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Anaemia and coagulopathy are common in critically ill patients and are associated with poor outcomes, including increased risk of mortality, myocardial infarction, failure to be liberated from mechanical ventilation and poor physical recovery. Transfusion of blood and blood products remains the corner stone of anaemia and coagulopathy treatment in critical care. However, determining when the benefits of transfusion outweigh the risks of anaemia may be challenging in some critically ill patients. Therefore, the European Society of Intensive Care Medicine prioritised the development of a clinical practice guideline to address anaemia and coagulopathy in non‐bleeding critically ill patients. The aims of this article are to: (1) review the evolution of transfusion practice in critical care and the direction for future developments in this important area of transfusion medicine and (2) to provide a brief synopsis of the guideline development process and recommendations in a format designed for busy clinicians and blood bank staff. These clinical practice guidelines provide recommendations to clinicians on how best to manage non‐bleeding critically ill patients at the bedside. More research is needed on alternative transfusion targets, use of transfusions in special populations (e.g., acute neurological injury, acute coronary syndromes), use of anaemia prevention strategies and point‐of‐care interventions to guide transfusion strategies. [ABSTRACT FROM AUTHOR]

Background: Intensive care unit (ICU) survivors experience high levels of morbidity after hospital discharge and are at high risk of unplanned hospital readmission. Identifying those at highest risk before hospital discharge may allow targeting of novel risk reduction strategies. We aimed to identify risk factors for unplanned 90-day readmission, develop a risk prediction model and assess its performance to screen for ICU survivors at highest readmission risk.Methods: Population cohort study linking registry data for patients discharged from general ICUs in Scotland (2005-2013). Independent risk factors for 90-day readmission and discriminant ability (c-index) of groups of variables were identified using multivariable logistic regression. Derivation and validation risk prediction models were constructed using a time-based split.Results: Of 55 975 ICU survivors, 24.1% (95%CI 23.7% to 24.4%) had unplanned 90-day readmission. Pre-existing health factors were fair discriminators of readmission (c-index 0.63, 95% CI 0.63 to 0.64) but better than acute illness factors (0.60) or demographics (0.54). In a subgroup of those with no comorbidity, acute illness factors (0.62) were better discriminators than pre-existing health factors (0.56). Overall model performance and calibration in the validation cohort was fair (0.65, 95% CI 0.64 to 0.66) but did not perform sufficiently well as a screening tool, demonstrating high false-positive/false-negative rates at clinically relevant thresholds.Conclusions: Unplanned 90-day hospital readmission is common. Pre-existing illness indices are better predictors of readmission than acute illness factors. Identifying additional patient-centred drivers of readmission may improve risk prediction models. Improved understanding of risk factors that are amenable to intervention could improve the clinical and cost-effectiveness of post-ICU care and rehabilitation. [ABSTRACT FROM AUTHOR]

Purpose: To establish the incidence of myocardial infarction (MI) in ICU patients with co-existing cardiovascular disease (CVD), and explore its association with long-term survival.Methods: In a multi-centre prospective cohort study in 11 UK ICUs, we enrolled 273 critically ill patients with co-existing CVD. We measured troponin I (cTnI) with a high sensitivity assay for 10 days; ECGs were carried out daily for 5 days and analysed by blinded cardiologists for dynamic changes. Data were combined to diagnose myocardial 'infarction', 'injury' or 'no injury' according to the third universal definition of MI. Patients were followed-up for 6 months. Regression and mediation analyses were used to explore relationships between acute physiological derangements, MI, and mortality.Results: cTnI was detected in all patients, with a rise/fall pattern consistent with an acute hit. In 73% of patients, this peaked on days 1-3 [median 114 ng/l (first, third quartiles: 27, 393)]. Serial ECGs indicated 24.2% (n = 66) of patients experienced MI, but > 95% were unrecognized by clinical teams. Type 2 MI was the most likely aetiology in all cases. A further 46.1% (n = 126) experienced injury (no ECG changes). Injury and MI were both associated with 6-month mortality (reference: no injury): OR injury 2.28 (95% CI 1.06-4.92, p = 0.035), OR MI 2.70 (95% CI 1.11-6.55, p = 0.028). Mediation analysis suggested MI partially mediated the relationship between acute physiological derangement and 6-month mortality (p = 0.002), suggesting a possible causal association.Conclusions: Undiagnosed MI occurs in around a quarter of critically ill patients with co-existing CVD and is associated with lower long-term survival. [ABSTRACT FROM AUTHOR]

