The Role of Transcriptomics in Redefining Critical Illness.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at  https://www.biomedcentral.com/collections/annualupdate2023 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 .

The Sequential Organ Failure Assessment (SOFA) Score: has the time come for an update?

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.

Redefining critical illness.

Research and practice in critical care medicine have long been defined by syndromes, which, despite being clinically recognizable entities, are, in fact, loose amalgams of heterogeneous states that may respond differently to therapy. Mounting translational evidence-supported by research on respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-suggests that the current syndrome-based framework of critical illness should be reconsidered. Here 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 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 critical care research, leading to a richer understanding of the pathobiology of critical illness and of the key determinants of patient outcomes. This, in turn, will support the design of more effective clinical trials and inform a more precise and more effective practice at the bedside.

Echocardiography findings in COVID-19 patients admitted to intensive care units: a multi-national observational study (the ECHO-COVID study).

PURPOSE: Severely ill patients affected by coronavirus disease 2019 (COVID-19) develop circulatory failure. We aimed to report patterns of left and right ventricular dysfunction in the first echocardiography following admission to intensive care unit (ICU). METHODS: Retrospective, descriptive study that collected echocardiographic and clinical information from severely ill COVID-19 patients admitted to 14 ICUs in 8 countries. Patients admitted to ICU who received at least one echocardiography between 1st February 2020 and 30th June 2021 were included. Clinical and echocardiographic data were uploaded using a secured web-based electronic database (REDCap). RESULTS: Six hundred and seventy-seven patients were included and the first echo was performed 2 [1, 4] days after ICU admission. The median age was 65 [56, 73] years, and 71% were male. Left ventricle (LV) and/or right ventricle (RV) systolic dysfunction were found in 234 (34.5%) patients. 149 (22%) patients had LV systolic dysfunction (with or without RV dysfunction) without LV dilatation and no elevation in filling pressure. 152 (22.5%) had RV systolic dysfunction. In 517 patients with information on both paradoxical septal motion and quantitative RV size, 90 (17.4%) had acute cor pulmonale (ACP). ACP was associated with mechanical ventilation (OR > 4), pulmonary embolism (OR > 5) and increased PaCO2. Exploratory analyses showed that patients with ACP and older age were more likely to die in hospital (including ICU). CONCLUSION: Almost one-third of this cohort of critically ill COVID-19 patients exhibited abnormal LV and/or RV systolic function in their first echocardiography assessment. While LV systolic dysfunction appears similar to septic cardiomyopathy, RV systolic dysfunction was related to pressure overload due to positive pressure ventilation, hypercapnia and pulmonary embolism. ACP and age seemed to be associated with mortality in this cohort.

The Role of Mitochondria in the Immune Response in Critical Illness.

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 .

Blood transcriptome analysis of patients with uncomplicated bacterial infection and sepsis.

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.

Basic echocardiography competence program in intensive care units: A multinational survey of intensive care units accredited by the College of Intensive Care Medicine.

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.

Echocardiographic assessment of left ventricular diastolic pressure.

PURPOSE OF REVIEW: Knowledge of the left ventricular pressures throughout the cardiac cycle is of considerable assistance in managing a haemodynamically unstable patient. Invasive pressure measurement is the only accurate way to analyze ventricular diastolic pressures but this is not feasible outside the catheterization laboratory, whereas the use of a pulmonary artery catheter or Doppler echocardiography, using surrogate measurements, is available at the bedside. The ever-increasing trend toward noninvasive monitoring puts echocardiography at the forefront and considerable effort has been made to define its role in this setting. RECENT FINDINGS: Ongoing refinement of guidelines used to evaluate left ventricular diastolic function have provided a pathway for critical care physicians to better understand how to evaluate left ventricular end-diastolic pressure and/or left atrial pressures. A number of recent studies have investigated the accuracy of combined or single echocardiographic parameters in determining left ventricular diastolic pressures as compared to those obtained invasively. Specifically selected combined parameters have moderate accuracy. SUMMARY: The recent literature on the clinical application of echocardiography on the accuracy in determining left ventricular noninvasively demonstrates that although far from perfect, it can be a very useful tool.

