Search

Background: Preventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition., Methods: This is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery., Results: Among 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56; 1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95% CI] 0.34 [0.13-0.86])., Conclusions: A single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916)., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Postoperative pulmonary complications after major abdominal surgery are frequent and carry high morbidity and mortality. Early identification of patients at risk of pulmonary complications by lung ultrasound may allow the implementation of preemptive strategies. The authors hypothesized that lung ultrasound score would be associated with pulmonary postoperative complications. The main objective of the study was to evaluate the performance of lung ultrasound score on postoperative day 1 in predicting pulmonary complications after major abdominal surgery. Secondary objectives included the evaluation of other related measures for their potential prediction accuracy., Methods: A total of 149 patients scheduled for major abdominal surgery were enrolled in a bicenter observational study. Lung ultrasound score was performed before the surgery and on days 1, 4, and 7 after surgery. Pulmonary complications occurring before postoperative day 10 were recorded., Results: Lung ultrasound score on postoperative day 1 was higher in patients developing pulmonary complications before day 10 (median, 13; interquartile range, 8.25 to 18; vs. median, 10; interquartile range, 6.5 to 12; Mann-Whitney P = 0.002). The area under the curve for predicting postoperative pulmonary complications before day 10 was 0.65 (95% CI, 0.55 to 0.75; P = 0.003). Lung ultrasound score greater than 12 had a sensitivity of 0.54 (95% CI, 0.40 to 0.67), specificity of 0.77 (95% CI, 0.67 to 0.85), and negative predictive value of 0.74 (95% CI, 0.65 to 0.83). Lung ultrasound score greater than 17 had sensitivity of 0.33 (95% CI, 0.21 to 0.47), specificity of 0.95 (95% CI, 0.88 to 0.98), and positive predictive value of 0.78 (95% CI, 0.56 to 0.93). Anterolateral lung ultrasound score and composite scores using lung ultrasound score and other patient characteristics showed similar predictive accuracies., Conclusions: An elevated lung ultrasound score on postoperative day 1 is associated with the occurrence of pulmonary complications within the first 10 days after major abdominal surgery., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Background: Current guidelines suggest the introduction of early nutrition support within the first 48 h of admission to the intensive care unit (ICU) for patients who cannot eat. In that context, we aimed to describe nutrition practices in the ICU and study the association between the introduction of early nutrition support (< 48 h) in the ICU and patient mortality at day 28 (D28) using data from a multicentre prospective cohort., Methods: The 'French-Speaking ICU Nutritional Survey' (FRANS) study was conducted in 26 ICUs in France and Belgium over 3 months in 2015. Adult patients with a predicted ICU length of stay > 3 days were consecutively included and followed for 10 days. Their mortality was assessed at D28. We investigated the association between early nutrition (< 48 h) and mortality at D28 using univariate and multivariate propensity-score-weighted logistic regression analyses., Results: During the study period, 1206 patients were included. Early nutrition support was administered to 718 patients (59.5%), with 504 patients receiving enteral nutrition and 214 parenteral nutrition. Early nutrition was more frequently prescribed in the presence of multiple organ failure and less frequently in overweight and obese patients. Early nutrition was significantly associated with D28 mortality in the univariate analysis (crude odds ratio (OR) 1.69, 95% confidence interval (CI) 1.23-2.34) and propensity-weighted multivariate analysis (adjusted OR (aOR) 1.05, 95% CI 1.00-1.10). In subgroup analyses, this association was stronger in patients ≤ 65 years and with SOFA scores ≤ 8. Compared with no early nutrition, a significant association was found of D28 mortality with early enteral (aOR 1.06, 95% CI 1.01-1.11) but not early parenteral nutrition (aOR 1.04, 95% CI 0.98-1.11)., Conclusions: In this prospective cohort study, early nutrition support in the ICU was significantly associated with increased mortality at D28, particularly in younger patients with less severe disease. Compared to no early nutrition, only early enteral nutrition appeared to be associated with increased mortality. Such findings are in contrast with current guidelines on the provision of early nutrition support in the ICU and may challenge our current practices, particularly concerning patients at low nutrition risk. Trial registration ClinicalTrials.gov Identifier: NCT02599948. Retrospectively registered on November 5th 2015., (© 2023. The Author(s).)

Background: In intensive care units, patients are frequently unable to take oral drugs because of orotracheal intubation or sedation., Local Problem: Adverse events occurred during the administration of drugs by feeding tube. This study assessed the impact of implementing good practice guidelines by a clinical pharmacist on the prescription and administration of drugs through feeding tubes., Methods: Nonconformity of drug prescription and administration in patients with feeding tubes was assessed before and after implementation of good practice guidelines in the intensive care unit of a large teaching hospital. Data were collected from medical records and interviews with physicians and nurses using a standardized form. Assessment of prescription nonconformity included compatibility of a drug's absorption site with the administration route. Assessment of administration nonconformity included the preparation method., Results: The analysis included 288 prescriptions and 80 administrations before implementation and 385 prescriptions and 211 administrations after implementation. Prescriptions in which the drug's absorption site was not compatible with the administration route decreased significantly after implementation (19.8% vs 7.5%, P < .01). Administration nonconformity decreased significantly in regard to crushing tablets and opening capsules (51.2% vs 4.3%, P < .01) and the solvent used (67.1% vs 3.5%, P < .01). Simultaneous mixing of drugs in the same syringe did not decrease significantly (71.2% vs 62.9%, P = .17)., Conclusion: Implementation of good practice guidelines by a multidisciplinary team in the intensive care unit significantly improved practices for administering crushed, opened, and dissolved oral forms of drugs by feeding tube., (©2022 American Association of Critical-Care Nurses.)

