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BackgroundSeverity-of-illness scoring systems are widely used for quality assurance and research. Although validated by trained data collectors, there is little data on the accuracy of real-world data collection practices.ObjectiveTo evaluate the influence of formal data collection training on the accuracy of scoring system data in intensive care units (ICUs).Study design and methodsQuality assurance audit conducted using survey methodology principles. Between June and December 2018, an electronic document with details of three fictitious ICU patients was emailed to staff from 19 Australian ICUs who voluntarily submitted data on a web-based data entry form. Their entries were used to generate severity-of-illness scores and risks of death (RoDs) for four scoring systems. The primary outcome was the variation of severity-of-illness scores and RoDs from a reference standard.Results50/83 staff (60.3%) submitted data. Using Bayesian multilevel analysis, severity-of-illness scores and RoDs were found to be significantly higher for untrained staff. The mean (95% high-density interval) overestimation in RoD due to training effect for patients 1, 2 and 3, respectively, were 0.24 (0.16, 0.31), 0.19 (0.09, 0.29) and 0.24 (0.1, 0.38) respectively (Bayesian factor >300, decisive evidence). Both groups (trained and untrained) had wide coefficients of variation up to 38.1%, indicating wide variability. Untrained staff made more errors in interpreting scoring system definitions.InterpretationIn a fictitious patient dataset, data collection staff without formal training significantly overestimated the severity-of-illness scores and RoDs compared with trained staff. Both groups exhibited wide variability. Strategies to improve practice may include providing adequate training for all data collection staff, refresher training for previously trained staff and auditing the raw data submitted by individual ICUs. The results of this simulated study need revalidation on real patients.

Transpulmonary thermodilution devices have been widely shown to be accurate in septic shock patients in assessing fluid responsiveness. We conducted a systematic review to assess the relationship between fluid therapy protocols guided by transpulmonary thermodilution devices on fluid balance and the amount of intravenous fluid used in septic shock. We searched MEDLINE, Embase and The Cochrane Library. Studies were eligible for inclusion if they were prospective, parallel trials that were conducted in an intensive care setting in patients with septic shock. The comparator group was either central venous pressure, early goal-directed therapy or pulmonary artery occlusion pressure. Studies assessing only the accuracy of fluid responsiveness prediction by transpulmonary thermodilution devices were excluded. Two reviewers independently performed the search, extracted data and assessed the bias of each study. In total 27 full-text articles were identified for eligibility; of these, nine studies were identified for inclusion in the systematic review. Three of these trials used dynamic parameters derived from transpulmonary thermodilution devices and six used primarily static parameters to guide fluid therapy. There was evidence for a significant reduction in positive fluid balance in four out of the nine studies. From the available studies, the results suggest the benefit of transpulmonary thermodilution monitoring in the septic shock population with regard to reducing positive fluid balance is seen when the devices are utilised for at least 72 hours. Both dynamic and static parameters derived from transpulmonary thermodilution devices appear to lead to a reduction in positive fluid balance in septic shock patients compared to measurements of central venous pressure and early goal-directed therapy.

Objectives Hospitalized patients who presented within the last 24 h with a bacterial infection were recruited. Participants were assigned into sepsis and uncomplicated infection groups. In addition, healthy volunteers were recruited as controls. RNA was prepared from whole blood, depleted from beta-globin mRNA and sequenced. This dataset represents a highly valuable resource to better understand the biology of sepsis and to identify biomarkers for severe sepsis in humans. Data description The data presented here consists of raw and processed transcriptome data obtained by next generation RNA sequencing from 105 peripheral blood samples from patients with uncomplicated infections, patients who developed sepsis, septic shock patients, and healthy controls. It is provided as raw sequenced reads and as normalized log2 transformed relative expression levels. This data will allow performing detailed analyses of gene expression changes between uncomplicated infections and sepsis patients, such as identification of differentially expressed genes, co-regulated modules as well as pathway activation studies.

Background The effect of premorbid β-blocker exposure on clinical outcomes in patients with sepsis is not well characterized. We aimed to examine the association between premorbid β-blocker exposure and mortality in sepsis. Methods EMBase, MEDLINE, and Cochrane databases were searched for all studies of premorbid β-blocker and sepsis. The search was last updated on 22 June 2019. Two reviewers independently assessed, selected, and abstracted data from studies reporting chronic β-blocker use prior to sepsis and mortality. Main data extracted were premorbid β-blocker exposure, mortality, study design, and patient data. Two reviewers independently assessed the risk of bias and quality of evidence. Results In total, nine studies comprising 56,414 patients with sepsis including 6576 patients with premorbid exposure to β-blockers were eligible. For the primary outcome of mortality, two retrospective studies reported adjusted odds ratios showing a reduction in mortality with premorbid β-blocker exposure. One study showed that premorbid β-blocker exposure decreases mortality in patients with septic shock. Another study showed that continued β-blockade during sepsis is associated with decreased mortality. Conclusion This systematic review suggests that β-blocker exposure prior to sepsis is associated with reduced mortality. There was insufficient data to conduct a bona fide meta-analysis. Whether the apparent reduction in mortality may be attributed to the mitigation of catecholamine excess is unclear. Trial registration PROSPERO, CRD42019130558 registered June 12, 2019. Electronic supplementary material The online version of this article (10.1186/s13054-019-2562-y) contains supplementary material, which is available to authorized users.

Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack of reliable prognostic factors needed to guide such therapy. Here, we use a network analysis approach to identify host factors associated with severe influenza and fatal outcome. In influenza patients with moderate-to-severe diseases, we uncover a complex landscape of immunological pathways, with the main changes occurring in pathways related to circulating neutrophils. Patients with severe disease display excessive neutrophil extracellular traps formation, neutrophil-inflammation and delayed apoptosis, all of which have been associated with fatal outcome in animal models. Excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome (AUROC 0.817–0.898). These findings provide new evidence that neutrophil-dominated host response is associated with poor outcomes. Measuring neutrophil-related changes may improve risk stratification and patient selection, a critical first step in developing host-directed immune therapy., Identification of host factors associated with severe influenza infection could provide insights into treatment options. Here, the authors provide transcriptomic analyses of blood from >100 influenza infected patients and show that changes in circulating neutrophils are associated with severe influenza infection.

