Cardiovascular Subphenotypes in ARDS: Diagnostic and Therapeutic Implications and Overlap with Other ARDS Subphenotypes.

Acute respiratory distress syndrome (ARDS) is a highly heterogeneous clinical condition. Shock is a poor prognostic sign in ARDS, and heterogeneity in its pathophysiology may be a barrier to its effective treatment. Although right ventricular dysfunction is commonly implicated, there is no consensus definition for its diagnosis, and left ventricular function is neglected. There is a need to identify the homogenous subgroups within ARDS, that have a similar pathobiology, which can then be treated with targeted therapies. Haemodynamic clustering analyses in patients with ARDS have identified two subphenotypes of increasingly severe right ventricular injury, and a further subphenotype of hyperdynamic left ventricular function. In this review, we discuss how phenotyping the cardiovascular system in ARDS may align with haemodynamic pathophysiology, can aid in optimally defining right ventricular dysfunction and can identify tailored therapeutic targets for shock in ARDS. Additionally, clustering analyses of inflammatory, clinical and radiographic data describe other subphenotypes in ARDS. We detail the potential overlap between these and the cardiovascular phenotypes.

Cardiovascular Subphenotypes in Acute Respiratory Distress Syndrome.

OBJECTIVES: To use clustering methods on transthoracic echocardiography (TTE) findings and hemodynamic parameters to characterize circulatory failure subphenotypes and potentially elucidate underlying mechanisms in patients with acute respiratory distress syndrome (ARDS) and to describe their association with mortality compared with current definitions of right ventricular dysfunction (RVD). DESIGN: Retrospective, single-center cohort study. SETTING: University Hospital ICU, Birmingham, United Kingdom. PATIENTS: ICU patients that received TTE within 7 days of ARDS onset between April 2016 and December 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Latent class analysis (LCA) of TTE/hemodynamic parameters was performed in 801 patients, 62 years old (interquartile range, 50-72 yr old), 63% male, and 40% 90-day mortality rate. Four cardiovascular subphenotypes were identified: class 1 (43%; mostly normal left and right ventricular [LV/RV] function), class 2 (24%; mostly dilated RV with preserved systolic function), class 3 (13%, mostly dilated RV with impaired systolic function), and class 4 (21%; mostly high cardiac output, with hyperdynamic LV function). The four subphenotypes differed in their characteristics and outcomes, with 90-day mortality rates of 19%, 40%, 78%, and 59% in classes 1-4, respectively ( p < 0.0001). Following multivariable logistic regression analysis, class 3 had the highest odds ratio (OR) for mortality (OR, 6.9; 95% CI, 4.0-11.8) compared with other RVD definitions. Different three-variable models had high diagnostic accuracy in identifying each of these latent subphenotypes. CONCLUSIONS: LCA of TTE parameters identified four cardiovascular subphenotypes in ARDS that more closely aligned with circulatory failure mechanisms and mortality than current RVD definitions.

Mechanisms of Post-critical Illness Cardiovascular Disease.

Prolonged critical care stays commonly follow trauma, severe burn injury, sepsis, ARDS, and complications of major surgery. Although patients leave critical care following homeostatic recovery, significant additional diseases affect these patients during and beyond the convalescent phase. New cardiovascular and renal disease is commonly seen and roughly one third of all deaths in the year following discharge from critical care may come from this cluster of diseases. During prolonged critical care stays, the immunometabolic, inflammatory and neurohumoral response to severe illness in conjunction with resuscitative treatments primes the immune system and parenchymal tissues to develop a long-lived pro-inflammatory and immunosenescent state. This state is perpetuated by persistent Toll-like receptor signaling, free radical mediated isolevuglandin protein adduct formation and presentation by antigen presenting cells, abnormal circulating HDL and LDL isoforms, redox and metabolite mediated epigenetic reprogramming of the innate immune arm (trained immunity), and the development of immunosenescence through T-cell exhaustion/anergy through epigenetic modification of the T-cell genome. Under this state, tissue remodeling in the vascular, cardiac, and renal parenchymal beds occurs through the activation of pro-fibrotic cellular signaling pathways, causing vascular dysfunction and atherosclerosis, adverse cardiac remodeling and dysfunction, and proteinuria and accelerated chronic kidney disease.

