Development and validation of a clinico-biological score to predict outcomes in patients with drowning-associated cardiac arrest.

BACKGROUND: While several scoring systems have been developed to predict short-term outcome in out-of-hospital cardiac arrest patients, there is currently no dedicated prognostic tool for drowning-associated cardiac arrest (DACA) patients. METHODS: Patients experiencing DACA from two retrospective multicenter cohorts of drowning patients were included in the present study. Among the patients from the development cohort, risk-factors for day-28 mortality were assessed by logistic regression. A prediction score was conceived and assessed in patients from the validation cohort. RESULTS: Among the 103 included patients from the development cohort, the day-28 mortality rate reached 51% (53/103). Identified independent early risk-factors for day-28 mortality included cardiopulmonary resuscitation duration longer than 20 min (OR 6.40 [95% CI 1.88-23.32]; p = 0.003), temperature at Intensive Care Unit admission <34 °C (OR 8.84 [95% CI 2.66-32.92]; p < 0.001), need for invasive mechanical ventilation (OR 6.83 [95% CI 1.47-40.87]; p = 0.02) and lactate concentration > 7 mmol/L (OR 3.56 [95% CI 1.01-13.07]; p = 0.04). The Area Under the ROC Curve (AUC) of the developed score based on those variables reached 0.91 (95% CI, 0.86-0.97). The optimal cut-off for predicting poor outcomes was 4 points with a sensitivity of 92% (95% CI, 82-98%), a specificity of 82% (95% CI, 67-91%), a positive predictive value (PPV) of 84% (95% CI, 72-95%) and a negative predictive value (NPV) of 91% (95% CI, 79-96%). The assessment of this score on the validation cohort of 81 patients exhibited an AUC of 0.82. Using the same 4 points threshold, sensitivity, specificity, PPV and NPV values of the validation cohort were: 81%, 67%, 72% and 77%, respectively. CONCLUSION: In patients suffering from drowning induced initial cardiac arrest admitted to ICU with a DACA score ≥ 4, the likelihood of survival at day-28 is significantly lower. Prospective validation of the DACA score and assessment of its usefulness are warranted in the future.

Covid-19-associated pulmonary aspergillosis in mechanically ventilated patients: incidence and outcome in a French multicenter observational cohort (APICOVID).

BACKGROUND: Recent studies identified coronavirus disease 2019 (COVID-19) as a risk factor for invasive pulmonary aspergillosis (IPA) but produced conflicting data on IPA incidence and impact on patient outcomes. We aimed to determine the incidence and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) in mechanically ventilated patients. METHODS: We performed a multicenter retrospective observational cohort study in consecutive adults admitted to 15 French intensive care units (ICUs) in 2020 for COVID-19 requiring mechanical ventilation. CAPA was diagnosed and graded according to 2020 ECMM/ISHAM consensus criteria. The primary objective was to determine the incidence of proven/probable CAPA, and the secondary objectives were to identify risk factors for proven/probable CAPA and to assess associations between proven/probable CAPA and patient outcomes. RESULTS: The 708 included patients (522 [73.7%] men) had a mean age of 65.2 ± 10.8 years, a median mechanical ventilation duration of 15.0 [8.0-27.0] days, and a day-90 mortality rate of 28.5%. Underlying immunosuppression was present in 113 (16.0%) patients. Corticosteroids were used in 348 (63.1%) patients. Criteria for probable CAPA were met by 18 (2.5%) patients; no patient had histologically proven CAPA. Older age was the only factor significantly associated with probable CAPA (hazard ratio [HR], 1.04; 95% CI 1.00-1.09; P = 0.04). Probable CAPA was associated with significantly higher day-90 mortality (HR, 2.07; 95% CI 1.32-3.25; P = 0.001) but not with longer mechanical ventilation or ICU length of stay. CONCLUSION: Probable CAPA is a rare but serious complication of severe COVID-19 requiring mechanical ventilation and is associated with higher day-90 mortality.

Prediction of pulmonary aspergillosis in patients with ventilator-associated pneumonia.