Background Diagnosis of significant coronary artery disease (CAD) and acute coronary artery occlusion in ICU can be difficult, and an inappropriate intervention is potentially harmful. Myocardial contrast perfusion echo (MCPE) examines ultrasound contrast intensity replenishment curves in individual myocardial segments measuring peak contrast intensity and slope of return as an index of myocardial blood flow (units = intensity of ultrasound per second [dB/s]). MCPE could possibly serve as a triage tool to invasive angiography by estimating blood flow in the myocardium. We sought to assess feasibility in the critically ill and if MCPE could add incremental value to the clinical acumen in predicting significant CAD. Methods This is a single-centre, prospective, observational study. Inclusion criteria were as follows: adult ICU patients with troponin I > 50 ng/L and cardiology referral being made for consideration of inpatient angiography. Exclusion criteria were as follows: poor echo windows (2 patients), known ischaemic heart disease, and contrast contraindications. Seven cardiologists and 6 intensivists blinded to outcome assessed medical history, ECG, troponin, and 2D echo images to estimate likelihood of significant CAD needing intervention (clinical acumen). Clinical acumen, quantitative MCPE, and subjective (visual) MCPE were assessed to predict significant CAD. Results Forty patients underwent MCPE analysis, 6 (15%) had significant CAD, and median 11 of 16 segments (IQR 8–13) could be imaged (68.8% [IQR 50–81]). No adverse events occurred. A significant difference was found in overall MCPE blood flow estimation between those diagnosed with significant CAD and those without (3.3 vs 2.4 dB/s, p = 0.050). A MCPE value of 2.8 dB/s had 67% sensitivity and 88% specificity in detecting significant CAD. Clinical acumen showed no association in prediction of CAD (OR 0.6, p = 0.09); however, if quantitative or visual MCPE analysis was included, a significant association occurred (OR 17.1, p = 0.01; OR 23.0, p = 0.01 respectively). Conclusions MCPE is feasible in the critically ill and shows better association with predicting significant CAD vs clinical acumen alone. MCPE adds incremental value to initial assessment of the presence of significant CAD which may help guide those who require urgent angiography.

This narrative review focusing on critical care echocardiography (CCE) has been written by a group of experts in the field, with the aim of outlining the state of the art in CCE in the 10 years after its official recognition and definition. In the last 10 years, CCE has become an essential branch of critical care ultrasonography and has gained general acceptance. Its use, both as a diagnostic tool and for hemodynamic monitoring, has increased markedly, influencing contemporary cardiorespiratory management. Recent studies suggest that the use of CCE may have a positive impact on outcomes. CCE may be used in critically ill patients in many different clinical situations, both in their early evaluation of in the emergency department and during intensive care unit (ICU) admission and stay. CCE has also proven its utility in perioperative settings, as well as in the management of mechanical circulatory support. CCE may be performed with very simple diagnostic objectives. This application, referred to as basic CCE, does not require a high level of training. Advanced CCE, on the other hand, uses ultrasonography for full evaluation of cardiac function and hemodynamics, and requires extensive training, with formal certification now available. Indeed, recent years have seen the creation of worldwide certification in advanced CCE. While transthoracic CCE remains the most commonly used method, the transesophageal route has gained importance, particularly for intubated and ventilated patients. CCE is now widely accepted by the critical care community as a valuable tool in the ICU and emergency department, and in perioperative settings.

IntroductionAccurate triage is an important first step to effectively manage the clinical treatment of severe cases in a pandemic outbreak. In the current COVID-19 global pandemic, there is a lack of reliable clinical tools to assist clinicians to perform accurate triage. Host response biomarkers have recently shown promise in risk stratification of disease progression; however, the role of these biomarkers in predicting disease progression in patients with COVID-19 is unknown. Here, we present a protocol outlining a prospective validation study to evaluate the biomarkers’ performance in predicting clinical outcomes of patients with COVID-19.Methods and analysisThis prospective validation study assesses patients infected with COVID-19, in whom blood samples are prospectively collected. Recruited patients include a range of infection severity from asymptomatic to critically ill patients, recruited from the community, outpatient clinics, emergency departments and hospitals. Study samples consist of peripheral blood samples collected into RNA-preserving (PAXgene/Tempus) tubes on patient presentation or immediately on study enrolment. Real-time PCR (RT-PCR) will be performed on total RNA extracted from collected blood samples using primers specific to host response gene expression biomarkers that have been previously identified in studies of respiratory viral infections. The RT-PCR data will be analysed to assess the diagnostic performance of individual biomarkers in predicting COVID-19-related outcomes, such as viral pneumonia, acute respiratory distress syndrome or bacterial pneumonia. Biomarker performance will be evaluated using sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operating characteristic curve.Ethics and disseminationThis research protocol aims to study the host response gene expression biomarkers in severe respiratory viral infections with a pandemic potential (COVID-19). It has been approved by the local ethics committee with approval number 2020/ETH00886. The results of this project will be disseminated in international peer-reviewed scientific journals.

Purpose: Echocardiography is a common tool for cardiac and hemodynamic assessments in critical care research. However, interpretation (and applications) of results and between-study comparisons are often difficult due to the lack of certain important details in the studies. PRICES (Preferred Reporting Items for Critical care Echocardiography Studies) is a project endorsed by the European Society of Intensive Care Medicine and conducted by the Echocardiography Working Group, aiming at producing recommendations for standardized reporting of critical care echocardiography (CCE) research studies.Methods: The PRICE panel identified lists of clinical and echocardiographic parameters (the "items") deemed important in four main areas of CCE research: left ventricular systolic and diastolic functions, right ventricular function and fluid management. Each item was graded using a critical index (CI) that combined the relative importance of each item and the fraction of studies that did not report it, also taking experts' opinion into account.Results: A list of items in each area that deemed essential for the proper interpretation and application of research results is recommended. Additional items which aid interpretation were also proposed.Conclusion: The PRICES recommendations reported in this document, as a checklist, represent an international consensus of experts as to which parameters and information should be included in the design of echocardiography research studies. PRICES recommendations provide guidance to scientists in the field of CCE with the objective of providing a recommended framework for reporting of CCE methodology and results.

