Peri-operative night-time work of anaesthesiologists: A qualitative study of critical issues and proposals.

BACKGROUND: Qualitative data on the opinions of anaesthesiologists regarding the impact of peri-operative night-time working conditions on patient safety are lacking. OBJECTIVES: This study aimed to achieve in-depth understanding of anaesthesiologists' perceptions regarding the impact of night-time working conditions on peri-operative patient safety and actions that may be undertaken to mitigate perceived risks. DESIGN: Qualitative analysis of responses to two open-ended questions. SETTING: Online platform questionnaire promoted by the European Society of Anaesthesiology and Intensive Care (ESAIC). PARTICIPANTS: The survey sample consisted of an international cohort of anaesthesiologists. MAIN OUTCOME MEASURES: We identified and classified recurrent themes in the responses to questions addressing perceptions regarding (Q1) peri-operative night-time working conditions, which may affect patient safety and (Q2) potential solutions. RESULTS: We analysed 2112 and 2113 responses to Q1 and Q2, respectively. The most frequently reported themes in relation to Q1 were a perceived reduction in professional performance accompanied by concerns regarding the possible consequences of work with fatigue (27%), and poor working conditions at night-time (35%). The most frequently proposed solutions in response to Q2 were a reduction of working hours and avoidance of 24-h shifts (21%), an increase in human resources (14%) and performance of only urgent or emergency surgeries at night (14%). CONCLUSION: Overall, the surveyed anaesthesiologists believe that workload-to-staff imbalance and excessive working hours were potential bases for increased peri-operative risk for their patients, partly because of fatigue-related medical errors during night-time work. The performance of nonemergency elective surgical cases at night and lack of facilities were among the reported issues and potential targets for improvement measures. Further studies should investigate whether countermeasures can improve patient safety as well as the quality of life of anaesthesia professionals. Regulations to improve homogeneity, safety, and quality of anaesthesia practice at night seem to be urgently needed.

European Society of Anaesthesiology and Intensive Care consensus document on sustainability: 4 scopes to achieve a more sustainable practice.

Climate change is a defining issue for our generation. The carbon footprint of clinical practice accounts for 4.7% of European greenhouse gas emissions, with the European Union ranking as the third largest contributor to the global healthcare industry's carbon footprint, after the United States and China. Recognising the importance of urgent action, the European Society of Anaesthesiology and Intensive Care (ESAIC) adopted the Glasgow Declaration on Environmental Sustainability in June 2023. Building on this initiative, the ESAIC Sustainability Committee now presents a consensus document in perioperative sustainability. Acknowledging wider dimensions of sustainability, beyond the environmental one, the document recognizes healthcare professionals as cornerstones for sustainable care, and puts forward recommendations in four main areas: direct emissions, energy, supply chain and waste management, and psychological and self-care of healthcare professionals. Given the urgent need to cut global carbon emissions, and the scarcity of evidence-based literature on perioperative sustainability, our methodology is based on expert opinion recommendations. A total of 90 recommendations were drafted by 13 sustainability experts in anaesthesia in March 2023, then validated by 36 experts from 24 different countries in a two-step Delphi validation process in May and June 2023. To accommodate different possibilities for action in high- versus middle-income countries, an 80% agreement threshold was set to ease implementation of the recommendations Europe-wide. All recommendations surpassed the 80% agreement threshold in the first Delphi round, and 88 recommendations achieved an agreement >90% in the second round. Recommendations include the use of very low fresh gas flow, choice of anaesthetic drug, energy and water preserving measures, "5R" policies including choice of plastics and their disposal, and recommendations to keep a healthy work environment or on the importance of fatigue in clinical practice. Executive summaries of recommendations in areas 1, 2 and 3 are available as cognitive aids that can be made available for quick reference in the operating room.