Sepsis is defined as a dysregulated host response to infection leading to organs failure. Among them, sepsis induces skeletal muscle (SM) alterations that contribute to acquired-weakness in critically ill patients. Proteomics and metabolomics could unravel biological mechanisms in sepsis-related organ dysfunction. Our objective was to characterize a distinctive signature of septic shock in human SM by using an integrative multi-omics approach. Muscle biopsies were obtained as part of a multicenter non-interventional prospective study. Study population included patients in septic shock (S group, with intra-abdominal source of sepsis) and two critically ill control populations: cardiogenic shock (C group) and brain dead (BD group). The proteins and metabolites were extracted and analyzed by High-Performance Liquid Chromatography-coupled to tandem Mass Spectrometry, respectively. Fifty patients were included, 19 for the S group (53% male, 64 ± 17 years, SAPS II 45 ± 14), 12 for the C group (75% male, 63 ± 4 years, SAPS II 43 ± 15), 19 for the BD group (63% male, 58 ± 10 years, SAPS II 58 ± 9). Biopsies were performed in median 3 days [interquartile range 1-4]) after intensive care unit admission. Respectively 31 patients and 40 patients were included in the proteomics and metabolomics analyses of 2264 proteins and 259 annotated metabolites. Enrichment analysis revealed that mitochondrial pathways were significantly decreased in the S group at protein level: oxidative phosphorylation (adjusted p = 0.008); branched chained amino acids degradation (adjusted p = 0.005); citrate cycle (adjusted p = 0.005); ketone body metabolism (adjusted p = 0.003) or fatty acid degradation (adjusted p = 0.008). Metabolic reprogramming was also suggested (i) by the differential abundance of the peroxisome proliferator-activated receptors signaling pathway (adjusted p = 0.007), and (ii) by the accumulation of fatty acids like octanedioic acid dimethyl or hydroxydecanoic. Increased polyamines and depletion of mitochondrial thioredoxin or mitochondrial peroxiredoxin indicated a high level of oxidative stress in the S group. Coordinated alterations in the proteomic and metabolomic profiles reveal a septic shock signature in SM, highlighting a global impairment of mitochondria-related metabolic pathways, the depletion of antioxidant capacities, and a metabolic shift towards lipid accumulation.ClinicalTrial registration: NCT02789995. Date of first registration 03/06/2016., (© 2022. The Author(s).)

Background: Although predictive models have already integrated demographic factors and comorbidities as risk factors for a prolonged hospital stay, factors related to anaesthesia management in ambulatory surgery have not been yet characterized. This study aims to identify anaesthetic factors associated with a prolonged discharge time in ambulatory surgery., Methods: All clinical records of patients who underwent ambulatory cholecystectomy in a French University Hospital (Hôpital Saint Antoine, Paris) between January 1st, 2012 and December 31st, 2018 were retrospectively reviewed. The primary endpoint was the discharge time, defined as the time between the end of surgery and discharge. A multivariable Cox proportional-hazards model was fitted to investigate the factors associated with a prolonged discharge time., Results: Five hundred and thirty-five (535) patients were included. The median time for discharge was 150 min (interquartile range - IQR [129-192]). A bivariable analysis highlighted a positive correlation between discharge timeline and the doses-weight of ketamine and sufentanil. In the multivariable Cox proportional hazards model analysis, the anaesthesia-related factors independently associated with prolonged discharge time were the dose-weight of ketamine in interaction with the dose weight of sufentanil (HR 0.10 per increment of 0.1 mg/kg of ketamine or 0.2 μg/kg of sufentanil, CI 95% [0.01-0.61], p = 0.013) and the non-use of a non-steroidal anti-inflammatory drug (NSAID) (HR 0.81 [0.67-0.98], p = 0.034). Twenty patients (4%) had unscheduled hospitalization following surgery., Conclusion: Anaesthesia management, namely the use of ketamine and the non-use of NSAID, affects time to hospital discharge., (Copyright © 2022 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: We aimed to assess the incidence and the risk factors for secondary wound infections associated to high-energy ammunition injuries (HEAI) in the cohort of civilian casualties from the 2015 terrorist attacks in Paris., Methods: This retrospective multi-centric study included casualties presenting at least one HEAI who underwent surgery during the first 48 h following hospital admission. HEAI-associated infection was defined as a wound infection occurring within the initial 30 days following trauma. Risk factors were assessed using univariate and multivariate analysis., Results: Among the 200 included victims, the rate of infected wounds was 11.5%. The median time between admission and the surgical revision for secondary wound infection was 11 days [IQR 9-20]. No patient died from an infectious cause. Infections were polymicrobial in 44% of the cases. The major risk factors for secondary wound infection were ISS (p < 0.001), SAPS II (p < 0.001), MGAP (p < 0.001), haemorrhagic shock (p = 0.003), use of vasopressors (p < 0.001), blood transfusion (p < 0.001), abdominal penetrating trauma (p = 0.003), open fracture (p = 0.01), vascular injury (p = 0.001), duration of surgery (p = 0.009), presence of surgical material (p = 0.01). In the multivariate analysis, the SAPS II score (OR 1.07 [1.014-1.182], p = 0.019) and the duration of surgery (OR 1.005 [1.000-1.012], p = 0.041) were the only risk factors identified., Conclusion: We report an 11.5% rate of secondary wound infection following high-energy ammunition injuries. Risk factors were an immediately severe condition and a prolonged surgery., (Copyright © 2021 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Regional anesthesia (RA) is an anesthetic technique essential for the performance of ambulatory surgery. Failure rates range from 6% to 20%, and the consequences of these failures have been poorly investigated. We determined the incidence and the impact of regional block failure on patient management in the ambulatory setting. This retrospective cohort study includes all adult patients who were admitted to a French University Hospital (Hôpital Saint-Antoine, AP-HP) between 1 January 2016 and 31 December 2017 for unplanned ambulatory distal upper limb surgery. Univariate and stepwise multivariate analyses were performed to determine factors associated with block failure. Among the 562 patients included, 48 (8.5%) had a block failure. RA failure was associated with a longer surgery duration ( p = 0.02), more frequent intraoperative analgesics administration ( p < 0.01), increased incidence of unplanned hospitalizations ( p < 0.001), and a 39% prolongation of Post-Anesthesia Care Unit (PACU) length of stay ( p < 0.0001). In the multivariate analysis, the risk factors associated with block failure were female sex ( p = 0.04), an American Society of Anesthesiologists (ASA) score > 2 ( p = 0.03), history of substance abuse ( p = 0.01), and performance of the surgery outside of the specific ambulatory surgical unit ( p = 0.01). Here, we have documented a significant incidence of block failure in ambulatory hand surgery, with impairment in the organization of care. Identifying patients at risk of failure could help improve their management, especially by focusing on providing care in a dedicated ambulatory circuit.