In 2014, basic critical care echocardiography (BCCE) competence became a mandatory requirement for trainees registered with the College of Intensive Care Medicine (CICM). To determine the proportion of CICM intensive care units (ICUs) that conduct a BCCE competence program and to learn about the barriers/challenges and successful strategies, we conducted a survey of intensivists working in ICUs accredited by CICM for basic/advanced training in Australia, New Zealand, Hong Kong, Singapore, Ireland and India. Following consultations with content experts and a trial phase to improve clarity and minimise ambiguity, an 11-point questionnaire survey was sent to one intensivist from every CICM-accredited ICU by several methods. Participation was voluntary. Consent was implied. No incentives were offered. Results are reported as numbers and percentages. Of the 104 ICUs surveyed, 99 (95.1%) responded, with 75 (75.8%) having no BCCE teaching whatsoever. In the remaining 24 (24.2%) ICUs, the teaching process was widely variable. Only 5/99 (5.1%) ICUs provided a structured BCCE competence program through which trainees performed and archived BCCE scans, maintained a logbook and underwent formative and summative assessments for credentialling. Six more ICUs provided formative assessment but relied on external bodies for competence assessment. Overall, 20/99 (20.2%) ICUs allowed trainees to perform unsupervised scans for clinical management, even if they were not BCCE competent. Nineteen intensivists perceived management errors due to misinterpretation of echocardiographic findings. Very few CICM-accredited ICUs offer a structured BCCE competence program. To fulfil the objective of universal BCCE competence, potential solutions are presented.

Background Respiratory viruses circulate constantly in the ambient air. The risk of opportunistic infection from these viruses can be increased in mechanically ventilated patients. The present study evaluates the feasibility of detecting airborne respiratory viruses in mechanically ventilated patients using a novel sample collection method involving ventilator filters. Methods We collected inspiratory and expiratory filters from the ventilator circuits of mechanically ventilated patients in an intensive care unit over a 14-month period. To evaluate whether we could detect respiratory viruses collected in these filters, we performed a reverse transcription polymerase chain reaction on the extracted filter membrane with primers specific for rhinovirus, respiratory syncytial virus, influenza virus A and B, parainfluenza virus (type 1, 2 and 3) and human metapneumovirus. For each patient, we also performed a full virology screen (virus particles, antibody titres and virus-induced biomarkers) on respiratory samples (nasopharyngeal swab, tracheal aspirate or bronchoalveolar fluid) and blood samples. Results Respiratory viruses were detected in the ventilator filters of nearly half the patients in the study cohort (n = 33/70). The most common virus detected was influenza A virus (n = 29). There were more viruses detected in the inspiratory filters (n = 18) than in the expiratory filters (n = 15). A third of the patients with a positive virus detection in the ventilator filters had a hospital laboratory confirmed viral infection. In the remaining cases, the detected viruses were different from viruses already identified in the same patient, suggesting that these additional viruses come from the ambient air or from cross-contamination (staff or visitors). In patients in whom new viruses were detected in the ventilator filters, there was no evidence of clinical signs of an active viral infection. Additionally, the levels of virus-induced biomarker in these patients were not statistically different from those of non-infected patients (p = 0.33). Conclusions Respiratory viruses were present within the ventilator circuits of patients receiving mechanical ventilation. Although no adverse clinical effect was evident in these patients, further studies are warranted, given the small sample size of the study and the recognition that ventilated patients are potentially susceptible to opportunistic infection from airborne respiratory viruses. Electronic supplementary material The online version of this article (10.1186/s13613-018-0396-4) contains supplementary material, which is available to authorized users.

Abnormal septal motion (commonly referred to as septal bounce) is a common echocardiographic finding that occurs with several conditions, including the following: mitral stenosis, left bundle branch block, pericardial syndromes and severe pulmonary hypertension. We explore the subtle changes that occur on M-mode imaging of the septum, other associated echocardiographic features, the impact of inspiratory effort on septal motion and relevant clinical findings. Finally, we discuss the impact of abnormal septal motion on cardiac form and function, proposing there is a clinically significant impact on biventricular filling and ejection.

In patients with septic shock, a correlation between positive fluid balance and worsened outcomes has been reported in multiple observational studies worldwide. No published data exists in an Australasian cohort. We set out to explore this association in our institution. We conducted a retrospective audit of patient records from August 2012 to May 2015 in a single-centre, 24-bed surgical and medical intensive care unit (ICU) in Sydney, Australia. All patients with septic shock were included. Exclusion criteria included length of stay less than 24 hours or vasopressors needed for less than six hours. Data was gathered on fluid balance for the first seven days of ICU admission, biochemical data and other clinical indices. The primary outcome measure was survival to hospital discharge. One hundred and eighty-six patients with septic shock were included, with an overall hospital mortality of 23.7%. Seventy-five percent of patients required mechanical ventilation, and 27.4% required haemodialysis. The mean daily fluid balance on the first day of admission was positive 1,424 ml and 1,394 ml for ICU and hospital survivors, respectively. On average, the daily fluid balance for non-survivors was higher than the survivors: ICU non-survivors were 602 (95% confidence intervals 230, 974) ml (P=0.0015) and hospital non-survivors were 530 [95% confidence intervals 197, 863] ml (P=0.0017) higher than the survivors. In line with other recently published data, after adjustment for confounders (severity of illness based on the Acute Physiology and Chronic Health Evaluation score) we found a correlation between positive fluid balance and worsened hospital mortality in critically ill patients with sepsis and septic shock. Further research investigating rational use of fluids in this patient group is needed.

