Severe mental illness and mortality in sepsis and septic shock: a systematic review and meta-analysis.

BACKGROUND: There have been conflicting reports regarding the case-fatality outcomes associated with sepsis and septic shock in patients with severe mental illness (SMI). METHODS: We searched Medline®, Web of Science® and the Cochrane Library® databases (from inception to 4-July-2023) for papers reporting outcomes associated with sepsis and septic shock in adult with (cases) vs. without SMI (controls). The main study outcome was the unadjusted case-fatality rate at hospital discharge, or 30 days if unavailable. Secondary outcomes included the rates of adjusted case-fatality at hospital discharge. RESULTS: A total of six studies were included in the systematic review, of which four provided data for meta-analysis involving 2,124,072 patients. Compared to controls, patients with SMI were younger and more frequently women. Unadjusted analyses showed that SMI patients had a lower case-fatality rate associated with sepsis and septic shock than their non-SMI counterparts (OR 0.61, 95% CI [0.58-0.65], PI 95% CI [0.49-0.77], I2 = 91%). Meta-regression and subgroup analyses showed that the denominator of the study population (i.e. septic shock or sepsis) was associated with the outcome with an R2 of 59.7%. CONCLUSION: In conclusion, our study reveals a survival advantage of SMI patients over their non-SMI counterparts. Further research is needed to fully elucidate the mechanisms involved and to develop targeted interventions that can improve the prognosis of both SMI and non-SMI patients facing sepsis.

Position Paper on the Reporting of Norepinephrine Formulations in Critical Care from the Society of Critical Care Medicine and European Society of Intensive Care Medicine Joint Task Force.

OBJECTIVES: To provide guidance on the reporting of norepinephrine formulation labeling, reporting in publications, and use in clinical practice. DESIGN: Review and task force position statements with necessary guidance. SETTING: A series of group conference calls were conducted from August 2023 to October 2023, along with a review of the available evidence and scope of the problem. SUBJECTS: A task force of multinational and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. INTERVENTIONS: The implications of a variation in norepinephrine labeled as conjugated salt (i.e., bitartrate or tartrate) or base drug in terms of effective concentration of norepinephrine were examined, and guidance was provided. MEASUREMENTS AND MAIN RESULTS: There were significant implications for clinical care, dose calculations for enrollment in clinical trials, and results of datasets reporting maximal norepinephrine equivalents. These differences were especially important in the setting of collaborative efforts across countries with reported differences. CONCLUSIONS: A joint task force position statement was created outlining the scope of norepinephrine-dose formulation variations, and implications for research, patient safety, and clinical care. The task force advocated for a uniform norepinephrine-base formulation for global use, and offered advice aimed at appropriate stakeholders.

Cancer and sepsis: future challenges for long-term outcome.

PURPOSE OF REVIEW: The purpose of this review is to investigate the long-term outcomes of cancer patients who experience sepsis or septic shock. RECENT FINDINGS: Sepsis is a frequent cause of ICU admission in cancer patients, accounting for approximately 15% of such cases. Short-term mortality rates among these patients vary widely across studies, but they are consistently found to be slightly higher than those of noncancer patients. However, there is a lack of evidence regarding the long-term outcomes of cancer patients who have experienced sepsis or septic shock. The few available studies have reported relatively high mortality rates, reaching around 80% in a few cohort studies. Although several observational studies have noted a decrease in 1-year mortality rates over time, observational data also suggest that sepsis may increase the risk of cancer in the long run. SUMMARY: As cancer is becoming a chronic disease, there is an urgent need for studies on the quality of life of cancer patients who have experienced sepsis. The relationship between sepsis and cancer extends beyond its impact on the progression of cancer, as sepsis might also contribute to the development of cancer.

Impact of COVID-19 on posttraumatic stress disorder in ICU survivors: a prospective observational comparative cohort study.

