Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial.

BACKGROUND: Patients with acute brain injury are at high risk of ventilator-associated pneumonia (VAP). The benefit of short-term antibiotic prophylaxis remains debated. We aimed to establish the effect of an early, single dose of the antibiotic ceftriaxone on the incidence of early VAP in patients with severe brain injury who required mechanical ventilation. METHODS: PROPHY-VAP was a multicentre, randomised, double-blind, placebo-controlled, assessor-masked, superiority trial conducted in nine intensive care units in eight French university hospitals. We randomly assigned comatose (Glasgow Coma Scale score [GCS] ≤12) adult patients (age ≥18 years) who required mechanical ventilation for at least 48 h after acute brain injury to receive intravenous ceftriaxone 2 g or placebo once within the 12 h following tracheal intubation. Participants did not receive selective oropharyngeal and digestive tract decontamination. The primary outcome was the proportion of patients developing early VAP from the 2nd to the 7th day of mechanical ventilation, confirmed by masked assessors. The analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew or did not give consent to continue and those who did not receive the allocated treatment because they met a criterion for non-eligibility. The trial is registered with ClinicalTrials.gov, NCT02265406. FINDINGS: From Oct 14, 2015, to May 27, 2020, 345 patients were randomly assigned (1:1) to receive ceftriaxone (n=171) or placebo (n=174); 330 received the allocated intervention and 319 were included in the analysis (162 in the ceftriaxone group and 157 in the placebo group). 166 (52%) participants in the analysis were men and 153 (48%) were women. 15 patients did not receive the allocated intervention after randomisation and 11 withdrew their consent. Adjudication confirmed 93 cases of VAP, including 74 early infections. The incidence of early VAP was lower in the ceftriaxone group than in the placebo group (23 [14%] vs 51 [32%]; hazard ratio 0·60 [95% CI 0·38-0·95], p=0·030), with no microbiological impact and no adverse effects attributable to ceftriaxone. INTERPRETATION: In patients with acute brain injury, a single ceftriaxone dose decreased the risk of early VAP. On the basis of our findings, we recommend that an early, single dose of ceftriaxone be included in all bundles for the prevention of VAP in patients with brain injury who require mechanical ventilation. FUNDING: French Ministry of Social Affairs and Health.

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.

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.

Ability of neutrophil-to-lymphocyte ratio to predict secondary neurological impairment in patients with mild to moderate head injury. A retrospective study.

BACKGROUND: The main objective was to assess the performance of the neutrophil-lymphocyte ratio (NLR) for early prediction of delayed neurological impairment and cerebral contusion worsening in patients with mild-to-moderate traumatic brain injury (TBI). METHODS: Over a 3-year period, every adult patient triaged to our level 1 trauma center with brain contusion and Glasgow Coma Scale (GCS) of 10 or greater were retrospectively included. The main study outcome was the occurrence of delayed clinical deterioration, defined as a GCS < 10 and/or a secondary need for mechanical ventilation, within 5 days after TBI. The performance of NLR for prediction of delayed clinical deterioration was assessed by receiver operating characteristic (ROC) curve. RESULTS: Overall, 115 patients were included and 16 (14%) presented a delayed clinical deterioration. Overall, the NLR at ED admission was higher in patients who developed a delayed clinical deterioration (18 [12-29] vs 8 [5-13], p = 0.0003). The area under the ROC curves for NLR at ED admission in predicting delayed clinical deterioration was 0.79 [0.65-0.93] and NLR > 15 was found to be independently associated with the occurrence of delayed clinical deterioration (adjusted OR = 10.1 [95%CI: 2.3-45.6]). CONCLUSION: The NLR at ED admission was independently associated with the occurrence of delayed clinical deterioration, although limited by a poor discriminative value by itself. Further studies are needed to test the predictive value of composite scoring systems including NLR for prevention of under-triage of patients with mild-to-moderate TBI.

Salt wasting syndrome in brain trauma patients: a pathophysiologic approach using sodium balance and urinary biochemical analysis.