Objective:To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for

Background Despite the evidence for calibrated cardiac monitored devices to determine fluid responsiveness, there is minimal evidence that the use of cardiac output monitor devices leads to an overall change in IV fluid use. We sought to investigate the feasibility of performing a randomised controlled study using calibrated cardiac output monitoring devices in shocked ICU patients and whether the use of these devices led to a difference in total volume of IV fluid administered. Methods We performed a single-centre non-blinded randomised controlled study which included patients who met the clinical criteria for shock on admission to ICU. Patients were divided into two groups (cardiac output monitors or standard) by block randomisation. Patients allocated to the cardiac output monitor all received EV1000 with Volume View sets. Daily intravenous fluid administration and cumulative fluid balance was recorded for 3 days. The primary outcome assessed was the difference in daily intravenous fluid administration and cumulative fluid balance at 72 h between the two groups. We also assessed how often the clinicians used the cardiac monitor to guide fluid therapy and the different reasoning for initiating further intravenous fluids. Results Eighty patients were randomised and 37 received calibrated cardiac output monitors. We found no adverse outcomes in the use of calibrated cardiac output monitoring devices and that was feasible to perform a randomised controlled trial. There was no significant difference between the standard care group vs the cardiac monitoring group for cumulative fluid balance (2503 ± 3764 ml vs 2458 ± 3560 ml, p = 0.96). There was no significant difference between the groups for daily intravenous fluid administration on days 1, 2 or 3. In the cardiac monitored group, only 43% of the time was the EV1000 output incorporated into the decision to give further intravenous fluids. Conclusion It is feasible to perform a randomised controlled trial using calibrated cardiac output monitoring devices. In addition, there was no trend to suggest that the use of a cardiac monitors leads to lower IV fluid use in the shocked patient. Further trials will require study designs to optimise the use of a cardiac output monitor to determine the utility of these devices in the shocked patient. Trial registration ANZCTR, ACTRN12618001373268. Registered 15 August 2018—retrospectively registered. Electronic supplementary material The online version of this article (10.1186/s40560-018-0356-y) contains supplementary material, which is available to authorized users.

In the publication of this article [1], there was an error in the cited reference 23 [2] within the Family Name. This has now been updated in the original article.

Background Tricuspid annular plane systolic excursion (TAPSE) is frequently used as an objective measure of right-ventricular dysfunction. Abnormal TAPSE values are associated with poor prognosis in a number of disease states; however, the measure is not always easy to obtain in the critically ill. The purpose of this study is to assess the feasibility and accuracy of using a subcostal view and TAPSE measurement as a measure of right-ventricular dysfunction. A secondary aim was to perform a pilot study to assess whether right-ventricular dysfunction was associated with adverse outcomes including mortality. Results Subcostal TAPSE corresponds well with TAPSE obtained from the apical window at low and moderate TAPSE values (mean difference 1.2 mm (CI 0.04–2.36; 100% data pairs

Objectives Doppler echocardiography is a well-recognized technique for the noninvasive evaluation of pulmonary artery pressure; however, little information is available concerning patients receiving mechanical ventilation. Furthermore, recent studies have debatable results regarding the relevance of this technique to assess pulmonary artery pressure. The aim of our study was to reassess the accuracy of Doppler echocardiography to evaluate pulmonary artery pressure and to predict pulmonary hypertension. Design Prospective observational study. Setting Amiens ICU, France. Patients ICU patients receiving mechanical ventilation. Interventions In 40 patients, we simultaneously recorded Doppler echocardiography variables (including tricuspid regurgitation and pulmonary regurgitation) and invasive central venous pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, and mean pulmonary artery pressure. Measurements and main results Systolic pulmonary artery pressure assessed from the tricuspid regurgitation derived maximal pressure gradient added to the central venous pressure demonstrated the best correlation with the invasive systolic pulmonary artery pressure (r = 0.87) with a small bias (-3 mm Hg) and a precision of 9 mm Hg. A Doppler echocardiography systolic pulmonary artery pressure greater than 39 mm Hg predicted pulmonary hypertension (mean pulmonary artery pressure ≥ 25 mm Hg) with 100% sensitivity and specificity. Tricuspid regurgitation maximal velocity greater than 2.82 m/s as well as tricuspid regurgitation pressure gradient greater than 32 mm Hg predicted the presence of pulmonary hypertension. Pulmonary regurgitation was recorded in 10 patients (25%). No correlation was found between pulmonary regurgitation velocities and either mean pulmonary artery pressure or diastolic pulmonary artery pressure. Pulmonary acceleration time less than 57 ms and isovolumic relaxation time less than 40 ms respectively predicted pulmonary hypertension 100% of the time and had a 100% negative predictive value. Conclusions Tricuspid regurgitation maximal velocity pressure gradient added to invasive central venous pressure accurately estimates systolic pulmonary artery pressure and mean pulmonary artery pressure in ICU patients receiving mechanical ventilation and may predict pulmonary hypertension.