Impact of ethnicity on the accuracy of measurements of oxygen saturations: A retrospective observational cohort study.

Background: Pulse oximeters are routinely used in community and hospital settings worldwide as a rapid, non-invasive, and readily available bedside tool to approximate blood oxygenation. Potential racial biases in peripheral oxygen saturation (SpO2) measurements may influence the accuracy of pulse oximetry readings and impact clinical decision making. We aimed to assess whether the accuracy of oxygen saturation measured by SpO2, relative to arterial blood gas (SaO2), varies by ethnicity. Methods: In this large retrospective observational cohort study covering four NHS Hospitals serving a large urban population in Birmingham, United Kingdom, consecutive pairs of SpO2 and SaO2 measurements taken on the same patient within an interval of less than 20 min were identified from electronic patient records. Where multiple pairs of measurements were recorded in a spell, only the first was included in the analysis. The differences between SpO2 and SaO2 measurements were compared across groups of self-identified ethnicity. These differences were subsequently adjusted for age, sex, bilirubin, systolic blood pressure, carboxyhaemaglobin saturations and the time interval between SpO2 and SaO2 measurements. Findings: Paired O2 saturation measurements from 16,818 inpatient spells between 1st January 2017 and 18th February 2021 were analysed. The cohort self-identified as being of White (81.2%), Asian (11.7%), Black (4.0%), or Other (3.2%) ethnicities. Across the cohort, SpO2 was statistically significantly higher than SaO2 (p < 0.0001), with medians of 98% (interquartile range [IQR]: 95-100%) vs. 97% (IQR: 96-99%), and a median difference of 0.5% points (pps; 95% confidence interval [CI]: 0.5-0.6). However, the size of this difference varied considerably with the magnitude of SaO2, with SpO2 overestimating by a median by 3.8pp (IQR: 0.4, 8.8) for SaO2 values <90% but underestimating by a median of 0.4pp (IQR: -2.0, 1.4) for an SaO2 of 95%. The differences between SpO2 and SaO2 were also found to vary by ethnicity, with this difference being 0.8pp (95% CI: 0.6-1.0, p < 0.0001) greater in those of Black vs. White ethnicity. These differences resulted in 8.7% vs. 6.1% of Black vs. White patients who were classified as normoxic on SpO2 actually being hypoxic on the gold standard SaO2 (odds ratio: 1.47, 95% CI: 1.09-1.98, p = 0.012). Interpretation: Pulse oximetry may overestimate O2 saturation, and this is possibly more pronounced in patients of Black ethnicity. Prospective studies are urgently warranted to assess the impact of ethnicity on the accuracy of pulse oximetry, to ensure care is optimised for all. Funding: PIONEER, the Health Data Research UK (HDR-UK) Health Data Research Hub in acute care.

Hyperdynamic Left Ventricular Ejection Fraction in ICU Patients With Sepsis.

