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Objectives Individualizing a target mean arterial pressure is challenging during the initial resuscitation of patients with septic shock. The Sepsis and Mean Arterial Pressure (SEPSISPAM) trial suggested that targeting high mean arterial pressure might reduce the occurrence of acute kidney injury among those included patients with a past history of chronic hypertension. We investigated whether the class of antihypertensive medications used before the ICU stay in chronic hypertensive patients was associated with the severity of acute kidney injury occurring after inclusion, according to mean arterial pressure target. Design Post hoc analysis of the SEPSISPAM trial. Setting The primary outcome was the occurrence of severe acute kidney injury during the ICU stay defined as kidney disease improving global outcome stage 2 or higher. Secondary outcomes were mortality at day 28 and mortality at day 90. Patients All patients with chronic hypertension included in SEPSISPAM with available antihypertensive medications data in the hospitalization report were included. Measurements and main results We analyzed 297 patients. Severe acute kidney injury occurred in 184 patients, without difference according to pre-ICU exposure to antihypertensive medications. Patients with pre-ICU exposure to angiotensin II receptor blockers had significantly less severe acute kidney injury in the high mean arterial pressure target group (adjusted odd ratio 0.24 with 95% CI [0.09-0.66]; p = 0.006). No statistically significant association was found after adjustment for pre-ICU exposure to antihypertensive medications and survival. Conclusions Our results suggest that patients with septic shock and chronic hypertension treated with angiotensin II receptor blocker may benefit from a high mean arterial pressure target to reduce the risk of acute kidney injury occurrence.

Recent reports have suggested an increased risk of pulmonary embolism (PE) related to COVID-19. The aim of this cohort study is to compare the incidence of PE during a 3-year period and to assess the characteristics of PE in COVID-19. We studied consecutive patients presenting with PE (January 2017–April 2020). Clinical presentation, computed tomography (CT) and biological markers were systematically assessed. We recorded the global number of hospitalizations during the COVID-19 pandemic and during the same period in 2018-2019. We included 347 patients: 326 without COVID-19 and 21 with COVID-19. Patients with COVID-19 experienced more likely dyspnea (p=0.04), had lower arterial oxygen saturation (p

Objectives The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge. Design Ancillary investigation of a prospective observational study. Setting Twenty-one ICUs with 1-year follow-up. Patients Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included. Interventions Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors. Measurements and main results The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25-47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease). Conclusions Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge.

Ascitic fluid infection (AFI) is a life-threatening complication of cirrhosis. We aimed to identify early indicators of secondary peritonitis (SP), which requires emergency surgery, and to describe the outcomes of SP and spontaneous bacterial/fungal peritonitis (SBFP). Adults with cirrhosis and AFI admitted to 16 university or university-affiliated ICUs in France between 2002 and 2017 were studied retrospectively. Cases were identified by searching the hospital databases for relevant ICD-10 codes and hospital charts for AFI. Logistic multivariate regression was performed to identify factors associated with SP. Secondary outcomes were short- and long-term mortality and survivors’ functional outcomes. Of 178 included patients (137 men and 41 women; mean age, 58 ± 11 years), 21 (11.8%) had SP, confirmed by surgery in 16 cases and by abdominal computed tomography in 5 cases. Time to diagnosis exceeded 24 h in 7/21 patients with SP. By multivariate analysis, factors independently associated with SP were ascitic leukocyte count > 10,000/mm3 (OR 3.70; 95%CI 1.38–9.85; P = 0.009) and absence of laboratory signs of decompensated cirrhosis (OR 4.53; 95%CI 1.30–15.68; P = 0.017). The 1-year mortality rates in patients with SBFP and SP were 81.0% and 77.5%, respectively (Log-rank test, P = 0.92). Patients with SP vs. SBFP had no differences in 1-year functional outcomes. This multicenter retrospective study identified two indicators of SP as opposed to SBFP in patients with cirrhosis. Using these indicators may help to provide early surgical treatment.

BackgroundWhile acute kidney injury (AKI) is frequent in severe SARS-CoV2-related pneumonia ICU patients, few data are still available about its risk factors.MethodsRetrospective observational study performed in four university affiliated hospitals in Paris. AKI was defined according to the KIDGO guidelines. Factors associated with AKI were picked up using multivariable mixed-effects logistic regression. Independent risk factors of day 28 mortality were assessed using Cox model.Results379 patients (median age 62 [53,69], 77% of male) were included. Half of the patients had AKI (n = 195, 52%) including 58 patients (15%) with AKI stage 1, 44 patients (12%) with AKI stage 2, and 93 patients (25% with AKI stage 3). Chronic kidney disease (OR 7.41; 95% CI 2.98–18.4), need for invasive mechanical ventilation at day 1 (OR 4.83; 95% CI 2.26–10.3), need for vasopressors at day 1 (OR 2.1; 95% CI 1.05–4.21) were associated with increased risk of AKI. Day 28 mortality in the cohort was 26.4% and was higher in patients with AKI (37.4 vs. 14.7%,P ConclusionIn this large cohort of SARS-CoV2-related pneumonia patients admitted to the ICU, AKI was frequent, mostly driven by preexisting chronic kidney disease and life sustaining therapies, with unclear adjusted relationship with day 28 outcome.

Background It is unknown whether the recommended mean arterial pressure (MAP) target of 65 mmHg during initial resuscitation of septic shock is sufficient to maintain cerebral perfusion. Thus, we tested the hypothesis that a higher MAP target in patients with septic shock may improve level of arousal. Methods We performed a post hoc exploratory analysis of the SEPSISPAM trial, which assessed the effect of a “high-target” level of MAP (80–85 mmHg) versus the recommended “low-target” MAP (65–70 mm Hg) on mortality in patients with septic shock. Among the 776 patients originally recruited in SEPSISPAM trial, we selected those who were mechanically ventilated and sedated and with available evaluation of arousal level assessed by the Richmond Agitation and Sedation Scale (RASS). Results We restricted our analysis to the period in which patients were treated with vasoactive drugs. Cumulative sedative drugs were assessed daily. A total of 532 patients were included in this study: 253 (47.6%) in the low-target group and 279 (52.4%) in the high-target group. Daily cumulative sedative drugs were similar in both groups. Compared to the low-target group, minimal and maximal RASS were significantly higher in the high-target group at day 2, 4 and 5. Furthermore, in order to consider the fact that multiple measures were done for each patient and to consider the global effect of time on these measures, we used a mixed linear regression and multivariate models: we confirmed that maximal RASS values were significantly higher in the high-target group. Conclusion In patients with septic shock who were mechanically ventilated and sedated, resuscitation with MAP target between 80 and 85 mmHg was associated with higher arousal level as compared to a MAP target between 65 and 70 mmHg. Electronic supplementary material The online version of this article (10.1186/s13613-019-0528-5) contains supplementary material, which is available to authorized users.