Background Transthoracic 3D cardiac analysis is enticing in its potential simplicity and wealth of data available. It has been suggested to be accurate vs magnetic resonance imaging in relatively stable patients, but feasibility and agreement with conventional echocardiographic assessment of stroke volume (SV) have not been thoroughly assessed in critically ill patients, who are traditionally harder to image. The objectives of this study were to compare 3D transthoracic volumetric analysis vs Doppler assessment of SV (which is suggested to be accurate in the critically ill) and Simpson’s biplane assessment in a cohort typical of the intensive care unit (ICU), where accurate assessment is important: mechanically ventilated patients with a significant ventilation/perfusion (V/Q) mismatch. We hypothesised that it would be feasible but might lack agreement. Methods Patients were imaged within 24 hours of admission. Inclusion criteria were adult patients, V/Q mismatch present (defined as a ratio of arterial oxygen partial pressure to fractional inspired oxygen

Open lung ventilation with a recruitment maneuver could be beneficial for acute respiratory distress syndrome patients. However, the increased airway pressures resulting from the recruitment maneuver may induce cardiac dysfunction, limiting the benefit of this maneuver. We analyzed the effect of a recruitment maneuver and decremental positive end-expiratory pressure titration on cardiac function.Medical ICU Amiens, France.Twenty patients with moderate to severe acute respiratory distress syndrome INTERVENTIONS:: Patients underwent a stepwise recruitment maneuver with respiratory evaluation and echocardiography assessment of cardiac function including longitudinal strain at baseline, peak positive end-expiratory pressure of recruitment maneuver (positive end-expiratory pressure 40 cm H2O), and at "optimal" positive end-expiratory pressure. The patients were divided into two groups based on change on the PaO2/FIO2 ratio (nonresponders50%; responders ≥ 50%).At peak positive end-expiratory pressure during the recruitment maneuver, the arterial pressure, cardiac output, left ventricular size decreased and right ventricular size increased. The left ventricular ejection fraction decreased from 60% ± 13% to 48% ± 18% (p = 0.05). Both left and right ventricular global longitudinal strain were impaired (-15.8% ± 4.5% to -11% ± 4.7% and -19% ± 5% to -14% ± 6% [p = 0.05] respectively). Fifty percent of patients were nonresponders and demonstrated a lower hemodynamic tolerance to the recruitment maneuver than responders. Optimal positive end-expiratory pressure was 14 ± 5 cm H2O (vs 11 ± 4 cm H2O at baseline), and PaO2/FIO2 ratio increased from 111 ± 25 to 197 ± 89 mm Hg (p0.0001). All hemodynamic variables returned to their baseline value after the recruitment maneuver despite a higher positive end-expiratory pressure.An open lung strategy with a stepwise recruitment maneuver permitted a higher positive end-expiratory pressure and improved oxygenation without any cardiac impairment. The recruitment maneuver was associated with mild and transient, cardiac dysfunction, with nonresponders demonstrating poorer tolerance.

Catastrophic antiphospholipid syndrome is a rare multisystem autoimmune condition characterised by rapid development of widespread thrombotic disease and subsequent multi-organ failure. It is the most severe complication of antiphospholipid syndrome, carrying significant morbidity and mortality. We report a patient with post-partum catastrophic antiphospholipid syndrome with cardiac, hepatic, renal and cutaneous manifestations. The diagnostic challenges in establishing a definitive diagnosis in catastrophic antiphospholipid syndrome is discussed, along with the difficulties in managing these patients in the intensive care unit.

Many echocardiographic indices (or methods) for assessing right ventricular (RV) function are available, but each has its strengths and limitations. In some cases, there might be discordance between the indices. We conducted a systematic review to audit the echocardiographic RV assessments in critical care research to see if a consistent pattern existed. We specifically looked into the kind and number of RV indices used, and how RV dysfunction was defined in each study. Studies conducted in critical care settings and reported echocardiographic RV function indices from 1997 to 2017 were searched systematically from three databases. Non-adult studies, case reports, reviews and secondary studies were excluded. These studies’ characteristics and RV indices reported were summarized. Out of 495 non-duplicated publications found, 81 studies were included in our systematic review. There has been an increasing trend of studying RV function by echocardiography since 2001, and most were conducted in ICU. Thirty-one studies use a single index, mostly TAPSE, to define RV dysfunction; 33 used composite indices and the combinations varied between studies. Seventeen studies did not define RV dysfunction. For those using composite indices, many did not explain their choices. TAPSE seemed to be the most popular index in the last 2–3 years. Many studies used combinations of indices but, apart from cor pulmonale, we could not find a consistent pattern of RV assessment and definition of RV dysfunction amongst these studies.

Background Left ventricular diastolic dysfunction is suggested to be associated with higher mortality in severe sepsis and septic shock, yet the methods of diagnosis described in the literature are often inconsistent. The recently published 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) guidelines offer the opportunity to apply a simple pragmatic diagnostic algorithm for the detection of diastolic dysfunction; however, it has not been tested in this cohort. Aims We sought to assess the applicability in septic patients of recently published 2016 ASE/EACVI guidelines on diastolic dysfunction compared with the 2009 ASE guidelines. Our hypothesis was that there would be poor agreement in classifying patients. Methods Prospective observational study includes patients identified as having severe sepsis and septic shock. Patients underwent transthoracic echocardiography on day 1 and day 3 of their ICU admission. Patients with normal and abnormal (ejection fraction

Cardiac assessment in the critically ill septic patient has become increasingly sophisticated [1]; yet, the relationship between the heart and systemic arterial system remains an area of unfulfilled hope, with precise evaluation continuing to elude the practicing clinician. The concept of “cardiovascular (CV) performance or efficiency” is an attractive one, a tool promising to bridge the knowledge gulf that currently exists [2]. That said, its clinical application is challenging. First, there seems to be a lack of consensus as to which parameters best represent CV performance, whether it be stroke volume (SV), stroke work (SW), work efficiency, or the ventriculo arterial coupling (V-A coupling) [3]. Second, pragmatic methods for measuring some theoretical parameters, such as unstressed ventricular volume (V0), end-systolic pressure (Pes), and arterial compliance (Cart), are still lacking, let alone the challenge of the time-variable nature of these parameters. Over a quarter of a century ago, in the effort to match the heart function and the arterial load from an evolutionary viewpoint, Elzinga and Westerhof postulated that to attain minimum ventricular size a mammalian heart evolved with its working point quite close to optimum power and optimum efficient, and that a specific heart rate is required to guarantee sufficient pressure during diastole [4]. A decade prior to this, Sunagawa et al. predicted that maximal SW results when the end-systolic elastance (Ees) of the ventricle and arterial load (Ea, effective arterial elastance) are equal Ea/Ees= 1 [5, 6]. The Ea/Ees ratio has been used in various studies as a means to reflect V-A coupling [2, 7, 8]. In these studies, a high Ea/Ees ratio is taken to imply V-A uncoupling. Ea has a determinative effect on V-A coupling if ventricular contractility, hence Ees, is constant. On the basis of the pressure–volume relationship, Sunagawa et al. predicted, using the ratio of left ventricular Pes to SV, that Ea remains constant under a given steady-state vascular impedance load [5]. Hence, this gives rise to

Critical care echocardiography is developing rapidly with an increasing number of specialists now performing comprehensive studies using Doppler and other advanced techniques. However, this imaging can be challenging, interpretation is far from simple in the complex critically ill patient and mistakes can be easy to make. We aim to address clinically relevant areas where potential errors may occur and suggest methods to hopefully improve accuracy of imaging and interpretation.