Intraoperative individualization of positive-end-expiratory pressure through electrical impedance tomography or esophageal pressure assessment: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review of randomized-controlled trials (RCTs) with meta-analyses aimed to compare the effects on intraoperative arterial oxygen tension to inspired oxygen fraction ratio (PaO2/FiO2), exerted by positive end-expiratory pressure (PEEP) individualized trough electrical impedance tomography (EIT) or esophageal pressure (Pes) assessment (intervention) vs. PEEP not tailored on EIT or Pes (control), in patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach. METHODS: PUBMED®, EMBASE®, and Cochrane Controlled Clinical trials register were searched for observational studies and RCTs from inception to the end of August 2022. Inclusion criteria were: RCTs comparing PEEP titrated on EIT/Pes assessment vs. PEEP not individualized on EIT/Pes and reporting intraoperative PaO2/FiO2. Two authors independently extracted data from the enrolled investigations. Data are reported as mean difference and 95% confidence interval (CI). RESULTS: Six RCTs were included for a total of 240 patients undergoing general anesthesia for surgery, of whom 117 subjects in the intervention group and 123 subjects in the control group. The intraoperative mean PaO2/FiO2 was 69.6 (95%CI 32.-106.4 ) mmHg higher in the intervention group as compared with the control group with 81.4% between-study heterogeneity (p < 0.01). However, at meta-regression, the between-study heterogeneity diminished to 44.96% when data were moderated for body mass index (estimate 3.45, 95%CI 0.78-6.11, p = 0.011). CONCLUSIONS: In patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach, PEEP personalized by EIT or Pes allowed the achievement of a better intraoperative oxygenation compared to PEEP not individualized through EIT or Pes. PROSPERO REGISTRATION NUMBER: CRD 42021218306, 30/01/2023.

Intraoperative lung protection: strategies and their impact on outcomes.

PURPOSE OF REVIEW: The present review summarizes the current knowledge and the barriers encountered when implementing tailoring lung-protective ventilation strategies to individual patients based on advanced monitoring systems. RECENT FINDINGS: Lung-protective ventilation has become a pivotal component of perioperative care, aiming to enhance patient outcomes and reduce the incidence of postoperative pulmonary complications (PPCs). High-quality research has established the benefits of strategies such as low tidal volume ventilation and low driving pressures. Debate is still ongoing on the most suitable levels of positive end-expiratory pressure (PEEP) and the role of recruitment maneuvers. Adapting PEEP according to patient-specific factors offers potential benefits in maintaining ventilation distribution uniformity, especially in challenging scenarios like pneumoperitoneum and steep Trendelenburg positions. Advanced monitoring systems, which continuously assess patient responses and enable the fine-tuning of ventilation parameters, offer real-time data analytics to predict and prevent impending lung complications. However, their impact on postoperative outcomes, particularly PPCs, is an ongoing area of research. SUMMARY: Refining protective lung ventilation is crucial to provide patients with the best possible care during surgery, reduce the incidence of PPCs, and improve their overall surgical journey.

Unexpected intensive care unit admission after surgery: impact on clinical outcome.

PURPOSE OF REVIEW: This review is focused on providing insights into unplanned admission to the intensive care unit (ICU) after surgery, including its causes, effects on clinical outcome, and potential strategies to mitigate the strain on healthcare systems. RECENT FINDINGS: Postoperative unplanned ICU admission results from a combination of several factors including patient's clinical status, the type of surgical procedure, the level of supportive care and clinical monitoring outside the ICU, and the unexpected occurrence of major perioperative and postoperative complications. The actual impact of unplanned admission to ICU after surgery on clinical outcome remains uncertain, given the conflicting results from several observational studies and recent randomized clinical trials. Nonetheless, unplanned ICU admission after surgery results a significant strain on hospital resources. Consequently, this issue should be addressed in hospital policy with the aim of implementing preoperative risk assessment and patient evaluation, effective communication, vigilant supervision, and the promotion of cooperative healthcare. SUMMARY: Unplanned ICU admission after surgery is a multifactorial phenomenon that imposes a significant burden on healthcare systems without a clear impact on clinical outcome. Thus, the early identification of patient necessitating ICU interventions is imperative.

Advanced Point-of-care Bedside Monitoring for Acute Respiratory Failure.

Advanced respiratory monitoring involves several mini- or noninvasive tools, applicable at bedside, focused on assessing lung aeration and morphology, lung recruitment and overdistention, ventilation-perfusion distribution, inspiratory effort, respiratory drive, respiratory muscle contraction, and patient-ventilator asynchrony, in dealing with acute respiratory failure. Compared to a conventional approach, advanced respiratory monitoring has the potential to provide more insights into the pathologic modifications of lung aeration induced by the underlying disease, follow the response to therapies, and support clinicians in setting up a respiratory support strategy aimed at protecting the lung and respiratory muscles. Thus, in the clinical management of the acute respiratory failure, advanced respiratory monitoring could play a key role when a therapeutic strategy, relying on individualization of the treatments, is adopted.