BACKGROUND: Predictors of ICU-acquired pulmonary aspergillosis (IPA) are not well-established in critically ill patients with ventilator-associated pneumonia (VAP), making IPA commonly misdiagnosed and anti-fungal therapy delayed. We aimed to develop a clinical score for prediction of IPA among patients with VAP. METHODS: Mechanically ventilated patients who developed VAP in 4 ICUs in Bretagne, Western France, were included. The score was constructed in a learning cohort, based on predictors of IPA in logistic regression model, and validated in a validation cohort. RESULTS: Among 1636 mechanically ventilated patients, 215 developed VAP but only 39 developed IPA (4 possible and 35 probable/putative) (18%). Most cases (31/39) were documented through a positive broncho-alveolar sample culture. Independent predictors of IPA were immunodepression (including onco-hematological disorder, immunomodulatory treatment, solid organ transplant, neutropenia < 0.5G/L and high-dose steroids ≥ 1 mg/kg/day of prednisolone equivalent) (p = 0.001; score = 1 point) and lymphocyte count at admission < 0.8 G/L (p = 0.019; score = 1 point). Operational values of the predictive score in the learning/validation cohort were 50%/52% sensitivity and 90%/87% specificity, respectively, for high PiPa score (score = 2) and 94%/91% sensitivity and 44%/46% specificity, respectively, for moderate PiPa score (score = 1). Finally, the AUC for the prediction of IPA was 0.783 in the learning cohort and 0.770 in the validation cohort. CONCLUSIONS: We evaluated a clinical score with good predictive value which may help to predict IPA in patient with VAP. External validation will be needed to confirm our preliminary findings.

Clinical features, etiologies, and outcomes in adult patients with meningoencephalitis requiring intensive care (EURECA): an international prospective multicenter cohort study.

PURPOSE: We aimed to characterize the outcomes of patients with severe meningoencephalitis requiring intensive care. METHODS: We conducted a prospective multicenter international cohort study (2017-2020) in 68 centers across 7 countries. Eligible patients were adults admitted to the intensive care unit (ICU) with meningoencephalitis, defined by an acute onset of encephalopathy (Glasgow coma scale (GCS) score [Formula: see text] 13), a cerebrospinal fluid pleocytosis [Formula: see text] 5 cells/mm3, and at least two of the following criteria: fever, seizures, focal neurological deficit, abnormal neuroimaging, and/or electroencephalogram. The primary endpoint was poor functional outcome at 3 months, defined by a score of three to six on the modified Rankin scale. Multivariable analyses stratified on centers investigated ICU admission variables associated with the primary endpoint. RESULTS: Among 599 patients enrolled, 589 (98.3%) completed the 3-month follow-up and were included. Overall, 591 etiologies were identified in those patients which were categorized into five groups: acute bacterial meningitis (n = 247, 41.9%); infectious encephalitis of viral, subacute bacterial, or fungal/parasitic origin (n = 140, 23.7%); autoimmune encephalitis (n = 38, 6.4%); neoplastic/toxic encephalitis (n = 11, 1.9%); and encephalitis of unknown origin (n = 155, 26.2%). Overall, 298 patients (50.5%, 95% CI 46.6-54.6%) had a poor functional outcome, including 152 deaths (25.8%). Variables independently associated with a poor functional outcome were age > 60 years (OR 1.75, 95% CI 1.22-2.51), immunodepression (OR 1.98, 95% CI 1.27-3.08), time between hospital and ICU admission > 1 day (OR 2.02, 95% CI 1.44-2.99), a motor component on the GCS [Formula: see text] 3 (OR 2.23, 95% CI 1.49-3.45), hemiparesis/hemiplegia (OR 2.48, 95% CI 1.47-4.18), respiratory failure (OR 1.76, 95% CI 1.05-2.94), and cardiovascular failure (OR 1.72, 95% CI 1.07-2.75). In contrast, administration of a third-generation cephalosporin (OR 0.54, 95% CI 0.37-0.78) and acyclovir (OR 0.55, 95% CI 0.38-0.80) on ICU admission were protective. CONCLUSION: Meningoencephalitis is a severe neurologic syndrome associated with high mortality and disability rates at 3 months. Actionable factors for which improvement could be made include time from hospital to ICU admission, early antimicrobial therapy, and detection of respiratory and cardiovascular complications at admission.

Anticoagulation strategy and safety in critically ill COVID-19 patients: a French retrospective multicentre study.

