Targeted temperature control following traumatic brain injury: ESICM/NACCS best practice consensus recommendations.

AIMS AND SCOPE: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management. METHODS: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements. RESULTS: Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0-37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. CONCLUSIONS: Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting.

Development and validation of the tic score for early detection of traumatic coagulopathy upon hospital admission: a cohort study.

BACKGROUND: Critically injured patients need rapid and appropriate hemostatic treatment, which requires prompt identification of trauma-induced coagulopathy (TIC) upon hospital admission. We developed and validated the performance of a clinical score based on prehospital resuscitation parameters and vital signs at hospital admission for early diagnosis of TIC. METHODS: The score was derived from a level-1 trauma center registry (training set). It was then validated on data from two other level-1 trauma centers: first on a trauma registry (retrospective validation set), and then on a prospective cohort (prospective validation set). TIC was defined as a PTratio > 1.2 at hospital admission. Prehospital (vital signs and resuscitation care) and admission data (vital signs and laboratory parameters) were collected. We considered parameters independently associated with TIC in the score (binomial logistic regression). We estimated the score's performance for the prediction of TIC. RESULTS: A total of 3489 patients were included, and among these a TIC was observed in 22% (95% CI 21-24%) of cases. Five criteria were identified and included in the TIC Score: Glasgow coma scale < 9, Shock Index > 0.9, hemoglobin < 11 g.dL-1, prehospital fluid volume > 1000 ml, and prehospital use of norepinephrine (yes/no). The score, ranging from 0 and 9 points, had good performance for the identification of TIC (AUC: 0.82, 95% CI: 0.81-0.84) without differences between the three sets used. A score value < 2 had a negative predictive value of 93% and was selected to rule-out TIC. Conversely, a score value ≥ 6 had a positive predictive value of 92% and was selected to indicate TIC. CONCLUSION: The TIC Score is quick and easy to calculate and can accurately identify patients with TIC upon hospital admission.

Trauma systems in high socioeconomic index countries in 2050.

Considerable political, structural, environmental and epidemiological change will affect high socioeconomic index (SDI) countries over the next 25 years. These changes will impact healthcare provision and consequently trauma systems. This review attempts to anticipate the potential impact on trauma systems and how they could adapt to meet the changing priorities. The first section describes possible epidemiological trajectories. A second section exposes existing governance and funding challenges, how these can be met, and the need to incorporate data and information science into a learning and adaptive trauma system. The last section suggests an international harmonization of trauma education to improve care standards, optimize immediate and long-term patient needs and enhance disaster preparedness and crisis resilience. By demonstrating their capacity for adaptation, trauma systems can play a leading role in the transformation of care systems to tackle future health challenges.

Are coagulation profiles in Andean highlanders with excessive erythrocytosis favouring hypercoagulability?

Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE-). Blood samples were collected from 30 EE+ and 15 EE- in La Rinconada (Peru, 5100-5300 m a.s.l.), with special attention given to the sampling pre-analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet-poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE- and LL (all P < 0.01). At normalized haematocrit, clotting times were normalized in most individuals. Conversely, maximal clot firmness was normalized only in FIBTEM and not in EXTEM/INTEM assays, suggesting abnormal platelet activity. Thrombin generation, levels of plasma clotting factors and inhibitors, and standard coagulation assays were mostly normal in all groups. No highlanders reported a history of venous thromboembolism based on the dedicated survey. Collectively, these results indicate that EE+ do not present a hypercoagulable profile potentially favouring thrombosis.

Prevalence of Drug Use in Ultraendurance Athletes.