A platelet lipidomics signature in patients with COVID-19.

Ischemic cardiovascular and venous thromboembolic events are a frequent cause of death in severe COVID-19 patients. Platelet activation plays a key role in these complications, however platelet lipidomics have not been studied yet. The aim of our pilot investigation was to perform a preliminary study of platelet lipidomics in COVID-19 patients compared to healthy subjects. Lipid extraction and identification of ultrapurified platelets from eight hospitalized COVID-19 patients and eight age- and sex-matched healthy controls showed a lipidomic pattern almost completely separating COVID-19 patients from healthy controls. In particular, a significant decrease of ether phospholipids and increased levels of ganglioside GM3 were observed in platelets from COVID-19 patients. In conclusion, our study shows for the first time that platelets from COVID-19 patients display a different lipidomics signature distinguishing them from healthy controls, and suggests that altered platelet lipid metabolism may play a role in viral spreading and in the thrombotic complications of COVID-19.

What is the context? Besides respiratory system involvement, venous thromboembolism is a severe complication of COVID-19, largely due to the strong derangement of hemostasis, with platelets playing a central role.Great attention has recently been devoted to lipid alterations in COVID-19, both because viruses by reprogramming cellular lipid metabolism remodel lipid membranes to fuel their replication, and because the COVID-19-associated cytokine storm may affect cell/plasma lipidomic signatures.Lipidomics studies in COVID-19 patients have been performed mainly in plasma and serum.To the best of our knowledge, platelet lipidomics have not been examined despite the central role played by platelets in COVID-19 complications.What is the aim of the study?The aim of our pilot study was to preliminarily explore whether platelet lipidomics is altered in COVID-19 patients compared to age- and sex-matched healthy subjects, analyzing lipidomic profile of ultrapurified platelets.What are the results of our study? Our study shows for the first time that platelets from COVID-19 patients display a different lipidomics signature distinguishing them from healthy controls.Ether phospholipids and, intriguingly, two phytoceramides were lower, while ganglioside GM3 was higher in COVID-19 samples compared to healthy controls.What is the impact?Despite the small number of COVID-19 patients enrolled, recognized as a limitation of our study, we show, for the first time, that platelets from COVID-19 patients present a different lipidomics signature and suggest that altered platelet lipid metabolism may play a significant role in viral spreading and in the thrombotic complications of COVID-19.

The burden of peri-operative work at night as perceived by anaesthesiologists: An international survey.

BACKGROUND: No international data are available on the night working conditions and workload of anaesthesiologists and their opinions about associated risks. OBJECTIVE: The aim of this international survey was to describe the peri-operative night working conditions of anaesthesiologists and their perception of the impact these conditions have on patient outcomes and their own quality of life. DESIGN: Cross-sectional survey. SETTING: Not applicable. PARTICIPANTS: Anaesthesiologists providing peri-operative care during night shifts responded to an online survey promoted by the European Society of Anaesthesiology and Intensive Care (ESAIC). INTERVENTIONS: None. MAIN OUTCOME MEASURE: Twenty-eight closed questions. RESULTS: Overall 5292 complete responses were analysed. Of these, 920 were from trainees. The median reported monthly number of night shifts was 4 [IQR 3-6]. An irregular weekly night shift schedule was most common (51%). Almost all the respondents (98%) declared that their centres have no relevant institutional programmes to monitor stress or fatigue. Most respondents (90%) had received no training or information regarding performance improvement methods for night work. Most respondents were of the opinion that sleep deprivation affects their professional performance (71%) and that their fatigue during night work may increase the peri-operative risk for their patients (74%). Furthermore, 81% of the respondents agreed or strongly agreed that night work represents an additional risk per se for patient safety, and 77% stated that their night work affects the quality of their daily life significantly or extremely. CONCLUSION: Anaesthesiologists commonly perform perioperative night work without appropriate training, education or support on this specific condition. They perceive current practice as adversely affecting their professional performance and the safety of their patients. They also report significant effects on their own quality of life. Adequate training and education for night work may ally some of these concerns and programmes to monitor workers' stress and fatigue should be mandated to assess whether these concerns are justified. TRIAL REGISTRATION: Not applicable.

