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Infection with the severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) was first identified in December 2019 and has since become a worldwide pandemic, challenging and sometimes overwhelming healthcare systems as well as causing more than a million deaths thus far. In just 10 months, over 80,000 indexed publications have appeared that reference SARS-CoV-2 and the associated Coronavirus disease 2019 (COVID-19). In this article, we highlight 20 papers that are of particular relevance to the critical care clinician. The papers are divided into four broad topics: manifestations of severe COVID- 19 disease, pharmacological therapy for COVID-19, ventilatory support for COVID-19 acute respiratory distress syndrome (ARDS), and healthcare system and worker stress. This list is not designed to be comprehensive but rather to give the reader an overview of important early papers and their findings. info:eu-repo/semantics/publishedVersion

In 2020, a new pandemic caused by SARS-CoV-2 was declared [1], and since the first cases of coronavirus disease 2019 (COVID-19), clinicians had to apply different modes of respiratory support, previously used on patients with severe respiratory failure from other etiologies. In particular, high-flow nasal cannulae (HFNC) and non-invasive ventilation (NIV) were variably applied in early reports from China [2] and Europe [3]. Yet, the extent of airborne contamination of clinical areas during the use of HFNC has sparked intense debate and highlighted the need for inclusive investigation in this area.

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Introduction Diversity has become a key-strategic element of success in various political and economic fields. The European Society of Intensive Care Medicine (ESICM) decided to make diversity a key strategic priority for the future and appointed a Task-Force on this topic. Methods In a consensus process, three Working-Groups, nominated by Task-Force members, developed statements on strategic future topics. In addition, diversity-related data available from the membership database have been analyzed and reported in aggregated form. Results The Task-Force decided to nominate working groups on (1) “sex, gender identity and sexual orientation”, (2) “ethnicity, culture and socio-economic status”, and (3) “multiprofessionalism”. These are the first prioritized topics for the near future. The first diversity-report shows targetable items in all three domains. Conclusion The diversity Task-Force defined actionable items for a one- and three-year plan that are especially aiming at the identification of potential gaps and an implementation of concrete projects for members of the ESICM. Electronic supplementary material The online version of this article (10.1007/s00134-019-05606-0) contains supplementary material, which is available to authorized users.

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Elderly patients represent an increasing proportion of the general medical take and of the inpatient population in our hospitals.[1][1] Older patients are at increased risk of falls while in hospital. Most falls are multifactorial in nature. Delirium in the context of acute illness and unfamiliar

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Sepsis is a life-threatening condition characterized by one or more organ dysfunctions due to a dysregulated host response to infection [1] or, in certain cases, due to direct pathogen effects. Sepsis is not only associated with bacterial or fungal infections but also with any other infection such as viral disease, protozoal (e.g., malaria), or tropical infections. Although the literature suggests that sepsis is predominantly a healthcare issue in resource-rich countries, the global burden of acute infections is highest in resource-limited areas [2]. Successful sepsis management relies on various components of which early recognition is essential. Evidence and recommendations for sepsis recognition are mainly based on research performed in resource-rich settings [3]. However, resource-rich and -limited countries differ in healthcare accessibility [4] and infectious disease epidemiology [5–7]. It is therefore unreasonable to directly translate evidence between these settings. The Global Intensive Care working group of the European Society of Intensive Care Medicine together with the Mahidol-Oxford Research Unit formed an international team of physicians to revise existent recommendations for sepsis management in resource-limited settings [8]. In this manuscript, we summarize recommendations on sepsis recognition. A detailed description of the guideline team, conflicts of interest, methods, rationales, and references is given in the Online supplement.

