Search

Background: The vasopressor dose needed is a common measure to assess the severity of cardiovascular failure, but there is no consensus on the ranges of vasopressor doses determining different levels of cardiovascular support. We aimed to identify cutoffs for determining low, intermediate and high doses of noradrenaline (norepinephrine), the primary vasopressor used in intensive care, based on association with hospital mortality., Methods: We conducted a binational registry study to determine cutoffs between low, intermediate and high noradrenaline doses. We required the cutoffs to be statistically rational and practical (rounded to the first decimal and easy to remember), and to result in increasing mortality with increasing doses. The highest noradrenaline dose in the first 24 h after intensive care unit (ICU) admission was used. The cutoffs were developed using data from 8079 ICU patients treated in the ICU at Kuopio University Hospital, Finland, between 2013 and 2019. Subsequently, the cutoffs were validated in the eICU database, including 39,007 ICU admissions to 29 ICUs in the United States of America in 2014-2015. The log-rank statistic, with the Contal and O'Quigley method, was used to determine the cutoffs resulting in the most significant split between the noradrenaline dose groups with regard to hospital mortality., Results: The two most prominent peaks in the log-rank statistic corresponded to noradrenaline doses 0.20 and 0.44 μg/kg/min. Accordingly, we determined three dose ranges: low (<0.2 μg/kg/min), intermediate (0.2-0.4 μg/kg/min) and high (>0.4 μg/kg/min). Mortality increased, whereas the number of patients decreased consistently with increasing noradrenaline doses in both cohorts. In the development cohort, hospital mortality was 6.5% in the group without noradrenaline administered and 14.0%, 26.4% and 40.2%, respectively, in the low-dose, intermediate-dose and high-dose groups. Compared to patients who received no noradrenaline, the hazard ratio for in-hospital death was 1.4 for the low-dose group, 4.0 for the intermediate-dose group and 7.5 for the high-dose group in the validation cohort (p < .001)., Conclusions: The highest noradrenaline dose is a useful measure for quantifying circulatory failure. Cutoffs 0.2 and 0.4 μg/kg/min seem to be suitable for defining low, intermediate and high doses., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: To our knowledge, no large observational study has compared the incidence and risk factors for extubation failure within 48 h and during ICU stay in the same cohort of unselected critically ill patients with and without obesity., Research Question: Which are the incidence and risk factors of extubation failure in patients with and without obesity?, Study Design and Methods: In this prospective multicenter observational FREE-REA study in 26 ICUs, the primary objective was to compare the incidence of extubation failure within 48 h in patients with and without obesity. Secondary objectives were to describe and to identify the independent specific risk factors for extubation failure, using first a logistic regression model and second a decision tree analysis., Results: Of 1,370 extubation procedures analyzed, 288 (21%) were performed in patients with obesity and 1,082 (79%) in patients without obesity. The incidence of extubation failure within 48 h among patients with or without obesity was 23 of 288 (8.0%) vs 118 of 1,082 (11%), respectively (unadjusted OR, 0.71; 95% CI, 0.45-1.13; P = .15); alongside patients with obesity receiving significantly more noninvasive ventilation [87 of 288 (30%) vs 233 of 1,082 (22%); P = .002] and physiotherapy [165 of 288 (57%) vs 527 of 1,082 (49%); P = .02] than patients without obesity. Risk factors for extubation failure also differed according to obesity status: female sex (adjusted OR, 4.88; 95% CI, 1.61-13.9; P = .002) and agitation before extubation (adjusted OR, 6.39; 95% CI, 1.91-19.8; P = .001) in patients with obesity, and absence of strong cough before extubation (adjusted OR, 2.38; 95% CI, 1.53-3.84; P = .0002) and duration of invasive mechanical ventilation before extubation (adjusted OR, 1.03/d; 95% CI, 1.01-1.06; P = .01) in patients without obesity. The decision tree analysis found similar risk factors., Interpretation: Our findings indicate that anticipation and application of preventive measures for patients with obesity before and after extubation led to similar rate of extubation failure among patients with and without obesity., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02450669; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: S. J. reports receiving consulting fees from Drager, Medtronic, Mindray, Fresenius, Baxter, and Fisher & Paykel. A. D. J. reports receiving remuneration for presentations from Medtronic, Drager, and Fisher & Paykel. E. A. has received fees from Gilead Sciences, Alexion, Astellas, MSD, and Drager. J. Pottecher has received fees from Medtronic, Baxter, and Getinge. None declared (M. Capdevila, Y. A., M. Cros, J. Pensier, I. L., C. M., H. Q., R. C., K. A., J.-M. A., C. G., C. P.-B., P. A., A. M.-D., K. L., S. L., G. P., B. C., P. C., C. I., N. M., G. C., L. P.)., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Norepinephrine is the first-line vasopressor used in acute cardio-circulatory failure. At the bedside, its dose is critical as it serves to determine the severity of patients, to compare the patients between different studies, and to start specific interventions. Recently, several investigators underlined differences in the expression of norepinephrine doses according to countries and manufacturers. For various reasons, all norepinephrine products are processed to a salt formulation thereby generating a stable and soluble conjugated acid in a slightly acidic solution. Depending on the salt used, the total weight will differ, but the weight of pure norepinephrine base is the same. This results in at-risk situations with large variations in terms of practices, evaluation and treatment. In this technical note, we summarized the evidence and provided a few suggestions to improve the practices at different levels., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Acute mesenteric ischaemia (AMI) is a life-threatening disease where early diagnosis is critical to avoid morbidity and mortality from extensive irreversible bowel necrosis. Appropriate prediction of presence of bowel necrosis is currently not available but would help to choose the optimal method of treatment. The study aims to identify combinations of biomarkers that can reliably identify AMI and distinguish between potentially reversible and irreversible bowel ischaemia., Methods: This is a prospective multicentre study. Adult patients with clinical suspicion of AMI (n = 250) will be included. Blood will be sampled on admission, at and after interventions, or during the first 48 h of suspicion of AMI if no intervention undertaken. Samples will be collected and the following serum or plasma biomarkers measured at Tartu University Hospital laboratory: intestinal fatty acid-binding protein (I-FABP), alpha-glutathione S-transferase (Alpha- GST), interleukin 6 (IL-6), procalcitonin (PCT), ischaemia-modified albumin (IMA), D-lactate, D-dimer, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and lipopolysaccharide-binding protein (LBP). Additionally, more common laboratory markers will be measured in routine clinical practice at study sites. Diagnosis of AMI will be confirmed by computed tomography angiography, surgery, endoscopy or autopsy. Student's t or Wilcoxon rank tests will be used for comparisons between transmural vs. suspected (but not confirmed) AMI (comparison A), confirmed AMI of any stage vs suspected AMI (comparison B) and non-transmural AMI vs transmural AMI (comparison C). Optimal cut-off values for each comparison will be identified based on the AUROC analysis and likelihood ratios calculated. Positive likelihood ratio > 10 (> 5) and negative likelihood ratio < 0.1 (< 0.2) indicate high (moderate) diagnostic accuracy, respectively. All biomarkers with at least moderate accuracy will be entered as binary covariates (using the best cutoffs) into the multivariable stepwise regression analysis to identify the best combination of biomarkers for all comparisons separately. The best models for each comparison will be used to construct a practical score to distinguish between no AMI, non-transmural AMI and transmural AMI., Discussion: As a result of this study, we aim to propose a score including set of biomarkers that can be used for diagnosis and decision-making in patients with suspected AMI., Trial Registration: NCT06212921 (Registration Date 19-01-2024)., (© 2024. The Author(s).)