Objective: Anemia is very common in critical care patients, on admission (affecting about two-thirds of patients), but also during and after their stay, due to repeated blood loss, the effects of inflammation on erythropoiesis, a decreased red blood cell life span, and haemodilution. Anemia is associated with severity of illness and length of stay., Methods: A committee composed of 16 experts from four scientific societies, SFAR, SRLF, SFTS and SFVTT, evaluated three fields: (1) anemia prevention, (2) transfusion strategies and (3) non-transfusion treatment of anemia. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE ® methodology., Results: The SFAR-SRLF guideline panel provided ten statements concerning the management of anemia in adult critical care patients. Acute haemorrhage and chronic anemia were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for ten recommendations. Three of these recommendations had a high level of evidence (GRADE 1±) and four had a low level of evidence (GRADE 2±). No GRADE recommendation could be provided for two questions in the absence of strong consensus., Conclusions: The experts reached a substantial consensus for several strong recommendations for optimal patient management. The experts recommended phlebotomy reduction strategies, restrictive red blood cell transfusion and a single-unit transfusion policy, the use of red blood cells regardless of storage time, treatment of anaemic patients with erythropoietin, especially after trauma, in the absence of contraindications and avoidance of iron therapy (except in the context of erythropoietin therapy).

Purpose: The reduction of length of hospitalization without compromising the patient's safety constitutes the challenge of the enhanced recovery after surgery (ERAS) programs. Our aim was to evaluate the feasibility and safety of a 3-day hospitalization after colectomy and 5-day hospitalization after proctectomy in the setting of an ERAS program., Methods: An ERAS program was prospectively proposed to all patients who required a colorectal resection (January 2014-December 2018) with a 3- or 5-day discharge objective. The success of the program was defined by a 3-/5-day hospitalization without complications and without readmissions., Results: Among 283 patients included, 232 patients had a colectomy (82%) and 51 (18%) patients a proctectomy. Eighty-six patients experienced complications (30%) including fifteen severe complications (5%). Mean hospital stay was 5.1 ± 3.7 (2-33) days. A total of 136 patients (48%) were discharged at 3-/5-day, within 9 were readmitted (3%). Discharge was delayed after 3-/5-day for complications (n = 65, 23%), CRP > 120 (n = 45, 16%) or refusal without medical reason (n = 37, 13%). The success rate of the program was 45% (n = 127). This success rate was similar between colectomy and proctectomy (p = 0.277) and between right and left colectomy (p = 0.450). In multivariate analysis, predictive factors associated with the program success were intraoperative use of lidocaine (OR 2.1 [1.1-4.1], p = 0.022), time to remove perfusion ≤ 2 days (OR 10.3 [5.4-19.6], p = 0.001), time to recover bowel movement ≤ 2 days (OR 4.0 [1.7-9.6], p = 0.002) and time to walk out of the room ≤ 2 days (OR 2.6 [1.1-6.0], p = 0.022)., Conclusion: Integrating a realistic hospitalization duration objective into an ERAS program guarantees its safety, feasibility and effectiveness in reducing hospitalization duration.

Background: Acute diverticulitis is a common disease with public health significance. Many studies with a high level of evidence have been published recently on the surgical management of acute diverticulitis., Objective: The aim of this systematic review was to define the accurate surgical management of acute diverticulitis., Data Sources: Medline, Embase, and the Cochrane Library were sources used., Study Selection: One reviewer conducted a systematic study with combinations of key words for the disease and the surgical procedure. Additional studies were searched in the reference lists of all included articles. The results of the systematic review were submitted to a working group composed of 13 practitioners. All of the conclusions were obtained by full consensus and validated by an external committee., Interventions: The interventions assessed were laparoscopic peritoneal lavage, primary resection with anastomosis with or without ileostomy, and the Hartmann procedure, with either a laparoscopic or an open approach., Main Outcome Measures: Morbidity, mortality, long-term stoma rates, and quality of life were measured., Results: Seventy-one articles were included. Five guidelines were retrieved, along with 4 meta-analyses, 14 systematic reviews, and 5 randomized controlled trials that generated 8 publications, all with a low risk of bias, except for blinding. Laparoscopic peritoneal lavage showed concerning results of deep abscesses and unplanned reoperations. Studies on Hinchey III/IV diverticulitis showed similar morbidity and mortality. A reduced length of stay with Hartmann procedure compared with primary resection with anastomosis was reported in the short term, and in the long term, more definite stoma along with poorer quality of life was reported with Hartmann procedure. No high-quality data were found to support the laparoscopic approach., Limitations: Trials specifically assessing Hinchey IV diverticulitis have not yet been completed., Conclusions: High-quality studies showed that laparoscopic peritoneal lavage was associated with an increased morbidity and that Hartmann procedure was associated with poorer long-term outcomes than primary resection with anastomosis with ileostomy, but Hartmann procedure is still acceptable, especially in high-risk patients.

