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Author(s): Frédérique Schortgen [sup.1], Miet Schetz [sup.2] Author Affiliations: (1) 0000 0001 2175 4109, grid.50550.35, Medical Intensive Care Unit, Henri Mondor University Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), , Créteil, [...]

Author(s): Frédérique Schortgen [sup.1], Anaïs Charles-Nelson [sup.2] [sup.7], Lila Bouadma [sup.3], Geoffray Bizouard [sup.4], Laurent Brochard [sup.5] [sup.6], Sandrine Katsahian [sup.2] [sup.7] Author Affiliations: (1) grid.412116.1, 0000000122921474, Réanimation médicale, Hôpital [...], Purpose We previously showed that external cooling decreases day 14 mortality in febrile septic shock. Because cooling may participate in heart rate control, we studied the respective impact of heart rate and temperature lowering on mortality. Methods Post hoc analysis of the Sepsiscool randomized controlled trial database (NCT00527007). Cooling was applied to maintain normothermia (36.5-37 °C) during 48 h. We assessed the time spent below different thresholds of temperature and heart rate on day 14 mortality. The best threshold was selected by AUC-ROC and tested as a potential mediator of mortality reduction. Mediation analysis was adjusted for severity and treatments influencing temperature and heart rate evolution. Sensitivity analysis was done using only patients with appropriate antimicrobial therapy. Results A total of 197/200 patients with adequate heart rate and temperature monitoring were analyzed. The best threshold differentiating survivors and nonsurvivors was 38.4 °C for temperature and 95 b/min for heart rate. During the 48 h of intervention, cooling significantly increased the time spent with a temperature below 38.4 °C, p = 0.001, and with a heart rate below 95 b/min, p < 0.01. The longer was the time spent with a temperature below 38.4 °C, the lower was the mortality [adjOR 0.17 (0.06-0.49), p = 0.001]. The time spent with a heart rate below 95 b/min was similar in survivors and nonsurvivors [adjOR 0.68 (0.27-1.72), p = 0.42]. Mediation analysis showed that the time spent with a temperature below 38.4 °C was a significant mediator of mortality. Conclusion The time spent with a temperature below 38.4 °C was independently associated with patient's outcome and explained 73 % of the effect of the randomization on the day 14 mortality. Heart rate lowering was not a mediator of mortality.

Author(s): Frédérique Schortgen [sup.1], Pascal Andujar [sup.2], Amine Si Ali [sup.3], Layla Yahyaoui [sup.4], Mounira Smati-Lafarge [sup.5] Author Affiliations: (1) grid.414145.1, 0000 0004 1765 2136, Intensive Care Unit, Centre Hospitalier [...]

Author(s): Frédérique Schortgen [sup.1] Author Affiliations: (1) grid.411388.7, 0000000417993934, Service de réanimation médicale, CHU Henri Mondor-APHP, , 51 avenue du Maréchal de Lattre de Tassigny, 94000, Créteil, France Long-term mortality [...]

Author(s): Matthieu Schmidt [sup.1], David Hajage, Alexandre Demoule, Tài Pham, Alain Combes, Martin Dres, Said Lebbah, Antoine Kimmoun, Alain Mercat, Gaëtan Beduneau, Jessica Palmyre, Margot Prevost, Pierre Asfar, François Beloncle, [...], Purpose To describe acute respiratory distress syndrome (ARDS) severity, ventilation management, and the outcomes of ICU patients with laboratory-confirmed COVID-19 and to determine risk factors of 90-day mortality post-ICU admission. Methods COVID-ICU is a multi-center, prospective cohort study conducted in 138 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, adjunctive interventions, ICU length-of-stay, and survival data were collected. Results From February 25 to May 4, 2020, 4643 patients (median [IQR] age 63 [54-71] years and SAPS II 37 [28-50]) were admitted in ICU, with day-90 post-ICU admission status available for 4244. On ICU admission, standard oxygen therapy, high-flow oxygen, and non-invasive ventilation were applied to 29%, 19%, and 6% patients, respectively. 2635 (63%) patients were intubated during the first 24 h whereas overall 3376 (80%) received invasive mechanical ventilation (MV) at one point during their ICU stay. Median (IQR) positive end-expiratory and plateau pressures were 12 (10-14) cmH.sub.2O, and 24 (21-27) cmH.sub.2O, respectively. The mechanical power transmitted by the MV to the lung was 26.5 (18.6-34.9) J/min. Paralyzing agents and prone position were applied to 88% and 70% of patients intubated at Day-1, respectively. Pulmonary embolism and ventilator-associated pneumonia were diagnosed in 207 (9%) and 1209 (58%) of these patients. On day 90, 1298/4244 (31%) patients had died. Among patients who received invasive or non-invasive ventilation on the day of ICU admission, day-90 mortality increased with the severity of ARDS at ICU admission (30%, 34%, and 50% for mild, moderate, and severe ARDS, respectively) and decreased from 42 to 25% over the study period. Early independent predictors of 90-day mortality were older age, immunosuppression, severe obesity, diabetes, higher renal and cardiovascular SOFA score components, lower PaO.sub.2/FiO.sub.2 ratio and a shorter time between first symptoms and ICU admission. Conclusion Among more than 4000 critically ill patients with COVID-19 admitted to our ICUs, 90-day mortality was 31% and decreased from 42 to 25% over the study period. Mortality was higher in older, diabetic, obese and severe ARDS patients.

