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Coronavirus disease 19 (COVID-19) has posed unprecedented healthcare system challenges, some of which will lead to transformative change. It is obvious to healthcare workers and policymakers alike that an effective critical care surge response must be nested within the overall care delivery model. The COVID-19 pandemic has highlighted key elements of emergency preparedness. These include having national or regional strategic reserves of personal protective equipment, intensive care unit (ICU) devices, consumables and pharmaceuticals, as well as effective supply chains and efficient utilization protocols. ICUs must also be prepared to accommodate surges of patients and ICU staffing models should allow for fluctuations in demand. Pre-existing ICU triage and end-of-life care principles should be established, implemented and updated. Daily workflow processes should be restructured to include remote connection with multidisciplinary healthcare workers and frequent communication with relatives. The pandemic has also demonstrated the benefits of digital transformation and the value of remote monitoring technologies, such as wireless monitoring. Finally, the pandemic has highlighted the value of pre-existing epidemiological registries and agile randomized controlled platform trials in generating fast, reliable data. The COVID-19 pandemic is a reminder that besides our duty to care, we are committed to improve. By meeting these challenges today, we will be able to provide better care to future patients.

BackgroundThe novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. MethodsWe formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. ResultsThe Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy. ConclusionThe Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.

Intensive Care organization varies across Europe where the number of intensive care unit (ICU) beds is 11.5/100,000 people but varies from 4.2/100,000 (Portugal) to nearly 30/100,000 (Germany). This variation also applies to nurse ratio: from one to three patients/nurse according to countries [2]. The need for ICU beds is growing continuously, not only in response to a pandemic but also to our aging societies’ needs. Recent medical progress (complex surgical operations, cell therapy with CAR-T cells, etc.) required more ICU beds. During the pandemic, critical care outreach has allowed opening more beds in the wards, where noninvasive respiratory support has been provided [3]. Expanding ICU’s beds automatically requires increasing the number of competent, skilled ICU specialists, nurses and other allied professionals. Failure to do so will mean ICU beds’ shortage across Europe.

ObjectiveTo identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock.DesignA consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations.MethodsEach committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 - supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science.ResultsThe Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction?ConclusionsWhile the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

There is controversy about how to manage requests by patients or surrogates for treatments that clinicians believe should not be administered. This multisociety statement provides recommendations to prevent and manage intractable disagreements about the use of such treatments in intensive care units. The recommendations were developed using an iterative consensus process, including expert committee development and peer review by designated committees of each of the participating professional societies (American Thoracic Society, American Association for Critical Care Nurses, American College of Chest Physicians, European Society for Intensive Care Medicine, and Society of Critical Care). The committee recommends: (1) Institutions should implement strategies to prevent intractable treatment conflicts, including proactive communication and early involvement of expert consultants. (2) The term \"potentially inappropriate\" should be used, rather than futile, to describe treatments that have at least some chance of accomplishing the effect sought by the patient, but clinicians believe that competing ethical considerations justify not providing them. Clinicians should explain and advocate for the treatment plan they believe is appropriate. Conflicts regarding potentially inappropriate treatments that remain intractable despite intensive communication and negotiation should be managed by a fair process of conflict resolution; this process should include hospital review, attempts to find a willing provider at another institution, and opportunity for external review of decisions. When time pressures make it infeasible to complete all steps of the conflict-resolution process and clinicians have a high degree of certainty that the requested treatment is outside accepted practice, they should seek procedural oversight to the extent allowed by the clinical situation and need not provide the requested treatment. (3) Use of the term \"futile\" should be restricted to the rare situations in which surrogates request interventions that simply cannot accomplish their intended physiologic goal. Clinicians should not provide futile interventions. (4) The medical profession should lead public engagement efforts and advocate for policies and legislation about when life-prolonging technologies should not be used. The multisociety statement on responding to requests for potentially inappropriate treatments in intensive care units provides guidance for clinicians to prevent and manage disputes in patients with advanced critical illness.

Background There is little evidence to support the management of severe COVID-19 patients. Methods To document this variation in practices, we performed an online survey (April 30–May 25, 2020) on behalf of the European Society of Intensive Care Medicine (ESICM). A case vignette was sent to ESICM members. Questions investigated practices for a previously healthy 39-year-old patient presenting with severe hypoxemia from COVID-19 infection. Results A total of 1132 ICU specialists (response rate 20%) from 85 countries (12 regions) responded to the survey. The survey provides information on the heterogeneity in patient’s management, more particularly regarding the timing of ICU admission, the first line oxygenation strategy, optimization of management, and ventilatory settings in case of refractory hypoxemia. Practices related to antibacterial, antiviral, and anti-inflammatory therapies are also investigated. Conclusions There are important practice variations in the management of severe COVID-19 patients, including differences at regional and individual levels. Large outcome studies based on multinational registries are warranted.

