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Background Current guidelines and literature support the use of therapeutic drug monitoring (TDM) to optimize β-lactam treatment in adult ICU patients. Objectives To describe the current practice of β-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 β-lactam TDM, including 52 (59.8%) with on-site access. β-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 β-lactam concentrations in the TDM results were expressed as unbound fractions or total concentrations. The 100% unbound fraction of the β-lactam above the MIC was the most frequent pharmacokinetic and pharmacodynamic target used (n = 62; 73.0%). Conclusions Despite the publication of international guidelines, β-lactam TDM is not optimally used in French ICUs. The two major barriers are β-lactam TDM interpretation and the required time for results.

IntroductionIn vitroandin vivopharmacokinetic/pharmacodynamic data describe improved activity of beta-lactam antibiotics when administered by prolonged infusion compared with standard intermittent infusion. There remains insufficient robust clinical trial data to support a widespread practice change. Patients with sepsis and septic shock are a population in whom prolonged infusion of beta-lactam antibiotics may improve survival. Two large multicentre randomised controlled trials (RCTs) comparing prolonged versus intermittent infusion of beta-lactam antibiotics in critically ill patients with sepsis or septic shock are due for completion in 2023. With existing RCT evidence, this systematic review and meta-analysis will include these new data to measure the clinical benefits of prolonged beta-lactam infusion in critically ill patients with sepsis.Methods and analysisThis protocol has been prepared according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) statement. This systematic review and meta-analysis will include RCTs that compare prolonged infusion with intermittent infusion of beta-lactam antibiotics in critically ill adult patients with sepsis. Medline (via PubMed), CINAHL, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and other clinical trials registries will be searched to identify eligible RCTs for review. Two reviewers will perform the study selection and extraction processes with disagreements resolved by discussion or referral to a third reviewer if needed. The Cochrane Collaboration’s Risk-of-Bias Tool for Randomised Trials version 2 (RoB 2) will be used to evaluate the quality of included studies. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be used to evaluate the overall quality of evidence for each outcome measures Thea prioriprimary outcome is all-cause 90-day mortality. Secondary outcomes include intensive care unit (ICU) mortality, ICU length of stay, clinical cure, microbiological cure, and the development of adverse events. Bayesian random-effects meta-analyses will be conducted, with frequentist analyses planned for sensitivity analysis.Ethics and disseminationHuman research ethics approval is not required as the study involves the use of existing collections of data that are de-identified. It is expected that findings will be presented at national and international intensive care and infectious diseases meetings, and will be submitted to a peer-reviewed journal for publication.PROSPERO Registration Number: CRD42023399434

Background: The delayed diagnosis of the presence of Candida in severe intra-abdominal infections exposes patients to an increased risk of mortality. The prevalence of intra-abdominal candidiasis (IAC) varies with the type of intra-abdominal infection, the underlying conditions and the presence of risk factors for Candida infection. This study aims to evaluate the interest of the measure of 1.3-β-D-glucan (BDG) in the peritoneal fluid for the early diagnosis of IAC. Methods and analysis: This is a prospective multicenter (n = 5) non-interventional study, focusing on all critically ill patients with an intra-abdominal infection requiring intra-abdominal surgery. The primary objective is to assess the diagnostic performance of the BDG measured in the peritoneal fluid for the early detection of IAC using the Candida culture as the gold standard. The secondary objective is to report the prevalence of IAC in the selected population. This study aims to enroll 200 patients within 48 months. By estimating the prevalence of IAC in the selected population at 30%, 50 patients with IAC (cases) are expected. These 50 IAC cases will be matched with 50 non-IAC patients (as a control group). The peritoneal BDG will be measured a posteriori in all of these 100 selected patients. This article presents the protocol and the current status of the study. Only the prevalence of IAC is reported as preliminary result.

Background Little is known about the outcomes of elderly patients admitted to the intensive care unit (ICU) with severe acute cholangitis (SAC). The objectives were to describe the 6-month mortality in patients with SAC ≥75 years and to identify factors associated with this mortality. Methods Bi-center retrospective study of critically ill elderly patients with SAC conducted between 2013 and 2017. Demographic and clinical variables of ICU and hospital stays with a 6-month follow-up were analyzed. Results 85 patients, with a median [Q1–Q3] age of 83 [80–89] years were enrolled of whom 51 (60%) were men. SAC was due to choledocholithiasis in 72 (85%) patients. Median [Q1–Q3] ICU length of stay was 3 [2–6] days. Median [Q1–Q3] admission SAPS II was 50 [42–70]. The ICU and 6-month mortality rates were 18% and 48% respectively. Multivariate analysis showed that malnutrition (OR = 34.5, 95% CI [1.4–817.9]) and a decrease in SOFA score at 48 h (OR by unit 0.7, 95% CI [0.5–0.9]) were associated with higher 6-month mortality. Conclusion In their decision-making process, ICU physicians and hepato-pancreato-biliary surgeons could use these data to estimate the probability of survival of an elderly patient presenting with SAC and to offer time-limited trials of intensive care. Trial registration NCT03831529.