BACKGROUND: Patients with critical illness due to COVID-19 exhibit increased coagulability associated with a high risk of venous thrombo-embolism (VTE). Data on prophylactic anticoagulation for these patients are limited and conflicting. The purpose of this study was to evaluate whether intermediate-dose prophylactic anticoagulation in patients with COVID-19 requiring ICU admission was associated with better outcomes compared to standard-dose prophylactic anticoagulation. METHODS: We retrospectively included adults admitted with severe COVID-19 to any of 15 ICUs, in 2020 or 2021. We compared the groups given intermediate-dose vs. standard-dose prophylactic anticoagulation. The primary outcome was all-cause day-90 mortality. Secondary outcomes were VTE (pulmonary embolism or deep vein thrombosis), ICU stay length, and adverse effects of anticoagulation. RESULTS: Of 1174 included patients (mean age, 63 years), 399 received standard-dose and 775 intermediate-dose prophylactic anticoagulation. Of the 211 patients who died within 90 days, 86 (21%) received intermediate and 125 (16%) standard doses. After adjustment on early corticosteroid therapy and critical illness severity, there were no significant between-group differences in day-90 mortality (hazard ratio [HR], 0.73; 95%CI, 0.52-1.04; p = 0.09) or ICU stay length (HR, 0.93; 95%CI, 0.79-1.10; p = 0.38). Intermediate-dose anticoagulation was significantly associated with fewer VTE events (HR, 0.55; 95%CI, 0.38-0.80; p < 0.001). Bleeding events occurred in similar proportions of patients in the two groups (odds ratio, 0.86; 95%CI, 0.50-1.47; p = 0.57). CONCLUSIONS: Mortality on day 90 did not differ between the groups given standard-dose and intermediate-dose prophylactic anticoagulation, despite a higher incidence of VTE in the standard-dose group.

Critically ill severe hypothyroidism: a retrospective multicenter cohort study.

BACKGROUND: Severe hypothyroidism (SH) is a rare but life-threatening endocrine emergency. Only a few data are available on its management and outcomes of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management, and in-ICU and 6-month survival rates of these patients. METHODS: We conducted a retrospective, multicenter study over 18 years in 32 French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Disease 10th revision. Inclusion criteria were the presence of biological hypothyroidism associated with at least one cardinal sign among alteration of consciousness, hypothermia and circulatory failure, and at least one SH-related organ failure. RESULTS: Eighty-two patients were included in the study. Thyroiditis and thyroidectomy represented the main SH etiologies (29% and 19%, respectively), while hypothyroidism was unknown in 44 patients (54%) before ICU admission. The most frequent SH triggers were levothyroxine discontinuation (28%), sepsis (15%), and amiodarone-related hypothyroidism (11%). Clinical presentations included hypothermia (66%), hemodynamic failure (57%), and coma (52%). In-ICU and 6-month mortality rates were 26% and 39%, respectively. Multivariable analyses retained age > 70 years [odds ratio OR 6.01 (1.75-24.1)] Sequential Organ-Failure Assessment score cardiovascular component ≥ 2 [OR 11.1 (2.47-84.2)] and ventilation component ≥ 2 [OR 4.52 (1.27-18.6)] as being independently associated with in-ICU mortality. CONCLUSIONS: SH is a rare life-threatening emergency with various clinical presentations. Hemodynamic and respiratory failures are strongly associated with worse outcomes. The very high mortality prompts early diagnosis and rapid levothyroxine administration with close cardiac and hemodynamic monitoring.

Multiple-site decontamination in mechanically ventilated ICU patients: A real-life study.

INTRODUCTION: Decontamination regimen decreases acquired infection (ICU-AI) incidence but has remained controversial, mostly because it contains a course of intravenous antibiotic. Multiple-site decontamination (MSD), which does not include systemic antibiotics, has been less widely studied but is associated with lower risks of ventilator-associated pneumonia (VAP), bloodstream infection (BSI) and multidrug resistant micro-organism (MDRO) acquisition. We aimed to confirm these favorable outcomes. METHODS: A prospective pre/post-observational study was conducted in 5 ICUs in western France. Among them, 4 implemented MSD, whereas the fifth applied standard care (SC) throughout the study period. Patients who required intubation were eligible for study and divided into two groups: the MSD group if they were admitted to an ICU that already implemented MSD, or the SC group. The primary objective was to measure ICU-AI incidence. RESULTS: Close to 1400 (1346) patients were available for analysis (334 in the MSD and 1012 patients in the SC group). In a multivariable Poisson regression model, MSD was independently associated with decreased incidence of ICU-AI (IRR = 0.33; 95 %CI [0.18-0.60] p < 0.001). Non-parsimonious propensity-score matching resulted in 334 patient-pairs with well-balanced baseline characteristics. There was a lower incidence of ICU-AI(6.3 % vs 20.7 % p < 0.001), VAP (3.6 % vs 16.2 % p < 0.001) and BSI (3.0 % vs 7.2 % p = 0.029) in the MSD group as compared with the SC group. Five (1.5 %) and 11 (3.3 %) patients respectively acquired MDRO (p = 0.206). CONCLUSION: MSD is associated with decreased risk of ICU-AI, VAP and BSI, with no increase in MDRO acquisition.

Continued enteral nutrition until extubation compared with fasting before extubation in patients in the intensive care unit: an open-label, cluster-randomised, parallel-group, non-inferiority trial.

