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Rationale: Norepinephrine (NE) is commonly used in combination with fluid during resuscitation of hemorrhagic shock, but its impact on kidney microcirculation, oxygenation, and function is still unknown in this setting. Objectives: During hemorrhagic shock resuscitation, does a combination of fluid and NE affect kidney oxygenation tension, kidney microcirculatory perfusion, and 48-hour kidney function, as compared with fluid alone? Methods: Hemorrhagic shock was induced in 24 pigs, and 8 pigs were included as a sham group. Resuscitation of hemorrhagic shock was performed, using a closed-loop device, either by fluid alone (0.9% NaCl; fluid group) or associated with the administration of NE at two doses (moderate dose: mean rate of 0.64 μg ⋅ kg -1  ⋅ min -1 ; high dose: mean rate of 1.57 μg ⋅ kg -1  ⋅ min -1 ) to obtain a target systolic arterial pressure of 80 to 90 mm Hg. Resuscitation was followed by transfusion of the withdrawn blood. Measurements and Main Results: The amount of fluid required to reach the target systolic arterial pressure was lower in the NE groups than in the fluid group, with subsequently less hemodilution. NE restored kidney microcirculation, oxygenation, and function in a manner comparable to that achieved with fluid resuscitation alone. There were no histologic differences between animals resuscitated with fluid and those resuscitated with NE. Conclusions: In pigs with hemorrhagic shock, resuscitation with a combination of NE and fluid restored kidney microcirculation and oxygenation, as well as renal function, in a manner comparable to fluid resuscitation alone and without differences between the two NE doses. NE administration led to a fluid volume-sparing effect with subsequently less hemodilution.

Background: Optimal management of community-acquired intra-abdominal infections (IAI) requires timely surgical source control and adequate anti-infective treatment., Objective: To describe the initial management of community-acquired IAI admitted to the emergency department and assess the association between the length of time to either diagnosis or therapeutic procedures and patient outcomes., Design: A prospective, multicentre, observational study., Setting: Thirteen teaching hospitals in France between April 2018 and February 2019., Patients: Two hundred and five patients aged at least 18 years diagnosed with community-acquired IAI., Main Outcome Measures: The primary outcome was hospital length of stay. The secondary outcome was hospital mortality., Results: Patients had a mean age of 56 (± 21) years and a median [interquartile] SAPS II of 26 [17 to 34]. Among the study cohort, 18% were postoperatively transferred to intensive care unit and 7% had died by day 28. Median [IQR] time to imaging, antibiotic therapy and surgery were 4 [2 to 6], 7.5 [4 to 12.5] and 9 [5.5 to 17] hours, respectively. The length of time to surgical source control [0.99, 95% confidence interval (CI), 0.98 to 0.99], SOFA greater than 2 [0.36 (95% CI, 0.26 to 0.651)], age greater than 60 years [0.65 (95% CI, 0.45 to 0.94)], generalized peritonitis [0.7 (95% CI, 0.56 to 0.89)] and laparotomy surgery [0.657 (95% CI, 0.42 to 0.78)] were associated with longer hospital length of stay. The duration of time to surgical source control [1.02 (95% CI, 1.01 to 1.04)], generalized peritonitis [2.41 (95% CI, 1.27 to 4.61)], and SOFA score greater than 2 [6.14 (95% CI, 1.40 to 26.88)] were identified as independent risk factors for 28-day mortality., Conclusion: This multicentre observational study revealed that the time to surgical source control, patient severity and generalized peritonitis were identified as independent risk factors for increased hospital LOS and mortality in community-acquired IAI. Organisational strategies to reduce the time to surgical management of intra-abdominal infections should be further evaluated., Study Registration: ClinicalTrials.gov on 1 April 2018, NCT03544203., (Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: This study aimed to determine the prevalence of withholding or withdrawal of life-sustaining therapy (WLST) decisions in trauma ICU patients, using a large registry. We hypothesised that this prevalence is similar to that of the general population admitted to an ICU. As secondary aims, it sought to describe the trauma patients for whom the decision was made for WLST and the factors associated with this decision., Design: This observational study assessed data from 14 French centres listed in the TraumaBaseTM registry. All trauma patients hospitalised for more than 48 h were pro-spectively included., Results: Data from 8569 trauma patients, obtained from January 2016 to December 2018, were included in this study. A WLST decision was made in 6% of all cases. In the WLST group, 67% of the patients were older men (age: 62 versus 36, P  < 0.001); more often they had a prior medical history and higher median severity scores than the patients in the no WLST decision group; SAPS II 58 (46 to 69) versus 21 (13 to 35) and ISS 26 (22 to 24) versus 12 (5 to 22), P  < 0.001. Neurological status was strongly associated with WLST decisions. The geographic area of the ICUs affected the rate of the WLST decisions. The ICU mortality was 11% (n = 907) of which 47% (n = 422) were preceded by WLST decisions. Fourteen percent of WLST orders were not associated to the death., Conclusion: Among 8569 patients, medical history, trauma severity criteria, notably neurological status and geographical areas were associated with WLST. These regional differences deserve to be investigated in future studies., (Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Rationale: The characteristics of patients with respiratory complaints and/or lung radiologic abnormalities after hospitalisation for coronavirus disease 2019 (COVID-19) are unknown. The objectives were to determine their characteristics and the relationships between dyspnoea, radiologic abnormalities and functional impairment., Methods: In the COMEBAC (Consultation Multi-Expertise de Bicêtre Après COVID-19) cohort study, 478 hospital survivors were evaluated by telephone 4 months after hospital discharge, and 177 who had been hospitalised in an intensive care unit (ICU) or presented relevant symptoms underwent an ambulatory evaluation. New-onset dyspnoea and cough were evaluated, and the results of pulmonary function tests and high-resolution computed tomography of the chest were collected., Results: Among the 478 patients, 78 (16.3%) reported new-onset dyspnoea, and 23 (4.8%) new-onset cough. The patients with new-onset dyspnoea were younger (56.1±12.3 versus 61.9±16.6 years), had more severe COVID-19 (ICU admission 56.4% versus 24.5%) and more frequent pulmonary embolism (18.0% versus 6.8%) (all p≤0.001) than patients without dyspnoea. Among the patients reassessed at the ambulatory care visit, the prevalence of fibrotic lung lesions was 19.3%, with extent <25% in 97% of the patients. The patients with fibrotic lesions were older (61±11 versus 56±14 years, p=0.03), more frequently managed in an ICU (87.9 versus 47.4%, p<0.001), had lower total lung capacity (74.1±13.7 versus 84.9±14.8% pred, p<0.001) and diffusing capacity of the lung for carbon monoxide ( D LCO ) (73.3±17.9 versus 89.7±22.8% pred, p<0.001). The combination of new-onset dyspnoea, fibrotic lesions and D LCO <70% pred was observed in eight out of 478 patients., Conclusions: New-onset dyspnoea and mild fibrotic lesions were frequent at 4 months, but the association of new-onset dyspnoea, fibrotic lesions and low D LCO was rare., Competing Interests: Conflict of interest: E-M. Jutant has nothing to disclose. Conflict of interest: O. Meyrignac has nothing to disclose. Conflict of interest: A. Beurnier has nothing to disclose. Conflict of interest: X. Jaïs has nothing to disclose. Conflict of interest: T. Pham has nothing to disclose. Conflict of interest: L. Morin has nothing to disclose. Conflict of interest: A. Boucly has nothing to disclose. Conflict of interest: S. Bulifon has nothing to disclose. Conflict of interest: S. Figueiredo has nothing to disclose. Conflict of interest: A. Harrois has nothing to disclose. Conflict of interest: M. Jevnikar has nothing to disclose. Conflict of interest: N. Noël has nothing to disclose. Conflict of interest: J. Pichon has nothing to disclose. Conflict of interest: A. Roche has nothing to disclose. Conflict of interest: A. Seferian has nothing to disclose. Conflict of interest: S. Soliman has nothing to disclose. Conflict of interest: J. Duranteau has nothing to disclose. Conflict of interest: L. Becquemont has nothing to disclose. Conflict of interest: X. Monnet has nothing to disclose. Conflict of interest: O. Sitbon has nothing to disclose. Conflict of interest: M-F. Bellin has nothing to disclose. Conflict of interest: M. Humbert has nothing to disclose. Conflict of interest: L. Savale has nothing to disclose. Conflict of interest: D. Montani has nothing to disclose., (Copyright ©The authors 2022.)