Mechanisms of circulatory failure are complex and frequently intricate in septic shock. Better characterization could help to optimize hemodynamic support. Two published prospective databases from 12 different ICUs including echocardiographic monitoring performed by a transesophageal route at the initial phase of septic shock were merged for post hoc analysis. Hierarchical clustering in a principal components approach was used to define cardiovascular phenotypes using clinical and echocardiographic parameters. Missing data were imputed. A total of 360 patients (median age 64 [55; 74]) were included in the analysis. Five different clusters were defined: patients well resuscitated (cluster 1, n = 61, 16.9%) without left ventricular (LV) systolic dysfunction, right ventricular (RV) failure or fluid responsiveness, patients with LV systolic dysfunction (cluster 2, n = 64, 17.7%), patients with hyperkinetic profile (cluster 3, n = 84, 23.3%), patients with RV failure (cluster 4, n = 81, 22.5%) and patients with persistent hypovolemia (cluster 5, n = 70, 19.4%). Day 7 mortality was 9.8%, 32.8%, 8.3%, 27.2%, and 23.2%, while ICU mortality was 21.3%, 50.0%, 23.8%, 42.0%, and 38.6% in clusters 1, 2, 3, 4, and 5, respectively (p

Purpose To explore diagnostic pitfalls and treatment issues in out-of-hospital cardiac arrest of neurological cause (OHCA-NC). Methods Retrospective analysis of all consecutive patients from the Paris Sudden Death Expertise Centre (France) registry from May 2011 to September 2015 presenting with a sustained return of spontaneous circulation (ROSC) at hospital admission and a final diagnosis of OHCA-NC. Description of the early diagnostic check-up performed to identify the cause of cardiac arrest. Logistic multivariate regression to identify factors associated with immediate coronary angiography (iCAG) in OHCA-NC patients. Results Among 3542 patients with ROSC, a final diagnosis of OHCA-NC was established in 247 (7%). The early diagnostic check-up consisted in a total of 207 (84%) immediate cranial CT-scan, 66 (27%) iCAG and 25 (10%) chest CT-scan. The brain CT-scan allowed identifying a neurovascular cause in 116 (47%) patients. An iCAG was performed as the first line exam in 57 (23%) patients, in whom a final diagnosis of neurovascular cause for OHCA-NC was later identified in 41 patients. By multivariate analysis, decision for iCAG was independently associated with ST-segment elevation on post-ROSC electrocardiogram (OR, 5.94; 95%CI, 2.14–18.28; P = 0.0009), whereas an obvious cause of cardiac arrest on scene was negatively associated with iCAG (OR, 0.14; 95%CI, 0.02–0.51; P = 0.01). Conclusions OHCA-NC is a rare event that is mainly related to neurovascular causes. The initial ECG pattern may be a confounder regarding triage for early diagnostic check-up. Further studies are required to explore the potential harmfulness associated with decision to perform an iCAG in this population.

Purpose of review Recent studies have failed to show significant benefit from a uniform strategy, suggesting that hemodynamic management must be individually adapted in septic shock depending on different phenotypes. Different approaches that may be used to this end will be discussed. Recent findings Fluid management is a cornerstone of resuscitation, as the positive fluid balance has been associated with higher mortality and right ventricular failure. Myocardial evaluation is mandatory, as sepsis patients may present with a hyperkinetic state, left ventricular (systolic and diastolic) and/or right ventricular dysfunction, the latter being associated with higher mortality. Statistical approaches with the identification of hemodynamic clusters based on echocardiographic and clinical parameters might be integrated into daily practice to develop precision medicine. Such approaches may also predict the progression of septic shock. Summary Different hemodynamic phenotypes can occur at any stage of sepsis and be associated with one another. The clinician must regularly assess dynamic changes in phenotypes in septic shock patients. Statistical approaches based on machine learning need to be validated by prospective studies.

BACKGROUND: Mechanical ventilation (MV) in ICU patients may impact hemodynamics and renal function. We aimed to describe the interactions of MV settings, hemodynamic parameters and worsening of renal function (WRF). METHODS: We included adult patients admitted for the first time in the ICU from the MIMIC-III database. Mean arterial blood pressure (mABP), central venous pressure (CVP) and positive end-expiratory pressure (PEEP) were collected and summarized as a time-weighted mean. The main outcome was WRF defined as acute kidney injury (AKI) occurrence or one-KDIGO stage worsening compared to the KDIGO stage the day before. We used a multinomial logistic regression at day 1 (ldmk-1) and day 2 (ldmk-2) according to a landmark-approach, with a two-days sliding perspective. RESULTS: 27,248/61,051 patients met the inclusion criteria (15,258 male (56.0%); 60.1% over 60y). ICU and hospital mortality were 7.4 and 10.7%, respectively. MV was independently associated with WRF in the ldmrk-1 and −2 models (relative risk ratio [RRR] 8.15 [6.58;10.11] and 7.08 [3.97;12.61] at day-3 and 4, respectively). In MV patients, PEEP was associated with WRF in the ldmrk-1 and −2 models (RRR 1.36 [1.16, 1.6] and 1.17 [0.88, 1.56] by 1cmH(2)O increase at day-3 and 4, respectively). Mean perfusion pressure decreased while central venous pressure increased over PEEP categories. In multivariable analysis, mABP, CVP and PEEP were independently associated with WRF. CONCLUSION: In this large cohort of ICU patients, we observed a strong relationship between MV and WRF. PEEP was associated with WRF in MV patients. This association relied at least partly on renal venous congestion.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a poorly understood disease involving a high inflammatory status. Neutrophil extracellular traps (NETs) have been described as a new pathway to contain infectious diseases but can also participate in the imbalance of the inflammatory and the coagulation systems. NETs could be a therapeutic target in COVID-19 patients.Methods: Consecutive patients with SARS-CoV2 related pneumonia admitted to the intensive care unit were included in a prospective bicentric study. Neutrophil extracellular trap concentrations were quantified in whole blood samples at day-1 and day-3 by flow cytometry. The primary outcome was the association between the blood NET quantification at ICU admission and the number of days with refractory hypoxemia defined by a PaO2/FIO2 ratio ≤100 mmHg.Results: Among 181 patients admitted to the ICUs for acute respiratory failure related to SARS-CoV2 pneumonia, 58 were included in the analysis. Patients were 62 [54, 69] years old in median, mostly male (75.9%). The median number of days with severe hypoxemia was 4 [2, 6] days and day-28 mortality was 27.6% (n = 16). The blood level of NETs significantly decreased between day-1 and day-3 in patients who survived (59.5 [30.5, 116.6] to 47 [33.2, 62.4] p = 0.006; 8.6 [3.4, 18.0] to 4 [1.4, 10.7] p = 0.001 and 7.4 [4.0, 16.7] to 2.6 [1.0, 8.3] p = 0.001 for MPO+, Cit-H3+, and MPO+ Cit-H3+ NETs, respectively) while it remained stable in patients who died (38.4 [26.0, 54.8] to 44.5 [36.4, 77.7] p = 0.542; 4.9 [1.3, 13.0] to 5.5 [2.8, 6.9] p = 0.839 and 4 [1.3, 13.6] to 2.7 [1.4, 4.5] p = 0.421 for MPO+, Cit-H3+, and MPO+ Cit-H3+ NETs, respectively). In multivariable negative binomial regression, the blood level of MPO+ NETs was negatively associated with the number of days with severe hypoxemia within 7 days (0.84 [0.73, 0.97]), while neither Cit-H3+ NETs nor double-positive NETs were significantly associated with the primary outcome.Conclusion: The whole blood level of NETs at day-1 was negatively associated with the number of days with severe hypoxemia in patients admitted to the intensive care unit for SARS-CoV2 related pneumonia. The lack of decrease of the blood level of NETs between day-1 and day-3 discriminated patients who died within day-28.

