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.

Herpes Simplex Virus Hepatitis in Patients Requiring Intensive Care Unit Admission: A Retrospective, Multicenter, Observational Study.

The clinical features and short-term prognosis of patients admitted to the intensive care unit for herpes hepatitis are lacking. Of 33 patients admitted between 2006 and 2022, 22 were immunocompromised, 4 were pregnant women, and 23 died. Sixteen patients developed a hemophagocytic syndrome. Acyclovir was initiated a median (interquartile range) of 1 (0-3) day after admission.

Bacterial Lipopolysaccharides Exacerbate Neurogenic Heterotopic Ossification Development.

Neurogenic heterotopic ossifications (NHO) are heterotopic bones that develop in periarticular muscles after severe central nervous system (CNS) injuries. Several retrospective studies have shown that NHO prevalence is higher in patients who suffer concomitant infections. However, it is unclear whether these infections directly contribute to NHO development or reflect the immunodepression observed in patients with CNS injury. Using our mouse model of NHO induced by spinal cord injury (SCI) between vertebrae T11 to T13 , we demonstrate that lipopolysaccharides (LPS) from gram-negative bacteria exacerbate NHO development in a toll-like receptor-4 (TLR4)-dependent manner, signaling through the TIR-domain-containing adapter-inducing interferon-ß (TRIF/TICAM1) adaptor rather than the myeloid differentiation primary response-88 (MYD88) adaptor. We find that T11 to T13 SCI did not significantly alter intestinal integrity nor cause intestinal bacteria translocation or endotoxemia, suggesting that NHO development is not driven by endotoxins from the gut in this model of SCI-induced NHO. Relevant to the human pathology, LPS increased expression of osteoblast markers in cultures of human fibro-adipogenic progenitors isolated from muscles surrounding NHO biopsies. In a case-control retrospective study in patients with traumatic brain injuries, infections with gram-negative Pseudomonas species were significantly associated with NHO development. Together these data suggest a functional association between gram-negative bacterial infections and NHO development and highlights infection management as a key consideration to avoid NHO development in patients. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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.

Multiple trauma in pregnant women: injury assessment, fetal radiation exposure and mortality. A multicentre observational study.

BACKGROUND: Fetal radiation exposure in pregnant women with trauma is a concern. The purpose of this study was to evaluate fetal radiation exposure with regard to the type of injury assessment performed. METHODS: It is a multicentre observational study. The cohort study included all pregnant women suspected of severe traumatic injury in the participating centres of a national trauma research network. The primary outcome was the cumulative radiation dose (mGy) received by the fetus with respect to the type of injury assessment initiated by the physician in charge of the pregnant patient. Secondary outcomes were maternal and fetal morbi-mortality, the incidence of haemorrhagic shock and the physicians' imaging assessment with consideration of their medical specialty. RESULTS: Fifty-four pregnant women were admitted for potential major trauma between September 2011 and December 2019 in the 21 participating centres. The median gestational age was 22 weeks [12-30]. 78% of women (n = 42) underwent WBCT. The remaining patients underwent radiographs, ultrasound or selective CT scans based on clinical examination. The median fetal radiation doses were 38 mGy [23-63] and 0 mGy [0-1]. Maternal mortality (6%) was lower than fetal mortality (17%). Two women (out of 3 maternal deaths) and 7 fetuses (out of 9 fetal deaths) died within the first 24 h following trauma. CONCLUSIONS: Immediate WBCT for initial injury assessment in pregnant women with trauma was associated with a fetal radiation dose below the 100 mGy threshold. Among the selected population with either a stable status with a moderate and nonthreatening injury pattern or isolated penetrating trauma, a selective strategy seemed safe in experienced centres.

Evaluation of transcranial Doppler use in patients with acute liver failure listed for emergency liver transplantation.