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has resulted in millions of deaths and a major strain on health systems worldwide. Medical treatments for COVID-19 (anticoagulants, corticosteroids, anti-inflammatory drugs, oxygenation therapy and ventilation) and vaccination have improved patient outcomes. The majority of patients will recover spontaneously or after acute-phase management, but clinicians are now faced with long-term complications of COVID-19 including a large variety of symptoms, defined as "post-acute COVID-19 syndrome". Most studies have focused on patients hospitalised for severe COVID-19, but acute COVID-19 syndrome is not restricted to these patients and exists in outpatients. Given the diversity of symptoms and the high prevalence of persistent symptoms, the management of these patients requires a multidisciplinary team approach, which will result in the consumption of large amounts of health resources in the coming months. In this review, we discuss the presentation, prevalence, pathophysiology and evolution of respiratory complications and other organ-related injuries associated with post-acute COVID-19 syndrome., Competing Interests: Conflict of interest: D. Montani has no conflicts to disclose. Conflict of interest: L. Savale has no conflicts to disclose. Conflict of interest: N. Noel has no conflicts to disclose. Conflict of interest: O. Meyrignac has no conflicts to disclose. Conflict of interest: R. Colle has no conflicts to disclose. Conflict of interest: M. Gasnier has no conflicts to disclose. Conflict of interest: E. Corruble has no conflicts to disclose. Conflict of interest: A. Beurnier has no conflicts to disclose. Conflict of interest: E-M. Jutant has no conflicts to disclose. Conflict of interest: T. Pham has no conflicts to disclose. Conflict of interest: A-L. Lecoq has no conflicts to disclose. Conflict of interest: J-F. Papon has no conflicts to disclose. Conflict of interest: S. Figuereido has no conflicts to disclose. Conflict of interest: A. Harrois has no conflicts to disclose. Conflict of interest: M. Humbert has no conflicts to disclose. Conflict of interest: X. Monnet has no conflicts to disclose., (Copyright ©The authors 2022.)

