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Purpose: To determine the effect of depth of sedation on intensive care mortality, duration of mechanical ventilation, and other clinically important outcomes., Methods: We searched MEDLINE, Embase, Cochrane Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, PsycINFO from 2000 to 2020. Randomised controlled trials (RCTs) and cohort studies that examined the effect of sedation depth were included. Two reviewers independently screened, selected articles, extracted data and appraised quality. Data on study design, population, setting, patient characteristics, study interventions, depth of sedation and relevant outcomes were extracted. Quality was assessed using Critical Appraisal Skills Programme tools., Results: We included data from 26 studies (n=7865 patients): 8 RCTs and 18 cohort studies. Heterogeneity of studies was substantial. There was no significant effect of lighter sedation on intensive care mortality. Lighter sedation did not affect duration of mechanical ventilation in RCTs (mean difference (MD): -1.44 days (95% CI -3.79 to 0.91)) but did in cohort studies (MD: -1.52 days (95% CI -2.71 to -0.34)). No statistically significant benefit of lighter sedation was identified in RCTs. In cohort studies, lighter sedation improved time to extubation, intensive care and hospital length of stay and ventilator-associated pneumonia. We found no significant effects for hospital mortality, delirium or adverse events., Conclusion: Evidence of benefit from lighter sedation is limited, with inconsistency between observational and randomised studies. Positive effects were mainly limited to low quality evidence from observational studies, which could be attributable to bias and confounding factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Data describing long-term outcomes following ICU for patients with alcohol-related liver disease are scarce. We aimed to report long-term mortality and emergency hospital resource use for patients with alcohol-related liver disease and compare this with two comparator cohorts., Design: Retrospective cohort study linking population registry data., Setting: All adult general Scottish ICUs (2005-2010) serving 5 million population., Patients: ICU patients with alcohol-related liver disease were compared with an unmatched cohort with Acute Physiology and Chronic Health Evaluation defined diagnoses of severe cardiovascular, respiratory, or renal comorbidity and a matched general ICU cohort., Interventions: None., Measurements and Main Results: Outcomes were 5-year mortality, emergency hospital resource use, and emergency hospital readmission. Multivariable regression was used to identify risk factors and adjust for confounders. Of 47,779 ICU admissions, 2,463 patients with alcohol-related liver disease and 3,590 patients with severe comorbidities were identified; 2,391(97.1%) were matched to a general ICU cohort. The alcohol-related liver disease cohort had greater 5-year mortality than comorbid (79.2% vs 75.3%; p < 0.001) and matched general (79.8% vs 63.3%; p < 0.001) cohorts. High liver Sequential Organ Failure Assessment score and three-organ support were associated with 90% 5-year mortality in alcohol-related liver disease patients. After confounder adjustment, alcohol-related liver disease patients had 31% higher hazard of death (adjusted hazard ratio, 1.31; 95% CI, 1.17-1.47; p < 0.001) and used greater resource than the severe comorbid comparator group. Findings were similar compared with the matched cohort., Conclusions: ICU patients with alcohol-related liver disease have higher 5-year mortality and emergency readmission rates than ICU patients with other severe comorbidities and matched general ICU patients. These data can contribute to shared decision-making for alcohol-related liver disease patients.

Objectives: ICU survivors frequently report reduced health-related quality of life, but the relative importance of preillness versus acute illness factors in survivor populations is not well understood. We aimed to explore health-related quality of life trajectories over 12 months following ICU discharge, patterns of improvement, or deterioration over this period, and the relative importance of demographics (age, gender, social deprivation), preexisting health (Functional Comorbidity Index), and acute illness severity (Acute Physiology and Chronic Health Evaluation II score, ventilation days) as determinants of health-related quality of life and relevant patient-reported symptoms during the year following ICU discharge., Design: Nested cohort study within a previously published randomized controlled trial., Setting: Two ICUs in Edinburgh, Scotland., Patients: Adult ICU survivors (n = 240) who required more than 48 hours of mechanical ventilation., Interventions: None., Measurements and Main Results: We prospectively collected data for age, gender, social deprivation (Scottish index of multiple deprivation), preexisting comorbidity (Functional Comorbidity Index), Acute Physiology and Chronic Health Evaluation II score, and days of mechanical ventilation. Health-related quality of life (Medical Outcomes Study Short Form version 2 Physical Component Score and Mental Component Score) and patient-reported symptoms (appetite, fatigue, pain, joint stiffness, and breathlessness) were measured at 3, 6, and 12 months. Mean Physical Component Score and Mental Component Score were reduced at all time points with minimal change between 3 and 12 months. In multivariable analysis, increasing pre-ICU comorbidity count was strongly associated with lower health-related quality of life (Physical Component Score β = -1.56 [-2.44 to -0.68]; p = 0.001; Mental Component Score β = -1.45 [-2.37 to -0.53]; p = 0.002) and more severe self-reported symptoms. In contrast, Acute Physiology and Chronic Health Evaluation II score and mechanical ventilation days were not associated with health-related quality of life. Older age (β = 0.33 [0.19-0.47]; p < 0.001) and lower social deprivation (β = 1.38 [0.03-2.74]; p = 0.045) were associated with better Mental Component Score health-related quality of life., Conclusions: Preexisting comorbidity counts, but not severity of ICU illness, are strongly associated with health-related quality of life and physical symptoms in the year following critical illness.

