Cerebral net uptake of lactate contributes to neurological injury after experimental cardiac arrest in rabbits.

During focal ischemia, neurons can use lactate as an alternative source of energy through its oxidation into pyruvate by the lactate dehydrogenase (LDH). After cardiac arrest, the neurological consequences of this phenomenon are unknown. Experimental study. Experimental laboratory. Male New-Zealand rabbits. Animals were surgically instrumented and randomly divided into five groups receiving short infusion duration of either lactate or pyruvate or a pre-cardiac arrest infusion of oxamate (an inhibitor of the lactate dehydrogenase) or injection of fluorocitrate (an inhibitor of astrocytic tricarboxylic acid), or Saline (lactate, pyruvate, Oxa, FC and Control groups, respectively). After randomization, animals were submitted to 10 min of ventricular fibrillation and subsequent resuscitation. All animals were then either followed during 4 h, for the evaluation of the cerebral net uptake and concentrations of metabolites by microdialysis (n = 6 in each experimental group, n = 12 in control group), or during 48 h for the evaluation of their neurological outcome (n = 7 in each groups and n = 14 in control group). Cardiac arrest was associated with a dramatic increase in cerebral net uptake of lactate during 120 min after resuscitation, which was increased by lactate or pyruvate administration. This was associated with an increase in the mean neurological dysfunction score (66.7 ± 4.7, 79.0 ± 4.5 vs 57.7 ± 1.5 in Lactate, Pyruvate and Control group respectively) at 48 h after cardiac arrest. Oxamate and FC administration were associated with a lower lactate cerebral uptake after cardiac arrest and with an improvement of the neurological recovery (28.85 ± 9.4, 23.86 ± 6.2 vs 57.7 ± 1.5 in Oxa, FC and Control group respectively). After cardiac arrest, immediate isotonic lactate or pyruvate administration is deleterious. Pre-cardiac arrest LDH inhibition was potently neuroprotective in this setting.

Early rehabilitation after spinal cord injury: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to identify the timings and types of early rehabilitation after spinal cord injury (SCI) that are documented in the literature, as well as identify possible research gaps in this field. INTRODUCTION: Preclinical and clinical studies support the idea that early rehabilitation may be beneficial for patients with acute SCI. However, the timings and types of rehabilitation that should and could be used in the acute stage are still unclear. The first step towards such knowledge is to extensively review what is documented in the literature. INCLUSION CRITERIA: This review will consider all papers focusing on early rehabilitation after SCI in adult humans or animals (<3 months' post-SCI for humans and other primates and <3 weeks' post-SCI for other animals). Interventions in the included papers must aim at sensorimotor or functional improvement and take place in a hospital or a rehabilitation center if they target human subjects. This review will include published and unpublished experimental and observational studies, research protocols, conference abstracts, systematic reviews, and guidelines. METHODS: MEDLINE (PubMed), Scopus, Embase, PEDro, Web of Science Core Collection, CINAHL (EBSCOhost), Cochrane Database of Systematic Reviews, Cochrane CENTRAL, PROSPERO, ClinicalTrials.gov, and gray literature sources will be searched for eligible articles. No language or date limits will be applied. Two independent reviewers will perform study selection and data extraction, and the results will be presented according to the SCI type and severity. REVIEW REGISTRATION: Open Science Framework https://osf.io/q45er.

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.

Femoral blood gas analysis, another tool to assess hemorrhage severity following trauma: an exploratory prospective study.