In this chapter we discuss recommendations on the identification of patients with acute respiratory distress syndrome (ARDS), indications for mechanical ventilation, and strategies for lung-protective ventilation in resource-limited settings. Where blood gas analyzers are unavailable, it can be replaced by the plethysmographic oxygen saturation/fractional inspirational oxygen concentration (SpO2/FiO2) gradient. Bedside lung ultrasound is a valuable diagnostic tool assessing pulmonary edema and other pathologies. A number of recommendations for safe and lung-protective mechanical ventilation in patients with sepsis and respiratory failure are provided. However, many of these have not been trialed specifically in resource-limited settings. These recommendations include an elevated head-of-bed position and a minimum level of positive end-expiratory pressure (PEEP) of 5 cm H2O only to be in patients with moderate or severe ARDS. In addition, low FiO2 and low oxygenation goals are suggested, using PEEP/FiO2 tables. Recruitment maneuvers are indicated in refractory hypoxia, but require experienced staff. Low tidal volumes (5–7 ml/kg predicted body weight, avoiding >10 ml/kg) are recommended and if at all possible in combination with end-tidal carbon dioxide (CO2) monitoring for recognition of dislodgement of the endotracheal tube and under- or overventilation. “Volume-controlled” modes could be safer than “pressure-controlled” modes, and we recommend to check regularly whether a patient tolerates a “support” mode; we also suggest to perform spontaneous breathing trials to timely identify patients who are ready for extubation, but also to plan extubating patients when sufficient staff is around to guarantee safe re-intubation.

The emergence of the Ebola virus disease (EVD) outbreak in West Africa threatens regional and global public health security. This epidemic, first announced in March 2014 in Guinea Conakry, has grown dramatically since June 2014 with an extension into Liberia and Sierra Leone. Nigeria, Mali, and Democratic Republic of the Congo were also transiently affected. It was declared to be a public health emergency of international concern by the World Health Organization (WHO) on 8 August 2014. On 21 January 2015, a cumulative total of more than 21,800 cases was reported by the WHO [1], with a case fatality rate (CFR) of between 57 and 59 % among hospitalized patients. A total of 828 healthcare workers (HCWs) have been infected with the Ebola virus since the beginning of the epidemic, with a CFR of 60 %. Some Western countries have also reported imported cases: six patients in the USA, Spain and UK, including one death (CFR of 16.7 %). Direct contact with infected bodily fluids—usually feces, vomit, or blood—is necessary for transmission. Once the Ebola virus is suspected, based on national versions of WHO’s case definition recommendations [2], specific laboratory tests can confirm or disprove diagnoses in a few hours, but for this, the patient has to be transported to a specialized center with specific management conditions [3]. In this article, the authors compared procedures for the transport of Ebola patients in their respective countries (USA, UK, and France) to identify common principles.

Critical care environments are magnets for drug-resistant organisms. Patients are extremely vulnerable to nosocomial infections due to the severity of their clinical condition, the siting of multiple invasive medical devices and their proximity to other infected patients. Use of broad spectrum antibiotics is high in intensive care units (ICUs) compared to other hospital departments, making selection of drug-resistant bacteria more likely. In low- and middle-income countries (LMICs), nosocomial infections are thought to be more common than in high-income countries (HICs), although objective incidence rates are unknown, since routine bacteriological surveillance does not usually occur. In tropical settings, severe malaria is a common cause of sepsis, and antimalarial drug resistance is an increasing problem. Here, we give our perspective on the important threat of antimicrobial drug resistance (AMR) in critical care patients in LMICs, contributing factors and initiatives to address this. For further reading, we refer to the supplement listing additional references.