Background: At present, red blood cells (RBCs) are stored for up to 42 days prior to transfusion. The relative effectiveness and safety of different RBC storage times prior to transfusion is uncertain., Objective: To assess the clinical effectiveness and cost-effectiveness of transfusing fresher RBCs (stored for ≤ 7 days) compared with current standard-aged RBCs in critically ill patients requiring blood transfusions., Design: The international Age of BLood Evaluation (ABLE) trial was a multicentre, randomised, blinded trial undertaken in Canada, the UK, the Netherlands and France. The UK trial was funded to contribute patients to the international trial and undertake a UK-specific health economic evaluation., Setting: Twenty intensive care units (ICUs) in the UK, as part of 64 international centres., Participants: Critically ill patients aged ≥ 18 years (≥ 16 years in Scotland) expected to require mechanical ventilation for ≥ 48 hours and requiring a first RBC transfusion during the first 7 days in the ICU., Interventions: All decisions to transfuse RBCs were made by clinicians. One patient group received exclusively fresh RBCs stored for ≤ 7 days whenever transfusion was required from randomisation until hospital discharge. The other group received standard-issue RBCs throughout their hospital stay., Main Outcome Measures: The primary outcome was 90-day mortality. Secondary outcomes included development of organ dysfunction, new thrombosis, infections and transfusion reactions. The primary economic evaluation was a cost-utility analysis., Results: The international trial took place between March 2009 and October 2014 (UK recruitment took place between January 2012 and October 2014). In total, 1211 patients were assigned to receive fresh blood and 1219 patients to receive standard-aged blood. RBCs were stored for a mean of 6.1 days [standard deviation (SD) ± 4.9 days] in the group allocated to receive fresh blood and 22.0 days (SD ± 8.4 days) in the group allocated to receive standard-aged blood. Patients received a mean of 4.3 RBC units (SD ± 5.2 RBC units) and 4.3 RBC units (SD ± 5.5 RBC units) in the groups receiving fresh blood and standard-aged blood, respectively. At 90 days, 37.0% of patients in the group allocated to receive fresh blood and 35.3% of patients in the group allocated to receive standard-aged blood had died {absolute risk difference 1.7% [95% confidence interval (CI) -2.1% to 5.5%]}. There were no between-group differences in any secondary outcomes. The UK cohort comprised 359 patients randomised and followed up for 12 months for the cost-utility analysis. UK patients had similar characteristics and outcomes to the international cohort. Mean total costs per patient were £32,346 (95% CI £29,306 to £35,385) in the group allocated to receive fresh blood and £33,353 (95% CI £29,729 to £36,978) in the group allocated to receive standard-aged blood. Approximately 85% of the total costs were incurred during the index hospital admission. There were no significant cost differences between the two groups [mean incremental costs for those receiving fresh vs. standard-aged blood: -£231 (95% CI -£4876 to £4415)], nor were there significant differences in outcomes (mean difference in quality-adjusted life-years -0.010, 95% CI -0.078 to 0.057)., Limitations: Adverse effects from the exclusive use of older RBCs compared with standard or fresh RBCs cannot be excluded., Conclusions: The use of RBCs aged ≤ 7 days confers no clinical or economic benefit in critically ill patients compared with standard-aged RBCs., Future Work: Future studies should address the safety of RBCs near the end of the current permitted storage age., Trial Registration: Current Controlled Trials ISRCTN44878718., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 62. See the NIHR Journals Library website for further project information. The international ABLE trial was also supported by peer-reviewed grants from the Canadian Institutes of Health Research (177453), Fonds de Recherche du Québec - Santé (24460), the French Ministry of Health Programme Hospitalier de Recherche Clinique (12.07, 2011) and by funding from Établissement Français du Sang and Sanquin Blood Supply.

We propose an integrated and adaptable approach to improve patient care and clinical outcomes through analgesia and light sedation, initiated early during an episode of critical illness and as a priority of care. This strategy, which may be regarded as an evolution of the Pain, Agitation and Delirium guidelines, is conveyed in the mnemonic eCASH-early Comfort using Analgesia, minimal Sedatives and maximal Humane care. eCASH aims to establish optimal patient comfort with minimal sedation as the default presumption for intensive care unit (ICU) patients in the absence of recognised medical requirements for deeper sedation. Effective pain relief is the first priority for implementation of eCASH: we advocate flexible multimodal analgesia designed to minimise use of opioids. Sedation is secondary to pain relief and where possible should be based on agents that can be titrated to a prespecified target level that is subject to regular review and adjustment; routine use of benzodiazepines should be minimised. From the outset, the objective of sedation strategy is to eliminate the use of sedatives at the earliest medically justifiable opportunity. Effective analgesia and minimal sedation contribute to the larger aims of eCASH by facilitating promotion of sleep, early mobilization strategies and improved communication of patients with staff and relatives, all of which may be expected to assist rehabilitation and avoid isolation, confusion and possible long-term psychological complications of an ICU stay. eCASH represents a new paradigm for patient-centred care in the ICU. Some organizational challenges to the implementation of eCASH are identified.