BACKGROUND: Veno-arterial carbon dioxide tension difference (ΔPCO2) and mixed venous oxygen saturation (SvO2) have been shown to be markers of the adequacy between cardiac output and metabolic needs in critical care patients. However, they have hardly been assessed in trauma patients. We hypothesized that femoral ΔPCO2 (ΔPCO2 fem) and SvO2 (SvO2 fem) could predict the need for red blood cell (RBC) transfusion following severe trauma. METHODS: We conducted a prospective and observational study in a French level I trauma center. Patients admitted to the trauma room following severe trauma with an Injury Severity Score (ISS) > 15, who had arterial and venous femoral catheters inserted were included. ΔPCO2 fem, SvO2 fem and arterial blood lactate were measured over the first 24 h of admission. Their abilities to predict the transfusion of at least one pack of RBC (pRBCH6) or hemostatic procedure during the first six hours of admission were assessed using receiver operating characteristics curve. RESULTS: 59 trauma patients were included in the study. Median ISS was 26 (22-32). 28 patients (47%) received at least one pRBCH6 and 21 patients (35,6%) had a hemostatic procedure performed during the first six hours of admission. At admission, ΔPCO2 fem was 9.1 ± 6.0 mmHg, SvO2 fem 61.5 ± 21.6% and blood lactate was 2.7 ± 1.9 mmol/l. ΔPCO2 fem was significantly higher (11.6 ± 7.1 mmHg vs. 6.8 ± 3.7 mmHg, P = 0.003) and SvO2 fem was significantly lower (50 ± 23 mmHg vs. 71.8 ± 14.1 mmHg, P < 0.001) in patients who were transfused than in those who were not transfused. Best thresholds to predict pRBCH6 were 8.1 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Best thresholds to predict the need for a hemostatic procedure were 5.9 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Blood lactate was not predictive of pRBCH6 or the need for a hemostatic procedure. CONCLUSION: In severe trauma patients, ΔPCO2 fem and SvO2 fem at admission were predictive for the need of RBC transfusion and hemostatic procedures during the first six hours of management while admission lactate was not. ΔPCO2 fem and SvO2 fem appear thus to be more sensitive to blood loss than blood lactate in trauma patients, which might be of importance to early assess the adequation of tissue blood flow with metabolic needs.

Comprehensive analysis of coagulation factor delivery strategies in a cohort of trauma patients.

PURPOSE: The 5th edition of The European recommendations for the management of major bleeding and coagulopathy following trauma leaves room for various coagulation factor administration strategies. The present study examines these strategies reporting prevalence and timing of administration, quantity dispensed, and transfusion ratios in French trauma centers and their compliance with recommendations alongside associated mortality data. METHODS: All adult patients, admitted directly to participating centers between 2011 and 2019, were extracted from a trauma registry. Two subpopulations were studied: severe hemorrhage (SH) and massive transfusion (MT) groups. RESULTS: A total of 19,396 patients were included, among whom 8.4% (1630) experienced SH and 3% (579) received MT. Within the first 24 hours, 10% received fresh frozen plasma (FFP), rising to 93% and 99% in the subgroups of patients experiencing SH and MT respectively. Only, 8% received fibrinogen concentrate (FC), increasing to 75% and 92% in subgroups SH and MT respectively. Co-administration of FFP and FC became the dominant strategy with 68% of patients at 6 h and 72% at 24 h in SH subgroup. In unadjusted data, mortality was systematically lower in groups that complied with recommendations, a lower mortality than expected was mostly observed in contrast to non-compliant subgroups. The per-patient compliance to studied recommendations was 21% and 22% in SH and MT subgroups. CONCLUSION: The main hemostatic strategy for major bleeding combined the administration of both FFP and FC, favoring an early additional supply of fibrinogen. Compliance with the recommendations was low in SH and MT subgroups.

Comparison Between Transcranial Color-Coded Duplex Doppler and Contrast Enhanced Transcranial Color-Coded Duplex Doppler After Subarachnoid Aneurysmal Hemorrhage.