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In this chapter, we outline important elements for the general supportive care for patients with sepsis in resource-limited settings. We discuss the use of corticosteroids, sedation, neuromuscular blocking agents, deep venous thrombosis (DVT) prophylaxis, gastric ulcer prevention, glucose control, enteral feeding, renal replacement therapy, and initial fluid resuscitation. Low-dose corticosteroids are recommended in septic patients with refractory shock, pending completion of current trials. Important issues around sedation include the availability of selected opiates and benzodiazepines, ways of administration, and availability of expertise and (human) resources essential for dosing and monitoring of sedation to care for mechanically ventilated patients with sepsis. Venous thromboembolism prophylaxis with proton-pump inhibitors and histamine-2 receptor antagonists is generally available for stress ulcer prophylaxis in resource-limited ICUs and can be delivered feasibly and safely. Critical illness-associated hyperglycemia is common, and short-acting insulin is widely available and inexpensive. However, stringent blood glucose control is not recommended, since this is dangerous in settings where continuous intravenous insulin with frequent monitoring is not feasible. Enteral feeding can be with hospital-prepared foods where commercial feeds are not available or expensive. Risk of aspiration pneumonia starts early in comatose non-intubated patients. Although not as effective as hemodialysis or hemofiltration methods, peritoneal dialysis is a feasible and cost-effective alternative for renal replacement therapy in very resource-limited settings. Initial fluid resuscitation in severe sepsis or septic shock should be more conservative in resource-limited settings where positive-pressure mechanical ventilation is not readily available.

The recent year marked a milestone in the field of sepsis in adults, with the revised Sepsis-3 definitions [1] and the updated Surviving Sepsis Campaign [2] published. But what about paediatric sepsis: how does Sepsis-3 fit in with what we know on paediatric sepsis and can we relate it to the way we treat children with sepsis?

In a very real sense, sepsis illustrates the multiple dimensions of the immune response of critically ill patients. On the one hand, sepsis can be viewed as the simple result of the interplay between a pathogen and the immune response to that pathogen. On the other hand, it is becoming clearer that this interplay is much more complex than it appeared. It often leads to major defects in immunity during recovery, conferring increased susceptibility to secondary infections and leading to worsened outcomes [1, 2]. Sepsis: a syndrome with different clinical presentations

Introduction Studies indicate that sepsis and septic shock in resourcelimited settings are at least as common as in resourcerich settings. The surviving sepsis campaign (SSC) guidelines have been widely adopted throughout the world, but in resource-limited settings are often unfeasible [1]. The guidelines are based almost exclusively on evidence from resource-rich settings and are not necessarily applicable elsewhere due to differences in etiology and diagnostic or treatment capacity. An international team of physicians with extensive practical experience in resource-limited intensive care units (ICUs) identified key questions concerning the SSC’s infection management recommendations, and evidence from resourcelimited settings regarding these was evaluated using the grading of recommendations assessment, development and evaluation (GRADE) tools. This article focuses primarily on bacterial causes of sepsis and septic shock. Other infections common in resource-limited settings, such as malaria, are covered in a separate article in this series. Evidence quality was scored as high (grade A), moderate (B), low (C), or very low (D), and recommendations as strong (1) or weak (2). The major difference from the grading of recommendations in the SSC-guidelines was in taking account of contextual factors relevant to resource-limited settings, such as the availability, affordability and feasibility of interventions in resource-limited ICUs. Strong recommendations have been worded as ‘we recommend’ and weak recommendations as ‘we suggest’ (details in online supplement).

The article ECDC definitions and methods for the surveillance of healthcare‑associated infections in intensive care units.

Importance In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial. Objective To assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response. Design, Setting, and Participants Multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response, which was defined as a level of C-reactive protein greater than 150 mg/L at admission. Patients were recruited and followed up from June 2004 through February 2012. Interventions Patients were randomized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission. Main Outcomes and Measures The primary outcome was treatment failure (composite outcome of early treatment failure defined as [1] clinical deterioration indicated by development of shock, [2] need for invasive mechanical ventilation not present at baseline, or [3] death within 72 hours of treatment; or composite outcome of late treatment failure defined as [1] radiographic progression, [2] persistence of severe respiratory failure, [3] development of shock, [4] need for invasive mechanical ventilation not present at baseline, or [5] death between 72 hours and 120 hours after treatment initiation; or both early and late treatment failure). In-hospital mortality was a secondary outcome and adverse events were assessed. Results There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) ( P = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37); the difference between groups was 5% (95% CI, −6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group ( P = .34). Conclusions and Relevance Among patients with severe community-acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone compared with placebo decreased treatment failure. If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population. Trial Registration clinicaltrials.gov Identifier:NCT00908713