Objectives: To describe the rationale, design and methodology for a trial of three novel interventions developed to improve sedation-analgesia quality in adult intensive care units (ICUs)., Participants and Setting: 8 clusters, each a Scottish ICU. All mechanically ventilated sedated patients were potentially eligible for inclusion in data analysis., Design: Cluster randomised design in 8 ICUs, with ICUs randomised after 45 weeks baseline data collection to implement one of four intervention combinations: a web-based educational programme (2 ICUs); education plus regular sedation quality feedback using process control charts (2 ICUs); education plus a novel sedation monitoring technology (2 ICUs); or all three interventions. ICUs measured sedation-analgesia quality, relevant drug use and clinical outcomes, during a 45-week preintervention and 45-week postintervention period separated by an 8-week implementation period. The intended sample size was >100 patients per site per study period., Main Outcome Measures: The primary outcome was the proportion of 12 h care periods with optimum sedation-analgesia, defined as the absence of agitation, unnecessary deep sedation, poor relaxation and poor ventilator synchronisation. Secondary outcomes were proportions of care periods with each of these four components of optimum sedation and rates of sedation-related adverse events. Sedative and analgesic drug use, and ICU and hospital outcomes were also measured., Analytic Approach: Multilevel generalised linear regression mixed models will explore the effects of each intervention taking clustering into account, and adjusting for age, gender and APACHE II score. Sedation-analgesia quality outcomes will be explored at ICU level and individual patient level. A process evaluation using mixed methods including quantitative description of intervention implementation, focus groups and direct observation will provide explanatory information regarding any effects observed., Conclusions: The DESIST study uses a novel design to provide system-level evaluation of three contrasting complex interventions on sedation-analgesia quality. Recruitment is complete and analysis ongoing., Trial Registration Number: NCT01634451., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To compare elderly (≥ 80 yr), older (65-79 yr), and younger (< 65 yr) ICU admissions in Scotland in relation to trends in admission rates, regional variation in admissions, ICU treatment intensity, and ICU and 1-year mortality., Design: National 5-year cohort study of ICU first admissions (January 1, 2005, to December 31, 2009)., Setting: All admissions to ICUs and combined units (level 2/3 care) in Scotland captured by the Scottish Intensive Care Society Audit Group database, linked with hospital discharge data and death records., Patients: A total of 40,142 patients: 3,865 were 80 years old or older (9.6%), 13,904 (34.6%) were 65-79 years old; and 22,373 were younger than 65 years (55.7%)., Interventions: None., Measurements and Main Results: Between 2005 and 2009, elderly admission rates decreased from 36.6/10,000 (95% CI, 34.0-39.2) in 2005 to 28.7/10,000 (95% CI, 26.5-30.9) in 2009 (p < 0.001; relative decrease, 22.0%); older admission rates also decreased, but less steeply (31.1 [95% CI, 29.9-32.2] to 26.1 [95% CI, 25.1-27.1] per 10,000 population; p < 0.001; relative decrease, 16.1%). Rates were static for younger patients. Restricted to mechanically ventilated elderly patients, rates ranged from 13.9 to 30.1/10,000 between healthboard administrative regions (p < 0.001). Emergency surgical diagnoses were more prevalent for elderly patients (elderly, 39.8%; older, 25.1%; younger, 20.3%; p < 0.001). Subgroup analyses limited to pneumonia admissions (elderly, n = 242; older, n = 1,226; younger, n = 1,836) indicated similar acute physiology scores, but fewer preexisting comorbidities among elderly patients (p = 0.007), who received a shorter duration of organ support and ICU stay. Mortality rates were higher in elderly patients at ICU discharge (elderly, 26.5%; older, 25.0%; younger, 17.0%; p < 0.001; confounder adjusted odds ratio elderly vs younger, 2.33 [95% CI, 2.11-2.58]; p < 0.001). Differences persisted at 1 year (elderly, 52.2%; older, 43.8%; younger, 27.6%; adjusted odds ratio elderly vs younger, 3.72 [95% CI, 3.42-4.06]; p < 0.001)., Conclusions: In Scotland, elderly and older ICU admission rates are decreasing, with regional geographic variation. Although limited by an absence of a measure of frailty, patient characteristics and treatment intensity suggest selection of less comorbid elderly patients, indicating possible rationing based on chronologic age.

Objectives: Early goal-directed therapy (EGDT) is recommended for sepsis management in current guidelines, but the underpinning evidence is controversial. Clinician beliefs and the capacity to implement all recommended elements of EGDT in emergency departments (EDs) are uncertain. Our study aimed to explore self-reported management of early sepsis by Scottish emergency medicine (EM) and intensive care medicine (ICM) consultants, delineate important differences and determine the guideline recommendations rated most important and deliverable within the ED., Methods: A postal survey using a hypothetical patient with septic shock was sent to all EM and ICM consultants practising in Scotland., Results: 67% (76/114) EM and 61% (96/157) ICM consultants responded. Normal saline was preferred by EM respondents ('always/often used': EM 86%, ICM 23%, p<0.0001), whereas ICM respondents preferred Hartmann's solution (EM 42%, ICM 72%, p=0.0164), gelofusin (EM 10%, ICM 63%, p<0.0001) and starch (EM 0%, ICM 24%, p<0.0001). More ICM respondents indicated they used central venous pressure and invasive arterial pressure monitoring in the ED, and initiated vasopressors (EM 57%, ICM 90%, p<0.0001). More ICM consultants used specific haemoglobin transfusion triggers (48% EM, 77% ICM, p=0.0002), but marked variation in haemoglobin triggers and targets was reported. Lactate was rated the most important single resuscitation parameter by both specialties; no ED and only two ICM consultants rated ScVO2 most important., Conclusions: Differences in early fluid and vasopressor management of sepsis exist between Scottish ICM and EM consultants. Transfusion practice is highly variable, suggesting clinical uncertainty. Lactate is considered more important than ScVO2 measurement., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: To compare hemoglobin concentration (Hb), RBC use, and patient outcomes when restrictive or liberal blood transfusion strategies are used to treat anemic (Hb≤90 g/L) critically ill patients of age≥55 years requiring≥4 days of mechanical ventilation in ICU., Design: Parallel-group randomized multicenter pilot trial., Setting: Six ICUs in the United Kingdom participated between August 2009 and December 2010., Patients: One hundred patients (51 restrictive and 49 liberal groups)., Interventions: Patients were randomized to a restrictive (Hb trigger, 70 g/L; target, 71-90 g/L) or liberal (90 g/L; target, 91-110 g/L) transfusion strategy for 14 days or the remainder of ICU stay, whichever was longest., Measurements and Main Results: Baseline comorbidity rates and illness severity were high, notably for ischemic heart disease (32%). The Hb difference among groups was 13.8 g/L (95% CI, 11.5-16.0 g/L); p<0.0001); mean Hb during intervention was 81.9 (SD, 5.1) versus 95.7 (6.3) g/L; 21.6% fewer patients in the restrictive group were transfused postrandomization (p<0.001) and received a median 1 (95% CI, 1-2; p=0.002) fewer RBC units. Protocol compliance was high. No major differences in organ dysfunction, duration of ventilation, infections, or cardiovascular complications were observed during intensive care and hospital follow-up. Mortality at 180 days postrandomization trended toward higher rates in the liberal group (55%) than in the restrictive group (37%); relative risk was 0.68 (95% CI, 0.44-1.05; p=0.073). This trend remained in a survival model adjusted for age, gender, ischemic heart disease, Acute Physiology and Chronic Health Evaluation II score, and total non-neurologic Sequential Organ Failure Assessment score at baseline (hazard ratio, 0.54 [95% CI, 0.28-1.03]; p=0.061)., Conclusions: A large trial of transfusion strategies in older mechanically ventilated patients is feasible. This pilot trial found a nonsignificant trend toward lower mortality with restrictive transfusion practice.