BACKGROUND: Fasting is frequently imposed before extubation in patients in intensive care units, with the aim to reduce risk of aspiration. This unevaluated practice might delay extubation, increase workload, and reduce caloric intake. We aimed to compare continued enteral nutrition until extubation with fasting before extubation in patients in the intensive care unit. METHODS: We conducted an open-label, cluster-randomised, parallel-group, non-inferiority trial in 22 intensive care units in France. Patients aged 18 years or older were eligible for enrolment if they had received invasive mechanical ventilation for at least 48 h in the intensive care unit and received prepyloric enteral nutrition for at least 24 h at the time of extubation decision. Centres were randomly assigned (1:1) to continued enteral nutrition until extubation or 6-h fasting with concomitant gastric suctioning before extubation, to be applied for all patients within the unit. Masking was not possible because of the nature of the trial. The primary outcome was extubation failure (composite criteria of reintubation or death) within 7 days after extubation, assessed in both the intention-to-treat and per-protocol populations. The non-inferiority margin was set at 10%. Pneumonia within 14 days of extubation was a key secondary endpoint. This trial is now complete and is registered with ClinicalTrials.gov, NCT03335345. FINDINGS: Between April 1, 2018, and Oct 31, 2019, 7056 patients receiving enteral nutrition and mechanical ventilation were admitted to the intensive care units and 4198 were assessed for eligibility. 1130 patients were enrolled and included in the intention-to-treat population and 1008 were included in the per-protocol population. In the intention-to-treat population, extubation failure occurred in 106 (17·2%) of 617 patients assigned to receive continued enteral nutrition until extubation versus 90 (17·5%) of 513 assigned to fasting, meeting the a priori defined non-inferiority criterion (absolute difference -0·4%, 95% CI -5·2 to 4·5). In the per-protocol population, extubation failure occurred in 101 (17·0%) of 595 patients assigned to receive continued enteral nutrition versus 74 (17·9%) of 413 assigned to fasting (absolute difference -0·9%, 95% CI -5·6 to 3·7). Pneumonia within 14 days of extubation occurred in ten (1·6%) patients assigned to receive continued enteral nutrition and 13 (2·5%) assigned to fasting (rate ratio 0·77, 95% CI 0·22 to 2·69). INTERPRETATION: Continued enteral nutrition until extubation in critically ill patients in the intensive care unit was non-inferior to a 6-h fasting maximum gastric vacuity strategy comprising continuous gastric tube suctioning, in terms of extubation failure within 7 days (a patient-centred outcome), and thus represents a potential alternative in this population. FUNDING: French Ministry of Health. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Clinical and microbiological features of drowning-associated pneumonia: a retrospective multicentre cohort study.

OBJECTIVE: Pneumonia is the most frequent infectious complication in patients who have experienced drowning that requires intensive care unit (ICU) admission. We aimed to describe clinical, microbiological, and therapeutic data as well as predictors and impacts of such pneumonia on patients' outcomes. METHODS: We conducted a retrospective, multicentre study (2013-2020) of 270 consecutive patients admitted for drowning to 14 ICUs in Western France. Their baseline characteristics and outcomes were compared according to the occurrence of drowning-associated pneumonia (DAP), defined as pneumonia diagnosed within 48 hours of ICU admission. A Cox regression model was used to compare survival on day 28, and logistic regression was used to identify risk factors for DAP. Microbiological characteristics and empirical antibacterial treatment were also analysed. RESULTS: Among the 270 patients admitted to the ICU for drowning, 101 (37.4%) and 33 (12.2%) experienced pneumonia and microbiologically proven DAP, respectively. The occurrence of pneumonia was associated with higher severity scores at ICU admission (median Simplified Acute Physiology Score II, 34 [interquartile range {IQR}, 25-55] vs. 45 [IQR, 28-67]; p 0.006) and longer ICU length of stay (2 days [IQR, 1-3] vs. 4 days [IQR, 2-7]; p < 0.001). The 28-day mortality rate was higher among these patients (29/101 [28.7%] vs. 26/169 [15.4%]; p 0.013). Microbiologically proven DAP remained associated with higher 28-day mortality after adjustments for cardiac arrest and water salinity (adjusted hazard ratio, 1.86 [95% CI, 1.06-3.28]; p 0.03). A microbiological analysis of respiratory samples showed a high proportion of gram-negative bacilli (23/56; 41.1%), with a high prevalence of amoxicillin-clavulanate resistance (12/33; 36.4%). CONCLUSIONS: Pneumonia is a common complication in patients admitted in the ICU for drowning and is associated with increased mortality.

MONOCYTIC MYELOID-DERIVED SUPPRESSOR CELL EXPANSION AFTER CARDIAC SURGERY WITH CARDIOPULMONARY BYPASS INDUCES LYMPHOCYTE DYSFUNCTION.