BACKGROUND: To explore the underlying mechanisms leading to the occurrence of hyponatremia and enhanced urinary sodium excretion in brain trauma patients using sodium balance and urinary biochemical analysis. METHODS: We conducted a retrospective analysis of a local database prospectively collected in 60 brain trauma patients without chronic renal dysfunction. Metabolic and hemodynamic parameters were averaged over three consecutive periods over the first seven days after admission. The main outcome investigated in this study was the occurrence of at least one episode of hyponatremia. RESULTS: Over the study period, there was a prompt decrease in sodium balance (163 ± 193 vs. -12 ± 154 mmol/day, p < 0.0001) and free water clearance (- 0.7 ± 0.7 vs. -1.8 ± 2.3 ml/min, p < 0.0001). The area under the ROC curves for sodium balance in predicting the occurrence of hyponatremia during the next period was 0.81 [95% CI: 0.64-0.97]. Variables associated with averaged urinary sodium excretion were sodium intake (R2 = 0.26, p < 0.0001) and fractional excretion of urate (R2 = 0.15, p = 0.009). Urinary sodium excretion was also higher in patients with sustained augmented renal clearance over the study period (318 ± 106 vs. 255 ± 135 mmol/day, p = 0.034). CONCLUSION: The decreased vascular volume resulting from a negative sodium balance is a major precipitating factor of hyponatremia in brain trauma patients. Predisposing factors for enhanced urinary sodium excretion were high sodium intake, high fractional excretion of urate and augmented renal clearance over the first seven days after ICU admission.

Long-term disability after blunt chest trauma: Don't miss chronic neuropathic pain!

Introduction The main objective of this prospective study was to assess the incidence of chronic pain and long-term respiratory disability in a single-center cohort of severe blunt chest trauma patients. Methods Over a 10-month period, all consecutive blunt chest trauma patients admitted in Intensive Care Unit (ICU) were screened to participate in a 3-month and 12-month follow-up. The following variables were prospectively assessed: persistence of chronic chest pain requiring regular used of analgesics, neuropathic pain, respiratory disability, physical and mental health status. Univariate and multivariable analysis were conducted to assess variables associated with chronic chest pain, neuropathic chest pain and respiratory disability. Results During the study period, 65 patients were included in the study. Chronic chest pain and respiratory disability were reported in 62% and 57% of patients respectively at 3 months postinjury. Neuropathic pain was reported in 22% of patients, associated with higher impairment of quality of life. A thoracic trauma severity score ≥12 and a pain score ≥4 at SICU discharge were the only variables significantly associated with the occurrence of neuropathic pain at 3 months (OR = 7 [2-32], p = 0.01 and OR = 16 [4-70], p < 0.0001). Conclusion According to the current study, chronic pain and long-term respiratory disability are very common after severe blunt chest trauma patients. Special attention should be paid to neuropathic pain, frequently under-diagnosed and responsible for significant impairment of quality of life.

Prevention of early ventilation-acquired pneumonia (VAP) in comatose brain-injured patients by a single dose of ceftriaxone: PROPHY-VAP study protocol, a multicentre, randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is the first cause of healthcare-associated infections in intensive care units (ICUs) and brain injury is one of the main risk factors for early-onset VAP. Antibiotic prophylaxis has been reported to decrease their occurrence in brain-injured patients, but a lack of controlled randomised trials and the risk of induction of bacterial resistance explain the low level of recommendations. The goal of this study is to determine whether a single dose of ceftriaxone within the 12 hours postintubation after severe brain injury can decrease the risk of early-onset VAP. METHODS AND ANALYSIS: The PROPHY-VAP is a French multicentre, randomised, double-blind, placebo-controlled, clinical trial. Adult brain-injured patients (n=320) with a Glasgow Coma Scale ≤12, requiring mechanical ventilation for more than 48 hours, are randomised to receive either a single dose of ceftriaxone 2 g or a placebo within the 12 hours after tracheal intubation. The primary endpoint is the proportion of patients developing VAP from the 2nd to the 7th day after mechanical ventilation. Secondary endpoints include the proportion of patients developing late VAP (>7 days after tracheal intubation), the number of ventilator-free days, VAP-free days and antibiotic-free days, length of stay in the ICU, proportion of patients with ventilator-associated events and mortality during their ICU stay. ETHICS AND DISSEMINATION: The initial research project was approved by the Institutional Review Board of OUEST III (France) on 20 October 2014 (registration No 2014-001668-36) and carried out according to the principles of the Declaration of Helsinki and the Clinical Trials Directive 2001/20/EC of the European Parliament relating to the Good Clinical Practice guidelines. The results of this study will be presented in national and international meetings and published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02265406; Pre-results.