Objectives: Intensive care survivors continue to experience significant morbidity following acute hospital discharge, but healthcare costs associated with this ongoing morbidity are poorly described. As the demand for intensive care increases, understanding the magnitude of postacute hospital healthcare costs is of increasing relevance to clinicians and healthcare planners. We undertook a systematic review of the literature reporting major healthcare resource use by intensive care survivors following discharge from the hospital and identified factors associated with increased resource use., Data Sources: Seven electronic databases (1990 to August 2012), conference proceedings, and reference lists were searched., Study Selection: Studies published in English were included that reported postacute hospital discharge healthcare resource use at the individual level for survivors of intensive care., Data Extraction: Two reviewers screened abstracts and one abstracted data using standardized templates. Study quality was assessed using recognized appraisal methods specific to economic evaluation, epidemiological studies, and randomized trials., Data Synthesis: From 4,909 articles, 18 articles representing 14 cohorts fulfilled inclusion criteria. There was substantial variation in methodology, especially the resource categories included in the studies. Following standardization to a common currency and year, variation in cost of resource use was evident (range 2011 US $18,847-$148,454 for year 1 postdischarge). Studies undertaken within the United States reported the highest costs; those in the United Kingdom reported substantially lower costs. Factors associated with increased resource use included increasing age, comorbidities, organ dysfunction score, and previous resource use., Conclusions: Wide variation in methodological approaches limited study comparability and external validity of findings. We found substantial variation in the cost of resource use, especially among countries. Careful description of patient cohorts and healthcare systems is required to maximize generalizability. We give recommendations for a more standardized approach to improve design and reporting of future studies.

Objectives: Ventilator-associated pneumonia is the most common intensive care unit-acquired infection. Although there is widespread consensus that evidenced-based interventions reduce the risk of ventilator-associated pneumonia, controversy has surrounded the importance of implementing them as a "bundle" of care. This study aimed to determine the effects of implementing such a bundle while controlling for potential confounding variables seen in similar studies., Design: A before-and-after study conducted within the context of an existing, independent, infection surveillance program., Setting: An 18-bed, mixed medical-surgical teaching hospital intensive care unit., Patients: All patients admitted to intensive care for 48 hrs or more during the periods before and after intervention., Interventions: A four-element ventilator-associated pneumonia prevention bundle, consisting of head-of-bed elevation, oral chlorhexidine gel, sedation holds, and a weaning protocol implemented as part of the Scottish Patient Safety Program using Institute of Health Care Improvement methods., Measurements and Main Results: Compliance with head-of-bed elevation and chlorhexidine gel were 95%-100%; documented compliance with "wake and wean" elements was 70%, giving overall bundle compliance rates of 70%. Compared to the preintervention period, there was a significant reduction in ventilator-associated pneumonia in the postintervention period (32 cases per 1,000 ventilator days to 12 cases per 1,000 ventilator days; p<.001). Statistical process control charts showed the decrease was most marked after bundle implementation. Patient cohorts staying ≥6 and ≥14 days had greater reduction in ventilator-associated pneumonia acquisition and also had reduced antibiotic use (reduced by 1 and 3 days; p=.008/.007, respectively). Rates of methicillin-resistant Staphylococcus aureus acquisition also decreased (10% to 3.6%; p<.001)., Conclusions: Implementation of a ventilator-associated pneumonia prevention bundle was associated with a statistically significant reduction in ventilator-associated pneumonia, which had not been achieved with earlier ad hoc ventilator-associated pneumonia prevention guidelines in our unit. This occurred despite an inability to meet bundle compliance targets of 95% for all elements. Our data support the systematic approach to achieving high rates of process compliance and suggest systematic introduction can decrease both infection incidence and antibiotic use, especially for patients requiring longer duration of ventilation.

Introduction: The number of patients requiring prolonged mechanical ventilation (PMV) is likely to increase. Transferring patients to specialised weaning units may improve outcomes and reduce costs. The aim of this study was to establish the incidence and outcomes of PMV in a UK administrative health care region without a dedicated weaning unit, and model the potential impact of establishing a dedicated weaning unit., Methods: A retrospective cohort study was undertaken using a database of admissions to three intensive care units (ICU) in a UK region from 2002 to 2006. Using a 21 day cut-off to define PMV, incidence was calculated using all ICU admissions and ventilated ICU admissions as denominators. Outcomes for the PMV cohort (mortality and hospital resource use) were compared with the non-PMV cohort. Length of ICU stay beyond 21 days was used to model the effect of establishing a weaning unit in terms of unit occupancy rates, admission refusal rates, and healthcare costs., Results: Out of 8290 ICU admission episodes, 7848 were included in the analysis. Mechanical ventilation was required during 5552 admission episodes, of which 349 required PMV. The incidence of PMV was 4.4 per 100 ICU admissions, and 6.3 per 100 ventilated ICU admissions. PMV patients used 29.1% of all general ICU bed days, spent longer in hospital after ICU discharge than non-PMV patients (median 17 vs 7 days, P < 0.001) and had higher hospital mortality (40.3% vs 33.8%, P = 0.02). For the region, in which about 70 PMV patients were treated each year, a weaning unit with a capacity of three beds appeared most cost efficient, resulting in an occupancy rate of 73%, admission refusal rate at 21 days of 36%, and potential cost saving of £344,000 (€418,000) using UK healthcare tariffs., Conclusions: One in every sixteen ventilated patients requires PMV in our region and this group use a substantial amount of health care resource. Establishing a weaning unit would potentially reduce acute bed occupancy by 8-10% and could reduce overall treatment costs. Restructuring the current configuration of critical care services to introduce weaning units should be considered if the expected increase in PMV incidence occurs.