Background : Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care. Methods : We retrieved data on patients with COVID-19 admitted to an intensive care unit (ICU) between March and October 2020 from the RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry. We applied the Extreme Gradient Boosting (XGBoost) algorithm to the data to predict as a binary outcome the increase or decrease in patients’ Sequential Organ Failure Assessment (SOFA) score on day 5 after ICU admission. The model was iteratively cross-validated in different subsets of the study cohort. Results : The final study population consisted of 675 patients. The XGBoost model correctly predicted a decrease in SOFA score in 320/385 (83%) critically ill COVID-19 patients, and an increase in the score in 210/290 (72%) patients. The area under the mean receiver operating characteristic curve for XGBoost was significantly higher than that for the logistic regression model {0.86 vs. 0.69, P

Background Critically ill patients with severe intra-abdominal infections (IAIs) requiring surgery may undergo several pharmacokinetic (PK) alterations that can lead to β-lactam underdosage. Objectives To measure serum and peritoneal exudate concentrations of β-lactams after high doses and optimal administration schemes. Methods This observational prospective study included critically ill patients with suspicion of IAI who required surgery and a β-lactam antibiotic as empirical therapy. Serum and peritoneal exudate concentrations were measured during surgery and after a 24 h steady-state period. The PK/pharmacodynamic (PD) target was to obtain serum β-lactam concentrations of 100% fT>4×MIC based on a worst-case scenario (based on the EUCAST highest epidemiological cut-off values) before bacterial documentation (a priori) and redefined following determination of the MIC for the isolated bacteria (a posteriori). Registered with ClinicalTrials.gov (NCT03310606). Results Forty-eight patients were included with a median (IQR) age of 64 (53–74) years and a SAPS II of 40 (32–65). The main diagnosis was secondary nosocomial peritonitis. Piperacillin/tazobactam was the most administered β-lactam antibiotic (75%). The serum/peritoneal piperacillin/tazobactam ratio was 0.88 (0.64–0.97) after a 24 h steady-state period. Prior to bacterial documentation, 16 patients (33.3%) achieved the a priori PK/PD target. The identification of microorganisms was available for 34 patients (71%). Based on the MIC for isolated bacteria, 78% of the patients achieved the serum PK/PD target. Conclusions In severe IAIs, high doses of β-lactams ensured 100% fT>4×MIC in the serum for 78% of critically ill patients with severe IAIs within the first 24 h. In order to define optimal β-lactam dosing, the PK/PD target should take into account the tissue penetration and local ecology.

BACKGROUND Analysis of pupillary reflex dilation (PRD) assesses the balance of nociception--antinociception. Laparoscopic surgery induces haemodynamic variations that are misleading. During laparoscopy, PRD guidance helps differentiate haemodynamic changes because of excess nociception from secondary changes related to the reflex release of endocrine factors. OBJECTIVE The present study evaluated the effect of PRD-guided antinociception on the administration of intra-operative remifentanil and immediate postoperative morphine consumption in patients undergoing elective laparoscopic surgery. DESIGN The study was a single-blind, randomised controlled trial. SETTING The study took place at two sites at the University Hospital of Nancy from March 2014 to November 2017. PATIENTS A total of 100 patients who underwent scheduled laparoscopic surgery were included. INTERVENTIONS Patients were randomly given remifentanil guided by PRD (PRD-guided) or standard anaesthesia care (control). MAIN OUTCOME MEASURES The primary outcome was intra-operative remifentanil consumption. Secondary outcomes included morphine consumption in the immediate postoperative period and the number of intra-operative haemodynamic events. RESULTS Data from 95 patients were analysed. Intraoperative remifentanil consumption was lower in the PRD-guided group than in the control group: median [IQR], 0.09 [0.07 to 0.11] vs. 0.14 [0.12 to 0.16] μg kg-1 min-1, with a mean difference (95% confidence Interval, CI) of 0.048 (0.035 to 0.060) μg kg-1 min-1; P

The FilmArray Pneumonia Panel has proven to be an effective tool for rapid detection of main respiratory pathogens. However, its rational use needs appropriate knowledge and formation regarding its indication and interpretation. Herein, we provide some advices to help with success of its daily routine use, particularly in critically ill ventilated COVID-19 patients. Clinical Trial registration number: NCT04453540.

A high inter-individual variability in pharmacokinetic parameters in obese patients is observed. The objective of this study was to evaluate the effect of obesity parameters on the pharmacokinetics of cefoxitin administered for antibiotic prophylaxis during bariatric surgery. This a secondary analysis of a pharmacokinetic study involving 174 obese patients scheduled for bariatric surgery and receiving a 4-g dose of cefoxitin. Blood samples were collected at incision and wound closure. The total plasma concentrations were assessed utilising a validated high-performance liquid chromatography–tandem mass spectrometry method. The pharmacokinetic and pharmacodynamic target was defined as an estimated free concentration of cefoxitin at the time of wound closure >8 mg/L. Specific evaluated obesity parameters were fat body mass, fat body mass/height2, lean body mass, lean body mass/height2, visceral adipose tissue and presence of a metabolic syndrome. A total of 174 patients (median age 47 years) with a majority of women (75.3%) and a median BMI of 44 kg/m2 were analysed. The percentage of patients who met the pharmacokinetic and pharmacodynamic target was 85.1%. In the whole population, a tendency to fail to reach the target was observed with a higher lean mass over height2 [OR = 0.79; 95% CI (0.62–1.01); P = 0.060]. In the female subgroup, higher lean mass over height2 [OR = 0.63; 95% CI (0.41–0.97); P = 0.037] and the presence of a metabolic syndrome [OR = 0.17; 95% CI (0.03–0.83); P = 0.030] were associated with failure to reach the pharmacokinetic and pharmacodynamic target. Obese patients with a higher lean mass and a metabolic syndrome could constitute a subgroup at risk for cefoxitin under-dosage.