Author(s): Arnaud-Félix Miailhe [sup.1], Emmanuelle Mercier [sup.2], Adel Maamar [sup.3], Jean-Claude Lacherade [sup.4], Aurélie Le Thuaut [sup.5], Aurélie Gaultier [sup.5], Pierre Asfar [sup.6], Laurent Argaud [sup.7], Antoine Ausseur [sup.8], Adel [...], Purpose To report the incidence, risk factors, clinical presentation, and outcome predictors of severe leptospirosis requiring intensive care unit (ICU) admission in a temperate zone. Methods LEPTOREA was a retrospective multicentre study conducted in 79 ICUs in metropolitan France. Consecutive adults admitted to the ICU for proven severe leptospirosis from January 2012 to September 2016 were included. Multiple correspondence analysis (MCA) and hierarchical classification on principal components (HCPC) were performed to distinguish different clinical phenotypes. Results The 160 included patients (0.04% of all ICU admissions) had median values of 54 years [38-65] for age, 40 [28-58] for the SAPSII, and 11 [8-14] for the SOFA score. Hospital mortality was 9% and was associated with older age; worse SOFA score and early need for endotracheal ventilation and/or renal replacement therapy; chronic alcohol abuse and worse hepatic dysfunction; confusion; and higher leucocyte count. Four phenotypes were identified: moderately severe leptospirosis (n = 34, 21%) with less organ failure and better outcomes; hepato-renal leptospirosis (n = 101, 63%) with prominent liver and kidney dysfunction; neurological leptospirosis (n = 8, 5%) with the most severe organ failures and highest mortality; and respiratory leptospirosis (n = 17, 11%) with pulmonary haemorrhage. The main risk factors for leptospirosis contamination were contact with animals, contact with river or lake water, and specific occupations. Conclusions Severe leptospirosis was an uncommon reason for ICU admission in metropolitan France and carried a lower mortality rate than expected based on the high severity and organ-failure scores. The identification in our population of several clinical presentations may help clinicians establish an appropriate index of suspicion for severe leptospirosis.

Author(s): Emmanuelle Cambau [sup.1] [sup.2], Isabelle Durand-Zaleski [sup.3] [sup.4], Stéphane Bretagne [sup.5] [sup.6] [sup.7] [sup.8], Christian Brun-Buisson [sup.9], Catherine Cordonnier [sup.10], Xavier Duval [sup.11], Stéphanie Herwegh [sup.12], Julien Pottecher [sup.13], [...], Purpose Microbiological diagnosis (MD) of infections remains insufficient. The resulting empirical antimicrobial therapy leads to multidrug resistance and inappropriate treatments. We therefore evaluated the cost-effectiveness of direct molecular detection of pathogens in blood for patients with severe sepsis (SES), febrile neutropenia (FN) and suspected infective endocarditis (SIE). Methods Patients were enrolled in a multicentre, open-label, cluster-randomised crossover trial conducted during two consecutive periods, randomly assigned as control period (CP; standard diagnostic workup) or intervention period (IP; additional testing with LightCycler.sup.®SeptiFast). Multilevel models used to account for clustering were stratified by clinical setting (SES, FN, SIE). Results A total of 1416 patients (907 SES, 440 FN, 69 SIE) were evaluated for the primary endpoint (rate of blood MD). For SES patients, the MD rate was higher during IP than during CP [42.6% (198/465) vs. 28.1% (125/442), odds ratio (OR) 1.89, 95% confidence interval (CI) 1.43-2.50; P < 0.001], with an absolute increase of 14.5% (95% CI 8.4-20.7). A trend towards an association was observed for SIE [35.4% (17/48) vs. 9.5% (2/21); OR 6.22 (0.98-39.6)], but not for FN [32.1% (70/218) vs. 30.2% (67/222), P = 0.66]. Overall, turn-around time was shorter during IP than during CP (22.9 vs. 49.5 h, P < 0.001) and hospital costs were similar (median, mean ± SD: IP [euro]14,826, [euro]18,118 ± 17,775; CP [euro]17,828, [euro]18,653 ± 15,966). Bootstrap analysis of the incremental cost-effectiveness ratio showed weak dominance of intervention in SES patients. Conclusion Addition of molecular detection to standard care improves MD and thus efficiency of healthcare resource usage in patients with SES. ClinicalTrials.gov registration number: NCT00709358.

Author(s): Manoj Saxena [sup.1] [sup.2], Paul Young [sup.3] [sup.4], David Pilcher [sup.5] [sup.6] [sup.7], Michael Bailey [sup.5], David Harrison [sup.8], Rinaldo Bellomo [sup.5], Simon Finfer [sup.1] [sup.9], Richard Beasley [sup.4], [...], Background Fever suppression may be beneficial for patients with traumatic brain injury (TBI) and stroke, but for patients with meningitis or encephalitis [central nervous system (CNS) infection], the febrile response may be advantageous. Objective To evaluate the relationship between peak temperature in the first 24 h of intensive care unit (ICU) admission and all-cause hospital mortality for acute neurological diseases. Design, setting and participants Retrospective cohort design from 2005 to 2013, including 934,159 admissions to 148 ICUs in Australia and New Zealand (ANZ) and 908,775 admissions to 236 ICUs in the UK. Results There were 53,942 (5.8 %) patients in ANZ and 56,696 (6.2 %) patients in the UK with a diagnosis of TBI, stroke or CNS infection. For both the ANZ (P = 0.02) and UK (P < 0.0001) cohorts there was a significant interaction between early peak temperature and CNS infection, indicating that the nature of the relationship between in-hospital mortality and peak temperature differed between TBI/stroke and CNS infection. For patients with CNS infection, elevated peak temperature was not associated with an increased risk of death, relative to the risk at 37-37.4 °C (normothermia). For patients with stroke and TBI, peak temperature below 37 °C and above 39 °C was associated with an increased risk of death, compared to normothermia. Conclusions The relationship between peak temperature in the first 24 h after ICU admission and in-hospital mortality differs for TBI/stroke compared to CNS infection. For CNS infection, increased temperature is not associated with increased risk of death.