The human body depends on an integrated neuro-endocrine response in order to adapt to external and internal stressors. In critical illness this stress response coordinates endocrine, neural, cardiovascular and immune systems with the aim to maximize survival chances. The hypothalamus–pituitary–adrenal (HPA) axis, which also includes elements producing the neurohypophysial hormone arginine–vasopressin (AVP), is one the key effectors within this system [1]. Relative HPA or AVP deficiency contributes to cardiovascular collapse in critically ill patients, leading to the rationale of therapy with these hormones in shock. Recent developments have implicated copeptin, a by-product of the AVP precursor, as a novel biomarker for early stages of critical illness that could influence clinical decision-making.

Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are among the few interventions in intensive care medicine that have been shown to improve patient survival, but their use is limited to a minority of European intensive care units (ICUs) (Tables 1, ​,2)2) [1]. Table 1 Large studies comparing SDD and SOD Table 2 Post hoc analyses and secondary studies on SDD and SOD In addition, when the microbiological data of patients receiving SDD or SOD were compared with those receiving standard care, ICU-acquired bacteremia was significantly reduced for Staphylococcus aureus, glucose-non-fermenting Gram-negative rods, and Enterobacteriaceae [4], In particular, the use of SDD was associated with a lower incidence of acquired bacteremia with Enterobacteriaceae. Similarly, ICU-acquired candidemia was lower in the SDD group than in the SOD group or standard care group, but the difference was not significant. These findings were confirmed in a recent study comparing SDD and SOD on antibiotic resistance. The incidence of ICU-acquired bacteremia was also lower for aminoglycoside-resistant Gram-negative bacteria in the SDD group [5]. Although the survival rate of ICU patients remains similar in both studies, the lower incidence of antibiotic resistance and nosocomial bacteremia as consistent findings are in favour of SDD. Common reasons for the reluctance to use SDD or SOD are related to only a few arguments regularly mentioned in editorials and by expert opinion expressing the fear that their use may promote antibiotic resistance and the possible increase of methicillin-resistant S. aureus [15]. These can be summarized as follows: The absence of emergence of resistance is against current microbiological concepts and contradicts the worldwide pandemic of multidrug-resistant microorganisms demonstrated to be directly related to the use of antibiotics. In a recent meta-analysis, no relation was observed between the use of SDD and the development of antimicrobial resistance, thus confirming earlier reports [16]. Recent studies have demonstrated similar findings (Table 2). In a large study showing lower mortality with the use of SDD or SOD compared with standard care, patients treated with SDD and SOD had a significantly lower incidence of carriage and infections with antibiotic-resistant bacteria [4]. Moreover, when compared with SOD, SDD was related with lower rectal carriage of antibiotic-resistant Gram-negative bacteria [5]. By contrast, the continuous application of antibiotics included in the paste, as well as the aerosolized colistin applied in the case of emergence of Gram-negative bacilli in the respiratory samples, may largely contribute to the absence of the documented emergence of resistance (footnote Table 1). One of the main reasons of bacterial resistance to antibiotics is the widespread use of antimicrobial agents. This represents the main reluctance for the use of