Background Prone positioning (PP) is a standard of care for patients with moderate–severe acute respiratory distress syndrome (ARDS). While adverse events associated with PP are well-documented in the literature, research examining the effect of PP on the risk of infectious complications of intravascular catheters is lacking. Method All consecutive ARDS patients treated with PP were recruited retrospectively over a two-year period and formed the exposed group. Intensive care unit (ICU) patients during the same period without ARDS for whom PP was not conducted but who had an equivalent disease severity were matched 1:1 to the exposed group based on age, sex, centre, length of ICU stay and SAPS II (unexposed group). Infection-related catheter complications were defined by a composite criterion, including catheter tip colonization or intravascular catheter-related infection. Results A total of 101 exposed patients were included in the study. Most had direct ARDS (pneumonia). The median [Q1–Q3] PP session number was 2 [1–4]. These patients were matched with 101 unexposed patients. The mortality rates of the exposed and unexposed groups were 31 and 30%, respectively. The incidence of the composite criterion was 14.2/1000 in the exposed group compared with 8.2/1000 days in the control group (p = 0.09). Multivariate analysis identified PP as a factor related to catheter colonization or infection (p = 0.04). Conclusion Our data suggest that PP is associated with a higher risk of CVC infectious complications.

Background Coronavirus disease 2019 (COVID-19) is associated with a high disease burden with 10% of confirmed cases progressing towards critical illness. Nevertheless, the disease course and predictors of mortality in critically ill patients are poorly understood. Methods Following the critical developments in ICUs in regions experiencing early inception of the pandemic, the European-based, international RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry was created to provide near real-time assessment of patients developing critical illness due to COVID-19. Findings As of April 22, 2020, 639 critically ill patients with confirmed SARS-CoV-2 infection were included in the RISC-19-ICU registry. Of these, 398 had deceased or been discharged from the ICU. ICU-mortality was 24%, median length of stay 12 (IQR, 5-21) days. ARDS was diagnosed in 74%, with a minimum P/F-ratio of 110 (IQR, 80-148). Prone positioning, ECCO2R, or ECMO were applied in 57%. Off-label therapies were prescribed in 265 (67%) patients, and 89% of all bloodstream infections were observed in this subgroup (n = 66; RR=3·2, 95% CI [1·7-6·0]). While PCT and IL-6 levels remained similar in ICU survivors and non-survivors throughout the ICU stay (p = 0·35, 0·34), CRP, creatinine, troponin, d-dimer, lactate, neutrophil count, P/F-ratio diverged within the first seven days (p

International audience; Background: Few data are available on patients who have experienced anaphylaxis and were admitted to ICUs. The purpose of this observational study was to describe the epidemiology and management of these patients.Methods: This was a multicentre retrospective study carried out in 23 French ICUs between 2012 and 2017. All patients who suffered anaphylaxis and were transferred to an ICU were included. Data were collected using an electronic database after approval by an ethics committee.Results: A total of 339 patients were included, and 17 (5%) died secondary to anaphylaxis. The main triggers were drugs (77%), contrast media (11%), and food (7%). Epinephrine was administered before ICU admission in 88% of patients with Grade III anaphylaxis and 100% of patients with Grade IV anaphylaxis. Most patients with Grades III and IV anaphylaxes did not receive the recommended dose of i.v. fluid of 30 ml kg-1 within the first 4 h of ICU admission. The time to epinephrine administration was not statistically different between survivors and non-survivors, but non-survivors received a higher dose of epinephrine (median: 5 [3-10] vs 3 [2-7] mg; P

Plasma neutrophil gelatinase-associated lipocalin (pNGAL) has been used as a biomarker in acute kidney injury (AKI). AKI is a common postoperative complication of aortic surgery. We sought to evaluate the performance of the immediately postoperative pNGAL level in comparison with the serum creatinine (SCr) level in predicting AKI and the need for renal replacement therapy (RRT).Prospective non-interventional study in a university hospital. Fifty patients undergoing elective or emergent major intra-abdominal aortic surgery were included. Comparisons between groups of patients with or without postoperative AKI, according to KDIGO staging, were made. Performance of NGAL was determined by examining the area under receiver operating characteristic (AUROC) curve.The incidence of AKI was 36%. At H+2, pNGAL values in AKI and non-AKI patients, respectively, were 221 [133-278] versus 50 [50-90] ng/mL (P0.0001), and SCr values were 115 [96-178] versus 90 [72-99] μmol/L (P0.0008). The AUROC of pNGAL for prediction of AKI was 0.90 (95% CI: 0.81-0.98) with an optimal cutoff of 112ng/mL, a sensitivity of 83%, specificity of 84%, and positive and negative predictive values of 75% and 90%, respectively. SCr produced an AUROC curve of 0.79 (0.65-0.92) at a cutoff of 110μmol/L. The diagnostic performance of pNGAL was significantly better than that of SCr (P=0.039). PNGAL at H+2 better predicted the RRT requirement [0.96 (0.90-1.0)] compared to SCr [0.86 (0.73-0.98)], but this difference was not statistically significant.A 2-hour postoperative determination of pNGAL outperformed SCr level in predicting postoperative AKI after major aortic surgery.