Objective: Coagulopathy occurs frequently in critically ill patients, but its epidemiology, current treatment, and relation to patient outcome are poorly understood. We described the prevalence, risk factors, and treatment of prolongation of the prothrombin time in critically ill patients using the international normalized ratio to standardize data and explored its association with intensive care unit survival., Design: Prospective multiple center observational cohort study., Setting: Twenty-nine adult intensive care units in the United Kingdom., Patients: All sequentially admitted patients over an 8-wk period., Interventions: None., Measurements and Main Results: Prospective daily data were collected concerning prevalence, predefined risk factors, and treatment of coagulopathy throughout intensive care unit admission. Of 1923 intensive care unit admissions, 30% developed abnormal international normalized ratio values (defined as an international normalized ratio > 1.5). Most international normalized ratio abnormalities were minor and short-lived (73% of worst international normalized ratio values 1.6-2.5). Male sex, chronic liver disease, sepsis, warfarin therapy, increments in Acute Physiology and Chronic Health Evaluation II score, severity of renal and hepatic dysfunction, and red cell transfusions were all independent risk factors for international normalized ratio abnormalities (all p < .001). In all regression models, there was a strong independent association between abnormal international normalized ratio values and greater intensive care unit mortality (p < .0001), particularly when international normalized ratio increased after intensive care unit admission. Among patients with abnormal international normalized ratios, 33% received fresh-frozen plasma transfusions during their intensive care unit stay, but the pretransfusion international normalized ratio value varied widely. Fifty-one percent of fresh-frozen plasma treatments were to nonbleeding patients and 40% to nonbleeding patients whose international normalized ratio was normal or only modestly deranged (≤ 2.5). The dose of fresh-frozen plasma administered was highly variable (median dose 10.8 mL/kg (first, third quartile 7.2, 14.4; range, 2.4-41.1 mL/kg)., Conclusions: Prothrombin time prolongation is prevalent in critically ill patients and is independently associated with greater intensive care unit mortality. Wide variation in fresh-frozen plasma treatment exists suggesting clinical uncertainty regarding best practice, particularly as a prophylactic treatment.

Objectives: Anemia is a common complication of critical illness, but its duration after intensive care discharge and possible contributory factors have not been studied. Our aim was to follow patients discharged anemic from the intensive care unit (ICU) for up to 6 months and determine the duration of and possible reasons for persisting anemia., Design: Prospective observational cohort study of intensive care (ICU) survivors with moderate-severe anemia at the time of ICU discharge. Erythropoietic and inflammatory markers were measured at regular intervals over six months to assess red cell production and factors limiting recovery from anemia., Setting: An 18-bed medico-surgical ICU in a Scottish university teaching hospital., Patients: Patients who required >24 hrs of ventilatory support and were discharged from intensive care with hemoglobin < 100 g/L were studied prospectively over 6 months. 30 patients were recruited; 19 completed 6 months follow-up, 6 died during the study period, and 5 completed part of the follow up. Patients with ongoing renal failure or chronic hematologic disorders were excluded., Measurements and Main Results: 47% (9 of 19) of patients completing 6 months follow up recovered from their anemia. The median time to recovery was 11 wks (1, 3 quartiles: 9, 26 wks). 10 patients (53%) were still anemic 6 months after ICU discharge. No patients developed iron, vitamin B12 or folate deficiency. An inappropriately low erythropoietin response to anemia was observed in virtually all patients and did not distinguish nonrecovering patients. Patients with delayed recovery or persisting anemia during the 13 wks following ICU discharge had higher levels of circulating inflammatory markers (IL-6 and C-reactive protein) and did not exhibit reticulocytosis during the weeks following discharge., Conclusions: Anemia persists in many patients following critical illness and is associated with ongoing inflammation, inappropriate erythropoietin response and poor marrow red cell production.

Objective: To document the prevalence of anemia among patients admitted to intensive care (ICU) and, among survivors, at ICU discharge when restrictive transfusion practice was used., Design: This was an observational cohort study., Setting: Ten of the 26 general ICUs in Scotland., Patients and Participants: One thousand twenty-three sequential ICU admissions over 100 days, representing 44% of all ICU admissions in Scotland during the study period, studied daily from admission to discharge or death in the ICU., Interventions: None., Measurements and Results: The median transfusion trigger used, in the absence of bleeding, was 78 g/l (interquartile range 73-84); <2% of transfusion triggers were above the upper limit of the national transfusion trigger guideline (100 g/l). Overall, 25% of admissions had a hemoglobin concentration <90 g/l at ICU admission. Seven hundred sixty-six patients admitted survived to ICU discharge. Among these, the prevalence of anemia (male <130 g/l; female <115 g/l) at ICU discharge was 87.0 (95% CI: 83.6 to 89.9)% for males and 79.6 (74.8 to 83.7)% for females. Of the male survivors 24.1 (20.3 to 28.3)% and of the female 27.9 (23.4 to 33.2)% had a hemoglobin <90 g/l at ICU discharge. The prevalence was similar for patients with and without pre-existing ischemic heart disease. Logistic regression found independent associations between having a hemoglobin concentration <90 g/l at ICU discharge and the first measured hemoglobin in ICU, the presence of acute renal failure and thrombocytopenia during ICU stay., Conclusions: Anemia is highly prevalent in ICUs that use restrictive transfusion triggers. The impact of anemia on functional recovery after intensive care requires investigation.

Background: Anemia commonly complicates critical illness. Restrictive transfusion triggers are appropriate in this setting, but no large studies have measured red cell (RBC) requirements for intensive care patients when evidence-based transfusion guidelines are followed consistently., Study Design and Methods: Data were recorded daily for 1023 of 1042 sequential admissions to 10 intensive care units (ICUs) over 100 days. The sample comprised 44 percent of all ICU admissions in Scotland during this period. RBC transfusions and the occurrence of clinically significant hemorrhage were recorded for every ICU day. Transfusion episodes were classified as either associated with or not associated with hemorrhage. Measures of RBC use were derived for the cohort and for Scotland with national audit data., Results: A total of 39.5 percent (95% confidence interval [CI], 36.5%-42.5%) of admissions received transfusions. Eighteen percent of admissions received at least one transfusion associated with hemorrhage and 26 percent received at least one transfusion not associated with hemorrhage. The median (interquartile range) transfusion trigger in the absence of hemorrhage was 78 (73-78) g/L. The overall mean RBC use was 1.87 (95% CI, 1.79-1.96) units per admission or 0.34 (95% CI, 0.33-0.36) units per ICU-day. Forty-seven percent of RBCs administered were not associated with clinically significant hemorrhage. Mean RBC requirements for intensive care in Scotland were estimated to be 3950 (95% CI, 3780-4140) per million-adult-population per year. This represented 7 to 8 percent of the Scottish blood supply., Conclusions: Despite evidence-based transfusion practice, 40 percent of ICU patients receive transfusions, which account for 7 to 8 percent of the national blood supply.