Importance: It is not known if use of colloid solutions containing hydroxyethyl starch (HES) to correct for intravascular deficits in high-risk surgical patients is either effective or safe., Objective: To evaluate the effect of HES 130/0.4 compared with 0.9% saline for intravascular volume expansion on mortality and postoperative complications after major abdominal surgery., Design, Setting, and Participants: Multicenter, double-blind, parallel-group, randomized clinical trial of 775 adult patients at increased risk of postoperative kidney injury undergoing major abdominal surgery at 20 university hospitals in France from February 2016 to July 2018; final follow-up was in October 2018., Interventions: Patients were randomized to receive fluid containing either 6% HES 130/0.4 diluted in 0.9% saline (n = 389) or 0.9% saline alone (n = 386) in 250-mL boluses using an individualized hemodynamic algorithm during surgery and for up to 24 hours on the first postoperative day, defined as ending at 7:59 am the following day., Main Outcomes and Measures: The primary outcome was a composite of death or major postoperative complications at 14 days after surgery. Secondary outcomes included predefined postoperative complications within 14 days after surgery, durations of intensive care unit and hospital stays, and all-cause mortality at postoperative days 28 and 90., Results: Among 826 patients enrolled (mean age, 68 [SD, 7] years; 91 women [12%]), 775 (94%) completed the trial. The primary outcome occurred in 139 of 389 patients (36%) in the HES group and 125 of 386 patients (32%) in the saline group (difference, 3.3% [95% CI, -3.3% to 10.0%]; relative risk, 1.10 [95% CI, 0.91-1.34]; P = .33). Among 12 prespecified secondary outcomes reported, 11 showed no significant difference, but a statistically significant difference was found in median volume of study fluid administered on day 1: 1250 mL (interquartile range, 750-2000 mL) in the HES group and 1500 mL (interquartile range, 750-2150 mL) in the saline group (median difference, 250 mL [95% CI, 83-417 mL]; P = .006). At 28 days after surgery, 4.1% and 2.3% of patients had died in the HES and saline groups, respectively (difference, 1.8% [95% CI, -0.7% to 4.3%]; relative risk, 1.76 [95% CI, 0.79-3.94]; P = .17)., Conclusions and Relevance: Among patients at risk of postoperative kidney injury undergoing major abdominal surgery, use of HES for volume replacement therapy compared with 0.9% saline resulted in no significant difference in a composite outcome of death or major postoperative complications within 14 days after surgery. These findings do not support the use of HES for volume replacement therapy in such patients., Trial Registration: ClinicalTrials.gov Identifier: NCT02502773.

When used as an add-on to regional anesthesia, virtual reality (VR) has been reported to provide anxiety-reducing benefits and sedation-sparing effects. However, its impact on patient satisfaction is still a matter of controversy. We investigated the feasibility and benefits of implementing intraoperative VR distraction in a French University Hospital (Hôpital Saint-Antoine, AP-HP). This monocentric observational before-after study included 100 patients who underwent ambulatory upper limb surgery under peripheral nerve block in January 2019, 50 before and 50 after implementation of an intraoperative VR distraction protocol. Primary outcome was patient self-rated satisfaction score evaluated right after surgery. Secondary outcomes included 2-month patient-reported satisfaction score, perioperative self-rated anxiety and intraoperative hemodynamic changes. Compared to former standard care, VR distraction was associated with significantly higher postoperative satisfaction scores (10 [IQR 9; 10] vs. 9 [8; 10], p < 0.001) still reported two months after surgery (10 [10;10] vs. 10 [8.5;10], p = 0.06). Patient median intraoperative anxiety score was lower in the VR group, compared to Standard Care group (0 [0; 2] vs. 3 [0.25; 7], p < 0.001), and occurrence of intraoperative hemodynamic changes was also lessened in the VR group (2% vs. 16%, 0R = 0.11[95% CI 0.002-0.87], p = 0.031). The present findings suggest that VR distraction program in the operating room could effectively improve patient satisfaction with anxiety-reduction and hemodynamic benefits.

Background: Recent international guidelines for acute pancreatitis (AP) recommend limiting anti-infective therapy (AIT) to cases of suspected necrotizing AP or nosocomial extrapancreatic infection. Limited data are available concerning empirical and documented AIT prescribing practices in patients admitted to the intensive care unit (ICU) for the management of AP., Methods: Using a multicentre, retrospective (2009-2014), observational database of ICU patients admitted for AP, our primary objective was to assess the incidence of AIT prescribing practices during the first 30 days following admission. Secondary objectives were to assess the independent impact of centre characteristics on the incidence of AIT and to identify factors associated with crude hospital mortality in a logistic regression model., Results: In this cohort of 860 patients, 359 (42%) received AIT on admission. Before day 30, 340/359 (95%) AIT patients and 226/501 (45%) AIT-free patients on admission received additional AIT, mainly for intra-abdominal and lung infections. A large heterogeneity was observed between centres in terms of the incidence of infections, therapeutic management including AIT and prognosis. Administration of AIT on admission or until day 30 was not associated with an increased mortality rate. Patients receiving AIT on admission had increased rates of complications (septic shock, intra-abdominal and pulmonary infections), therapeutic (surgical, percutaneous, endoscopic) interventions and increased length of ICU stay compared to AIT-free patients. Patients receiving delayed AIT after admission and until day 30 had increased rates of complications (respiratory distress syndrome, intra-abdominal and pulmonary infections), therapeutic interventions and increased length of ICU stay compared to those receiving AIT on admission. Risk factors for hospital mortality assessed on admission were age (adjusted odds ratio [95% confidence interval] 1.03 [1.02-1.05]; p < 0.0001), Balthazar score E (2.26 [1.43-3.56]; p < 0.0001), oliguria/anuria (2.18 [1.82-4.33]; p < 0.0001), vasoactive support (2.83 [1.73-4.62]; p < 0.0001) and mechanical ventilation (1.90 [1.15-3.14]; p = 0.011), but not AIT (0.63 [0.40-1.01]; p = 0.057)., Conclusions: High proportions of ICU patients admitted for AP receive AIT, both on admission and during their ICU stay. A large heterogeneity was observed between centres in terms of incidence of infections, AIT prescribing practices, therapeutic management and outcome. AIT reflects the initial severity and complications of AP, but is not a risk factor for death.