OBJECTIVES: To evaluate the cause and prognosis of hyperdynamic left ventricular ejection fraction in critically ill patients with sepsis. DESIGN: Retrospective, single-center cohort study. SETTING: University Hospital ICU, Birmingham, United Kingdom. PATIENTS: ICU patients who received a transthoracic echocardiogram within 7 days of sepsis between April 2016 and December 2019. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The 90-day mortality rates of normal (55-70%), depressed (< 55%), and hyperdynamic left ventricular ejection fraction (> 70%) were compared. Multivariate logistic regression analysis was performed to determine the association of left ventricular ejection fraction phenotypes with mortality and the association of clinical variables with left ventricular ejection fraction phenotypes. One thousand fourteen patients met inclusion criteria and were 62 years old (interquartile range, 47-72), with mostly respiratory infections (n = 557; 54.9%). Ninety-day mortality was 32.1% (n = 325). Patients with hyperdynamic left ventricular ejection fraction had a higher mortality than depressed and normal left ventricular ejection fraction cohorts (58.9% [n = 103] vs 34.0% [n = 55] vs 24.7% [n = 167]; p < 0.0001, respectively). After multivariate logistic regression, hyperdynamic left ventricular ejection fraction was independently associated with mortality (odds ratio, 3.90 [2.09-7.40]), whereas depressed left ventricular ejection fraction did not (odds ratio, 0.62 [0.28-1.37]). Systemic vascular resistance was inversely associated with hyperdynamic left ventricular ejection fraction (odds ratio, 0.79 [0.58-0.95]), and age, frailty, and ischemic heart disease were associated with depressed left ventricular ejection fraction. CONCLUSIONS: Hyperdynamic left ventricular ejection fraction was associated with mortality in septic ICU patients and may reflect unmitigated vasoplegia from sepsis. Depressed left ventricular ejection fraction was not associated with mortality but was associated with cardiovascular disease.

Incidence and risk factors of acute kidney injury in COVID-19 patients with and without acute respiratory distress syndrome (ARDS) during the first wave of COVID-19: a systematic review and Meta-Analysis.

BACKGROUND: Acute kidney injury (AKI) is common among patients with COVID-19. However, AKI incidence may increase when COVID-19 patients develop acute respiratory distress syndrome (ARDS). Thus, this systematic review and meta-analysis aimed to assess the incidence and risk factors of AKI, need for kidney replacement therapy (KRT), and mortality rate among COVID-19 patients with and without ARDS from the first wave of COVID-19. METHODS: The databases MEDLINE and EMBASE were searched using relevant keywords. Only articles available in English published between December 1, 2019, and November 1, 2020, were included. Studies that included AKI in COVID-19 patients with or without ARDS were included. Meta-analyses were conducted using random-effects models. RESULTS: Out of 618 studies identified and screened, 31 studies met the inclusion criteria. A total of 27,500 patients with confirmed COVID-19 were included. The overall incidence of AKI in patients with COVID-19 was 26% (95% CI 19% to 33%). The incidence of AKI was significantly higher among COVID-19 patients with ARDS than COVID-19 patients without ARDS (59% vs. 6%, p < 0.001). Comparing ARDS with non-ARDS COVID-19 cohorts, the need for KRT was also higher in ARDS cohorts (20% vs. 1%). The mortality among COVID-19 patients with AKI was significantly higher (Risk ratio = 4.46; 95% CI 3.31-6; p < 0.00001) than patients without AKI. CONCLUSION: This study shows that ARDS development in COVID-19-patients leads to a higher incidence of AKI and increased mortality rate. Therefore, healthcare providers should be aware of kidney dysfunction, especially among elderly patients with multiple comorbidities. Early kidney function assessment and treatments are vital in COVID-19 patients with ARDS.

Viability-Resolved Metagenomics Reveals Antagonistic Colonization Dynamics of Staphylococcus epidermidis Strains on Preterm Infant Skin.