International audience; Introduction: Pancreatic surgery is associated with high morbidity, mainly due to infectious complications, so many centres use postoperative antibiotics (ATBpo) for all patients. However, antibiotic regimens vary according to local practices. The aims of this study were to describe the occurrence of surgical site infection (SSI) and ATBpo prescription after pancreatic surgery, and to determine the risk factors of postoperative SSI, in order to better define the clinical indications for ATBpo in this context.Patients and methods: All patients undergoing scheduled major pancreatic surgery from January 2007 to November 2018 were included in this retrospective study. Patients were classified into four groups according to SSI and routine ATBpo prescription: SSI+/ATBpo+, SSI-/ATBpo+, SSI+/ATBpo- and SSI-/ATBpo-. In addition, risk factors (fever and pre-operative biliary prosthesis) associated with the occurrence of SSI and ATBpo were analysed using a logistic regression model.Results: Data from 149 patients (115 pancreaticoduodenectomies and 34 splenopancreatectomies) were analysed. Thirty (20.1%) patients experienced SSI and 42 (28.2%) received ATBpo. No difference was found in routine ATBpo prescription between patients with and without SSI (26.7% vs 28.6%, respectively; P=0.9). Amongst the 107 patients who did not receive routine ATBpo, 85 (79.4%) did not develop an SSI. In-hospital mortality did not differ between infected and uninfected patients (7% vs 2%, respectively; P=0.13). The occurrence of postoperative fever differed between SSI+ and SSI- patients (73.3% vs 34.2%, respectively; P

International audience; Today, proficiency in cardiopulmonary ultrasound is considered essential for anesthesiologists and critical care physicians. Conventional 2-dimensional images, however, do not permit optimal characterization of specific conditions (eg, diaphragmatic paralysis, major atelectasis, and pneumothorax) that may have relevant clinical implications in critical care and perioperative settings. By contrast, M-mode (motion-based) ultrasonographic imaging modality offers the highest temporal resolution in ultrasonography; this modality, therefore, can provide important information in ultrasound-driven approaches performed by anesthesiologists and intensivists for diagnosis, monitoring, and procedural guidance. Despite its practicability, M-mode has been progressively abandoned in echocardiography and is often underused in lung and diaphragmatic ultrasound. This review describes contemporary applications of M-mode ultrasonography in the practice of critical care and perioperative medicine. Information presented for each clinical application includes image acquisition and interpretation, evidence-based clinical implications in critically ill and surgical patients, and main limitations. The article focuses on tracheal, lung, and diaphragmatic ultrasound. It reviews tracheal ultrasound for procedural guidance during endotracheal intubation, confirmation of correct tube placement, and detection of esophageal intubation; lung ultrasound for the confirmation of endotracheal and endobronchial (selective) intubation and for the diagnosis of pneumothorax, alveolar-interstitial syndrome (cardiogenic v noncardiogenic pulmonary edema), pulmonary consolidation (pneumonia v major atelectasis) and pleural effusion; and diaphragmatic ultrasound for the diagnosis of diaphragmatic dysfunction and prediction of extubation success.

Introduction Prognostic assessment of pulmonary embolism (PE) by transthoracic echocardiography (TTE) and CT-scan has been proposed in patients with intermediate risk according to the ESC guidelines. The aim of this study is to assess the accuracy of this multimodality imaging strategy in routine practice. Method We reviewed from our database all consecutive patients hospitalized for acute PE between July 2011 and June 2019. Right ventricular (RV) size/dysfunction was systematically assessed by TTE and CT-scan in patients classified as intermediate risk (defined as a sPESI score ≥ 1) and was defined as RV/LV ratio ≥ 1. In-hospital outcome was systematically assessed and was compared according to the classification of PE severity and the combined use of TTE and CT-scan and the separated use of these 2 imaging modalities. Results We studied 708 patients (49.5% female, median age 68 years) presenting with acute PE. 50 patients (7%) had shock or hypotension on arrival, meeting the criteria for high-risk PE with an in-hospital mortality of 38%. Among the 658 patients without high-risk PE, 336 patients had a sPESI score ≥ 1 and were considered as intermediate risk PE. TTE classified 124 patients as intermediate–high risk PE versus 132 patients by CT-scan, 165 patients by TTE or CT-scan and 91 patients by both TTE and CT-scan. In intermediate-high risk PE (RV dysfunction), in-hospital mortality was 11.3% using TTE alone, 9.8% using CT-scan alone, 9.1% with positive TTE or CT-scan and 13.2% using TTE and CT-scan (P = 0.75). In-hospital mortality was 5.6% in intermediate-low risk PE and 0.6% in low risk PE (sPESI = 0). Conclusion In intermediate-high risk PE, the accuracy of combined TTE and CT-scan or TTE or CT-scan used alone is similar for the assessment of PE prognosis.

Background: Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock. Methods: From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions. Results: A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81–90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement). Conclusion: Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes., La lista completa de autores que integran el documento puede consultarse en el archivo., Facultad de Ciencias Médicas

Background Immune checkpoint inhibitors have reshaped the standard of care in oncology. However, they have been associated with potentially life-threatening immune-related adverse events. With the growing indications of immune checkpoint inhibitors and their position as a pillar of cancer treatment, intensive care physicians will be increasingly confronted with their side effects. The outcome of patients with severe immune-related adverse events in the intensive care unit remains unknown. This retrospective multicentric study aims to describe the characteristics of patients admitted to the intensive care units of 4 academic hospitals in Paris area while receiving immune checkpoint inhibitor treatment between January 2013 and October 2019. Results Over the study period, 112 cancer patients who received immune checkpoint inhibitors were admitted to the intensive care unit within 60 days after the last dose. ICU admission was related to immune-related adverse events (n = 29, 26%), other intercurrent events (n = 39, 35%), or complications related to tumor progression (n = 44, 39%). Immune-related adverse events were pneumonitis (n = 8), colitis (n = 4), myocarditis (n = 3), metabolic disorders related to diabetes (n = 3), hypophysitis (n = 2), nephritis (n = 2), meningitis or encephalitis (n = 2), hepatitis (n = 2), anaphylaxis (n = 2) and pericarditis (n = 1). Primary tumors were mostly melanomas (n = 14, 48%), non-small-cell lung cancers (n = 7, 24%), and urothelial carcinomas (n = 5, 17%). Diagnosis of melanoma and a neutrophil/lymphocyte ratio n = 7), mechanical ventilation (n = 6), and extra-corporeal membrane oxygenation (n = 2). One-year survival was significantly higher for patients admitted for irAE compared to patients admitted for other reasons (p = 0.004). Conclusions Admission to the intensive care unit related to immune-related adverse event was associated with better outcome in cancer patients treated with immune checkpoint inhibitors. Our results support the admission for an intensive care unit trial for patients with suspected immune-related adverse events.

