Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

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.

Knowledge-based, computerized, patient clinical decision support system for perioperative pain, nausea and constipation management: a clinical feasibility study.

Opioid administration is particularly challenging in the perioperative period. Computerized-based Clinical Decision Support Systems (CDSS) are a promising innovation that might improve perioperative pain control. We report the development and feasibility validation of a knowledge-based CDSS aiming at optimizing the management of perioperative pain, postoperative nausea and vomiting (PONV), and laxative medications. This novel CDSS uses patient adaptive testing through a smartphone display, literature-based rules, and individual medical prescriptions to produce direct medical advice for the patient user. Our objective was to test the feasibility of the clinical use of our CDSS in the perioperative setting. This was a prospective single arm, single center, cohort study conducted in Strasbourg University Hospital. The primary outcome was the agreement between the recommendation provided by the experimental device and the recommendation provided by study personnel who interpreted the same care algorithm (control). Thirty-seven patients were included in the study of which 30 (81%) used the experimental device. Agreement between these two care recommendations (computer driven vs. clinician driven) was observed in 51 out 54 uses of the device (94.2% [95% CI 85.9-98.4%]). The agreement level had a probability of 86.6% to exceed the 90% clinically relevant agreement threshold. The knowledge-based, patient CDSS we developed was feasible at providing recommendations for the treatment of pain, PONV and constipation in a perioperative clinical setting.Trial registration number & date The study protocol was registered in ClinicalTrial.gov before enrollment began (NCT05707247 on January 26th, 2023).

Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome.

BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network recommends a target partial pressure of arterial oxygen (Pao2) between 55 and 80 mm Hg. Prospective validation of this range in patients with ARDS is lacking. We hypothesized that targeting the lower limit of this range would improve outcomes in patients with ARDS. METHODS: In this multicenter, randomized trial, we assigned patients with ARDS to receive either conservative oxygen therapy (target Pao2, 55 to 70 mm Hg; oxygen saturation as measured by pulse oximetry [Spo2], 88 to 92%) or liberal oxygen therapy (target Pao2, 90 to 105 mm Hg; Spo2, ≥96%) for 7 days. The same mechanical-ventilation strategies were used in both groups. The primary outcome was death from any cause at 28 days. RESULTS: After the enrollment of 205 patients, the trial was prematurely stopped by the data and safety monitoring board because of safety concerns and a low likelihood of a significant difference between the two groups in the primary outcome. Four patients who did not meet the eligibility criteria were excluded. At day 28, a total of 34 of 99 patients (34.3%) in the conservative-oxygen group and 27 of 102 patients (26.5%) in the liberal-oxygen group had died (difference, 7.8 percentage points; 95% confidence interval [CI], -4.8 to 20.6). At day 90, 44.4% of the patients in the conservative-oxygen group and 30.4% of the patients in the liberal-oxygen group had died (difference, 14.0 percentage points; 95% CI, 0.7 to 27.2). Five mesenteric ischemic events occurred in the conservative-oxygen group. CONCLUSIONS: Among patients with ARDS, early exposure to a conservative-oxygenation strategy with a Pao2 between 55 and 70 mm Hg did not increase survival at 28 days. (Funded by the French Ministry of Health; LOCO2 ClinicalTrials.gov number, NCT02713451.).

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.

Early non-invasive ventilation and high-flow nasal oxygen therapy for preventing endotracheal intubation in hypoxemic blunt chest trauma patients: the OptiTHO randomized trial.