BACKGROUND: Posttraumatic stress disorder (PTSD) after a stay in the intensive care unit (ICU) can affect one in five ICU survivors. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, admission to the ICU for COVID-19 was stressful due to the severity of this disease. This study assessed whether admission to the ICU for COVID-19 was associated with a higher prevalence of PTSD compared with other causes of ICU admission after adjustment for pre-ICU psychological factors. METHODS: This prospective observational comparative cohort study included 31 ICUs. Eligible patients were adult ICU survivors hospitalized during the first wave of COVID-19 pandemic in France, regardless of the reason for admission. The prevalence of presumptive diagnosis of PTSD at 6 months was assessed using the PTSD Checklist for DSM-5 (PCL-5). Sociodemographics, clinical data, history of childhood trauma (Childhood Trauma Questionnaire [CTQ]), and exposure to potentially traumatic events (Life Events Checklist for DSM-5 [LEC-5]) were assessed. RESULTS: Of the 778 ICU survivors included during the first wave of COVID-19 pandemic in France, 417 and 361 were assigned to the COVID-19 and non-COVID-19 cohorts, respectively. Fourteen (4.9%) and 11 (4.9%), respectively, presented with presumptive diagnosis of PTSD at 6 months (p = 0.976). After adjusting for age, sex, severity score at admission, use of invasive mechanical ventilation, ICU duration, CTQ and LEC-5, COVID-19 status was not associated with presumptive diagnosis of PTSD using the PCL-5. Only female sex was associated with presumptive diagnosis of PTSD. However, COVID-19 patients reported significantly more intrusion and avoidance symptoms than non-COVID patients (39% vs. 29%, p = 0.015 and 27% vs. 19%, p = 0.030), respectively. The median PCL-5 score was higher in the COVID-19 than non-COVID-19 cohort (9 [3, 20] vs. 4 [2, 16], p = 0.034). CONCLUSION: Admission to the ICU for COVID-19 was not associated with a higher prevalence of PTSD compared with admission for another cause during the first wave of the COVID-19 pandemic in France. However, intrusion and avoidance symptoms were more frequent in COVID-19 patients than in non-COVID-19 patients. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03991611, registered on June 19, 2019.

Prevalence and factors associated with high-risk gastric contents in women admitted to the maternity unit for childbirth: a prospective multicentre cohort study.

BACKGROUND: This multicentre prospective observational study sought to determine the prevalence and the factors associated with high-risk gastric contents in women admitted to the maternity unit for childbirth, and to identify the clinical situations in which ultrasound assessment of gastric contents would be most helpful (i.e. when the prevalence of high-risk gastric contents is close to 50%). METHODS: Ultrasound assessments of gastric contents were performed within the first hour after admission to the maternity unit. The prevalence of high-risk gastric contents was calculated and variables associated with high-risk gastric contents were identified using logistic regression analyses. RESULTS: A total of 1003 parturients were analysed. The prevalence of high-risk gastric contents was 70% (379/544; 95% confidence interval: 66-74%) in women admitted in spontaneous labour and 65% (646/1003; 95% confidence interval: 61-67%) in the whole cohort. Lower gestational age, increased fasting duration for solids, and elective Caesarean delivery were independently associated with reduced likelihood of high-risk gastric contents. In women admitted in spontaneous labour and in the whole cohort, the prevalence of high-risk gastric contents ranged from 85% to 86% for fasting duration for solids <6 h, 63%-68% for fasting 6-8 h, 54%-55% for fasting 8-12 h, and 47%-51% for fasting ≥12 h. CONCLUSIONS: Around two-thirds of parturients had high-risk gastric contents within the first hour after admission to the maternity unit. Our results suggest that gastric emptying for solids continues in labouring women, and that gastric ultrasound would be most helpful when fasting duration is ≥8 h.

Association of severe mental illness and septic shock case fatality rate in patients admitted to the intensive care unit: A national population-based cohort study.

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.

Mortality among inpatients with bipolar disorders and COVID-19: a propensity score matching analysis in a national French cohort study.