Purpose Septic induced cardiomyopathy has a wide spectrum of presentation, being associated with systolic and/or diastolic dysfunction. There is currently no evidence of association between left ventricular (LV) systolic dysfunction and mortality in septic patients. Methods We conducted a systematic review and meta-analysis to investigate the association between systolic wave (s') obtained with Tissue Doppler Imaging (TDI) and mortality in septic patients. Secondary outcome was the association of LV ejection fraction with mortality. Results In the primary analysis we included a total of 13 studies (1197 patients, mortality 39.9%); overall s' wave was not significantly different between survivors and non-survivors (Standardized Mean Difference 0.20, 95%Confidence-Interval − 0.18, 0.59). This result was confirmed also in sub-groups analyses according to regional criteria of TDI sampling. A post-hoc analysis including only septic shock patients confirmed that s' wave was not associated with mortality. Several sensitivity analyses confirmed these results. We found no evidence of publication bias. The secondary analysis (11 studies, 1081 patients, mortality 36.7%) showed that LV ejection fraction was not associated with mortality (Mean Difference 0.98, 95% Confidence-Interval − 1.79,3.75). Conclusions There is no association between mortality and LV systolic function as evaluated by TDI s' wave in septic patients.

Purpose Coronavirus disease 2019 (COVID-19) is creating an unprecedented healthcare crisis. Understanding the determinants of mortality is crucial to optimise intensive care unit (ICU) resource use and to identify targets for improving survival. Methods In a multicentre retrospective study, we included 379 COVID-19 patients admitted to four ICUs between 20 February and 24 April 2020 and categorised according to time from disease onset to ICU admission. A Cox proportional-hazards model identified factors associated with 28-day mortality. Results Median age was 66 years (53–68) and 292 (77%) were men. The main comorbidities included obesity and overweight (67%), hypertension (49.6%) and diabetes (30.1%). Median time from disease onset (i.e., viral symptoms) to ICU admission was 8 (6–11) days (missing for three); 161 (42.5%) patients were admitted within a week of disease onset, 173 (45.6%) between 8 and 14 days, and 42 (11.1%) > 14 days after disease onset; day 28 mortality was 26.4% (22–31) and decreased as time from disease onset to ICU admission increased, from 37 to 21% and 12%, respectively. Patients admitted within the first week had higher SOFA scores, more often had thrombocytopenia or acute kidney injury, had more limited radiographic involvement, and had significantly higher blood IL-6 levels. Age, COPD, immunocompromised status, time from disease onset, troponin concentration, and acute kidney injury were independently associated with mortality. Conclusion The excess mortality in patients admitted within a week of disease onset reflected greater non-respiratory severity. Therapeutic interventions against SARS-CoV-2 might impact different clinical endpoints according to time since disease onset. Electronic supplementary material The online version of this article (10.1007/s00134-020-06202-3) contains supplementary material, which is available to authorized users.

International audience; Rationale: Subclinical acute kidney injury (sub-AKI) refers to patients with low serum creatinine but elevated alternative biomarkers of AKI. Its incidence and outcome in critically ill patients remain, however, largely unknown. Plasma proenkephalin A 119–159 (penKid) has been proposed as a sensitive biomarker of glomerular function.Objectives: In this ancillary study of two cohorts, we explored the incidence and outcome of sub-AKI based on penKid.Methods: A prospective observational study in ICUs was conducted. FROG-ICU (French and European Outcome Registry in ICUs) enrolled 2,087 critically ill patients, and AdrenOSS-1 (Adrenomedullin and Outcome in Severe Sepsis and Septic Shock-1) enrolled 583 septic patients. The primary endpoint was 28-day mortality after ICU admission. Sub-AKI was defined by an admission penKid concentration above the normal range (i.e., >80 pmol/L) in patients not meeting the definition of AKI. A sensitivity analysis was performed among patients with estimated glomerular filtration rate above 60 ml/min/1.73 m2 at ICU admission.Measurements and Main Results: In total, 6.1% (122/2,004) and 6.7% (39/583) of patients from the FROG-ICU and AdrenOSS-1 cohorts met the definition of sub-AKI (11.6% and 17.5% of patients without AKI). In patients without AKI or with high estimated glomerular filtration rate, penKid was associated with higher mortality (adjusted standardized hazard ratio [HR], 1.4 [95% confidence interval, 1.1–1.8]; P = 0.010; and HR, 1.6 [95% confidence interval, 1.3–1.8]; P

RV failure occurred in around 22% of moderate to severe ARDS, even when ventilated with a lung protective approach. Risk factors are a plateau pressure ≥27 cmH2O, a driving pressure ≥18 cm H2O, a PaCO2 ≥48 mmHg, a PaO2/FiO2

RV function is key in critically ill patients, especially when mechanically ventilated. Echocardiography is very suitable for the evaluation of RV function, allowing to easily appreciate the preload, the afterload, and the pericardium. Three views, with five parameters, are mandatory, by TTE or TEE: the RV outflow track (respiratory variation of RV ejection flow and acceleration time), the upper esophageal view at 90° (collapsibility index of the superior vena cava), a four-chamber view (ratio between the end-diastolic area of the RV to the LV), and an LV short-axis view (movement of the interventricular septum). Evaluation of pulmonary artery pressure, by measuring the pressure gradient on the tricuspid regurgitation, may be considered. A pattern of cor pulmonale is the association of RV dilatation with a paradoxical sepal motion in a context or the presence of pulmonary hypertension. It is acute according to the clinical context, the absence of RV hypertrophy, and a limited pulmonary hypertension. TEE has a better sensitivity than TTE with the same specificity for the diagnosis of cor pulmonale. Tricuspid annular plan systolic excursion is probably not a good parameter for RV function evaluation in the ICU.

In ARDS patients, the change from supine to prone position generates a more even distribution of the gas–tissue ratios along the dependent–nondependent axis and a more homogeneous distribution of lung stress and strain. The change to prone position is generally accompanied by a marked improvement in arterial blood gases, which is mainly due to a better overall ventilation/perfusion matching. Improvement in oxygenation and reduction in mortality are the main reasons to implement prone position in patients with ARDS. The main reason explaining a decreased mortality is less overdistension in non-dependent lung regions and less cyclical opening and closing in dependent lung regions. The only absolute contraindication for implementing prone position is an unstable spinal fracture. The maneuver to change from supine to prone and vice versa requires a skilled team of 4–5 caregivers. The most frequent adverse events are pressure sores and facial edema. Recently, the use of prone position has been extended to non-intubated spontaneously breathing patients affected with COVID-19 ARDS. The effects of this intervention on outcomes are still uncertain. Electronic supplementary material The online version of this article (10.1007/s00134-020-06306-w) contains supplementary material, which is available to authorized users.