Cardiac arrest in the perioperative period: a consensus guideline for identification, treatment, and prevention from the European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery.

INTRODUCTION: Cardiac arrest in the operating room is a rare but potentially life-threatening event with mortality rates of more than 50%. Contributing factors are often known, and the event is recognised rapidly as patients are usually under full monitoring. This guideline covers the perioperative period and is complementary to the European Resuscitation Council (ERC) guidelines. MATERIAL AND METHODS: The European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery jointly nominated a panel of experts to develop guidelines for the recognition, treatment and prevention of cardiac arrest in the perioperative period. A literature search was conducted in MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. All searches were restricted to publications from 1980 to 2019 inclusive and to the English, French, Italian and Spanish languages. The authors also contributed individual, independent literature searches. RESULTS: This guideline contains background information and recommendation for the treatment of cardiac arrest in the operating room environment, and addresses controversial topics such as open chest cardiac massage (OCCM), resuscitative endovascular balloon occlusion (REBOA) and resuscitative thoracotomy, pericardiocentesis, needle decompression and thoracostomy. CONCLUSION: Successful prevention and management of cardiac arrest during anaesthesia and surgery requires anticipation, early recognition and a clear treatment plan. The ready availability of expert staff and equipment must also be taken into consideration. Success not only depends on medical knowledge, technical skills and a well organised team using crew resource management but also on an institutional safety culture embedded in everyday practice through continuous education, training and multidisciplinary co-operation.

Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care: Second update 2022.

BACKGROUND: Management of peri-operative bleeding is complex and involves multiple assessment tools and strategies to ensure optimal patient care with the goal of reducing morbidity and mortality. These updated guidelines from the European Society of Anaesthesiology and Intensive Care (ESAIC) aim to provide an evidence-based set of recommendations for healthcare professionals to help ensure improved clinical management. DESIGN: A systematic literature search from 2015 to 2021 of several electronic databases was performed without language restrictions. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to assess the methodological quality of the included studies and to formulate recommendations. A Delphi methodology was used to prepare a clinical practice guideline. RESULTS: These searches identified 137 999 articles. All articles were assessed, and the existing 2017 guidelines were revised to incorporate new evidence. Sixteen recommendations derived from the systematic literature search, and four clinical guidances retained from previous ESAIC guidelines were formulated. Using the Delphi process on 253 sentences of guidance, strong consensus (>90% agreement) was achieved in 97% and consensus (75 to 90% agreement) in 3%. DISCUSSION: Peri-operative bleeding management encompasses the patient's journey from the pre-operative state through the postoperative period. Along this journey, many features of the patient's pre-operative coagulation status, underlying comorbidities, general health and the procedures that they are undergoing need to be taken into account. Due to the many important aspects in peri-operative nontrauma bleeding management, guidance as to how best approach and treat each individual patient are key. Understanding which therapeutic approaches are most valuable at each timepoint can only enhance patient care, ensuring the best outcomes by reducing blood loss and, therefore, overall morbidity and mortality. CONCLUSION: All healthcare professionals involved in the management of patients at risk for surgical bleeding should be aware of the current therapeutic options and approaches that are available to them. These guidelines aim to provide specific guidance for bleeding management in a variety of clinical situations.

Treatment of patients with 'do not intubate orders'.

PURPOSE OF REVIEW: Do-not-intubate (DNI) orders are more frequently encountered over time. This widespread diffusion of DNI orders make it essential to develop therapeutic strategies matching patient's and his family willingness. The present review sheds light on the therapeutic approaches employed to support respiratory function of patients with DNI orders. RECENT FINDINGS: In DNI patients, several approaches have been described to relieve dyspnoea and address acute respiratory failure (ARF). Despite its extensive use, supplemental oxygen is not so useful in assuring dyspnoea relief. Noninvasive respiratory support (NIRS) is frequently employed to treat ARF in DNI patients. Also, to enhance DNI patients comfort during NIRS, it is worthy to point out the role of analgo-sedative medications. Lastly, a particular aspect concerns the first waves of coronavirus disease 2019 pandemic, when DNI orders have been pursued on factors unrelated to patient's wishes, in the total absence of family support due to the lockdown policy. In this setting, NIRS has been extensively employed in DNI patients with a survival rate of around 20%. SUMMARY: In dealing with DNI patients, the individualization of treatments is of pivotal importance to respect patient's preferences and improve quality of life at the same time.

