Rationale: Whether patients with coronavirus disease (COVID-19) may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. Objectives: To estimate the effect of ECMO on 90-day mortality versus IMV only. Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO versus no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 < 80 or PaCO2 ⩾ 60 mm Hg). We controlled for confounding using a multivariable Cox model on the basis of predefined variables. Measurements and Main Results: A total of 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability on Day 7 from the onset of eligibility criteria (87% vs. 83%; risk difference, 4%; 95% confidence interval, 0–9%), which decreased during follow-up (survival on Day 90: 63% vs. 65%; risk difference, −2%; 95% confidence interval, −10 to 5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand and when initiated within the first 4 days of IMV and in patients who are profoundly hypoxemic. Conclusions: In an emulated trial on the basis of a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and regions with ECMO capacities specifically organized to handle high demand.
Purpose of review Thoracic injuries are directly responsible for 20–30% of deaths in severe trauma patients and represent one of the main regions involved in preventable or potentially preventable deaths. Controlling bleeding in thoracic trauma is a major challenge because intrathoracic hemorrhagic lesions can lead to hemodynamic instability and respiratory failure. Recent findings The aim of managing intrathoracic hemorrhagic lesions is to control bleeding as quickly as possible and to control any respiratory distress. Extended focus assessment with sonography for trauma enables us to identify intrathoracic bleeding much more quickly and to determine the most appropriate therapeutic strategy. Summary Thoracic bleeding can result from the diaphragm, intrathoracic vessels (aorta, but also inferior or superior vena cava, and suprahepatic veins), lung, cardiac, or chest wall injuries. Depending on thoracic lesions (such as hemothorax or hemopericardium), hemodynamic instability, and respiratory failure, a pericardial window approach, sternotomy, thoracotomy, or emergency resuscitation thoracotomy may be considered after discussion with the surgeon. Alongside treatment of injuries, managing oxygenation, ventilation, hemodynamic, and coagulopathy are essential for the patient’s outcome.
Limitations of life-sustaining therapies (LST) practices are frequent and vary among intensive care units (ICUs). However, scarce data were available during the COVID-19 pandemic when ICUs were under intense pressure. We aimed to investigate the prevalence, cumulative incidence, timing, modalities, and factors associated with LST decisions in critically ill COVID-19 patients. We did an ancillary analysis of the European multicentre COVID-ICU study, which collected data from 163 ICUs in France, Belgium and Switzerland. ICU load, a parameter reflecting stress on ICU capacities, was calculated at the patient level using daily ICU bed occupancy data from official country epidemiological reports. Mixed effects logistic regression was used to assess the association of variables with LST limitation decisions. Among 4671 severe COVID-19 patients admitted from February 25 to May 4, 2020, the prevalence of in-ICU LST limitations was 14.5%, with a nearly six-fold variability between centres. Overall 28-day cumulative incidence of LST limitations was 12.4%, which occurred at a median of 8 days (3-21). Median ICU load at the patient level was 126%. Age, clinical frailty scale score, and respiratory severity were associated with LST limitations, while ICU load was not. In-ICU death occurred in 74% and 95% of patients, respectively, after LST withholding and withdrawal, while median survival time was 3 days (1-11) after LST limitations. In this study, LST limitations frequently preceded death, with a major impact on time of death. In contrast to ICU load, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations.