BACKGROUND: The benefit-risk ratio of prophylactic non-invasive ventilation (NIV) and high-flow nasal oxygen therapy (HFNC-O2) during the early stage of blunt chest trauma remains controversial because of limited data. The main objective of this study was to compare the rate of endotracheal intubation between two NIV strategies in high-risk blunt chest trauma patients. METHODS: The OptiTHO trial was a randomized, open-label, multicenter trial over a two-year period. Every adult patients admitted in intensive care unit within 48 h after a high-risk blunt chest trauma (Thoracic Trauma Severity Score ≥ 8), an estimated PaO2/FiO2 ratio < 300 and no evidence of acute respiratory failure were eligible for study enrollment (Clinical Trial Registration: NCT03943914). The primary objective was to compare the rate of endotracheal intubation for delayed respiratory failure between two NIV strategies: i) a prompt association of HFNC-O2 and "early" NIV in every patient for at least 48 h with vs. ii) the standard of care associating COT and "late" NIV, indicated in patients with respiratory deterioration and/or PaO2/FiO2 ratio ≤ 200 mmHg. Secondary outcomes were the occurrence of chest trauma-related complications (pulmonary infection, delayed hemothorax or moderate-to-severe ARDS). RESULTS: Study enrollment was stopped for futility after a 2-year study period and randomization of 141 patients. Overall, 11 patients (7.8%) required endotracheal intubation for delayed respiratory failure. The rate of endotracheal intubation was not significantly lower in patients treated with the experimental strategy (7% [5/71]) when compared to the control group (8.6% [6/70]), with an adjusted OR = 0.72 (95%IC: 0.20-2.43), p = 0.60. The occurrence of pulmonary infection, delayed hemothorax or delayed ARDS was not significantly lower in patients treated by the experimental strategy (adjusted OR = 1.99 [95%IC: 0.73-5.89], p = 0.18, 0.85 [95%IC: 0.33-2.20], p = 0.74 and 2.14 [95%IC: 0.36-20.77], p = 0.41, respectively). CONCLUSION: A prompt association of HFNC-O2 with preventive NIV did not reduce the rate of endotracheal intubation or secondary respiratory complications when compared to COT and late NIV in high-risk blunt chest trauma patients with non-severe hypoxemia and no sign of acute respiratory failure. CLINICAL TRIAL REGISTRATION: NCT03943914, Registered 7 May 2019.

Combination of serum and peritoneal 1.3-beta-D-glucan can rule out intra-abdominal candidiasis in surgical critically ill patients: a multicenter prospective study.

BACKGROUND: Intra-abdominal candidiasis (IAC) is difficult to predict in critically ill patients with intra-abdominal infection, leading to the overuse of antifungal treatments. Serum and peritoneal 1.3-beta-D-glucan (sBDG and pBDG) have been proposed to confirm or invalidate the diagnosis of IAC, but clinical studies have reported inconsistent results, notably because of heterogeneous populations with a low IAC prevalence. This study aimed to identify a high-risk IAC population and evaluate pBDG and sBDG in diagnosing IAC. METHODS: This prospective multicenter noninterventional French study included consecutive critically ill patients undergoing abdominal surgery for abdominal sepsis. The primary objective was to establish the IAC prevalence. The secondary objective was to explore whether sBDG and pBDG could be used to diagnose IAC. Wako® beta-glucan test (WT, Fujifilm Wako Chemicals Europe, Neuss, Germany) was used for pBDG measurements. WT and Fungitell® beta-D-glucan assay (FA, Associate of Cape Cod, East Falmouth, USA) were used for sBDG measurements. RESULTS: Between 1 January 2020 and 31 December 2022, 199 patients were included. Patients were predominantly male (63%), with a median age of 66 [54-72] years. The IAC prevalence was 44% (87/199). The main IAC type was secondary peritonitis. Septic shock occurred in 63% of cases. After multivariate analysis, a nosocomial origin was associated with more IAC cases (P = 0.0399). The median pBDG level was significantly elevated in IAC (448 [107.5-1578.0] pg/ml) compared to non-IAC patients (133 [16.0-831.0] pg/ml), P = 0.0021. For a pBDG threshold of 45 pg/ml, the negative predictive value in assessing IAC was 82.3%. The median sBDG level with WT (n = 42) at day 1 was higher in IAC (5 [3.0-9.0] pg/ml) than in non-IAC patients (3 [3.0-3.0] pg/ml), P = 0.012. Similarly, median sBDG level with FA (n = 140) at day 1 was higher in IAC (104 [38.0-211.0] pg/ml) than in non-IAC patients (50 [23.0-141.0] pg/ml), P = 0.009. Combining a peritonitis score < 3, sBDG < 3.3 pg/ml (WT) and pBDG < 45 pg/ml (WT) yielded a negative predictive value of 100%. CONCLUSION: In critically ill patients with intra-abdominal infection requiring surgery, the IAC prevalence was 44%. Combining low sBDG and pBDG with a low peritonitis score effectively excluded IAC and could limit unnecessary antifungal agent exposure. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (ID number 03997929, first registered on June 24, 2019).