BACKGROUND: Transcranial color-coded duplex Doppler (TCCD) is commonly used to detect and monitor vasospasm in subarachnoid aneurysmal hemorrhage (aSAH). However, contrast enhanced TCCD (CE-TCCD) may be more effective. The objective of this study was to compare the accuracy of TCCD and CE-TCCD in the detection of vasospasm. METHODS: This study was a prospective comparison of TCCD and CE-TCCD for the detection of vasospasm, using computed tomography angiography (CT Angio) as a reference examination. The setting was the Department of Anesthesiology and Intensive Care at the Bicêtre University Hospital in Le Kremlin Bicêtre, France. TCCD and CE-TCCD were performed in 47 patients admitted to the intensive care unit (ICU) following aSAH over a 7-month period. TCCD and CE-TCCD were performed at ICU admission and between days 7 and 10. We aimed to visualize the seven intracranial arteries of the circle of Willis. Vasospasm diagnosis was assessed by CT Angio  and graded as moderate when the percentage change in arterial diameter since admission was between 25 and 50% or as severe when the percentage change was greater than 50%. RESULTS: On ICU admission, TCCD allowed visualization of all intracranial arteries in 16 (34%) of 47 patients, whereas CE-TCCD allowed visualization of all vessels in 37 (79%) of 47 patients (p < 0.001). These results were consistent between days 7 and 10. The proportions of middle cerebral arteries (MCAs), anterior cerebral arteries (ACAs) and posterior cerebral arteries (PCAs) visualized were greater with CE-TCCD. There was no difference in the visualization of basilar arteries (BAs). We performed vasospasm analysis on 67 of 94 MCAs in 47 patients. Area under the curve (AUC) of mean flow velocity to detect MCA vasospasm (moderate and severe) was 0.86 (0.58-1.00) for TCCD and 0.90 (0.77-1.00) for CE-TCCD. AUC of mean velocity to detect severe MCA vasospasm was 0.86 (0.58-1.00) for TCCD and 0.90 (0.77-1.00) for CE-TCCD, without any significant difference between the two techniques. For other arteries, the accuracy of TCCD and CE-TCCD to diagnose vasospasm was poor. CONCLUSIONS: CE-TCCD allows better visualization of intracranial arteries in patients with aSAH. The accuracy of CE-TCCD to screen severe MCA vasospasm is similar to that of TCCD. CE-TCCD is an alternative tool for monitoring patients with aSAH without a temporal bone window for an ultrasound.

A One-Day Prospective National Observational Study on Sedation-Analgesia of Patients with Brain Injury in French Intensive Care Units: The SEDA-BIP-ICU (Sedation-Analgesia in Brain Injury Patient in ICU) Study.

BACKGROUND: Sedation/analgesia is a daily challenge faced by intensivists managing patients with brain injury (BI) in intensive care units (ICUs). The optimization of sedation in patients with BI presents particular challenges. A choice must be made between the potential benefit of a rapid clinical evaluation and the potential exacerbation of intracranial hypertension in patients with impaired cerebral compliance. In the ICU, a pragmatic approach to the use of sedation/analgesia, including the optimal titration, management of multiple drugs, and use of any type of brain monitor, is needed. Our research question was as follows: the aim of the study is to identify what is the current daily practice regarding sedation/analgesia in the management of patients with BI in the ICU in France? METHODS: This study was composed of two parts. The first part was a descriptive survey of sedation practices and characteristics in 30 French ICUs and 27 academic hospitals specializing in care for patients with BI. This first step validates ICU participation in data collection regarding sedation-analgesia practices. The second part was a 1-day prospective cross-sectional snapshot of all characteristics and prescriptions of patients with BI. RESULTS: On the study day, among the 246 patients with BI, 106 (43%) had a brain monitoring device and 74 patients (30%) were sedated. Thirty-nine of the sedated patients (53%) suffered from intracranial hypertension, 14 patients (19%) suffered from agitation and delirium, and 7 patients (9%) were sedated because of respiratory failure. Fourteen patients (19%) no longer had a formal indication for sedation. In 60% of the sedated patients, the sedatives were titrated by nurses based on sedation scales. The Richmond Agitation Sedation Scale was used in 80% of the patients, and the Behavioral Pain Scale was used in 92%. The common sedatives and opioids used were midazolam (58.1%), propofol (40.5%), and sufentanil (67.5%). The cerebral monitoring devices available in the participating ICUs were transcranial Doppler ultrasound (100%), intracranial and intraventricular pressure monitoring (93.3%), and brain tissue oxygenation (60%). Cerebral monitoring by one or more monitoring devices was performed in 62% of the sedated patients. This proportion increased to 74% in the subgroup of patients with intracranial hypertension, with multimodal cerebral monitoring in 43.6%. The doses of midazolam and sufentanil were lower in sedated patients managed based on a sedation/analgesia scale. CONCLUSIONS: Midazolam and sufentanil are frequently used, often in combination, in French ICUs instead of alternative drugs. In our study, cerebral monitoring was performed in more than 60% of the sedated patients, although that proportion is still insufficient. Future efforts should stress the use of multiple monitoring modes and adherence to the indications for sedation to improve care of patients with BI. Our study suggests that the use of sedation and analgesia scales by nurses involved in the management of patients with BI could decrease the dosages of midazolam and sufentanil administered. Updated guidelines are needed for the management of sedation/analgesia in patients with BI.

Admission serum myoglobin and the development of acute kidney injury after major trauma.