Background : new-onset atrial fibrillation remains a common complication in critical care settings, often necessitating treatment when the correction of triggers is insufficient to restore hemodynamics. The treatment strategy includes electric cardioversion in cases of hemodynamic instability and either rhythm control or rate control in the absence of instability. Landiolol, an ultrashort beta-blocker, effectively controls heart rate with the potential to regulate rhythm. Objectives This review aims to compare the efficacy of landiolol in controlling heart rate and converting to sinus rhythm in the critical care setting. Methods : We conducted a comprehensive review of the published literature from 2000 to 2022 describing the use of landiolol to treat atrial fibrillation in critical care settings, excluding both cardiac surgery and medical cardiac care settings. The primary outcome assessed was sinus conversion following landiolol treatment. Results : Our analysis identified 17 publications detailing the use of landiolol for the treatment of 324 critical care patients. While the quality of the data was generally low, primarily comprising non-comparative studies, landiolol consistently demonstrated similar efficacy in controlling heart rate and facilitating conversion to sinus rhythm in both non-surgical (75.7%) and surgical (70.1%) settings. The incidence of hypotension associated with landiolol use was 13%. Conclusions : The use of landiolol in critical care patients with new-onset atrial fibrillation exhibited comparable efficacy and tolerance in both non-surgical and surgical settings. Despite these promising results, further validation through randomized controlled trials is necessary.

Background: Qualitative data on the opinions of anaesthesiologists regarding the impact of peri-operative night-time working conditions on patient safety are lacking., Objectives: This study aimed to achieve in-depth understanding of anaesthesiologists' perceptions regarding the impact of night-time working conditions on peri-operative patient safety and actions that may be undertaken to mitigate perceived risks., Design: Qualitative analysis of responses to two open-ended questions., Setting: Online platform questionnaire promoted by the European Society of Anaesthesiology and Intensive Care (ESAIC)., Participants: The survey sample consisted of an international cohort of anaesthesiologists., Main Outcome Measures: We identified and classified recurrent themes in the responses to questions addressing perceptions regarding (Q1) peri-operative night-time working conditions, which may affect patient safety and (Q2) potential solutions., Results: We analysed 2112 and 2113 responses to Q1 and Q2, respectively. The most frequently reported themes in relation to Q1 were a perceived reduction in professional performance accompanied by concerns regarding the possible consequences of work with fatigue (27%), and poor working conditions at night-time (35%). The most frequently proposed solutions in response to Q2 were a reduction of working hours and avoidance of 24-h shifts (21%), an increase in human resources (14%) and performance of only urgent or emergency surgeries at night (14%)., Conclusion: Overall, the surveyed anaesthesiologists believe that workload-to-staff imbalance and excessive working hours were potential bases for increased peri-operative risk for their patients, partly because of fatigue-related medical errors during night-time work. The performance of nonemergency elective surgical cases at night and lack of facilities were among the reported issues and potential targets for improvement measures. Further studies should investigate whether countermeasures can improve patient safety as well as the quality of life of anaesthesia professionals. Regulations to improve homogeneity, safety, and quality of anaesthesia practice at night seem to be urgently needed., (Copyright © 2023 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Antimicrobial resistance (AMR) is associated with increased mortality and resources consumption in critically ill patients. However, the causality of AMR in this mortality remains unclear. This opinion paper aims to overview the effects of multidrug resistant (MDR) pathogens on the outcomes of critically ill patients, considering different variables as appropriateness of empirical antimicrobial therapy, severity of sepsis, comorbid conditions and frailty. Large studies based on national database associated MDR and increased mortality in critically ill patients. However, the patients carrying MDR pathogens, as compared with those carrying non-MDR pathogens, are those with co-morbid conditions, high risk of frailty and invasive procedures. In addition, inappropriate empirical antibiotics are more often used in these patients as well as withholding and withdrawing of life-sustained therapy. Future studies on AMR should report the rate of appropriateness of empirical antimicrobial therapy, withholding and withdrawing of life-sustained therapy., Competing Interests: Conflict of interest ML served as consultant for Viatris, LFB, AOP Pharma, Gilead. GD, IL, IML, SE have no conflict of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: In studies prior to lung-protective ventilation, liver cirrhosis in acute respiratory distress syndrome (ARDS) was associated with high mortality rates. Since patients with cirrhosis have been excluded from many trials on ARDS, their outcome when treated with lung-protective ventilation is unclear. The objectives were to assess whether cirrhosis is associated with mortality in ARDS and trends over time in mortality and severity., Methods: We conducted a retrospective analysis of a prospective observational cohort conducted in a 20-bed tertiary ICU from October 2003 to December 2021. All consecutive adult critically ill patients with ARDS were included. ARDS was defined by the Berlin criteria. The primary outcome was 90 day mortality, assessed with Kaplan-Meier curves and multivariate Cox analysis. Time trends were assessed on 90 day mortality, Sequential Organ-Function Assessment score (SOFA) and non-hepatic SOFA. Ventilation settings were compared between patients with and without cirrhosis., Results: Of the 7155 patients screened, 863 had a diagnosis of ARDS. Among these ARDS patients, 157(18%) had cirrhosis. The overall 90 day mortality was of 43% (378/863), 57% (90/157) in patients with cirrhosis and 41% (288/706) in patients without cirrhosis (p < 0.001). On survival curves, cirrhosis was associated with 90 day mortality (p < 0.001). Cirrhosis was independently associated with 90 day mortality in multivariate analysis (hazard ratio = 1.56, 95% confidence interval 1.20-2.02). There was no change in mortality over time in ARDS patients with and without cirrhosis. SOFA (p = 0.04) and non-hepatic SOFA (p = 0.02) increased over time in ARDS patients without cirrhosis, and remained stable in ARDS patients with cirrhosis. Tidal volume, positive end-expiratory pressure, plateau pressure and driving pressure were not different between ARDS patients with and without cirrhosis., Conclusions: Although ARDS management improved over the last decades, the 90 day mortality remained high and stable over time for both ARDS patients with (57%) and without cirrhosis (41%). Nevertheless, the severity of patients without cirrhosis has increased over time, while the severity of patients with cirrhosis has remained stable., (© 2023. La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF).)