International audience; Aim: Describing acute respiratory distress syndrome patterns, therapeutics management, and outcomes of ICU COVID-19 patients and indentifying risk factors of 28-day mortality.Methods: Prospective multicentre, cohort study conducted in 29 French ICUs. Baseline characteristics, comorbidities, adjunctive therapies, ventilatory support at ICU admission and survival data were collected.Results: From March to July 2020, 966 patients were enrolled with a median age of 66 (interquartile range 58-73) years and a median SAPS II of 37 (29-48). During the first 24 h of ICU admission, COVID-19 patients received one of the following respiratory supports: mechanical ventilation for 559 (58%), standard oxygen therapy for 228 (24%) and high-flow nasal cannula (HFNC) for 179 (19%) patients. Overall, 721 (75%) patients were mechanically ventilated during their ICU stay. Prone positioning and neuromuscular blocking agents were used in 494 (51%) and 460 (48%) patients, respectively. Bacterial co-infections and ventilator-associated pneumonia were diagnosed in 79 (3%) and 411 (43%) patients, respectively. The overall 28-day mortality was 18%. Age, pre-existing comorbidities, severity of respiratory failure and the absence of antiviral therapy on admission were identified as independent predictors of 28-day outcome.Conclusion: Severity of hypoxaemia on admission, older age (> 70 years), cardiovascular and renal comorbidities were associated with worse outcome in COVID-19 patients. Antiviral treatment on admission was identified as a protective factor for 28-day mortality. Ascertaining the outcomes of critically ill COVID-19 patients is crucial to optimise hospital and ICU resources and provide the appropriate intensity level of care.

International audience

The optimal dose of cefoxitin for antibiotic prophylaxis in obese patients remains uncertain. We evaluated the adequacy of a 4-g dosing regimen of cefoxitin against the most common pathogens that infect patients undergoing bariatric surgery. This observational prospective study included obese patients who required bariatric surgery and a 4-g dose of cefoxitin as an antibiotic prophylaxis. Serum concentrations were measured during surgery (incision, wound closure, and in case of reinjection). The pharmacokinetic/pharmacodynamic (PK/PD) target was to obtain free cefoxitin concentrations above 4× MIC, from incision to wound closure (100% fT>4×MIC). The targeted MIC was based on the worst-case scenario (the highest ECOFF value of Staphylococcus aureus, Enterobacteriaceae, and anaerobic bacteria). The secondary outcomes were the factors related to underdosage. A total of 200 patients were included. The mean age of the patients was 46 ± 12 years old, and the mean body mass index (BMI) was 45.8 ± 6.9 kg/m(2). Bypass surgery was the preferred technique (84%). The percentages of patients who met the PK/PD target (100% fT>4×MIC) of cefoxitin were 37.3, 1.1, and 0% for S. aureus, Enterobacteriaceae and anaerobic bacteria, respectively. BMIs below 50 kg/m(2) (odds ratio [OR] = 0.29, 95% confidence interval [CI] = 0.11 to 0.75, P = 0.0107) and a shorter duration of surgery (OR = 0.97, 95% CI = 0.95 to 0.99, P = 0.004) were associated with reaching the target concentrations. In obese patients undergoing bariatric surgery, a regimen of 4 g of cefoxitin led to an inadequate coverage for most common pathogens. A longer surgery duration and a BMI of >50 kg/m(2) increase the risk of underdosage. (This study was registered on ClinicalTrials.gov under identifier NCT03306290.)

Background Smartphone to-do list app was hypothesized to be more efficient than a paper-based list in the management of workflow and to provide additional benefits. Purpose To analyze the impact of a mobile task-management application on the workflow of an ICU medical staff. Methods Superiority by a margin test, quasi-experimental study comparing the use of a smartphone application versus standard practice regarding tasks management in an academic ICU. Superiority margin was set at 8 % based on a pilot study. During two periods of 20 working days each (October 2018 and January 2019), medical staff managed tasks with both methods on a weekly rotation basis. Primary outcome was the proportion of daily tasks completed. Secondary outcomes assessed users’ satisfaction and the impact of the app in terms of changes in clinical practice. Results 25 ICU physicians were enrolled. A total of 1983 tasks were recorded. The proportion of completed tasks per day was higher when using the smartphone app (99 % [96–100] versus 95 % [93–98] for the standard group, p = 0.006), but did not reach the superiority margin. Smartphone application was perceived as positive experience, as participants felt that they forgot fewer tasks (p = 0.02), were more aware of their progress on ongoing or remaining tasks (p = 0.03) and observed an improvement in communication among the medical staff (p = 0.03). Conclusion This study failed to demonstrate the superiority of a smartphone app over paper-based lists regarding the proportion of daily tasks completed. However, positive feedback regarding the application was received from the medical staff.

Background Antibiotic stewardship programmes have a pivotal role in ICUs, but the level of implementation of these programmes at the regional or national level is not well known. Objectives The aim of our study was to assess the level of implementation of antibiotic stewardship programmes in French ICUs. Methods We conducted a nationwide cross-sectional survey from January to March 2018 using an online questionnaire sent as an E-mail link to ICU specialists (one questionnaire per ICU). Results Overall, 113 out of 206 (55%) ICUs participated. Access to local epidemiology regarding bacterial resistance and antibiotic consumption data was reported in 84% and 65% of ICUs, respectively. Local guidelines for antibiotic use were available in 54% of ICUs. The duration of empirical antibiotic therapy was limited in 46% of cases, following the recommendation of an external expert in 33%. An antibiotic stewardship programme leader was reported at the hospital level by 94% of respondents, being an infectious disease physician in 80%. His/her role in the ICU was mostly to discuss specific cases (50%) and to provide advice on antibiotic prescriptions (26%). Regarding microbiological diagnosis, blood cultures were not processed at night or during weekends in 57%. Molecular biology and MS techniques were available in 62% and 59% of cases, respectively. Therapeutic drug monitoring of β-lactams was available in 46% of cases. Forty-three percent of respondents knew the expression 'antimicrobial/antibiotic stewardship'. Conclusions Antibiotic stewardship programmes are not optimally implemented in French ICUs. Improvement efforts and regular monitoring of the level of implementation are needed.

