Comparison of mannitol and hypertonic saline solution for the treatment of suspected brain herniation during prehospital management of traumatic brain injury patients.

BACKGROUND AND IMPORTANCE: Occurrence of mydriasis during the prehospital management of traumatic brain injury (TBI) may suggest severe intracranial hypertension (ICH) subsequent to brain herniation. The initiation of hyperosmolar therapy to reduce ICH and brain herniation is recommended. Whether mannitol or hypertonic saline solution (HSS) should be preferred is unknown. OBJECTIVES: The objective of this study is to assess whether HSS, compared with mannitol, is associated with improved survival in adult trauma patients with TBI and mydriasis. DESIGN/SETTING AND PARTICIPANTS: A retrospective observational cohort study using the French Traumabase national registry to compare the ICU mortality of patients receiving either HSS or mannitol. Patients aged 16 years or older with moderate to severe TBI who presented with mydriasis during prehospital management were included. OUTCOME MEASURES AND ANALYSIS: We performed propensity score matching on a priori selected variables [i.e. age, sex and initial Coma Glasgow Scale (GCS)] with a ratio of 1 : 3 to ensure comparability between the two groups. The primary outcome was ICU mortality. The secondary outcomes were regression of pupillary abnormality during prehospital management, pulsatility index and diastolic velocity on transcranial Doppler within 24 h after TBI, early ICU mortality (within 48 h), ICU and hospital length of stay. RESULTS: Of 31 579 patients recorded in the registry between 2011 and 2021, 1417 presented with prehospital mydriasis and were included: 1172 (82.7%) received mannitol and 245 (17.3%) received HSS. After propensity score matching, 720 in the mannitol group matched 240 patients in the HSS group. Median age was 41 years [interquartile ranges (IQR) 26-60], 1058 were men (73%) and median GCS was 4 (IQR 3-6). No significant difference was observed in terms of characteristics and prehospital management between the two groups. ICU mortality was lower in the HSS group (45%) than in the mannitol group (54%) after matching [odds ratio (OR) 0.68 (0.5-0.9), P = 0.014]. No differences were identified between the groups in terms of secondary outcomes. CONCLUSION: In this propensity-matched observational study, the prehospital osmotherapy with HSS in TBI patients with prehospital mydriasis was associated with a lower ICU mortality compared to osmotherapy with mannitol.

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).

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.

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).

Intracranial pressure monitoring with and without brain tissue oxygen pressure monitoring for severe traumatic brain injury in France (OXY-TC): an open-label, randomised controlled superiority trial.

BACKGROUND: Optimisation of brain oxygenation might improve neurological outcome after traumatic brain injury. The OXY-TC trial explored the superiority of a strategy combining intracranial pressure and brain tissue oxygen pressure (PbtO2) monitoring over a strategy of intracranial pressure monitoring only to reduce the proportion of patients with poor neurological outcome at 6 months. METHODS: We did an open-label, randomised controlled superiority trial at 25 French tertiary referral centres. Within 16 h of brain injury, patients with severe traumatic brain injury (aged 18-75 years) were randomly assigned via a website to be managed during the first 5 days of admission to the intensive care unit either by intracranial pressure monitoring only or by both intracranial pressure and PbtO2 monitoring. Randomisation was stratified by age and centre. The study was open label due to the visibility of the intervention, but the statisticians and outcome assessors were masked to group allocation. The therapeutic objectives were to maintain intracranial pressure of 20 mm Hg or lower, and to keep PbtO2 (for those in the dual-monitoring group) above 20 mm Hg, at all times. The primary outcome was the proportion of patients with an extended Glasgow Outcome Scale (GOSE) score of 1-4 (death to upper severe disability) at 6 months after injury. The primary analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew consent or had protocol violations. This trial is registered with ClinicalTrials.gov, NCT02754063, and is completed. FINDINGS: Between June 15, 2016, and April 17, 2021, 318 patients were randomly assigned to receive either intracranial pressure monitoring only (n=160) or both intracranial pressure and PbtO2 monitoring (n=158). 27 individuals with protocol violations were not included in the modified intention-to-treat analysis. Thus, the primary outcome was analysed for 144 patients in the intracranial pressure only group and 147 patients in the intracranial pressure and PbtO2 group. Compared with intracranial pressure monitoring only, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with GOSE score 1-4 (51% [95% CI 43-60] in the intracranial pressure monitoring only group vs 52% [43-60] in the intracranial pressure and PbtO2 monitoring group; odds ratio 1·0 [95% CI 0·6-1·7]; p=0·95). Two (1%) of 144 participants in the intracranial pressure only group and 12 (8%) of 147 participants in the intracranial pressure and PbtO2 group had catheter dysfunction (p=0.011). Six patients (4%) in the intracranial pressure and PbtO2 group had an intracrebral haematoma related to the catheter, compared with none in the intracranial pressure only group (p=0.030). No significant difference in deaths was found between the two groups at 12 months after injury. At 12 months, 33 deaths had occurred in the intracranial pressure group: 25 (76%) were attributable to the brain trauma, six (18%) were end-of-life decisions, and two (6%) due to sepsis. 34 deaths had occured in the intracranial pressure and PbtO2 group at 12 months: 25 (74%) were attributable to the brain trauma, six (18%) were end-of-life decisions, one (3%) due to pulmonary embolism, one (3%) due to haemorrhagic shock, and one (3%) due to cardiac arrest. INTERPRETATION: After severe non-penetrating traumatic brain injury, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with poor neurological outcome at 6 months. Technical failures related to intracerebral catheter and intracerebral haematoma were more frequent in the intracranial pressure and PbtO2 group. Further research is needed to assess whether a targeted approach to multimodal brain monitoring could be useful in subgroups of patients with severe traumatic brain injury-eg, those with high intracranial pressure on admission. FUNDING: The French National Program for Clinical Research, La Fondation des Gueules Cassées, and Integra Lifesciences.