BACKGROUND: Myoglobin and creatine kinase (CK) are both established markers of muscle injury but their hospital admission values have never been compared to predict post-traumatic acute kidney injury (AKI). METHODS: An observational registry study of consecutive trauma patients admitted to a major regional trauma centre. The primary outcome was stage 1 or more AKI in the first 7 days after trauma. We assessed the association of hospital admission myoglobin or CK with development of AKI both alone and when added to two existing risk prediction models for post traumatic AKI. RESULTS: Of the 857 trauma patients (median age 36 [25-52], 96% blunt trauma, median ISS of 20 [12-47]) included, 102 (12%) developed AKI. Admission myoglobin performed better than CK to predict AKI any stage with an AUC-ROC of 0.74 (95% CI 0.68-0.79) and 0.63 (95% CI 0.57-0.69), respectively (p < 0.001). Admission myoglobin also performed better than CK to predict AKI stage 2 or 3 [AUC-ROC of 0.79 (95% CI 0.74-0.84) and 0.74 (95% CI 0.69-0.79), respectively (p < 0.001)] with a best cutoff value of 1217 µg/L (sensitivity 74%, specificity 77%). Admission myoglobin added predictive value to two established models of AKI prediction and showed significant ability to reclassify subjects regarding AKI status, while admission CK did not. Decision curve analysis also revealed that myoglobin added net benefit to established predictive models. Admission myoglobin was better than CK at predicting development of significant rhabdomyolysis. CONCLUSIONS: Admission myoglobin better predicts the development of AKI and severe rhabdomyolysis after major trauma. Admission myoglobin should be added in established predictive models of post-traumatic AKI to early identify high-risk patients.

Comparison of Pressure Reactivity Index and Mean Velocity Index to Evaluate Cerebrovascular Reactivity During Induced Arterial Blood Pressure Variations in Severe Brain Injury.

OBJECTIVES: To compare the assessment of cerebral autoregulation by cerebrovascular reactivity indices based on intracranial pressure (Pressure Reactivity Index, PRx) and on transcranial Doppler (Mean Velocity Index, Mx) during controlled variations of arterial blood pressure in severe brain injury. Primary outcome was the agreement between both cerebrovascular reactivity indices measured by the Bland-and-Altman method. Secondary outcomes were the association of cerebrovascular reactivity indices with arterial blood pressure variation, and the comparison of optimal cerebral perfusion pressures determined by both indices. METHODS: All consecutive comatose (Glasgow Coma Scale < 8) patients from the surgical intensive care unit of Bicetre Hospital who had an acute brain injury on computerized tomography and needed vasopressor support were prospectively included. Step-by-step arterial pressure variations using vasopressors were performed to compare PRx and Mx and to calculate optimal cerebral perfusion pressure (CPPopt). MEASUREMENTS AND MAIN RESULTS: 15 patients were included. Mean difference between both indices measured by Bland-and-Altman plot was - 0.07 (IC 95% [- 1.02 to 0.87]). Mx was significantly associated with arterial pressure variation (one-way ANOVA test, p = 0.007), whereas PRx was not (p = 0.44). Optimal cerebral perfusion pressure calculated with PRx and Mx was respectively 11 and 15mmHg higher than the mean perfusion pressure prescribed. Optimal cerebral perfusion pressure calculation was possible in all cases. CONCLUSIONS: Cerebral vasoreactivity indices calculated with intracranial pressure or transcranial Doppler show only moderate agreement. Both indices nonetheless suggest substantially higher optimal cerebral perfusion pressure than those currently provided by international guidelines.

[Communication with patients' relatives in intensive care]. / Dialogue avec l'entourage des patients en réanimation.

The place of relatives of our patients is the deepest change in intensive care units in 20 years. Working on collegial discussions and recognizing the voices of patients and their loved ones in care projects have become a mandatory part of our daily work. This change is also related to the attention and time given to ethical decisions in the daily life of resuscitation. We need to recognize the need for trust in the health care system as well as with medical providers so that the therapeutic relationship can be achieved peacefully. We must therefore organize ourselves to improve reception of the families, place of the team members, regular formal meetings of information with relatives or the representative of our patient. Post-traumatic stress is not only a prerogative of our patients, it is also described in accompanying people. If trust is acquired few conflicts are challenging, only interfamily conflicts force medical team to defend its opinion. The realization that a specific care project after intensive care is more likely to succeed when it is done with the support of the entourage makes possible to understand the importance to take care to the stress of the relatives.