Background Assessment of competence in basic critical care echocardiography is complex. Competence relies on not only imaging accuracy but also interpretation and appropriate management decisions. The experience to achieve these skills, real-time, is likely more than required for imaging accuracy alone. We aimed to assess the feasibility of using simulation to assess number of studies required to attain competence in basic critical care echocardiography. Methods This is a prospective pilot study recruiting trainees at various degrees of experience in basic critical care echocardiography using experts as reference standard. We used high fidelity simulation to assess speed and accuracy using total time taken, total position difference and total angle difference across the basic acoustic windows. Interpretation and clinical application skills were assessed using a clinical scenario. ‘Cut-off’ values for number of studies required for competence were estimated. Results Twenty-seven trainees and eight experts were included. The subcostal view was achieved quickest by trainees (median 23 s, IQR 19–37). Eighty-seven percent of trainees did not achieve accuracy across all views; 81% achieved accuracy with the parasternal long axis and the least accurate was the parasternal short axis (44% of trainees). Fewer studies were required to be considered competent with imaging acquisition compared with competence in correct interpretation and integration (15 vs. 40 vs. 50, respectively). Discussion The use of echocardiography simulation to determine competence in basic critical care echocardiography is feasible. Competence in image acquisition appears to be achieved with less experience than correct interpretation and correct management decisions. Further studies are required.

Background Left ventricular longitudinal strain (LVLS) is a modern measurement for LV function. However, strain measurement is often difficult in critically ill patients. We sought to show LVLS can be estimated using M-mode-derived longitudinal wall fractional shortening (LWFS), which is less dependent on image quality and is easier to perform in critically ill patients. Methods Transthoracic echocardiographic records were retrospectively screened and 80 studies suitable for strain and M-mode measurements in the apical 4-chamber view were selected. Longitudinal wall fractional shortening was derived from conventional M-mode (LWFS) and curved anatomical M-mode (CAMMFS). The relationships between LVLS and mitral annular plane systolic excusion (MAPSE) and M-mode-derived fractional shortening were examined using univariate generalized linear model in a training set (n = 50) and was validated in a separate validation set (n = 30). Results MAPSE, CAMMFS, and LWFS demonstrated very good correlations with LVLS (r = 0.852, 0.875 and 0.909, respectively). LWFS was the best unbiased predictor for LVLS (LVLS = 1.180 x LWFS - 0.737, P

The current trend to treat hypotension in critically ill patients is to place a greater emphasis on inotropic support and less on fluid resuscitation in order to limit the potential harm from fluid overload. This combination may trigger left ventricular outflow tract obstruction (LVOTO) in susceptible patients. Although LVOTO is classically described in patients with hypertrophic cardiomyopathy it has been reported in other conditions including septic shock, apical ballooning syndrome, myocardial infarction, respiratory failure, and post valvular surgery. It is more common in the elderly, females, and in patients with hypertension, diabetes, and chronic vascular disease because of predisposing anatomical conditions such as left ventricular hypertrophy, small left ventricle size, sigmoid septum and alterations in the positions of the aortic and mitral valve annular planes. The onset of LVOTO is largely unpredictable due to a complex interplay between preload, afterload, heart rhythm and rate in susceptible patients. The consequences of missing this treatable condition may lead to life-threatening hypotension refractory to, or exacerbated by, a further increase in inotropic support. Dynamic LVOTO should be considered in any hypotensive intensive care patient. Echocardiography is perhaps the best tool to assess LVOTO and its underlying pathophysiology in the critically ill. Detection of LVOTO is a relatively simple task using a combination of two-dimensional, M-mode and spectral Doppler imaging by an operator alert to the possible diagnosis.

Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods: The panel consisted of five sections: hemodynamics infection adjunctive therapies metabolic and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. Results: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Conclusions: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality. © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Critical care ultrasonography has utility for the diagnosis and management of critical illness and is in widespread use by frontline intensivists. As there is a need for research to validate and extend its utility, the Editor of Intensive Care Medicine included critical care ultrasonography as a topic in the ICM Research Agenda issue. Eleven international experts in the field of critical care ultrasonography contributed to the writing project. With the intention of developing a research agenda for the field, they reviewed best standards of care, new advances in the field, common beliefs that have been contradicted by recent trials, and unanswered questions related to critical care ultrasonography. The writing group focused on the provision of training in critical care ultrasonography, technological advances, and some specific clinical applications. The writing group identified several fields of interest for research and proposed ten research studies that would address important aspects of critical care ultrasonography.