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.

Pictorial adaptation of the quality of recovery 15 scale and psychometric validation into a pediatric surgical population.

Patient reported outcomes measures (PROMS) are important endpoints to measure patient health status in the perioperative setting. However, there are no good tools to measure PROMS in the pediatric surgical population. Patients 7 to 17 years old undergoing surgery were included and followed up for 1 day after surgery (POD1). At POD1 the patients were asked to rate their overall postoperative recovery using a 100-mm visual analog scale (VAS). The primary outcome was the pediatric QoR-15 score on postoperative day 1 (POD1). 150 patients completed the study. The mean (SD) pediatric QoR-15F scores were 132.1 (14.1) and 111.0 (27.0), preoperatively and on POD1, respectively. Convergent validity confirmed with Pearson (r) correlation between the postoperative pediatric QoR-15F and the patient-rated global recovery assessment was 0.72 (95% confidence interval [0.63-0.79]; p < 10-16). Concerning reliability, internal consistency of the pediatric QoR-15 assessed by Cronbach's alpha was 0.90. The test-retest concordance correlation coefficient was 0.92; 95% CI [0.83-0.96]. Split-half alpha was 0.74. The pictorial pediatric version of the QoR-15F showed good validity, reliability, responsiveness, acceptability and feasibility. This PROMS should be considered for clinical care and research in the perioperative pediatric patient setting.Trial Registration: NCT04453410 on clinicaltrials.gov.

Comparison of Injuries Associated With Electric Scooters, Motorbikes, and Bicycles in France, 2019-2022.

Importance: Electric scooter (e-scooter) use is increasing in France and in many urban environments worldwide. Yet little is known about injuries associated with use of e-scooters. Objective: To describe characteristics and outcomes of major trauma involving e-scooters. Design, Setting, and Participants: A multicenter cohort study was conducted in France using the national major trauma registry between January 1, 2019, and December 20, 2022. All patients admitted to a participating major trauma center following a road traffic crash (RTC) involving an e-scooter, a bicycle, or a motorbike were included. Exposure: Included patients were compared according to the 3 mechanisms. Main Outcomes and Measures: The primary outcome was trauma severity as defined by the Injury Severity Score (ISS). Secondary outcomes included the trends of the number of patients per year, a comparison of the RTC epidemiologic factors, injury severity, resources used, and in-hospital outcomes. Results: A total of 5233 patients involved in RTCs were admitted (median age, 33 [IQR, 24-48] years; 4629 [88.5%] men; median ISS, 13 [IQR, 8-22]). The population included 229 e-scooter RTCs (4.4%), 4094 motorbike RTCs (78.2%), and 910 bicycle RTCs (17.4%). The number of patients treated following e-scooter RTCs increased by 2.8-fold in 4 years (from 31 in 2019 to 88 in 2022), while bicycle RTCs increased by 1.2-fold and motorbike RTCs decreased by 0.9-fold. At admission, 36.7% of e-scooter users had a blood alcohol content higher than the legal threshold (n = 84) and 22.5% wore a protective helmet (n = 32). Among e-scooter RTCs, 102 patients (45.5%) had an ISS of 16 or higher. This proportion was similar for patients with motorbike RTCs (1557 [39.7%]; P = .10) and bicycle RTCs (411 [47.3%]; P = .69). With a proportion of 25.9% (n = 50), patients with e-scooter RTCs had twice as many severe traumatic brain injuries (Glasgow Coma Scale ≤8) as motorbike RTCs (445 [11.8%]) and a proportion comparable to bicycle RTCs (174 [22.1%]). The mortality of e-scooter RTCs was 9.2% (n = 20), compared with 5.2% (n = 196) (P = .02) for motorbikes and 10.0% (n = 84) (P = .82) for bicycles. Conclusions and Relevance: The findings of this study suggest that trauma involving e-scooters in France has significantly increased over the past 4 years. These patients presented with injury profiles as severe as those of individuals who experienced bicycle or motorbike RTCs, with a higher proportion of severe traumatic brain injury.