Higher than standard dosing regimen are needed to achieve optimal antibiotic exposure in critically ill patients with augmented renal clearance receiving piperacillin-tazobactam administered by continuous infusion.

PURPOSE: To determine whether augmented renal clearance (ARC) impacts negatively on piperacillin-tazobactam unbound concentrations in critically ill patients receiving 16 g/2 g/day administered continuously. MATERIAL AND METHODS: Fifty nine critically ill patients without renal impairment underwent 24-h creatinine clearance (CrCL) measurement and therapeutic drug monitoring during the first three days of antimicrobial therapy by piperacillin-tazobactam. The main outcome was the rate of piperacillin underexposure, defined by at least one of three samples under 16 mg/L. Monte Carlo simulation was performed to predict the distribution of piperacillin concentrations for various CrCL and minimal inhibitory concentration (MIC) values. RESULTS: The rate of piperacillin underexposure was 19%, significantly higher in ARC patients (0 vs. 31%, p = .003). A threshold of CrCL ≥ 170 mL/min had a sensitivity and specificity of 1 (95%CI: 0.79-1) and 0.69 (95%CI: 0.61-0.76) to predict piperacillin underexposure. In ARC patients, a 20 g/2.5 g/24 h PTZ dosing regimen was associated with the highest probability to reach the 16 mg/L empirical target, without risk of excessive dosing. CONCLUSIONS: When targeting a theoretical MIC at the upper limit of the susceptibility range, the desirable target (100%fT>16) may not be achieved in patients with CrCL ≥ 170 mL/min receiving PTZ 16 g/2 g/day administered continuously.

Use of brain diffusion tensor imaging for the prediction of long-term neurological outcomes in patients after cardiac arrest: a multicentre, international, prospective, observational, cohort study.

BACKGROUND: Prediction of neurological outcome after cardiac arrest is a major challenge. The aim of this study was to assess whether quantitative whole-brain white matter fractional anisotropy (WWM-FA) measured by diffusion tensor imaging between day 7 and day 28 after cardiac arrest can predict long-term neurological outcome. METHODS: This prospective, observational, cohort study (part of the MRI-COMA study) was done in 14 centres in France, Italy, and Belgium. We enrolled patients aged 18 years or older who had been unconscious for at least 7 days after cardiac arrest into the derivation cohort. The following year, we recruited the validation cohort on the same basis. We also recruited a minimum of five healthy volunteers at each centre for the normalisation procedure. WWM-FA values were compared with standard criteria for unfavourable outcome, conventional MRI sequences (fluid-attenuated inversion recovery and diffusion-weighted imaging), and proton magnetic resonance spectroscopy. The primary outcome was the best achieved Glasgow-Pittsburgh Cerebral Performance Categories (CPC) at 6 months, dichotomised as favourable (CPC 1-2) and unfavourable outcome (CPC 3-5). Prognostication performance was assessed by the area under the receiver operating characteristic (ROC) curves and compared between groups. This study was registered with ClinicalTrials.gov, number NCT00577954. FINDINGS: Between Oct 1, 2006, and June 30, 2014, 185 patients were enrolled in the derivation cohort, of whom 150 had an interpretable multimodal MRI and were included in the analysis. 33 (22%) patients had a favourable neurological outcome at 6 months. Prognostic accuracy, as quantified by the area under the ROC curve, was significantly higher with the normalised WWM-FA value (area under the ROC curve 0·95, 95% CI 0·91-0·98) than with the standard criteria for unfavourable outcome or other MRI sequences. In a subsequent validation cohort of 50 patients (enrolled between April 1, 2015, and March 31, 2016), a normalised WWM-FA value lower than 0·91, set from the derivation cohort, had a negative predictive value of 71·4% (95% CI 41·9-91·6) and a positive predictive value of 100% (90·0-100), with 89·7% sensitivity (75·8-97·1) and 100% specificity (69·1-100) for the prediction of unfavourable outcome. INTERPRETATION: In patients who are unconscious 7 days after cardiac arrest, the normalised WWM-FA value, measured by diffusion tensor imaging, could be used to accurately predict neurological outcome at 6 months. This evidence requires confirmation from future large-scale trials with a strict protocol of withdrawal or limitation-of-care decisions and time window for MRI. FUNDING: French Ministry of Health, French National Agency for Research, Italian Ministry of Health, and Regione Lombardia.

