Marcus J. Schultz

Critical Care in Resource-Restricted Settings.

In many lowand middle-income countries, with improved public health services like sanitation and immunization, the relative contribution of curative care for critically ill patients to overall health and life expectancy has increased considerably. The importance of intensive care facilities as a global good was emphasized by recent epidemics in which survival was highly dependent on adequate critical care. Examples include the SARS coronavirus (2002-2003), avian influenza H5N1 (2004 and onward), pandemic influenza A(H1N1) (2009), the MERS coronavirus (2012 and onward), and Ebola virus disease (2014-2015). An important impediment for capacity planning in resource-restricted settings is the limited data on critical care usage and capacity.1 However, basic intensive care facilities are becoming increasingly available in developing countries. For example, the number of intensive care unit (ICU) beds in Sri Lanka, a lowerto middle-income country, is now 2.5 per 100 000 inhabitants, compared with 3.5 ICU beds per 100 000 in the United Kingdom and 20 per 100 000 in the United States.2 In low-income countries, such as Bangladesh, with 0.3 ICU beds per 100 000 population, availability of intensive care is more limited and often only accessible to those members of society who can afford private hospitals. Beyond the quantity of ICU beds, there may also be concerns about the quality of care, as suggested by higher than expected ICU case

Continuous glucose monitoring in the ICU: clinical considerations and consensus

Glucose management in intensive care unit (ICU) patients has been a matter of debate for almost two decades. Compared to intermittent monitoring systems, continuous glucose monitoring (CGM) can offer benefit in the prevention of severe hyperglycemia and hypoglycemia by enabling insulin infusions to be adjusted more rapidly and potentially more accurately because trends in glucose concentrations can be more readily identified. Increasingly, it is apparent that a single glucose target/range may not be optimal for all patients at all times and, as with many other aspects of critical care patient management, a personalized approach to glucose control may be more appropriate. Here we consider some of the evidence supporting different glucose targets in various groups of patients, focusing on those with and without diabetes and neurological ICU patients. We also discuss some of the reasons why, despite evidence of benefit, CGM devices are still not widely employed in the ICU and propose areas of research needed to help move CGM from the research arena to routine clinical use.

Respiratory support in patients with acute respiratory distress syndrome: An expert opinion

Acute respiratory distress syndrome (ARDS) is a common condition in intensive care unit patients and remains a major concern, with mortality rates of around 30–45% and considerable long-term morbidity. Respiratory support in these patients must be optimized to ensure adequate gas exchange while minimizing the risks of ventilator-induced lung injury. The aim of this expert opinion document is to review the available clinical evidence related to ventilator support and adjuvant therapies in order to provide evidence-based and experience-based clinical recommendations for the management of patients with ARDS.

ARDS: challenges in patient care and frontiers in research

This review discusses the clinical challenges associated with ventilatory support and pharmacological interventions in patients with acute respiratory distress syndrome (ARDS). In addition, it discusses current scientific challenges facing researchers when planning and performing trials of ventilatory support or pharmacological interventions in these patients. Noninvasive mechanical ventilation is used in some patients with ARDS. When intubated and mechanically ventilated, ARDS patients should be ventilated with low tidal volumes. A plateau pressure <30u2005cmH2O is recommended in all patients. It is suggested that a plateau pressure <15 cmH2O should be considered safe. Patient with moderate and severe ARDS should receive higher levels of positive end-expiratory pressure (PEEP). Rescue therapies include prone position and neuromuscular blocking agents. Extracorporeal support for decapneisation and oxygenation should only be considered when lung-protective ventilation is no longer possible, or in cases of refractory hypoxaemia, respectively. Tracheotomy is only recommended when prolonged mechanical ventilation is expected. Of all tested pharmacological interventions for ARDS, only treatment with steroids is considered to have benefit. Proper identification of phenotypes, known to respond differently to specific interventions, is increasingly considered important for clinical trials of interventions for ARDS. Such phenotypes could be defined based on clinical parameters, such as the arterial oxygen tension/inspiratory oxygen fraction ratio, but biological marker profiles could be more promising. Treatment of ARDS is mainly through the prevention of ventilation-induced lung injury http://ow.ly/DeJC30hGWfi

Optimizing the Settings on the Ventilator: High PEEP for All?

Mechanical ventilation is an effective life-support technique widely deployed across a variety of clinical settings in the care of many millions of patients each year worldwide. However, it is not a panacea. A central issue is that artificial ventilation works by pushing air into the lungs via positive pressure, whereas physiologic respiration works by generating negative pressure to draw air into the lungs. Pushing air into the lungs is a challenge because not all lung areas distend and collapse at the same driving pressure. Thus, a positive pressure breath may overstretch one lung area while failing to open another one, compromising gas exchange and causing direct mechanical injury to the lung (so-called ventilator-induced lung injury). Both the volume and pressure settings on a ventilator have been implicated in ventilator-induced lung injury, with tidal volumes that are too large implicated in overdistension and positive end-expiratory pressure (PEEP) settings that are too low implicated in alveolar collapse. Thus, current guidelines endorse a low tidal volume and a high or at least avoidance of low PEEP level. But, these “one size fits all” recommendations may not be optimal for all patients.