'The most sophisticated intensive care often becomes unnecessarily expensive terminal care where the pre-ICU system is uncoordinated or undeveloped' – Peter Safar, 1974 Critical illness refers to life-threatening conditions resulting from an acute disease, injury, adverse environmental influence, poisoning, surgery, or decompensation of a chronic disease. It is an exquisitely time-sensitive condition, and early identification, support, and treatment significantly impact outcome. Pathologies which have the potential to become life-threatening often originate before the patient presents to the hospital, which explains the prevalence of evolving or established critical illness seen in the emergency departments (EDs). The common maxim where 'prevention is better than cure' implies that the earlier the treatment the better the outcome in other words, 'the earlier the better'. It is obvious and advantageous that evidence-based critical care should not be limited to the ICU but rather initiated as early as possible and regardless of the geographical location, whether in the prehospital setting or ED. Peter Safar was the first to indicate that efforts to enhance the chances of survival and organ recovery from critical illness must not only focus on patient management in the ICU, but address the entire patient pathway from the prehospital scene, the ED to the ICU, further including the operating room and general wards [1]. He referred to critical care as the continuum of care the critically ill or injured patient requires to recover. An USA study reported that the number of ED admissions to an ICU increased by 79% between 2001 and 2009. The time that these critically ill patients spent in the ED also increased in parallel [2]. A systematic review showed that ED boarding of critically ill patients was common, and this specific aspect alone was associated with worse clinical outcomes [3,4]. Gaieski et al. observed an increased delay in critical care as ED occupancy increased, implying that ED overcrowding might affect patient outcome [5]. A 2009 study described low rates of critical care interventions in the ED as a contributing factor to poor outcome [6]. However, more recent publications demonstrate no association between ED boarding and mortality, when appropriate critical care is delivered in the ED [7,8]. Essential critical care interventions such as basic airway management in patients with compromised airways as well as chest compressions and defibrillation in cardiac arrest are known to save lives [9]. Even advanced techniques such as extracorporeal life support further improve the chances of survival in patients with refractory cardiac arrest, when introduced early after collapse or on ED arrival [9–11]. After the initial resuscitation phase, critical care must be continued without interruption to optimally stabilize vital functions, minimize organ damage, and avoid renewed deterioration. Current scientific evidence suggests that early delivery of critical care in the ED can halt and, in some patients, even reverse acute organ dysfunction [12,13], reduce the need for ICU admission, shorten ICU and hospital length of stay, and improve both short-term as well as long-term survival [12–17]. These positive effects on patient outcome further translate into increased ICU bed availability for critically ill patients originating from other hospital areas than the ED (e.g. patients after major elective surgery or those deteriorating on hospital wards). An economic analysis revealed that critical care delivery in the ED is cost-effective [18], a finding that is of particular importance in healthcare systems with payment-per-diagnosis reimbursement. Several models on how to provide critical care in the ED have been published. These critical care delivery solutions vary substantially ranging from the 'ICU without walls' model, where ICU staff goes to the ED when needed, to direct ICU or coronary angiography suite admission of selected emergency patients (e.g. those with ST-elevation myocardial infarction), ED-based early intervention teams, telemonitoring solutions, dedicated critical care resuscitation units, and ED-ICUs staffed by emergency physicians [13,14,17,19]. Although scientific data on the comparative effectiveness of the different ED critical care delivery models are lacking, it is unlikely that a single model will be suitable and effective in all settings. Given the substantial differences in ED structures, organization, staffing and processes between hospitals, regions, and countries in Europe [20], it appears that EDs must choose the most feasible and appropriate ED critical care delivery model for their setting. Regardless of the model chosen, the practicability of critical care in the ED hinges on the availability of specific prerequisites (Fig. 1).Fig. 1: Overview of prerequisites, critical care interventions, and associated effects of critical care provision in the emergency department on patient outcomes. 