Echocardiography is developing rapidly. Speckle tracking echocardiography is the latest semi-automatic tool that has potential to quantitatively describe cardiac dysfunction that may be unrecognised by conventional echocardiography. It is a non-Doppler, angle-independent, feasible and reproducible method to evaluate myocardial function in both non–critically ill and critically ill populations. Increasingly it has become a standard measure of both left and right ventricle function in specific patient groups, e.g. chemotherapy-induced cardiomyopathy or pulmonary hypertension. To date there are few studies in the critically ill, predominantly in sepsis, yet all describe dysfunction beyond standard measures. Other areas of interest include heart–lung interactions, right ventricle function and twist and torsion of the heart. A word of caution is required, however, in that speckle tracking echocardiography is far from perfect and is more challenging, particularly in the critically ill, than implied by many published studies. It takes time to learn and perform and most values are not validated, particularly in the critically ill. We should be cautious in accepting that the latest software used in cardiology cohorts will automatically be the answer in the critically ill. Even with these limitations the technology is enticing and results fascinating. We are uncovering previously undescribed dysfunction and although it currently is essentially a research-based activity, there is great promise as a clinical tool as echocardiography analysis becomes more automated, and potentially speckle tracking echocardiography could help describe cardiac function in critical illness more accurately than is possible with current techniques.

Echocardiography is pivotal in the diagnosis and management of the shocked patient. Important characteristics in the setting of shock are that it is non-invasive and can be rapidly applied. In the acute situation a basic study often yields immediate results allowing for the initiation of therapy, while a follow-up advanced study brings the advantage of further refining the diagnosis and providing an in-depth hemodynamic assessment. Competency in basic critical care echocardiography is now regarded as a mandatory part of critical care training with clear guidelines available. The majority of pathologies found in shocked patients are readily identified using basic level 2D and M-mode echocardiography. A more comprehensive diagnosis can be achieved with advanced levels of competency, for which practice guidelines are also now available. Hemodynamic evaluation and ongoing monitoring are possible with advanced levels of competency, which includes the use of colour Doppler, spectral Doppler, and tissue Doppler imaging and occasionally the use of more recent technological advances such as 3D or speckled tracking. The four core types of shock—cardiogenic, hypovolemic, obstructive, and vasoplegic—can readily be identified by echocardiography. Even within each of the main headings contained in the shock classification, a variety of pathologies may be the cause and echocardiography will differentiate which of these is responsible. Increasingly, as a result of more complex and elderly patients, the shock may be multifactorial, such as a combination of cardiogenic and septic shock or hypovolemia and ventricular outflow obstruction. The diagnostic benefit of echocardiography in the shocked patient is obvious. The increasing prevalence of critical care physicians experienced in advanced techniques means echocardiography often supplants the need for more invasive hemodynamic assessment and monitoring in shock.

Air sampling directly onto a methicillin-resistant Staphylococcus aureus (MRSA) selective agar was performed at six locations three times weekly over a period of 32 weeks in a new, initially MRSA-free Intensive Care Unit to examine if MRSA is present in air sample cultures and, if so, whether it is affected by the number of MRSA colonized patients present. A total of 480 air samples were collected on 80 days. A total of 39/480 (8.1%) samples were found to be MRSA positive of which 24/160 (15%) positive air samples were from the single rooms, where MRSA colonised patients were isolated, and 15/320 (4.7%) were from the open bed areas. A significant correlation was found between the daily number of MRSA colonized or infected patients in the Unit and the daily number of MRSA positive air samples cultures obtained (r2=0.128; P

Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers.In this study, we combined an integrated genomic analysis of 1071 individuals with in vitro experiments using well-established infection models.We identified a single-gene biomarker, IFI27, which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers. In vitro studies showed that IFI27 was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria. In vivo studies confirmed that IFI27 was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions), IFI27 displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections.IFI27 represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting; its implementation may improve the diagnosis and management of respiratory infection.

Background Aromatase inhibitors (AIs) are recommended as adjuvant hormone treatment for postmenopausal women with early breast cancer. A substantial proportion of women taking AIs experience joint pain and stiffness. Studies have suggested that acupuncture may be effective in treating joint pain. Objective A pilot study was conducted to evaluate the feasibility, safety and efficacy of using acupuncture to treat AI-induced arthralgia. Methods A total of 32 patients were randomised to receive either sham or real electroacupuncture (EA) twice weekly for 6 weeks. Outcomes of joint pain, stiffness and physical function were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), overall pain severity and interference with the BPI-SF and quality of life (QOL) with the Functional Assessment of Cancer Therapy-General (FACT-G) instrument. Hand strength was assessed by a grip test, and a serum marker of inflammation (C reactive protein (CRP)) was also measured. All assessments were performed at baseline, 6 weeks and 12 weeks, except for blood samples at baseline and 6 weeks only. Results No serious adverse events were reported during or after acupuncture treatments. There were no significant differences in outcome measures. However, positive trends were observed in stiffness and physical function at week 12 in favour of real EA. Conclusions Findings suggest that acupuncture is feasible and safe in patients with breast cancer with joint pain caused by AI. A larger study with adequately powered to confirm these results and detect clinically relevant effects is needed.

Sepsis is a syndromic illness that has traditionally been defined by a set of broad, highly sensitive clinical parameters. As a result, numerous distinct pathophysiologic states may meet diagnostic criteria for sepsis, leading to syndrome heterogeneity. The existence of biologically distinct sepsis subtypes may in part explain the lack of actionable evidence from clinical trials of sepsis therapies. We used microarray-based gene expression data from adult patients with sepsis in order to identify molecularly distinct sepsis subtypes.We used partitioning around medoids (PAM) and hierarchical clustering of gene expression profiles from neutrophils taken from a cohort of septic patients in order to identify distinct subtypes. Using the medoids learned from this cohort, we then clustered a second independent cohort of septic patients, and used the resulting class labels to evaluate differences in clinical parameters, as well as the expression of relevant pharmacogenes.We identified two sepsis subtypes based on gene expression patterns. Subtype 1 was characterized by increased expression of genes involved in inflammatory and Toll receptor mediated signaling pathways, as well as a higher prevalence of severe sepsis. There were differences between subtypes in the expression of pharmacogenes related to hydrocortisone, vasopressin, norepinephrine, and drotrecogin alpha.Sepsis subtypes can be identified based on different gene expression patterns. These patterns may generate hypotheses about the underlying pathophysiology of sepsis and suggest new ways of classifying septic patients both in clinical practice, and in the design of clinical trials.