SDD. Surprisingly, some investigators have even advocated for the use of SOD due to the absence of widespread systemic prophylaxis with cephalosporins and a lower volume of topical antibiotics [4]. Indeed, when SDD was compared with standard care, the use of cephalosporins was increased due to the SDD regimen, but the use of antimicrobial agents was reduced significantly for broad-spectrum penicillins, carbapenems, lincosamides, and quinolones [4]. This was also true for SOD, but the difference with standard care was less pronounced [4]. Recent SDD/SOD studies were all performed in the Netherlands where antimicrobial resistance is a minor concern with a low reported use of broad-spectrum antibiotics, such as piperacillin/tazobactam, cefepime, and carbapenems. Hence, a more pronounced gradual increase was observed with aminoglycoside-resistant Gram-negative bacteria with SDD [5]. The effects of the prolonged use of SDD and SOD on colistin resistance have been determined in a study performed on two different large ICU cohorts [13]. No association was observed between the use of SDD or SOD and increased acquisition of colistin-resistant Gram-negative bacteria in the respiratory tract. In another study performed on patients colonized with Enterobacteriaceae in the intestinal tract at ICU admission, SDD was shown to eradicate cephalosporin-resistant Enterobacteriaceae from the intestinal tract [11]. These findings are usually related to the fact that the studies are performed in environments with a lower incidence of highly-resistant microorganisms. By contrast, studies performed in countries with a higher incidence of highly-resistant microorganisms have also reported similar effects [17, 18]. Some observations were performed over a short period of time and resistance may not have been immediately apparent. Hence, a rebound effect after stopping SDD/SOD has been suggested in one of the post hoc analyses, as well as the emergence of colistin-resistant strains during persistent Gram-negative bacteria colonization over the study period (24 months) [13, 7]. Indirect evidence suggests that SDD/SOD is associated with the long-term alteration of the microbiota of the digestive tract and a potential increase in the associated resistome, but this remains largely speculative at the present time [19]. However, these effects were not confirmed in a very recent report on continuous surveillance of the impact of SDD and SOD up to 7 years [14]. This large study confirmed a continuous reduction of the rate of tobramycin resistance and the absence of emergence of resistance to colistin in both respiratory and rectal samples (Table 2). The occurrence of a rebound effect after the discontinuation of SDD/SOD use in these centres remains to be determined. In conclusion, SDD and SOD are used in a minority of ICUs, despite the available data on survival benefit. Although antibiotic resistance is not shown to be associated with the use of SDD and SOD in the particular setting of experienced Dutch ICUs, some ecological changes in ICUs have been reported (Table 2). SDD has resulted in lower rectal carriage of antibiotic-resistant Gram-negative bacteria compared to SOD. SDD has demonstrated superiority over SOD, but both are related to a lower use of systemic antibiotics, other than those used during the first 4 days of SDD, and result in a lower mortality in ICU patients compared to standard care. Therefore, SOD can be viewed as a good alternative to SDD. However, the lower rate of bacteremia and bacterial resistance observed with SDD pleads in favor of this regimen. Further studies are planned in higher endemic resistance regions to assess the effect of SDD or SOD on long-term resistance development.