Importance: In adults in whom weaning from invasive mechanical ventilation is difficult, noninvasive ventilation may facilitate early liberation, but there is uncertainty about its effectiveness in a general intensive care patient population.Objective: To investigate among patients with difficulty weaning the effects of protocolized weaning with early extubation to noninvasive ventilation on time to liberation from ventilation compared with protocolized invasive weaning.Design, Setting, and Participants: Randomized, allocation-concealed, open-label, multicenter clinical trial enrolling patients between March 2013 and October 2016 from 41 intensive care units in the UK National Health Service. Follow-up continued until April 2017. Adults who received invasive mechanical ventilation for more than 48 hours and in whom a spontaneous breathing trial failed were enrolled.Interventions: Patients were randomized to receive either protocolized weaning via early extubation to noninvasive ventilation (n = 182) or protocolized standard weaning (continued invasive ventilation until successful spontaneous breathing trial, followed by extubation) (n = 182).Main Outcomes and Measures: Primary outcome was time from randomization to successful liberation from all forms of mechanical ventilation among survivors, measured in days, with the minimal clinically important difference defined as 1 day. Secondary outcomes were duration of invasive and total ventilation (days), reintubation or tracheostomy rates, and survival.Results: Among 364 randomized patients (mean age, 63.1 [SD, 14.8] years; 50.5% male), 319 were evaluable for the primary effectiveness outcome (41 died before liberation, 2 withdrew, and 2 were discharged with ongoing ventilation). The median time to liberation was 4.3 days in the noninvasive group vs 4.5 days in the invasive group (adjusted hazard ratio, 1.1; 95% CI, 0.89-1.40). Competing risk analysis accounting for deaths had a similar result (adjusted hazard ratio, 1.1; 95% CI, 0.86-1.34). The noninvasive group received less invasive ventilation (median, 1 day vs 4 days; incidence rate ratio, 0.6; 95% CI, 0.47-0.87) and fewer total ventilator days (median, 3 days vs 4 days; incidence rate ratio, 0.8; 95% CI, 0.62-1.0). There was no significant difference in reintubation, tracheostomy rates, or survival. Adverse events occurred in 45 patients (24.7%) in the noninvasive group compared with 47 (25.8%) in the invasive group.Conclusions and Relevance: Among patients requiring mechanical ventilation in whom a spontaneous breathing trial had failed, early extubation to noninvasive ventilation did not shorten time to liberation from any ventilation.Trial Registration: ISRCTN Identifier: ISRCTN15635197. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a neutrophil-dominant disorder with no effective pharmacological therapies. While the cyclin-dependent kinase inhibitor AT7519 induces neutrophil apoptosis to promote inflammation resolution in preclinical models of lung inflammation, its potential efficacy in ARDS has not been examined. Untreated peripheral blood sepsis-related ARDS neutrophils demonstrated prolonged survival after 20 hours in vitro culture. AT7519 was able to override this phenotype to induce apoptosis in ARDS neutrophils with reduced expression of the pro-survival protein Mcl-1. We demonstrate the first pharmacological compound to induce neutrophil apoptosis in sepsis-related ARDS, highlighting cyclin-dependent kinase inhibitors as potential novel therapeutic agents. [ABSTRACT FROM AUTHOR]

Summary Background Optimal sedation of patients in intensive care units (ICUs) requires the avoidance of pain, agitation, and unnecessary deep sedation, but these outcomes are challenging to achieve. Excessive sedation can prolong ICU stay, whereas light sedation can increase pain and frightening memories, which are commonly recalled by ICU survivors. We aimed to assess the effectiveness of three interventions to improve sedation and analgesia quality: an online education programme; regular feedback of sedation–analgesia quality data; and use of a novel sedation-monitoring technology (the Responsiveness Index [RI]). Methods We did a cluster randomised trial in eight ICUs, which were randomly allocated to receive education alone (two ICUs), education plus sedation–analgesia quality feedback (two ICUs), education plus RI monitoring technology (two ICUs), or all three interventions (two ICUs). Randomisation was done with computer-generated random permuted blocks, stratified according to recruitment start date. A 45 week baseline period was followed by a 45 week intervention period, separated by an 8 week implementation period in which the interventions were introduced. ICU and research staff were not masked to study group assignment during the intervention period. All mechanically ventilated patients were potentially eligible. We assessed patients' sedation–analgesia quality for each 12 h period of nursing care, and sedation-related adverse events daily. Our primary outcome was the proportion of care periods with optimal sedation–analgesia, defined as being free from excessive sedation, agitation, poor limb relaxation, and poor ventilator synchronisation. Analysis used multilevel generalised linear mixed modelling to explore intervention effects in a single model taking clustering and patient-level factors into account. A concurrent mixed-methods process evaluation was undertaken to help understand the trial findings. The trial is registered with ClinicalTrials.gov , number NCT01634451 . Findings Between June 1, 2012, and Dec 31, 2014, we included 881 patients (9187 care periods) during the baseline period and 591 patients (6947 care periods) during the intervention period. During the baseline period, optimal sedation–analgesia was present for 5150 (56%) care periods. We found a significant improvement in optimal sedation–analgesia with RI monitoring (odds ratio [OR] 1·44 [95% CI 1·07–1·95]; p=0·017), which was mainly due to increased periods free from excessive sedation (OR 1·59 [1·09–2·31]) and poor ventilator synchronisation (OR 1·55 [1·05–2·30]). However, more patients experienced sedation-related adverse events (OR 1·91 [1·02–3·58]). We found no improvement in overall optimal sedation–analgesia with education (OR 1·13 [95% CI 0·86–1·48]), but fewer patients experienced sedation-related adverse events (OR 0·56 [0·32–0·99]). The sedation–analgesia quality data feedback did not improve quality (OR 0·74 [95% CI 0·54–1·00]) or sedation-related adverse events (OR 1·15 [0·61–2·15]). The process evaluation suggested many clinicians found the RI monitoring useful, but it was often not used for decision making as intended. Education was valued and considered useful by staff. By contrast, sedation–analgesia quality feedback was poorly understood and thought to lack relevance to bedside nursing practice. Interpretation Combination of RI monitoring and online education has the potential to improve sedation–analgesia quality and patient safety in mechanically ventilated ICU patients. The RI monitoring seemed to improve sedation–analgesia quality, but inconsistent adoption by bedside nurses limited its impact. The online education programme resulted in a clinically relevant improvement in patient safety and was valued by nurses, but any changes to behaviours did not seem to alter other measures of sedation–analgesia quality. Providing sedation–analgesia quality feedback to ICUs did not appear to improve any quality metrics, probably because staff did not think it relevant to bedside practice. Funding Chief Scientist Office, Scotland; GE Healthcare. [ABSTRACT FROM AUTHOR]