Consistency of data reporting in fluid responsiveness studies in the critically ill setting: the CODEFIRE consensus from the Cardiovascular Dynamic section of the European Society of Intensive Care Medicine.

PURPOSE: To provide consensus recommendations regarding hemodynamic data reporting in studies investigating fluid responsiveness and fluid challenge (FC) use in the intensive care unit (ICU). METHODS: The Executive Committee of the European Society of Intensive Care Medicine (ESICM) commissioned and supervised the project. A panel of 18 international experts and a methodologist identified main domains and items from a systematic literature, plus 2 ancillary domains. A three-step Delphi process based on an iterative approach was used to obtain the final consensus. In the Delphi 1 and 2, the items were selected with strong (≥ 80% of votes) or week agreement (70-80% of votes), while the Delphi 3 generated recommended (≥ 90% of votes) or suggested (80-90% of votes) items (RI and SI, respectively). RESULTS: We identified 5 main domains initially including 117 items and the consensus finally resulted in 52 recommendations or suggestions: 18 RIs and 2 SIs statements were obtained for the domain "ICU admission", 11 RIs and 1 SI for the domain "mechanical ventilation", 5 RIs for the domain "reason for giving a FC", 8 RIs for the domain pre- and post-FC "hemodynamic data", and 7 RIs for the domain "pre-FC infused drugs". We had no consensus on the use of echocardiography, strong agreement regarding the volume (4 ml/kg) and the reference variable (cardiac output), while weak on administration rate (within 10 min) of FC in this setting. CONCLUSION: This consensus found 5 main domains and provided 52 recommendations for data reporting in studies investigating fluid responsiveness in ICU patients.

Effects of closed loop ventilation on ventilator settings, patient outcomes and ICU staff workloads - a systematic review.

BACKGROUND: Lung protective ventilation is considered standard of care in the intensive care unit. However, modifying the ventilator settings can be challenging and is time consuming. Closed loop modes of ventilation are increasingly attractive for use in critically ill patients. With closed loop ventilation, settings that are typically managed by the ICU professionals are under control of the ventilator's algorithms. OBJECTIVES: To describe the effectiveness, safety, efficacy and workload with currently available closed loop ventilation modes. DESIGN: Systematic review of randomised clinical trials. DATA SOURCES: A comprehensive systematic search in PubMed, Embase and the Cochrane Central register of Controlled Trials search was performed in January 2023. ELIGIBILITY CRITERIA: Randomised clinical trials that compared closed loop ventilation with conventional ventilation modes and reported on effectiveness, safety, efficacy or workload. RESULTS: The search identified 51 studies that met the inclusion criteria. Closed loop ventilation, when compared with conventional ventilation, demonstrates enhanced management of crucial ventilator variables and parameters essential for lung protection across diverse patient cohorts. Adverse events were seldom reported. Several studies indicate potential improvements in patient outcomes with closed loop ventilation; however, it is worth noting that these studies might have been underpowered to conclusively demonstrate such benefits. Closed loop ventilation resulted in a reduction of various aspects associated with the workload of ICU professionals but there have been no studies that studied workload in sufficient detail. CONCLUSIONS: Closed loop ventilation modes are at least as effective in choosing correct ventilator settings as ventilation performed by ICU professionals and have the potential to reduce the workload related to ventilation. Nevertheless, there is a lack of sufficient research to comprehensively assess the overall impact of these modes on patient outcomes, and on the workload of ICU staff.

Association between left ventricular systolic function parameters and myocardial injury, organ failure and mortality in patients with septic shock.