Background: No evidence exists to date on which to base the selection of outcome measures for assessing nutritional interventions in critically ill patients. We conducted a systematic literature review to describe the outcomes used in recent randomised controlled trials (RCTs) assessing nutritional interventions in critically ill patients. Our objective was to set the foundation for the development of a core set of outcome measures for use in future RCTs., Methods: We searched the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for RCTs of nutritional interventions in critically ill patients aged 18 years or older, published and/or registered between January 2000 and August 2018. Outcomes were divided into six categories (mortality, length of stay, duration of organ dysfunction, complications, functional outcomes, and others) and analysed according to the study characteristics and publication year., Results: Of the 885 references retrieved, 170 were included in the review. Of these, 136 (80%) defined a primary outcome, 114 (67%) defined secondary outcomes (two per study on average), and 34 (20%) did not specify whether outcomes were primary or secondary. We identified 24 different outcomes in all, of which 19 were primary. Complications were the most widely used primary outcome (65/136, 48%). Mortality was the primary outcome in 17/136 (13%) studies, with six different timepoints. The main secondary outcomes were length of stay (90/114, 79%), mortality (82/114, 72%), and duration of organ dysfunction (75/114, 65%)., Conclusions: This systematic review highlights the heterogeneity of outcomes used in recent randomized controlled trials evaluating nutritional interventions in critically ill patients. The results of our systematic review may have implications for designing future RCTs of nutritional interventions in the ICU.

Background: Muscle wasting in critically ill patients is associated with negative clinical outcomes. Ultrasound quadriceps femoris muscle assessment may constitute a convenient tool to evaluate muscle wasting. Nevertheless, its reliability remains uncertain. Our primary aim was to study the intra- and inter-observer reliability of this technique. Our secondary aim was to assess the evolution of the quadriceps muscle during the first 3 weeks after ICU admission and its possible association with nutritional intake., Methods: This observational study included patients expected to stay more than 7 days in the ICU. Ultrasound quadriceps muscle thickness was measured with a 12 MHz linear transducer, by two trained physicians, on D1, D3, D5, D7 and D21. Two measurements sites were evaluated: on the midpoint or on the two-thirds of the length between the anterior superior iliac spine and the upper border of the patella. Intra and inter-observer reliability was assessed by calculating the intra-class correlation coefficient (ICC)., Results: A total of 280 ultrasound quadriceps thickness measurements were performed on 29 critically ill patients. Intra-observer reliability's ICC was 0.74 [95% CI 0.63; 0.84] at the "midpoint" site and 0.83 [95% CI 0.75; 0.9] at the "two-thirds" site. Inter-observer reliability's ICC was 0.76 [95% CI, 0.66; 0.86] at the "midpoint" site and 0.81 [95% CI, 0.7; 0.9] at the "two-thirds" site. Quadriceps femoris muscle thickness decreased over 16% within the first week after ICU admission. No correlation was found between muscle loss and caloric (p = 0.96) or protein (p = 0.80) debt over the first week., Conclusion: The assessment by ultrasonography of the quadriceps muscle thickness reveals good intra- and inter-observer reliability and may constitute a promising tool to evaluate the effect of nutritional-based interventions on muscle wasting in critically ill patients., Trial Registration: "Committee for the Protection of Human Subjects in Biomedical Research" - Paris Ile de France VI Pitié-Salpêtrière - 10/07/2014. French Data Protection Committee ("Commission Nationale Informatique et Libertés") - #1771144.

Background: Infected pancreatic necrosis, which occurs in about 40% of patients admitted for acute necrotizing pancreatitis, requires combined antibiotic therapy and local drainage. Since 2010, drainage by open surgical necrosectomy has been increasingly replaced by less invasive methods such as percutaneous radiological drainage, endoscopic necrosectomy, and laparoscopic surgery, which proved effective in small randomized controlled trials in highly selected patients. Few studies have evaluated minimally invasive drainage methods used under the conditions of everyday hospital practice. The aim of this study was to determine whether, compared with conventional open surgery, minimally invasive drainage was associated with improved outcomes of critically ill patients with infection complicating acute necrotizing pancreatitis., Methods: A single-center observational study was conducted in patients admitted to the intensive care unit for severe acute necrotizing pancreatitis to compare the characteristics, drainage techniques, and outcomes of the 62 patients managed between September 2006 and December 2010, chiefly with conventional open surgery, and of the 81 patients managed between January 2011 and August 2015 after the introduction of a minimally invasive drainage protocol., Results: Surgical necrosectomy was more common in the early period (74% versus 41%; P <0.001), and use of minimally invasive drainage increased between the early and late periods (19% and 52%, respectively; P <0.001). The numbers of ventilator-free days and catecholamine-free days by day 30 were higher during the later period. The proportions of patients discharged from intensive care within the first 30 days and from the hospital within the first 90 days were higher during the second period. Hospital mortality was not significantly different between the early and late periods (19% and 22%, respectively)., Conclusion: In our study, the implementation of a minimally invasive drainage protocol in patients with infected pancreatic necrosis was associated with shorter times spent with organ dysfunction, in the intensive care unit, and in the hospital. Mortality was not significantly different. These results should be interpreted bearing in mind the limitations inherent in the before-after study design.