1, including training and experience in technical and non-technical skills; 2, area where critically ill patients can be resuscitated, stabilized, and monitored until disposition to an ICU, non-ICU ward, or ED discharge; 3, equipment, drugs, and consumables needed for continuous patient monitoring (e.g. end-tidal carbon dioxide, invasive pressure measurement), rapid diagnostic work-up (e.g. point-of-care tests including blood gas analysis and viscoelastic tests, bedside point-of-care ultrasound), and critical care interventions (e.g. rapid sequence induction, noninvasive and invasive mechanical ventilation, continuous infusion of vasodilators, vasopressors or inotropic agents, extracorporeal life support). ED, emergency department.ED critical care encompasses more than resuscitation, interventions, and continuous patient monitoring. In patients too old, frail, and/or sick to benefit from ICU admissions, effective and timely diagnostics and noninvasive critical care interventions (e.g. noninvasive positive pressure ventilation) can rapidly help to clarify the underlying pathology, relieve symptoms, and may even reverse organ dysfunction. A time-limited trial of noninvasive organ support in the ED facilitates the assessment of physiological reserves contributing to the decision whether to continue with organ support or turn focus to palliative care measures [21]. Another key patient-centred aspect of providing critical care in the ED is the creation of an opportunity to discuss and document patient preferences and advanced care planning before ICU and hospital admission. As a minimum, the first-line, foundational care of critically ill patients, termed Essential Emergency and Critical Care [22], should be provided to all critically ill patients in the ED and throughout the hospital. A further advantage of the systematic delivery of critical care in the ED is the possibility to harmonize and expand critical care research to early phases of critical illness. Delayed study inclusion (e.g. only after ICU admission) may be one of the reasons why some putatively effective therapies did not translate into improved outcomes [23]. As a European group of emergency and critical care physicians, we would like to emphasize the importance and unquestionable need for timely critical care delivery in the ED. The ED treatment phase is a crucial part of the continuum of care for critically ill patients. Early evidence-based critical care interventions in the ED can effectively attenuate or even reverse organ dysfunction and possibly even improve the chances of survival. Further research will be essential to validate these findings across the various healthcare systems and geographical regions. Acknowledgements The Critical Care in Emergency Medicine Interest Group: Mo Al-Hadad, MD, Intensive Care Unit, Queen Elizabeth University Hospital, Glasgow, United Kingdom; Raed Arafat, MD, Department of Emergency Situations, Ministry of Internal Affairs, Bucharest, Romania; Tim Baker, MBChB, PhD, Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden; Martin Balik, MD, PhD, Department of Anaesthesiology and Intensive Care, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Czechia; Wilhelm Behringer, MD, MBA, MSc, Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria; Ruth Brown, MD, Emergency Department, St. Mary's Hospital, Imperial College Healthcare, London, United Kingdom; Luca Carenzo, MD, Department of Anesthesia and Intensive Care Medicine, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; Jim Connolly, MD, Accident and Emergency, Great North Trauma and Emergency Care, Newcastle-upon-Tyne, United Kingdom; Daniel Dankl, MD, Department of Anesthesiology, Perioperative and General Intensive Care, Salzburg University Hospital and Paracelsus Private Medical University, Salzburg, Austria; Christoph Dodt, MD, Department of Emergency Medicine, München Klinik, Munich, Germany; Martin W. Dünser, MD, Department of Anaesthesiology and Critical Care Medicine, Kepler University Hospital and Johannes Kepler University Linz, Linz, Austria; Aristomenis Exadaktylos, MD, Department of Emergency Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Tobias Gauss, MD, Anesthesia and Critical Care, Grenoble Alpes, University Hospital, Grenoble, France; Srdjan Gavrilovic, MD, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia and Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia; Said Hachimi-Idrissi, MD, PhD, Department of Emergency Medicine, Ghent University Hospital, Ghent, Belgium and Faculty of Medicine and Pharmacy, Vrije Universiteit Brussels, Brussels, Belgium; Matthias Haenggi, MD, Institute of Intensive Care Medicine, University Hospital Zürich and University of Zürich, Zürich, Switzerland; Harald Herkner, MD; Michael Joannidis, MD, Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria; Abdo Khoury, MD, PhD, Department of Emergency Medicine and Critical Care, Besançon University Hospital, Besançon; Michaela Klinglmair, RN, Department of Anaesthesiology and Critical Care Medicine, Kepler University Hospital and Johannes Kepler University Linz, Linz, Austria; Robert