ABSTRACT: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with an immune paresis that predisposes to the development of postoperative infections and sepsis. Among factors responsible for CPB-induced immunosuppression, circulating myeloid-derived suppressor cells (MDSCs) have been found to induce early lymphocyte apoptosis and lymphocyte proliferation inhibition. However, the mechanisms involved are not fully understood. In this study, we found that the main lymphocyte subsets decreased significantly 24 h after cardiac surgery with CBP. As expected, cardiac surgery with CPB induced a monocytic MDSC expansion associated with an increased T-cell apoptosis and decreased proliferation capacity. Noteworthy, granulocytic MDSCs remain stable. Myeloid-derived suppressor cell depletion restored the ability of T-cell to proliferate ex vivo . After CPB, indoleamine 2,3-dioxygenase activity and IL-10 plasma level were increased such as programmed death-ligand 1 monocytic expression, whereas plasma level of arginine significantly decreased. Neither the inhibition of indoleamine 2,3-dioxygenase activity nor the use of anti-programmed death-ligand 1 or anti-IL-10 blocking antibody restored the ability of T-cell to proliferate ex vivo . Only arginine supplementation restored partially the ability of T-cell to proliferate.

Association of early dexamethasone therapy with mortality in critically Ill COVID-19 patients: a French multicenter study.

BACKGROUND: Dexamethasone is recommended for COVID-19 patients who require oxygen therapy. However, its effectiveness in reducing mortality and intubation, and its safety, remain debated. We aimed to investigate whether dexamethasone reduces day-28 mortality in unselected patients with critical COVID-19. METHODS: We performed an observational cohort study in consecutive COVID-19 patients admitted to any of 13 French intensive care units (ICUs) in 2020. The primary objective was to determine whether early dexamethasone therapy was associated with day-28 mortality and the secondary objectives were to assess whether early dexamethasone decreased intubation requirements and to collect adverse events. RESULTS: Of 1058 included patients, 611 (57.75%) received early dexamethasone (early dexamethasone group), 358 (33.83%) did not receive any steroids (no steroids group), and 89 (8.41%) received late dexamethasone or other steroids. Day-28 mortality was similar between the early dexamethasone and the no steroids groups (15.06% and 14.25%, respectively; P = 0.59). Factors associated with day-28 mortality were older age (adjusted hazard ratio [aHR], 1.06; 1.04-1.09; P < 0.001), worse SOFA score (aHR, 1.13; 1.06-1.20; P < 0.001), and immunocompromised status (aHR, 1.59; 1.01-2.50; P = 0.043). Early dexamethasone was associated with fewer intubations (48.55% vs. 61.49%, P < 0.001) and more ventilator-free days by day 28 (22 [2-28] vs. 17 [1-28] days, P = 0.003), compared to no steroids. Ventilator-associated pneumonia (VAP) was more common with early dexamethasone (HR, 1.29 [1.01-1.63], P = 0.04) than with no steroids, whereas no differences were noted for bloodstream infection, fungal infection, or gastrointestinal bleeding. CONCLUSIONS: Early dexamethasone in critically ill COVID-19 patients was not associated with lower day-28 mortality. However, early dexamethasone was associated with lower intubation needs and more ventilator-free days by day 28. In patients treated with invasive mechanical ventilation, early dexamethasone was associated with a higher risk of VAP.

Multiple-site decontamination regimen decreases acquired infection incidence in mechanically ventilated COVID-19 patients.

BACKGROUND: Among strategies that aimed to prevent acquired infections (AIs), selective decontamination regimens have been poorly studied in the COVID-19 setting. We assessed the impact of a multiple-site decontamination (MSD) regimen on the incidence of bloodstream infections (BSI) and ventilator-associated pneumonia (VAP) in COVID-19 patients receiving mechanical ventilation. METHODS: We performed an ancillary analysis of a multicenter retrospective observational study in 15 ICUs in western France. In addition to standard-care (SC), 3 ICUs used MSD, a variant of selective digestive decontamination, which consists of the administration of topical antibiotics four times daily in the oropharynx and the gastric tube, chlorhexidine body wash and a 5-day nasal mupirocin course. AIs were compared between the 3 ICUs using MSD (MSD group) and the 12 ICUs using SC. RESULTS: During study period, 614 of 1158 COVID-19 patients admitted in our ICU were intubated for at least 48 h. Due to missing data in 153 patients, 461 patients were finally included of whom 89 received MSD. There were 34 AIs in the MSD group (2117 patient-days), as compared with 274 AIs in the SC group (8957 patient-days) (p < 0.001). MSD was independently associated with a lower risk of AI (IRR = 0.56 [0.38-0.83]; p = 0.004) (Table 2). When the same model was used for each site of infection, MSD remained independently associated with a lower risk of VAP (IRR = 0.52 [0.33-0.89]; p = 0.005) but not of BSI (IRR = 0.58, [0.25-1.34], p = 0.21). Hospital mortality was lower in the MSD group (16.9% vs 30.1%, p = 0.017). CONCLUSIONS: In ventilated COVID-19 patients, MSD was independently associated with lower AI incidence.