BACKGROUND: Left ventricular ejection fraction (LVEF) is inconsistently associated with poor outcomes in patients with sepsis. Newer parameters such as LV longitudinal strain (LVLS), mitral annular plane systolic excursion (MAPSE) and LV longitudinal wall fractional shortening (LV-LWFS) may be more sensitive indicators of LV dysfunction, but are sparsely investigated. Our objective was to evaluate the association between five traditional and novel echocardiographic parameters of LV systolic function (LVEF, peak tissue Doppler velocity at the mitral valve (s´), LVLS, MAPSE and LV-LWFS) and outcomes in patients admitted to the Intensive Care Unit (ICU) with septic shock. METHODS: A total of 152 patients admitted to the ICU with septic shock from two data repositories were included. Transthoracic echocardiograms were performed within 24 h of ICU admission. The primary outcome was myocardial injury, defined as high-sensitivity troponin T ≥ 45 ng/L on ICU admission. Secondary outcomes were organ support-free days (OSFD) and 30-day mortality. We also tested for the prognostic value of the systolic function parameters using multivariable analysis. RESULTS: LVLS, MAPSE and LV-LWFS, but not LVEF and s´, differed between patients with and without myocardial injury. After adjustment for age, pre-existing cardiac disease, Simplified Acute Physiology (SAPS3) score, Sequential Organ Failure Assessment (SOFA) score, plasma creatinine and presence of right ventricular dysfunction, only MAPSE and LV-LWFS were independently associated with myocardial injury. None of the systolic function parameters were associated with OSFD or 30-day mortality. CONCLUSIONS: MAPSE and LV-LWFS are independently associated with myocardial injury and outperform LVEF, s´ and LVLS. Whether these parameters are associated with clinical outcomes such as the need for organ support and short-term mortality is still unclear. Trial registration NCT01747187 and NCT04695119.

Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

BACKGROUND: Awake proning in spontaneously breathing patients with hypoxemic acute respiratory failure was applied during the coronavirus disease 2019 (COVID-19) pandemic to improve oxygenation while avoiding tracheal intubation. An updated systematic review and meta-analysis on the topic was published. METHODS: The Clinical practice committee (CPC) of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) assessed the clinical practice guideline "Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline" for possible endorsement. The Appraisal of Guidelines for REsearch and Evaluation (AGREE) II tool was used. RESULTS: Four out of six SSAI CPC members completed the appraisal. The individual domain totals were: Scope and Purpose 90%; Stakeholder Involvement 89%; Rigour of Development 74%; Clarity of Presentation 85%; Applicability 75%; Editorial Independence 98%; Overall Assessment 79%. CONCLUSION: The SSAI CPC endorses the clinical practice guideline "Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline". This guideline serves as a useful decision aid for clinicians caring for critically ill patients with COVID-19-related acute hypoxemic respiratory failure and can be used to provide guidance on use of prone positioning in this group of patients.

Mortality in patients with septic cardiomyopathy identified by longitudinal strain by speckle tracking echocardiography: An updated systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Septic cardiomyopathy is associated with poor outcomes but its definition remains unclear. In a previous meta-analysis, left ventricular (LV) longitudinal strain (LS) showed significant prognostic value in septic patients, but findings were not robust due to a limited number of studies, differences in effect size and no adjustment for confounders. METHODS: We conducted an updated systematic review (PubMed and Scopus up to 14.02.2023) and meta-analysis to investigate the association between LS and survival in septic patients. We included studies reporting global (from three apical views) or regional LS (one or two apical windows). A secondary analysis evaluated the association between LV ejection fraction (EF) and survival using data from the selected studies. RESULTS: We included fourteen studies (1678 patients, survival 69.6%) and demonstrated an association between better performance (more negative LS) and survival with a mean difference (MD) of -1.45%[-2.10, -0.80] (p < 0.0001;I2 = 42%). No subgroup differences were found stratifying studies according to number of views used to calculate LS (p = 0.31;I2 = 16%), severity of sepsis (p = 0.42;I2 = 0%), and sepsis criteria (p = 0.59;I2 = 0%). Trial sequential analysis and sensitivity analyses confirmed the primary findings. Grade of evidence was low. In the included studies, thirteen reported LVEF and we found an association between higher LVEF and survival (MD = 2.44% [0.44,4.45]; p = 0.02;I2 = 42%). CONCLUSIONS: We confirmed that more negative LS values are associated with higher survival in septic patients. The clinical relevance of this difference and whether the use of LS may improve understanding of septic cardiomyopathy and prognostication deserve further investigation. The association found between LVEF and survival is of unlikely clinical meaning. REGISTRATION: PROSPERO number CRD42023432354.

ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation

In recent years, there has been increasing focus on the use of cardiac biomarkers in patients undergoing noncardiac surgery. The aim of this focused guideline was to provide updated guidance regarding the pre-, post- and combined pre-and postoperative use of cardiac troponin and B-type natriuretic peptides in adult patients undergoing noncardiac surgery. The guidelines were prepared using Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. This included the definition of critical outcomes, a systematic literature search, appraisal of certainty of evidence, evaluation of biomarker measurement in terms of the balance of desirable and undesirable effects including clinical outcomes, resource use, health inequality, stakeholder acceptance, and implementation. The panel differentiated between three different scopes of applications: cardiac biomarkers as prognostic factors, as tools for risk prediction, and for biomarker-enhanced management strategies. In a modified Delphi process, the task force defined 12 critical outcomes. The systematic literature search resulted in over 25,000 hits, of which 115 full-text articles formed the body of evidence for recommendations. The evidence appraisal indicated heterogeneity in the certainty of evidence across critical outcomes. Further, there was relevant gradient in the certainty of evidence across the three scopes of application. Recommendations were issued and if this was not possible due to limited evidence, clinical practice statements were produced. The ESAIC focused guidelines provide guidance on the perioperative use of cardiac troponin and B-type natriuretic peptides in patients undergoing noncardiac surgery, for three different scopes of application.

Reliability of pulse pressure and stroke volume variation in assessing fluid responsiveness in the operating room: a metanalysis and a metaregression.

BACKGROUND: Pulse pressure and stroke volume variation (PPV and SVV) have been widely used in surgical patients as predictors of fluid challenge (FC) response. Several factors may affect the reliability of these indices in predicting fluid responsiveness, such as the position of the patient, the use of laparoscopy and the opening of the abdomen or the chest, combined FC characteristics, the tidal volume (Vt) and the type of anesthesia. METHODS: Systematic review and metanalysis of PPV and SVV use in surgical adult patients. The QUADAS-2 scale was used to assess the risk of bias of included studies. We adopted a metanalysis pooling of aggregate data from 5 subgroups of studies with random effects models using the common-effect inverse variance model. The area under the curve (AUC) of pooled receiving operating characteristics (ROC) curves was reported. A metaregression was performed using FC type, volume, and rate as independent variables. RESULTS: We selected 59 studies enrolling 2,947 patients, with a median of fluid responders of 55% (46-63). The pooled AUC for the PPV was 0.77 (0.73-0.80), with a mean threshold of 10.8 (10.6-11.0). The pooled AUC for the SVV was 0.76 (0.72-0.80), with a mean threshold of 12.1 (11.6-12.7); 19 studies (32.2%) reported the grey zone of PPV or SVV, with a median of 56% (40-62) and 57% (46-83) of patients included, respectively. In the different subgroups, the AUC and the best thresholds ranged from 0.69 and 0.81 and from 6.9 to 11.5% for the PPV, and from 0.73 to 0.79 and 9.9 to 10.8% for the SVV. A high Vt and the choice of colloids positively impacted on PPV performance, especially among patients with closed chest and abdomen, or in prone position. CONCLUSION: The overall performance of PPV and SVV in operating room in predicting fluid responsiveness is moderate, ranging close to an AUC of 0.80 only some subgroups of surgical patients. The grey zone of these dynamic indices is wide and should be carefully considered during the assessment of fluid responsiveness. A high Vt and the choice of colloids for the FC are factors potentially influencing PPV reliability. TRIAL REGISTRATION: PROSPERO (CRD42022379120), December 2022. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=379120.

Surviving Sepsis After Burn Campaign.

INTRODUCTION: The Surviving Sepsis Campaign was developed to improve outcomes for all patients with sepsis. Despite sepsis being the primary cause of death after thermal injury, burns have always been excluded from the Surviving Sepsis efforts. To improve sepsis outcomes in burn patients, an international group of burn experts developed the Surviving Sepsis After Burn Campaign (SSABC) as a testable guideline to improve burn sepsis outcomes. METHODS: The International Society for Burn Injuries (ISBI) reached out to regional or national burn organizations to recommend members to participate in the program. Two members of the ISBI developed specific "patient/population, intervention, comparison and outcome" (PICO) questions that paralleled the 2021 Surviving Sepsis Campaign [1]. SSABC participants were asked to search the current literature and rate its quality for each topic. At the Congress of the ISBI, in Guadalajara, Mexico, August 28, 2022, a majority of the participants met to create "statements" based on the literature. The "summary statements" were then sent to all members for comment with the hope of developing an 80% consensus. After four reviews, a consensus statement for each topic was created or "no consensus" was reported. RESULTS: The committee developed sixty statements within fourteen topics that provide guidance for the early treatment of sepsis in burn patients. These statements should be used to improve the care of sepsis in burn patients. The statements should not be considered as "static" comments but should rather be used as guidelines for future testing of the best treatments for sepsis in burn patients. They should be updated on a regular basis. CONCLUSION: Members of the burn community from the around the world have developed the Surviving Sepsis After Burn Campaign guidelines with the goal of improving the outcome of sepsis in burn patients.

Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction.

BACKGROUND AND AIMS: The triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory alarmin abundantly secreted by activated neutrophils during infection and inflammation. We investigated the efficacy of S100A8/A9 blockade as a potential new treatment in SIMD. METHODS: The relationship between plasma S100A8/A9 and cardiac dysfunction was assessed in a cohort of 62 patients with severe sepsis admitted to the intensive care unit of Linköping University Hospital, Sweden. We used S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 and S100A9-/- mice for therapeutic and mechanistic studies on endotoxemia-induced cardiac dysfunction in mice. RESULTS: In sepsis patients, elevated plasma S100A8/A9 was associated with left-ventricular (LV) systolic dysfunction and increased SOFA score. In wild-type mice, 5 mg/kg of bacterial lipopolysaccharide (LPS) induced rapid plasma S100A8/A9 increase and acute LV dysfunction. Two ABR-238901 doses (30 mg/kg) administered intraperitoneally with a 6 h interval, starting directly after LPS or at a later time-point when LV dysfunction is fully established, efficiently prevented and reversed the phenotype, respectively. In contrast, dexamethasone did not improve cardiac function compared to PBS-treated endotoxemic controls. S100A8/A9 inhibition potently reduced systemic levels of inflammatory mediators, prevented upregulation of inflammatory genes and restored mitochondrial function in the myocardium. The S100A9-/- mice were protected against LPS-induced LV dysfunction to an extent comparable with pharmacologic S100A8/A9 blockade. The ABR-238901 treatment did not induce an additional improvement of LV function in the S100A9-/- mice, confirming target specificity. CONCLUSION: Elevated S100A8/A9 is associated with the development of LV dysfunction in severe sepsis patients and in a mouse model of endotoxemia. Pharmacological blockade of S100A8/A9 with ABR-238901 has potent anti-inflammatory effects, mitigates myocardial dysfunction and might represent a novel therapeutic strategy for patients with severe sepsis.

A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure.

BACKGROUND: When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers. METHODS: We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice. RESULTS: The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF. CONCLUSIONS: The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.

Outcomes following perioperative red blood cell transfusion in patients undergoing elective major abdominal surgery: a systematic review and meta-analysis.

BACKGROUND: Perioperative red blood cell transfusion is a double-edged sword for surgical patients. While transfusion of red cells can increase oxygen delivery by increasing haemoglobin levels, its impact on short- and long-term postoperative outcomes, particularly in patients undergoing elective major abdominal surgery, is unclear. METHODS: We conducted a systematic review and meta-analysis on the effect of perioperative blood transfusions on postoperative outcomes in elective major abdominal surgery. PubMed, Cochrane, and Scopus databases were searched for studies with data collected between January 1, 2000 and June 6, 2020. The primary outcome was short-term mortality, including all-cause 30-day or in-hospital mortality. Secondary outcomes included long-term all-cause mortality, any morbidity, infectious complications, overall survival, and recurrence-free survival. No randomised controlled trials were found. Thirty-nine observational studies were identified, of which 37 were included in the meta-analysis. RESULTS: Perioperative blood transfusion was associated with short-term all-cause mortality (odds ratio [OR] 2.72, 95% confidence interval [CI] 1.89-3.91, P<0.001), long-term all-cause mortality (hazard ratio 1.35, 95% CI 1.09-1.67, P=0.007), any morbidity (OR 2.18, 95% CI 1.81-2.64, P<0.001), and infectious complications (OR 1.90, 95% CI 1.60-2.26, P<0.001). Perioperative blood transfusion remained associated with short-term mortality in the sensitivity analysis after excluding studies that did not control for preoperative anaemia (OR 2.27, 95% CI 1.59-3.24, P<0.001). CONCLUSIONS: Perioperative blood transfusion in patients undergoing elective major abdominal surgery is associated with poorer short- and long-term postoperative outcomes. This highlights the need to implement patient blood management strategies to manage and preserve the patient's own blood and reduce the need for red blood cell transfusion. TRIAL REGISTRATION: PROSPERO (CRD42021254360).