Leach, MD, Department of Emergency Medicine, Centre Hospitalier de Wallonie Picarde, Tournai, Belgium; Marc Leone, MD, Department of Anesthesiology and Intensive Care Unit, North Hospital, Aix Marseille Université, Assistance Publique Hôpitaux Universitaires de Marseille, Marseille, France; David Lockey, MD, University of Bristol, Bristol, United Kingdom; Jens Meier, MD, Department of Anaesthesiology and Critical Care Medicine, Kepler University Hospital and Johannes Kepler University Linz, Linz, Austria; Matthias Noitz, MD, Department of Anaesthesiology and Critical Care Medicine, Kepler University Hospital and Johannes Kepler University Linz, Linz, Austria; Roberta Petrino, MD, Emergency Medicine Unit, Ospedale Regionale di Lugano, EOC, Switzerland; Sirak Petros, MD, Medical ICU, University Hospital of Leipzig, Leipzig, Germany; Patrick Plaisance, MD, PhD, Emergency Department, Hôpital Lariboisière, Paris, France; Jacobus Preller, FRCP, John Farman ICU, Cambridge University Hospital NHS Foundation Trust, Cambridge, United Kingdom; Luis Garcia-Castrillo Riesgo, MD, Emergency Department, Hospital Marqués de Valdecilla, Santander, Spain; Carl Otto Schell, MD, Centre for Clinical Research, Sörmland, Uppsala University, Uppsala, Sweden; Jana Šeblová, MD, PhD, Paediatric Emergency Department, Motol University Hospital, Prague, Czechia; Christian Sitzwohl, MD, Department of Anaesthesiology and Intensive Care Medicine, St. Josef Hospital Vienna, Vienna, Austria; Christian Baaner Skjaerbaek, MD, Emergency Department, Regionshospitalet Randers, Randers, Denmark; Markus Skrifvars, MD, PhD, Department of Emergency Care and Services, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Kjetil Sunde, MD, PhD, Department of Anesthesia and Intensive Care Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Tina Tomić Mahečić, MD, PhD, Department of Anesthesiology and Intensive Care Medicine, Clinical Hospital Centre Zagreb, Zagreb, Croatia; Helmut Trimmel, MD, Department of Anesthesiology, Emergency and Critical Care Medicine General Hospital Wiener Neustadt, Wiener Neustadt, Austria; Andreas Valentin, MD, Department of Internal Medicine, Cardiology and Intensive Care Medicine, Klinik Donaustadt, Vienna, Austria; Volker Wenzel, MD, Department of Anesthesiology, Intensive Care Medicine, Pain Therapy and Emergency Medicine, Klinikum Friedrichshafen, Friedrichshafen, Germany and Department of Anesthesiology, University of Florida, Gainesville, Florida, USA Conflicts of interest There are no conflicts of interest.
Abstract Background Predicting outcomes of critically ill intensive care unit (ICU) patients with coronavirus-19 disease (COVID-19) is a major challenge to avoid futile, and prolonged ICU stays. Methods The objective was to develop predictive survival models for patients with COVID-19 after 1-to-2 weeks in ICU. Based on the COVID–ICU cohort, which prospectively collected characteristics, management, and outcomes of critically ill patients with COVID-19. Machine learning was used to develop dynamic, clinically useful models able to predict 90-day mortality using ICU data collected on day (D) 1, D7 or D14. Results Survival of Severely Ill COVID (SOSIC)-1, SOSIC-7, and SOSIC-14 scores were constructed with 4244, 2877, and 1349 patients, respectively, randomly assigned to development or test datasets. The three models selected 15 ICU-entry variables recorded on D1, D7, or D14. Cardiovascular, renal, and pulmonary functions on prediction D7 or D14 were among the most heavily weighted inputs for both models. For the test dataset, SOSIC-7’s area under the ROC curve was slightly higher (0.80 [0.74–0.86]) than those for SOSIC-1 (0.76 [0.71–0.81]) and SOSIC-14 (0.76 [0.68–0.83]). Similarly, SOSIC-1 and SOSIC-7 had excellent calibration curves, with similar Brier scores for the three models. Conclusion The SOSIC scores showed that entering 15 to 27 baseline and dynamic clinical parameters into an automatable XGBoost algorithm can potentially accurately predict the likely 90-day mortality post-ICU admission (sosic.shinyapps.io/shiny). Although external SOSIC-score validation is still needed, it is an additional tool to strengthen decisions about life-sustaining treatments and informing family members of likely prognosis.
Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19).
Objective
To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia.
Design, Setting, and Particpants
This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes.
Interventions
Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.
Main Outcomes and Measures
Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events.
Results
Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21).
Conclusions and Relevance
In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care unit, TCZ did not reduce WHO-CPS scores lower than 5 at day 4 but might have reduced the risk of NIV, MV, or death by day 14. No difference on day 28 mortality was found. Further studies are necessary for confirming these preliminary results.