Background: Deviation from guidelines is frequent in emergency situations, and this may lead to increased mortality. Probably because of time constraints, 55% is the greatest reported guidelines compliance rate in severe trauma patients. This study aimed to identify among all available recommendations a reasonable bundle of items that should be followed to optimize the outcome of hemorrhagic shocks (HSs) and severe traumatic brain injuries (TBIs)., Methods: We first estimated the compliance with French and European guidelines using the data from the French TraumaBase registry. Then, we used a machine learning procedure to reduce the number of recommendations into a minimal set of items to be followed to minimize 7-day mortality. We evaluated the bundles using an external validation cohort., Results: This study included 5,924 trauma patients (1,414 HS and 4,955 TBI) between 2011 and August 2019 and studied compliance to 36 recommendation items. Overall compliance rate to recommendation items was 71.6% and 66.9% for HS and TBI, respectively. In HS, compliance was significantly associated with 7-day decreased mortality in univariate analysis but not in multivariate analysis (risk ratio [RR], 0.91; 95% confidence interval [CI], 0.90-1.17; p = 0.06). In TBI, compliance was significantly associated with decreased mortality in univariate and multivariate analysis (RR, 0.85; 95% CI, 0.75-0.92; p = 0.01). For HS, the bundle included 13 recommendation items. In the validation cohort, when this bundle was applied, patients were found to have a lower 7-day mortality rate (RR, 0.46; 95% CI, 0.27-0.63; p = 0.01). In TBI, the bundle included seven items. In the validation cohort, when this bundle was applied, patients had a lower 7-day mortality rate (RR, 0.55; 95% CI, 0.34-0.71; p = 0.02)., Discussion: Using a machine-learning procedure, we were able to identify a subset of recommendations that minimizes 7-day mortality following traumatic HS and TBI. These two bundles remain to be evaluated in a prospective manner., Level of Evidence: Care Management, level II., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We evaluated the performance of a new device to control the administration of fluid alone or co-administration of fluid and norepinephrine in a pig model of haemorrhagic shock in two sets of experiments. In the first one, resuscitation was guided using continuous arterial pressure measurements (three groups: resuscitation with fluid by a physician, CL resuscitation with fluid, and CL resuscitation with fluid and norepinephrine). In the second one, resuscitation was guided using discontinuous arterial pressure measurements (three groups: CL resuscitation with fluid alone, CL resuscitation with fluid and moderate dose norepinephrine, and CL resuscitation with fluid and a high dose of norepinephrine). Pigs were resuscitated for 1 h. In the first set of experiments, proportion of time spent in the target area of 78-88 mmHg of systolic arterial pressure was not statistically different between the three groups: manual, 71.2% (39.1-80.1); CL with fluid, 87.8% (68.3-97.4); and CL with fluid and norepinephrine, 78.1% (59.2-83.6), p = 0.151. In the second set of experiments, performance of CL resuscitation with fluid or with combination of fluid and high or moderate dose of norepinephrine was not significantly different (p = 0.543 for time in target). Pigs resuscitated with norepinephrine required less fluid and had less haemodilution than pigs resuscitated with fluid alone. Performance of CL resuscitation using continuous arterial pressure measurement was not significantly different than optimised manual treatment by a dedicated physician. Performance of CL resuscitation was reduced with discontinuous arterial pressure measurements in comparison with continuous arterial pressure measurements., (© 2020. Springer Nature B.V.)

Purpose: Examine effects of dexmedetomidine on bladder urinary oxygen tension (PuO 2 ) in critically ill patients and delineate mechanisms in an ovine model., Materials and Methods: In 12 critically ill patients: oxygen-sensing probe inserted in the bladder catheter and dexmedetomidine infusion at a mean (SD) rate of 0.9 ± 0.3 μg/kg/h for 24-h. In 9 sheep: implantation of flow probes around the renal and pulmonary arteries, and oxygen-sensing probes in the renal cortex, renal medulla and bladder catheter; dexmedetomidine infusion at 0.5 μg/kg/h for 4-h and 1.0 μg/kg/h for 4-h then 16 h observation., Results: In patients, dexmedetomidine decreased bladder PuO 2 at 2 (-Δ11 (95% CI 7-16)mmHg), 8 (-Δ 7 (0.1-13)mmHg) and 24 h (-Δ 11 (0.4-21)mmHg). In sheep, dexmedetomidine at 1 μg/kg/h reduced renal medullary oxygenation (-Δ 19 (14-24)mmHg) and bladder PuO 2 (-Δ 12 (7-17)mmHg). There was moderate correlation between renal medullary oxygenation and bladder PuO 2 ; intraclass correlation co-efficient 0.59 (0.34-0.80). Reductions in renal medullary oxygenation were associated with reductions in blood pressure, cardiac output and renal blood flow (P < 0.01)., Conclusions: Dexmedetomidine decreases PuO 2 in critically ill patients and in sheep. In sheep this reflects a decrease in renal medullary oxygenation, associated with reductions in cardiac output, blood pressure and renal blood flow., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/objective: Dysnatremia is common in severe traumatic brain injury (TBI) patients and may contribute to mortality. However, serum sodium variability has not been studied in TBI patients. We hypothesized that such variability would be independently associated with mortality., Methods: We collected 6-hourly serum sodium levels for the first 7 days of ICU admission from 240 severe TBI patients in 14 neurotrauma ICUs in Europe and Australia. We evaluated the association between daily serum sodium standard deviation (dNa SD ), an index of variability, and 28-day mortality., Results: Patients were 46 ± 19 years of age with a median initial GCS of 6 [4-8]. Overall hospital mortality was 28%. Hypernatremia and hyponatremia occurred in 64% and 24% of patients, respectively. Over the first 7 days in ICU, serum sodium standard deviation was 2.8 [2.0-3.9] mmol/L. Maximum daily serum sodium standard deviation (dNa SD ) occurred at a median of 2 [1-4] days after admission. There was a significant progressive decrease in dNa SD over the first 7 days (coefficient - 0.15 95% CI [- 0.18 to - 0.12], p < 0.001). After adjusting for baseline TBI severity, diabetes insipidus, the use of osmotherapy, the occurrence of hypernatremia, and hyponatremia and center, dNa SD was significantly independently associated with 28-day mortality (HR 1.27 95% CI (1.01-1.61), p = 0.048)., Conclusions: Our study demonstrates that daily serum sodium variability is an independent predictor of 28-day mortality in severe TBI patients. Further prospective investigations are necessary to confirm the significance of sodium variability in larger cohorts of TBI patients and test whether attenuating such variability confers outcome benefits to such patients.