Background: No data are available on the working conditions and workload of anesthesiologists during perioperative nighttime work in Italy and on the perceived risks., Results: We analyzed 1085 responses out of the 5292 from the whole dataset. Most of the responders (76%) declared working a median of 12 consecutive hours during night shifts, with an irregular nightshift schedule (70%). More than half of the responders stated to receive a call 2-4 (40%) or 5 times or more (25%) to perform emergency procedures and/or ICU activities during night shifts. More than 70% of the responders declared having relaxation rooms for nighttime work (74%) but none to be used after a nightshift before going back home (82%) and no free meals, snacks, or beverages (89%). Furthermore, almost all (95%) of the surveyed anesthesiologists declared not having received specifical training or education on how to work at night, and that no institutional program has been held by the hospital to monitor fatigue or stress for night workers (99%). More than half of the responders stated having the possibility, sometimes (38%) or always (45%), to involve another colleague in difficult medical decisions and to feel comfortable, sometimes (31%) or always (35%), to call the on-call colleague. Participants declared that nighttime work affects their quality of life extremely (14%) or significantly (63%), and that sleep deprivation, fatigue, and current working conditions may reduce performance (67%) and increase risk for the patients (74%)., Conclusions: Italian anesthesiologists declare current nighttime practice to negatively affect their quality of life, and their performance, and are thus concerned for their patients' safety. Proper education on night work, starting from traineeship, and implementing institutional programs to monitor stress and fatigue of operators and to support them during nighttime work could be a mean to improve nighttime work conditions and safety for both patients and healthcare workers., (© 2023. Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care.)

Background: Procalcitonin (PCT) protocols to guide antibiotic treatment for ventilator-associated pneumonia (VAP) in the intensive care unit aim at reducing antibiotic exposure. Our study goal was to measure compliance with a PCT protocol for VAP and to determine the associated variables., Methods: From 2017 to 2021, we conducted a retrospective, monocentric study including patients treated for VAP. In our PCT protocol, PCT was measured at the initiation of antibiotic treatment and every 48 h until treatment completion; antibiotics were stopped if PCT decreased by more than 80% from its highest value or fell below 0.5 ng/mL. We assessed the compliance with the PCT protocol and compared the compliant and noncompliant groups., Results: Among the 177 included patients, compliance with the PCT protocol was assessed at 58%. Noncompliance was due to lack of PCT measurements in 76% of cases. Compliance was higher in the medical patients ( p = 0.04) and in those admitted for SARS-CoV-2 ( p = 0.02). Compliance regarding the interruption of antibiotic therapy based on PCT was lower on weekends and holidays ( p = 0.01). Outcomes did not differ according to compliance., Conclusion: This study assessed real-life compliance with the PCT protocol to monitor antibiotic treatment for VAP. Improving the measurement of PCT at the bedside would increase the rate.