Recommendations on infrastructure and organization of adult ICUs in resource-limited settings

Introduction Published guidelines regarding optimal infrastructure and organization of intensive care units (ICUs) are based on evidence primarily from resource-rich settings [1, 2]. These guidelines may be less applicable to resourcelimited settings [3]. An international team of physicians from the Mahidol–Oxford Tropical Medicine Research Unit and the Global Intensive Care working group of the European Society of Intensive Care Medicine, all with extensive experience in resource-limited ICUs, evaluated a list of seven clearly defined questions regarding ICU organization in resource-limited settings using literature review and a modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool [4]. Evidence quality was scored from very high (A) to very low (D), and recommendation strength was strong (1) or weak (2). Availability, feasibility, affordability and safety of recommendations in resource-limited settings were specially emphasized (Table 1). Full scoring details are available in the online supplement. The authors recognize that ICUs around the world differ in available resources. Definitions of ICU have been set forth by our working group [3] and others [1]. Recommendations and suggestions

Intraoperative ventilation settings and their associations with postoperative pulmonary complications in obese patients

Background: There is limited information concerning the current practice of intraoperative mechanical ventilation in obese patients, and the optimal ventilator settings for these patients are debated. We investigated intraoperative ventilation parameters and their associations with the development of postoperative pulmonary complications (PPCs) in obese patients. Methods: We performed a secondary analysis of the international multicentre Local ASsessment of VEntilatory management during General Anesthesia for Surgery’ (LAS VEGAS) study, restricted to obese patients, with a predefined composite outcome of PPCs as primary end‐point. Results: We analysed 2012 obese patients from 135 hospitals across 29 countries in Europe, North America, North Africa, and the Middle East. Tidal volume was 8.8 [25th–75th percentiles: 7.8–9.9] ml kg−1 predicted body weight, PEEP was 4 [1–5] cm H2O, and recruitment manoeuvres were performed in 7.7% of patients. PPCs occurred in 11.7% of patients and were independently associated with age (P<0.001), body mass index ≥40 kg m−2 (P=0.033), obstructive sleep apnoea (P=0.002), duration of anaesthesia (P<0.001), peak airway pressure (P<0.001), use of rescue recruitment manoeuvres (P<0.05) and routine recruitment manoeuvres performed by bag squeezing (P=0.021). PPCs were associated with an increased length of hospital stay (P<0.001). Conclusions: Obese patients are frequently ventilated with high tidal volume and low PEEP, and seldom receive recruitment manoeuvres. PPCs increase hospital stay, and are associated with preoperative conditions, duration of anaesthesia and intraoperative ventilation settings. Randomised trials are warranted to clarify the role of different ventilatory parameters in obese patients. Clinical trial registration: NCT01601223.

The fragility of statistically significant findings in randomised controlled anaesthesiology trials: systematic review of the medical literature

&NA; The fragility index (FI), the number of events the statistical significance a result depends on, and the number of patients lost to follow‐up are important parameters for interpreting randomised clinical trial results. We evaluated these two parameters in randomised controlled trials in anaesthesiology. For this, we performed a systematic search of the medical literature, seeking articles reporting on anaesthesiology trials with a statistically significant difference in the primary outcome and published in the top five general medicine journals, or the top 15 anaesthesiology journals. We restricted the analysis to trials reporting clinically important primary outcome measures. The search identified 139 articles, 35 published in general medicine journals and 104 in anaesthesiology journals. The median (inter‐quartile range) sample size was 150 (70–300) patients. The FI was 4 (2–17) and 3 (2–7), and the number of patients lost to follow‐up was 0 (0–18) and 0 (0–6) patients in trials published in general medicine and anaesthesiology journals, respectively. The number of patients lost to follow‐up exceeded the FI in 41 and 27% in trials in general medicine journals and anaesthesiology journals, respectively. The FI positively correlated with sample size and number of primary outcome events, and negatively correlated with the reported P‐values. The results of this systematic review suggest that statistically significant differences in randomised controlled anaesthesiology trials are regularly fragile, implying that the primary outcome status of patients lost to follow‐up could possibly have changed the reported effect.

CONTINUOUS EXHALED BREATH ANALYSIS ON THE ICU

During admittance to the ICU, critically ill patients frequently develop secondary infections and/or multiple organ failure. Continuous monitoring of biological markers is very much needed. This study describes a new method to continuously monitor biomarkers in exhaled breath with an electronic nose.

Treatment with broadly neutralizing influenza antibodies reduces severity of secondary pneumococcal pneumonia in mice: VAN SOMEREN GRÉVE et al.

Secondary bacterial pneumonia is a frequent complication of influenza, associated with high morbidity and mortality. We hypothesized that treatment with neutralizing influenza A antibody AT10_002 protects against severe secondary pneumococcal infection in a mouse model of influenza A infection. Influenza A (H3N2) virus–infected male C57Bl6 mice were treated intravenously with either AT10_002 or a control 2 days postinfection. Seven days later, both groups were infected with Streptococcus pneumoniae and killed 18u2009hours later. Mice receiving AT10_002 showed less loss of bodyweight compared with controls (+1% vs −12%, Pu2009<u2009.001), lower viral loads in bronchoalveolar lavage fluids (BALFs) (7 vs 194 RNA copies per µL; Pu2009<u2009.001), and reduced bacterial outgrowth in lung homogenates (3.3u2009×u2009101 vs 2.5u2009×u2009105 colony‐forming units per mg; Pu2009<u2009.001). The treatment group showed lower pulmonary wet weights, lower cell counts, and lower protein levels in BALF compared with controls. Treatment with AT10_002 was associated with lower levels of tumor necrosis factor‐α, interleukin (IL)‐6, cytokine‐induced neutrophil chemoattractant (KC), and interferon‐γ in BALF and lower IL‐6 and KC in lung homogenates. Treatment with anti‐influenza antibody AT10_002 is associated with reduced weight loss, viral load, bacterial outgrowth, and lung injury in a murine model of secondary pneumococcal pneumonia following influenza infection.