Prediction of perioperative myocardial infarction/injury in high-risk patients after noncardiac surgery.

AIMS: Perioperative myocardial infarction/injury (PMI) is a surprisingly common yet difficult-to-predict cardiac complication in patients undergoing noncardiac surgery. We aimed to assess the incremental value of preoperative cardiac troponin (cTn) concentration in the prediction of PMI. METHODS AND RESULTS: Among prospectively recruited patients at high cardiovascular risk (age ≥65 years or ≥45 years with preexisting cardiovascular disease), PMI was defined as an absolute increase in high-sensitivity cTnT (hs-cTnT) concentration of ≥14 ng/L (the 99th percentile) above the preoperative concentration. Perioperative myocardial infarction/injury was centrally adjudicated by two independent cardiologists using serial measurements of hs-cTnT. Using logistic regression, three models were derived: Model 1 including patient- and procedure-related information, Model 2 adding routinely available laboratory values, and Model 3 further adding preoperative hs-cTnT concentration. Models were also compared vs. preoperative hs-cTnT alone. The findings were validated in two independent cohorts. Among 6944 patients, PMI occurred in 1058 patients (15.2%). The predictive accuracy as quantified by the area under the receiver operating characteristic curve was 0.73 [95% confidence interval (CI) 0.71-0.74] for Model 1, 0.75 (95% CI 0.74-0.77) for Model 2, 0.79 (95% CI 0.77-0.80) for Model 3, and 0.74 for hs-cTnT alone. Model 3 included 10 preoperative variables: age, body mass index, known coronary artery disease, metabolic equivalent >4, risk of surgery, emergency surgery, planned duration of surgery, haemoglobin, platelet count, and hs-cTnT. These findings were confirmed in both independent validation cohorts (n = 722 and n = 966). CONCLUSION: Preoperative cTn adds incremental value above patient- and procedure-related variables as well as routine laboratory variables in the prediction of PMI.

Echocardiography phenotypes of right ventricular involvement in COVID-19 ARDS patients and ICU mortality: post-hoc (exploratory) analysis of repeated data from the ECHO-COVID study.

PURPOSE: Exploratory study to evaluate the association of different phenotypes of right ventricular (RV) involvement and mortality in the intensive care unit (ICU) in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). METHODS: Post-hoc analysis of longitudinal data from the multicenter ECHO-COVID observational study in ICU patients who underwent at least two echocardiography examinations. Echocardiography phenotypes were acute cor pulmonale (ACP, RV cavity dilatation with paradoxical septal motion), RV failure (RVF, RV cavity dilatation and systemic venous congestion), and RV dysfunction (tricuspid annular plane systolic excursion ≤ 16 mm). Accelerated failure time model and multistate model were used for analysis. RESULTS: Of 281 patients who underwent 948 echocardiography studies during ICU stay, 189 (67%) were found to have at least 1 type of RV involvements during one or several examinations: ACP (105/281, 37.4%), RVF (140/256, 54.7%) and/or RV dysfunction (74/255, 29%). Patients with all examinations displaying ACP had survival time shortened by 0.479 [0.284-0.803] times when compared to patients with all examinations depicting no ACP (P = 0.005). RVF showed a trend towards shortened survival time by a factor of 0.642 [0.405-1.018] (P = 0.059), whereas the impact of RV dysfunction on survival time was inconclusive (P = 0.451). Multistate analysis showed that patients might transit in and out of RV involvement, and those who exhibited ACP in their last critical care echocardiography (CCE) examination had the highest risk of mortality (hazard ratio (HR) 3.25 [2.38-4.45], P < 0.001). CONCLUSION: RV involvement is prevalent in patients ventilated for COVID-19 ARDS. Different phenotypes of RV involvement might lead to different ICU mortality, with ACP having the worst outcome.

Saudi Critical Care Society clinical practice guidelines on the prevention of venous thromboembolism in adults with trauma: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Saudi Critical Care Society clinical practice guidelines on the prevention of venous thromboembolism in adults with trauma: reviewed for evidence-based integrity and endorsed by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine. This clinical practice guideline serves as a useful decision aid for Nordic anaesthesiologists managing adult trauma patients in the operating room and in the intensive care unit.