PURPOSE: In competitive sport, classic methods of measuring drug prevalence, such as doping controls or questionnaires, are challenging. Here we describe a novel urine sampling method to measure drug use in athletes. We hypothesize that the prevalence of drug use in ultramarathon runners is measured more accurately with our sampling method than randomized-response questionnaires. METHODS: Urine samples and associated demographic data were collected from male participants using blind, automated urinals at the start of ultramarathon races. Various nonprohibited and prohibited substances were subsequently screened. Concomitantly, 2931 male and female runners participating in the same ultramarathons completed an anonymized, randomized-response questionnaire regarding drug use. RESULTS: Among 412 individual urine samples, 205 (49.8%) contained at least one substance, and 16.3% of the samples contained one or more prohibited substances. Substances detected in urine included nonsteroid anti-inflammatory drugs (NSAID) (22.1%), acetaminophen (15.5%), opioids (6.6%), diuretics (4.9%), hypnotics (4.4%), glucocorticoids (2.7%), beta-2 agonists (2.2%), cannabinoids (1.9%), and stimulants (1.2%). None of the samples contained erythropoietin-receptor agonists or suspicious testosterone. Drug use was not associated with the participants' characteristics or ranking. Respondents to the questionnaire reported using acetaminophen (13.6%) and NSAID (12.9%); however, no prohibited substances were declared. CONCLUSIONS: There was a high prevalence of drug use among male ultramarathon runners, in particular, NSAID and painkillers; however, performance-enhancing drugs were marginally used. Blind urine sampling highlighted prohibited drug use not declared in questionnaires, and it is useful to assess the prevalence of drug use and/or doping in competitive athletes.

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.

Prediction of neurocritical care intensity through automated infrared pupillometry and transcranial doppler in blunt traumatic brain injury: the NOPE study.

PURPOSE: This pilot study aimed to determine the capacity of automated infrared pupillometry (AIP) alone and in combination with transcranial doppler (TCD) on admission to rule out need for intense neuroAQ2 critical care (INCC) in severe traumatic brain injury (TBI). METHODS: In this observational pilot study clinicians performed AIP and TCD measurements on admission in blunt TBI patients with a Glasgow Coma Score (GCS) < 9 and/or motor score < 6. A Neurological Pupil index (NPi) < 3, Pulsatility Index (PI) > 1,4 or diastolic blood flow velocity (dV) of < 20 cm/s were used to rule out the need for INCC (exceeding the tier 0 Seattle Consensus Conference). The primary outcome was the negative likelihood ratio (nLR) of NPi < 3 alone or in combination with TCD to detect need for INCC. RESULTS: A total of 69 TBI patients were included from May 2019 to September 2020. Of those, 52/69 (75%) median age was 45 [28-67], median prehospital GCS of 7 [5-8], median Injury Severity Scale of 13.0 [6.5-25.5], median Marshall Score of 4 [3-5], the median Glasgow Outcome Scale at discharge was 3 [1-5]. NPi < 3 was an independent predictor of INCC. NPi demonstrated a nLR of 0,6 (95%CI 0.4-0.9; AUROC, 0.65, 95% CI 0.51-0.79), a combination of NPi and TCD showed a nLR of 0.6 (95% CI 0.4-1.0; AUROC 0.67 95% CI 0.52-0.83) to predict INCC. CONCLUSION: This pilot study suggests a possible useful contribution of NPi to determine the need for INCC in severe blunt TBI patients on admission.

Prediction of therapeutic intensity level from automatic multiclass segmentation of traumatic brain injury lesions on CT-scans.