BACKGROUND: It remains unknown whether coronavirus disease 2019 (COVID-19) patients with bipolar disorders (BDs) are at an increased risk of mortality. We aimed to establish whether health outcomes and care differed between patients infected with COVID-19 with BD and patients without a diagnosis of severe mental illness. METHODS: We conducted a population-based cohort study of all patients with identified COVID-19 and respiratory symptoms who were hospitalized in France between February and June 2020. The outcomes were in-hospital mortality and intensive care unit (ICU) admission. We used propensity score matching to control for confounding factors. RESULTS: In total, 50 407 patients were included, of whom 480 were patients with BD. Patients with BD were 2 years older, more frequently women and had more comorbidities than controls without a diagnosis of severe mental illness. Patients with BD had an increased in-hospital mortality rate (26.6% v. 21.9%; p = 0.034) and similar ICU admission rate (27.9% v. 28.4%, p = 0.799), as confirmed by propensity analysis [odds ratio, 95% confidence interval (OR, 95% CI) for mortality: 1.30 (1.16-1.45), p < 0.0001]. Significant interactions between BD and age and between BD and social deprivation were found, highlighting that the most important inequalities in mortality were observed in the youngest [OR, 95% CI 2.28 (1.18-4.41), p = 0.0015] and most deprived patients with BD [OR, 95% CI 1.60 (1.33-1.92), p < 0.001]. CONCLUSIONS: COVID-19 patients with BD were at an increased risk of mortality, which was exacerbated in the youngest and most deprived patients with BD. Patients with BD should thus be targeted as a high-risk population for severe forms of COVID-19, requiring enhanced preventive and disease management strategies.

Association between combination antibiotic therapy as opposed as monotherapy and outcomes of ICU patients with Pseudomonas aeruginosa ventilator-associated pneumonia: an ancillary study of the iDIAPASON trial.

BACKGROUND: The optimal treatment duration and the nature of regimen of antibiotics (monotherapy or combination therapy) for Pseudomonas aeruginosa ventilator­associated pneumonia (PA-VAP) remain debated. The aim of this study was to evaluate whether a combination antibiotic therapy is superior to a monotherapy in patients with PA-VAP in terms of reduction in recurrence and death, based on the 186 patients included in the iDIAPASON trial, a multicenter, randomized controlled trial comparing 8 versus 15 days of antibiotic therapy for PA-VAP. METHODS: Patients with PA-VAP randomized in the iDIAPASON trial (short-duration-8 days vs. long-duration-15 days) and who received appropriate antibiotic therapy were eligible in the present study. The main objective is to compare mortality at day 90 according to the antibiotic therapy received by the patient: monotherapy versus combination therapy. The primary outcome was the mortality rate at day 90. The primary outcome was compared between groups using a Chi-square test. Time from appropriate antibiotic therapy to death in ICU or to censure at day 90 was represented using Kaplan-Meier survival curves and compared between groups using a Log-rank test. RESULTS: A total of 169 patients were included in the analysis. The median duration of appropriate antibiotic therapy was 14 days. At day 90, among 37 patients (21.9%) who died, 17 received monotherapy and 20 received a combination therapy (P = 0.180). Monotherapy and combination antibiotic therapy were similar for the recurrence rate of VAP, the number of extra pulmonary infections, or the acquisition of multidrug-resistant (MDR) bacteria during the ICU stay. Patients in combination therapy were exposed to mechanical ventilation for 28 ± 12 days, as compared with 23 ± 11 days for those receiving monotherapy (P = 0.0243). Results remain similar after adjustment for randomization arm of iDIAPASON trial and SOFA score at ICU admission. CONCLUSIONS: Except longer durations of antibiotic therapy and mechanical ventilation, potentially related to increased difficulty in achieving clinical cure, the patients in the combination therapy group had similar outcomes to those in the monotherapy group. TRIAL REGISTRATION: NCT02634411 , Registered 15 December 2015.

Ventilation strategy during urological and gynaecological robotic-assisted surgery: a narrative review.