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus-driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high-quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in-hospital management. Chioncel, O (corresponding author), Univ Med & Pharm Carol Davila, Inst Emergency Cardiovasc Dis Prof CC Iliescu, Bucharest 950474, Romania. ochioncel@yahoo.co.uk

Background: Vasopressors are commonly applied to restore and maintain blood pressure in patients with sepsis. We aimed to evaluate the current practice and therapeutic goals regarding vasopressor use in septic shock as a basis for future studies and to provide some recommendations on their use. Methods: From November 2016 to April 2017, an anonymous web-based survey on the use of vasoactive drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 17 questions focused on the profile of respondents, triggering factors, first choice agent, dosing, timing, targets, additional treatments, and effects of vasopressors. We investigated whether the answers complied with current guidelines. In addition, a group of 34 international ESICM experts was asked to formulate recommendations for the use of vasopressors based on 6 questions with sub-questions (total 14). Results: A total of 839 physicians from 82 countries (65% main specialty/activity intensive care) responded. The main trigger for vasopressor use was an insufficient mean arterial pressure (MAP) response to initial fluid resuscitation (83%). The first-line vasopressor was norepinephrine (97%), targeting predominantly a MAP > 60–65 mmHg (70%), with higher targets in patients with chronic arterial hypertension (79%). The experts agreed on 10 recommendations, 9 of which were based on unanimous or strong (≥ 80%) agreement. They recommended not to delay vasopressor treatment until fluid resuscitation is completed but rather to start with norepinephrine early to achieve a target MAP of ≥ 65 mmHg. Conclusion: Reported vasopressor use in septic shock is compliant with contemporary guidelines. Future studies should focus on individualized treatment targets including earlier use of vasopressors., SCOPUS: ar.j, info:eu-repo/semantics/published

International audience; Purpose: Acute kidney injury (AKI) is associated with the activation of the renin–angiotensin system. Whether angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB) improve outcome in patients recovering from AKI remains unexplored. The purpose was to investigate the association between prescription of ACEi/ARB at intensive care unit (ICU) discharge and 1-year outcome in patients recovering from AKI.Methods: Association between ACEi/ARB and 1-year mortality rate was explored in 1551 patients discharged from 21 European ICUs in an observational cohort. One-year all-cause mortality after ICU discharge was the primary endpoint. AKI was defined using the kidney disease improvement global outcome definition. Propensity score matching was used to consider the probability to receive ACEi/ARB at ICU discharge and included chronic heart failure, ACEi/ARB on ICU admission, Charlson Comorbidity Index, age, diabetes mellitus, chronic kidney disease, estimated glomerular filtration rate and arterial blood pressure at ICU discharge vasopressors and renal replacement therapy.Results: Overall, 1-year mortality was 28 and 15% in patients with AKI (n = 611, 39%) and without AKI (n = 940), respectively. In patients with AKI, unadjusted, adjusted and propensity-score matched 1-year mortality rates were lower in patients treated with ACEi/ARB at ICU discharge [HR of 0.55 (0.35–0.89), HR of 0.45 (0.27–0.75), and HR of 0.48 (0.27–0.85, p

This paper provides a practical clinical application of guideline recommendations relating to the inpatient monitoring of patients with acute heart failure, through the evaluation of various clinical, biomarker, imaging, invasive and non-invasive approaches. Comprehensive inpatient monitoring is crucial to the optimal management of acute heart failure patients. The European Society of Cardiology heart failure guidelines provide recommendations for the inpatient monitoring of acute heart failure, but the level of evidence underpinning most recommendations is limited. Many tools are available for the in-hospital monitoring of patients with acute heart failure, and each plays a role at various points throughout the patient's treatment course, including the emergency department, intensive care or coronary care unit, and the general ward. Clinical judgment is the preeminent factor guiding application of inpatient monitoring tools, as the various techniques have different patient population targets. When applied appropriately, these techniques enable decision making. However, there is limited evidence demonstrating that implementation of these tools improves patient outcome. Research priorities are identified to address these gaps in evidence. Future research initiatives should aim to identify the optimal in-hospital monitoring strategies that decrease morbidity and prolong survival in patients with acute heart failure. The authors acknowledge the Heart Failure Association of theEuropean Society of Cardiology for organizing the meeting duringwhich this topic was discussed.The authors acknowledge Wendy Gattis Stough, PharmD(Campbell University College of Pharmacy and Health Sciences),supported by the Heart Failure Association of the EuropeanSociety of Cardiology for contributions to content development,writing, and editing the manuscript.The work of JelenaˇCelutkien ̇e was supported by the grant fromLithuanian Research Council Nr. MIP-049/2015.

Background Myocardial dysfunction may contribute to circulatory failure in sepsis. There is growing evidence of an association between left ventricular diastolic dysfunction (LVDD) and mortality in septic patients. Utilizing echocardiography, we know that tissue Doppler imaging (TDI) variables e′ and E/e′ are reliable predictors of LVDD and are useful measurements to estimate left ventricular (LV) filling pressures. Methods We conducted a systematic review and meta-analysis to investigate the association of e′ and E/e′ with mortality of patients with severe sepsis or septic shock. In the primary analysis, we included studies providing transthoracic TDI data for e′ and E/e′ and their association with mortality. Subgroup analyses were conducted according to myocardial regional focus of TDI assessment (septal, lateral or averaged). Three secondary analyses were performed: one included data from a transoesophageal study, another excluded studies reporting data at a very early ( 48 h) stage following diagnosis, and the third pooled data only from studies excluding patients with heart valve disease. Results The primary analysis included 16 studies with 1507 patients with severe sepsis and/or septic shock. A significant association was found between mortality and both lower e′ [standard mean difference (SMD) 0.33; 95% confidence interval (CI): 0.05, 0.62; P=0.02] and higher E/e′ (SMD –0.33; 95% CI: –0.57, –0.10; P=0.006). In the subgroup analyses, only the lateral TDI values showed significant association with mortality (lower e′ SMD 0.45; 95% CI: 0.11, 0.78; P=0.009; higher E/e′ SMD –0.49; 95% CI: –0.76, –0.22; P=0.0003). The findings of the primary analysis were confirmed by all secondary analyses. Conclusions There is a strong association between both lower e′ and higher E/e′ and mortality in septic patients.

To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS).We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality.We included 1899 patients with ARDS in this study. The relationship between maximum PaCOSevere hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS.Clinicaltrials.gov identifier, NCT01093482.