PURPOSE: Acute liver failure (ALF) is characterized by hepatic encephalopathy (HE) often due to intracranial hypertension (ICH). The risk/benefit-balance of intraparenchymal pressure catheter monitoring is controversial during ALF. AIMS: Perform an evaluation of transcranial Doppler (TCD) use in patients with ALF listed for emergency liver transplantation. MATERIAL AND METHODS: Single center retrospective cohort study including all patients registered on high emergency LT list between 2012 and 2018. All TCD measurements performed during ICU stay after listing and after LT (when performed) were recorded. TCD was considered abnormal when pulsatility index (PI) was >1.2. RESULTS: Among 106 patients with ALF, forty-seven (44%) had a TCD while on list. They had more severe liver and extrahepatic organ failure. When performed, TCD was abnormal in 51% of patients. These patients more frequently developed ICH events (45% vs. 13%, p = .02) and more frequently required increase in sedative drugs and vasopressors. While 22% of patients with normal TCD spontaneously survived, all of those with abnormal TCD died or were transplanted (p = .02). All transplanted patients who had abnormal exams normalized their TCD within 2 (1-2) days after LT. CONCLUSION: TCD may be a useful non-invasive tool for ICH detection and management, then guide sedation withdrawal.

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.

Effect of non-invasive ventilation after extubation in critically ill patients with obesity in France: a multicentre, unblinded, pragmatic randomised clinical trial.

BACKGROUND: Non-invasive ventilation (NIV) and oxygen therapy (high-flow nasal oxygen [HFNO] or standard oxygen) following extubation have never been compared in critically ill patients with obesity. We aimed to compare NIV (alternating with HFNO or standard oxygen) and oxygen therapy (HFNO or standard oxygen) following extubation of critically ill patients with obesity. METHODS: In this multicentre, parallel group, pragmatic randomised controlled trial, conducted in 39 intensive care units in France, critically ill patients with obesity undergoing extubation were randomly assigned (1:1) to either the NIV group or the oxygen therapy group. Two randomisations were performed: first, randomisation to either NIV or oxygen therapy, and second, randomisation to either HFNO or standard oxygen (also 1:1), which was nested within the first randomisation. Blinding of the randomisation was not possible, but the statistician was masked to group assignment. The primary outcome was treatment failure within 3 days after extubation, a composite of reintubation for mechanical ventilation, switch to the other study treatment, or premature discontinuation of study treatment. The primary outcome was analysed by intention to treat. Effect of medical and surgical status was assessed. The reintubation within 3 days was analysed by intention to treat and after a post-hoc crossover analysis. This study is registered with ClinicalTrials.gov, number NCT04014920. FINDINGS: From Oct 2, 2019, to July 17, 2021, of the 1650 screened patients, 981 were enrolled. Treatment failure occurred in 66 (13·5%) of 490 patients in the NIV group and in 130 (26·5%) of 491 patients in the oxygen-therapy group (relative risk 0·43; 95% CI 0·31-0·60, p<0·0001). Medical or surgical status did not modify the effect of NIV group on the treatment-failure rate. Reintubation within 3 days after extubation was similar in the non-invasive ventilation group and in the oxygen therapy group in the intention-to-treat analysis (48 (10%) of 490 patients and 59 (12%) of 491 patients, p=0·26) and lower in the NIV group than in the oxygen-therapy group in the post-hoc cross-over (51 (9%) of 560 patients and 56 (13%) of 421 patients, p=0·037) analysis. No severe adverse events were reported. INTERPRETATION: Among critically ill adults with obesity undergoing extubation, the use of NIV was effective to reduce treatment-failure within 3 days. Our results are relevant to clinical practice, supporting the use of NIV after extubation of critically ill patients with obesity. However, most of the difference in the primary outcome was due to patients in the oxygen therapy group switching to NIV, and more evidence is needed to conclude that an NIV strategy leads to improved patient-centred outcomes. FUNDING: French Ministry of Health.

External ventricular drainage for intracranial hypertension after traumatic brain injury: is it really useful?

