred to as extracorporeal interval support for organ retrieval (EISOR). The use of EISOR is increasing in Europe, even if variably regulated. A-NRP has been demonstrated to be effective in decreasing the risk associated with transplantation of abdominal organs from DCD donors, and was recommended by the European Society for Organ Transplantation (ESOT) in a recent consensus document. We aim to explain how we select the candidates for DCD, to describe our regionalized model for implementing EISOR provision, and to introduce the health care professionals involved in this complex process, with their strictly defined roles, responsibilities, and boundaries. Finally, we report the results of our program, recruiting cDCD donors over a large network of hospitals, all pertaining to a Local Health Authority (Azienda Unità Sanitaria Locale, AUSL) in Romagna, Italy.

Background: Trauma is a leading cause of death and disability. Patients with trauma undergoing invasive mechanical ventilation (IMV) are at risk for ventilator-associated events (VAEs) potentially associated with a longer duration of IMV and increased stay in the intensive care unit (ICU). Methods: We conducted a retrospective cohort study aimed to evaluate the incidence of infection-related ventilator-associated complications (IVACs), possible ventilator-associated pneumonia (PVAP), and their characteristics among patients experiencing severe trauma that required ICU admission and IMV for at least four days. We also determined pathogens implicated in PVAP episodes and characterized the use of antimicrobial therapy. Results: In total, 88 adult patients were included in the main analysis. In this study, we observed that 29.5% of patients developed a respiratory infection during ICU stay. Among them, five patients (19.2%) suffered from respiratory infections due to multi-drug resistant bacteria. Patients who developed IVAC/PVAP presented lower total GCS (median value, 7; (IQR, 9) vs. 12.5, (IQR, 8); p = 0.068) than those who did not develop IVAC/PVAP. Conclusions: We observed that less than one-third of trauma patients fulfilling criteria for ventilator associated events developed a respiratory infection during the ICU stay.

Donation after circulatory death (DCD) programs are expanding in Europe, in the attempt to expand donors pool. Even in controlled DCD donors, however, a protracted warm ischemia time occurring in the perimortem period might damage organs, making these unsuitable for transplantation. Implementing a strategy of extracorporeal interval support for organ retrieval (EISOR), a regional reperfusion with normothermic, oxygenated blood provides a physiologic environment allowing extensive assessment of potential grafts, and potentially promotes recovery of native function. Here we report the results of a multi-center retrospective cohort study including 29 Maastricht Category III controlled DCD donors undergoing extracorporeal support in a regional DCD/EISOR Training Center, and in the network of referring In-Training Centers, under the liaison of the regional Transplant Coordination Center during COVID-19 pandemic, between March 2020 and November 2021. The study aims to understand whether a mobile, experienced EISOR team implementing a consistent technique and sharing its equipe, expertise and equipment in a regional network of hospitals, might be effective and efficient in implementing the regional DCD program activity even in a highly stressed healthcare system.

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BackgroundTo describe an innovative and functional method to deal with the increased COVID-19 pandemic-related intensive care unit bed requirements.MethodsWe describe the emergencial creation of integrated system of internistic ward, step-down unit and intensive care unit, physically located in reciprocal vicinity at the same floor. The run under the control of a single intensive care staff, sharing clinical protocols and informatic system, following a single director supervision. The intention was to create a dynamic and flexible system, allowing for rapid and fluid patient admission/discharge, depending on the requirements due to the third Italian peak of COVID-19 pandemic in March 2021.Results142 COVID-19 patients and 66 non-COVID-19 patients were admitted, no critical patient was left unadmitted and no COVID-19 severe patients referring to our centre had to be redirected to other hospitals due to bed saturation. This system allowed shorter hospital length-of-stay in general wards (5.9 ± 4 days) than in other internistic COVID-19 wards and an overall mortality in line with those reported in literature despite the peak raging.ConclusionThis case report shows the feasibility and the efficiency of this dynamic model of hospital rearrangement to deal with COVID-19 pandemic peaks.

Background Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is usually performed in cases of severe respiratory failure in which conventional and advanced mechanical ventilation strategies are ineffective in achieving true lung-protective ventilation, thus triggering ventilatory-induced lung injury. If circulatory failure coexists, veno-arterial ECMO (VA-ECMO) may be preferred over VV-ECMO because of its potential for circulatory support. In VA-ECMO, the respiratory contribution is less effective and the complication rate is higher than in the VV configuration. Case presentation The authors present a case in which VV-ECMO was performed in an emergency setting to treat a 68-year-old White male patient who experienced acute respiratory failure after massive aspiration. Despite intubation and intensive care unit admission, multiple organ failure occurred suddenly, thus prompting referral to a level-1 trauma center with an ECMO facility. The patient’s condition slowly improved with VV-ECMO support along with standard treatment for hemodynamic impairment. VV-ECMO was discontinued on day 8. The patient was extubated on day 14 and discharged home fully recovered 34 days after the event. Conclusions Attention was focused on the decision to initiate VV-ECMO support even in the presence of severe hemodynamic derangement, although VA-ECMO could have provided better hemodynamic support but less effective respiratory support.