Objectives: To describe the hemodynamic response to fluid boluses for hypotension in children in a cardiac ICU., Design: A prospective, observational study., Setting: Single-centered cardiac ICU., Patients: Children in a cardiac ICU with hypotension., Interventions: Clinician prescribed fluid bolus., Measurements and Main Results: Sixty-four fluid boluses were administered to 52 children. Fluid composition was 4% albumin in 36/64 (56%), 0.9% saline in 18/64 (28%), and cardiopulmonary bypass pump blood in 10/64 (16%). The median volume and duration were 5.0 mL/kg (interquartile range, 4.8-5.4) and 8 minutes (interquartile range, 4-19), respectively. Hypovolemia/low filling pressures was the most common additional indication (25/102 [25%]). Mean arterial pressure response, defined as a 10% increase from baseline, occurred in 42/64 (66%) of all fluid boluses at a median time of 6 minutes (interquartile range, 4-11). Mean arterial pressure responders had a median peak increase in the mean arterial pressure of 15 mm Hg (43 mm Hg [interquartile range, 29-50 mm Hg] to 58 mm Hg [interquartile range, 49-65 mm Hg]) at 17 minutes (interquartile range, 14-24 min) compared with 4 mm Hg (48 mm Hg [interquartile range, 40-51 mm Hg] to 52 mm Hg [interquartile range, 45-56 mm Hg]) at 10 minutes (interquartile range, 3-18 min) in nonresponders. Dissipation of mean arterial pressure response, when defined as a subsequent decrement in mean arterial pressure below 10%, 5%, and 2% increases from baseline, occurred in 28/42 (67%), 18/42 (43%), and 13/42 (31%) of mean arterial pressure responders, respectively. Cardiopulmonary bypass pump blood was strongly associated with peak change in mean arterial pressure from baseline (coefficient 11.0 [95% CI, 4.3-17.7]; p = 0.02). Fifty out of 64 (78%) were receiving a vasoactive agent. However, change in vasoactive inotrope score was not associated with change in mean arterial pressure (coefficient 2.3 [95% CI, -2.5 to -7.2]; p = 0.35). Timing from admission, nor fluid bolus duration, influenced mean arterial pressure response., Conclusions: In children with hypotension in a cardiac ICU, the median dose and duration of fluid boluses were 5 mL/kg and 8 minutes. Peak response occurred shortly following administration and commonly returned to baseline., Competing Interests: Dr. Harrois received funding from Edwards Company (educational courses). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Viral respiratory infections are the main causes of asthma exacerbation. The susceptibility of patients with asthma to develop an exacerbation when they present with severe pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. The objective of this study was to investigate the characteristics and outcomes of asthmatic patients with coronavirus disease 2019 (COVID-19) pneumonia who required hospitalisation during the spring 2020 outbreak in Paris, France., Methods: A prospective cohort follow-up was carried out from 15 March to 15 April 2020 in Bicêtre Hospital, University Paris-Saclay, France. All hospitalised patients with a SARS-CoV-2 infection who reported a history of asthma were included., Results: Among 768 hospitalised patients, 37 (4.8%) reported a history of asthma, which had been previously confirmed by a pulmonologist in 85% of cases. These asthmatic patients were mainly female (70%) and nonsmokers (85%), with a median age of 54 years (interquartile range (IQR) 42-67 years). None of them presented with an asthma exacerbation. 22 (59%) had major comorbidities and 31 (84%) had a body mass index ≥25 kg·m -2 . The most common comorbidities were obesity (36%), hypertension (27%) and diabetes (19%). All patients had a confirmed diagnosis of COVID-19 pneumonia on computed tomography of the chest. Eosinopenia was a typical biological feature with a median count of 0 cells·mm -3 (IQR 0-0 cells·mm -3 ). 11 patients (30%) were admitted into the intensive care unit, with three deaths (8.1%) occurring in the context of comorbidities., Conclusion: Asthma patients were not overrepresented among those with severe pneumonia due to SARS-CoV-2 infection who required hospitalisation. The worst outcomes were observed mainly in patients with major comorbidities., Competing Interests: Conflict of interest: A. Beurnier has nothing to disclose. Conflict of interest: E-M. Jutant has nothing to disclose. Conflict of interest: M. Jevnikar has nothing to disclose. Conflict of interest: A. Boucly has nothing to disclose. Conflict of interest: J. Pichon has nothing to disclose. Conflict of interest: M. Preda has nothing to disclose. Conflict of interest: M. Frank has nothing to disclose. Conflict of interest: J. Laurent has nothing to disclose. Conflict of interest: C. Richard has nothing to disclose. Conflict of interest: X. Monnet has nothing to disclose. Conflict of interest: J. Duranteau has nothing to disclose. Conflict of interest: A. Harrois has nothing to disclose. Conflict of interest: M-C. Chaumais has nothing to disclose. Conflict of interest: M-F. Bellin has nothing to disclose. Conflict of interest: N. Noël has nothing to disclose. Conflict of interest: S. Bulifon has nothing to disclose. Conflict of interest: X. Jaïs has nothing to disclose. Conflict of interest: F. Parent has nothing to disclose. Conflict of interest: A. Seferian has nothing to disclose. Conflict of interest: L. Savale has nothing to disclose. Conflict of interest: O. Sitbon reports grants, personal fees and non-financial support from Actelion Pharmaceuticals and MSD, personal fees from Acceleron Pharmaceuticals, Gossamer Bio and Ferrer, grants and personal fees from Bayer, grants from GlaxoSmithKline, outside the submitted work. Conflict of interest: D. Montani has nothing to disclose. Conflict of interest: M. Humbert reports grants, personal fees and non-financial support from GlaxoSmithKline, personal fees from AstraZeneca, Novartis, Roche, Sanofi and Teva, outside the submitted work., (Copyright ©ERS 2020.)