PURPOSES: External ventricular drainage (EVD) is frequently used to control raised intracranial pressure after traumatic brain injury. However, the available evidence about its effectiveness in this context is limited. The aim of this study is to evaluate the effectiveness of EVD to control intracranial pressure and to identify the clinical and radiological factors associated with its success. METHODS: For this retrospective cohort study conducted in a Level 1 traumacenter in Paris area between May 2011 and March 2019, all patients with intracranial hypertension and treated with EVD were included. EVD success was defined as an efficient and continuous control of intracranial hypertension avoiding the use of third tier therapies (therapeutic hypothermia, decompressive craniectomy, and barbiturate coma) or avoiding a decision to withdraw life sustaining treatment due to both refractory intracranial hypertension and severity of brain injury lesions. RESULTS: 83 patients with EVD were included. EVD was successful in 33 patients (40%). Thirty-two patients (39%) required a decompressive craniectomy, eight patients (9%) received barbiturate coma. In ten cases (12%) refractory intracranial hypertension prompted a protocolized withdrawal of care. Complications occurred in nine patients (11%) (three cases of ventriculitis, six cases of catheter occlusion). Multivariate analysis identified no independent factors associated with EVD success. CONCLUSION: In a protocol-based management for traumatic brain injury, EVD allowed intracranial pressure control and avoided third tier therapeutic measures in 40% of cases with a favorable risk-benefit ratio.

The conundrum of the definition of haemorrhagic shock: a pragmatic exploration based on a scoping review, experts' survey and a cohort analysis.

PURPOSE: Traumatic hemorrhagic shock (THS) is a complex, dynamic process and, no consensual definition of THS is available. This study aims (1) to explore existing definitions of traumatic hemorrhagic shock (THS), (2) to identify essential components of these definitions and (3) to illustrate in a pragmatic way the consequences of applying five of these definitions to a trauma registry. METHODS: We conducted (1) a scoping review to identify the definitions used for traumatic hemorrhagic shock (THS); (2) an international experts survey to rank by relevance a selection of components extracted from these definitions and (3) a registry-based analysis where several candidate definitions were tested in a large trauma registry to evaluate how the use of different definitions affected baseline characteristics, resources use and patient outcome. RESULTS: Sixty-eight studies were included revealing 52 distinct definitions. The most frequently used was "a systolic blood pressure (SBP) less than or equal to 70 mmHg or between 71 and 90 mmHg if the heart rate is greater than or equal to 108 beats per min". The expert panel identified base excess, blood lactate concentration, SBP and shock index as the most relevant physiological components to define THS. Five definitions of THS were tested and highlighted significant differences across groups on important outcomes such as the proportion of massive transfusion, the need for surgery, in-hospital length of stay or in-hospital mortality. CONCLUSIONS: This study demonstrates a large heterogeneity in the definitions of THS suggesting a need for standardization. Five candidate definitions were identified in a three-step process to illustrate how each shapes study cohort composition and impacts outcome. The results inform research stakeholders in the choice of a consensual definition.

Long-term outcome following blunt cerebrovascular injuries: occurrence of ischemic complications, treatment, and outcome.

PURPOSE: Blunt cerebrovascular injuries (BCVI) are a rare but serious complication after trauma. Among patients with BCVI, neurological status is altered in 30% of cases and the prognosis seems to be associated with ischemic complications. The aim of this study was to assess the long-term outcome of BCVI-associated ischemic events. METHODS: This retrospective cohort study (2011-2017) included all patients admitted for severe trauma with identified BCVI in two level-1 trauma centers. Patients were considered to have a poor neurological outcome with a GOS-E between 2 and 5 and a good neurological outcome with GOS-E between 6 and 8. A multivariate logistic regression identified risk factors for poor neurological outcome at 1 year. RESULTS: Of the 6,294 patients admitted in both trauma centers between 2011 and 2017, 81 patients presenting BCVI were identified (incidence of 1.3%). The median age was 35 years (24-44) with a median Injury Severity Score of 28 (17-41). 29 patients (50%) had a good neurological prognosis, while 25 patients (43%) had a poor neurological prognosis at 1 year. Ischemic stroke occurred in 11 patients (13.6%) within a median time of 2 days (2-2.5). No ischemic stroke occurred in the first year after ICU discharge in both groups. In our study, good prognosis at 1 year was not associated with ischemic complications [3 (10) vs 3 (12) p = 1]. CONCLUSION: Ischemic complications after BCVI are rare, occur within the first week and do not seem to impact independently the 1-year neurological prognosis.

Clinical decision support for severe trauma patients: Machine learning based definition of a bundle of care for hemorrhagic shock and traumatic brain injury.