GEAcute ischemic stroke is one of the leading causes of death and long-term disability for adults. Endovascular therapy is the standard of care for severe acute ischemic stroke, caused by large-vessel occlusion in the anterior circulation; however, the optimal anaesthetic management during the procedure is still a matter of debate. The best anesthetic treatment should mainly be related to patients’ clinical conditions and the site of arterial occlusion. With this article, we share our experience based on the use of ketamine as the choosen hypnotic drug for general anesthesia, in order to avoid a sudden drop in blood pressure. The core of our proposal approach is the general anesthesia management by the medical emergency team with skills on both time-dependent diseases and neurocritical care.

Even with encouraging recipient outcomes, transplantation using donation after circulatory death (DCD) is still limited. A major barrier to this type of transplantation is the consequences of warm ischemia on graft survival; however, preservation techniques may reduce the consequences of cardiac arrest and provide better organ conservation. Furthermore, DCD in trauma patients could further expand organ donation. We present five cases in which organs were retrieved and transplanted successfully using normothermic regional perfusion (NRP) in trauma patients. Prompt critical care support and surgical treatment allowed us to overcome the acute phase. Unfortunately, owing to the severity of their injuries, all of the donors died. However, the advanced and continuous organ-specific supportive treatment allowed the maintenance of general clinical stability and organ preservation. Consequently, it was possible to retrieve and transplant the donors’ organs. Death was ascertained in accordance with cardio-circulatory criteria, which was followed by NRP. We consider that DCD in trauma patients may represent an important source of organs.

Background: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date. Methods: We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality. Findings: Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4–40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20–2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6–41·5). Interpretation: In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19. Funding: None.

Background Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis. Methods We performed an observational study during the peak of pandemic in our intensive care unit, dosing D-dimer, C-reactive protein, troponin T, lactate dehydrogenase, ferritin, serum iron, transferrin, transferrin saturation, transferrin soluble receptor, lymphocyte count and NK, CD3, CD4, CD8 and B subgroups of 31 patients during the first 2 weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with the Spearman coefficient and Mann–Whitney test. Trends over time were tested with the Kruskal–Wallis analysis. Results Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 109/L; interquartile range (IQR) 0.450 109/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither ferritin nor lymphocyte count follows significant trends in ICU patients. Transferrin saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at days 3 to 6 (median 33%, IQR 26.5%, p value 0.026). The same trend is observed with serum iron levels (median 25.5 μg/L, IQR 69 μg/L at admission; median 73 μg/L, IQR 56 μg/L on days 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing haemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 μg/L; IQR 1285 μg/L) to days 3 to 6 (median 6820 μg/L; IQR 6619 μg/L), despite not reaching significant results. We describe trends of all the abovementioned parameters during ICU stay. Conclusions The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the intensive care unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology.

Background This study was conceived to provide systematic data about lung mechanics during early phases of CoVID-19 pneumonia, as long as to explore its variations during prone positioning. Methods We enrolled four patients hospitalized in the Intensive Care Unit of “M. Bufalini” hospital, Cesena (Italy); after the positioning of an esophageal balloon, we measured mechanical power, respiratory system and transpulmonary parameters and arterial blood gases every 6 hours, just before decubitus change and 1 hour after prono-supination. Results Both respiratory system and transpulmonary compliance and driving pressure confirmed the pseudo-normal respiratory mechanics of early CoVID-19 pneumonia (respectively, CRS 40.8 ml/cmH2O and DPRS 9.7 cmH2O; CL 53.1 ml/cmH2O and DPL 7.9 cmH2O). Interestingly, prone positioning involved a worsening in respiratory mechanical properties throughout time (CRS,SUP 56.3 ml/cmH2O and CRS,PR 41.5 ml/cmH2O – P 0.37; CL,SUP 80.8 ml/cmH2O and CL,PR 53.2 ml/cmH2O – P 0.23). Conclusions Despite the severe ARDS pattern, respiratory system and lung mechanical properties during CoVID-19 pneumonia are pseudo-normal and tend to worsen during pronation. Trial registration Restrospectively registered.