BACKGROUND Decision to start an anti-fungal therapy in intra-abdominal candidiasis (IAC) is complex. Yeast culture, considered the gold standard, suffers from a delayed response time and exposes the patient to delayed introduction of anti-fungal therapy. We sought to evaluate the performance and feasibility of measuring 1,3-β-D-glucan (1,3-BDG) in the peritoneal fluid (PF) for the diagnosis of IAC. METHODS We analyzed retrospectively all PF obtained during abdominal surgery for critically ill adult patients presenting intra-abdominal infections. For each PF sample, direct examination, bacterial and fungal culture, fungal PCR and 1,3-BDG measurements were performed. The diagnostic performance of each technique and the Peritonitis score were calculated considering the positive yeast culture as the reference. The levels of 1,3-BDG were compared between IAC and non-IAC patients. RESULTS During an 8-month period in 2016, 33 PF samples were recovered. Median (interquartile range) SAPS 2 and SOFA scores were 44 (9-94) and 9 (4-15), respectively. There were seven cases of IAC, 14 of bacterial peritonitis and 12 of undocumented peritonitis. All IAC cases were secondary peritonitis, with a 1,3-BDG level of 1461 (325-5000) versus 224 (68-1357) pg/mL in the non-IAC group (P=0.03). When the 1,3-BDG level was ≤310 pg/mL, its negative predictive value was 100%. CONCLUSIONS In secondary peritonitis, a peritoneal measurement of 1,3-BDG ≤310 pg/mL could rule out IAC.

Lactic acidosis is a very common biological issue for shock patients. Experimental data clearly demonstrate that metabolic acidosis, including lactic acidosis, participates in the reduction of cardiac contractility and in the vascular hyporesponsiveness to vasopressors through various mechanisms. However, the contributions of each mechanism responsible for these deleterious effects have not been fully determined and their respective consequences on organ failure are still poorly defined, particularly in humans. Despite some convincing experimental data, no clinical trial has established the level at which pH becomes deleterious for hemodynamics. Consequently, the essential treatment for lactic acidosis in shock patients is to correct the cause. It is unknown, however, whether symptomatic pH correction is beneficial in shock patients. The latest Surviving Sepsis Campaign guidelines recommend against the use of buffer therapy with pH ≥7.15 and issue no recommendation for pH levels

Introduction Les programmes d’« antibiotic stewardship » (bon usage des antibiotiques) ont un role central dans les services de reanimation. A ce jour, le niveau de mise en oeuvre de ces programmes est mal connu. Notre objectif etait d’evaluer le niveau de mise en oeuvre des programmes de bon usage dans les services de reanimation francais. Materiels et methodes Nous avons mene une enquete nationale de janvier a mars 2018 a l’aide d’un questionnaire en ligne envoye par courrier electronique aux specialistes de reanimation (un questionnaire par service). Le questionnaire explorait les moyens a disposition des cliniciens pour optimiser la prescription d’antibiotique : acces aux donnees d’ecologie bacterienne et de consommation d’antibiotique, dispositifs d’aide a la prescription, outils de diagnostic microbiologique, possibilite de suivi therapeutique pharmacologique et acces a des avis d’experts. Quand elle etait presente, la qualite de la relation clinicien/expert infectiologue etait evaluee. Resultats Au total, 113 unites de reanimation sur 206 (55 %) ont participe. L’acces aux donnees d’ecologie locale concernant les donnees de resistance bacterienne et de consommation d’antibiotiques a ete rapporte respectivement par 84 % et 65 % des services. Des recommandations locales sur l’utilisation des antibiotiques etaient disponibles dans 54 % des services. La duree de l’antibiotherapie probabiliste etait limitee dans 46 % des cas, sur recommandation d’un expert exterieur dans 33 % des cas. Un referent d’etablissement concernant le bon usage des antibiotiques etait present dans 94 % des cas. Il s’agissait d’un infectiologue dans 80 % des reponses. Son role dans l’unite de reanimation consistait principalement a discuter de cas specifiques (50 %) et a donner des conseils sur les prescriptions d’antibiotiques (26 %). En ce qui concerne le diagnostic microbiologique, les hemocultures n’etaient pas traitees la nuit ou le week-end dans 57 % des cas. Les techniques de biologie moleculaire et de spectrometrie de masse etaient respectivement disponibles dans 62 % et 59 % des cas. Le dosage des beta-lactamines etait possible dans 46 % des cas. La qualite de la relation reanimateur/microbiologiste etait superieure a la relation reanimateur/infectiologue. Seuls 43 % des repondants ont declare avoir deja entendu parler du concept d’« antibiotic stewardship » avant l’enquete. Conclusion La promotion et l’application des programmes d’« antibiotic stewardship » ne sont pas optimales dans les reanimations francaises. Une meilleure connaissance des regles de bon usage et un suivi regulier du niveau de mise en oeuvre sont necessaires.