Early initiation of a multimodal treatment strategy in the management of vasopressors during septic shock has been advocated to reduce delays in restoring adequate organ perfusion and to mitigate side effects associated with the administration of high-dose catecholamines. We provide a review that summarises the pathophysiology of vasodilation, the physiologic response to the vascular response, and the different drugs used in this situation, focusing on the need to combine early different vasopressors. Fluid loading being insufficient for counteracting vasoplegia, norepinephrine is usually the first-line vasopressor used to restore hemodynamics. Norepinephrine sparing is discussed in further detail through the concomitant use of adrenergic, vasopressinergic, and renin-angiotensin systems and the optimisation of endothelial reactivity with methylene blue. A blueprint for the construction of new studies is outlined to address the question of vasopressor selection and timing in septic shock., (Copyright © 2023 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: We reviewed the different studies using the terms "refractory septic shock" and/or "catecholamine resistance" and/or "high dose norepinephrine" so as to highlight the heterogeneity of the definitions used by authors addressing such concepts., Method: A systematic review was conducted assessing the papers reporting data on refractory septic shock. We used keywords as exact phrases and subject headings according to database syntax., Results: Of 276 papers initially reviewed, we included 8 studies - 3 randomized controlled trials, 3 prospective studies and 2 retrospective studies, representing a total of 562 patients with septic shock. Catecholamine resistance was generally defined as "a decreased vascular responsiveness to catecholamine independently of the administered norepinephrine dose". Refractory septic shock was broadly defined as "a clinical condition characterized by persistent hyperdynamic shock even though adequate fluid resuscitation (individualized doses) and high doses of norepinephrine (≥ 1 μg/kg/min)". Reported "high doses" of norepinephrine were often ≥1 μg/kg/min. However, wide variability was found throughout the literature on the use of these terms., Discussion: Marked inconsistencies were identified in the usage of the terms for refractory septic shock. There is a pressing need to determine consensus definitions so as to establish a common language in the medical literature and to harmonize future studies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: No international data are available on the night working conditions and workload of anaesthesiologists and their opinions about associated risks., Objective: The aim of this international survey was to describe the peri-operative night working conditions of anaesthesiologists and their perception of the impact these conditions have on patient outcomes and their own quality of life., Design: Cross-sectional survey., Setting: Not applicable., Participants: Anaesthesiologists providing peri-operative care during night shifts responded to an online survey promoted by the European Society of Anaesthesiology and Intensive Care (ESAIC)., Interventions: None., Main Outcome Measure: Twenty-eight closed questions., Results: Overall 5292 complete responses were analysed. Of these, 920 were from trainees. The median reported monthly number of night shifts was 4 [IQR 3-6]. An irregular weekly night shift schedule was most common (51%). Almost all the respondents (98%) declared that their centres have no relevant institutional programmes to monitor stress or fatigue. Most respondents (90%) had received no training or information regarding performance improvement methods for night work. Most respondents were of the opinion that sleep deprivation affects their professional performance (71%) and that their fatigue during night work may increase the peri-operative risk for their patients (74%). Furthermore, 81% of the respondents agreed or strongly agreed that night work represents an additional risk per se for patient safety, and 77% stated that their night work affects the quality of their daily life significantly or extremely., Conclusion: Anaesthesiologists commonly perform perioperative night work without appropriate training, education or support on this specific condition. They perceive current practice as adversely affecting their professional performance and the safety of their patients. They also report significant effects on their own quality of life. Adequate training and education for night work may ally some of these concerns and programmes to monitor workers' stress and fatigue should be mandated to assess whether these concerns are justified., Trial Registration: Not applicable., (Copyright © 2023 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Traumatic hemorrhage guidelines include point-of-care viscoelastic tests as a standard of care. Quantra (Hemosonics) is a device based on sonic estimation of elasticity via resonance (SEER) sonorheometry to assess whole blood clot formation., Objectives: Our study aimed to assess the ability of an early SEER evaluation to detect blood coagulation test abnormalities in trauma patients., Methods: We conducted an observational retrospective cohort study with data collected at hospital admission of consecutive multiple trauma patients from September 2020 to February 2022 at a regional level 1 trauma center. We performed a receiving operator characteristic curve analysis to determine the ability of the SEER device to detect blood coagulation test abnormalities. Four values on the SEER device were analyzed: clot formation time, clot stiffness (CS), platelet contribution to CS, and fibrinogen contribution to CS., Results: A total of 156 trauma patients were analyzed. The clot formation time value predicted an activated partial thromboplastin time ratio of >1.5 with an area under the curve (AUC) of 0.93 (95% CI, 0.86-0.99). The AUC of the CS value in detecting an international normalized ratio of prothrombin time of >1.5 was 0.87 (95% CI, 0.79-0.95). The AUC of fibrinogen contribution to CS to detect a fibrinogen concentration of <1.5 g/L was 0.87 (95% CI, 0.80-0.94). The AUC of platelet contribution to CS to detect a platelet concentration of <50 G/L was 0.99 (95% CI, 0.99-1.00)., Conclusion: Our results suggest that the SEER device may be useful for the detection of blood coagulation test abnormalities at trauma admission., (© 2023 The Author(s).)