Background: Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis. Little is known about clinical management of severe forms of Covid-19. Methods: we performed an observational study during the peak of pandemic in our intensive care unit, serially dosing D-dimer, C-reactive protein, Troponin T, Lactate Dehydrogenase, Ferritin, Serum iron, Transferrin, Transferrin Saturation, Transferrin Soluble Receptor, Lymphocyte count and NK, CD3, CD4, CD8, B subgroups of 31 patients during the first two weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with Spearman coefficient and Mann-Whitney test. Trend over time were tested with Kruskall-Wallis analysis. Results: All patients show hyperferritinemia, and its dosage might be helpful in individuating patients developing hemophagocytic lymphohistiocytosis (we observed 1 case). Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 109/L; interquartile range (IQR) 0.450 109/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither Ferritin nor lymphocyte count follow significant trends in ICU patients. Transferrin Saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at day 3 to 6 (median 33%, IQR 26.5%, p-value 0.026). The same trend is observed with serum iron levels (median 25.5 µg/L, IQR 69 µg/L at admission; median 73 µg/L, IQR 56 µg/L on day 3 to 6) without reaching statistical significance. D-dimer is constantly elevated and progressively increases from admission (median 1319 µg/L; IQR 1285 µg/L) to day 3 to 6 (median 6820 µg/L; IQR 6619 µg/L), despite not reaching significant results. We describe trends of all the above mentioned parameters during ICU stay and provide a narrative review of our clinical experience about critical Covid-19 patients. D-dimer is constantly elevated in our ICU population and increases from admission to a maximum on day 3 to 6 of ICU stay (median 6820 µg/L; IQR 6619 µg/L) Conclusions: iron metabolism and lymphopenia are key clinical features of Covid-19 patients in the ICU setting and have been specifically described in this paper. Keywords – MeSH repository (3-10): Iron, COVID-19, SARS-CoV-2, Coronavirus, Critical Care, Lymphocytes, Lymphopenia, Ferritins, Immunity, Coagulation.

Extracorporeal Membrane Oxygenation in coronavirus disease 2019: a single Italian center experience.

Organ retrieved from donors after circulatory deaths (DCD) is vulnerable of the effects of warm ischemia with important consequence on graft survival and posttransplant outcome. Preservation techniques, such as normothermic regional perfusion (NRP), can be used to reduce the effects of the cardiac arrest and to generate a continuous flow to the organs, resulting in a better preservation of the organs for transplantation. However, technical complications may occur during NRP which can compromise the retrieve of donors' organs. We present a case report of a technical complication arisen during an NRP for DCD. During the extracorporeal circuit, we observed a dramatical decrease in the blood flow with excessive negative inlet pressure. It was because of a later recognized venous cannula malposition. In fact, we did not perform the radiological control for wire position. As a consequence, our clinical practice was modified. Currently, a radiological control of the wire is performed before the insertion of the catheter. Even if the donation was accomplished successfully, we reckon that it is fundamental to describe the technical issue that may occur during perfusion technique in order to improve the safety and the effectiveness of these procedures.

Background Trauma victims could be an important source of organs. This article presents two cases of successful organ donation and transplant, after Maastricht category III cardiac death in patients with successfully repaired AAST grade V traumatic cardiac injuries. Case presentation The first donor was an adult patient with self-inflicted heart stab wound and non-survivable burn injury. The second one was an adult patient with blunt cardiac and abdominal trauma and an anoxic brain injury due to a car accident. The cardiac injury was promptly repaired in both patients. In the first case, adequate organ perfusion ante-mortem was achieved thanks to venoarterial extracorporeal membrane oxygenation and intensive care unit support. The above procedure allowed successful organ donation and transplantation even after Maastricht category III cardiac death. This is the first case reported where, for organ donation purposes, it was made necessary first thing to avoid the immediate death of the patient, due to a rare and frequently not survivable cardiac injury. The challenge of preserving organ perfusion, due to major burn injury effects, was faced afterwards. Conclusions The outcomes of these two cases suggest that a repaired heart injury should not be considered as an absolute contraindication to organ donation, even if it is associated with non-survivable major burns. Therefore, cardiac death could provide an opportunity for these kinds of patients to contribute to the pool of potential organ donors.

Background Incidence of Blunt Cerebrovascular Injuries (BCVI) after head injury has been reported as 0.5-1% of all admissions for blunt trauma, with a high stroke and mortality rate. The purpose of this study is to evaluate if a modification of Memphis criteria could improve the rate of BCVI diagnosis. Methods Trauma patients consecutively admitted to Intensive Care Unit (ICU) from Jan 2008 to Oct 2009 were considered for the study. Memphis criteria comprehend: basilar skull fracture with involvement of the carotid canal, cervical spine fracture, neurological exam not explained by brain imaging, Horner's syndrome, LeFort II-III fractures, and neck soft tissue injury. As single criteria modification, we included all patients with petrous bone fracture, even without carotid canal involvement. In all patients at risk of BCVI, 64-slice angio-CT-scans was performed. Results During the study period, 266 patients were admitted to the ICU for blunt major trauma. Among them, 162 presented traumatic brain injury or cervical spine fracture. In accordance with the proposed modified-Memphis criteria, 53 patients showed risk factors for BCVI compared to 45 using the original Memphis criteria. Among the 53 patients, 6 resulted as having carotid lesions (2.2% of all blunt major traumas; one patient more than when using Memphis criteria). Anticoagulant therapy with low molecular weight heparin was administered in all patients. No stroke or hemorrhagic complications occurred. Clinical examination at 6-months showed no central neurological deficit. Conclusion A modification of a single criteria of Memphis screening protocol might permit the identification of a higher percentage of BCVI. Limited by sample size, this study needs to be validated.