Preterm infants are at increased risk of infections caused by coagulase-negative staphylococci (CoNS) that colonize skin. Technical barriers in sequencing low-microbial-biomass skin swabs from preterm infants hinder attempts to gain a strain-level understanding of CoNS colonization dynamics within their developing skin microbiome. Here, the microbiome of five skin sites and available stool was studied from four preterm infants hospitalized over their first 2 months of life. We used propidium monoazide treatment of samples to enrich for the viable microbiome and metagenomic shotgun sequencing to resolve species and strains. The microbiome of different skin sites overlapped with each other, was dominated by the CoNS species Staphylococcus epidermidis and Staphylococcus capitis, and was distinct from stool. Species diversity on skin increased over time despite antibiotic exposure. Evidence of antagonism between the most common S. epidermidis strains, ST2 and ST59, included negative relationships for species correlation networks and in situ replication rates and that ST2 colonized skin earlier but was often replaced by ST59 over time. Experiments done with reference isolates showed that ST2 produced more biofilm than ST59 on plastic surfaces, which was reduced in mixed culture. We also discovered that a rare S. epidermidis strain, ST5, grew rapidly in stool in association with Stenotrophomonas maltophilia from a suspected episode of infection. Viability treatment of samples and moderate throughput shotgun sequencing provides strain-level information about CoNS colonization dynamics of preterm infant skin that ultimately might be exploited to prevent infections. IMPORTANCE The skin is a habitat for microbes that commonly infect preterm infants, but the use of sequencing for fine-scale study of the microbial communities of skin that develop in these infants has been limited by technical barriers. We treated skin swabs of preterm infants with a photoreactive dye that eliminates DNA from nonviable microbes and then sequenced the remaining DNA. We found that two strains of the most common species, Staphylococcus epidermidis, showed an antagonistic relationship on skin by cooccurring with different species, replicating fastest in different samples, and dominating skin sites at different times. Representatives of these strains also differed in their ability to stick to plastic surfaces-an important pathogenicity trait of this species. Our study shows the feasibility of gaining detailed information about strain colonization dynamics from this difficult-to-sequence body site of preterm infants, which might be used to guide novel approaches to prevent infections.

Right Ventricular Dysfunction and Its Association With Mortality in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome.

OBJECTIVES: To assess whether right ventricular dilation or systolic impairment is associated with mortality and/or disease severity in invasively ventilated patients with coronavirus disease 2019 acute respiratory distress syndrome. DESIGN: Retrospective cohort study. SETTING: Single-center U.K. ICU. PATIENTS: Patients with coronavirus disease 2019 acute respiratory distress syndrome undergoing invasive mechanical ventilation that received a transthoracic echocardiogram between March and December 2020. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Right ventricular dilation was defined as right ventricular:left ventricular end-diastolic area greater than 0.6, right ventricular systolic impairment as fractional area change less than 35%, or tricuspid annular plane systolic excursion less than 17 mm. One hundred seventy-two patients were included, 59 years old (interquartile range, 49-67), with mostly moderate acute respiratory distress syndrome (n = 101; 59%). Ninety-day mortality was 41% (n = 70): 49% in patients with right ventricular dilation, 53% in right ventricular systolic impairment, and 72% in right ventricular dilation with systolic impairment. The right ventricular dilation with systolic impairment phenotype was independently associated with mortality (odds ratio, 3.11 [95% CI, 1.15-7.60]), but either disease state alone was not. Right ventricular fractional area change correlated with Pao2:Fio2 ratio, Paco2, chest radiograph opacification, and dynamic compliance, whereas right ventricular:left ventricle end-diastolic area correlated negatively with urine output. CONCLUSIONS: Right ventricular systolic impairment correlated with pulmonary pathophysiology, whereas right ventricular dilation correlated with renal dysfunction. Right ventricular dilation with systolic impairment was the only right ventricular phenotype that was independently associated with mortality.

Simvastatin Improves Neutrophil Function and Clinical Outcomes in Pneumonia. A Pilot Randomized Controlled Clinical Trial.