Importance: There is limited evidence on the optimal strategy for liberating infants and children from invasive mechanical ventilation in the pediatric intensive care unit.Objective: To determine if a sedation and ventilator liberation protocol intervention reduces the duration of invasive mechanical ventilation in infants and children anticipated to require prolonged mechanical ventilation.Design, Setting, and Participants: A pragmatic multicenter, stepped-wedge, cluster randomized clinical trial was conducted that included 17 hospital sites (18 pediatric intensive care units) in the UK sequentially randomized from usual care to the protocol intervention. From February 2018 to October 2019, 8843 critically ill infants and children anticipated to require prolonged mechanical ventilation were recruited. The last date of follow-up was November 11, 2019.Interventions: Pediatric intensive care units provided usual care (n = 4155 infants and children) or a sedation and ventilator liberation protocol intervention (n = 4688 infants and children) that consisted of assessment of sedation level, daily screening for readiness to undertake a spontaneous breathing trial, a spontaneous breathing trial to test ventilator liberation potential, and daily rounds to review sedation and readiness screening and set patient-relevant targets.Main Outcomes and Measures: The primary outcome was the duration of invasive mechanical ventilation from initiation of ventilation until the first successful extubation. The primary estimate of the treatment effect was a hazard ratio (with a 95% CI) adjusted for calendar time and cluster (hospital site) for infants and children anticipated to require prolonged mechanical ventilation.Results: There were a total of 8843 infants and children (median age, 8 months [interquartile range, 1 to 46 months]; 42% were female) who completed the trial. There was a significantly shorter median time to successful extubation for the protocol intervention compared with usual care (64.8 hours vs 66.2 hours, respectively; adjusted median difference, -6.1 hours [interquartile range, -8.2 to -5.3 hours]; adjusted hazard ratio, 1.11 [95% CI, 1.02 to 1.20], P = .02). The serious adverse event of hypoxia occurred in 9 (0.2%) infants and children for the protocol intervention vs 11 (0.3%) for usual care; nonvascular device dislodgement occurred in 2 (0.04%) vs 7 (0.1%), respectively.Conclusions and Relevance: Among infants and children anticipated to require prolonged mechanical ventilation, a sedation and ventilator liberation protocol intervention compared with usual care resulted in a statistically significant reduction in time to first successful extubation. However, the clinical importance of the effect size is uncertain.Trial Registration: isrctn.org Identifier: ISRCTN16998143. [ABSTRACT FROM AUTHOR]

Ventilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations of IL-1β and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion of ventilator-associated pneumonia. The VAPrapid2 trial aimed to determine whether measurement of bronchoalveolar lavage fluid IL-1β and IL-8 could effectively and safely improve antibiotic stewardship in patients with clinically suspected ventilator-associated pneumonia. VAPrapid2 was a multicentre, randomised controlled trial in patients admitted to 24 ICUs from 17 National Health Service hospital trusts across England, Scotland, and Northern Ireland. Patients were screened for eligibility and included if they were 18 years or older, intubated and mechanically ventilated for at least 48 h, and had suspected ventilator-associated pneumonia. Patients were randomly assigned (1:1) to biomarker-guided recommendation on antibiotics (intervention group) or routine use of antibiotics (control group) using a web-based randomisation service hosted by Newcastle Clinical Trials Unit. Patients were randomised using randomly permuted blocks of size four and six and stratified by site, with allocation concealment. Clinicians were masked to patient assignment for an initial period until biomarker results were reported. Bronchoalveolar lavage was done in all patients, with concentrations of IL-1β and IL-8 rapidly determined in bronchoalveolar lavage fluid from patients randomised to the biomarker-based antibiotic recommendation group. If concentrations were below a previously validated cutoff, clinicians were advised that ventilator-associated pneumonia was unlikely and to consider discontinuing antibiotics. Patients in the routine use of antibiotics group received antibiotics according to usual practice at sites. Microbiology was done on bronchoalveolar lavage fluid from all patients and ventilator-associated pneumonia was confirmed by at least 104 colony forming units per mL of bronchoalveolar lavage fluid. The primary outcome was the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage. Data were analysed on an intention-to-treat basis, with an additional per-protocol analysis that excluded patients randomly assigned to the intervention group who defaulted to routine use of antibiotics because of failure to return an adequate biomarker result. An embedded process evaluation assessed factors influencing trial adoption, recruitment, and decision making. This study is registered with ISRCTN, ISRCTN65937227, and ClinicalTrials.gov , NCT01972425. Between Nov 6, 2013, and Sept 13, 2016, 360 patients were screened for inclusion in the study. 146 patients were ineligible, leaving 214 who were recruited to the study. Four patients were excluded before randomisation, meaning that 210 patients were randomly assigned to biomarker-guided recommendation on antibiotics (n=104) or routine use of antibiotics (n=106). One patient in the biomarker-guided recommendation group was withdrawn by the clinical team before bronchoscopy and so was excluded from the intention-to-treat analysis. We found no significant difference in the primary outcome of the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage in the intention-to-treat analysis (p=0·58). Bronchoalveolar lavage was associated with a small and transient increase in oxygen requirements. Established prescribing practices, reluctance for bronchoalveolar lavage, and dependence on a chain of trial-related procedures emerged as factors that impaired trial processes. Antibiotic use remains high in patients with suspected ventilator-associated pneumonia. Antibiotic stewardship was not improved by a rapid, highly sensitive rule-out test. Prescribing culture, rather than poor test performance, might explain this absence of effect. UK Department of Health and the Wellcome Trust. [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]

Background/objectives: Reduced appetite is a recognised physiological symptom in survivors of critical illness. While reduced appetite has been reported by patients after intensive care unit (ICU) discharge, quantification using visual analogue scales (VAS) has not been previously performed, and follow-up duration has been limited. We aimed to describe appetite scores in ICU survivors during the first 3 months after ICU discharge and explore association with systemic inflammation.Subjects/methods: Secondary analysis of data collected in a complex rehabilitation intervention trial (RECOVER). A subgroup of 193 patients provided specific consent for inclusion in the blood sampling sub-study during consent for the main study. We studied appetite using a VAS; serum C-reactive protein (CRP); interleukin-1β and interleukin-6 (IL-1β and IL-6); and hand-grip strength.Results: Median (interquartile range) score on 0-10 appetite VAS was 4.3 (2.0-6.5) 1 week after ICU discharge, improving to 7.1 (4.6-8.9) by 3 months (mean difference 1.7 (0.9-2.4), p < 0.01). Number of days spent in an acute hospital following an intensive care stay was associated with poorer appetite scores (p = 0.03). CRP concentration and appetite were significantly associated at 1 week after ICU discharge (p = 0.01), but not at 3 months after ICU discharge (p = 0.67).Conclusions: ICU survivors experience reduced appetite during the acute recovery phase of critical illness that could impact on nutritional recovery and this was associated with CRP concentration 1 week after ICU discharge. [ABSTRACT FROM AUTHOR]