Association between augmented renal clearance and clinical failure of antibiotic treatment in brain-injured patients with ventilator-acquired pneumonia: A preliminary study.

OBJECTIVES: This preliminary study aimed to determine whether augmented renal clearance (ARC) impacts negatively on the clinical outcome in traumatic brain-injured patients (TBI) treated for a first episode of ventilator-acquired pneumonia (VAP). METHODS: During a 5-year period, all TBI patients who had developed VAP were retrospectively reviewed to assess variables associated with clinical failure in multivariate analysis. Clinical failure was defined as an impaired clinical response with a need for escalating antibiotics during treatment and/or within 15 days after the end-of-treatment. Recurrence was considered if at least one of the initial causative bacterial strains was growing at a significant concentration from a second sample. Augmented renal clearance (ARC) was defined by an enhanced creatinine clearance exceeding 130mL/min/1.73m2 calculated from a urinary sample during the first three days of antimicrobial therapy. MAIN RESULTS: During the study period, 223 TBI patients with VAP were included and 59 (26%) presented a clinical failure. Factors statistically associated with clinical failure were GSC≤7 (OR=2.2 [1.1-4.4], P=0.03), early VAP (OR=3.9 [1.9-7.8], P=0.0001), bacteraemia (OR=11 [2.2-54], P=0.003) and antimicrobial therapy≤7 days (OR=3.7 [1.8-7.4], P=0.0003). ARC was statistically associated with recurrent infections with an OR of 4.4 [1.2-16], P=0.03. CONCLUSION: ARC was associated with recurrent infection after a first episode of VAP in TBI patients. The optimal administration and dosing of the antimicrobial agents in this context remain to be determined.

Bundle of care for blunt chest trauma patients improves analgesia but increases rates of intensive care unit admission: A retrospective case-control study.

INTRODUCTION: This single-centre retrospective case-control study aimed to assess the effectiveness of a multidisciplinary clinical pathway for blunt chest trauma patients admitted in emergency department (ED). PATIENTS AND METHODS: All consecutive blunt chest trauma patients with more than 3 rib fractures and no indication of mechanical ventilation were compared to a retrospective cohort over two 24-month periods, before and after the introduction of the bundle of care. Improvement of analgesia was the main outcome investigated in this study. The secondary outcomes were the occurrence of secondary respiratory complications (pneumonia, indication for mechanical ventilation, secondary ICU admission for respiratory failure or death), the intensive care unit (ICU) and hospital length of stay (LOS). RESULTS: Sixty-nine pairs of patients were matched using a 1:1 nearest neighbour algorithm adjusted on age and indices of severity. Between the two periods, there was a significant reduction of the rate of uncontrolled analgesia (55 vs. 17%, P<0.001). A significant increase in the rate of primary ICU transfer during the post-protocol period (23 vs. 52%, P<0.001) was not associated with a reduction of secondary respiratory complications or a reduction of ICU or hospital LOS. Only the use of non-steroidal anti-inflammatory drugs appeared to be associated with a significant reduction of secondary respiratory complications (OR=0.3 [0.1-0.9], P=0.03). CONCLUSION: Implementation of a multidisciplinary clinical pathway significantly improves pain control after ED management, but increases the rate of primary ICU admission without significant reduction of secondary respiratory complications.

Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill septic patients receiving high doses of ß-lactams administered by continuous infusion: a prospective observational study.