Patient position change and tracheal suctioning are routine interventions in mechanically ventilated traumatic brain injury (TBI) patients. We sought to better understand the impact of these interventions on intracranial pressure (ICP) and cerebral hemodynamics. We conducted a prospective study in TBI patients requiring ICP monitoring. The timing of position changes and suctioning episodes were recorded with concurrent blood pressure and ICP measurements. We collected data on 460 patient position changes and 204 suctioning episodes over 2404 h in 18 ventilated patients (mean age 34 [13] years, median Glasgow Coma Score 4 [3-7]). We recorded 24 (20-31) positioning and 11 (6-18) suctioning episodes per patient, with 54% and 39% of position changes associated with ICP ≥22 mm Hg and cerebral perfusion pressure (CPP) <60 mm Hg, respectively, and 22% and 27% of suctioning episodes associated with an ICP ≥22 mm Hg and CPP <60 mm Hg. The median change in ICP was 11 (6-16) mm Hg after position changes and 3 (1-9) mm Hg after suctioning. Reduction in CPP to <60 mm Hg lasted ≥10 min in 17% of positioning and 11% of suctioning episodes. The baseline ICP and its amplitude were both predictive of a rise in ICP ≥22 mm Hg after positioning and suctioning episodes, whereas cerebral autoregulation was not. Baseline CPP was predictive of a decrease in CPP <60 mm Hg after both interventions. Increases in ICP and reductions in CPP are common following patient positioning and tracheal suctioning episodes. Frequently, these changes are substantial and sustained.

The optimal osmotic agent to treat intracranial hypertension in patients with severe traumatic brain injury (TBI) remains uncertain. We aimed to test whether the choice of mannitol or hypertonic saline (HTS) as early (first 96 h) osmotherapy in these patients might be associated with a difference in mortality. We retrospectively analyzed data from 2015 from 14 tertiary intensive care units (ICUs) in Australia, UK, and Europe treating severe TBI patients with intracranial pressure (ICP) monitoring and compared mortality in those who received mannitol only versus HTS only. We performed multi-variable analysis adjusting for site and illness severity (Injury Severity Score, extended IMPACT score, and mean ICP over the first 96 h) using Cox proportional hazards regression. We collected data on 262 patients and compared patients who received early osmotherapy with mannitol alone ( n  = 46) with those who received HTS alone ( n  = 46). Mannitol patients were older (median age, 49.2 (19.2) vs. 40.5 (16.8) years; p  = 0.02), with higher Injury Severity Scores (42 (15.9) vs. 32.1 [11.3]; p  = 0.001), and IMPACT-TBI predicted 6-month mortality (34.5% [23-46] vs. 25% [13-38]; p  = 0.02), but had similar APACHE-II scores, and mean and maximum ICPs over the first 96 h. The unadjusted hazard ratio for in-hospital mortality in patients receiving only mannitol was 3.35 (95% confidence interval [CI], 1.60-7.03; p  = 0.001). After adjustment for key mortality predictors, the hazard ratio for in-hospital mortality in patients receiving only mannitol was 2.64 (95% CI, 0.96-7.30; p  = 0.06). The choice of early osmotherapy in severe TBI patients may affect survival, or simply reflect clinician beliefs about their different roles, and warrants controlled investigation.