Robotic-assisted surgery has improved the precision and accuracy of surgical movements with subsequent improved outcomes. However, it requires steep Trendelenburg positioning combined with pneumoperitoneum that negatively affects respiratory mechanics and increases the risk of postoperative respiratory complications. This narrative review summarises the state of the art in ventilatory management of these patients in terms of levels of positive end-expiratory pressure (PEEP), tidal volume, recruitment manoeuvres, and ventilation modes during both urological and gynaecological robotic-assisted surgery. A review of the literature was conducted using PubMed/MEDLINE; after completing abstract and full-text review, 31 articles were included. Although different levels of PEEP were often evaluated within a protective ventilation strategy, including higher levels of PEEP, lower tidal volume, and recruitment manoeuvres vs a conventional ventilation strategy, we conclude that the best PEEP in terms of lung mechanics, gas exchange, and ventilation distribution has not been defined, but moderate PEEP levels (4-8 cm H2O) could be associated with better outcomes than lower or highest levels. Recruitment manoeuvres improved intraoperative arterial oxygenation, end-expiratory lung volume and the distribution of ventilation to dependent (dorsal) lung regions. Pressure-controlled compared with volume-controlled ventilation showed lower peak airway pressures with both higher compliance and higher carbon dioxide clearance. We propose directions to optimise ventilatory management during robotic surgery in light of the current evidence.

Pre-operative distraction using electric ride-on cars for children undergoing elective ambulatory surgery: A randomised controlled trial.

BACKGROUND: Pre-operative anxiety occurs in 18 to 60% of children undergoing surgery and results in poor outcomes. Nonpharmacological methods of distraction are effective in alleviating peri-operative anxiety. In our institution, ride-on electric cars (ride-on e-cars) are routinely used by children undergoing ambulatory surgery as a mean of nonpharmacological distraction. OBJECTIVES: The aim of this study is to assess the effect of pre-operative distraction with ride-on e-cars on children's pre-operative anxiety when undergoing elective ambulatory surgery. DESIGN: This was a prospective, randomised, controlled, open-label study. SETTING: The study was carried out from September 2019 to September 2021 in the ambulatory paediatric surgery unit of our teaching hospital, in Marseille, France. PATIENTS: Children aged 2 to 10 years and weighing less than 35 kg undergoing elective ambulatory surgery were eligible. One hundred and fifteen children were included, 56 in the control group and 59 in the intervention group. INTERVENTION: Children in the control group were transported from the operating room (OR) waiting area to the OR using a trolley, while children in the intervention group used the ride-on e-cars, without pharmacological premedication or parental presence. MAIN OUTCOME MEASURES: The primary outcome was pre-operative anxiety at the end of the transport (prior going into the OR assessed by the modified Yale Preoperative Anxiety Score Short Form (mYPAS-SF). Secondary outcomes were the anxiety levels in children over time, as well as postoperative pain and agitation assessed with the Face Legs Activity Cry Consolability (FLACC) and Paediatric Anaesthesia Emergence Delirium (PAED) scales, respectively. RESULTS: The mYPAS-SF anxiety scores did not differ between the control group and the intervention group (39 ±â€Š19 vs. 37 ±â€Š21, P  = 0.574). The secondary outcomes were similar between the two groups. CONCLUSIONS: Our randomised controlled trial showed that the use of ride-on e-cars did not alter pre-operative anxiety as compared with standard transport in children undergoing elective ambulatory surgery. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03961581.

Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial.

Importance: Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption. Objective: To investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion. Design, Setting, and Participants: Double-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021. Interventions: Intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines. Main Outcomes and Measures: The primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety). Results: Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, -2.99 to 3.33]; P = .72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P = .03). Conclusions and Relevance: Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion. Trial Registration: ClinicalTrials.gov Identifier: NCT03218722.

Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial.

BACKGROUND: Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy. METHODS: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed. FINDINGS: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups. INTERPRETATION: In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm. FUNDING: Programme Hospitalier de Recherche Clinique.

Assessment of current practice for ß-lactam therapeutic drug monitoring in French ICUs in 2021: a nationwide cross-sectional survey.

BACKGROUND: Current guidelines and literature support the use of therapeutic drug monitoring (TDM) to optimize ß-lactam treatment in adult ICU patients. OBJECTIVES: To describe the current practice of ß-lactam monitoring in French ICUs. METHODS: A nationwide cross-sectional survey was conducted from February 2021 to July 2021 utilizing an online questionnaire that was sent as an email link to ICU specialists (one questionnaire per ICU). RESULTS: Overall, 119 of 221 (53.8%) French ICUs participated. Eighty-seven (75%) respondents reported having access to ß-lactam TDM, including 52 (59.8%) with on-site access. ß-Lactam concentrations were available in 24-48 h and after 48 h for 36 (41.4%) and 26 (29.9%) respondents, respectively. Most respondents (n = 61; 70.1%) reported not knowing whether the ß-lactam concentrations in the TDM results were expressed as unbound fractions or total concentrations. The 100% unbound fraction of the ß-lactam above the MIC was the most frequent pharmacokinetic and pharmacodynamic target used (n = 62; 73.0%). CONCLUSIONS: Despite the publication of international guidelines, ß-lactam TDM is not optimally used in French ICUs. The two major barriers are ß-lactam TDM interpretation and the required time for results.