Aims and objectives To theorise intensive care unit survivorship after a critical illness based on longitudinal qualitative data. Background Increasingly, patients survive episodes of critical illness. However, the short- and long-term impact of critical illness includes physical, psychological, social and economic challenges long after hospital discharge. An appreciation is emerging that care needs to extend beyond critical illness to enable patients to reclaim their lives postdischarge with the term 'survivorship' being increasingly used in this context. What constitutes critical illness survivorship has, to date, not been theoretically explored. Design Longitudinal qualitative and constructivist grounded theory. Interviews (n = 46) with 17 participants were conducted at four time points: (1) before discharge from hospital, (2) four to six weeks postdischarge, (3) six months and (4) 12 months postdischarge across two adult intensive care unit setting. Method Individual face-to-face interviews. Data analysis followed the principles of Charmaz's constructivist grounded theory. 'Intensive care unit survivorship' emerged as the core category and was theorised using concepts such as status passages, liminality and temporality to understand the various transitions participants made postcritical illness. Findings Intensive care unit survivorship describes the unscheduled status passage of falling critically ill and being taken to the threshold of life and the journey to a life postcritical illness. Surviving critical illness goes beyond recovery; surviving means 'moving on' to life postcritical illness. 'Moving on' incorporates a redefinition of self that incorporates any lingering intensive care unit legacies and being in control of one's life again. Relevance to clinical practice For healthcare professionals and policymakers, it is important to realise that recovery and transitioning through to survivorship happen within an individual's time frame, not a schedule imposed by the healthcare system. Currently, there are no care pathways or policies in place for critical illness survivors that would support intensive care unit survivors and their families in the transitions to survivorship. [ABSTRACT FROM AUTHOR]

The authors comment on a study by Haines et al that explores themes into how approach to intensive care unit (ICU) aftercare activities could improve ICU care. They commend Haines et al for describing a construct mechanisms driving improvement in the ICU that are important to critical care medicine. Further, they claim that these constructs can also be used as basis of a theory for how post-ICU interventions may improve quality and outcomes that can be tested in future research.

Rationale: Survivors of critical illness experience significant morbidity, but the impact of surviving the intensive care unit (ICU) has not been quantified comprehensively at a population level.Objectives: To identify factors associated with increased hospital resource use and to ascertain whether ICU admission was associated with increased mortality and resource use.Methods: Matched cohort study and pre/post-analysis using national linked data registries with complete population coverage. The population consisted of patients admitted to all adult general ICUs during 2005 and surviving to hospital discharge, identified from the Scottish Intensive Care Society Audit Group registry, matched (1:1) with similar hospital control subjects. Five-year outcomes included mortality and hospital resource use. Confounder adjustment was based on multivariable regression and pre/post within-individual analyses.Measurements and Main Results: Of 7,656 ICU patients, 5,259 survived to hospital discharge (5,215 [99.2%] matched to hospital control subjects). Factors present before ICU admission (comorbidities/pre-ICU hospitalizations) were stronger predictors of hospital resource use than acute illness factors. In the 5 years after the initial hospital discharge, compared with hospital control subjects, the ICU cohort had higher mortality (32.3% vs. 22.7%; hazard ratio, 1.33; 95% confidence interval, 1.22-1.46; P < 0.001), used more hospital resources (mean hospital admission rate, 4.8 vs. 3.3/person/5 yr), and had 51% higher mean 5-year hospital costs ($25,608 vs. $16,913/patient). Increased resource use persisted after confounder adjustment (P < 0.001) and using pre/post-analyses (P < 0.001). Excess resource use and mortality were greatest for younger patients without significant comorbidity.Conclusions: This complete, national study demonstrates that ICU survivorship is associated with higher 5-year mortality and hospital resource use than hospital control subjects, representing a substantial burden on individuals, caregivers, and society. [ABSTRACT FROM AUTHOR]

Objective: To develop sedation, pain, and agitation quality measures using process control methodology and evaluate their properties in clinical practice.Design: A Sedation Quality Assessment Tool was developed and validated to capture data for 12-hour periods of nursing care. Domains included pain/discomfort and sedation-agitation behaviors; sedative, analgesic, and neuromuscular blocking drug administration; ventilation status; and conditions potentially justifying deep sedation. Predefined sedation-related adverse events were recorded daily. Using an iterative process, algorithms were developed to describe the proportion of care periods with poor limb relaxation, poor ventilator synchronization, unnecessary deep sedation, agitation, and an overall optimum sedation metric. Proportion charts described processes over time (2 monthly intervals) for each ICU. The numbers of patients treated between sedation-related adverse events were described with G charts. Automated algorithms generated charts for 12 months of sequential data. Mean values for each process were calculated, and variation within and between ICUs explored qualitatively.Setting: Eight Scottish ICUs over a 12-month period.Patients: Mechanically ventilated patients.Interventions: None.Measurements and Main Results: The Sedation Quality Assessment Tool agitation-sedation domains correlated with the Richmond Sedation Agitation Scale score (Spearman ρ = 0.75) and were reliable in clinician-clinician (weighted kappa; κ = 0.66) and clinician-researcher (κ = 0.82) comparisons. The limb movement domain had fair correlation with Behavioral Pain Scale (ρ = 0.24) and was reliable in clinician-clinician (κ = 0.58) and clinician-researcher (κ = 0.45) comparisons. Ventilator synchronization correlated with Behavioral Pain Scale (ρ = 0.54), and reliability in clinician-clinician (κ = 0.29) and clinician-researcher (κ = 0.42) comparisons was fair-moderate. Eight hundred twenty-five patients were enrolled (range, 59-235 across ICUs), providing 12,385 care periods for evaluation (range 655-3,481 across ICUs). The mean proportion of care periods with each quality metric varied between ICUs: excessive sedation 12-38%; agitation 4-17%; poor relaxation 13-21%; poor ventilator synchronization 8-17%; and overall optimum sedation 45-70%. Mean adverse event intervals ranged from 1.5 to 10.3 patients treated. The quality measures appeared relatively stable during the observation period.Conclusions: Process control methodology can be used to simultaneously monitor multiple aspects of pain-sedation-agitation management within ICUs. Variation within and between ICUs could be used as triggers to explore practice variation, improve quality, and monitor this over time. [ABSTRACT FROM AUTHOR]