Diaphragm ultrasound evaluation during weaning from mechanical ventilation in COVID-19 patients: a pragmatic, cross-section, multicenter study.

BACKGROUND: Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation. METHODS: This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure. RESULTS: Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7-22). Median DTF within 24 h since the start of weaning was 28% (IQR 22-39%), RASS score (- 2 vs - 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO2/FiO2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 1027; p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO2/FiO2 ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004). CONCLUSIONS: DTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021).

Clinical nutrition issues in 2022: What is missing to trust supplemental parenteral nutrition (SPN) in ICU patients?

A multidisciplinary group of international physicians involved in the medical nutrition therapy (MNT) of adult critically ill patients met to discuss the value, role, and open questions regarding supplemental parenteral nutrition (SPN) along with oral or enteral nutrition (EN), particularly in the intensive care unit (ICU) setting. This manuscript summarizes the discussions and results to highlight the importance of SPN as part of a comprehensive approach to MNT in critically ill adults and for researchers to generate new evidence based on well-powered randomized controlled trials (RCTs). The experts agreed on several key points: SPN has shown clinical benefits, resulting in this strategy being included in American and European guidelines. Nevertheless, its use is heterogeneous across European countries, due to the persistence of uncertainties, such as the optimal timing and the risk of overfeeding in absence of indirect calorimetry (IC), which results in divergent opinions and barriers to SPN implementation. Education is also insufficient. The experts agreed on actions needed to increase evidence quality on SPN use in specific patients at a given time point during acute critical illness or recovery.

Intensive care medicine in Europe: perspectives from the European Society of Anaesthesiology and Intensive Care.

BACKGROUND: Anaesthesiology represents a rapidly evolving medical specialty in global healthcare, currently covering advanced peri-operative, pre-hospital and in-hospital critical emergency management (CREM), intensive care medicine (ICM) and pain management. The aim of the European Society of Anaesthesiology and Intensive Care (ESAIC) is to develop and promote a coordinated interdisciplinary and multidisciplinary European network of Anaesthesiology and Intensive Care Medicine (AICM) societies for improvement of patient safety and outcome, and to enhance political and public awareness of the role of anaesthesiologists all over Europe. The ESAIC promotes coordinated interdisciplinary and multidisciplinary care for severely compromised patients, based on the European training requirements (ETR) within the European Union of Medical Specialists (UEMS). METHODS: To define the current situation of AICM in Europe, a survey was sent in April 2019 to the ESAIC Council and the ESAIC National Anaesthesiologists Societies Committee (NASC) members. The survey posed questions regarding the year of foundation, the inclusion of ICM in the society name, and if, and to what extent, various kinds (postoperative, general, specific, mixed) of national ICUs are being run by differing medical specialties. The study data were compiled and analysed by the ESAIC Board, Council and NASC in December 2019. RESULTS AND CONCLUSION: Amongst the 42 European national societies surveyed (41 members of ESAIC-NASC plus Luxembourg), nineteen (45%) also include terms related to critical care medicine or ICM in their names, seven (17%) include terms related to reanimation and three (7%) to resuscitation. In recent years, several national societies revised their names to better reflect their gradual embrace of peri-operative medicine, ICM, CREM and pain management. Approximately 70% of ICU beds in Europe, and 100% in Scandinavia, are being run by anaesthesiologists, the remaining 30% being managed by physicians from other surgical or medical specialties. To emphasise future needs and resources of European AICM, the ESAIC drafted an ICM roadmap in terms of clinical practice, organisation of healthcare, interprofessional and interdisciplinary collaboration, patient safety, outcome and empowerment, professional working conditions, and changes in research, teaching and training required to meet future challenges and expectations.

Level of Diffusion and Training of Lung Ultrasound during the COVID-19 Pandemic - A National Online Italian Survey (ITALUS) from the Lung Ultrasound Working Group of the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI).