Patients admitted to an Intensive Care Unit (ICU) frequently have underlying cardiac dysfunction. Early interventions are sometimes difficult to initiate because of diagnostic uncertainty as to whether cardiac failure is present As B-type natriuretic peptide (BNP) has been shown to be increased in cardiac dysfunction, we sought to demonstrate whether BNP can be used as a screening tool for cardiac dysfunction in patients admitted to ICU. All patients admitted to a combined medical and surgical ICU over a four-week period were included in the study. BNP was measured on the point of admission using a hand-held meter. Clinicians were blinded from the measurement when diagnoses were made as to whether or not the patients had clinically significant cardiac dysfunction. Patients with cardiac dysfunction had a significantly higher level of BNP when compared to the non-cardiac dysfunction group: 516±385 pg/ml (n = 26) v 67±89 pg/ml (n=58) (P< 0.0001) A BNP cut-off value at 144 pg/ml exhibited a 92% sensitivity, 86% specificity and 96% negative predictive value. The sensitivity improved to 96% when the analysis was confined to patients ≥ 55 years. At this cut-off value, BNP is a strong predictor of cardiac dysfunction. BNP measurement offers a rapid and affordable way to screen for cardiac dysfunction in patients admitted to ICU. An increased BNP level warrants further cardiac investigations so as to implement early interventions for cardiac decompensation in ICU patients.

Introduction Acute heart failure (AHF) is characterized by inadequate cardiac output (CO), congestive symptoms, poor peripheral perfusion and end-organ dysfunction. Treatment often includes a combination of diuretics, oxygen, positive pressure ventilation, inotropes and vasodilators or vasopressors. Lactate is a marker of illness severity but is also an important metabolic substrate for the myocardium at rest and during stress. We tested the effects of half-molar sodium lactate infusion on cardiac performance in AHF. Methods We conducted a prospective, randomised, controlled, open-label, pilot clinical trial in 40 patients fulfilling two of the following three criteria for AHF: (1) left ventricular ejection fraction

We evaluated the accuracy of cardiac output estimations by three transthoracic echocardiographic techniques in critically ill subjects. This study was a prospective comparison study carried out in a general intensive care unit of a teaching hospital. The subjects had a broad range of diagnoses including pulmonary embolus, cardiogenic shock, septic shock, Legionnaire's disease and perioperative myocardial infarction. All patients requiring pulmonary artery catheterization underwent echocardiographic cardiac assessment with comparison of findings to those obtained by thermodilution techniques. Nineteen studies on eighteen patients were performed, with cardiac output calculated by the two-chamber Simpson's, four-chamber Simpson's, and left ventricular outflow tract (LVOT) Doppler methods. Acceptable data was obtained in those patients without mitral regurgitation. There was good correlation between the thermodilution technique and Simpson's two-chamber method (r=0.91), but less so with the Simpson's four-chamber method (r=0.77). All studies were included in the LVOT Doppler method with a good correlation (r=0.94). A plot of differences between methods using the Bland and Altman statistical method indicated that only the LVOT Doppler method demonstrated acceptable agreement with a mean of 0.2 litres/minute, standard deviation of 0.82 litres/minute and 95% limits of agreement of –1.5 to +1.9 litres/minute.We concluded that the LVOT Doppler method was the only one which demonstrated acceptable agreement between the thermodilution method and echocardiographic techniques in all critically ill patients studied.

Echocardiography is fast becoming the technique of choice for noninvasive evaluation of left ventricular function in the critically ill patient. Current technology allows for assessment of overall left ventricular performance and for diastolic and systolic function. Doppler technology has greatly enhanced the diagnostic capability of two-dimensional echocardiography. The critical care physician should be aware not only of currently available techniques, but also those which will be used in the routine care of the critically ill subject in the foreseeable future.

The standard 0.5 to 1.0 mg dose of adrenaline used in cardiac resuscitation may be inadequate on the basis of theoretical and experimental evidence. Well designed clinical trials are indicated to test the hypothesis that higher doses of adrenaline could be more effective in specific subgroups of people experiencing cardiac arrest. The success in resuscitation is related to the aortic diastolic pressure and the effectiveness of adrenaline relates to its peripheral vasopressor effect. Other catecholamines such as noradrenaline may be more efficacious, as could be non-adrenergic vasopressors. Clinical studies are required, however, to evaluate these potential alternatives.

Background Critical illness causes a shift away from mitochondrial metabolism towards a greater dependence on glycolysis. This metabolic shift is thought to be associated with lactic acidosis, organ dysfunction and poor clinical outcomes. The current paradigm is that low oxygen supply causes regional hypoxia, which in turn drives such a metabolic shift. In this study, we evaluated whether the shift towards glycolysis can also occur in cells where oxygen supply is plentiful. Methods We used circulating blood cells from non-hypoxic critically ill patients (n = 47) as a model to study cellular metabolism in a normal oxygen milieu. We measured the transcriptomic profiles of canonical metabolic pathways in these cells and compared them to cells obtained from healthy controls (n = 18). Results Transcriptomic profiling revealed a significant reprogramming of metabolic pathways during critical illness. In well-oxygenated cells, there was a reduced expression of tricarboxylic acid cycle genes and genes associated with pyruvate entry into the mitochondria suggesting decreased mitochondrial oxidation. In contrast, glycolysis was accelerated, as reflected by an up-regulation of genes coding for enzymes of early and late glycolytic pathway that were associated with increased lactate production. The pentose phosphate pathway genes for NADPH production were also up-regulated suggesting enhanced antioxidant production during increased oxidative stress. Conclusions Contrary to the established paradigm, aerobic glycolysis does occur in non-hypoxic cells during critical illness and its occurrence may represent an adaptive strategy common to cells under increased oxidative stress. Further study of this previously under-recognized metabolic phenomenon might identify novel drug target for antioxidant therapy. Electronic supplementary material The online version of this article (doi:10.1186/s40635-016-0094-1) contains supplementary material, which is available to authorized users.