BACKGROUND: Deviation from guidelines is frequent in emergency situations, and this may lead to increased mortality. Probably because of time constraints, 55% is the greatest reported guidelines compliance rate in severe trauma patients. This study aimed to identify among all available recommendations a reasonable bundle of items that should be followed to optimize the outcome of hemorrhagic shocks (HSs) and severe traumatic brain injuries (TBIs). METHODS: We first estimated the compliance with French and European guidelines using the data from the French TraumaBase registry. Then, we used a machine learning procedure to reduce the number of recommendations into a minimal set of items to be followed to minimize 7-day mortality. We evaluated the bundles using an external validation cohort. RESULTS: This study included 5,924 trauma patients (1,414 HS and 4,955 TBI) between 2011 and August 2019 and studied compliance to 36 recommendation items. Overall compliance rate to recommendation items was 71.6% and 66.9% for HS and TBI, respectively. In HS, compliance was significantly associated with 7-day decreased mortality in univariate analysis but not in multivariate analysis (risk ratio [RR], 0.91; 95% confidence interval [CI], 0.90-1.17; p = 0.06). In TBI, compliance was significantly associated with decreased mortality in univariate and multivariate analysis (RR, 0.85; 95% CI, 0.75-0.92; p = 0.01). For HS, the bundle included 13 recommendation items. In the validation cohort, when this bundle was applied, patients were found to have a lower 7-day mortality rate (RR, 0.46; 95% CI, 0.27-0.63; p = 0.01). In TBI, the bundle included seven items. In the validation cohort, when this bundle was applied, patients had a lower 7-day mortality rate (RR, 0.55; 95% CI, 0.34-0.71; p = 0.02). DISCUSSION: Using a machine-learning procedure, we were able to identify a subset of recommendations that minimizes 7-day mortality following traumatic HS and TBI. These two bundles remain to be evaluated in a prospective manner. LEVEL OF EVIDENCE: Care Management, level II.

ISS is not an appropriate tool to estimate overtriage.

PURPOSE: The aim of this work is to study a cohort of patients of ISS < 15 admitted to a TC, and to determine the number of patients that ultimately benefited from the skills and resources specific of a level 1 trauma center. METHODS: Retrospective study from a prospective cohort of patients admitted to TC (Beaujon Hospital, APHP) for suspected severe trauma from January 2011 to December 2017. The main outcome criterion was the use of surgery or interventional radiology within the first 24 h after admission of patients with ISS < 15. The secondary outcomes were stratified into severe (mortality, resuscitation care, length of stay in intensive care units) and non-severe criteria (mild head injury, hospital discharge or transfer within 24 h). RESULTS: Of 3035 patients admitted during the study period, 1409 with an ISS < 15 were included, corresponding to a theoretical overtriage rate of 46.4%. Among these, 611 patients (43.4%) underwent emergency intervention within the first 24 h (586 surgical interventions, 19 direct transfers to the operating theater and 6 acts of interventional radiology), 238 (16.9%) of patients presented with severe and 531 (38%) with non-severe outcome criteria. CONCLUSION: This work demonstrates that in a cohort of patients classified as ISS < 15 admitted to a TC, a considerable amount of TC-specific resources are required, and patients present with severe outcome criteria despite being classified as overtriaged. These results suggest that triage of trauma patients should be based on resource use and clinical outcome rather than anatomic criteria.

Effect of 2020 containment strategies on trauma workflow in Ile-de-France region: another benefit of lockdown?

BACKGROUND: During the SARS-CoV-2 pandemic, the French Government imposed various containment strategies, such as severe lockdown (SL) or moderate lockdown (ML). The aim of this study was to evaluate the effect of both strategies on severe trauma admissions and ICU capacity in Ile-de-France region (Paris Area). MAIN TEXT: We conducted a multicenter cohort-based observational study from 1stJanuary 2017 to 31th December 2020, including all consecutive trauma patients admitted to the trauma centers of Ile-de-France region participating in the national registry (Traumabase®). Two periods were defined, the "non-pandemic period" (NPP) from 2017 to 2019, and the "pandemic period" (PP) concerning those admitted in 2020. The number of ICU beds released during 2020 pandemic period (overall period, SL and ML) was estimated by multiplying difference in trauma admissions by the median length of stay during the same week of pandemic period (ICU day-beds in 2020). A 15% yearly reduction of trauma patients was observed during the PP, associated with the release of 6422 ICU day-beds in 2020. During SL and ML, the observed decrease in trauma admission was respectively 49 and 39% compared with similar dates of the NPP. The number of beds released was 1531 days-beds in SL and 679 day-beds in ML. Those reductions respectively accounted for 4.5 and 6.0% of the overall ICU admission for COVID-19 in Ile-de-France. CONCLUSION: The lockdown strategies during pandemic resulted in a reduction of severe trauma admissions. In addition to the social distancing effect, lockdown strategies freed up an important number of ICU beds in trauma centers, available for severe COVID-19 patients.