This study assessed whether augmented renal clearance (ARC) impacts negatively on antibiotic concentrations and clinical outcomes in patients treated by high-dose ß-lactams administered continuously. Over a 9-month period, all critically ill patients without renal impairment treated by one of the monitored ß-lactams for a documented infection were eligible. During the first 3 days of antibiotic therapy, every patient underwent 24-h CLCr measurements and therapeutic drug monitoring. The main outcome was the rate of ß-lactam underdosing, defined as a free drug concentration <4 × MIC of the known pathogen. Secondary outcomes were rates of subexposure for ß-lactams and therapeutic failure. The performance of CLCr in predicting underdosing was assessed by a ROC curve, and multivariable logistic regression was performed to determine risk factors for subexposure and therapeutic failure. A total of 79 patients were included and 235 samples were analysed. The rate of underdosing<4×MIC was 12%, with a significant association with CLCr (P <0.0001). A threshold of CLCr ≥ 170 mL/min had a sensitivity and specificity of 0.93 (95% CI 0.77-0.99) and 0.65 (95% CI 0.58-0.71) for predicting ß-lactam underdosing<4×MIC. Mean CLCr values ≥170 mL/min were significantly associated with subexposure<4xMIC [OR = 10.1 (2.4-41.6); P = 0.001]. Patients with subexposure<4×MIC presented higher rates of therapeutic failure [OR = 6.3 (1.2-33.2); P = 0.03]. Mean CLCr values ≥170 mL/min remain a risk factor for subexposure to ß-lactams despite high doses of ß-lactams administered continuously. ß-Lactam subexposure was associated with higher rates of therapeutic failure in septic critically ill patients.

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.

Subclavian central venous catheter-related thrombosis in trauma patients: incidence, risk factors and influence of polyurethane type.

INTRODUCTION: The incidence of deep venous thrombosis (DVT) related to a central venous catheter varies considerably in ICUs depending on the population included. The aim of this study was to determine subclavian central venous catheter (SCVC)-related DVT risk factors in severely traumatized patients with regard to two kinds of polyurethane catheters. METHODS: Critically ill trauma patients needing a SCVC for their usual care were prospectively included in an observational study. Depending on the month of inclusion, patients received one of the two available products in the emergency unit: either an aromatic polyurethane SCVC or an aliphatic polyurethane SCVC. Patients were screened weekly by ultrasound for SCVC-related DVT. Potential risk factors were collected, including history-related, trauma-related and SCVC-related characteristics. RESULTS: A total of 186 patients were included with a median Injury Severity Sore of 30 and a high rate of severe brain injuries (21% of high intracranial pressure). Incidence of SCVC-related DVT was 37% (95% confidence interval: 26 to 40) in patients or 20/1,000 catheter-days. SCVC-related DVT occurred within 8 days in 65% of cases. There was no significant difference in DVT rates between the aromatic polyurethane and aliphatic polyurethane SCVC groups (38% vs. 36%). SCVC-related DVT independent risk factors were age>30 years, intracranial hypertension, massive transfusion (>10 packed red blood cell units), SCVC tip position in the internal jugular or in the innominate vein, and ipsilateral jugular catheter. CONCLUSION: SCVC-related DVT concerned one-third of these severely traumatized patients and was mostly clinically silent. Incidence did not depend on the type of polyurethane but was related to age>30 years, intracranial hypertension or misplacement of the SCVC. Further studies are needed to assess the cost-effectiveness of routine screening in these patients in whom thromboprophylaxis may be hazardous.

Assessment of white matter injury and outcome in severe brain trauma: a prospective multicenter cohort.

BACKGROUND: Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). METHODS: In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n=38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. RESULTS: Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75-0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54-0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. CONCLUSIONS: White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score.

Evaluation of stroke volume variations obtained with the pressure recording analytic method.