Background: Postoperative peritonitis (POP) following gastrointestinal surgery is associated with significant morbidity and mortality, with no clear management option proposed. The aim of this study was to report our surgical management of POP and identify pre- and perioperative risk factors for morbidity and mortality., Methods: All patients with POP undergoing relaparotomy in our department between January 2004 and December 2013 were included. Pre- and perioperative data were analyzed to identify predictors of morbidity and mortality., Results: A total of 191 patients required relaparotomy for POP, of which 16.8% required >1 reinterventions. The commonest cause of POP was anastomotic leakage (66.5%) followed by perforation (20.9%). POP was mostly treated by anastomotic takedown (51.8%), suture with derivative stoma (11.5%), enteral resection and stoma (12%), drainage of the leak (8.9%), stoma on perforation (8.4%), duodenal intubation (7.3%) or intubation of the leak (3.1%). The overall mortality rate was 14%, of which 40% died within the first 48 h. Major complications (Dindo-Clavien > 2) were seen in 47% of the cohort. Stoma formation occurred in 81.6% of patients following relaparotomy. Independent risk factors for mortality were: ASA > 2 (OR = 2.75, 95% CI = 1.07-7.62, p = 0.037), multiorgan failure (MOF) (OR = 5.22, 95% CI = 2.11-13.5, p = 0.0037), perioperative transfusion (OR = 2.7, 95% CI = 1.05-7.47, p = 0.04) and upper GI origin (OR = 3.55, 95% CI = 1.32-9.56, p = 0.013). Independent risk factors for morbidity were: MOF (OR = 2.74, 95% CI = 1.26-6.19, p = 0.013), upper GI origin (OR = 3.74, 95% CI = 1.59-9.44, p = 0.0034) and delayed extubation (OR = 0.27, 95% CI = 0.14-0.55, p = 0.0027)., Conclusion: Mortality following POP remains a significant issue; however, it is decreasing due to effective and aggressive surgical intervention. Predictors of poor outcomes will help tailor management options.

Background: Acute acidaemia is frequently observed during critical illness. Sodium bicarbonate infusion for the treatment of severe metabolic acidaemia is a possible treatment option but remains controversial, as no studies to date have examined its effect on clinical outcomes. Therefore, we aimed to evaluate whether sodium bicarbonate infusion would improve these outcomes in critically ill patients., Methods: We did a multicentre, open-label, randomised controlled, phase 3 trial. Local investigators screened eligible patients from 26 intensive care units (ICUs) in France. We included adult patients (aged ≥18 years) who were admitted within 48 h to the ICU with severe acidaemia (pH ≤7·20, PaCO 2 ≤45 mm Hg, and sodium bicarbonate concentration ≤20 mmol/L) and with a total Sequential Organ Failure Assessment score of 4 or more or an arterial lactate concentration of 2 mmol/L or more. We randomly assigned patients (1:1), by stratified randomisation with minimisation via a restricted web platform, to receive either no sodium bicarbonate (control group) or 4·2% of intravenous sodium bicarbonate infusion (bicarbonate group) to maintain the arterial pH above 7·30. Our protocol recommended that the volume of each infusion should be within the range of 125-250 mL in 30 min, with a maximum of 1000 mL within 24 h after inclusion. Randomisation criteria were stratified among three prespecified strata: age, sepsis status, and the Acute Kidney Injury Network (AKIN) score. The primary outcome was a composite of death from any cause by day 28 and the presence of at least one organ failure at day 7. All analyses were done on data from the intention-to-treat population, which included all patients who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02476253., Findings: Between May 5, 2015, and May 7, 2017, we enrolled 389 patients into the intention-to-treat analysis in the overall population (194 in the control group and 195 in the bicarbonate group). The primary outcome occurred in 138 (71%) of 194 patients in the control group and 128 (66%) of 195 in the bicarbonate group (absolute difference estimate -5·5%, 95% CI -15·2 to 4·2; p=0·24). The Kaplan-Meier method estimate of the probability of survival at day 28 between the control group and bicarbonate group was not significant (46% [95% CI 40-54] vs 55% [49-63]; p=0·09. In the prespecified AKIN stratum of patients with a score of 2 or 3, the Kaplan-Meier method estimate of survival by day 28 between the control group and bicarbonate group was significant (37% [95% CI 28-48] vs 54% [45-65]; p=0·0283). [corrected] Metabolic alkalosis, hypernatraemia, and hypocalcaemia were observed more frequently in the bicarbonate group than in the control group, with no life-threatening complications reported., Interpretation: In patients with severe metabolic acidaemia, sodium bicarbonate had no effect on the primary composite outcome. However, sodium bicarbonate decreased the primary composite outcome and day 28 mortality in the a-priori defined stratum of patients with acute kidney injury., Funding: French Ministry of Health and the Société Française d'Anesthésie Réanimation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Shortening the duration of antibiotic therapy (ABT) is a key measure in antimicrobial stewardship. The optimal duration of ABT for treatment of postoperative intra-abdominal infections (PIAI) in critically ill patients is unknown., Methods: A multicentre prospective randomised trial conducted in 21 French intensive care units (ICU) between May 2011 and February 2015 compared the efficacy and safety of 8-day versus 15-day antibiotic therapy in critically ill patients with PIAI. Among 410 eligible patients (adequate source control and ABT on day 0), 249 patients were randomly assigned on day 8 to either stop ABT immediately (n = 126) or to continue ABT until day 15 (n = 123). The primary endpoint was the number of antibiotic-free days between randomisation (day 8) and day 28. Secondary outcomes were death, ICU and hospital length of stay, emergence of multidrug-resistant (MDR) bacteria and reoperation rate, with 45-day follow-up., Results: Patients treated for 8 days had a higher median number of antibiotic-free days than those treated for 15 days (15 [6-20] vs 12 [6-13] days, respectively; P < 0.0001) (Wilcoxon rank difference 4.99 days [95% CI 2.99-6.00; P < 0.0001). Equivalence was established in terms of 45-day mortality (rate difference 0.038, 95% CI - 0.013 to 0.061). Treatments did not differ in terms of ICU and hospital length of stay, emergence of MDR bacteria or reoperation rate, while subsequent drainages between day 8 and day 45 were observed following short-course ABT (P = 0.041)., Conclusion: Short-course antibiotic therapy in critically ill ICU patients with PIAI reduces antibiotic exposure. Continuation of treatment until day 15 is not associated with any clinical benefit. CLINICALTRIALS., Gov Identifier: NCT01311765.