Terror in Paris: Incidence and risk factors for infections related to high-energy ammunition injuries.

BACKGROUND: We aimed to assess the incidence and the risk factors for secondary wound infections associated to high-energy ammunition injuries (HEAI) in the cohort of civilian casualties from the 2015 terrorist attacks in Paris. METHODS: This retrospective multi-centric study included casualties presenting at least one HEAI who underwent surgery during the first 48 h following hospital admission. HEAI-associated infection was defined as a wound infection occurring within the initial 30 days following trauma. Risk factors were assessed using univariate and multivariate analysis. RESULTS: Among the 200 included victims, the rate of infected wounds was 11.5%. The median time between admission and the surgical revision for secondary wound infection was 11 days [IQR 9-20]. No patient died from an infectious cause. Infections were polymicrobial in 44% of the cases. The major risk factors for secondary wound infection were ISS (p < 0.001), SAPS II (p < 0.001), MGAP (p < 0.001), haemorrhagic shock (p = 0.003), use of vasopressors (p < 0.001), blood transfusion (p < 0.001), abdominal penetrating trauma (p = 0.003), open fracture (p = 0.01), vascular injury (p = 0.001), duration of surgery (p = 0.009), presence of surgical material (p = 0.01). In the multivariate analysis, the SAPS II score (OR 1.07 [1.014-1.182], p = 0.019) and the duration of surgery (OR 1.005 [1.000-1.012], p = 0.041) were the only risk factors identified. CONCLUSION: We report an 11.5% rate of secondary wound infection following high-energy ammunition injuries. Risk factors were an immediately severe condition and a prolonged surgery.

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.

Effect of fibrinogen concentrate administration on early mortality in traumatic hemorrhagic shock: A propensity score analysis.

BACKGROUND: Fibrinogen concentrate is widely used in traumatic hemorrhagic shock despite weak evidence in the literature. The aim of the study was to evaluate the effect of fibrinogen concentrate administration within the first 6 hours on 24-hour all-cause mortality in traumatic hemorrhagic shock using a causal inference approach. METHODS: Observational study from a French multicenter prospective trauma registry was performed. Hemorrhagic shock was defined as transfusion of four or more red blood cell units within the first 6 hours after admission. The confounding variables for the outcome (24-hour all-cause mortality) and treatment allocation (fibrinogen concentrate administration within the first 6 hours) were chosen by a Delphi method. The propensity score was specified with a data-adaptive algorithm and a doubly-robust approach with inverse proportionality of treatment weighting allowed to compute the average treatment effect. Sensitivity analyses were performed. RESULTS: Of 14,336 patients in the registry during the study period, 1,027 in hemorrhagic shock were analyzed (758 receiving fibrinogen concentrate within 6 hours and 269 not receiving fibrinogen concentrate). The average treatment effect, expressed as a risk difference, was -0.031 (95% confidence interval, -0.084 to 0.021). All sensitivity analysis confirmed the results. CONCLUSIONS: Fibrinogen concentrate administration within the first 6 hours of a traumatic hemorrhagic shock did not decrease 24-hour all-cause mortality. LEVEL OF EVIDENCE: Prognostic, level III.

Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF.

