Relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study

International audienceIntroduction: Because of disturbed renal autoregulation, patients experiencing hypotension-induced renal insult might need higher levels of mean arterial pressure (MAP) than the 65 mmHg recommended level in order to avoid the progression of acute kidney insufficiency (AKI)

Comparison of prognostic factors between bacteraemic and non-bacteraemic critically ill immunocompetent patients in community-acquired severe pneumococcal pneumonia: a STREPTOGENE sub-study.

BACKGROUND: The presence of bacteraemia in pneumococcal pneumonia in critically ill patients does not appear to be a strong independent prognostic factor in the existing literature. However, there may be a specific pattern of factors associated with mortality for ICU patients with bacteraemic pneumococcal community-acquired pneumonia (CAP). We aimed to compare the factors associated with mortality, according to the presence of bacteraemia or not on admission, for patients hospitalised in intensive care for severe pneumococcal CAP. METHODS: This was a post hoc analysis of data from the prospective, observational, multicentre STREPTOGENE study in immunocompetent Caucasian adults admitted to intensive care in France between 2008 and 2012 for pneumococcal CAP. Patients were divided into two groups based on initial blood culture (positive vs. negative) for Streptococcus pneumoniae. The primary outcome was hospital mortality, which was compared between the two groups using odds ratios according to predefined variables to search for a prognostic interaction present in bacterial patients but not non-bacteraemic patients. Potential differences in the distribution of serotypes between the two groups were assessed. The prognostic consequences of the presence or not of initial bi-antibiotic therapy were assessed, specifically in bacteraemic patients. RESULTS: Among 614 included patients, 274 had a blood culture positive for S. pneumoniae at admission and 340 did not. The baseline difference between the groups was more frequent leukopaenia (26% vs. 14%, p = 0.0002) and less frequent pre-hospital antibiotic therapy (10% vs. 16.3%, p = 0.024) for the bacteraemic patients. Hospital mortality was not significantly different between the two groups (p = 0.11). We did not observe any prognostic factors specific to the bacteraemic patient population, as the statistical comparison of the odds ratios, as an indication of the association between the predefined prognostic parameters and mortality, showed them to be similar for the two groups. Bacteraemic patients more often had invasive serotypes but less often serotypes associated with high case fatality rates (p = 0.003). The antibiotic regimens were similar for the two groups. There was no difference in mortality for patients in either group given a beta-lactam alone vs. a beta-lactam combined with a macrolide or fluoroquinolone. CONCLUSION: Bacteraemia had no influence on the mortality of immunocompetent Caucasian adults admitted to intensive care for severe pneumococcal CAP, regardless of the profile of the associated prognostic factors

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A Machine Learning Approach to Estimate the Glomerular Filtration Rate in Intensive Care Unit Patients Based on Plasma Iohexol Concentrations and Covariates

International audienceObjective This work aims to evaluate whether a machine learning approach is appropriate to estimate the glomerular filtrationrate in intensive care unit patients based on sparse iohexol pharmacokinetic data and a limited number of predictors.Methods Eighty-six unstable patients received 3250 mg of iohexol intravenously and had nine blood samples collected 5,30, 60, 180, 360, 540, 720, 1080, and 1440 min thereafter. Data splitting was performed to obtain a training (75%) and a testset (25%). To estimate the glomerular filtration rate, 37 candidate potential predictors were considered and the best machinelearning approach among multivariate-adaptive regression spline and extreme gradient boosting (Xgboost) was selected basedon the root-mean-square error. The approach associated with the best results in a ten-fold cross-validation experiment wasthen used to select the best limited combination of predictors in the training set, which was finally evaluated in the test set.Results The Xgboost approach yielded the best performance in the training set. The best combination of covariates comprisediohexol concentrations at times 180 and 720 min; the relative deviation from these theoretical times; the difference betweenthese two concentrations; the Simplified Acute Physiology Score II; serum creatinine; and the fluid balance. It resulted in aroot-mean-square error of 6.2 mL/min and an r2 of 0.866 in the test set. Interestingly, the eight patients in the test set with aglomerular filtration rate < 30 mL/min were all predicted accordingly.Conclusions Xgboost provided accurate glomerular filtration rate estimation in intensive care unit patients based on twotimed blood concentrations after iohexol intravenous administration and three additional predictors

Failure of Deferasirox, an Iron Chelator Agent, Combined with Antifungals in a Case of Severe Zygomycosis

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Acute Respiratory Distress Syndrome (ARDS)-Associated Acute Cor Pulmonale and Patent Foramen Ovale: A Multicenter Noninvasive Hemodynamic Study

International audienceINTRODUCTION: Acute cor pulmonale (ACP) and patent foramen ovale (PFO) remain common in patients under protective ventilation for acute respiratory distress syndrome (ARDS). We sought to describe the hemodynamic profile associated with either ACP or PFO, or both, during the early course of moderate-to-severe ARDS using echocardiography. METHODS: In this 32-month prospective multicenter study, 195 patients with moderate-to-severe ARDS were assessed using echocardiography during the first 48~h of admission (age: 56 (SD: 15) years; Simplified Acute Physiology Score: 46 (17); PaO2/FiO2: 115 (39); VT: 6.5 (1.7) mL/kg; PEEP: 11 (3) cmH2O; driving pressure: 15 (5) cmH2O). ACP was defined by the association of right ventricular (RV) dilatation and systolic paradoxical ventricular septal motion. PFO was detected during a contrast study using agitated saline in the transesophageal bicaval view. RESULTS: ACP was present in 36 patients, PFO in 21 patients, both PFO and ACP in 8 patients and the 130 remaining patients had neither PFO nor ACP. Patients with ACP exhibited a restricted left ventricle (LV) secondary to RV dilatation and had concomitant RV dysfunction, irrespective of associated PFO, but preserved LV systolic function. Despite elevated systolic pulmonary artery pressure (sPAP), patients with isolated PFO had a normal RV systolic function. sPAP and PaCO2 levels were significantly correlated. CONCLUSIONS: In patients under protective mechanical ventilation with moderate-to-severe ARDS, ACP was associated with LV restriction and RV failure, whether PFO was present or not. Despite elevated sPAP, PFO shunting was associated with preserved RV systolic function