OBJECTIVE: To investigate whether stroke volume variations obtained with the pressure recording analytic method can predict fluid responsiveness in mechanically ventilated patients with circulatory failure. DESIGN: Prospective study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Thirty-five mechanically ventilated patients with circulatory failure for whom the decision to give fluid was taken by the physician were included. Exclusion criteria were: Arrhythmia, tidal volume <8 mL/kg, left ventricular ejection fraction<50%, right ventricular dysfunction, and heart rate/respiratory rate ratio <3.6. INTERVENTIONS: Fluid challenge with 500 mL of saline over 15 mins. MEASUREMENTS AND MAIN RESULTS: Stroke volume variations and cardiac output obtained with a pressure recording analytic method, pulse pressure variations, and cardiac output estimated by echocardiography were recorded before and after volume expansion. Patients were defined as responders if stroke volume obtained using echocardiography increased by ≥15% after volume expansion. Nineteen patients responded to the fluid challenge. Median [interquartile range, 25% to 75%] stroke volume variation values at baseline were not different in responders and nonresponders (10% [8-16] vs. 14% [12-16]), whereas pulse pressure variations were significantly higher in responders (17% [13-19] vs. 7% [5-10]; p < .0001). A 12.6% stroke volume variations threshold discriminated between responders and nonresponders with a sensitivity of 63% (95% confidence interval 38% to 84%) and a specificity of 69% (95% confidence interval 41% to 89%). A 10% pulse pressure variation threshold discriminated between responders and nonresponders with a sensitivity of 89% (95% confidence interval 67% to 99%) and a specificity of 88% (95% confidence interval 62% to 98%). The area under the receiver operating characteristic curves was different between pulse pressure variations (0.95; 95% confidence interval 0.82-0.99) and stroke volume variations (0.60; 95% confidence interval 0.43-0.76); p < .0001). Volume expansion-induced changes in cardiac output measured using echocardiography or pressure recording analytic method were not correlated (r = 0.14; p > .05) and the concordance rate of the direction of change in cardiac output was 60%. CONCLUSION: Stroke volume variations obtained with a pressure recording analytic method cannot predict fluid responsiveness in intensive care unit patients under mechanical ventilation. Cardiac output measured by this device is not able to track changes in cardiac output induced by volume expansion.

Impact of norepinephrine on the relationship between pleth variability index and pulse pressure variations in ICU adult patients.

INTRODUCTION: Pleth Variability Index (PVI) is an automated and continuous calculation of respiratory variations in the perfusion index. PVI correlates well with respiratory variations in pulse pressure (ΔPP) and is able to predict fluid responsiveness in the operating room. ICU patients may receive vasopressive drugs, which modify vascular tone and could affect PVI assessment. We hypothesized that the correlation between PVI and ΔPP and the ability of PVI to identify patients with ΔPP > 13% is dependent on norepinephrine (NE) use. METHODS: 67 consecutive mechanically ventilated patients in the ICU were prospectively included. Three were excluded. The administration and dosage of NE, heart rate, mean arterial pressure, PVI and ΔPP were measured simultaneously. RESULTS: In all patients, the correlation between PVI and ΔPP was weak (r2 = 0.21; p = 0.001). 23 patients exhibited a ΔPP > 13%. A PVI > 11% was able to identify patients with a ΔPP > 13% with a sensitivity of 70% (95% confidence interval: 47%-87%) and a specificity of 71% (95% confidence interval: 54%-84%). The area under the curve was 0.80 ± 0.06. 35 patients (53%) received norepinephrine (NE(+)). In NE(+) patients, PVI and ΔPP were not correlated (r2 = 0.04, p > 0.05) and a PVI > 10% was able to identify patients with a ΔPP > 13% with a sensitivity of 58% (95% confidence interval: 28%-85%) and a specificity of 61% (95% confidence interval:39%-80%). The area under the ROC (receiver operating characteristics) curve was 0.69 ± 0.01. In contrast, NE(-) patients exhibited a correlation between PVI and ΔPP (r2 = 0.52; p < 0.001) and a PVI > 10% was able to identify patients with a ΔPP > 13% with a sensitivity of 100% (95% confidence interval: 71%-100%) and a specificity of 72% (95% confidence interval: 49%-90%). The area under the ROC curve was 0.93 ± 0.06 for NE(-) patients and was significantly higher than the area under the ROC curve for NE(+) patients (p = 0.02). CONCLUSIONS: Our results suggest that in mechanically ventilated adult patients, NE alters the correlation between PVI and ΔPP and the ability of PVI to predict ΔPP > 13% in ICU patients.