Strategy to Develop a Common Simulation Training Program: Illustration with Anesthesia and Intensive Care Residency in France.

Phenomenon: The urgency of having fair and trustworthy competency-based assessment in medical training is growing. Simulation is increasingly recognized as a potent method for building and assessing applied competencies. The growing use of simulation and its application in summative assessment calls for comprehensive and rigorously designed programs. Defining the current baseline of what is available and feasible is a crucial first step. This paper uses anesthesia and intensive care (AIC) in France as a case study in how to document this baseline. Approach: An IRB-approved, online anonymous closed survey was submitted to AIC residency program directors and AIC simulation program directors in France from January to February 2021. The researcher-developed survey consisted of 65 questions across five sections: centers' characteristics, curricular characteristics, courses' characteristics, instructors' characteristics, and simulation perceptions and perspectives. Findings: The participation rate was 31/31 (100%) with 29 centers affiliated with a university hospital. All centers had AIC simulation activities. Resident training was structured in 94% of centers. Simulation uses were training (100%), research and development (61%), procedural or organizational testing (42%), and summative assessment (13%). Interprofessional full-scale simulation training existed in 90% of centers. Procedural training on simulators prior to clinical patients' care was performed "always" in 16%, "most often" in 45%, "sometimes" in 29% and "rarely" or "not" in 10% of centers. Simulated patients were used in 61% of centers. Main themes were identified for procedural skills, full-scale and simulated patient simulation training. Simulation activity was perceived as increasing in 68% of centers. Centers expressed a desire to participate in developing and using a national common AIC simulation program. Insights: Based on our findings in AIC, we demonstrated a baseline description of nationwide simulation activities. We now have a clearer perspective on a decentralized approach in which individual institutions or regional consortia conduct simulation for a discipline in a relatively homogeneous way, suggesting the feasibility for national guidelines. This approach provides useful clues for AIC and other disciplines to develop a comprehensive and meaningful program matching existing expectations and closing the identified gaps.

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.

Early perioperative quality of recovery after hip and knee arthroplasty: a retrospective comparative cohort study.

PURPOSE: Increasing our knowledge about postoperative global Quality-Of-Recovery (QoR) after THA and TKA is important to improve perioperative medicine, in particular for preoperative patient information and benchmarking of postoperative patient status. METHODS: This study is a single centre, retrospective cohort study of prospectively collected data, conducted in Strasbourg University Hospital, Strasbourg, France. The main outcome was the modified French version of the QoR-15 (mQoR-15F) score monitored preoperatively, at postoperative day one, three, 14 and 28. We questioned the hypothesis: would THA and TKA recovery patterns differ and would postoperative health status eventually overreach the preoperative reference? RESULTS: The mQoR-15F was statistically higher in the THA group compared to the TKA group in POD 1 and 28 (112 ± 17 vs. 107 ± 17; p < 0.01 and 131 ± 12 vs. 127 ± 15; p = 0.02, respectively). The mean postoperative time delay to reach preoperative mQoR-15F was seven and 16 days for THA and TKA patients, respectively. CONCLUSION: Early postoperative health status after THA and TKA differs significantly; TKA being associated with a larger early decrease of global health status compared to THA. Both THA and TKA groups global health status overreached preoperative levels after one and two weeks postoperatively. These surgery-specific recovery profiles may favor improved patient information to steer advised operative decision and set specific recovery goals as part of enhanced recovery pathways.

Cerebral perfusion using ASL in patients with COVID-19 and neurological manifestations: A retrospective multicenter observational study.

BACKGROUND AND PURPOSE: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences. METHODS: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex. RESULTS: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p = 0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies. CONCLUSION: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities.

Time to source control and outcome in community-acquired intra-abdominal infections: The multicentre observational PERICOM study.