Comparison of strategies for monitoring and treating patients at the early phase of severe traumatic brain injury: the multicentre randomised controlled OXY-TC trial study protocol.

INTRODUCTION: Intracranial hypertension is considered as an independent risk factor of mortality and neurological disabilities after severe traumatic brain injury (TBI). However, clinical studies have demonstrated that episodes of brain ischaemia/hypoxia are common despite normalisation of intracranial pressure (ICP). This study assesses the impact on neurological outcome of guiding therapeutic strategies based on the monitoring of both brain tissue oxygenation pressure (PbtO2) and ICP during the first 5 days following severe TBI. METHODS AND ANALYSIS: Multicentre, open-labelled, randomised controlled superiority trial with two parallel groups in 300 patients with severe TBI. Intracerebral monitoring must be in place within the first 16 hours post-trauma. Patients are randomly assigned to the ICP group or to the ICP + PbtO2 group. The ICP group is managed according to the international guidelines to maintain ICP≤20 mm Hg. The ICP + PbtO2 group is managed to maintain PbtO2 ≥20 mm Hg in addition to the conventional optimisation of ICP. The primary outcome measure is the neurological status at 6 months as assessed using the extended Glasgow Outcome Scale. Secondary outcome measures include quality-of-life assessment, mortality rate, therapeutic intensity and incidence of critical events during the first 5 days. Analysis will be performed according to the intention-to-treat principle and full statistical analysis plan developed prior to database freeze. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of Sud-Est V (14-CHUG-48) and from the National Agency for Medicines and Health Products Safety (Agence Nationale de Sécurité du Médicament et des produits de santé) (141 435B-31). Results will be presented at scientific meetings and published in peer-reviewed publications.The study was registered with ClinTrials NCT02754063 on 28 April 2016 (pre-results).

Development and validation of a pre-hospital "Red Flag" alert for activation of intra-hospital haemorrhage control response in blunt trauma.

BACKGROUND: Haemorrhagic shock is the leading cause of early preventable death in severe trauma. Delayed treatment is a recognized prognostic factor that can be prevented by efficient organization of care. This study aimed to develop and validate Red Flag, a binary alert identifying blunt trauma patients with high risk of severe haemorrhage (SH), to be used by the pre-hospital trauma team in order to trigger an adequate intra-hospital standardized haemorrhage control response: massive transfusion protocol and/or immediate haemostatic procedures. METHODS: A multicentre retrospective study of prospectively collected data from a trauma registry (Traumabase®) was performed. SH was defined as: packed red blood cell (RBC) transfusion in the trauma room, or transfusion ≥ 4 RBC in the first 6 h, or lactate ≥ 5 mmol/L, or immediate haemostatic surgery, or interventional radiology and/or death of haemorrhagic shock. Pre-hospital characteristics were selected using a multiple logistic regression model in a derivation cohort to develop a Red Flag binary alert whose performances were confirmed in a validation cohort. RESULTS: Among the 3675 patients of the derivation cohort, 672 (18%) had SH. The final prediction model included five pre-hospital variables: Shock Index ≥ 1, mean arterial blood pressure ≤ 70 mmHg, point of care haemoglobin ≤ 13 g/dl, unstable pelvis and pre-hospital intubation. The Red Flag alert was triggered by the presence of any combination of at least two criteria. Its predictive performances were sensitivity 75% (72-79%), specificity 79% (77-80%) and area under the receiver operating characteristic curve 0.83 (0.81-0.84) in the derivation cohort, and were not significantly different in the independent validation cohort of 2999 patients. CONCLUSION: The Red Flag alert developed and validated in this study has high performance to accurately predict or exclude SH.

Vitamin K antagonists and emergencies.