Endocarditis in the intensive care unit: an update.

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.

Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study.

BACKGROUND: The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. METHODS: We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients' characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. RESULTS: A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49-2.45). CONCLUSIONS: We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245 . Registered 3 May 2019.

Withholding and withdrawal of life-sustaining therapy in 8569 trauma patients: A multicentre, analytical registry study.

BACKGROUND: This study aimed to determine the prevalence of withholding or withdrawal of life-sustaining therapy (WLST) decisions in trauma ICU patients, using a large registry. We hypothesised that this prevalence is similar to that of the general population admitted to an ICU. As secondary aims, it sought to describe the trauma patients for whom the decision was made for WLST and the factors associated with this decision. DESIGN: This observational study assessed data from 14 French centres listed in the TraumaBaseTM registry. All trauma patients hospitalised for more than 48 h were pro-spectively included. RESULTS: Data from 8569 trauma patients, obtained from January 2016 to December 2018, were included in this study. A WLST decision was made in 6% of all cases. In the WLST group, 67% of the patients were older men (age: 62 versus 36, P  < 0.001); more often they had a prior medical history and higher median severity scores than the patients in the no WLST decision group; SAPS II 58 (46 to 69) versus 21 (13 to 35) and ISS 26 (22 to 24) versus 12 (5 to 22), P  < 0.001. Neurological status was strongly associated with WLST decisions. The geographic area of the ICUs affected the rate of the WLST decisions. The ICU mortality was 11% (n = 907) of which 47% (n = 422) were preceded by WLST decisions. Fourteen percent of WLST orders were not associated to the death. CONCLUSION: Among 8569 patients, medical history, trauma severity criteria, notably neurological status and geographical areas were associated with WLST. These regional differences deserve to be investigated in future studies.

Implementation of French Recommendations for the Prevention and the Treatment of Hospital-acquired Pneumonia: A Cluster-randomized Trial.

BACKGROUND: We determined whether an audit on the adherence to guidelines for hospital-acquired pneumonia (HAP) can improve the outcomes of patients in intensive care units (ICUs). METHODS: This study was conducted at 35 ICUs in 30 hospitals. We included consecutive, adult patients hospitalized in ICUs for 3 days or more. After a 3-month baseline period followed by the dissemination of recommendations, an audit on the compliance to recommendations (audit period) was followed by a 3-month cluster-randomized trial. We randomly assigned ICUs to either receive audit and feedback (intervention group) or participate in a national registry (control group). The primary outcome was the duration of ICU stay. RESULTS: Among 1856 patients enrolled, 602, 669, and 585 were recruited in the baseline, audit, and intervention periods, respectively. The composite measures of compliance were 47% (interquartile range [IQR], 38-56%) in the intervention group and 42% (IQR, 25-53%) in the control group (P = .001). As compared to the baseline period, the ICU lengths of stay were reduced by 3.2 days in the intervention period (P = .07) and by 2.8 days in the control period (P = .02). The durations of ICU stay were 7 days (IQR, 5-14 days) in the control group and 9 days (IQR, 5-20 days) in the intervention group (P = .10). After adjustment for unbalanced baseline characteristics, the hazard ratio for being discharged alive from the ICU in the control group was 1.17 (95% confidence interval, .69-2.01; P = .10). CONCLUSIONS: The publication of French guidelines for HAP was associated with a reduction of the ICU length of stay. However, the realization of an audit to improve their application did not further improve outcomes. CLINICAL TRIALS REGISTRATION: NCT03348579.

Daytime variation in SARS-CoV-2 infection and cytokine production.