Introduction: Multidrug-resistant bacteria (MDRB) carriage may impact the outcomes of intensive care unit (ICU) patients. In this study, we aimed to assess the effect of MDRB-related infection and colonization on the day 60 mortality rate., Methods: We conducted a retrospective, observational study in a single university hospital ICU. From January 2017 to December 2018, we screened all patients admitted to the ICU for at least 48 h for MDRB carriage. The primary outcome was the mortality rate on day 60 after MDRB-related infection. The secondary outcome was the mortality rate on day 60 of non-infected but colonized patients with MDRB. We considered the effect of potential confounders, such as the occurrence of septic shock, inadequate antibiotic therapy, Charlson score, and life-sustaining limitation order., Results: We included 719 patients during the aforementioned period; of this number, 281 (39%) had a microbiologically documented infection. MDRB was found in 40 (14%) patients. The crude mortality rate in the MDRB-related infection group was 35% vs. 32% in the non-MDRB-related infection group (p = 0.1). Logistic regression showed that MDRB-related infection was not associated with excess mortality, with an odds ratio of 0.52 and a 95% confidence interval from 0.17 to 1.39 (p = 0.2). Charlson score, septic shock, and life-sustaining limitation order were significantly associated with an increased mortality rate on day 60. No effect of MDRB colonization on mortality rate on day 60 was highlighted., Conclusion: MDRB-related infection or colonization was not associated with an increased mortality rate on day 60. Other confounders, such as comorbidities, may account for a higher mortality rate., (© 2023. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Sex and gender dimorphisms are found in a large variety of diseases, including sepsis and septic shock which are more prevalent in men than in women. Animal models show that the host response to pathogens differs in females and males. This difference is partially explained by sex polarization of the intracellular pathways responding to pathogen-cell receptor interactions. Sex hormones seem to be responsible for this polarization, although other factors, such as chromosomal effects, have yet to be investigated. In brief, females are less susceptible to sepsis and seem to recover more effectively than males. Clinical observations produce more nuanced findings, but men consistently have a higher incidence of sepsis, and some reports also claim higher mortality rates. However, variables other than hormonal differences complicate the interaction between sex and sepsis, including comorbidities as well as social and cultural differences between men and women. Conflicting data have also been reported regarding sepsis-attributable mortality rates among pregnant women, compared with non-pregnant females. We believe that unraveling sex differences in the host response to sepsis and its treatment could be the first step in personalized, phenotype-based management of patients with sepsis and septic shock.

Background: Patients with severe mental illness (SMI) (i.e., schizophrenia, bipolar disorder, or major depressive disorder) have been reported to have excess mortality rates from infection compared to patients without SMI, but whether SMI is associated with higher or lower case fatality rates (CFRs) among infected patients remains unclear. The primary objective was to compare the 90-day CFR in septic shock patients with and without SMI admitted to the intensive care unit (ICU), after adjusting for social disadvantage and physical health comorbidity., Methods and Findings: We conducted a nationwide, population-based cohort study of all adult patients with septic shock admitted to the ICU in France between January 1, 2014, and December 31, 2018, using the French national hospital database. We matched (within hospitals) in a ratio of 1:up to 4 patients with and without SMI (matched-controls) for age (5 years range), sex, degree of social deprivation, and year of hospitalization. Cox regression models were conducted with adjustment for smoking, alcohol and other substance addiction, overweight or obesity, Charlson comorbidity index, presence of trauma, surgical intervention, Simplified Acute Physiology Score II score, organ failures, source of hospital admission (home, transfer from other hospital ward), and the length of time between hospital admission and ICU admission. The primary outcome was 90-day CFR. Secondary outcomes were 30- and 365-day CFRs, and clinical profiles of patients. A total of 187,587 adult patients with septic shock admitted to the ICU were identified, including 3,812 with schizophrenia, 2,258 with bipolar disorder, and 5,246 with major depressive disorder. Compared to matched controls, the 90-day CFR was significantly lower in patients with schizophrenia (1,052/3,269 = 32.2% versus 5,000/10,894 = 45.5%; adjusted hazard ratio (aHR) = 0.70, 95% confidence interval (CI) 0.65,0.75, p < 0.001), bipolar disorder (632/1,923 = 32.9% versus 2,854/6,303 = 45.3%; aHR = 0.70, 95% CI = 0.63,0.76, p < 0.001), and major depressive disorder (1,834/4,432 = 41.4% versus 6,798/14,452 = 47.1%; aHR = 0.85, 95% CI = 0.81,0.90, p < 0.001). Study limitations include inability to capture deaths occurring outside hospital, lack of data on processes of care, and problems associated with missing data and miscoding in medico-administrative databases., Conclusions: Our findings suggest that, after adjusting for social disadvantage and physical health comorbidity, there are improved septic shock outcome in patients with SMI compared to patients without. This finding may be the result of different immunological profiles and exposures to psychotropic medications, which should be further explored., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: LB has received honoraria/has been a consultant for Lundbeck. PML participated in advisory boards for, received speaker’s honoraria and received consultation fees over the last 3 years from Eisai, Ethypharm, Janssen, Lundbeck, MSD, Neuraxpharm, Novartis, Otsuka, Roche, Rovi; Member of the Executive Committee of the Fondation FondaMental. GF has received honoraria/has been a consultant for Lundbeck. MS has received honoraria/has been a consultant for Angelini, Lundbeck, Otsuka. CUC has been a consultant and/or advisor to or has received honoraria from AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Damitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, and LB Pharma. ML has received honoraria from Gilead, AOP Pharma, Ambu, LFB and Viatris for consulting., (Copyright: © 2023 Lakbar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Myopia is a global public health problem affecting quality of life and work productivity. Data is scarce regarding the effects of near work on myopia. Providing a larger meta-analysis with life-long perspective, including adults and occupational exposure seemed needed., Methods: We searched PubMed, Cochrane Library, Embase and Science Direct for studies reporting myopia prevalence in near work. Myopia was defined as a mean spherical equivalent ≤ -0.50 diopter. We performed a meta-analysis using random-effects model on myopia prevalence, myopia progression per year, and odds ratio (OR) of myopia in near work, completed by subgroup analyses and meta-regressions on patients' characteristics, type of work in adults, geographic zones, time and characteristics of near work., Results: We included 78 studies, representing a total of 254,037 participants, aged from 6 to 39 years. The global prevalence of myopia in near work was 35% (95% CI: 30 to 41%), with a prevalence of 31% (95% CI: 26 to 37%) in children and 46% (95% CI: 30 to 62%) in adults. Myopia progression was -0.39 diopters per year (-0.53 to -0.24 D/year), ranging from -0.44 (-0.57 to -0.31) in children to -0.25 D/year (-0.56 to 0.06) in adults. The odds of myopia in workers exposed vs. non-exposed to near work were increased by 26% (18 to 34%), by 31% (21 to 42%) in children and 21% (6 to 35%) in adults. Prevalence of myopia was higher in adults compared to children (Coefficient 0.15, 95% CI: 0.03 to 0.27)., Conclusions: Near work conditions, including occupational exposure in adults, could be associated with myopia. Targeted prevention should be implemented in the workplace.