Fiberoptic endoscopic validation of a clinical screening test of swallowing function in critically ill patients performed within 24 h after extubation.

BACKGROUND: A bedside screening tool of swallowing dysfunction (SD) (BSSD) after extubation would be useful to identify patients who are at risk of SD. We aimed to evaluate the accuracy of our BSSD in comparison with fiberoptic endoscopic evaluation of swallowing (FEES) in critically ill patients after extubation. METHODS: We conducted a 1-year prospective monocentric study to evaluate the accuracy of our BSSD to diagnose SD following endotracheal intubation in comparison with FEES (gold standard). Patients intubated for longer than 48 h were included. Both tests were assessed within 24 h after extubation. Primary endpoint was the accuracy of the BSSD. Secondary endpoint was to assess risk factors of SD. RESULTS: Seventy-nine patients were included in the study. Thirty-three patients (42%) presented with a SD. The BSSD showed a sensitivity of 88% (95% CI 0.72-0.97) and a specificity of 91% (95% CI 0.79-0.98), a positive predictive value of 88% (95% CI 0.72-0.97) and a negative predictive value of 91% (95% CI 0.79-0.97). The AUC reached 0.83 (95% CI 0.74-0.92). CONCLUSION: Our study describes an accurate clinical screening tool to detect SD after extubation in critically ill patients. Screening-positive cases should be confirmed by instrumental tests, ideally using FEES.

Early steroids and ventilator-associated pneumonia in COVID-19-related ARDS.

RATIONALE: Early corticosteroid treatment is used to treat COVID-19-related acute respiratory distress syndrome (ARDS). Infection is a well-documented adverse effect of corticosteroid therapy. OBJECTIVES: To determine whether early corticosteroid therapy to treat COVID-19 ARDS was associated with ventilator-associated pneumonia (VAP). METHODS: We retrospectively included adults with COVID-19-ARDS requiring invasive mechanical ventilation (MV) for ≥ 48 h at any of 15 intensive care units in 2020. We divided the patients into two groups based on whether they did or did not receive corticosteroids within 24 h. The primary outcome was VAP incidence, with death and extubation as competing events. Secondary outcomes were day 90-mortality, MV duration, other organ dysfunctions, and VAP characteristics. MEASUREMENTS AND MAIN RESULTS: Of 670 patients (mean age, 65 years), 369 did and 301 did not receive early corticosteroids. The cumulative VAP incidence was higher with early corticosteroids (adjusted hazard ratio [aHR] 1.29; 95% confidence interval [95% CI] 1.05-1.58; P = 0.016). Antibiotic resistance of VAP bacteria was not different between the two groups (odds ratio 0.94, 95% CI 0.58-1.53; P = 0.81). 90-day mortality was 30.9% with and 24.3% without early corticosteroids, a nonsignificant difference after adjustment on age, SOFA score, and VAP occurrence (aHR 1.15; 95% CI 0.83-1.60; P = 0.411). VAP was associated with higher 90-day mortality (aHR 1.86; 95% CI 1.33-2.61; P = 0.0003). CONCLUSIONS: Early corticosteroid treatment was associated with VAP in patients with COVID-19-ARDS. Although VAP was associated with higher 90-day mortality, early corticosteroid treatment was not. Longitudinal randomized controlled trials of early corticosteroids in COVID-19-ARDS requiring MV are warranted.

Neutrophil function and bactericidal activity against Staphylococcus aureus after cardiac surgery with cardiopulmonary bypass.

Staphylococcus aureus is the main bacterial pathogen encountered in mediastinitis after cardiac surgical procedures; it remains a devastating complication with a high mortality rate. As neutrophils have a primordial role in the defense against staphylococcus infection and cardiopulmonary bypass (CPB) is known to induce immunosuppression, the aim of this study was to investigate CPB impact on neutrophil functions. Patients without known immunosuppression scheduled for cardiac surgery with CPB were included. Bone marrow and blood samples were harvested before, during, and after surgery. Neutrophil phenotypic maturation and functions (migration, adhesion, neutrophil extracellular trap [NET] release, reactive oxygen species (ROS) production, phagocytosis, and bacteria killing) were investigated. Two types of Staphylococcus aureus strains (one from asymptomatic nasal carriage and another from mediastinitis infected tissues) were used to assess in vitro bacterial direct impact on neutrophils. We found that CPB induced a systemic inflammation with an increase in circulating mature neutrophils after surgery. Bone marrow sample analysis did not reveal any modification of neutrophil maturation during CPB. Neutrophil lifespan was significantly increased and functions such as NET release and ROS production were enhanced after CPB whereas bacteria killing and phagocytosis were not impacted. Results were similar with the two different isolates of Staphylococcus aureus. These data suggest that CPB induces a recruitment of mature neutrophils via a demargination process rather than impacting their maturation in the bone marrow. In addition, neutrophils are fully efficient after CPB and do not contribute to postoperative immunosuppression.