The prediction of the therapeutic intensity level (TIL) for severe traumatic brain injury (TBI) patients at the early phase of intensive care unit (ICU) remains challenging. Computed tomography images are still manually quantified and then underexploited. In this study, we develop an artificial intelligence-based tool to segment brain lesions on admission CT-scan and predict TIL within the first week in the ICU. A cohort of 29 head injured patients (87 CT-scans; Dataset1) was used to localize (using a structural atlas), segment (manually or automatically with or without transfer learning) 4 or 7 types of lesions and use these metrics to train classifiers, evaluated with AUC on a nested cross-validation, to predict requirements for TIL sum of 11 points or more during the 8 first days in ICU. The validation of the performances of both segmentation and classification tasks was done with Dice and accuracy scores on a sub-dataset of Dataset1 (internal validation) and an external dataset of 12 TBI patients (12 CT-scans; Dataset2). Automatic 4-class segmentation (without transfer learning) was not able to correctly predict the apparition of a day of extreme TIL (AUC = 60 ± 23%). In contrast, manual quantification of volumes of 7 lesions and their spatial location provided a significantly better prediction power (AUC = 89 ± 17%). Transfer learning significantly improved the automatic 4-class segmentation (DICE scores 0.63 vs 0.34) and trained more efficiently a 7-class convolutional neural network (DICE = 0.64). Both validations showed that segmentations based on transfer learning were able to predict extreme TIL with better or equivalent accuracy (83%) as those made with manual segmentations. Our automatic characterization (volume, type and spatial location) of initial brain lesions observed on CT-scan, publicly available on a dedicated computing platform, could predict requirements for high TIL during the first 8 days after severe TBI. Transfer learning strategies may improve the accuracy of CNN-based segmentation models.Trial registrations Radiomic-TBI cohort; NCT04058379, first posted: 15 august 2019; Radioxy-TC cohort; Health Data Hub index F20220207212747, first posted: 7 February 2022.

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.

The Neurological Pupil index for outcome prognostication in people with acute brain injury (ORANGE): a prospective, observational, multicentre cohort study.

BACKGROUND: Improving the prognostication of acute brain injury is a key element of critical care. Standard assessment includes pupillary light reactivity testing with a hand-held light source, but findings are interpreted subjectively; automated pupillometry might be more precise and reproducible. We aimed to assess the association of the Neurological Pupil index (NPi)-a quantitative measure of pupillary reactivity computed by automated pupillometry-with outcomes of patients with severe non-anoxic acute brain injury. METHODS: ORANGE is a multicentre, prospective, observational cohort study at 13 hospitals in eight countries in Europe and North America. Patients admitted to the intensive care unit after traumatic brain injury, aneurysmal subarachnoid haemorrhage, or intracerebral haemorrhage were eligible for the study. Patients underwent automated infrared pupillometry assessment every 4 h during the first 7 days after admission to compute NPi, with values ranging from 0 to 5 (with abnormal NPi being <3). The co-primary outcomes of the study were neurological outcome (assessed with the extended Glasgow Outcome Scale [GOSE]) and mortality at 6 months. We used logistic regression to model the association between NPi and poor neurological outcome (GOSE ≤4) at 6 months and Cox regression to model the relation of NPi with 6-month mortality. This study is registered with ClinicalTrials.gov, NCT04490005. FINDINGS: Between Nov 1, 2020, and May 3, 2022, 514 patients (224 with traumatic brain injury, 139 with aneurysmal subarachnoid haemorrhage, and 151 with intracerebral haemorrhage) were enrolled. The median age of patients was 61 years (IQR 46-71), and the median Glasgow Coma Scale score on admission was 8 (5-11). 40 071 NPi measurements were taken (median 40 per patient [20-50]). The 6-month outcome was assessed in 497 (97%) patients, of whom 160 (32%) patients died, and 241 (47%) patients had at least one recording of abnormal NPi, which was associated with poor neurological outcome (for each 10% increase in the frequency of abnormal NPi, adjusted odds ratio 1·42 [95% CI 1·27-1·64]; p<0·0001) and in-hospital mortality (adjusted hazard ratio 5·58 [95% CI 3·92-7·95]; p<0·0001). INTERPRETATION: NPi has clinically and statistically significant prognostic value for neurological outcome and mortality after acute brain injury. Simple, automatic, repeat automated pupillometry assessment could improve the continuous monitoring of disease progression and the dynamics of outcome prediction at the bedside. FUNDING: NeurOptics.

Ferric derisomaltose and tranexamic acid, combined or alone, for reducing blood transfusion in patients with hip fracture (the HiFIT trial): a multicentre, 2 × 2 factorial, randomised, double-blind, controlled trial.