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.

Effect of surgical delay on 30-day mortality in patients receiving direct oral anticoagulants and admitted for hip fracture.

BACKGROUND: Early hip fracture surgery is recommended to decrease mortality, however the impact of a delay in surgery due to previous treatment with direct oral anticoagulants (DOA) is unknown. Our objective was to determine if early surgery, defined as surgery within 48 h of hospital admission is associated with decreased postoperative mortality. We tested the hypothesis that early surgery was beneficial with regard for mortality in patients treated with direct oral anticoagulants. METHODS: Retrospective cohort study in a French University Hospital including patient admitted for Hip fracture. The main exposure was wait time for surgery defined as the total time, in hours, between hospital admission and surgery. The main outcome was mortality within 30 days after hip fracture surgery. RESULTS: In 3429 patients, the overall 30-day mortality was 4.1% (95% CI 3.5%; 4.9%). In DOA + patients, the 30-day mortality rates in the early and delayed surgery groups were 1.2% and 5.9%, respectively, with estimated risk difference of -4.4 (with a 2% probability of this difference is > 0). In the DOA + group, early surgery tended to be associated with a higher percentage receiving red-blood cells (64.6% vs 54.8%, respectively, estimated risk difference of 9.9% with a 93% probability of this difference is > 0) and lower risk of pneumonia (1.2% vs 8.2%, respectively; estimated difference of -6.7% with 0.3% probability of superiority). CONCLUSION: Early hip fracture surgery was associated with improved survival in patients previously treated with DOAs.

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.

Association of Organizational Pathways With the Delay of Emergency Surgery.

Importance: Delayed admission of patients with surgical emergencies to the operating room occurs frequently and is associated with poor outcomes. In France, where 3 distinct organizational pathways in hospitals exist (a dedicated emergency operating room and team [DET], a dedicated operating room in a central operating theater [DOR], and no dedicated structure or team [NOR]), neither the incidence nor the influence of delayed urgent surgery is known, and no guidelines are available to date. Objective: To examine the overall frequency of delayed admission of patients with surgical emergencies to the operating room across the 3 organizational pathways in hospitals in France. Design, Setting, and Participants: This prospective multicenter cohort study was conducted in 10 French tertiary hospitals. All consecutive adult patients admitted for emergency surgery from October 5 to 16, 2020, were included and prospectively monitored. Patients requiring pediatric surgery, obstetrics, interventional radiology, or endoscopic procedures were excluded. Exposures: Emergency surgery. Main Outcomes and Measures: The main outcome was the global incidence of delayed emergency surgery across 3 predefined organizational pathways: DET, DOR, and NOR. The ratio between the actual time to surgery (observed duration between surgical indication and incision) and the ideal time to surgery (predefined optimal duration between surgical indication and incision according to the Non-Elective Surgery Triage classification) was calculated for each patient. Surgery was considered delayed when this ratio was greater than 1. Results: A total of 1149 patients were included (mean [SD] age, 55 [21] years; 685 [59.9%] males): 649 in the DET group, 320 in the DOR group, and 171 in the NOR group (missing data: n = 5). The global frequency of surgical delay was 32.5% (95% CI, 29.8%-35.3%) and varied across the 3 organizational pathways: DET, 28.4% (95% CI, 24.8%-31.9%); DOR, 32.2% (95% CI, 27.0%-37.4%); and NOR, 49.1% (95% CI, 41.6%-56.7%) (P < .001). The adjusted odds ratio for delay was 1.80 (95% CI, 1.17-2.78) when comparing NOR with DET. Conclusions and Relevance: In this cohort study, the frequency of delayed emergency surgery in France was 32.5%. Reduced delays were found in organizational pathways that included dedicated theaters and teams. These preliminary results may pave the way for comprehensive large-scale studies, from which results may potentially inform new guidelines for quicker and safer access to emergency surgery.