Neurological complications are frequent in infective endocarditis (IE) and increase morbidity and mortality rates. A wide spectrum of neurological disorders may be observed, including stroke or transient ischemic attack, cerebral hemorrhage, mycotic aneurysm, meningitis, cerebral abscess, or encephalopathy. Most complications occur early during the course of IE and are a hallmark of left-sided abnormalities of native or prosthetic valves. Ischemic lesions account for 40% to 50% of IE central nervous system complications. Systematic brain MRI may reveal cerebral abnormalities in up to 80% of patients, including cerebral embolism in 50%, mostly asymptomatic. Neurological complications affect both medical and surgical treatment and should be managed by an experimented multidisciplinary team including cardiologists, neurologists, intensive care specialists, and cardiac surgeons. Oral anticoagulant therapy given to patients presenting with cerebral ischemic lesions should be replaced by unfractionated heparin for at least 2 weeks, with a close monitoring of coagulation tests. Recently published data suggest that after an ischemic stroke, surgery indicated for heart failure, uncontrolled infection, abscess, or persisting high emboli risk should not be delayed, provided that the patient is not comatose or has no severe deficit. Surgery should be postponed for 2 to 3 weeks for patients with intracranial hemorrhage. Endovascular treatment is recommended for cerebral mycotic aneurysms, if there is no severe mass effect. Recent data suggests that neurological failure, which is associated with the location and extension of brain injury, is a major determinant for short-term prognosis.

Lesions involving the descending thoracic aorta apart from isthmus are rare and less known by anesthetists. We report the clinical course of two severely injured patients who sustained a thoracic aortic rupture in whom favorable outcome was achieved with endovascular treatment. Mechanisms, diagnosis and therapeutics aspects of these rare lesions are discussed according to literature.

A 32 year old parturient with a history of Tako-tsubo cardiomyopathy, who suffered from postpartum hemorrhage for which sulprostone was administered without any adverse events, is reported. Anesthetic considerations related to the management of patient with a history of Tako-tsubo cardiomyopathy, especially triggers that may cause a recurrence, are described. The potential deleterious effects of sulprostone in a patient with a history of Tako-tsubo cardiomyopathy are discussed.

We report two cases of inadvertent peripheral nerve catheter (PNC) shearing that occurred during placement under ultrasound guidance. Same PNC kits were used in two different hospitals. The possible causes of PNC shearing are exposed. Differences and mechanical properties of different PNC kits are discussed. The management of retained PNC carried out in these cases is presented.

International audience; Our objective was to assess current practices about the administration ă (intermittent, extended, or continuous infusions) and therapeutic drug ă monitoring (TDM) of beta-lactam antibiotics and vancomycin in France. We ă conducted a nationwide cross-sectional survey in May August 2015, using ă an online questionnaire, sent as an e-mail link to infectious disease ă specialists and intensive care specialists through national mailing ă lists. We used clinical vignettes of critically ill patients to assess ă physicians' practices about administration and TDM practices for ă amoxicillin, cloxacillin, piperacillin/tazobactam, cefotaxime, ă ceftazidime, cefepime, meropenem and vancomycin. In all, 507 physicians ă participated (507/1200, response rate 42%). TDM was rarely available ă for beta-lactams (from 16.5% (81/490) for cloxacillin to 30% (145/490) ă for ceftazidime), whereas vancomycin TDM was available in 97% (477/490) ă of the cases. In the clinical vignettes, ceftazidime and ă piperacillin/tazobactam were the beta-lactams administered most ă frequently by extended or continuous infusions (76% (336/440) and 57% ă (252/444), respectively). Gaps in knowledge about the duration of ă stability of intravenous beta-lactams were common (correct answers ă ranged from 8% (35/432) for cloxacillin to 33% (146/438) for ă ceftazidime). Most physicians (77%, 339/442) were convinced of the ă value of extended or continuous infusions for beta-lactams in critically ă ill patients, but 48% (211/442) did not have access to practical ă guidelines. Our survey found that most infectious disease and intensive ă care specialists are favourable to optimized administration of ă beta-lactams in critically ill patients. But the lack of guidelines and ă limited TDM availability for beta-lactams in hospitals are potential ă barriers to its implementation. (C) 2016 European Society of Clinical ă Microbiology and Infectious Diseases. Published by Elsevier Ltd. All ă rights reserved.

We herein report the first case of Takotsubo cardiomyopathy triggered by influenza A virus. Myocardial involvement in influenza virus infection has been described in 10% of cases. The literature has principally reported cases of acute myocarditis ranging from asymptomatic to fulminant heart failure and cardiac tamponade. Takotsubo cardiomyopathy frequently occurs in the setting of significant emotional or physical stress or acute medical illness, with a predominance in postmenopausal women. We report the diagnosis, management and outcomes presented in this case, with the aim of describing a new cardiovascular complication of influenza virus infection.