BACKGROUND: Optimal management of community-acquired intra-abdominal infections (IAI) requires timely surgical source control and adequate anti-infective treatment. OBJECTIVE: To describe the initial management of community-acquired IAI admitted to the emergency department and assess the association between the length of time to either diagnosis or therapeutic procedures and patient outcomes. DESIGN: A prospective, multicentre, observational study. SETTING: Thirteen teaching hospitals in France between April 2018 and February 2019. PATIENTS: Two hundred and five patients aged at least 18 years diagnosed with community-acquired IAI. MAIN OUTCOME MEASURES: The primary outcome was hospital length of stay. The secondary outcome was hospital mortality. RESULTS: Patients had a mean age of 56 (± 21) years and a median [interquartile] SAPS II of 26 [17 to 34]. Among the study cohort, 18% were postoperatively transferred to intensive care unit and 7% had died by day 28. Median [IQR] time to imaging, antibiotic therapy and surgery were 4 [2 to 6], 7.5 [4 to 12.5] and 9 [5.5 to 17] hours, respectively. The length of time to surgical source control [0.99, 95% confidence interval (CI), 0.98 to 0.99], SOFA greater than 2 [0.36 (95% CI, 0.26 to 0.651)], age greater than 60 years [0.65 (95% CI, 0.45 to 0.94)], generalized peritonitis [0.7 (95% CI, 0.56 to 0.89)] and laparotomy surgery [0.657 (95% CI, 0.42 to 0.78)] were associated with longer hospital length of stay. The duration of time to surgical source control [1.02 (95% CI, 1.01 to 1.04)], generalized peritonitis [2.41 (95% CI, 1.27 to 4.61)], and SOFA score greater than 2 [6.14 (95% CI, 1.40 to 26.88)] were identified as independent risk factors for 28-day mortality. CONCLUSION: This multicentre observational study revealed that the time to surgical source control, patient severity and generalized peritonitis were identified as independent risk factors for increased hospital LOS and mortality in community-acquired IAI. Organisational strategies to reduce the time to surgical management of intra-abdominal infections should be further evaluated. STUDY REGISTRATION: ClinicalTrials.gov on 1 April 2018, NCT03544203.

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.

Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients.

BACKGROUND: Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings. METHODS: The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed. RESULTS: Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%). CONCLUSIONS: Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.

Vascular endothelial growth factor D is a biomarker of fluid overload in haemodialysis patients.

BACKGROUND: Improved understanding and assessment of the complex physiology of volume regulation in haemodialysis (HD) patients are required to improve patient care and reduce mortality associated with fluid overload (FO). METHODS: We searched for FO-related biomarkers among 184 peptides associated with cardiovascular disease in a cohort of 30 HD patients. First, we assessed the direct impact of HD on the peptides of interest by comparing plasma concentrations before and after treatment. Then, we compared cardiovascular peptide profiles between patients with and without FO as defined by bioimpedance analysis (BIA). The plasma concentration of selected candidate biomarkers for FO was determined by enzyme-linked immunosorbent assay (ELISA) and correlated with previously described FO-related clinical and laboratory parameters. For validation, results were confirmed in an independent cohort of 144 HD patients. RESULTS: We found seven peptides positively [NT-proBNP, B-type natriuretic peptide (BNP), vascular endothelial growth factor D (VEGFD), tumour necrosis factor-related apoptosis-inducing ligand receptor 2, growth differentiation factor 15, tumour necrosis factor ligand superfamily member 13B, chitinase-3-like protein 1] and five negatively (leptin, renin, epidermal growth factor receptor, interleukin-1 receptor antagonist, myeloblastin) correlated to FO. In addition to natriuretic peptides, VEGFD emerged as third peptide highly correlated with BIA (ρ = 0.619, P < 0.0001). In line with this, VEGFD concentration verified by ELISA correlated with BIA, BNP and soluble CD146 but not with vascular endothelial growth factor C (VEGFC). Notably, levels of VEGFD were unrelated to cardiac systolic function (P = 0.63), contrary to BNP (P = 0.0003). Finally, we observed that 1-year all-cause mortality was higher in patients with high BNP (P = 0.0002), FO (defined by BIA, P = 0.04) and high VEGFD (P = 0.02), but not with high VEGFC (P = 0.48). CONCLUSION: VEGFD is a novel FO-related biomarker with unique diagnostic and prognostic properties.