Background: The literature is unresolved on whether female receive advanced cardiac life support less than do male and on whether female have a survival advantage over male after cardiopulmonary resuscitation., Methods: We systematically searched PubMed, Embase and Web of Science databases (from inception to 23-April-2022) for papers reporting outcomes in adult male and female after out-of-hospital cardiac arrest. The main study outcome was the rate of adjusted survival to hospital discharge or 30 days. Secondary outcomes included unadjusted survival to hospital discharge and favourable neurological outcome., Results: A total of 28 studies were included, involving 1,931,123 patients. Female were older than male, their cardiac arrests were less likely to be witnessed and less likely to present with a shockable rhythm. Unadjusted analysis showed that females had a lower likelihood of survival than males (OR 0.68 [0.62-0.74], I 2  = 97%). After adjustment, no significant difference was identified between male and female in survival at hospital discharge/30 days (OR 1.01 [0.93-1.11], I 2  = 87%). Data showed that male had a significantly higher likelihood of favorable neurological outcome in unadjusted analysis but this trend disappeared after adjustment. Both the primary outcome (adjusted for several variables) and the secondary outcomes were associated with substantial heterogeneity. The variables examined using meta-regression, subgroup and sensitivity analyses (i.e., study type, location, years, population, quality of adjustment, risk of bias) did not reduce heterogeneity., Conclusions: The adjusted rate of survival to hospital discharge/30 days was similar for male and female despite an initial seeming survival advantage for male. The validity of this finding is limited by substantial heterogeneity despite in-depth investigation of its causes, which raises concerns regarding latent inequalities in some reports nonetheless. Further study on this topic may require inclusion of factors not reported in the Utstein template and in-depth analysis of decision-making processes., (© 2022. The Author(s).)

The demographics and outcomes of ICU patients admitted for a COVID-19 infection have been characterized in extensive reports, but little is known about antimicrobial stewardship for these patients. We designed this retrospective, observational study to investigate our hypothesis that the COVID-19 pandemic has disrupted antimicrobial stewardship practices and likely affected the rate of antibiotic de-escalation (ADE), patient outcomes, infection recurrence, and multidrug-resistant bacteria acquisition. We reviewed the prescription of antibiotics in three ICUs during the pandemic from March 2020 to December 2021. All COVID-19 patients with suspected or proven bacterial superinfections who received antibiotic treatment were included. The primary outcome was the rate of ADE, and secondary outcomes included the rate of appropriate empirical treatment, mortality rates and a comparison with a control group of infected patients before the COVID-19 pandemic. We included 170 COVID-19 patients who received antibiotic treatment for a suspected or proven superinfection, of whom 141 received an empirical treatment. For the latter, antibiotic treatment was de-escalated in 47 (33.3%) patients, escalated in 5 (3.5%) patients, and continued in 89 (63.1%) patients. The empirical antibiotic treatment was appropriate for 87.2% of cases. ICU, hospital, and day 28 and day 90 mortality rates were not associated with the antibiotic treatment strategy. The ADE rate was 52.2% in the control group and 27.6% in the COVID-19 group (p < 0.001). Our data suggest that empirical antibiotic treatment was appropriate in most cases. The ADE rates were lower in the COVID-19 group than in the control group, suggesting that the stress associated with COVID-19 affected our practices.

Background: LUS is a validated tool for the management of COVID-19 pneumonia. Chair positioning (CP) may have beneficial effects on oxygenation and lung aeration, and may be an easier alternative to PP. This study assessed the effects of a CP session on oxygenation and lung aeration (LA) changes in non-intubated COVID-19 patients., Methods: A retrospective multicenter study was conducted in an ICU. We analyzed data from LUS exams and SpO 2 :FiO 2 performed before/after a CP session in non-intubated COVID-19 patients. Patients were divided into groups of responders or non-responders in terms of oxygenation or LA., Results: Thirty-three patients were included in the study; fourteen (44%) were oxygenation non-responders and eighteen (56%) were oxygenation responders, while thirteen (40.6%) and nineteen (59.4%) patients were classified as LA non-responders and responders, respectively. Changes in oxygenation and LA before/after a CP session were not correlated (r = -0.19, p = 0.3, 95% CI: -0.5-0.17). The reaeration scores did not differ between oxygenation responders and non-responders (1 (-0.75-3.75) vs. 4 (-1-6), p = 0.41). The LUS score was significantly correlated with SpO 2 :FiO 2 before a CP session (r = 0.37, p = 0.04, 95% CI: 0.03-0.64) but not after (r = 0.17, p = 0.35, 95% CI: -0.19-0.50)., Conclusion: A CP session was associated with improved oxygenation and LA in more than half of the non-intubated COVID-19 patients.