To assess long-term outcomes and the management of critical left-sided infective endocarditis (IE) and evaluate the impact of surgery.Among the 198 patients included prospectively for IE across 33 adult intensive care units (ICU) in France from 1 April 2007 to 1 October 2008, 137 (69%) were dead at a median follow-up time of 59.5 months. Characteristics significantly associated with mortality were: Sepsis-related Organ-Failure Assessment (SOFA) score at ICU admission [Hazard ratio (HR), 95% Confidence Interval (CI) of 1.43 (0.79-2.59) for SOFA 5-9; 2.01 (1.05-3.85) for SOFA 10-14; 3.53 (1.75-7.11) for SOFA 15-20; reference category SOFA 0-4; P = 0.003]; prosthetic mechanical valve IE [HR 2.01; 95% CI 1.09-3.69, P = 0.025]; vegetation size ≥15 mm [HR 1.64; 95% CI 1.03-2.63, P = 0.038]; and cardiac surgery [HR (95%CI), 0.33 (0.16-0.67) for surgery ≤1 day after IE diagnosis; 0.61 (0.29-1.26) for surgery 2-7 days after IE diagnosis; 0.42 (0.21-0.83) for surgery7 days after IE diagnosis; reference category no surgery; P = 0.005]. One hundred and three (52%) patients underwent cardiac surgery after a median time of 6 (16) days. Independent predictors of surgical intervention on multivariate analysis were: age ≤60 years [Odds ratio (OR) 5.30; 95% CI (2.46-11.41), P0.01], heart failure [OR 3.27; 95% CI (1.03-10.35), P = 0.04], cardiogenic shock [OR 3.31; 95% CI (1.47-7.46), P = 0.004], septic shock [OR 0.25; 95% CI (0.11-0.59), P = 0.002], immunosuppression [OR 0.15; 95% CI (0.04-0.55), P = 0.004], and diagnosis before or within 24 h of ICU admission [OR 2.81; 95% CI (1.14-6.95), P = 0.025]. SOFA score calculated the day of surgery was the only independently associated factor with long-term mortality [HR (95% CI) 1.59 (0.77-3.28) for SOFA 5-9; 3.56 (1.71-7.38) for SOFA 10-14; 11.58 (4.02-33.35) for SOFA 15-20; reference category SOFA 0-4; P0.0001]. Surgical timing was not associated with post-operative outcomes. Of the 158 patients with a theoretical indication for surgery, the 58 deemed not fit had a 95% mortality rate.Mortality in patients with critical IE remains unacceptably high. Factors associated with long-term outcomes are the severity of multiorgan failure, prosthetic mechanical valve IE, vegetation size ≥15 mm, and surgical treatment. Up to one-third of potential candidates do not undergo surgery and these patients experience extremely high mortality rates. The strongest independent predictor of post-operative mortality is the pre-operative multiorgan failure score while surgical timing does not seem to impact on outcomes.

Lactic acidosis is a very common biological issue for shock patients. Experimental data clearly demonstrate that metabolic acidosis, including lactic acidosis, participates in the reduction of cardiac contractility and in the vascular hyporesponsiveness to vasopressors through various mechanisms. However, the contributions of each mechanism responsible for these deleterious effects have not been fully determined and their respective consequences on organ failure are still poorly defined, particularly in humans. Despite some convincing experimental data, no clinical trial has established the level at which pH becomes deleterious for hemodynamics. Consequently, the essential treatment for lactic acidosis in shock patients is to correct the cause. It is unknown, however, whether symptomatic pH correction is beneficial in shock patients. The latest Surviving Sepsis Campaign guidelines recommend against the use of buffer therapy with pH ≥7.15 and issue no recommendation for pH levels

International audience; Background: Venous thromboembolism is a major complication of coronavirus disease 2019 (COVID-19). We hypothesized that a weight-adjusted intermediate dose of anticoagulation may decrease the risk of venous thromboembolism COVID-19 patients.Methods: In this multicenter, randomised, open-label, phase 4, superiority trial with blinded adjudication of outcomes, we randomly assigned adult patients hospitalised in 20 French centers and presenting with acute respiratory SARS-CoV-2. Eligible patients were randomly assigned (1:1 ratio) to receive an intermediate weight-adjusted prophylactic dose or a fixed-dose of subcutaneous low-molecular-weight heparin during the hospital stay. The primary outcome corresponded to symptomatic deep-vein thrombosis (fatal) pulmonary embolism during hospitalization (COVI-DOSE ClinicalTrials.gov number: NCT04373707).Findings: Between May 2020, and April 2021, 1000 patients underwent randomisation in medical wards (noncritically ill) (80.1%) and intensive care units (critically ill) (19.9%); 502 patients were assigned to receive a weight-adjusted intermediate dose, and 498 received fixed-dose thromboprophylaxis. Symptomatic venous thromboembolism occurred in 6 of 502 patients (1.2%) in the weight-adjusted dose group and in 10 of 498 patients (2.1%) in the fixed-dose group (subdistribution hazard ratio, 0.59; 95% CI, 0.22-1.63; P = 0.31). There was a twofold increased risk of major or clinically relevant nonmajor bleeding: 5.9% in the weight-adjusted dose group and 3.1% in the fixed-dose group (P = 0.034).Interpretation: In the COVI-DOSE trial, the observed rate of thromboembolic events was lower than expected in patients hospitalized for COVID-19 infection, and the study was unable to show a significant difference in the risk of venous thromboembolism between the two low-molecular-weight-heparin regimens.