International audience; on behalf of the FROG ICU study investigators Acute kidney injury (AKI) is a frequent condition in critically ill patients that affects both short-and long-term outcome [1]. Its early detection remains a challenge, and diagnosis frequently occurs too late with cell damage already present. Implementation of novel biomarkers that reliably identify patients at risk or at an early stage of AKI could offer more efficient management strategies leading to better outcomes. In our investigation, we compared two promising AKI biomarkers: a marker of tubular injury commercialized as a lateral-flow test (NephroCheck®) [2], the product of urinary TIMP-2 (Tissue inhibitor of metalloprotease), and IGFBP 7 (Insulin-like growth factor binding protein; overall TIMP2xIGFBP7), and the filtration marker proenkephalin A 119-159 (penKid). penKid has been recently described as a valuable plasma biomarker of AKI in the acutely ill, including septic patients [3] and patients suffering from acute heart failure [4]. Proenkephalin represents a stable surrogate analyte of labile enkephalins, which are known as endogenous opioids, but also affects kidney function [5]. The aim of our study was to conduct a parallel assessment of the two biomarkers in an intensive care unit (ICU) population from the data of the FROG-ICU study. FROG-ICU has been designed to better understand long-term outcome after ICU discharge as well as risk factors for all-cause and cardiovascular morbidity and associated mortality (FROG-ICU study, ClinicalTrials.gov identifier NCT01367093). It was a large prospective multicenter cohort study with biological (plasma and urine) collection and one-year follow-up of ICU patients. FROG-ICU aims to allow risk stratification of ICU survivors in order to recognize the subset of patients who may benefit from early intervention to allow decreased cardiovascular morbidity and related mortality. The methodology of the FROG-ICU study was published in 2015. From the FROG study including 2087 critically ill patients we randomly selected 200 requiring mechanical ventilation or vasopressor support for more than 24 h with respect to the four categories of the renal Sequential Organ Failure Assessment (SOFA) score (i.e., creatinine level on admission of < 1.2 mg/dL (n = 80), 1.2 to 1.9 mg/dL (n = 40), 2 to 3.4 mg/dL (n = 40), and ≥ 3.5 mg/dL (n = 40)); 78% were male, with a median age of 65 years (interquartile range (IQR) 54–75). In the investigated cohort of a standard population of critically ill, the main cause of ICU admission was septic shock (26%), the median age was 65 years (IQR 54–75), the median SAPS II score was 51 (IQR 41–68), and the ICU mortality was 26%. Other causes of admission include out-of-hospital cardiac arrest (10%), acute respiratory failure (16%), acute neurological disorder (11%), and cardiogenic shock (8%). On ICU admission, the median (and IQR) value of estimated glomerular filtration rate for penKid and TIMP2xIGFBP7 was 47 mL/min (22–88), 85 pmol/L (48–40), and 0.6 UNIT (0.3–2), respectively. AKI was defined using the Kidney Disease Improvement Global Outcome (KDIGO) definition. Accordingly, we used both the variation in serum creatinine during the first 48 h after ICU admission and the maximal value during the 7 days following ICU admission. Admission serum creatinine was used as baseline serum creatinine when the estimated glomerular filtration rate (eGFR) was above 60 ml/min/1.73 m 2 at admission. Otherwise (n = 117, 59% of the study population), baseline serum

International audience; Fifteen recommendations and a therapeutic algorithm regarding the management of acute respiratory distress syndrome (ARDS) at the early phase in adults are proposed. The Grade of Recommendation Assessment, Development and Evaluation (GRADE) methodology has been followed. Four recommendations (low tidal volume, plateau pressure limitation, no oscillatory ventilation, and prone position) had a high level of proof (GRADE 1 + or 1 -); four (high positive end-expiratory pressure [PEEP] in moderate and severe ARDS, muscle relaxants, recruitment maneuvers, and venovenous extracorporeal membrane oxygenation [ECMO]) a low level of proof (GRADE 2 + or 2 -); seven (surveillance, tidal volume for non ARDS mechanically ventilated patients, tidal volume limitation in the presence of low plateau pressure, PEEP > 5 cmH2O, high PEEP in the absence of deleterious effect, pressure mode allowing spontaneous ventilation after the acute phase, and nitric oxide) corresponded to a level of proof that did not allow use of the GRADE classification and were expert opinions. Lastly, for three aspects of ARDS management (driving pressure, early spontaneous ventilation, and extracorporeal carbon dioxide removal), the experts concluded that no sound recommendation was possible given current knowledge. The recommendations and the therapeutic algorithm were approved by the experts with strong agreement.

Echocardiography is a noninvasive and accurate tool used in the intensive care unit to assess cardiac function and monitor hemodynamics in shocked patients. During severe sepsis or septic shock, several mechanisms can lead to hemodynamic failure and have to be quickly and precisely diagnosed to propose adequate, personalized, and timely hemodynamic therapy. Echocardiography truly provides intensivists with this diagnostic possibility, whether or not there is fluid responsiveness, cardiac dysfunction, or persistent vasoplegia. Acquiring skills in critical care echocardiography is mandatory in improving management and monitoring of patients with sepsis at the bedside. How critical care echocardiography in managing patients with septic shock improves prognosis remains to be elucidated.

Acute right ventricular (RV) failure is a complex clinical syndrome that results from many causes. Research efforts have disproportionately focused on the failing left ventricle, but recently the need has been recognized to achieve a more comprehensive understanding of RV anatomy, physiology, and pathophysiology, and of management approaches. Right ventricular mechanics and function are altered in the setting of either pressure overload or volume overload. Failure may also result from a primary reduction of myocardial contractility owing to ischaemia, cardiomyopathy, or arrhythmia. Dysfunction leads to impaired RV filling and increased right atrial pressures. As dysfunction progresses to overt RV failure, the RV chamber becomes more spherical and tricuspid regurgitation is aggravated, a cascade leading to increasing venous congestion. Ventricular interdependence results in impaired left ventricular filling, a decrease in left ventricular stroke volume, and ultimately low cardiac output and cardiogenic shock. Identification and treatment of the underlying cause of RV failure, such as acute pulmonary embolism, acute respiratory distress syndrome, acute decompensation of chronic pulmonary hypertension, RV infarction, or arrhythmia, is the primary management strategy. Judicious fluid management, use of inotropes and vasopressors, assist devices, and a strategy focusing on RV protection for mechanical ventilation if required all play a role in the clinical care of these patients. Future research should aim to address the remaining areas of uncertainty which result from the complexity of RV haemodynamics and lack of conclusive evidence regarding RV-specific treatment approaches.

BACKGROUND: Right ventricular (RV) adaptation to acute and chronic pulmonary hypertensive syndromes is a significant determinant of short- and long-term outcomes. Although remarkable progress has been made in the understanding of RV function and failure since the meeting of the NIH Working Group on Cellular and Molecular Mechanisms of Right Heart Failure in 2005, significant gaps remain at many levels in the understanding of cellular and molecular mechanisms of RV responses to pressure and volume overload, in the validation of diagnostic modalities, and in the development of evidence-based therapies.METHODS: A multidisciplinary working group of 20 international experts from the American Thoracic Society Assemblies on Pulmonary Circulation and Critical Care, as well as external content experts, reviewed the literature, identified important knowledge gaps, and provided recommendations.RESULTS: This document reviews the knowledge in the field of RV failure, identifies and prioritizes the most pertinent research gaps, and provides a prioritized pathway for addressing these preclinical and clinical questions. The group identified knowledge gaps and research opportunities in three major topic areas: 1) optimizing the methodology to assess RV function in acute and chronic conditions in preclinical models, human studies, and clinical trials; 2) analyzing advanced RV hemodynamic parameters at rest and in response to exercise; and 3) deciphering the underlying molecular and pathogenic mechanisms of RV function and failure in diverse pulmonary hypertension syndromes.CONCLUSIONS: This statement provides a roadmap to further advance the state of knowledge, with the ultimate goal of developing RV-targeted therapies for patients with RV failure of any etiology.

