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.

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.

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.

Thoracic Epidural Analgesia and Mortality in Acute Pancreatitis: A Multicenter Propensity Analysis.

OBJECTIVE: Recent preclinical and clinical data suggest that thoracic epidural analgesia, a technique primarily aimed at decreasing pain, might exert anti-inflammatory effects, enhance splanchnic and pancreatic blood flow during acute pancreatitis; however, the influence of epidural analgesia on mortality remains under investigated in this setting. This study was therefore designed to assess the impact of epidural analgesia on mortality in ICU patients with acute pancreatitis. DESIGN: Multicenter retrospective, observational, cohort study. SETTING: Seventeen French and Belgian ICUs. PATIENTS: All patients admitted to with acute pancreatitis between June 2009 and March 2014. INTERVENTIONS: The primary exposure was thoracic epidural analgesia versus standard care without epidural analgesia. The primary outcome was 30-day mortality. Propensity analyses were used to control for bias in treatment assignment and prognostic imbalances. MEASUREMENTS AND MAIN RESULTS: One thousand three ICU patients with acute pancreatitis were enrolled, of whom 212 died within 30 days. Epidural analgesia was used in 46 patients and was associated with reduced mortality in unadjusted analyses (4% vs. 22%; p = 0.003). After adjustment for baseline variables associated with mortality, epidural analgesia was still an independent predictor of 30-day mortality (adjusted odds ratio, 0.10; [95% CI, 0.02-0.49]; p = 0.004). Using propensity score analysis, the risk of all-cause 30-day mortality in patients with acute pancreatitis receiving epidural analgesia was significantly lower than that in matched patients who did not receive epidural analgesia (2% vs. 17%; p = 0.01). CONCLUSIONS: Among critically ill patients with acute pancreatitis, mortality at 30 days was lower in patients who received epidural analgesia than in comparable patients who did not. These findings support ongoing research on the use of epidural analgesia as a therapeutic intervention in acute pancreatitis.

Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery: A Randomized Clinical Trial.

IMPORTANCE: It has not been established whether noninvasive ventilation (NIV) reduces the need for invasive mechanical ventilation in patients who develop hypoxemic acute respiratory failure after abdominal surgery. OBJECTIVE: To evaluate whether noninvasive ventilation improves outcomes among patients developing hypoxemic acute respiratory failure after abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, parallel-group clinical trial conducted between May 2013 and September 2014 in 20 French intensive care units among 293 patients who had undergone abdominal surgery and developed hypoxemic respiratory failure (partial oxygen pressure <60 mm Hg or oxygen saturation [SpO2] ≤90% when breathing room air or <80 mm Hg when breathing 15 L/min of oxygen, plus either [1] a respiratory rate above 30/min or [2] clinical signs suggestive of intense respiratory muscle work and/or labored breathing) if it occurred within 7 days after surgical procedure. INTERVENTIONS: Patients were randomly assigned to receive standard oxygen therapy (up to 15 L/min to maintain SpO2 of 94% or higher) (n = 145) or NIV delivered via facial mask (inspiratory pressure support level, 5-15 cm H2O; positive end-expiratory pressure, 5-10 cm H2O; fraction of inspired oxygen titrated to maintain SpO2 ≥94%) (n = 148). MAIN OUTCOMES AND MEASURES: The primary outcome was tracheal reintubation for any cause within 7 days of randomization. Secondary outcomes were gas exchange, invasive ventilation-free days at day 30, health care-associated infections, and 90-day mortality. RESULTS: Among the 293 patients (mean age, 63.4 [SD, 13.8] years; n=224 men) included in the intention-to-treat analysis, reintubation occurred in 49 of 148 (33.1%) in the NIV group and in 66 of 145 (45.5%) in the standard oxygen therapy group within+ 7 days after randomization (absolute difference, -12.4%; 95% CI, -23.5% to -1.3%; P = .03). Noninvasive ventilation was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (25.4 vs 23.2 days; absolute difference, -2.2 days; 95% CI, -0.1 to 4.6 days; P = .04), while fewer patients developed health care-associated infections (43/137 [31.4%] vs 63/128 [49.2%]; absolute difference, -17.8%; 95% CI, -30.2% to -5.4%; P = .003). At 90 days, 22 of 148 patients (14.9%) in the NIV group and 31 of 144 (21.5%) in the standard oxygen therapy group had died (absolute difference, -6.5%; 95% CI, -16.0% to 3.0%; P = .15). There were no significant differences in gas exchange. CONCLUSIONS AND RELEVANCE: Among patients with hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of tracheal reintubation within 7 days. These findings support use of NIV in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01971892.

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.

Prognosis of major trauma in patients older than 85 years admitted to the ICU, a registry-based study.

