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Both research and practice in critical care medicine have long been defined by syndromes. Though clinically recognizable entities, these are in fact loose amalgams of heterogeneous states, within which responses to therapy may vary. Mounting translational evidence suggests the current syndrome-based framework of critical illness should be reconsidered. Moreover, research done during the COVID-19 pandemic illustrates how the study of a more biologically homogeneous condition – respiratory failure due to SARS-CoV-2 infection – can increase the efficiency with which actionable results are generated. We discuss recent findings from basic science and clinical research in critical care, and explore how these might inform a new conceptual model of critical illness. De-emphasizing syndromes, we focus instead on the underlying biological changes that underpin critical illness states, and that may be amenable to treatment. We hypothesize that such an approach will accelerate translational critical care research, leading to a richer understanding of the pathobiology of critical illness, and of the proximate determinants of ICU outcomes. The specificity and granularity gained will support the design of more effective clinical trials, and inform a more precise, effective practice at the bedside.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2022. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2022 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

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.

BackgroundRobust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness.MethodsWe conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients.FindingsWe show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression is associated with the presence of a high viral load. We further demonstrate that systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 severity. For clinical outcome prediction (e.g. respiratory failure), IFI27 expression displays a high positive (0.83) and negative (0.95) predictive value, outperforming all other known predictors of COVID-19 severity. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 swine influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients.InterpretationThese data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.Research in contextEvidence before this studyWe searched the scientific literature using PubMed to identify studies that used the IFI27 biomarker to predict outcomes in COVID-19 patients. We used the search terms “IFI27”, “COVID-19, “gene expression” and “outcome prediction”. We did not identify any study that investigated the role of IFI27 biomarker in outcome prediction. Although ten studies were identified using the general terms of “gene expression” and “COVID-19”, IFI27 was only mentioned in passing as one of the identified genes. All these studies addressed the broader question of the host response to COVID-19; none focused solely on using IFI27 to improve the risk stratification of infected patients in a pandemic.Added value of this studyHere, we present the findings of a multi-cohort study of the IFI27 biomarker in COVID-19 patients. Our findings show that the host response, as reflected by blood IFI27 gene expression, accurately predicts COVID-19 disease progression (positive and negative predictive values; 0.83 and 0.95, respectively), outperforming age, comorbidity, C-reactive protein and all other known risk factors. The strong association of IFI27 with disease severity occurs not only in SARS-CoV-2 infection, but also in other respiratory viruses with pandemic potential, such as the influenza virus. These findings suggest that host response biomarkers, such as IFI27, could help identify high-risk COVID-19 patients - those who are more likely to develop infection complications - and therefore may help improve patient triage in a pandemic.Implications of all the available evidenceThis is the first systemic study of the clinical role of IFI27 in the current COVID-19 pandemic and its possible future application in other respiratory virus pandemics. The findings not only could help improve the current management of COVID-19 patients but may also improve future pandemic preparedness.

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.

PurposeDysregulated immune response is a key driver of disease progression in sepsis and known to be associated with impaired cellular metabolism. This association has been studied mostly in the late stage sepsis patients. Here, we investigate whether such impairment in cellular metabolism is present in uncomplicated infection patients who do not develop sepsis.MethodsForty sepsis (fulfilled Sepsis-3 criteria) and 27 uncomplicated infection patients were recruited from the emergency department along with 20 healthy volunteers. Whole blood was collected for measurement of gene expression, cytokine levels and cellular metabolic functions (including mitochondrial respiration, oxidative stress and apoptosis).ResultsOur analysis revealed the impairment of mitochondrial respiration in uncomplicated infection and sepsis patients (p value ConclusionsThese findings suggest that impaired immune cell metabolism is present in infection patients without presenting sepsis, thereby opening potential window for early diagnosis and intervention (e.g. antioxidant therapy) in such patients.