Rationale: Population studies suggest improved sepsis outcomes with statins, but the results of randomized controlled trials in patients with sepsis and organ dysfunction in critical care settings have broadly been negative. In vitro data suggest that statins modulate age-related neutrophil functions, improving neutrophil responses to infection, but only in older patients and at high doses.Objectives: To determine if high-dose simvastatin improves neutrophil functions and is safe and tolerated in hospitalized older adults with community-acquired pneumonia with sepsis (CAP + S) not admitted to critical care.Methods: We conducted a randomized, double-blind, placebo-controlled pilot study of simvastatin 80 mg or placebo for 7 days for patients with CAP + S aged 55 years or older admitted to a secondary care hospital. The Day 4 primary endpoint was change in neutrophil extracellular trap formation (NETosis). Day 4 secondary endpoints included neutrophil chemotaxis, safety and tolerability, Sequential Organ Failure Assessment score, mortality, readmission, and markers of tissue degradation/inflammation.Measurements and Main Results: Four days of simvastatin adjuvant therapy in patients with CAP + S was associated with improvements in systemic neutrophil function (NETosis and chemotaxis), a reduction in systemic neutrophil elastase burden, and improved Sequential Organ Failure Assessment scores compared with placebo. A post hoc analysis demonstrated that simvastatin therapy was associated with improved hospitalization-free survival compared with placebo. Simvastatin was well tolerated in this elderly and multimorbid patient group with common coprescription of macrolide antibiotics.Conclusions: This pilot study supports high-dose simvastatin as an adjuvant therapy for CAP + S in an older and milder disease cohort than assessed previously. A definitive multicenter study is now warranted in this population to assess the likelihood of benefit and harm.Clinical trial registered with EudraCT (2012-00343-29).

Sepsis Induces a Dysregulated Neutrophil Phenotype That Is Associated with Increased Mortality.

BACKGROUND: Neutrophil dysfunction in sepsis has been implicated in the pathogenesis of multiorgan failure; however, the role of neutrophil extracellular traps (NETs) remains uncertain. We aimed to determine the sequential changes in ex vivo NETosis and its relationship with mortality in patients with sepsis and severe sepsis. METHODS: This was a prospective observational cohort study enrolling 21 healthy age-matched controls and 39 sepsis and 60 severe sepsis patients from acute admissions to two UK hospitals. Patients had sequential bloods for the ex vivo assessment of NETosis in response to phorbol-myristate acetate (PMA) using a fluorometric technique and chemotaxis using time-lapse video microscopy. Continuous data was tested for normality, with appropriate parametric and nonparametric tests, whilst categorical data was analysed using a chi-squared test. Correlations were performed using Spearman's rho. RESULTS: Ex vivo NETosis was reduced in patients with severe sepsis, compared to patients with sepsis and controls (p = 0.002). PMA NETosis from patients with septic shock was reduced further (p < 0.001) compared to controls. The degree of metabolic acidosis correlated with reduced NETosis (p < 0.001), and this was replicated when neutrophils from healthy donors were incubated in acidotic media. Reduced NETosis at baseline was associated with an increased 30-day (p = 0.002) and 90-day mortality (p = 0.014) in sepsis patients. These findings were accompanied by defects in neutrophil migration and delayed apoptosis. Resolution of sepsis was not associated with the return to baseline levels of NETosis or migration. CONCLUSIONS: Sepsis induces significant changes in neutrophil function with the degree of dysfunction corresponding to the severity of the septic insult which persists beyond physiological recovery from sepsis. The changes induced lead to the failure to effectively contain and eliminate the invading pathogens and contribute to sepsis-induced immunosuppression. For the first time, we demonstrate that reduced ex vivo NETosis is associated with poorer outcomes from sepsis.

Development of a screening tool to predict the risk of chronic pain and disability following musculoskeletal trauma: protocol for a prospective observational study in the United Kingdom.