The acute respiratory distress syndrome (ARDS) causes morbidity and mortality in both resource-constrained and resource-rich settings, but diagnosis, therapy, and research priorities vary with context (Fig. 1). While ARDS exists in resource-constrained settings, it may be under-recognized and under-treated, and is certainly under-studied. This has consequences both for current ARDS patient in resource-constrained settings, as well as future patients who could benefit from context-specific interventions to improve outcomes in ARDS. Fig. 1 ARDS in resource-constrained and resource-rich settings: differences in incidence, outcomes, diagnostic approach, interventions, and research priorities The burden of ARDS in resource-constrained settings is poorly understood. One study recently reported the incidence and outcomes of ARDS in a Rwandan hospital using a modified definition of ARDS [1]. The study suggested that ARDS is both common and frequently lethal in resource-constrained settings: 4 % of adult patients met the modified definition of ARDS, and 50 % of these patients died. A direct comparison between resource-constrained and resource-rich settings is not possible because of differences in methodology of the available studies [1–3] and predicting where ARDS might be more common is not straightforward. Infection and trauma are the leading clinical insults leading to ARDS, and both are more prevalent in low-income countries [1, 2, 4]. On the other hand, ARDS could be more prevalent in high-income countries given evidence suggesting that mechanical ventilation, far more available in these settings, itself contributes to the development of ARDS [5]. In addition, the distinction between resource-constrained and resource-rich settings is more complicated in middle-income countries where resources exist but access to care may be extremely variable [6]. If ARDS is so common and lethal in resource-constrained settings, why is the data so sparse? One reason is a challenge not specific to ARDS but to all critical care research. Critical illness studies are often confined to patients in intensive care units (ICUs), of which there are very few in poorer settings [4]. The recent Intensive Care Over Nations (ICON) study is a good example of a large-scale effort to capture an international sample; yet in this study only 1.4 % of all patients were from the African continent [7]. A second reason explaining scarce ARDS data from resource-constrained settings is particular to the current Berlin definition of ARDS, which requires diagnostic and treatment capabilities that are almost universally absent in resource-limited settings [8]. Specifically, arterial blood gas analysis, which is necessary for calculation of the PaO2 to FiO2 ratio (P/F), and chest radiography, which is necessary to determine whether bilateral opacities are present, are often not accessible [9]. Validation of alternative criteria to the Berlin definition for ARDS could allow for better recognition and quantification of ARDS in resource-constrained settings. Lung ultrasound (US) may be easier to perform than chest radiography in resource-constrained settings, and increasing evidence suggests that lung US is at least as accurate as chest radiography for diagnosing ARDS [10]. Ultrasound can assess positive end-expiratory pressure (PEEP)-induced changes in lung aeration and thus has the potential to guide recruitment maneuvers. Furthermore, combining lung with bedside cardiac US can be helpful in differentiating ARDS from cardiogenic pulmonary edema and in assessing right ventricular function [11]. Advantages of US are many: fast learning curves, low costs, and requiring only basic US technology. Affordable, hand-held, battery-driven devices are increasingly available. Reasonable estimates of the P/F from SpO2 to FiO2 ratio (S/F) have been derived from large datasets, such that pulse oximetry could realistically replace oxygenation assessment by arterial blood gases [12]. The Rwandan study mentioned above demonstrated remarkable consistency in ARDS incidence using a variety of FiO2 estimates and S/F cutoffs [1]. Full validation of the Kigali modification of the Berlin definition for ARDS and definitive validation of the S/F would allow comparisons across different settings worldwide. Furthermore, S/F should be investigated as an alternative to P/F in the mounting evidence on better outcome prediction using oxygenation data at 24 h from ARDS diagnosis [13]. Does it matter that ARDS exists in resource-constrained settings but is rarely recognized? Yes. It matters because recognition is necessary to improve outcomes. First, recognition allows implementation of interventions that are clearly feasible in resource-constrained settings, such as conservative fluid management for both prevention and supportive care [14]. Second, recognition allows research into the risks and benefits of applying interventions that are known to be effective in resource-rich settings but could be less safe in settings with fewer trained staff (Fig. 1). For example, proning for severe ARDS is theoretically possible given that it requires no particular technology; however, the ability to perform it safely with the few staff available may be a barrier. A trial in Bangladesh that found possible harm from early enteral feeding in cerebral malaria is a good example of the need to test interventions in both resource-rich and resource-constrained environments, where the risks and benefits may be very different [15]. Third, recognition allows research into ARDS triggers and lung injury pathways that may be different in various contexts and populations. ARDS associated with malaria, HIV, or tuberculosis in Africa may represent a different set of molecular pathways than ARDS associated with community-acquired pneumonia in Europe. Just as research in sepsis requires one to pursue targeted molecular therapies that include resource-limited settings [16], so too does the heterogeneity of ARDS triggers and presentations highlight the need for trials in settings beyond resource-rich countries. Finally, recognition of ARDS could contribute to improvements in all aspects of healthcare. A good outcome for a patient with ARDS caused by peritonitis requires the capacity for safe surgery and adequate antibiotics in addition to lung-protective ventilation. This sobering limitation is nonetheless a platform for advocacy. Just as a ‘vertical’ approach to improving HIV outcomes has led to a recognition of a need for ‘horizontal’ health system strengthening, so too could a focus on ARDS strengthen advocacy for improved healthcare systems. ARDS exists worldwide, including in resource-poor settings where its incidence, triggers, modifiers, and outcomes remain largely unknown. Validation of a definition that can be applied in all settings, education about how to prevent and manage the syndrome, and research to expand treatment strategies are all desperately needed.