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PurposeMechanisms of circulatory failure are complex and frequently intricate in septic shock. Better characterization could help to optimize hemodynamic support.MethodsTwo 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.FindingsA 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 < 0.001 for both).ConclusionOur clustering approach on a large population of septic shock patients, based on clinical and echocardiographic parameters, was able to characterize five different cardiovascular phenotypes. How this could help physicians to optimize hemodynamic support should be evaluated in the future.

PurposeTo assess the role of left ventricular overload and cumulated fluid balance in the development weaning-induced pulmonary edema (WIPO).MethodsVentilated patients in sinus rhythm with COPD and/or heart failure (ejection fraction ≤ 40%) were studied. Echocardiography was performed immediately before and during a 30-min spontaneous breathing trial (SBT) using a T-tube. Patients who failed were treated according to echocardiography results before undergoing a second SBT.ResultsTwelve of 59 patients failed SBT, all of them developing WIPO. Patients who succeeded SBT had lower body weight (− 2.5 kg [− 4.8; − 1] vs. + 0.75 kg [− 2.95;  + 5.57]: p = 0.02) and cumulative fluid balance (− 2326 ml [− 3715;  + 863] vs. + 143 ml [− 2654; + 4434]: p = 0.007) than those who developed WIPO. SBT-induced central hemodynamic changes were more pronounced in patients who developed WIPO, with higher E wave velocity (122 cm/s [92; 159] vs. 93 cm/s [74; 109]: p = 0.017) and E/A ratio (2.1 [1.2; 3.6] vs. 0.9 [0.8; 1.4]: p = 0.001), and shorter E wave deceleration time (85 ms [72; 125] vs. 147 ms [103; 175]: p = 0.004). After echocardiography-guided treatment, all patients who failed the first SBT were successfully extubated. Fluid balance was then negative (− 2224 ml [− 7056; + 100] vs. + 146 ml [− 2654; + 4434]: p = 0.005). Left ventricular filling pressures were lower (E/E′: 7.3 [5; 10.4] vs. 8.9 [5.9; 13.1]: p = 0.028); SBT-induced increase in E wave velocity (+ 10.6% [− 2.7/ + 18] vs. + 25.6% [+ 12.7/ + 49]: p = 0.037) and of mitral regurgitation area were significantly smaller.ConclusionIn high-risk patients, WIPO appears related to overloaded left ventricle associated with excessive fluid balance. SBT-induced central hemodynamic changes monitored by CCE help in guiding therapy for successful weaning.

Approximately two-thirds of patients admitted to the intensive care unit (ICU) for coronavirus disease-19 (COVID-19) pneumonia present with the acute respiratory distress syndrome (ARDS) [1]. [...]we sought to describe cardiovascular phenotypes identified using transesophageal echocardiography (TEE) in ventilated COVID-19 patients with ARDS and to compare them to those of patients with flu-induced ARDS. Mekontso Dessap A, Boissier F, Charron C, Bégot E, Repessé X, Legras A, Brun-Buisson C, Vignon P, Vieillard-Baron A. Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact.

PurposeExploratory 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).MethodsPost-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.ResultsOf 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).ConclusionRV 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.

Background Left ventricular (LV) diastolic dysfunction is highly prevalent in the general population and associated with a significant morbidity and mortality. Its prognostic role in patients sustaining septic shock in the intensive care unit (ICU) remains controversial. Accordingly, we investigated whether LV diastolic function was independently associated with ICU mortality in a cohort of septic shock patients assessed using critical care echocardiography. Methods Over a 5-year period, patients hospitalized in a Medical–Surgical ICU who underwent an echocardiographic assessment with digitally stored images during the initial management of a septic shock were included in this retrospective single-center study. Off-line echocardiographic measurements were independently performed by an expert in critical care echocardiography who was unaware of patients’ outcome. LV diastolic dysfunction was defined by the presence of a lateral E ′ maximal velocity <10 cm/s. A multivariate analysis was performed to determine independent risk factors associated with ICU mortality. Results Among the 540 patients hospitalized in the ICU with septic shock during the study period, 223 were studied (140 men [63 %]; age 64 ± 13 years; SAPS II 55 ± 18; SOFA 10 ± 3; Charlson 3.5 ± 2.5) and 204 of them (91 %) were mechanically ventilated. ICU mortality was 35 %. LV diastolic dysfunction was observed in 31 % of patients. The proportion of LV diastolic dysfunction tended to be higher in non-survivors than in their counterparts (28/78 [36 %] vs. 41/145 [28 %]: p  = 0.15). Inappropriate initial antibiotic therapy (OR 4.17 [CI 95 % 1.33–12.5]: p  = 0.03), maximal dose of vasopressors (OR 1.38 [CI 95 % 1.16–1.63]: p  = 0.01), SOFA score (OR 1.16 [CI 95 % 1.02–1.32]: p  = 0.02) and lateral E ′ maximal velocity (OR 1.12 [CI 95 % 1.01–1.24]: p  = 0.02) were independently associated with ICU mortality. After adjusting for the SAPS II score, inappropriate initial antibiotic therapy and maximal dose of vasopressors remained independent factors for ICU mortality, whereas a trend was only observed for lateral E ′ maximal velocity (OR 1.11 [CI 95 % 0.99–1.23]: p  = 0.07). Conclusion The present study suggests that LV diastolic function might be associated with ICU mortality in patients with septic shock. A multicenter prospective study assessing a large cohort of patients using serial echocardiographic examinations remains required to confirm the prognostic value of LV diastolic dysfunction in septic shock.