Comparison of effects of equiosmolar doses of mannitol and hypertonic saline on cerebral blood flow and metabolism in traumatic brain injury.

The potential superiority of hypertonic saline (HTS) over mannitol (MTL) for control of intracranial pressure (ICP) following traumatic brain injury (TBI) is still debated. Forty-seven severe TBI patients with increased ICP were prospectively recruited in two university hospitals and randomly treated with equiosmolar infusions of either MTL 20% (4 mL/kg; n=25 patients) or HTS 7.5% (2 mL/kg; n=22 patients). Serum sodium, hematocrit, ICP, arterial blood pressure, cerebral perfusion pressure (CPP), shear rate, global indices of cerebral blood flow (CBF) and metabolism were measured before, and 30 and 120 min following each infusion during the course of illness. Outcome was assessed at 6 months. Both HTS and MTL effectively and equally reduced ICP levels with subsequent elevation of CPP and CBF, although this effect was significantly stronger and of longer duration after HTS and correlated with improved rheological blood properties induced by HTS. Further, effect of HTS on ICP appeared to be more robust in patients with diffuse brain injury. In contrast, oxygen and glucose metabolic rates were left equally unaffected by both solutions. Accordingly, there was no significant difference in neurological outcome between the two groups. In conclusion, MTL was as effective as HTS in decreasing ICP in TBI patients although both solutions failed to improved cerebral metabolism. HTS showed an additional and stronger effect on cerebral perfusion of potential benefit in the presence of cerebral ischemia. Treatment selection should therefore be individually based on sodium level and cerebral hemodynamics.

Changes in stroke volume induced by passive leg raising in spontaneously breathing patients: comparison between echocardiography and Vigileo/FloTrac device.

INTRODUCTION: Passive leg raising (PLR) is a simple reversible maneuver that mimics rapid fluid loading and increases cardiac preload. The effects of this endogenous volume expansion on stroke volume enable the testing of fluid responsiveness with accuracy in spontaneously breathing patients. However, this maneuver requires the determination of stroke volume with a fast-response device, because the hemodynamic changes may be transient. The Vigileo monitor (Vigileo; Flotrac; Edwards Lifesciences, Irvine, CA, USA) analyzes systemic arterial pressure wave and allows continuous stroke volume monitoring. The aims of this study were (i) to compare changes in stroke volume induced by passive leg raising measured with the Vigileo device and with transthoracic echocardiography and (ii) to compare their ability to predict fluid responsiveness. METHODS: Thirty-four patients with spontaneous breathing activity and considered for volume expansion were included. Measurements of stroke volume were obtained with transthoracic echocardiography (SV-TTE) and with the Vigileo (SV-Flotrac) in a semi-recumbent position, during PLR and after volume expansion (500 ml saline). Patients were responders to volume expansion if SV-TTE increased > or = 15%. RESULTS: Four patients were excluded. No patients received vasoactive drugs. Seven patients presented septic hypovolemia. PLR-induced changes in SV-TTE and in SV-Flotrac were correlated (r2 = 0.56, P < 0.0001). An increase in SV-TTE > or = 13% during PLR was predictive of response to volume expansion with a sensitivity of 100% and a specificity of 80%. An increase in SV-Flotrac > or =16% during PLR was predictive of response to volume expansion with a sensitivity of 85% and a specificity of 90%. There was no difference between the area under the ROC curve for PLR-induced changes in SV-TTE (AUC = 0.96 +/- 0.03) or SV-Flotrac (AUC = 0.92 +/- 0.05). Volume expansion-induced changes in SV-TTE correlated with volume expansion-induced changes in SV-Flotrac (r2 = 0.77, P < 0.0001). In all patients, the highest plateau value of SV-TTE recorded during PLR was obtained within the first 90 s following leg elevation, whereas it was 120 s for SV-Flotrac. CONCLUSIONS: PLR-induced changes in SV-Flotrac are able to predict the response to volume expansion in spontaneously breathing patients without vasoactive support.