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 Influenza infections produce a spectrum of disease severity, ranging from a mild respiratory illness to respiratory failure and death. The host-response pathways associated with the progression to severe influenza disease are not well understood. Methods To gain insight into the disease mechanisms associated with progression to severe infection, we analyzed the leukocyte transcriptome in severe and moderate influenza patients and healthy control subjects. Pathway analysis on differentially expressed genes was performed using a topology-based pathway analysis tool that takes into account the interaction between multiple cellular pathways. The pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza. Results 107 patients (44 severe and 63 moderate influenza patients) and 52 healthy control subjects were included in the study. Severe influenza was associated with upregulation in several neutrophil-related pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (NET) formation. The degree of upregulation in neutrophil-related pathways were significantly higher in severely infected patients compared to moderately infected patients. Severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation such as CD4+ T-cell co-stimulation, CD8+ T cell and Natural Killer (NK) cells effector functions. Apoptosis pathways were also downregulated in severe influenza patients compare to moderate and healthy controls. Conclusions These findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection.

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.

Supplemental Digital Content is available in the text., Objectives: To examine the association between premorbid metformin exposure and mortality, hyperlactatemia, and organ dysfunction in sepsis. Data Sources: PubMed and EMBASE (with Medline via Ovid) databases were searched for all studies of premorbid metformin exposure and sepsis published between January 1974 and August 2018. Study Selection: Studies of at least 20 patients with sepsis that reported data on metformin use, mortality, and/or organ dysfunction were independently selected. Data Extraction: Two reviewers abstracted data on study design, settings, study quality, participants, metformin exposure, mortality, initial lactate levels, and organ dysfunction. Risk of bias was independently assessed. Data Synthesis: Eight observational studies fulfilled our criteria, comprising 4,144 patients with sepsis including 562 diabetics on metformin. Premorbid metformin exposure was associated with reduced mortality in sepsis (odds ratio, 0.57; 95% CI, 0.40–0.80). Between studies heterogeneity was low (i2 = 43%; τ2 = 0.1; p = 0.09). Premorbid metformin exposure was not significantly associated with initial lactate levels (mean difference, 0.39 [–0.50 to 1.28]; i2 = 72%; p = 0.39). Conclusions: The meta-analysis suggests that premorbid metformin exposure is associated with decreased mortality in sepsis but not with hyperlactatemia. What are the potential mechanisms and whether there is any effect on organ dysfunction remain unclear.

Influenza viruses are among the most common causes of human respiratory infection, causing high morbidity and mortality. In the United States, influenza results in approximately 200,000 hospitalizations and 36,000 deaths during a seasonal epidemic [1]. During a pandemic, up to 50% of the population can be infected by influenza, increasing the number of deaths [2]. In 1918, the worst influenza pandemic recorded in history caused up to 50 million deaths worldwide, with elderly, infants, and people with underlying illness having the highest risk of fatality [3].

This article was migrated. The article was not marked as recommended. Introduction: AustralianResidents (Junior Doctors) identified their clinical experience for acute clinical episodes as insufficient. Absence of clinical assessments during their critical care experience, within their medical degree, was thought to be a reason. The 'deliberate practice' model was used to explore medical student learning, during the Critical Care Medicine Rotation (CCMR) at Sydney Medical School, Nepean. Method: The interpretative-constructive theoretical study utilized theory, practical (simulation/clinical) standardized assessments and focus groups. Focus group questions directed student exploration of their learning during the rotation, and use of an assessment of basic airway management skills. The mixed method study design was conducted over 18 months (Jan 2014-May 2015), 96% (46) of possible cohort (27 male,19 female) enrolled during their clinical years. The 'Biggs' Model of 'knowledge' was used to understand student declarative, procedural and conditional knowledge. Results: Analysis of pre/post declarative knowledge n=37(80%) demonstrated a significant p value < 0.00001. From within the total cohort, n=12(26%) students were assessed for both procedural and conditional knowledge. This change was not significant at p ≤ 0.05. In this complex clinical environment, knowledge did not automatically translate directly into practical skill attainment. Students (focus groups n=36(78%))identified the model of 'deliberate practice' effective, indicated a desire for more simulations and clinical experience, clear faculty direction for required learning activities and valued peer support. Discussion: Application of 'deliberate practice' model in the CCMR was effective. The pre-and-post assessments provided students the knowledge their own skill level and was effective in encouraging individual skill development. It highlighted a need to review other aspects of critical care clinical skills education. A follow up study, examining the role of peer/near peer assessment in this area has been conducted, with studies in different complex clinical environments, examining workplace learning contrasted with simulation, in post graduate trainees, a new area of research.