Proficiency in echocardiography and lung ultrasound has become essential for anesthesiologists and critical care physicians. Nonetheless, comprehensive echocardiography measurements often are time-consuming and technically challenging, and conventional 2-dimensional images do not permit evaluation of specific conditions (eg, systolic anterior motion of the mitral valve, pneumothorax), which have important clinical implications in the perioperative setting. M-mode (motion-based) ultrasonographic imaging, however, provides the most reliable temporal resolution in ultrasonography. Hence, M-mode can provide clinically relevant information in echocardiography and lung ultrasound-driven approaches for diagnosis, monitoring, and interventional procedures performed by anesthesiologists and intensivists. Although M-mode is feasible, this imaging modality progressively has been abandoned in echocardiography and is often underutilized in lung ultrasound. This article aims to comprehensively illustrate contemporary applications of M-mode ultrasonography in the anesthesia and critical care medicine practice. Information presented for each clinical application will include image acquisition and interpretation, evidence-based clinical implications in the critically ill and surgical patient, and limitations. The present article focuses on echocardiography and reviews left ventricular function (mitral annular plane systolic excursion, E-point septal separation, fractional shortening, and transmitral propagation velocity); right ventricular function (tricuspid annular plane systolic excursion, subcostal echocardiographic assessment of tricuspid annulus kick, outflow tract fractional shortening, ventricular septal motion, wall thickness, and outflow tract obstruction); volume status and responsiveness (inferior vena cava and superior vena cava diameter and respiratory variability [collapsibility and distensibility indexes]); cardiac tamponade; systolic anterior motion of the mitral valve; and aortic dissection.

INTRODUCTION: This is a state-of-the-art article of the diagnostic process, etiologies and management of acute right ventricular (RV) failure in critically ill patients. It is based on a large review of previously published articles in the field, as well as the expertise of the authors.RESULTS: The authors propose the ten key points and directions for future research in the field. RV failure (RVF) is frequent in the ICU, magnified by the frequent need for positive pressure ventilation. While no universal definition of RVF is accepted, we propose that RVF may be defined as a state in which the right ventricle is unable to meet the demands for blood flow without excessive use of the Frank-Starling mechanism (i.e. increase in stroke volume associated with increased preload). Both echocardiography and hemodynamic monitoring play a central role in the evaluation of RVF in the ICU. Management of RVF includes treatment of the causes, respiratory optimization and hemodynamic support. The administration of fluids is potentially deleterious and unlikely to lead to improvement in cardiac output in the majority of cases. Vasopressors are needed in the setting of shock to restore the systemic pressure and avoid RV ischemia; inotropic drug or inodilator therapies may also be needed. In the most severe cases, recent mechanical circulatory support devices are proposed to unload the RV and improve organ perfusion CONCLUSION: RV function evaluation is key in the critically-ill patients for hemodynamic management, as fluid optimization, vasopressor strategy and respiratory support. RV failure may be diagnosed by the association of different devices and parameters, while echocardiography is crucial.

Background Sepsis-induced myocardial dysfunction is associated with poor outcomes, but traditional measurements of systolic function such as left ventricular ejection fraction (LVEF) do not directly correlate with prognosis. Global longitudinal strain (GLS) utilizing speckle-tracking echocardiography (STE) could be a better marker of intrinsic left ventricular (LV) function, reflecting myocardial deformation rather than displacement and volume changes. We sought to investigate the prognostic value of GLS in patients with sepsis and/or septic shock. Methods We conducted a systematic review (PubMed and Embase up to 26 October 2017) and meta-analysis to investigate the association between GLS and mortality at longest follow up in patients with severe sepsis and/or septic shock. In the primary analysis, we included studies reporting transthoracic echocardiography data on GLS according to mortality. A secondary analysis evaluated the association between LVEF and mortality including data from studies reporting GLS. Results We included eight studies in the primary analysis with a total of 794 patients (survival 68%, n = 540). We found a significant association between worse LV function and GLS values and mortality: standard mean difference (SMD) − 0.26; 95% confidence interval (CI) − 0.47, − 0.04; p = 0.02 (low heterogeneity, I 2 = 43%). No significant association was found between LVEF and mortality in the same population of patients (eight studies; SMD, 0.02; 95% CI − 0.14, 0.17; p = 0.83; no heterogeneity, I 2 = 3%). Conclusions Worse GLS (less negative) values are associated with higher mortality in patients with severe sepsis or septic shock, while such association is not valid for LVEF. More critical care research is warranted to confirm the better ability of STE in demonstrating underlying intrinsic myocardial disease compared to LVEF.

Background Intensive care unit (ICU) survivors have reduced long-term survival compared to the general population. Identifying parameters at ICU discharge that are associated with poor long-term outcomes may prove useful in targeting an at-risk population. The main objective of the study was to identify clinical and biological determinants of death in the year following ICU discharge. Methods FROG-ICU was a prospective, observational, multicenter cohort study of ICU survivors followed 1 year after discharge, including 21 medical, surgical or mixed ICUs in France and Belgium. All consecutive patients admitted to intensive care with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 h following ICU admission and discharged from ICU were included. The main outcome measure was all-cause mortality at 1 year after ICU discharge. Clinical and biological parameters on ICU discharge were measured, including the circulating cardiovascular biomarkers N-terminal pro-B type natriuretic peptide, high-sensitive troponin I, bioactive-adrenomedullin and soluble-ST2. Socioeconomic status was assessed using a validated deprivation index (FDep). Results Of 1570 patients discharged alive from the ICU, 333 (21%) died over the following year. Multivariable analysis identified age, comorbidity, red blood cell transfusion, ICU length of stay and abnormalities in common clinical factors at the time of ICU discharge (low systolic blood pressure, temperature, total protein, platelet and white cell count) as independent factors associated with 1-year mortality. Elevated biomarkers of cardiac and vascular failure independently associated with 1-year death when they are added to multivariable model, with an almost 3-fold increase in the risk of death when combined (adjusted odds ratio 2.84 (95% confidence interval 1.73–4.65), p

While the use of transthoracic echocardiography (TTE) in the ICU is rapidly expanding, the contribution of TTE to altering patient outcomes among ICU patients with sepsis has not been examined. This study was designed to examine the association of TTE with 28-day mortality specifically in that population. The MIMIC-III database was employed to identify patients with sepsis who had and had not received TTE. The statistical approaches utilized included multivariate regression, propensity score analysis, doubly robust estimation, the gradient boosted model, and an inverse probability-weighting model to ensure the robustness of our findings. Significant benefit in terms of 28-day mortality was observed among the TTE patients compared to the control (no TTE) group (odds ratio = 0.78, 95% CI 0.68–0.90, p