Calibrated cardiac output monitoring versus standard care for fluid management in the shocked ICU patient: a pilot randomised controlled trial.

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.

The comparative effects of 3% saline and 0.5M sodium lactate on cardiac function:a randomised, crossover study in volunteers.

OBJECTIVE: To investigate the metabolic and cardiac effects of intravenous administration of two hypertonic solutions - 3% saline (SAL) and 0.5M sodium lactate (LAC). DESIGN, SETTING AND PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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; P < 0.01) and simplified strong ion difference (SID) (36.3 ± 4.6 mmol/L to 39.2 ± 3.6 mmol/L; P < 0.01) 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). CONCLUSIONS: 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.

The use of echocardiographic indices in defining and assessing right ventricular systolic function in critical care research.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A novel sampling method to detect airborne influenza and other respiratory viruses in mechanically ventilated patients: a feasibility study.

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.

Application of updated guidelines on diastolic dysfunction in patients with severe sepsis and septic shock.

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 < 52%) systolic function had their diastolic function stratified according to both the 2009 ASE and 2016 ASE/EACVI guidelines. RESULTS: On day 1 echocardiography, of the 62 patients analysed, 37 (60%) had diastolic dysfunction according to the 2016 ASE/EACVI guideline with a further 23% having indeterminate diastolic function, compared to the 2009 ASE guidelines where only 13 (21%) had confirmed diastolic dysfunction with 46 (74%) having indeterminate diastolic dysfunction. On day 3, of the 55 patients studied, 22 patients (40%) were defined as having diastolic dysfunction, with 6 (11%) having indeterminate diastolic dysfunction according to the 2016 ASE/EACVI guidelines, compared to the 2009 guidelines where 11 (20%) were confirmed to have diastolic dysfunction and 41 (75%) had indeterminate diastolic function. Systolic dysfunction was identified in 18 of 62 patients (29%) on day 1 and 18 of 55 (33%) on day 3. These patients were classified as having abnormal diastolic function in 94 and 89% with the 2016 guidelines on day 1 and day 3, respectively, compared with 50 and 28% using the 2009 guidelines. The 2016 guidelines had less patients with indeterminate diastolic function on days 1 and 3 (11 and 6%) compared to the 2009 guidelines (50 and 72%). Normal systolic function was identified in 44 patients on day 1 and 37 on day 3. In this group, abnormal diastolic function was present in 45 and 54% on days 1 and 3 according to the 2016 ASE/EACVI guidelines, compared with 9 and 16% using the 2009 guidelines, respectively. In those with normal systolic function, the 2016 guidelines had less indeterminate patients with 30 and 16% on days 1 and 3, respectively, compared to 84 and 76% in the 2009 guidelines. CONCLUSION: The 2016 ASE/EACVI diastolic function guidelines identify a significantly higher incidence of dysfunction in patients with severe sepsis and septic shock compared to the previous 2009 guidelines. Although the new guidelines seem to be an improvement, issues remain with the application of guidelines using traditional measures of diastolic dysfunction in this cohort.

Longitudinal wall fractional shortening: an M-mode index based on mitral annular plane systolic excursion (MAPSE) that correlates and predicts left ventricular longitudinal strain (LVLS) in intensive care patients.

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 < 0.001). Intra- and inter-rater agreement and reliability for LWFS measurement were good. CONCLUSIONS: LVLS can be estimated by LWFS in the critically ill patients. It provides a fast and accurate prediction of LVLS. LWFS is a reproducible and reliable measurement which can be used as a potential index in place of LVLS in the critically ill population.

Basic critical care echocardiography: How many studies equate to competence? A pilot study using high fidelity echocardiography simulation.

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.