Background and Aims: Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have immunosuppression, indicated by an increase in circulating immune-deficient monocytes. The aim of this study was to investigate simultaneously the major blood-immune cell subsets in these patients. Material and Methods: Blood taken from 67 patients with decompensated cirrhosis (including 35 critically ill with ACLF in the intensive care unit), and 12 healthy subjects, was assigned to either measurements of clinical blood counts and microarray (genomewide) analysis of RNA expression in whole-blood; microarray (genomewide) analysis of RNA expression in blood neutrophils; or assessment of neutrophil antimicrobial functions. Results: Several features were found in patients with ACLF and not in those without ACLF. Indeed, clinical blood count measurements showed that patients with ACLF were characterized by leukocytosis, neutrophilia, and lymphopenia. Using the CIBERSORT method to deconvolute the whole-blood RNA-expression data, revealed that the hallmark of ACLF was the association of neutrophilia with increased proportions of macrophages M0-like monocytes and decreased proportions of memory lymphocytes (of B-cell, CD4 T-cell lineages), CD8 T cells and natural killer cells. Microarray analysis of neutrophil RNA expression revealed that neutrophils from patients with ACLF had a unique phenotype including induction of glycolysis and granule genes, and downregulation of cell-migration and cell-cycle genes. Moreover, neutrophils from these patients had defective production of the antimicrobial superoxide anion. Conclusions: Genomic analysis revealed that, among patients with decompensated cirrhosis, those with ACLF were characterized by dysregulation of blood immune cells, including increases in neutrophils (that had a unique phenotype) and macrophages M0-like monocytes, and depletion of several lymphocyte subsets (including memory lymphocytes). All these lymphocyte alterations, along with defective neutrophil superoxide anion production, may contribute to immunosuppression in ACLF, suggesting targets for future therapies.

Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial.

BACKGROUND: Acute acidaemia is frequently observed during critical illness. Sodium bicarbonate infusion for the treatment of severe metabolic acidaemia is a possible treatment option but remains controversial, as no studies to date have examined its effect on clinical outcomes. Therefore, we aimed to evaluate whether sodium bicarbonate infusion would improve these outcomes in critically ill patients. METHODS: We did a multicentre, open-label, randomised controlled, phase 3 trial. Local investigators screened eligible patients from 26 intensive care units (ICUs) in France. We included adult patients (aged ≥18 years) who were admitted within 48 h to the ICU with severe acidaemia (pH ≤7·20, PaCO2 ≤45 mm Hg, and sodium bicarbonate concentration ≤20 mmol/L) and with a total Sequential Organ Failure Assessment score of 4 or more or an arterial lactate concentration of 2 mmol/L or more. We randomly assigned patients (1:1), by stratified randomisation with minimisation via a restricted web platform, to receive either no sodium bicarbonate (control group) or 4·2% of intravenous sodium bicarbonate infusion (bicarbonate group) to maintain the arterial pH above 7·30. Our protocol recommended that the volume of each infusion should be within the range of 125-250 mL in 30 min, with a maximum of 1000 mL within 24 h after inclusion. Randomisation criteria were stratified among three prespecified strata: age, sepsis status, and the Acute Kidney Injury Network (AKIN) score. The primary outcome was a composite of death from any cause by day 28 and the presence of at least one organ failure at day 7. All analyses were done on data from the intention-to-treat population, which included all patients who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02476253. FINDINGS: Between May 5, 2015, and May 7, 2017, we enrolled 389 patients into the intention-to-treat analysis in the overall population (194 in the control group and 195 in the bicarbonate group). The primary outcome occurred in 138 (71%) of 194 patients in the control group and 128 (66%) of 195 in the bicarbonate group (absolute difference estimate -5·5%, 95% CI -15·2 to 4·2; p=0·24). The Kaplan-Meier method estimate of the probability of survival at day 28 between the control group and bicarbonate group was not significant (46% [95% CI 40-54] vs 55% [49-63]; p=0·09. In the prespecified AKIN stratum of patients with a score of 2 or 3, the Kaplan-Meier method estimate of survival by day 28 between the control group and bicarbonate group was significant (37% [95% CI 28-48] vs 54% [45-65]; p=0·0283). [corrected] Metabolic alkalosis, hypernatraemia, and hypocalcaemia were observed more frequently in the bicarbonate group than in the control group, with no life-threatening complications reported. INTERPRETATION: In patients with severe metabolic acidaemia, sodium bicarbonate had no effect on the primary composite outcome. However, sodium bicarbonate decreased the primary composite outcome and day 28 mortality in the a-priori defined stratum of patients with acute kidney injury. FUNDING: French Ministry of Health and the Société Française d'Anesthésie Réanimation.