INTRODUCTION: Pain is an expected and appropriate experience following traumatic musculoskeletal injury. By contrast, chronic pain and disability are unhelpful yet common sequelae of trauma-related injuries. Presently, the mechanisms that underlie the transition from acute to chronic disabling post-traumatic pain are not fully understood. Such knowledge would facilitate the development and implementation of precision rehabilitation approaches that match interventions to projected risk of recovery, with the aim of preventing poor long-term outcomes. The aim of this study is to identify a set of predictive factors to identify patients at risk of developing ongoing post-traumatic pain and disability following acute musculoskeletal trauma. To achieve this, we will use a unique and comprehensive combination of patient-reported outcome measures, psychophysical testing and biomarkers. METHODS AND ANALYSIS: A prospective observational study will recruit two temporally staggered cohorts (n=250 each cohort; at least 10 cases per candidate predictor) of consecutive patients with acute musculoskeletal trauma aged ≥16 years, who are emergency admissions into a Major Trauma Centre in the United Kingdom, with an episode inception defined as the traumatic event. The first cohort will identify candidate predictors to develop a screening tool to predict development of chronic and disabling pain, and the second will allow evaluation of the predictive performance of the tool (validation). The outcome being predicted is an individual's absolute risk of poor outcome measured at a 6-month follow-up using the Chronic Pain Grade Scale (poor outcome ≥grade II). Candidate predictors encompass the four primary mechanisms of pain: nociceptive (eg, injury location), neuropathic (eg, painDETECT), inflammatory (biomarkers) and nociplastic (eg, quantitative sensory testing). Concurrently, patient-reported outcome measures will assess general health and psychosocial factors (eg, pain self-efficacy). Risk of poor outcome will be calculated using multiple variable regression analysis. ETHICS AND DISSEMINATION: Approved by the NHS Research Ethics Committee (17/WA/0421).

Pulmonary Infections in the Elderly Lead to Impaired Neutrophil Targeting, Which Is Improved by Simvastatin.

RATIONALE: Dysregulated neutrophil functions with age and sepsis are described. Statins are associated with improved infection survival in some observational studies, but trials in critically ill patients have not shown benefit. Statins also alter neutrophil responses in vitro. OBJECTIVES: To assess neutrophil migratory accuracy with age during respiratory infections and determine if and how a statin intervention could alter these blunted responses. METHODS: The migratory accuracy of blood neutrophils from young (aged <35 yr) and old (aged >60 yr) patients in health and during a lower respiratory tract infection, community-acquired pneumonia, and pneumonia associated with sepsis was assessed with and without simvastatin. In vitro results were confirmed in a double-blind randomized clinical trial in healthy elders. Cell adhesion markers were assessed. MEASUREMENTS AND MAIN RESULTS: In vitro neutrophil migratory accuracy in the elderly deteriorated as the severity of the infectious pulmonary insult increased, without recovery at 6 weeks. Simvastatin rescued neutrophil migration with age and during mild to moderate infection, at high dose in older adults, but not during more severe sepsis. Confirming in vitro results, high-dose (80-mg) simvastatin improved neutrophil migratory accuracy without impeding other neutrophil functions in a double-blind randomized clinical trial in healthy elders. Simvastatin modified surface adhesion molecule expression and activity, facilitating accurate migration in the elderly. CONCLUSIONS: Infections in older adults are associated with prolonged, impaired neutrophil migration, potentially contributing to poor outcomes. Statins improve neutrophil migration in vivo in health and in vitro in milder infective events, but not in severe sepsis, supporting their potential utility as an early intervention during pulmonary infections. Clinical trial registered with www.clinicaltrialsregister.eu (2011-002082-38).

Vitamin D Deficiency in Human and Murine Sepsis.

OBJECTIVES: Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and ICU mortality but causality of these associations has not been demonstrated. To determine whether sepsis and severe sepsis are associated with vitamin D deficiency and to determine whether vitamin D deficiency influences the severity of sepsis. DESIGN, SETTING, AND PATIENTS: Sixty-one patients with sepsis and severe sepsis from two large U.K. hospitals and 20 healthy controls were recruited. Murine models of cecal ligation and puncture and intratracheal lipopolysaccharide were undertaken in normal and vitamin D deficient mice to address the issue of causality. MEASUREMENTS AND MAIN RESULTS: Patients with severe sepsis had significantly lower concentrations of 25-hydroxyvitamin D3 than patients with either mild sepsis or age-matched healthy controls (15.7 vs 49.5 vs 66.5 nmol/L; p = 0.0001). 25-hydroxyvitamin D3 concentrations were significantly lower in patients who had positive microbiologic culture than those who were culture negative (p = 0.0023) as well as those who died within 30 days of hospital admission (p = 0.025). Vitamin D deficiency in murine sepsis was associated with increased peritoneal (p = 0.037), systemic (p = 0.019), and bronchoalveolar lavage (p = 0.011) quantitative bacterial culture. This was associated with reduced local expression of the cathelicidin-related antimicrobial peptide as well as evidence of defective macrophage phagocytosis (p = 0.029). In the intratracheal lipopolysaccharide model, 1,500 IU of intraperitoneal cholecalciferol treatment 6 hours postinjury reduced alveolar inflammation, cellular damage, and hypoxia. CONCLUSIONS: Vitamin D deficiency is common in severe sepsis. This appears to contribute to the development of the condition in clinically relevant murine models and approaches to correct vitamin D deficiency in patients with sepsis should be developed.