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.

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.

Anaesthetic and peri-operative management for thrombectomy procedures in stroke patients.

PURPOSE: To provide recommendations for the anaesthetic and peri-operative management for thrombectomy procedure in stroke patients DESIGN: A consensus committee of 15 experts issued from the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie et Réanimation, SFAR), the Association of French-language Neuro-Anaesthetists (Association des Neuro-Anesthésistes Réanimateurs de Langue Francaise, ANARLF), the French Neuro-Vascular Society (Société Francaise de Neuro-Vasculaire, SFNV), the French Neuro-Radiology Society (Société Francaise de Neuro-Radiologie, SFNR) and the French Study Group on Haemostasis and Thrombosis (Groupe Français d'Études sur l'Hémostase et la Thrombose, GFHT) was convened, under the supervision of two expert coordinators from the SFAR and the ANARLF. A formal conflict-of-interest policy was developed at the outset of the process and enforced throughout. The entire guideline elaboration process was conducted independently of any industry funding. The authors were required to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide their assessment of quality of evidence. METHODS: Four fields were defined prior to the literature search: (1) Peri-procedural management, (2) Prevention and management of secondary brain injuries, (3) Management of antiplatelet and anticoagulant treatments, (4) Post-procedural management and orientation of the patient. Questions were formulated using the PICO format (Population, Intervention, Comparison, and Outcomes) and updated as needed. Analysis of the literature was then conducted and the recommendations were formulated according to the GRADE methodology. RESULTS: The SFAR/ANARLF/SFNV/SFNR/GFHT guideline panel drew up 18 recommendations regarding anaesthetic management of mechanical thrombectomy procedures. Due to a lack of data in the literature allowing to conclude with high certainty on relevant clinical outcomes, the experts decided to formulate these guidelines as "Professional Practice Recommendations" (PPR) rather than "Formalized Expert Recommendations". After two rounds of rating and several amendments, a strong agreement was reached on 100% of the recommendations. No recommendation could be formulated for two questions. CONCLUSIONS: Strong agreement among experts was reached to provide a sizable number of recommendations aimed at optimising anaesthetic management for thrombectomy in patients suffering from stroke.

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.

Identifying biomarkers deciphering sepsis from trauma-induced sterile inflammation and trauma-induced sepsis.

Objective: The purpose of this study was to identify a panel of biomarkers for distinguishing early stage sepsis patients from non-infected trauma patients. Background: Accurate differentiation between trauma-induced sterile inflammation and real infective sepsis poses a complex life-threatening medical challenge because of their common symptoms albeit diverging clinical implications, namely different therapies. The timely and accurate identification of sepsis in trauma patients is therefore vital to ensure prompt and tailored medical interventions (provision of adequate antimicrobial agents and if possible eradication of infective foci) that can ultimately lead to improved therapeutic management and patient outcome. The adequate withholding of antimicrobials in trauma patients without sepsis is also important in aspects of both patient and environmental perspective. Methods: In this proof-of-concept study, we employed advanced technologies, including Matrix-Assisted Laser Desorption/Ionization (MALDI) and multiplex antibody arrays (MAA) to identify a panel of biomarkers distinguishing actual sepsis from trauma-induced sterile inflammation. Results: By comparing patient groups (controls, infected and non-infected trauma and septic shock patients under mechanical ventilation) at different time points, we uncovered distinct protein patterns associated with early trauma-induced sterile inflammation on the one hand and sepsis on the other hand. SYT13 and IL1F10 emerged as potential early sepsis biomarkers, while reduced levels of A2M were indicative of both trauma-induced inflammation and sepsis conditions. Additionally, higher levels of TREM1 were associated at a later stage in trauma patients. Furthermore, enrichment analyses revealed differences in the inflammatory response between trauma-induced inflammation and sepsis, with proteins related to complement and coagulation cascades being elevated whereas proteins relevant to focal adhesion were diminished in sepsis. Conclusions: Our findings, therefore, suggest that a combination of biomarkers is needed for the development of novel diagnostic approaches deciphering trauma-induced sterile inflammation from actual infective sepsis.

Appropriateness of Initial Course of Action in the Management of Blunt Trauma Based on a Diagnostic Workup Including an Extended Ultrasonography Scan.