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

BACKGROUND: Pre‐eclampsia is a disease of pregnancy characterised by the manifestations of multi‐organ dysfunction. The recent use of transthoracic echocardiography in the assessment of women with pre‐eclampsia has allowed the detection of cardiac systolic and diastolic dysfunction in the acute phase. Women with a history of pre‐eclampsia also have increased lifelong risks of cardiovascular disease and mortality that persists well beyond the post‐partum period. These developments raise the possibility that pre‐eclampsia may be an early marker of cardiovascular disease and the potential role for echocardiography in guiding the detection and management of this. This review aims to summarise the existing evidence of echocardiographic cardiac assessment of women with a history of pre‐eclampsia performed more than 12 weeks post‐partum. METHODS: A systematic search of PubMed and OVID EMBASE databases was performed to identify studies featuring assessment of cardiac function performed after 12 weeks post‐partum in women with a history of pre‐eclampsia. Studies without post‐partum cardiac assessment or with other documented causes for cardiomyopathy were excluded. RESULTS: Thirteen studies were identified that measured cardiac function by transthoracic echocardiography between 6 months and 18 years following a pregnancy complicated by pre‐eclampsia. Common findings across the studies were of increased diastolic dysfunction, increased left ventricular mass index (LVMI) and concentric hypertrophy in women with a history of pre‐eclampsia, as compared to women with uncomplicated pregnancy histories. This was predominantly seen in those with a history of early or preterm pre‐eclampsia. CONCLUSIONS: Women with a history of early or preterm pre‐eclampsia have an increased prevalence of diastolic dysfunction. This review demonstrates that the cardiac dysfunction associated with previous pre‐eclampsia is quantifiable and persistent. Progression of heart failure from asymptomatic to symptomatic stages carries a fivefold increase in mortality. The use of echocardiography could detect cardiac dysfunction in the asymptomatic stage and guide more intensive risk factor modification in these women.

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

To investigate the metabolic and cardiac effects of intravenous administration of two hypertonic solutions - 3% saline (SAL) and 0.5M sodium lactate (LAC).A randomised, doubleblind, crossover study in ten human volunteers. Intravenous bolus of either SAL or LAC at 3 mL/kg over 20 min followed by a 2 mL/kg infusion over 60 min.Acid base parameters and echocardiographic indices of cardiac function, cardiac output (CO), left ventricular ejection fraction (LVEF) and mitral annular peak systolic velocity (Sm) before and after infusion of SAL or LAC.Despite haemodilution, we observed an increase in sodium (139 ± 2 mmol/L to 142 ± 2 mmol/L in both groups) and respective anions, chloride (106 ± 2 mmol/L to 112 ± 3 mmol/L) and lactate (1.01 ± 0.28 mmol/L to 2.38 ± 0.38 mmol/L) with SAL and LAC, respectively. The pH (7.37 ± 0.03 to 7.45 ± 0.03; P0.01) and simplified strong ion difference (SID) (36.3 ± 4.6 mmol/L to 39.2 ± 3.6 mmol/L; P0.01) increased during the LAC infusion. The pH was unchanged, but SID decreased during SAL infusion (36.3 ± 2.5 mmol/L to 33.9 ± 3.1 mmol/L; P = 0.01). Both solutions led to an increase in preload and cardiac function, CO (4.36 ± 0.79 L/min to 4.98 ± 1.37 L/ min v 4.62 ± 1.30 L/min to 5.13 ± 1.44 L/min), LVEF (61 ± 6% to 63 ± 8% v 64 ± 6% to 68 ± 7%). The averaged Sm improved in the LAC group as compared with the SAL group (0.088 ± 0.008 to 0.096 ± 0.016 v 0.086 ± 0.012 to 0.082 ± 0.012; P = 0.032).The administration of SAL or LAC has opposing effects on acid base variables such as SID. Hypertonic fluid infusion lead to increased cardiac preload and performance with Sm, suggesting better left ventricular systolic function during LAC as compared with SAL. Lactated hypertonic solutions should be evaluated as resuscitation fluids.