Clinical spectrum and risk factors for mortality among seawater and freshwater critically ill drowning patients: a French multicenter study.

BACKGROUND: Drowning is a global threat and one of the leading causes of injury around the world. The impact of drowning conditions including water salinity on patients' prognosis remains poorly explored in Intensive Care Units (ICUs) patients. METHODS: We conducted a retrospective multicenter study on patients admitted to 14 ICUs in the west of France from January 2013 to January 2020. We first compared demographic and clinical characteristics at admission as well as clinical courses of these patients according to the salinity of drowning water. Then, we aimed to identify variables associated with 28-day survival using a Cox proportional hazard model. RESULTS: Of the 270 consecutive included patients, drowning occurred in seawater in 199 patients (73.7%) and in freshwater in 71 patients (26.3%). Day-28 mortality was observed in 55 patients (20.4%). Freshwater was independently associated with 28-day mortality (Adjusted Hazard Ratio (aHR) 1.84 [95% Confidence Interval (CI) 1.03-3.29], p = 0.04). A higher proportion of freshwater patients presented psychiatric comorbidities (47.9 vs. 19.1%; p < 0.0001) and the etiology of drowning appeared more frequently to be a suicide attempt in this population (25.7 vs. 4.2%; p < 0.0001). The other factors independently associated with 28-day mortality were the occurrence of a drowning-related cardiac arrest (aHR 11.5 [95% CI 2.51-52.43], p = 0.0017), duration of cardiopulmonary resuscitation (aHR 1.05 [95% CI 1.03-1.07], p < 0.0001) and SOFA score at day 1 (aHR 1.2 [95% CI 1.11-1.3], p < 0.0001). CONCLUSIONS: In this large multicenter cohort, freshwater drowning patients had a poorer prognosis than saltwater drowning patients. Reasons for such discrepancies include differences in underlying psychiatric comorbidity, drowning circumstances and severities. Patients with initial cardiac arrest secondary to drowning remain with a very poor prognosis.

Assessment of Magnetic Resonance Imaging Changes and Functional Outcomes Among Adults With Severe Herpes Simplex Encephalitis.

Importance: Current guidelines recommend brain magnetic resonance imaging (MRI) for clinical management of patients with severe herpes simplex encephalitis (HSE). However, the prognostic value of brain imaging has not been demonstrated in this setting. Objective: To investigate the association between early brain MRI data and functional outcomes of patients with HSE at 90 days after intensive care unit (ICU) admission. Design, Setting, and Participants: This multicenter cohort study was conducted in 34 ICUs in France from 2007 to 2019 and recruited all patients who received a clinical diagnosis of encephalitis and exhibited cerebrospinal fluid positivity for herpes simplex virus DNA in the polymerase chain reaction analysis. Data analysis was performed from January to April 2020. Exposures: All patients underwent a standard brain MRI during the first 30 days after ICU admission. Main Outcomes and Measures: MRI acquisitions were analyzed by radiologists blinded to patients' outcomes, using a predefined score. Multivariable logistic regression and supervised hierarchical classifiers methods were used to identify factors associated with poor outcome at 90 days, defined by a score of 3 to 6 (indicating moderate-to-severe disability or death) on the Modified Rankin Scale. Results: Overall, 138 patients (median [interquartile range {IQR}] age, 62.6 [54.0-72.0] years; 75 men [54.3%]) with an admission median (IQR) Glasgow Coma Scale score of 9 (6-12) were studied. The median (IQR) delay between ICU admission and MRI was 1 (1-7) days. At 90 days, 95 patients (68.8%) had a poor outcome, including 16 deaths (11.6%). The presence of fluid-attenuated inversion recovery MRI signal abnormalities in more than 3 brain lobes (odds ratio [OR], 25.71; 95% CI, 1.21-554.42), age older than 60 years (OR, 7.62; 95% CI, 2.02-28.91), and the presence of diffusion-weighted MRI signal abnormalities in the left thalamus (OR, 6.90; 95% CI, 1.12-43.00) were independently associated with poor outcome. Machine learning models identified bilateral diffusion abnormalities as an additional factor associated with poor outcome (34 of 39 patients [87.2%] with bilateral abnormalities had poor outcomes) and confirmed the functional burden of left thalamic lesions, particularly in older patients (all 11 patients aged >60 years had left thalamic lesions). Conclusions and Relevance: These findings suggest that in adult patients with HSE requiring ICU admission, extensive MRI changes in the brain are independently associated with poor functional outcome at 90 days. Thalamic diffusion signal changes were frequently observed and were associated with poor prognosis, mainly in older patients.