Intensive care unit (ICU) patients undergo several diagnostic and therapeutic procedures every day. The prevalence, intensity, and risk factors of pain related to these procedures are not well known. To assess self-reported procedural pain intensity versus baseline pain, examine pain intensity differences across procedures, and identify risk factors for procedural pain intensity. Prospective, cross-sectional, multicenter, multinational study of pain intensity associated with 12 procedures. Data were obtained from 3,851 patients who underwent 4,812 procedures in 192 ICUs in 28 countries. Pain intensity on a 0-10 numeric rating scale increased significantly from baseline pain during all procedures (P < 0.001). Chest tube removal, wound drain removal, and arterial line insertion were the three most painful procedures, with median pain scores of 5 (3-7), 4.5 (2-7), and 4 (2-6), respectively. By multivariate analysis, risk factors independently associated with greater procedural pain intensity were the specific procedure; opioid administration specifically for the procedure; preprocedural pain intensity; preprocedural pain distress; intensity of the worst pain on the same day, before the procedure; and procedure not performed by a nurse. A significant ICU effect was observed, with no visible effect of country because of its absorption by the ICU effect. Some of the risk factors became nonsignificant when each procedure was examined separately. Knowledge of risk factors for greater procedural pain intensity identified in this study may help clinicians select interventions that are needed to minimize procedural pain. Clinical trial registered with www.clinicaltrials.gov (NCT 01070082).

Background and Objective Therapeutic drug monitoring of tacrolimus whole-blood concentrations is standard care in thoracic organ transplantation. Nevertheless, toxicity may appear with alleged therapeutic concentrations possibly related to variability in unbound concentrations. However, pharmacokinetic data on unbound concentrations are not available. The objective of this study was to quantify the pharmacokinetics of whole-blood, total, and unbound plasma tacrolimus in patients early after heart and lung transplantation. Methods Twelve-hour tacrolimus whole-blood, total, and unbound plasma concentrations of 30 thoracic organ recipients were analyzed with high-performance liquid chromatography–tandem mass spectrometry directly after transplantation. Pharmacokinetic modeling was performed using non-linear mixed-effects modeling. Results Plasma concentration was < 1% of the whole-blood concentration. Maximum binding capacity of erythrocytes was directly proportional to hematocrit and estimated at 2700 pg/mL (95% confidence interval 1750–3835) with a dissociation constant of 0.142 pg/mL (95% confidence interval 0.087–0.195). The inter-individual variability in the binding constants was considerable (27% maximum binding capacity, and 29% for the linear binding constant of plasma). Conclusions Tacrolimus association with erythrocytes was high and suggested a non-linear distribution at high concentrations. Monitoring hematocrit-corrected whole-blood tacrolimus concentrations might improve clinical outcomes in clinically unstable thoracic organ transplants. Clinical Trial Registration NTR 3912/EudraCT 2012-001909-24.

Delirium is frequently diagnosed in critically ill patients and is associated with adverse outcome. Impaired cholinergic neurotransmission seems to have an important role in the development of delirium. We aimed to establish the effect of the cholinesterase inhibitor rivastigmine on the duration of delirium in critically ill patients. Patients (aged ≥18 years) who were diagnosed with delirium were enrolled from six intensive care units in the Netherlands, and treated between November, 2008, and January, 2010. Patients were randomised (1:1 ratio) to receive an increasing dose of rivastigmine or placebo, starting at 0·75 mL (1·5 mg rivastigmine) twice daily and increasing in increments to 3 mL (6 mg rivastigmine) twice daily from day 10 onwards, as an adjunct to usual care based on haloperidol. The trial pharmacist generated the randomisation sequence by computer, and consecutively numbered bottles of the study drug according to this sequence to conceal allocation. The primary outcome was the duration of delirium during hospital admission. Analysis was by intention to treat. Duration of delirium was censored for patients who died or were discharged from hospital while delirious. Patients, medical staff, and investigators were masked to treatment allocation. Members of the data safety and monitoring board (DSMB) were unmasked and did interim analyses every 3 months. This trial is registered with ClinicalTrials.gov, number NCT00704301. Although a sample size of 440 patients was planned, after inclusion of 104 patients with delirium who were eligible for the intention-to-treat analysis (n=54 on rivastigmine, n=50 on placebo), the DSMB recommended that the trial be halted because mortality in the rivastigmine group (n=12, 22%) was higher than in the placebo group (n=4, 8%; p=0·07). Median duration of delirium was longer in the rivastigmine group (5·0 days, IQR 2·7–14·2) than in the placebo group (3·0 days, IQR 1·0–9·3; p=0·06). Rivastigmine did not decrease duration of delirium and might have increased mortality so we do not recommend use of rivastigmine to treat delirium in critically ill patients. ZonMw, the Netherlands Brain Foundation, and Novartis.