Deleterious Effects of Remote Ischaemic Per-conditioning During Lower Limb Ischaemia-Reperfusion in Mice.

OBJECTIVE: The aim of this study was to investigate whether remote ischaemic per-conditioning might protect skeletal muscle during lower limb ischaemia-reperfusion (IR). METHODS: Twenty-three male C57BL/6 mice were randomised into three groups: sham group (n = 7), IR group (unilateral tourniquet induced three hours of ischaemia followed by 24 hours of reperfusion, n = 8), and remote ischaemic per-conditioning group (RIPerC) (three cycles of 10 minute IR episodes on the non-ischaemic contralateral hindlimb, n = 8). Oxygraphy, spectrofluorometry, and electron paramagnetic resonance spectroscopy were performed in order to determine mitochondrial respiratory chain complexes activities, mitochondrial calcium retention capacity (CRC) and reactive oxygen species (ROS) production in skeletal muscle. RESULTS: IR impaired mitochondrial respiration (3.66 ± 0.98 vs. 7.31 ± 0. 54 µmol/min/g in ischaemic and sham muscles, p = .009 and p = .003 respectively) and tended to impair CRC (2.53 ± 0.32 vs. 3.64 ± 0.66 µmol/mg in ischaemic and sham muscles respectively, p = .066). IR did not modify ROS production (0.082 ± 0.004 vs. 0.070 ± 0.004 µmol/min/mg in ischaemic and sham muscles respectively, p = .74). RIPerC failed to restore mitochondrial respiration (3.82 ± 0.40 vs. 3.66 ± 0.98 µmol/min/g in ischaemic muscles from the RIPerC group and the IR group respectively, p = .45) and CRC (2.76 ± 0.3 vs. 2.53 ± 0.32 µmol/mg in ischaemic muscles from the RIPerC group and the IR group respectively, p = .25). RIPerC even impaired contralateral limb mitochondrial respiration (3.85 ± 0.34 vs. 7.31 ± 0. 54 µmol/min/g in contralateral muscles and sham muscles respectively, -47.3%, p = .009). CONCLUSION: RIPerC failed to protect ischaemic muscles and induced deleterious effects on the contralateral non-ischaemic muscles. These data do not support the concept of RIPerC.

Early hyperoxemia is associated with lower adjusted mortality after severe trauma: results from a French registry.

BACKGROUND: Hyperoxemia has been associated with increased mortality in critically ill patients, but little is known about its effect in trauma patients. The objective of this study was to assess the association between early hyperoxemia and in-hospital mortality after severe trauma. We hypothesized that a PaO2 ≥ 150 mmHg on admission was associated with increased in-hospital mortality. METHODS: Using data issued from a multicenter prospective trauma registry in France, we included trauma patients managed by the emergency medical services between May 2016 and March 2019 and admitted to a level I trauma center. Early hyperoxemia was defined as an arterial oxygen tension (PaO2) above 150 mmHg measured on hospital admission. In-hospital mortality was compared between normoxemic (150 > PaO2 ≥ 60 mmHg) and hyperoxemic patients using a propensity-score model with predetermined variables (gender, age, prehospital heart rate and systolic blood pressure, temperature, hemoglobin and arterial lactate, use of mechanical ventilation, presence of traumatic brain injury (TBI), initial Glasgow Coma Scale score, Injury Severity Score (ISS), American Society of Anesthesiologists physical health class > I, and presence of hemorrhagic shock). RESULTS: A total of 5912 patients were analyzed. The median age was 39 [26-55] years and 78% were male. More than half (53%) of the patients had an ISS above 15, and 32% had traumatic brain injury. On univariate analysis, the in-hospital mortality was higher in hyperoxemic patients compared to normoxemic patients (12% versus 9%, p < 0.0001). However, after propensity score matching, we found a significantly lower in-hospital mortality in hyperoxemic patients compared to normoxemic patients (OR 0.59 [0.50-0.70], p < 0.0001). CONCLUSION: In this large observational study, early hyperoxemia in trauma patients was associated with reduced adjusted in-hospital mortality. This result contrasts the unadjusted in-hospital mortality as well as numerous other findings reported in acutely and critically ill patients. The study calls for a randomized clinical trial to further investigate this association.