PURPOSE: The goal of this survey was to describe the use and diffusion of lung ultrasound (LUS), the level of training received before and during the COVID-19 pandemic, and the clinical impact LUS has had on COVID-19 cases in intensive care units (ICU) from February 2020 to May 2020. MATERIALS AND METHODS: The Italian Lung Ultrasound Survey (ITALUS) was a nationwide online survey proposed to Italian anesthesiologists and intensive care physicians carried out after the first wave of the COVID-19 pandemic. It consisted of 27 questions, both quantitative and qualitative. RESULTS: 807 responded to the survey. The median previous LUS experience was 3 years (IQR 1.0-6.0). 473 (60.9 %) reported having attended at least one training course on LUS before the COVID-19 pandemic. 519 (73.9 %) reported knowing how to use the LUS score. 404 (52 %) reported being able to use LUS without any supervision. 479 (68.2 %) said that LUS influenced their clinical decision-making, mostly with respect to patient monitoring. During the pandemic, the median of patients daily evaluated with LUS increased 3-fold (p < 0.001), daily use of general LUS increased from 10.4 % to 28.9 % (p < 0.001), and the daily use of LUS score in particular increased from 1.6 % to 9.0 % (p < 0.001). CONCLUSION: This survey showed that LUS was already extensively used during the first wave of the COVID-19 pandemic by anesthesiologists and intensive care physicians in Italy, and then its adoption increased further. Residency programs are already progressively implementing LUS teaching. However, 76.7 % of the sample did not undertake any LUS certification.

Effects of Varying Levels of Inspiratory Assistance with Pressure Support Ventilation and Neurally Adjusted Ventilatory Assist on Driving Pressure in Patients Recovering from Hypoxemic Respiratory Failure.

BACKGROUND: Driving pressure can be readily measured during assisted modes of ventilation such as pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA). The present prospective randomized crossover study aimed to assess the changes in driving pressure in response to variations in the level of assistance delivered by PSV vs NAVA. METHODS: 16 intubated adult patients, recovering from hypoxemic acute respiratory failure (ARF) and undergoing assisted ventilation, were randomly subjected to six 30-min-lasting trials. At baseline, PSV (PSV100) was set with the same regulation present at patient enrollment. The corresponding level of NAVA (NAVA100) was set to match the same inspiratory peak of airway pressure obtained in PSV100. Therefore, the level of assistance was reduced and increased by 50% in both ventilatory modes (PSV50, NAVA50; PSV150, NAVA150). At the end of each trial, driving pressure obtained in response to four short (2-3 s) end-expiratory and end-inspiratory occlusions was analyzed. RESULTS: Driving pressure at PSV50 (6.6 [6.1-7.8] cmH2O) was lower than that recorded at PSV100 (7.9 [7.2-9.1] cmH2O, P = 0.005) and PSV150 (9.9 [9.1-13.2] cmH2O, P < 0.0001). In NAVA, driving pressure at NAVA50 was reduced compared to NAVA150 (7.7 [5.1-8.1] cmH2O vs 8.3 [6.4-11.4] cmH2O, P = 0.013), whereas there were no changes between baseline and NAVA150 (8.5 [6.3-9.8] cmH2O vs 8.3 [6.4-11.4] cmH2O, P = 0.331, respectively). Driving pressure at PSV150 was higher than that observed in NAVA150 (P = 0.011). CONCLUSIONS: NAVA delivers better lung-protective ventilation compared to PSV in hypoxemic ARF patients. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: The present trial was prospectively registered at www.clinicatrials.gov (NCT03719365) on 24 October 2018.

Association of Neutrophil Activation, More Than Platelet Activation, With Thrombotic Complications in Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection is associated with hypercoagulability, which predisposes to venous thromboembolism (VTE). We analyzed platelet and neutrophil activation in patients with coronavirus disease 2019 (COVID-19) and their association with VTE. METHODS: Hospitalized patients with COVID-19 and age- and sex-matched healthy controls were studied. Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase 9, a neutrophil-released enzyme, were measured. Four patients were restudied after recovery. The activating effect of plasma from patients with COVID-19 on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied. RESULTS: A total of 36 patients with COVID-19 and 31 healthy controls were studied; VTE developed in 8 of 36 patients with COVID-19 (22.2%). Platelets and neutrophils were activated in patients with COVID-19. NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis. Plasmatic matrix metalloproteinase 9 was significantly increased in patients with COVID-19. Platelet and neutrophil activation markers, but less so NETs, normalized after recovery. In vitro, plasma from patients with COVID-19 triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic-dose low-molecular-weight heparin, but not by aspirin or dypiridamole. CONCLUSIONS: Platelet and neutrophil activation are key features of patients with COVID-19. NET biomarkers may help to predict clinical worsening and VTE and may guide low-molecular-weight heparin treatment.