The recent emergence of 'non-VKA' oral anticoagulants may have led to some forgetting that vitamin K antagonists (VKA) are by far the most widely prescribed oral anticoagulants worldwide. Consequently, we decided to summarize the information available on them. This paper presents the problems facing emergency physicians confronted with patients on VKAs in 10 points, from pharmacological data to emergency management. Vitamin K antagonists remain preferable in many situations including in the elderly, in patients with extreme body weights, severe chronic kidney or liver disease or valvular heart disease, and in patients taking VKAs with well-controlled international normalized ratios (INRs). Given the way VKAs work, a stable anticoagulant state can only be achieved at the earliest 5 days after starting therapy. The induction phase of VKA treatment is associated with the highest risk of bleeding; validated algorithms based on INR values have to be followed. VKA asymptomatic overdoses and 'non-severe' hemorrhage are managed by omitting a dose or stopping treatment plus administering vitamin K depending on the INR. Major bleeding is managed using a VKA reversal strategy. A prothrombin complex concentrate infusion plus vitamin K is preferred to rapidly achieve an INR of up to 1.5 and maintain a normal coagulation profile. The INR must be measured 30 min after the infusion. Before an invasive procedure, if an INR of less than 1.5 (<1.3 in neurosurgery) is required, it can be achieved by combining prothrombin complex concentrate and vitamin K. A well-codified strategy is essential for managing patients requiring emergency invasive procedures or presenting bleeding complications.

Targeted temperature management in the ICU: Guidelines from a French expert panel.

Over the recent period, the use of induced hypothermia has gained an increasing interest for critically ill patients, in particular in brain-injured patients. The term "targeted temperature management" (TTM) has now emerged as the most appropriate when referring to interventions used to reach and maintain a specific level temperature for each individual. TTM may be used to prevent fever, to maintain normothermia, or to lower core temperature. This treatment is widely used in intensive care units, mostly as a primary neuroprotective method. Indications are, however, associated with variable levels of evidence based on inhomogeneous or even contradictory literature. Our aim was to conduct a systematic analysis of the published data in order to provide guidelines. We present herein recommendations for the use of TTM in adult and paediatric critically ill patients developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. These guidelines were conducted by a group of experts from the French Intensive Care Society (Société de réanimation de langue française [SRLF]) and the French Society of Anesthesia and Intensive Care Medicine (Société francaise d'anesthésie réanimation [SFAR]) with the participation of the French Emergency Medicine Association (Société française de médecine d'urgence [SFMU]), the French Group for Pediatric Intensive Care and Emergencies (Groupe francophone de réanimation et urgences pédiatriques [GFRUP]), the French National Association of Neuro-Anesthesiology and Critical Care (Association nationale de neuro-anesthésie réanimation française [ANARLF]), and the French Neurovascular Society (Société française neurovasculaire [SFNV]). Fifteen experts and two coordinators agreed to consider questions concerning TTM and its practical implementation in five clinical situations: cardiac arrest, traumatic brain injury, stroke, other brain injuries, and shock. This resulted in 30 recommendations: 3 recommendations were strong (Grade 1), 13 were weak (Grade 2), and 14 were experts' opinions. After two rounds of rating and various amendments, a strong agreement from voting participants was obtained for all 30 (100%) recommendations, which are exposed in the present article.

Management of severe traumatic brain injury (first 24hours).

The latest French Guidelines for the management in the first 24hours of patients with severe traumatic brain injury (TBI) were published in 1998. Due to recent changes (intracerebral monitoring, cerebral perfusion pressure management, treatment of raised intracranial pressure), an update was required. Our objective has been to specify the significant developments since 1998. These guidelines were conducted by a group of experts for the French Society of Anesthesia and Intensive Care Medicine (Société francaise d'anesthésie et de réanimation [SFAR]) in partnership with the Association de neuro-anesthésie-réanimation de langue française (ANARLF), The French Society of Emergency Medicine (Société française de médecine d'urgence (SFMU), the Société française de neurochirurgie (SFN), the Groupe francophone de réanimation et d'urgences pédiatriques (GFRUP) and the Association des anesthésistes-réanimateurs pédiatriques d'expression française (ADARPEF). The method used to elaborate these guidelines was the Grade® method. After two Delphi rounds, 32 recommendations were formally developed by the experts focusing on the evaluation the initial severity of traumatic brain injury, the modalities of prehospital management, imaging strategies, indications for neurosurgical interventions, sedation and analgesia, indications and modalities of cerebral monitoring, medical management of raised intracranial pressure, management of multiple trauma with severe traumatic brain injury, detection and prevention of post-traumatic epilepsia, biological homeostasis (osmolarity, glycaemia, adrenal axis) and paediatric specificities.