BACKGROUND: The aging population in France and Western Europe is on the rise, particularly among individuals aged 65 years and older. Although older adults are susceptible to traumatic injuries, they constitute a minority of trauma center admissions especially those aged 85 and above. The aim of our study was to investigate the prognostic factors for mortality among the older old population (aged 85 years and above) managed in ICU of Traumabase group trauma centers. METHODS: This retrospective observational cohort study, conducted from 2013 to 2022, analyzed all severely injured older patients (aged ≥ 85 years) managed in 14 ICU trauma centers enrolled in the Traumabase registry. The study examined sociodemographic, clinical, and outcome variables. Frailty was assessed using the Clinical Frailty Scale. RESULTS: Among the 365 older trauma patients, 190 (52.1%) were classified as non-frail (CFS 1-3), 80 (21.9%) as pre-frail (CFS 4,5), and 95 (26%) as frail (CFS 6-9). Falls were the most common mechanism of injury. High mortality rates were observed, with 43.5% ICU mortality and 45.5% mortality at day 30. Factors most associated with ICU mortality included traumatic brain injury (CGS < 13), pre-hospital micromethod hemoglobin < 13 and severity of injury (ISS > 16). CONCLUSION: Factors such as traumatic brain injury and severe hemorrhage (micromethod hemoglobin < 13) and ISS > 16 are associated with ICU mortality in in patients older than 85 years trauma patient. Early geriatric intervention is crucial for optimizing outcomes in this vulnerable population.

Noninvasive ventilation on reintubation in patients with obesity and hypoxemic respiratory failure following abdominal surgery: a post hoc analysis of a randomized clinical trial.

PURPOSE: Although noninvasive ventilation (NIV) may reduce reintubation in patients with acute hypoxemic respiratory failure following abdominal surgery, this strategy has not been specifically assessed in patients with obesity. METHODS: We conducted a post hoc analysis of a multicenter randomized controlled trial comparing NIV delivered via facial mask to standard oxygen therapy among patients with obesity and acute hypoxemic respiratory failure within 7 days after abdominal surgery. The primary outcome was reintubation within 7 days. Secondary outcomes were invasive ventilation-free days at day 30, intensive care unit (ICU)-acquired pneumonia and 30-day survival. RESULTS: Among 293 patients with hypoxemic respiratory failure following abdominal surgery, 76 (26%) patients had obesity and were included in the intention-to-treat analysis. Reintubation rate was significantly lower with NIV (13/42, 31%) than with standard oxygen therapy (19/34, 56%) within 7 days (absolute difference: - 25%, 95% confidence interval (CI) - 49 to - 1%, p = 0.03). NIV was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (27.1 ± 8.6 vs 22.7 ± 11.1 days; p = 0.02), while fewer patients developed ICU-acquired pneumonia (1/42, 2% vs 6/34, 18%; p = 0.04). The 30-day survival was 98% in the NIV group (41/42) versus 85% in the standard oxygen therapy (p = 0.08). In patients with body mass index (BMI) < 30 kg/m2, no significant difference was observed between NIV (36/105, 34%) and standard oxygen therapy (47/109, 43%, p = 0.03). An interaction test showed no statistically significant difference between the two subsets (BMI ≥ 30 kg/m2 and BMI < 30 kg/m2). CONCLUSIONS: Among patients with obesity and hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of reintubation within 7 days, contrary to patients without obesity. However, no interaction was found according to the presence of obesity or not, suggesting either a lack of power to conclude in the non-obese subgroup despite existing differences, or that the statistical difference found in the overall sample was driven by a large effect in the obese subsets.

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.

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.

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).

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.

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.

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.

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.

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.

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.

Ketamine for perioperative pain management in children: a meta-analysis of published studies.

INTRODUCTION: Balanced analgesia, using both opioid and nonopioids agents, has become the standard care for postoperative pain management. Ketamine, a compound with analgesic and antihyperalgesic properties, has been shown to decrease postoperative pain and opioid requirements in adults. The goal of the present meta-analysis was to investigate postoperative analgesic properties of ketamine in pediatric patients. MATERIAL AND METHODS: A comprehensive literature search was conducted to identify clinical trials that used ketamine as a perioperative analgesic compound in children and infants. Outcomes measured were postoperative analgesic consumption, pain intensity and duration of sensory block (when ketamine was used by caudal route) during the postoperative care unit (PACU) stay and the early postoperative period (6-24 h after leaving the operative room). The data from each trial were combined to calculate the pooled odds ratios or standard mean differences and their 95% confidence intervals. RESULTS: Thirty-five randomized, blinded controlled studies were retrieved from the literature. Systemic ketamine was effective in decreasing PACU pain intensity and analgesic requirement but failed to influence early (6-24 h) pain intensity and analgesic requirement. Ketamine administered locally during tonsillectomy, decreased PACU and early (6-24 h) pain intensity and PACU analgesic requirements. Used as an adjuvant for caudal analgesia, ketamine increased the duration of sensory block and PACU analgesic requirement without impacting PACU pain intensity. Ketamine failed to exhibit a postoperative opioid-sparing effect. CONCLUSIONS: This meta-analysis found that administration of ketamine was associated with decreased PACU postoperative pain intensity and nonopioid analgesic requirement. However, ketamine failed to exhibit a postoperative opioid-sparing effect.