BACKGROUND: Anaemia and blood transfusion are associated with poor outcomes after hip fracture. We evaluated the efficacy of intravenous iron and tranexamic acid in reducing blood transfusions after hip fracture surgery. METHODS: In this double-blind, randomised, 2 × 2 factorial trial, we recruited adults hospitalised for hip fractures in 12 medical centres in France who had preoperative haemoglobin concentrations between 9·5 and 13·0 g/dL. We randomly allocated participants (1:1:1:1), via a secure web-based service, to ferric derisomaltose (20 mg/kg intravenously) and tranexamic acid (1 g bolus followed by 1 g over 8 h intravenously at inclusion and 3 g topically during surgery), iron plus placebo (normal saline), tranexamic acid plus placebo, or double placebo. Unmasked nurses administered study drugs; participants and other clinical and research staff remained masked to treatment allocation. The primary outcome was the percentage of patients transfused during hospitalisation (or by day 30). The primary analysis included all randomised patients. This study is registered on ClinicalTrials.gov (NCT02972294) and is closed to new participants. FINDINGS: Of 413 patients (51-104 years old, median [IQR] 86 [78-91], 312 [76%] women, 101 [24%] men), 104 received iron plus tranexamic acid, 103 iron plus placebo, 103 tranexamic acid plus placebo, and 103 double placebo between March 31, 2017 and June 18, 2021 (study stopped early for efficacy after the planned interim analysis done on the first 390 patients included on May 25, 2021). Data for the primary outcome were available for all participants. Among patients on double placebo, 31 (30%) were transfused versus 16 (15%) on both drugs (relative risk 0·51 [98·3% CI 0·27-0·97]; p=0·012). 27 (26%) participants on iron (0·81 [0·50-1·29]; p=0·28) and 28 (27%) on tranexamic acid (0·85 [0·54-1·33]; p=0·39) were transfused. 487 adverse events were reported with similar event rates among the groups; among prespecified safety endpoints, severe postoperative anaemia (haemoglobin <8 g/dL) was more frequent in the double placebo group. Main common adverse event were sepsis, pneumonia, and urinary infection, with similar rates among all groups. INTERPRETATION: In patients hospitalised for hip fracture surgery with a haemoglobin concentration 9·5-13·0 g/dL, preoperative infusion of ferric derisomaltose plus tranexamic acid reduced the risk of blood transfusion by 50%. Our results suggest that combining treatments from two different pillars improves patient blood-management programmes. Either treatment alone did not reduce transfusion rates, but we might not have had the power to detect it. FUNDING: French Ministry of Health, HiFIT trial.

Management of patients suffering from mild traumatic brain injury 2023.

OBJECTIVE: To develop a multidisciplinary French reference that addresses initial pre- and in-hospital management of a mild traumatic brain injury patient. DESIGN: A panel of 22 experts was formed on request from the French Society of Emergency Medicine (SFMU) and the French Society of Anaesthesiology and Critical Care Medicine (SFAR). A policy of declaration and monitoring of links of interest was applied and respected throughout the process of producing the guidelines. Similarly, no funding was received from any company marketing a health product (drug or medical device). The expert panel had to respect and follow the Grade® (Grading of Recommendations Assessment, Development and Evaluation) methodology to evaluate the quality of the evidence on which the recommendations were based. Given the impossibility of obtaining a high level of evidence for most of the recommendations, it was decided to adopt a "Recommendations for Professional Practice" (RPP) format, rather than a Formalized Expert Recommendation (FER) format, and to formulate the recommendations using the terminology of the SFMU and SFAR Guidelines. METHODS: Three fields were defined: 1) pre-hospital assessment, 2) emergency room management, and 3) emergency room discharge modalities. The group assessed 11 questions related to mild traumatic brain injury. Each question was formulated using a PICO (Patients Intervention Comparison Outcome) format. RESULTS: The experts' synthesis work and the application of the GRADE® method resulted in the formulation of 14 recommendations. After two rounds of rating, strong agreement was obtained for all recommendations. For one question, no recommendation could be made. CONCLUSION: There was strong agreement among the experts on important, transdisciplinary recommendations, the purpose of which is to improve management practices for patients with mild head injury.