Purpose of Review: The incidence of infective endocarditis (IE) is increasing worldwide, resulting in a higher number of patients with IE being admitted to intensive care units (ICU). Nearly half of patients with IE develop a complication during their clinical course. However, few well conducted studies or reviews are devoted to critically ill IE patients. This review discusses the contemporary perioperative and intensive care literature., Recent Findings: IE epidemiology is changing towards elderly and frail patients. ICU patients are at risk of risk of developing IE because they are often in a pro-inflammatory state and many also have several indwelling catheters, which favors infection. Increased performance and recent advances in cardiac imaging allow for easier diagnosis of EI, but the applicability of these techniques to ICU patients is still relatively limited. New developments in antibiotic treatment and adjunctive therapies are explored further in this review., Summary: The lack of evidence on ICU patients with IE highlights the critical importance of multidisciplinary decision-making and the need for further research., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

(1) Background: The effects of lockdown repetition on work-related stress, expressed through Effort-Reward Imbalance (ERI), during the COVID-19 pandemic are poorly documented. We investigated the effect of repetitive lockdowns on the ERI in French workers, its difference across occupations, and the change in its influencing factors across time. (2) Methods: Participants were included in a prospective cross-sectional observational study from 30 March 2020 to 28 May 2021. The primary outcome was the ERI score (visual analog scale). The ERI score of the population was examined via Generalized Estimating Equations. For each period, the factors influencing ERI were studied by multivariate linear regression. (3) Results: In 8121 participants, the ERI score decreased in the first 2 lockdowns (53.2 ± 0.3, p < 0.001; 50.5 ± 0.7, p < 0.001) and after lockdown 2 (54.8 ± 0.8, p = 0.004) compared with the pre-pandemic period (59 ± 0.4). ERI was higher in medical than in paramedical professionals in the pre-pandemic and the first 2 lockdowns. Higher workloads were associated with better ERI scores. (4) Conclusions: In a large French sample, Effort-Reward Imbalance worsened during the COVID-19 pandemic until the end of the 2nd lockdown. Paramedical professionals experienced a higher burden of stress compared with medical professionals.

Introduction: Septic shock is responsible for high morbidity and mortality rates and its incidence is increasing worldwide. Its evolution over the last few years and the leverage points for action to improve associated outcomes remain unclear. Our aim was to determine trends in the incidence and mortality of septic shock and associated risk factors in intensive care unit (ICU) patients and readmission rates after hospital discharge., Methods: We performed a retrospective cohort study using data from the French national hospitalisation database, including adult patients with septic shock from 2014 to 2018. Primary outcomes were the incidence of septic shock and the hospital mortality rate at 30, 90 and 365 days. Secondary outcomes were all-cause hospital readmission., Results: Septic shock was identified in 187,587 ICU stays. The age- and sex-adjusted incidence rate of septic shock per 100 ICU admissions increased from 6.5% to 6.8% (P < .001); age- and sex-adjusted hospital mortality rates decreased from 47.3% to 44.5% (P < .001). The hospital readmission rate at 365 days was 65.0%. Older age, higher Charlson score, occurrence of organ failure and previous hospitalisation were associated with increased risk of mortality. Identification of a specific microorganism and a time between hospitalisation and ICU admission of less than one day were associated with a decreased risk of death., Conclusions: Our study revealed an increase in the incidence of septic shock and a decrease in mortality rates. Pathogen identification and rapid admission to the ICU were associated with better outcomes. The rate of hospital readmission increased, raising questions about the discharge criteria for these patients., (Copyright © 2022 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: To compare the effects of two therapeutic bundles of management in SARS-CoV2 ICU patients., Materials and Methods: Our retrospective, observational study was performed in a university ICU from March to June 2020 (first wave) and from September 2020 to January 2021 (second wave). In first wave, patients received bundle 1 including early invasive ventilation, hydroxychloroquine, cefotaxime and azithromycin. In second wave, bundle 2 included non-invasive oxygenation support and dexamethasone. The main outcome was in-hospital mortality. Secondary outcomes included ICU and hospital length of stay, ICU supportive therapies, viral clearance and antimicrobial resistance emergence., Results: 129 patients with SARS-CoV-2 pneumonia were admitted to our ICU. Thirty-five were treated according to bundle 1 and 76 to bundle 2. In-hospital mortality was similar in the two groups (23%, p = 1). The hospital (p = 0.003) and ICU (p = 0.01) length of stay and ventilator-free days at 28 days (p = 0.03) were significantly reduced in bundle 2. Increasing age, vasopressor use and PaO 2 /FiO 2 ratio < 125 were associated with in-hospital mortality., Conclusion: Within the limitations of our study, changes in therapeutic bundles for SARS-Cov-2 ICU patients might have no effect on in-hospital mortality but were associated with less exposure to mechanical ventilation and reduced hospital length of stay., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Data on the relationship between antimicrobial resistance and mortality remain scarce, and this relationship needs to be investigated in intensive care units (ICUs). The aim of this study was to compare the ICU mortality rates between patients with ICU-acquired pneumonia due to highly antimicrobial-resistant (HAMR) bacteria and those with ICU-acquired pneumonia due to non-HAMR bacteria. We conducted a multicenter, retrospective cohort study using the French National Surveillance Network for Healthcare Associated Infection in ICUs ("REA-Raisin") database, gathering data from 200 ICUs from January 2007 to December 2016. We assessed all adult patients who were hospitalized for at least 48 h and presented with ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii. The association between pneumonia caused by HAMR bacteria and ICU mortality was analyzed using the whole sample and using a 1:2 matched sample. Among the 18,497 patients with at least one documented case of ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii, 3081 (16.4%) had HAMR bacteria. The HAMR group was associated with increased ICU mortality (40.3% vs. 30%, odds ratio (OR) 95%, CI 1.57 [1.45-1.70], P < 0.001). This association was confirmed in the matched sample (3006 HAMR and 5640 non-HAMR, OR 95%, CI 1.39 [1.27-1.52], P < 0.001) and after adjusting for confounding factors (OR ranged from 1.34 to 1.39, all P < 0.001). Our findings suggest that ICU-acquired pneumonia due to HAMR bacteria is associated with an increased ICU mortality rate, ICU length of stay, and mechanical ventilation duration., (© 2021. The Author(s).)