International audience; OBJECTIVES: To describe the prevalence, associated factors, and clinical impact of an initial negative herpes simplex virus (HSV) polymerase chain reaction (PCR) in critically ill patients with PCR-proven HSV encephalitis. DESIGN: Retrospective multicenter study from 2007 to 2017. SETTING: Forty-seven French ICUs. PATIENTS: Critically ill patients admitted to the ICU with possible/probable acute encephalitis and a positive cerebrospinal fluid (CSF) PCR for HSV. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 273 patients with a median Glasgow Coma Scale score of 9 (6-12) at ICU admission. CSF HSV PCR was negative in 11 cases (4%), exclusively in lumbar punctures (LPs) performed less than 4 days after symptoms onset. Patients with an initial negative PCR presented with more frequent focal neurologic signs (4/11 [36.4%] vs 35/256 [13.7%]; p = 0.04) and lower CSF leukocytosis (4 cells/mm3 [3-25 cells/mm3] vs 52 cells/mm3 [12-160 cells/mm3]; p \textless 0.01). An initial negative PCR was associated with an increased delay between LP and acyclovir treatment (3 d [2-7 ] vs 0 d [0-0 d]; p \textless 0.01) and was independently associated with a poor neurologic outcome at hospital discharge (modified Rankin Scale score ≥ 4) (adjusted odds ratio, 9.89; 95% CI, 1.18-82.78). CONCLUSIONS: In severe herpes simplex encephalitis, initial negative CSF HSV PCR occurred in 4% of cases and was independently associated with worse neurologic outcome at hospital discharge. In these patients, a systematic multimodal diagnostic approach including early brain MRI and EEG will help clinicians avoid delayed acyclovir initiation or early inappropriate discontinuation.

L'auteur de la thèse a souhaité limiter l'accès aux membres de l'Enseignement supérieur français.; INTRODUCTION : La prise en charge des patients âgés (> 75 ans) en réanimation constitue un challenge majeur. L'angiocholite aiguë est une pathologie qui augmente avec l'âge et qui est associée à une mortalité importante. L'objectif principal était de décrire la mortalité des patients de 75 ans et plus admis en réanimation pour angiocholite aiguë. L'objectif secondaire était d'identifier les facteurs associés à la mortalité. MATÉRIEL ET MÉTHODE : Cette étude rétrospective, observationnelle et bicentrique incluait les patients de 75 ans ou plus admis en réanimation au CHRU de Nancy et au CHR de Metz pour angiocholite aiguë entre le 1er janvier 2013 et le 31 décembre 2017. Le critère de jugement principal était la mortalité en réanimation, à 3mois et à 6 mois. La mortalité à 6 mois des patients du même âge hospitalisés en dehors de la réanimation pour le même diagnostic au CHRU de Nancy était également collectée. RÉSULTATS : 85 patients étaient inclus avec un âge médian de 84±6 ans, un séjour en réanimation de 4.6 ± 4.3 jours et un score IGS 2 et SOFA à l'admission respectivement de 50 [42-70] et 8.0 [5.0-10.5]. L'angiocholite était principalement d'origine lithiasique (85%) et la cholangiopancréatographie rétrograde endoscopique a été réalisé chez la majorité des patients (87%) dont 76%% dans les 24 premières heures. Le taux de mortalité était de 18% en réanimation, 39% à 3 mois et 48% à 6 mois. Le taux de mortalité à 6 mois des patients non admis en réanimation était de 30%. La dénutrition sévère était significativement associée à la mortalité à 6 mois (OR 34.5 [1.5-818]) ainsi que la faible différence entre le score SOFA à l'admission et le score SOFA à 48h (OR par unité de 0.7 [0.5-0.9]). CONCLUSION : La mortalité en réanimation des patients âgés admis en réanimation pour angiocholite aiguë était de 18% et augmentait jusqu'à 48% à 6 mois. Le statut nutritionnel et le nombre de défaillances d'organes associé à leurs évolutions durant les 48 premières heures étaient significativement associés à la mortalité chez ces patients.

Introduction : L’ECMO (extracorporeal membrane oxygenation) est une technique d’assistance permettant de suppléer temporairement des patients souffrant de défaillances cardio-respiratoires réfractaires au traitement conventionnel. Son utilisation est en pleine expansion. Malgré une meilleure connaissance de la technique sa morbi-mortalité reste élevée. Le but de notre étude était de décrire notre activité d’ECMO cinq ans après sa mise en place, d’en étudier la morbi-mortalité et d’identifier des facteurs associés à la mortalité. Méthode : Il s’agit d’une étude observationnelle, rétrospective, monocentrique réalisée dans le service de réanimation médicale du CHRU de Nancy. Ont été inclus tous les patients traités par ECMO périphérique veino-artérielle (VA) ou veino-veineuse (VV) de Janvier 2010 à Décembre 2014. Résultats : 129 patients ont été inclus ; 89 ECMO VA et 40 ECMO VV. La mortalité à 90 jours était respectivement de 60% et 46% dans les groupes VA et VV. Les principals complications étaient les hémorragies et les infections. La transfusion en produits sanguins au cours des 24 heures après l’implantation était associée à la mortalité à 28 et 90 jours dans le groupe VA (OR=5.85, p=0.0005 et OR=3.80, p=0.004). Pour les ECMO VV, l’âge était significativement associé à la mortalité à 90 jours (OR=1.28, p=0.029). Conclusion : Cinq ans après la mise en oeuvre de l’ECMO dans notre service, la mortalité globale s’élevait à 56% avec un taux plus important dans les ECMO VA. Les complications hémorragiques étaient les plus fréquentes. Les facteurs de risque de mortalité identifiés étaient la transfusion sanguine pour les ECMO VA et l’âge pour les ECMO VV.