Objectives: The Paris terrorist attacks on 13 November 2015 caused 482 casualties, including 130 deaths and 352 wounded. Facing these multisite terrorist attacks, Parisian public and military hospitals simultaneously managed numerous patients with penetrating thoracic injuries. The aim of this study was to analyse this cohort, the injury patterns, and assess the results of this mobilization., Methods: The clinical records of all patients admitted to Parisian public and military hospitals with a penetrating thoracic injury related to the Paris 13 November terrorist attacks were reviewed., Results: The study group included 25 patients (7% of the casualties) with a mean age of 34 ± 8 years and a majority of gunshot wounds ( n =  20, 80%). Most patients presented with severe thoracic injury (Abbreviated Injury Score Thorax 3.3 ± 1.2), and also associated non-thoracic injuries in 21 cases (84%). The mean Injury Severity Score was 26.8 ± 9.4. Eight patients (32%) were managed with chest tube insertion and 17 (68%) required thoracic surgery. Lung resection, diaphragmatic repair, and lung suture were performed in 6 (36%), 6 (35%), and 5 cases (29%), respectively. Extra-thoracic surgical procedures were performed in 16 patients, mostly for injuries to the extremities. Postoperative mortality was 12% ( n =  3) and postoperative morbidity was 60% ( n =  15)., Conclusions: The coordination of Parisian military and civilian hospitals allowed the surgical management of 25 patients. The mortality is high but consistent with what has been reported in previous series. The current times expose us to the threat of new terrorist attacks and require that the medical community be prepared., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Positive end-expiratory pressure (PEEP) has beneficial pulmonary effects but may worsen the hemodynamic repercussions induced by pneumoperitoneum (PNP) in patients undergoing laparoscopic liver resection. However, by increasing intraluminal vena cava (VC) pressures, PEEP may prevent PNP-induced VC collapse. The aim of this study was to test the validity of this hypothesis., Methods: After IRB approval and written informed consent, 20 patients were evaluated prospectively. Measurements were performed before and after the application of 10 cmH 2 O PEEP on patients without PNP (Control group) and during a 12 cmH 2 0 PNP. Results are provided as means [95%CI]. Comparison used paired-sample t test., Results: PEEP induced a decrease in CI in Control subgroup (2.3 [2.0-2.6] and 2.1 [1.8-2.4] l min -1  m -2 before and after PEEP. P < 0.05). In contrast, PEEP on a pre-established PNP did not significantly modify cardiac index (CI). Transmural pressure on the abdominal vena cava decreased with PNP but was partly reversed by the addition of PEEP., Conclusion: The application of PEEP on a pre-established PNP during laparoscopic liver resection in normovolemic patients did not decrease CI. Analysis of transmural VC pressure variations confirms that the addition of PEEP may prevent the vena caval collapse induced by PNP., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

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.

While, in France, various health professionals are authorised to prescribe, they approach this activity in a different way, depending on the professional category to which they belong. The areas and products concerned are specific to each profession, and inevitably evolve. This article presents the different perspectives of a doctor, a midwife and a nurse., (Copyright © 2016. Published by Elsevier Masson SAS.)

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

Surgical necrosectomy, but is still associated with a high morbidity. Indications of the endoscopic route, a new less invasive technique are not defined yet. To compare characteristics and clinical outcome of patients treated by the two techniques, a bi-centric retrospective comparison of 21 patients treated by surgical necrosectomy in one center (group S) with 11 patients treated in another center by endoscopic transgastric necrosectomy (group E) was performed. Clinical severity scores were significantly higher in group S although CT severity score did not differ between groups. Acute postoperative complications including pancreatic fistula occurred more frequently in group S (86% vs. 27%, P=0.002). ICU and hospital length of stay were higher in group S (84 vs. 4 days; P=0.008 and 58 vs. 15 days; P=0.005 respectively). Long-term complication did not differ between groups. Compared to surgery, endoscopic necrosectomy exhibited lower rate of complications and reduced hospital length of stays. Endoscopic transgastric necrosectomy appears as a safe and effective procedure and has to be included in the therapeutic algorithm of infected pancreatic necrosis., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: Increasing evidence suggests that inflammation associated with microglial cell activation in the substantia nigra (SN) of patients with Parkinson disease (PD) is not only a consequence of neuronal degeneration, but may actively sustain dopaminergic (DA) cell loss over time. We aimed to study whether the intracellular chaperone heat shock protein 60 (Hsp60) could serve as a signal of CNS injury for activation of microglial cells., Methods: Hsp60 mRNA expression in the mesencephalon and the striatum of C57/BL6 mice treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and the Hsp60/TH mRNA ratios in the SN of PD patients and aged-matched subjects were measured. To further investigate a possible link between the neuronal Hsp60 response and PD-related cellular stress, Hsp60 immunoblot analysis and quantification in cell lysates from SH-SY5Y after treatment with 100 μM MPP+ (1-methyl-4-phenylpyridinium) at different time points (6, 12, 24 and 48 hours) compared to control cells were performed. Additional MTT and LDH assay were used. We next addressed the question as to whether Hsp60 influences the survival of TH+ neurons in mesencephalic neuron-glia cultures treated either with MPP+ (1 μM), hHsp60 (10 μg/ml) or a combination of both. Finally, we measured IL-1β, IL-6, TNF-α and NO-release by ELISA in primary microglial cell cultures following treatment with different hHsp60 preparations. Control cultures were exposed to LPS., Results: In the mesencephalon and striatum of mice treated with MPTP and also in the SN of PD patients, we found that Hsp60 mRNA was up-regulated. MPP+, the active metabolite of MPTP, also caused an increased expression and release of Hsp60 in the human dopaminergic cell line SH-SY5Y. Interestingly, in addition to being toxic to DA neurons in primary mesencephalic cultures, exogenous Hsp60 aggravated the effects of MPP+. Yet, although we demonstrated that Hsp60 specifically binds to microglial cells, it failed to stimulate the production of pro-inflammatory cytokines or NO by these cells., Conclusions: Overall, our data suggest that Hsp60 is likely to participate in DA cell death in PD but via a mechanism unrelated to cytokine release.