Epidemiological studies and clinical observations show evidence of sexual dimorphism in infectious diseases. Women are at less risk than men when it comes to developing most infectious diseases. However, understanding these observations requires a gender approach that takes into account an analysis of both biological and social factors. The host's response to infection differs in males and females because sex differences have an impact on hormonal and chromosomal control of immunity. Estradiol appears to confer protective immunity, while progesterone and testosterone suppress anti-infectious responses. In addition, genetic factors, including those associated with sex chromosomes, also affect susceptibility to infections. Finally, differences in occupational activities, lifestyle, and comorbidities play major roles in exposure to pathogens and management of diseases. Hence, considering sexual dimorphism as a critical variable for infectious diseases should be one of the steps taken toward developing personalized therapeutic approaches., Competing Interests: ML served as speaker for MSD, Aspen and as consultant for Amomed, Ambuand Gilead. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gay, Melenotte, Lakbar, Mezouar, Devaux, Raoult, Bendiane, Leone and Mège.)

Background: Non-invasive respiratory support including high-flow nasal oxygen (HFNO), continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) is routinely used in the perioperative period., Objectives: The aim of this narrative review was to discuss some of the existing literature on perioperative non-invasive respiratory support outlining its potential roles in each of the three perioperative periods (pre-, intra- and postoperatively) and to propose the way forward., Results: During induction of anesthesia, non-invasive ventilation (NIV) was associated with improved ventilatory variables and reduced risk of postoperative respiratory complications. HFNO did not seem to confer an advantage in terms of peri-intubation hypoxemia. Intraoperative data on NIV are scarce. Upper airway obstruction and worsening hypoventilation are two risks associated with its use. Compared with conventional oxygenation, HFNO is associated with a reduced risk of hypoxemia. Postoperative NIV has been associated with improved arterial blood gases and a reduced reintubation rate, but no difference was reported for mortality, hospital length of stay, rate of anastomotic leakage, pneumonia-related complications and sepsis or infections. Head-to-head comparison of HFNO versus BiPAP showed no advantage to either mode of support., Conclusion: In the preoperative setting, NIV seems to be associated with improved clinical outcomes in specific patient subgroups (obesity, pregnancy). In the postoperative setting, both NIV and HFNO were associated with lower reintubation rates. The literature has provided little evidence regarding the use of non-invasive ventilatory support in other patient subgroups or intraoperatively. There is also little literature regarding the appropriateness of combining different modes of support. In the next years, the combination of several modes of respiratory support should be assessed in targeted populations.

Introduction: Infective endocarditis is one of the most difficult-to-treat infectious diseases., Areas Covered: We restricted this review to the anti-infective treatment of the main bacteria responsible for infective endocarditis, i.e. staphylococci, streptococci, enterococci, and Gram-negative bacilli, including HACEK. Specific topics of major interest in treatment strategy are covered as well, including empirical treatment, oral switch, and treatment duration. We searched in the MEDLINE database to identify relevant studies, trials, reviews, or meta-analyses until May 2020., Expert Opinion: The use of aminoglycosides for the treatment of endocarditis has been dramatically reduced over the last 20 years. It should be administered once daily, and no longer than 2 weeks. For staphylococcal endocarditis, recent data reinforced the role of anti-staphylococcal penicillins, for methicillin-susceptible isolates (alternative, cefazolin), and vancomycin for methicillin-resistant isolates (alternative, daptomycin). For staphylococcal prosthetic-valve endocarditis, these treatments will be reinforced by the addition of gentamicin during the first 2 weeks, and rifampin throughout the whole treatment duration, i.e. 6 weeks. The optimal duration of antibacterial treatment is 4 weeks for most native valve endocarditis, and 6 weeks for prosthetic-valve endocarditis. The oral switch is safe in patients stabilized after the initial intravenous course.

Background: Epidemiological differences between men and women have been reported with regards to sepsis, influenza and severe coronavirus infections including SARS-CoV and MERS-CoV., Aim: To systematically review the literature relating to men versus women on SARS-CoV-2 in order to seek differences in disease characteristics (e.g. infectivity, severity) and outcomes (e.g. mortality)., Methods: We searched 3 electronic databases up or observational studies reporting differences between men and women in the SARS-CoV-2 disease characteristics stated. We identified and included 47 studies, reporting data for 21,454 patients mainly from China., Results: The unadjusted mortality rates of men were higher than those of women, with a mortality OR 0.51 [0.42, 0.61] (p<0.001) for women. The proportion of men presenting with severe disease and admitted to the intensive care unit (ICU) was also higher than that of women (OR 0.75 [0.60-0.93] p<0.001 and OR 0.45 [0.40-0.52] p<0.001 respectively). Adjusted analyses could not be conducted due to lack of data., Conclusion: COVID-19 may be associated with worse outcomes in males than in females. However, until more detailed data are provided in further studies enabling adjusted analysis, this remains an unproven assumption., Competing Interests: IL, DLP, SE and JLM have no conflict of interest to disclose. ML served as speaker for MSD, Pfizer and as consultant for Amomed, Aguettant and Gilead. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Antimicrobial de-escalation (ADE) is a component of antimicrobial stewardship (AMS) aimed to reduce exposure to broad-spectrum antimicrobials. In the intensive care unit, ADE is a strong recommendation that is moderately applied in clinical practice. Following a systematic review of the literature, we assessed the studies identified on the topic which included one randomized controlled trial and 20 observational studies. The literature shows a low level of evidence, although observational studies suggested that this procedure is safe. The effects of ADE on the level of resistance of ecological systems and especially on the microbiota are unclear. The reviewers recommend de-escalating antimicrobial treatment in patients requiring long-term antibiotic therapy and considering de-escalation in short-term treatments.