Importance: The association between total prehospital time and mortality in physician-staffed trauma systems remains uncertain., Objective: To describe the association of total prehospital time and in-hospital mortality in prehospital, physician-staffed trauma systems in France, with the hypothesis that total prehospital time is associated with increased mortality., Design, Setting, and Participants: This cohort study was conducted from January 2009 to December 2016. Data for this study were derived from 2 distinct regional trauma registries in France (1 urban and 1 rural) that both have a physician-staffed emergency medical service. Consecutive adult trauma patients admitted to either of the regional trauma referral centers during the study period were included. Data analysis took place from March 2018 to September 2018., Main Outcomes and Measures: The association between death and prehospital time was assessed with a multivariable model adjusted with confounders. Total prehospital time was the primary exposure variable, recorded as the time from the arrival of the physician-led prehospital care team on scene to the arrival at the hospital. The main outcome of interest was all-cause in-hospital mortality., Results: A total of 10 216 patients were included (mean [SD] age, 41 [18] years; 7937 men [78.3%]) affected by predominantly nonpenetrating injuries (9265 [91.5%]), with a mean (SD) Injury Severity Score of 17 (14) points. Of the patients, 6737 (66.5%) had at least 1 body region with an Abbreviated Injury Scale score of 3 or more. A total of 1259 patients (12.4%) presented in shock (with systolic pressure <90 mm Hg) and 2724 (26.9%) with severe head injury (Abbreviated Injury Scale score ≥3 points). On unadjusted analysis, increasing prehospital times (in 30-minute categories) were associated with a markedly and constant increase in the risk of in-hospital death. The odds of death increased by 9% for each 10-minute increase in prehospital time (odds ratio, 1.09 [95% CI, 1.07-1.11]) and after adjustment by 4% (odds ratio, 1.04 [95% CI, 1.01-1.07])., Conclusions and Relevance: In this study, an increase in total prehospital time was associated with increasing in-hospital all-cause mortality in trauma patients at a physician-staffed emergency medical system, after adjustment for case complexity. Prehospital time is a management objective in analogy to physiological targets. These findings plead for a further streamlining of prehospital trauma care and the need to define the optimal intervention-to-time ratio.

In this road map for trauma in France, we focus on the main challenges for system implementation, surgical and radiology training and upon innovative training techniques. Regarding system organisation: procedures for triage, designation and certification of trauma centres are mandatory to implement trauma networks on a national scale. Data collection with registries must be created, with a core dataset defined and applied through all registries. Regarding surgical and radiology training, diagnostic-imaging processes should be standardised and the role of the interventional radiologist within the trauma team and the trauma network should be clearly defined. Education in surgery for trauma is crucial and recent changes in medical training in France will promote trauma surgery as a specific sub-specialty. Innovative training techniques should be implemented and be based on common objectives, scenarios and evaluation, so as to improve individual and team performances. The group formulated 14 proposals that should help to structure and improve major trauma management in France over the next 10 years., (Copyright © 2018 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion lie at opposite ends of the spectrum of disordered renal handling of water. Whereas renal retention of water insidiously causes hypotonic hyponatremia in syndrome of inappropriate antidiuretic hormone secretion, diabetes insipidus may lead to free water loss, hypernatremia, and volume depletion. Hypernatremia and hyponatremia are associated with worse outcomes and longer intensive care stays. Moreover, pathologies causing polyuria and hyponatremia in patients in intensive care may be multiple, making diagnosis challenging. We provide an approach to the diagnosis and management of these conditions in intensive care patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Tranexamic acid (TXA) use in severe trauma remains controversial notably because of concerns of the applicability of the CRASH-2 study findings in mature trauma systems. The aim of our study was to evaluate the outcomes of TXA administration in severely injured trauma patients managed in a mature trauma care system., Methods: We performed a retrospective study of data prospectively collected in the TraumaBase registry (a regional registry collecting the prehospital and hospital data of trauma patients admitted in six Level I trauma centers in Paris Area, France). In hospital mortality was compared between patients having received TXA or not in the early phase of resuscitation among those presenting an unstable hemodynamic state. Propensity score for TXA administration was calculated and results were adjusted for this score. Hemodynamic instability was defined by the need of packed red blood cells (pRBC) transfusion and/or vasopressor administration in the emergency room (ER)., Results: Among patients meeting inclusion criteria (n = 1,476), the propensity score could be calculated in 797, and survival analysis could be achieved in 684 of 797. Four hundred seventy (59%) received TXA, and 327 (41%) did not. The overall hospital mortality rate was 25.7%. There was no effect of TXA use in the whole population but mortality was lowered by the use of TXA in patients requiring pRBC transfusion in the ER (hazard ratio, 0.3; 95% confidence interval, 0.3-0.6)., Conclusion: The use of TXA in the management of severely injured trauma patients, in a mature trauma care system, was not associated with reduction in the hospital mortality. An independent association with a better survival was found in a selected population of patients requiring pRBC transfusion in the ER., Level of Evidence: Therapeutic study, level III.