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.

The gradual integration of echocardiography with other noninvasive imaging techniques continues to progress, giving the practicing critical care clinician increasing diagnostic capability. Such capability can be divided into four main areas – coronary artery disease, myocardial pathology, valvular disease, and cardiac function. Coronary artery disease The presence of segmental wall defects on echocardiography alerts the clinician as to a high likelihood of underlying epicardial coronary artery disease (CAD). At the bedside the use of echocardiographic myocardial perfusion techniques can often further differentiate between ischaemic and nonischaemic aetiologies. Coronary computerized Tomographic Angiography (CCTA) over the last decade has moved from being a guide to the presence of CAD, to now offering accurate anatomical assessment, often being used as a first line diagnostic tool.The addition of Fractional Flow Reserve (FFR-CT) now adds a functional assessment of perfusion, reaching an accuracy of that obtained with invasive coronary angiography FFR studies.A noninvasive nuclear medicine alternative is SPECT or Single Photon Emission Computed Tomography which also has high diagnostic capability. Myocardial Pathology When abnormal myocardial appearances are found with echocardiography, it is difficult to be certain of the underlying pathology and historically a myocardial biopsy is considered when seeking to identify presumed inflammatory changes of unknown aetiology. The advent of Cardiac Magnetic Resonance (CMR) assists the physician in the differential diagnosis. The judicious use of T1 mapping, T2 mapping and gadolinium helps differentiate between fibrosis,inflammation and oedema. Valve pathology Although echocardiography remains the major modality is assessing valve function in the critically ill patient, CMR can improve evaluation with prosthetic valves. Myocardial function Echocardiography using Strain have enhance our ability to assess myocardial function. Positron Emission Tomography (PET) using isotopic-labelled substrates offers opportunities to exam metabolic function in the myocardium.It can determine glucose and fatty acid uptake in addition to targeting the mitochondria and angiogenesis. Although challenges arise in the need for a patient to be transferred, information gained may outweigh the risks in some patients. The sophistication of echocardiographic techniques continues to evolve but the wise physician will be cognizant of other noninvasive imaging modalities in an effort to further optimize patient management.

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.