Risk factors and events in the adult intensive care unit associated with pain as self-reported at the end of the intensive care unit stay.

BACKGROUND: The short-term and long-term consequences of the most frequent painful procedures performed in the ICU are unclear. This study aimed to identify the risk factors associated with pain-related discomfort perceived by critically ill patients during the whole ICU stay as self-reported by patients at the end of their ICU stay. METHODS: The study involved 34 ICUs. Adult patients who survived an ICU stay of 3 calendar days or more were eligible for inclusion. Discomforts, including the pain-related discomfort, were assessed using the French 18-item questionnaire on discomfort in ICU patients, the "Inconforts des Patients de REAnimation" (IPREA). Patients scored each item from 0 (minimal discomfort) to 10 (maximal discomfort). Associations between patient characteristics at ICU admission, life support therapies and main potentially painful procedures performed during the ICU stay and pain-related discomfort scores assessed at the end of the ICU stay were analyzed. RESULTS: Patients with complete IPREA questionnaires (n = 2130) were included. The median pain-related discomfort score was 3 (IQR 0-5). From the univariate analysis, pain-related discomfort scores were negatively correlated with age and positively correlated with ICU stay duration; surgical patients reported significant higher pain-related discomfort scores than medical patients; chest drain insertion, chest drain removal, use of bladder catheter, central venous catheter (CVC) insertion, complex dressing change, and intra-hospital transport were associated with pain-related discomfort scores. From the multivariate analyses using generalized estimating equations models, only age, chest drain removal, use of a bladder catheter, CVC insertion, and intra-hospital transport were the main risk factors associated with pain-related discomfort scores. CONCLUSION: Patients who underwent chest drain removal, bladder catheter, CVC insertion, and intra-hospital transport during their ICU stay reported higher pain-related discomfort scores (with respect to the whole ICU stay and assessed at the end of their ICU stay) than patients who did not experience these events. This study may pave the way for further targeted studies aiming at investigating a causal link between these common procedures in the ICU and adult critically ill patients' perceptions of their ICU stay regarding recalled pain. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT02442934, retrospectively registered on May 13, 2015.

Theory and practical use of Bayesian methods in interpreting clinical trial data: a narrative review.

The critical reading of scientific articles is necessary for the daily practice of evidence-based medicine. Rigorous comprehension of statistical methods is essential, as reflected by the extensive use of statistics in the biomedical literature. In contrast to the customary frequentist approach, which never uses or gives the probability of a hypothesis, Bayesian theory uses probabilities for both hypotheses and data. This statistical approach is increasingly used for analyses of clinical trial data and for applied machine learning. The aim of this review is to compare general Bayesian concepts with frequentist methods to facilitate a better understanding of Bayesian theory for readers who are not familiar with this approach. The review is intended to be used in combination with a checklist we have devised for reading reports analysed by Bayesian methods. We compare and contrast the different approaches of Bayesian vs frequentist statistical methods by considering data from a clinical trial that lends itself to this comparative approach.

A consensus checklist to help clinicians interpret clinical trial results analysed by Bayesian methods.

INTRODUCTION: In the context of an increasing number of publications of trial data analysed by Bayesian methods, clinicians need support to better understand Bayesian statistical methods. The existing checklists are intended for people who already know these methods. We aimed to establish and validate a checklist that contains a group of items considered crucial in interpreting the results of a phase III RCT analysed with Bayesian methods. METHODS: A team of biostatisticians created a checklist of previously reported items and additional items identified from a literature review. Using three different articles in three rounds, the items were then validated by residents in anaesthesiology with no skills in statistics. RESULTS: Based on an initial item list, three rounds led to a consensus checklist. Eleven items were considered important information to be specified for understanding the validity of the results. Of these, three were considered essential: specification of the prior, source of the prior (when prior is informative), and the effect size point estimate with its credible interval. CONCLUSION: The checklist can help clinicians interpret the results of a phase III randomised clinical trial analysed by Bayesian methods, even clinicians with no particular knowledge of statistics, to ensure that the major elements of the statistical section are present and valid. Care should be taken in interpreting the results of a trial analysed by Bayesian methods that are not reported with these three essential items because the validity of the results cannot be established.