Ventilator-associated pneumonia (VAP) remains a challenge to intensive care units, with secure diagnosis relying on microbiological cultures that take up to 72 hours to provide a result. We sought to derive and validate a novel, real-time 16S rRNA gene PCR for rapid exclusion of VAP. Bronchoalveolar lavage (BAL) was obtained from two independent cohorts of patients with suspected VAP. Patients were recruited in a 2-centre derivation cohort and a 12-centre confirmation cohort. Confirmed VAP was defined as growth of >104 colony forming units/ml on semiquantitative culture and compared with a 16S PCR assay. Samples were tested from 67 patients in the derivation cohort, 10 (15%) of whom had confirmed VAP. Using cycles to cross threshold (Ct) values as the result of the 16S PCR test, the area under the receiver operating characteristic (ROC) curve (AUROC) was 0.94 (95% CI 0.86 to 1.0, p<0.0001). Samples from 92 patients were available from the confirmation cohort, 26 (28%) of whom had confirmed VAP. The AUROC for Ct in this cohort was 0.89 (95% CI 0.83 to 0.95, p<0.0001). This study has derived and assessed the diagnostic accuracy of a novel application for 16S PCR. This suggests that 16S PCR in BAL could be used as a rapid test in suspected VAP and may allow better stewardship of antibiotics.Trial Registration Number: VAPRAPID trial ref NCT01972425. [ABSTRACT FROM AUTHOR]

Background Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare. Objectives We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP. Methods A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >104 colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1β), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination. Results Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (p<0.001). The area under the receiver operator characteristic curve for IL-1β was 0.81; IL-8, 0.74; MMP-8, 0.76; MMP-9, 0.79 and HNE, 0.78. A combination of IL-1β and IL-8, at the optimal cut-point, excluded VAP with a sensitivity of 100%, a specificity of 44.3% and a post-test probability of 0% (95% CI 0% to 9.2%). Conclusions Low BALF IL-1β in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship. [ABSTRACT FROM AUTHOR]

We agree with many points, especially their call for further research into the clinical effects of erythropoietin (EPO) in critically ill patients. With increasingly widespread adoption of restrictive transfusion practices [[2]] the benefits of EPO are likely even smaller than those identified in our meta-analysis and will need to be reassessed if transfusion triggers other than hemoglobin become routine. [Extracted from the article]

BACKGROUND: Platelet (PLT) transfusions are widely used, but few studies have described patterns of use in critical care. STUDY DESIGN AND METHODS: As part of a prospective multicenter observational study of all sequentially admitted patients to UK general intensive care units (ICUs) over 8 weeks, daily data were collected throughout admission on frequency of thrombocytopenia and use of PLT transfusions, in addition to clinical outcomes, including bleeding. RESULTS: There were 1923 admissions recruited across 29 ICUs for analysis (96.6% of all eligible admissions). The period prevalences of severe thrombocytopenia (<50 × 109/L) for the entire ICU stay were 12.4% (234/1881) and 13.7% (263/1914) when the 24 hours before admission was also included. A total of 35.4% of patients who experienced severe thrombocytopenia died in the ICU. A total of 169 patients (9% of study population) received 534 units of transfused PLTs (median number of units per patient admission was 2; interquartile range, 1-3; maximum, 38). Pretransfusion PLT counts were more than 50 × 109 for 40% of PLT transfusions overall, and even when no clinically significant bleeding was recorded on the day of transfusion, the lowest recorded PLT count was more than 50 × 109 for 34% of transfusions. There was evidence of only modest increments in PLT count. CONCLUSION: Thrombocytopenia is common in critical care, but there is wide variation in PLT transfusion use. Patients commonly received PLT transfusions on days without clinically significant hemorrhage. The high prevalence of thrombocytopenia in the critically ill population and inconsistent patterns of PLT transfusions indicate the importance of improving the evidence base for PLT use. [ABSTRACT FROM AUTHOR]

Background: Physical recovery following critical illness is slow, often incomplete and is resistant to rehabilitation interventions. We aimed to explore the contribution of persisting inflammation to recovery, and investigated the potential role of human cytomegalovirus (HCMV) infection in its pathogenesis.Methods: In an a priori nested inflammatory biomarker study in a post-intensive care unit (ICU) rehabilitation trial (RECOVER; ISRCTN09412438), surviving adult ICU patients ventilated >48 h were enrolled at ICU discharge and blood sampled at ICU discharge (n=184) and 3 month follow-up (N=123). C-reactive protein (CRP), human neutrophil elastase (HNE), interleukin (IL)-1β, IL-6, IL-8, transforming growth factor β1 (TGFβ1) and secretory leucocyte protease inhibitor (SLPI) were measured. HCMV IgG status was determined (previous exposure), and DNA PCR measured among seropositive patients (lytic infection). Physical outcome measures including the Rivermead Mobility Index (RMI) were measured at 3 months.Results: Many patients had persisting inflammation at 3 months (CRP >3 mg/L in 59%; >10 mg/L in 28%), with proinflammatory phenotype (elevated HNE, IL-6, IL-8, SLPI; low TGFβ1). Poorer mobility (RMI) was associated with higher CRP (β=0.13; p<0.01) and HNE (β=0.32; p=0.03), even after adjustment for severity of acute illness and pre-existing co-morbidity (CRP β=0.14; p<0.01; HNE β=0.30; p=0.04). Patients seropositive for HCMV at ICU discharge (63%) had a more proinflammatory phenotype at 3 months than seronegative patients, despite undetectable HMCV by PCR testing.Conclusions: Inflammation is prevalent after critical illness and is associated with poor physical recovery during the first 3 months post-ICU discharge. Previous HCMV exposure is associated with a proinflammatory phenotype despite the absence of detectable systemic viraemia.Trial Registration Number: ISRCTN09412438, post results. [ABSTRACT FROM AUTHOR]