S. Ray and A. Reddy recently anticipated the implication of circadian rhythm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of the coronavirus disease (Covid-19). In addition to its key role in the regulation of biological functions, the circadian rhythm has been suggested as a regulator of viral infections. Specifically, the time of day of infection was found critical for illness progression, as has been reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. We analyzed circadian rhythm implication in SARS-CoV-2 virus infection of isolated human monocytes, key actor cells in Covid-19 disease, from healthy subjects. The circadian gene expression of BMAL1 and CLOCK genes was investigated with q-RTPCR. Monocytes were infected with SARS-CoV-2 virus strain and viral infection was investigated by One-Step qRT-PCR and immunofluorescence. Interleukin (IL)-6, IL-1ß and IL-10 levels were also measured in supernatants of infected monocytes. Using Cosinor analysis, we showed that BMAL1 and CLOCK transcripts exhibited circadian rhythm in monocytes with an acrophase and a bathyphase at Circadian Time (CT)6 and CT17. After 48 h, the amount of SARS-CoV-2 virus increased in the monocyte infected at CT6 compared to CT17. The high virus amount at CT6 was associated with significant increased release in IL-6, IL-1ß and IL-10 compared to CT17. Our results suggest that time day of SARS-CoV-2 infection affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease progression and we propose circadian rhythm as a novel target for managing viral progression.

Management of the patient with the open abdomen.

PURPOSE OF REVIEW: The aim of this study was to outline the management of the patient with the open abdomen. RECENT FINDINGS: An open abdomen approach is used after damage control laparotomy, to decrease risk for postsurgery intra-abdominal hypertension, if reoperation is likely and after primary abdominal decompression.Temporary abdominal wall closure without negative pressure is associated with higher rates of intra-abdominal infection and evisceration. Negative pressure systems improve fascial closure rates but increase fistula formation. Definitive abdominal wall closure should be considered once oedema has subsided and the patient has stabilized. Delayed abdominal closure after trauma (>24-48 h) is associated with less achievement of fascial closure and more complications. Protective lung ventilation should be employed early, particularly if respiratory compromise is evident. Conservative fluid management and less sedation may decrease delirium and increase definitive abdominal closure rates. Extubation may be performed before definitive abdominal closure in selected patients. Antibiotic therapy should be brief, targeted and guideline concordant. Survival depends on the underlying disease, the closure method and the course of hospitalization. SUMMARY: Changes in the treatment of patients with the open abdomen include negative temporary closure, conservative fluid management, early protective lung ventilation, decreased sedation and extubation before abdominal closure in selected patients.

Bedside POCUS during ward emergencies is associated with improved diagnosis and outcome: an observational, prospective, controlled study.

BACKGROUND: Rapid response teams are intended to improve early diagnosis and intervention in ward patients who develop acute respiratory or circulatory failure. A management protocol including the use of a handheld ultrasound device for immediate point-of-care ultrasound (POCUS) examination at the bedside may improve team performance. The main objective of the study was to assess the impact of implementing such a POCUS-guided management on the proportion of adequate immediate diagnoses in two groups. Secondary endpoints included time to treatment and patient outcomes. METHODS: A prospective, observational, controlled study was conducted in a single university hospital. Two teams alternated every other day for managing in-hospital ward patients developing acute respiratory and/or circulatory failures. Only one of the team used an ultrasound device (POCUS group). RESULTS: We included 165 patients (POCUS group 83, control group 82). Proportion of adequate immediate diagnoses was 94% in the POCUS group and 80% in the control group (p = 0.009). Time to first treatment/intervention was shorter in the POCUS group (15 [10-25] min vs. 34 [15-40] min, p < 0.001). In-hospital mortality rates were 17% in the POCUS group and 35% in the control group (p = 0.007), but this difference was not confirmed in the propensity score sample (29% vs. 34%, p = 0.53). CONCLUSION: Our study suggests that protocolized use of a handheld POCUS device at the bedside in the ward may improve the proportion of adequate diagnosis, the time to initial treatment and perhaps also survival of ward patients developing acute respiratory or circulatory failure. Clinical Trial Registration NCT02967809. Registered 18 November 2016, https://clinicaltrials.gov/ct2/show/NCT02967809 .