Prostatic abscesses are an uncommon disease usually caused by enterobacteria. They mostly occur in immunodeficient patients. It is thus extremely rare to have a Staphylococcal prostatic abscess in a young immunocompetent patient. A 20-year-old patient was treated with ofloxacin for a suspicion of prostatitis. An ultrasonography was performed because of persisting symptoms and showed acute urinary retention and prostatic abscesses. So the empirical antibiotic therapy was modified with ceftriaxone/amikacin. The disease worsened to severe sepsis and the patient was admitted in ICU. CT-scan and MRI confirmed three abscesses with perirectal infiltration and the bacteriological samples (abscesses and blood cultures) were positive to methicillin-susceptible Staphylococcus aureus producing Panton-Valentine leukocidine. The treatment was changed with fosfomycin/ofloxacin which resulted in a general improvement and the regression of the abscesses. Staphyloccocus aureus producing Panton-Valentine leukocidin are most commonly responsible for skin and soft tissue infections. To this day, no other case of prostatic abscess due to this strain but susceptible to methicillin has been described.

BackgroundThe objective of this study was to evaluate the ability of endothelial biomarkers to early predict clinical deterioration of patients admitted to the emergency department (ED) with a suspected sepsis. This was a prospective, multicentre, international study conducted in EDs. Adult patients with suspected acute bacterial infection and sepsis were enrolled but only those with confirmed infection were analysed. The kinetics of biomarkers and organ dysfunction were collected at T0, T6 and T24 hours after ED admission to assess prognostic performances of sVEGFR2, suPAR and procalcitonin (PCT). The primary outcome was the deterioration within 72 h and was defined as a composite of relevant outcomes such as death, intensive care unit admission and/or SOFA score increase validated by an independent adjudication committee.ResultsAfter adjudication of 602 patients, 462 were analysed including 124 who deteriorated (27%). On admission, those who deteriorated were significantly older (73 [60–82] vs 63 [45–78] y-o, p < 0.001) and presented significantly higher SOFA scores (2.15 ± 1.61 vs 1.56 ± 1.40, p = 0.003). At T0, sVEGFR2 (5794 [5026–6788] vs 6681 [5516–8059], p < 0.0001), suPAR (6.04 [4.42–8.85] vs 4.68 [3.50–6.43], p < 0.0001) and PCT (7.8 ± 25.0 vs 5.4 ± 17.9 ng/mL, p = 0.001) were associated with clinical deterioration. In multivariate analysis, low sVEGFR2 expression and high suPAR and PCT levels were significantly associated with early deterioration, independently of confounding parameters (sVEGFR2, OR = 1.53 [1.07–2.23], p < 0.001; suPAR, OR = 1.57 [1.21–2.07], p = 0.003; PCT, OR = 1.10 [1.04–1.17], p = 0.0019). Combination of sVEGFR2 and suPAR had the best prognostic performance (AUC = 0.7 [0.65–0.75]) compared to clinical or biological variables.ConclusionssVEGFR2, either alone or combined with suPAR, seems of interest to predict deterioration of patients with suspected bacterial acute infection upon ED admission and could help front-line physicians in the triage process.

PurposeInvestigate safety and tolerability of adrecizumab, a humanized monoclonal adrenomedullin antibody, in septic shock patients with high adrenomedullin.MethodsPhase-2a, double-blind, randomized, placebo-controlled biomarker-guided trial with a single infusion of adrecizumab (2 or 4 mg/kg b.w.) compared to placebo. Patients with adrenomedullin above 70 pg/mL, < 12 h of vasopressor start for septic shock were eligible. Randomization was 1:1:2. Primary safety (90-day mortality, treatment emergent adverse events (TEAE)) and tolerability (drug interruption, hemodynamics) endpoints were recorded. Efficacy endpoints included the Sepsis Support Index (SSI, reflecting ventilator- and shock-free days alive), change in Sequential-related Organ Failure Assessment (SOFA) and 28-day mortality.Results301 patients were enrolled (median time of 8.5 h after vasopressor start). Adrecizumab was well tolerated (one interruption, no hemodynamic alteration) with no differences in frequency and severity in TEAEs between treatment arms (TEAE of grade 3 or higher: 70.5% in the adrecizumab group and 71.1% in the placebo group) nor in 90-day mortality. Difference in change in SSI between adrecizumab and placebo was 0.72 (CI −1.93–0.49, p = 0.24). Among various secondary endpoints, delta SOFA score (defined as maximum versus minimum SOFA) was more pronounced in the adrecizumab combined group compared to placebo [difference at 0.76 (95% CI 0.18–1.35); p = 0.007]. 28-day mortality in the adrecizumab group was 23.9% and 27.7% in placebo with a hazard ratio of 0.84 (95% confidence interval 0.53–1.31, log-rank p = 0.44).ConclusionsOverall, we successfully completed a randomized trial evaluating selecting patients for enrolment who had a disease-related biomarker. There were no overt signals of harm with using two doses of the adrenomedullin antibody adrecizumab; however, further randomized controlled trials are required to confirm efficacy and safety of this agent in septic shock patients.