Supplemental Digital Content is available in the text., Objectives: We performed a meta-analysis to assess whether the newly introduced quick Sequential Organ Failure Assessment score could predict sepsis outcomes and compared its performance to systematic inflammatory response syndrome, the previously widely used screening criteria for sepsis. Data Sources: We searched multiple electronic databases including MEDLINE, the Cochrane Library, Embase, Web of Science, and Google Scholar (up to March 1, 2019) that evaluated quick Sequential Organ Failure Assessment score, systemic inflammatory response syndrome, or both (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42018103327). Study Selection: Studies were included if the outcome was mortality, organ dysfunction, admission to ICU, ventilatory support, or prolonged ICU stay and if prediction performance was reported as either area under the curve, odds ratio, sensitivity, or specificity. Data Extraction: The criterion validity of the quick Sequential Organ Failure Assessment score and systemic inflammatory response syndrome criteria were assessed by measuring its predictive validity for primary (mortality) and secondary outcomes in pooled metrics as mentioned. The data were analyzed using random effects model, and heterogeneity was explored using prespecified subgroups analyses. Data Synthesis: We screened 1,340 studies, of which 121 studies (including data for 1,716,017 individuals) were analyzed. For mortality prediction, the pooled area under the curve was higher for quick Sequential Organ Failure Assessment score (0.702; 95% CI, 0.685–0.718; I2 = 99.41%; p < 0.001) than for systemic inflammatory response syndrome (0.607; 95% CI, 0.589–0.624; I2 = 96.49%; p < 0.001). Quick Sequential Organ Failure Assessment score consistently outperformed systemic inflammatory response syndrome across all subgroup analyses (area under the curve of quick Sequential Organ Failure Assessment vs. area under the curve of systemic inflammatory response syndrome p < 0.001), including patient populations (emergency department vs ICU), study design (retrospective vs prospective), and countries (developed vs resource-limited). Quick Sequential Organ Failure Assessment score was more specific (specificity, 74.58%; 95% CI, 73.55–75.61%) than systemic inflammatory response syndrome (specificity, 35.24%; 95% CI, 22.80–47.69%) but less sensitive (56.39%; 95% CI, 50.52–62.27%) than systemic inflammatory response syndrome (78.84%; 95% CI, 74.48–83.19%). Conclusions: Overall, quick Sequential Organ Failure Assessment score outperforms systemic inflammatory response syndrome in predicting sepsis outcome, but quick Sequential Organ Failure Assessment score has relative strengths/weaknesses (more specific but less sensitive) compared with systemic inflammatory response syndrome.

The use of ultrasound has moved to centre stage in the management of haemodynamically unstable patient. The ability to apply rapidly, the mobility of devices, and bedside delivery are amongst the advantages in using it. In particular, the widespread application of echocardiography has greatly changed the way in which shocked patients are diagnosed and treated. Most importantly is the ability for the clinician to rapidly identify the type of underlying shock, identify pathophysiology that requires immediate treatment and then to clearly outline the need for further imaging or other diagnostic tests. The great majority of patients fall into either one of the following four shock categories, or not infrequently, experience a combination of these. The physician dealing with critically ill patients may have only attained skills in basic echocardiography such as with performing RACE (Rapid Assessment by Cardiac Echo) which is generally adequate in many patients. However an increasing number of clinicians now have advanced skills using a combination of Doppler techniques in addition to newer techniques such as strain or 3 D. These skills add to the diagnostic repertoire. The chart below is a guide to the evaluation in determining the type of shock in a deteriorating patient.

There is currently no reliable tool available to measure immune dysfunction in septic patients in the clinical setting. This proof-of-concept study assesses the potential of gene expression profiling of whole blood as a tool to monitor immune dysfunction in critically ill septic patients. Whole-blood samples were collected daily for up to 5 days from patients admitted to the intensive care unit with sepsis. RNA isolated from whole-blood samples was assayed on Illumina HT-12 gene expression microarrays consisting of 48,804 probes. Microarray analysis identified 3,677 genes as differentially expressed across 5 days between septic patients and healthy controls. Of the 3,677 genes, biological pathway analysis identified 86 genes significantly downregulated in the sepsis patients were present in pathways relating to immune response. These 86 genes correspond to known immune pathways implicated in sepsis, including lymphocyte depletion, reduced T-lymphocyte activation, and deficient antigen presentation. Furthermore, expression levels of these genes correlated with clinical severity, with a significantly greater degree of downregulation found in nonsurvivors compared with survivors. The results show that whole-blood gene expression analysis can capture systemic immune dysfunctions in septic patients. Our study provides an experimental basis to support further study on the use of a gene expression-based assay, to assess immunosuppression, and to guide immunotherapy in future clinical trials.