Importance: The extended Focused Assessment With Sonography for Trauma (E-FAST) has become a cornerstone of the diagnostic workup in patients with trauma. The added value of a diagnostic workup including an E-FAST to support decision-making remains unknown. Objective: To determine how often an immediate course of action adopted in the resuscitation room based on a diagnostic workup that included an E-FAST and before whole-body computed tomography scanning (WBCT) in patients with blunt trauma was appropriate. Design, Setting, and Participants: This cohort study was conducted at 6 French level I trauma centers between November 5, 2018, and November 5, 2019. Consecutive patients treated for blunt trauma were assessed at the participating centers. Data analysis took place in February 2022. Exposures: Diagnostic workup associating E-FAST (including abdominal, thoracic, pubic, and transcranial Doppler ultrasonography scan), systematic clinical examination, and chest and pelvic radiographs. Main Outcomes and Measures: The main outcome criterion was the appropriateness of the observed course of action (including abstention) in the resuscitation room according to evaluation by a masked expert panel. Results: Of 515 patients screened, 510 patients (99.0%) were included. Among the 510 patients included, 394 were men (77.3%), the median (IQR) age was 46 years (29-61 years), and the median (IQR) Injury Severity Score (ISS) was 24 (17-34). Based on the initial diagnostic workup, no immediate therapeutic action was deemed necessary in 233 cases (45.7%). Conversely, the following immediate therapeutic actions were initiated before WBCT: 6 emergency laparotomies (1.2%), 2 pelvic angioembolisations (0.4%), 52 pelvic binders (10.2%), 41 chest drains (8.0%) and 16 chest decompressions (3.1%), 60 osmotherapies (11.8%), and 6 thoracotomies (1.2%). To improve cerebral blood flow based on transcranial doppler recordings, norepinephrine was initiated in 108 cases (21.2%). In summary, the expert panel considered the course of action appropriate in 493 of 510 cases (96.7%; 95% CI, 94.7%-98.0%). Among the 17 cases (3.3%) with inappropriate course of action, 13 (76%) corresponded to a deviation from existing guidelines and 4 (24%) resulted from an erroneous interpretation of the E-FAST. Conclusions and Relevance: This prospective, multicenter cohort study found that a diagnostic resuscitation room workup for patients with blunt trauma that included E-FAST with clinical assessment and targeted chest and pelvic radiographs was associated with the determination of an appropriate course of action prior to WBCT.

Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery: multicentre, randomised, double blind, placebo controlled trial.

OBJECTIVE: To investigate whether oral antimicrobial prophylaxis as an adjunct to intravenous antibiotic prophylaxis reduces surgical site infections after elective colorectal surgery. DESIGN: Multicentre, randomised, double blind, placebo controlled trial. SETTING: 11 university and non-university hospitals in France between 25 May 2016 and 8 August 2019. PARTICIPANTS: 926 adults scheduled for elective colorectal surgery. INTERVENTION: Patients were randomised to receive either a single 1 g dose of ornidazole (n=463) or placebo (n=463) orally 12 hours before surgery, in addition to intravenous antimicrobial prophylaxis before surgical incision. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients with surgical site infection within 30 days after surgery. Secondary outcomes included individual types of surgical site infections and major postoperative complications (Clavien-Dindo classification grade 3 or higher) within 30 days after surgery. RESULTS: Of the 960 patients who were enrolled, 926 (96%) were included in the analysis. The mean age of participants was 63 years and 554 (60%) were men. Surgical site infection within 30 days after surgery occurred in 60 of 463 patients (13%) in the oral prophylaxis group and 100 of 463 (22%) in the placebo group (absolute difference -8.6%, 95% confidence interval -13.5% to -3.8%; relative risk 0.60, 95% confidence interval 0.45 to 0.80). The proportion of patients with deep infections was 4.8% in the oral prophylaxis group and 8.0% in the placebo group (absolute difference -3.2%, 95% confidence interval -6.4% to -0.1%). The proportion of patients with organ space infections was 5.0% in the oral prophylaxis group and 8.4% in the placebo group (absolute difference -3.4%, -6.7% to -0.2%). Major postoperative complications occurred in 9.1% patients in the oral prophylaxis group and 13.6% in the placebo group (absolute difference -4.5%, -8.6% to -0.5%). CONCLUSION: Among adults undergoing elective colorectal surgery, the addition of a single 1 g dose of ornidazole compared with placebo before surgery significantly reduced surgical site infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT02618720.