Monitoring Transcutaneously Measured Partial Pressure of CO2 During Intubation in Critically Ill Subjects.

BACKGROUND: The risk for severe hypoxemia during endotracheal intubation is a major concern in the ICU, but little attention has been paid to CO2 variability. The objective of this study was to assess transcutaneously measured partial pressure of CO2 ([Formula: see text]) throughout intubation in subjects in the ICU who received standard oxygen therapy, high-flow nasal cannula oxygen therapy, or noninvasive ventilation for preoxygenation. We hypothesized that the 3 methods differ in terms of ventilation and CO2 removal. METHODS: In this single-center, prospective, observational study, we recorded [Formula: see text] from preoxygenation to 3 h after the initiation of mechanical ventilation among subjects requiring endotracheal intubation. Subjects were sorted into 3 groups according to the preoxygenation method. We then assessed the link between [Formula: see text] variability and the development of postintubation hypotension. RESULTS: A total of 202 subjects were included in the study. The [Formula: see text] values recorded at endotracheal intubation, at the initiation of mechanical ventilation, and after 30 min and 1 h of mechanical ventilation were significantly higher than those recorded during preoxygenation (P < .05). [Formula: see text] variability differed significantly according to the preoxygenation method (P < .001, linear mixed model). A decrease in [Formula: see text] by > 5 mm Hg within 30 min after the start of mechanical ventilation was independently associated with postintubation hypotension (odds ratio = 2.14 [95% CI 1.03-4.44], P = .039) after adjustments for age, Simplified Acute Physiology Score II, COPD, cardiac comorbidity, the use of propofol for anesthetic induction, and minute ventilation at the start of mechanical ventilation. CONCLUSIONS: [Formula: see text] variability during intubation is significant and differs with the method of preoxygenation. A decrease in [Formula: see text] after the beginning of mechanical ventilation was associated with postintubation hypotension. (ClinicalTrials.gov registration NCT0388430.).

The Extent of Aspergillosis in Critically Ill Patients With Severe Influenza Pneumonia: A Multicenter Cohort Study.

OBJECTIVES: To determine the frequency and prognosis of invasive pulmonary aspergillosis in critically ill patients with severe influenza pneumonia. DESIGN: Retrospective multicenter cohort study. SETTING: Five French ICUs. PATIENTS: Patients with influenza admitted to ICU between 2009 and 2018. MEASUREMENTS AND MAIN RESULTS: Of the 524 patients admitted for severe influenza diagnosed with a positive airway reverse-transcriptase polymerase chain reaction test, 450 (86%) required mechanical ventilation. A lower respiratory tract sample yielded with Aspergillus (Asp+) in 28 patients (5.3%). Ten patients (1.9%) were diagnosed with putative or proven invasive pulmonary aspergillosis, based on the validated AspICU algorithm. A multivariate model was built to identify independent risk factors for Aspergillus-positive pulmonary culture. Factors independently associated with Aspergillus-positive culture were liver cirrhosis (odds ratio = 6.7 [2.1-19.4]; p < 0.01), hematologic malignancy (odds ratio = 3.3 [1.2-8.5]; p = 0.02), Influenza A(H1N1)pdm09 subtype (odds ratio = 3.9 [1.6-9.1]; p < 0.01), and vasopressor requirement (odds ratio = 4.1 [1.6-12.7]; p < 0.01). In-hospital mortality of Asp+ patients was 36% versus 21% in patients without Aspergillus-positive pulmonary culture (p = 0.09). CONCLUSIONS: In this large retrospective multicenter cohort of critically ill patients, putative invasive pulmonary aspergillosis according to AspICU algorithm was a relatively rare complication of influenza. Patients at higher risk of Aspergillus pulmonary colonization included those with liver cirrhosis, hematologic malignancy, H1N1pdm09 influenza A virus, and requiring vasopressors. Our results provide additional data on the controversial association between severe influenza and invasive pulmonary aspergillosis. Reaching a consensual definition of invasive pulmonary aspergillosis becomes mandatory and confers further prospective research.