Impact of extended monitoring-guided intensive care on outcome after severe traumatic brain injury: A prospective multicentre cohort study (PariS-TBI study).

OBJECTIVE: We evaluated whether an integrated monitoring with systemic and specific monitoring affect mortality and disability in adults with severe traumatic brain injury (sTBI). METHODS: Adults with severeTBI (Glasgow Coma Scale [GCS] ≤ 8) admitted alive in intensive care units (ICUs) were prospectively included. Primary endpoints were in-hospital 30-day mortality and extended Glasgow outcome score (GOSE) at 3 years. Association with the intensity of monitoring and outcome was studied by comparing a high level of monitoring (HLM) (systemic and ≥3 specific monitoring) and low level of monitoring (LLM) (systemic and 0-2 specific monitoring) and using inverse probability weighting procedure. RESULTS: 476 patients were included and IPW was used to improve the balance between the two groups of treatments (HLM/LMM). Overall hospital mortality (at 30 days) was 43%, being significantly lower in HLM than LLM group (27% vs. 53%: RR, 1.63: 95% CI: 1.23-2.15). The 14-day hospital mortality was also lower in the HLM group than expected, based upon the CRASH prediction model (35%). At 3 years, disability was not significantly different between the monitoring groups. CONCLUSIONS: After adjustment, HLM group improved short-term mortality but did not show any improvement in the 3-year outcome compared with LLM.

Low HDL levels in sepsis versus trauma patients in intensive care unit.

BACKGROUND: The protective cardiovascular effect of high-density lipoproteins (HDLs) is considered to chiefly rely on reverse cholesterol transport from peripheral tissues back to the liver. However, HDL particles display pleiotropic properties, including anti-inflammatory, anti-apoptotic or antioxidant functions. Some studies suggest that HDL concentration decreases during sepsis, and an association was reported between low HDL levels and a poor outcome. Like sepsis, trauma is also associated with a systemic inflammatory response syndrome. However, no study has yet explored changes in lipid profiles during trauma. We sought to compare lipid profiles between sepsis and trauma patients in intensive care unit (ICU). In septic patients, we analyzed the association between lipid profile, severity and prognosis. METHODS: A prospective, observational, single-centered study was conducted in a surgical ICU. For each patient, total cholesterol, HDL, triglyceride and low-density lipoprotein cholesterol levels were assessed at admission. Short-term prognosis outcome was prospectively assessed. RESULTS: Seventy-five consecutive patients were admitted (50 sepsis and 25 trauma). There was no difference in SOFA and SAPSII scores between the two groups. Patients with sepsis had lower total cholesterol levels than patients with trauma. Regarding the lipoprotein profile, only HDLs differed significantly between the two groups (median [IQR] = 0.33 mmol/l [0.17-0.78] in sepsis patients versus median [IQR] = 0.99 mmol/l [0.74-1.28] in trauma patients; P < 0.0001). Whereas ICU mortality was not associated with lipid levels in the sepsis group, a significant negative correlation was found between HDL concentration and the length of ICU stay (r = -0.35; P = 0.03) in the group of survivor septic patients at ICU discharge. In addition, poor outcome defined as death or a SOFA score >6 at day 3 was associated with lower HDL levels (median [IQR] = 0.20 mmol/l [0.11-0.41] vs. 0.35 mmol/l [0.19-0.86] in patients with poor outcome versus others; P = 0.03). CONCLUSIONS: Lipid profile was totally different between sepsis and trauma in ICU patients: HDL levels were low in septic patients, whereas their concentration was not altered in trauma patients. This major difference reinforces the necessity to explore the therapeutic potential of HDL in sepsis.

Targeted temperature management in the ICU: guidelines from a French expert panel.