Background: Early recognition of low fibrinogen concentrations in trauma patients is crucial for timely haemostatic treatment and laboratory testing is too slow to inform decision-making., Objective: To develop a simple clinical tool to predict low fibrinogen concentrations in trauma patients on arrival., Design: Retrospective cohort study., Setting: Three designated level 1 trauma centres in the Paris Region, from January 2011 to December 2013., Patients: Patients admitted in accordance with national triage guidelines for major trauma and plasma fibrinogen concentration testing on admission., Intervention: Construction of a clinical score [Fibrinogen on Admission in Trauma (FibAT) score] in a derivation cohort to predict fibrinogen plasma concentration 1.5 g l or less after multiple regressions. One point was given for each predictive factor. The score was the sum of all. Validation was performed in a separate validation cohort., Main Outcome Measure: Predictive accuracy of FibAT score., Results: In total, 2936 patients were included, 2124 in the derivation cohort and 812 in the validation cohort. In the derivation cohort, a multivariate logistic model identified the following predictive factors for plasma fibrinogen concentrations 1.5 g l or less: age less than 33 years, prehospital heart rate more than 100 beats per minute, prehospital SBP less than 100 mmHg, blood lactate concentration on admission more than 2.5 mmol l, free intraabdominal fluid on sonography, decrease in haemoglobin concentration from prehospital to admission of more than 2 g dl, capillary haemoglobin concentration on admission less than 12 g dl and temperature on admission less than 36°C. The FibAT score had an area under the receiver operating characteristic curve of 0.87 [95% confidence interval (0.86 to 0.91)] in the derivation cohort and of 0.82 (95% confidence interval (0.86 to 0.91)] in the validation cohort to predict a low plasma fibrinogen., Conclusion: The FibAT score accurately predicts plasma fibrinogen levels 1.5 g l or less on admission in trauma patients. This easy-to-use score could allow early, goal-directed therapy to trauma patients.

Purpose of Review: To review epidemiology and pathophysiology of acute kidney injury (AKI) in trauma patients and propose strategies that aim at preventing AKI after trauma., Recent Findings: AKI in trauma patients has been reported to be as frequent as 50% with an association to a prolonged length of stay and a raise in mortality. Among the specific risk factors encountered in trauma patients, hemorrhagic shock, rhabdomyolysis severity, age, and comorbidities are independently associated with AKI occurrence. Resuscitation with balanced solutes seems to have beneficial effects on renal outcome compared with NaCl 0.9%, particularly in the context of rhabdomyolysis. However, randomized clinical studies are needed to confirm this signal. Abdominal compartment syndrome (ACS) is rare but has to be diagnosed to initiate a dedicated therapy., Summary: The high incidence of AKI in trauma patients should lead to early identification of those at risk of AKI to establish a resuscitation strategy that aims at preventing AKI.

Background: Hypotensive resuscitation is the standard of care of hemorrhagic shock resuscitation. The optimal level of arterial pressure is debated and there is a lack of data on relationships between arterial pressure, microcirculation and tissue oxygenation. We investigated the relationship between mean arterial pressure, intestinal microcirculation and mucosal oxygen tension during hemorrhagic shock and resuscitation at different inspired oxygen fraction concentration., Methods: The study was divided into two phases: 32 mice were progressively exsanguinated and then transfused in mean arterial pressure (MAP)-titrated steps of 10 mm Hg. Mice were randomized to four experimental groups: a control group in which sham mice underwent a laparotomy and three interventional groups with a common phase of exsanguination followed by progressive resuscitation at three different inspired oxygen concentrations (FIO2) (15%, 30%, and 100%). Intestinal mucosal oxygenation (intestinal PO2) and microcirculatory parameters were recorded at each 10 mm Hg MAP step., Results: During exsanguination, intestinal PO2 decreased linearly with MAP levels. Microcirculatory parameters decreased nonlinearly with MAP levels while they had a linear relationship with intestinal PO2. Intestinal mucosal hypoxia (PO2 ≤ 20 mm Hg) began at a MAP of 60 mm Hg and MAP < 60 mm Hg was associated with a high percentage of animal with intestinal hypoxia (≥32%). Combination of MAP and microcirculatory parameters was superior to MAP alone at predicting mucosal oxygenation. Inversely, during resuscitation with FIO2 = 30%, the microcirculatory parameters increased linearly with MAP levels while they had a nonlinear relationship with intestinal PO2. Hypoxia (FIO2 = 15%) was poorly tolerated. In hyperoxic group (FIO2 = 100%) intestinal PO2 became significantly higher than baseline values as soon as 50 mm Hg MAP., Conclusion: During hemorrhagic shock, intestinal PO2 decreased linearly with MAP levels and microcirculatory parameters. Associating MAP and microcirculatory parameters allowed a better prediction of intestinal PO2 than MAP alone. A MAP < 60 mm Hg was associated with a high percentage of animal with intestinal hypoxia. Normoxic resuscitation (FIO2 = 30%) was sufficient to restore intestinal PO2.