Intra-operative adherence to lung-protective ventilation: a prospective observational study.

BACKGROUND: Lung-protective ventilation in patients with acute respiratory distress syndrome improves mortality. Adopting this strategy in the perioperative period has been shown to reduce lung inflammation and postoperative pulmonary and non-pulmonary sepsis complications in patients undergoing major abdominal surgery. We conducted a prospective observational study into the intra-operative ventilation practice across the West Midlands to assess the use of lung-protective ventilation. METHODS: Data was collected from all adult ventilated patients undergoing surgery across 14 hospital trusts in the West Midlands over a 2-day period in November 2013. Data collected included surgical specialty, patient's biometric data, duration of procedure, grade of anesthetist, and ventilatory parameters. Lung-protective ventilation was defined as the delivery of a tidal volume between 6 and 8 ml/kg/predicted body weight, a peak pressure of less than 30 cmH2O, and the use of positive end expiratory pressure of 6-8 cmH2O. Categorical data are presented descriptively, while non-parametric data are displayed as medians with statistical tests from Mann-Whitney U tests or Kruskal-Wallis tests for independent samples while paired samples are represented by Wilcoxon signed rank tests. RESULTS: Four hundred six patients with a median age of 56 years (16-91) were included. The majority of operations (78 %) were elective procedures with the principal anesthetist being a consultant. The commonest surgical specialties were general (29 %), trauma and orthopedic (19 %), and ENT (17 %). Volume-controlled ventilation was the preferred ventilation strategy in 70 % of cases. No patients were ventilated using lung-protective ventilation. Overall peak airway pressure (pPeak) was low (median 20 cmH2O (inter-quartile range [IQR] 10-43 cmH2O)) with median delivered tidal volumes of 8.4 ml/kg/predicted body weight (PBW) (IQR 3.5-14.5 ml/kg/PBW). The median positive end expiratory pressure (PEEP) was only 4 cmH2O (0-5 cmH2O) with PEEP not used in 152 cases. CONCLUSIONS: Perioperative lung protection ventilation can improve patient outcomes from major surgery. This large prospective study demonstrates that within the West Midlands lung-protective ventilation during the perioperative period is uncommon, especially in relation to the use of PEEP, and that perhaps further trials are required to promote wider adoption of practice.

A complete audit cycle to assess adherence to a lung protective ventilation strategy.

There is clear evidence for the use of a protective ventilation protocol in patients with acute respiratory distress syndrome (ARDS). There is evidence to suggest that protective ventilation is beneficial in patients at risk of ARDS. A protective ventilation strategy was implemented on our intensive care unit in critical care patients who required mechanical ventilation for over 48 h, with and at risk for ARDS. A complete audit cycle was performed over 13 months to assess compliance with a safe ventilation protocol in intensive care. The ARDS network mechanical ventilation protocol was used as the standard for our protective ventilation strategy. This recommends ventilation with a tidal volume (V t) of 6 ml/kg of ideal body weight (IBW) and plateau airway pressure of ≤30 cm H2O. The initial audit failed to meet this standard with V t's of 9.5 ml/kg of IBW. Following the implementation of a ventilation strategy and an educational program, we demonstrate a significant improvement in practice with V t's of 6.6 ml/kg of IBW in the re-audit. This highlights the importance of simple interventions and continuous education in maintaining high standards of care.