We sought to determine the diagnostic ability of the end-expiratory inferior vena cava diameter (IVCEE) to predict fluid responsiveness (FR) and the potential confounding effect of intra-abdominal pressure (IAP). In this multicenter study, 540 consecutive ventilated patients with shock of various origins underwent an echocardiographic assessment by experts. The IVCEE, velocity time integral (VTI) of the left ventricular outflow tract (LVOT) and intra-abdominal pressure (IAP) were measured. Passive leg raising (PLR) was then systematically used to perform a reversible central blood volume expansion. FR was defined by an increase in LVOT VTI ≥ 10% after 1 min of PLR. Since IVCEE was not obtained in 117 patients (22%), 423 were studied (septic shock: 56%), 129 of them (30%) having elevated IAP (≥ 12 mmHg) and 172 of them (41%) exhibiting FR. IVCEE ≤ 13 mm predicted FR with a specificity of at least 80% in 62 patients (15%), while IVCEE ≥ 25 mm predicted the absence of FR with a specificity of at least 80% in 61 patients (14%). In the remaining 300 patients (71%), the intermediate value of IVCEE did not allow predicting FR. An adjusted relationship between IVCEE and FR was observed while this relationship was less pronounced in patients with IAP ≥ 12 mmHg. Measurement of IVCEE in ventilated patients is moderately feasible and poorly predicts FR, with IAP acting as a confounding factor. IVCEE might add some value to guide fluid therapy but should not be used alone for fluid prediction purposes.

Pocket ultrasound devices (PUDs) increase the scope of transthoracic echocardiography. We assessed the ability of emergency physicians (EPs) to obtain and interpret views using PUDs in prehospital emergencies.Nine EPs underwent a 2-day training program focused on acquisition of four views and on evaluation of left ventricular function, right ventricular size, the inferior vena cava, and detection of pericardial effusion. Then, EPs used a PUD to perform transthoracic echocardiography in patients with shock or acute respiratory failure. The quality and interpretation of views were graded by an expert as not obtained/inadequate, adequate, or optimal. Agreement between the expert and the physicians was evaluated using Cohen's κ test.One hundred consecutive exams were evaluated in patients with shock or acute respiratory failure. Parasternal long-axis and short-axis views, and a subcostal view were not obtained or inadequate in 56, 54, and 54 patients, respectively. An apical four-chamber view was not obtained or inadequate in 33 patients. One, two, or three views were graded as adequate or optimal in 86, 65, and 35 patients. Agreement between physicians and experts for left ventricular systolic function, right ventricular size, and pericardial effusion was weak [κ 0.37 (0.17; 0.59), 0.27 (0.023; 0.53), and 0.33 (-0.008; 0.67)]. Agreement for inferior vena cava evaluation was very weak [0.13 (-0.17; 0.43)].After a very short training program, echocardiography using a PUD in prehospital emergencies was feasible in half of patients. Acquisition of technical skills is reasonable, but accurate evaluation of cardiac function may require more extensive training.

Critical care echocardiography (CCE) is a well-established method to evaluate and monitor patients with hemodynamic failure. Use of CCE is a routine part of critical care practice coincident with its introduction into training programs and the widespread availability of courses for attending level intensivists who seek competence in the field [1–3]. We have identified a number of false perceptions regarding CCE (Fig. 1). The editor of Intensive Care Medicine has asked us to review ten of these false myths, the discussion of which is the subject of this editorial.

Intensive Care Medicine is changing. New types of pa pers, such as “What’s New in Intensive Care?”, “Understanding the Disease” and “My Paper 20 Years Later”, form a stable proportion of the articles published in the 2014 issues. This diversification has been received with an extraordinary enthusiasm and appreciation by the worldwide readership, as evidenced by the massive number of hits and downloads. In this first of three 2014 “Year in Review” articles, we cover those papers published in Intensive Care Medicine during the past year which focus on cardiac arrest, ultrasonography in critically ill patients, neurocritical care, ICU-acquired weakness, nutrition, acute kidney injury, as well as a number of miscellaneous topics.

Sepsis induces alterations of coagulation suggesting both hypercoagulable or hypocoagulable features. The result of their combination remains unknown, making it difficult to predict whether one prevails over the other. Thrombin generation tests (TGTs) stand as an interesting tool to establish an integrative phenotype of coagulation. It has been reported that septic patients display a hypocoagulable trait using TGT. However, protein C (PC) system response was not evaluated. We aimed at describing the thrombin generation profile in patients with septic shock under conditions that are sensitive to PC system to evaluate the net results of coagulation abnormalities and to determine whether hypercoagulable or hypocoagulable traits coexist within a given individual. Thrombin generation was studied in plasma from patients presenting with septic shock at diagnosis and 6 h after a conventional therapeutic management using calibrated automated thrombography with or without thrombomodulin (TM) addition. Patients exhibit clear alterations of TGT that present as both consumption-related hypocoagulability (evidenced without TM addition) but also hypercoagulability by decreased sensitivity to the PC system evidenced with TM addition. No difference could be demonstrated between survivors and nonsurvivors at Day 28, but patients who do not respond to therapeutics at 6 h seem to be more hypercoagulable. More importantly, if our results evidence heterogeneity between patients, we show that alterations of coagulation result in an equilibrium in the majority of patients, thus suggesting "normocoagulability"; but, in the presence of a biological imbalance between baseline thrombin generation and sensitivity to TM, the global effect mostly tends toward hypercoagulability. Thus, TGT may help identify distinct biological coagulation phenotypes in the complex alterations induced by sepsis.

The ventilatory strategy for ARDS has been regularly amended over the last 40 years as knowledge of the pathophysiology of ARDS has increased. Initially focused mainly on the lung with the objectives of "opening the lung" and optimizing arterial oxygen saturation, this strategy now also takes into account pulmonary vascular injury and its effects on the right ventricle and on hemodynamics. Hemodynamic devices now available at the bedside, such as echocardiography, allow intensivists to evaluate respiratory settings according to right ventricular tolerance. Here, we review the pathophysiology of pulmonary vascular dysfunction in ARDS, consider the beneficial and deleterious effects of mechanical ventilation, describe the incidence and meaning of acute cor pulmonale based on recent studies in large series of patients, and propose a new, although not strictly validated, approach based on the protection of both the lung and right ventricle. One of our conclusions is that evaluating the right ventricle may help intensivists to assess the balance between recruitment and overdistension induced by the ventilatory strategy. Prone positioning with its beneficial effects on the lung and also on hemodynamics (the right ventricle) is a good illustration of this. Readers should be aware that most of the information given in this article reflects the point of view of the authors. Although based on clinical observations, clinical studies, and well-known pathophysiology, there is no evidence-based medicine to support this clinical commentary. Other approaches may be favored, in which case our article should be read as another attempt to help intensivists to improve management of ARDS.

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