Is recurrence possible in coronavirus disease 2019 (COVID-19)? Case series and systematic review of literature.

Can a patient diagnosed with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) be infected again? This question is still unsolved. We tried to analyze local and literature cases with a positive respiratory swab after recovery. We collected data from symptomatic patients diagnosed with SARS-CoV-2 infection in the Italian Umbria Region that, after recovery, were again positive for SARS-CoV-2 in respiratory tract specimens. Samples were also assessed for infectivity in vitro. A systematic review of similar cases reported in the literature was performed. The study population was composed of 9 patients during a 4-month study period. Among the new positive samples, six were inoculated in Vero-E6 cells and showed no growth and negative molecular test in culture supernatants. All patients were positive for IgG against SARS-CoV-2 nucleoprotein and/or S protein. Conducting a review of the literature, 1350 similar cases have been found. The presumptive reactivation occurred in 34.5 days on average (standard deviation, SD, 18.7 days) after COVID-19 onset, when the 5.6% of patients presented fever and the 27.6% symptoms. The outcome was favorable in 96.7% of patients, while the 1.1% of them were still hospitalized at the time of data collection and the 2.1% died. Several hypotheses have been formulated to explain new positive respiratory samples after confirmed negativity. According to this study, the phenomenon seems to be due to the prolonged detection of SARS-CoV-2 RNA traces in respiratory samples of recovered patients. The failure of the virus to replicate in vitro suggests its inability to replicate in vivo.

Effect of awake prone position on diaphragmatic thickening fraction in patients assisted by noninvasive ventilation for hypoxemic acute respiratory failure related to novel coronavirus disease.

BACKGROUND: Awake prone position is an emerging rescue therapy applied in patients undergoing noninvasive ventilation (NIV) for acute hypoxemic respiratory failure (ARF) related to novel coronavirus disease (COVID-19). Although applied to stabilize respiratory status, in awake patients, the application of prone position may reduce comfort with a consequent increase in the workload imposed on respiratory muscles. Thus, we primarily ascertained the effect of awake prone position on diaphragmatic thickening fraction, assessed through ultrasound, in COVID-19 patients undergoing NIV. METHODS: We enrolled all COVID-19 adult critically ill patients, admitted to intensive care unit (ICU) for hypoxemic ARF and undergoing NIV, deserving of awake prone positioning as a rescue therapy. Exclusion criteria were pregnancy and any contraindication to awake prone position and NIV. On ICU admission, after NIV onset, in supine position, and at 1 h following awake prone position application, diaphragmatic thickening fraction was obtained on the right side. Across all the study phases, NIV was maintained with the same setting present at study entry. Vital signs were monitored throughout the entire study period. Comfort was assessed through numerical rating scale (0 the worst comfort and 10 the highest comfort level). Data were presented in median and 25th-75th percentile range. RESULTS: From February to May 2021, 20 patients were enrolled and finally analyzed. Despite peripheral oxygen saturation improvement [96 (94-97)% supine vs 98 (96-99)% prone, p = 0.008], turning to prone position induced a worsening in comfort score from 7.0 (6.0-8.0) to 6.0 (5.0-7.0) (p = 0.012) and an increase in diaphragmatic thickening fraction from 33.3 (25.7-40.5)% to 41.5 (29.8-50.0)% (p = 0.025). CONCLUSIONS: In our COVID-19 patients assisted by NIV in ICU, the application of awake prone position improved the oxygenation at the expense of a greater diaphragmatic thickening fraction compared to supine position. Trial registration ClinicalTrials.gov, number NCT04904731. Registered on 05/25/2021, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04904731 .

Noninvasive respiratory support outside the intensive care unit for acute respiratory failure related to coronavirus-19 disease: a systematic review and meta-analysis.

BACKGROUND: Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU. METHODS: We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with 'do-not-intubate' (DNI) orders. RESULTS: Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30-41%]. 26% [21-30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36-54%]. 23% [15-32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65-78%]. Oxygenation on admission was the main source of between-study heterogeneity. CONCLUSIONS: During COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance. REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/prospero/ , CRD42020224788, December 11, 2020.