In case of haemorrhage, a combination of low volume fluid resuscitation and permissive hypotension is used to avoid the adverse effects of early aggressive fluid resuscitation. During this phase, occult microvascular hypoperfusion can possibly develop over time. After controlling the bleeding, it is expected that optimization of macrocirculation will result in an improvement in microcirculation. However, this is the case only without alterations in microcirculation regulation. Haemodynamic coherence must be maintained to expect the restoration of microcirculation through systemic haemodynamic-driven resuscitation. However, haemorrhagic shock, reperfusion, traumatic injury and inflammation can damage microcirculation and thus lead to a loss of haemodynamic coherence. In these cases, a systemic haemodynamic-driven resuscitation would not be effective in restoring microcirculation and tissue oxygenation. A real-time technique enabling microcirculation monitoring can create an opportunity for microcirculatory haemodynamic-driven resuscitation to become the gold standard in the future., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Early alterations in tissue oxygenation may worsen patient outcome following traumatic haemorrhagic shock. We hypothesized that muscle oxygenation measured using near-infrared spectroscopy (NIRS) on admission could be associated with subsequent change in the SOFA score after resuscitation., Methods: The study was conducted in two Level I trauma centres and included 54 consecutive trauma patients with haemorrhagic shock, presenting within 6 hours of injury. Baseline tissue haemoglobin oxygen saturation (StO2) in the thenar eminence muscle and StO2 changes during a vascular occlusion test (VOT) were determined at 6 hours (H6) and 72 hours (H72) after the admission to the emergency room. Patients showing an improved SOFA score at H72 (SOFA improvers) were compared to those for whom it was unchanged or worse (SOFA non-improvers)., Results: Of the 54 patients, 34 patients were SOFA improvers and 20 SOFA non-improvers. They had comparable injury severity scores on admission. SOFA improvers had higher baseline StO2 values and a steeper StO2 desaturation slope at H6 compared to the SOFA non-improvers. These StO2 variables similarly correlated with the intra-hospital mortality. The StO2 reperfusion slope at H6 was similar between the two groups of patients., Conclusions: Differences in StO2 parameters on admission of traumatic haemorrhagic shock were found between patients who had an improvement in organ failure in the first 72 hours and those who had unchanged or worse conditions. The use of NIRS to guide the initial management of trauma patients with haemorrhagic shock warrants further investigations.

Pelvic trauma care is complex since it is frequently associated with multiple injuries and may lead to dramatic and uncontrollable haemorrhage. After pelvic trauma, the mortality, around 8 to 10%, is mainly related to severe pelvic hemorrhage but also to extrapelvic injuries (thoracic, abdominal or brain injuries). It is therefore crucial to manage pelvic trauma in specialized trauma center. The initial trauma assessment aims to determine the role of the pelvic injury in hemorrhage to define the therapeutic strategy of pelvic trauma care (arterial embolisation/pelvic ring stabilisation). This review was performed with a systematic review of the literature; it describes the pelvic fracture pathophysiology, and the efficacy and safety of haemostatic procedures and with their respective indications. A decision making algorithm is proposed for the treatment of trauma patients with pelvic fracture., (Copyright © 2014. Published by Elsevier SAS.)

Managing trauma patients with hemorrhagic shock is complex and difficult. Despite our knowledge of the pathophysiology of hemorrhagic shock in trauma patients that we have accumulated during recent decades, the mortality rate of these patients remains high. In the acute phase of hemorrhage, the therapeutic priority is to stop the bleeding as quickly as possible. As long as this bleeding is uncontrolled, the physician must maintain oxygen delivery to limit tissue hypoxia, inflammation, and organ dysfunction. This process involves fluid resuscitation, the use of vasopressors, and blood transfusion to prevent or correct acute coagulopathy of trauma. The optimal resuscitative strategy is controversial. To move forward, we need to establish optimal therapeutic approaches with clear objectives for fluid resuscitation, blood pressure, and hemoglobin levels to guide resuscitation and limit the risk of fluid overload and transfusion.

Endothelial activation and dysfunction play a key role in the pathogenesis of sepsis. During septic shock, endothelial dysfunction is involved in microcirculation impairment and organ dysfunction. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have several potentially important effects on endothelial function and are implicated in physiological regulation and disease pathophysiology. The imbalance between the production of ROS and their effective removal by non-enzymatic and enzymatic antioxidants systems could induce endothelial dysfunction with alterations of vascular tone, increases in cell adhesion properties (leukocytes and platelet adhesion), increase in vascular wall permeability and a pro-coagulant state. Increasing evidence supports the idea that the principal cause of EC dysfunction during sepsis is cell injury. ROS and RNS contribute to mitochondrial dysfunction by a range of mechanisms and induce both necrotic and apoptotic cell death. Understanding the mechanisms underlying the generation of ROS and RNS in endothelial cells and the causes of endothelial dysfunction in sepsis may help provide therapeutic strategies to tackle endothelial dysfunction and microcirculatory failure in sepsis.

Hemorrhagic shock generates a prolonged alteration of organ perfusion due to the decrease in oxygen delivery. Hemorrhagic shock is mainly due to three etiologies: traumatology, gastrointestinal bleeding and high risk surgery. If intensive cares are not rapidly performed, severe complications occur, as organ failure with a high mortality rate. Primary cares aim at restoring a perfusion pressure to prevent tissue hypoperfusion while waiting for the radical therapy of bleeding. Priority during initial treatment is to restore tissue perfusion and achieve haemostasis in vital functions. Fluid resuscitation and transfusion are common to every case of hemorrhagic shock but the strategy to localise the hemorrhage and stop the bleeding differs between the situations. Key factors in the management of hemorrhagic shock are the communication between surgical, anaesthetic, and critical care teams and the application of pathology.