Over the recent period, the use of induced hypothermia has gained an increasing interest for critically ill patients, in particular in brain-injured patients. The term "targeted temperature management" (TTM) has now emerged as the most appropriate when referring to interventions used to reach and maintain a specific level temperature for each individual. TTM may be used to prevent fever, to maintain normothermia, or to lower core temperature. This treatment is widely used in intensive care units, mostly as a primary neuroprotective method. Indications are, however, associated with variable levels of evidence based on inhomogeneous or even contradictory literature. Our aim was to conduct a systematic analysis of the published data in order to provide guidelines. We present herein recommendations for the use of TTM in adult and paediatric critically ill patients developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. These guidelines were conducted by a group of experts from the French Intensive Care Society (Société de Réanimation de Langue Française [SRLF]) and the French Society of Anesthesia and Intensive Care Medicine (Société Francaise d'Anesthésie Réanimation [SFAR]) with the participation of the French Emergency Medicine Association (Société Française de Médecine d'Urgence [SFMU]), the French Group for Pediatric Intensive Care and Emergencies (Groupe Francophone de Réanimation et Urgences Pédiatriques [GFRUP]), the French National Association of Neuro-Anesthesiology and Critical Care (Association Nationale de Neuro-Anesthésie Réanimation Française [ANARLF]), and the French Neurovascular Society (Société Française Neurovasculaire [SFNV]). Fifteen experts and two coordinators agreed to consider questions concerning TTM and its practical implementation in five clinical situations: cardiac arrest, traumatic brain injury, stroke, other brain injuries, and shock. This resulted in 30 recommendations: 3 recommendations were strong (Grade 1), 13 were weak (Grade 2), and 14 were experts' opinions. After two rounds of rating and various amendments, a strong agreement from voting participants was obtained for all 30 (100%) recommendations, which are exposed in the present article.

Comparison of the Prognostic Significance of Initial Blood Lactate and Base Deficit in Trauma Patients.

BACKGROUND: Initial blood lactate and base deficit have been shown to be prognostic biomarkers in trauma, but their respective performances have not been compared. METHODS: Blood lactate levels and base deficit were measured at admission in trauma patients in three level 1 trauma centers. This was a retrospective analysis of prospectively acquired data. The association of initial blood lactate and base deficit with mortality was tested using receiver operating characteristics curve, logistic regression using triage scores (Revised Trauma Score and Mechanism Glasgow scale and Arterial Pressure score), and Trauma Related Injury Severity Score as a reference standard. The authors also used a reclassification method. RESULTS: The authors evaluated 1,075 trauma patients (mean age, 39 ± 18 yr, with 90% blunt and 10% penetrating injuries and a mortality of 13%). At admission, blood lactate was elevated in 425 (39%) patients and base deficit was elevated in 725 (67%) patients. Blood lactate was correlated with base deficit (R = 0.54; P < 0.001). Using logistic regression, blood lactate was a better predictor of death than base deficit when considering its additional predictive value to triage scores and Trauma Related Injury Severity Score. This result was confirmed using a reclassification method but only in the subgroup of normotensive patients (n = 745). CONCLUSIONS: Initial blood lactate should be preferred to base deficit as a biologic variable in scoring systems built to assess the initial severity of trauma patients.

Mid-regional pro-adrenomedullin (MR-proADM), a marker of positive fluid balance in critically ill patients: results of the ENVOL study.

BACKGROUND: The optimal control of blood volume without fluid overload is a main challenge in the daily care of intensive care unit (ICU) patients. Accordingly this study focused on the identification of biomarkers to help characterize fluid overload status. METHODS: Sixty-seven patients were studied from ICU admission to day 7 (D7). Blood and urine samples were taken daily and sodium and water balance strictly calculated resulting in a total cumulative assessment of ∆Na+ and ∆H2O. Furthermore, plasmatic biomarkers (cortisol, epinephrine, norepinephrine, renin, angiotensin II, aldosterone, pro-endothelin, copeptine, atrial natriuretic peptide, erythropoietin, mid-regional pro-adrenomedullin (MR-proADM)) and Sequential Organ Failure Assessment (SOFA) scores were measured at D2, D5 and D7. Blood volumes were measured with 51Cr fixed on red blood cells at D2 and D7. RESULTS: The ∆Na+ or ∆H2O were increased in all patients but never related to blood volumes at D2 nor D7. Total blood volumes were at normal values with constantly low red blood cell volumes and normal or decreased plasmatic volume. Weight, plasmatic proteins, and hemoglobin were weakly related to ∆Na+ or ∆H2O. Amongst all tested biomarkers, only MR-proADM was related to sodium and fluid overload. This biomarker was also a predictor of SOFA scores. CONCLUSIONS: Plasmatic concentration in MR-proADM seems to be a good surrogate for evaluation of ∆Na+ or ∆H2O and predicts sodium and extracellular fluid overload. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01858675 in May 13, 2013.