Background: After pancreaticoduodenectomy, severe pancreatic fistula may require salvage relaparotomy in patients with largely disrupted pancreaticojejunal anastomosis. Completion pancreatectomy remains the gold standard but yields high mortality and severe long-term repercussions. The authors report the results of a pancreas-preserving strategy used in this life-threatening condition., Methods: Two hundred fifty-four pancreaticoduodenectomies with pancreaticojejunal anastomosis were performed between 2005 and 2011; 21 patients underwent salvage relaparotomy for grade C pancreatic fistula. Largely dehiscent pancreaticojejunal anastomoses were dismantled in 16 patients. Four patients underwent completion pancreatectomy, whereas in 12 patients detailed here, the remaining pancreas was preserved and drained by wirsungostomy with exteriorization or closure of the jejunal stump. Repeat pancreaticojejunal anastomosis was later planned to preserve pancreatic function., Results: One patient died of recurrent hemorrhage on day 1 after wirsungostomy (8.3%). All but 1 survivor developed postoperative complications, and 3 needed reoperation before hospital discharge. The median hospital stay was 62 days (range, 29 to 156 days). After a median delay of 130 days (range, 91 to 240 days) from salvage relaparotomy, repeat pancreaticojejunostomy was attempted in 10 patients and was successful in 9 (1 completion pancreatectomy was performed). One patient died postoperatively (10%). Long-term endocrine function was unaltered in 66% of patients who benefited from this conservative strategy., Conclusions: This pancreas-preserving strategy yielded a whole mortality rate of 17% for largely disrupted pancreaticojejunal anastomosis requiring salvage relaparotomy. It compares favorably with systematic completion pancreatectomy and achieved preservation of remnant pancreatic function in 75% of patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Delirium is common in intensive care unit patients and is associated with worse outcome., Objective: To identify early risk factors for delirium in patients admitted to the intensive care unit following orthotopic liver transplantation (OLT)., Methods: An observational study of patients admitted to the intensive care unit from January 2000 to May 2010 for elective or semi-elective OLT was conducted. The primary end point was delirium in the intensive care unit. Pre- and post-transplantation and intraoperative factors potentially associated with this outcome were examined., Results: Of the 281 patients included in the study, 28 (10.03%) developed delirium in the intensive care unit at a median of two days (interquartile range one to seven days) after OLT. According to multivariate analysis, independent risk factors for delirium were intraoperative transfusion of packed red blood cells (OR 1.15 [95% CI 1.01 to 1.18]), renal replacement therapy during the pretransplantation period (OR 13.12 [95% CI 2.82 to 72.12]) and Acute Physiologic and Health Evaluation (APACHE) II score (OR per unit increase 1.10 [95% CI 1.03 to 1.29]). Using Cox proportional hazards models adjusted for baseline covariates, delirium was associated with an almost twofold risk of remaining in hospital, a fourfold increased risk of dying in hospital and an almost threefold increased rate of death by one year., Conclusion: Intraoperative transfusion of packed red blood cells, pretransplantation renal replacement therapy and APACHE II score are predictors for the development of delirium in intensive care unit patients post-OLT and are associated with increased hospital lengths of stay and mortality.

Introduction: Critically ill cirrhosis patients awaiting liver transplantation (LT) often receive prioritization for organ allocation. Identification of patients most likely to benefit is essential. The purpose of this study was to examine whether the Sequential Organ Failure Assessment (SOFA) score can predict 90-day mortality in critically ill recipients of LT and whether it can predict receipt of LT among critically ill cirrhosis listed awaiting LT., Methods: We performed a multicenter retrospective cohort study consisting of two datasets: (a) all critically-ill cirrhosis patients requiring intensive care unit (ICU) admission before LT at five transplant centers in Canada from 2000 through 2009 (one site, 1990 through 2009), and (b) critically ill cirrhosis patients receiving LT from ICU (n = 115) and those listed but not receiving LT before death (n = 106) from two centers where complete data were available., Results: In the first dataset, 198 critically ill cirrhosis patients receiving LT (mean (SD) age 53 (10) years, 66% male, median (IQR) model for end-stage liver disease (MELD) 34 (26-39)) were included. Mean (SD) SOFA scores at ICU admission, at 48 hours, and at LT were 12.5 (4), 13.0 (5), and 14.0 (4). Survival at 90 days was 84% (n = 166). In multivariable analysis, only older age was independently associated with reduced 90-day survival (odds ratio (OR), 1.07; 95% CI, 1.01 to 1.14; P = 0.013). SOFA score did not predict 90-day mortality at any time. In the second dataset, 47.9% (n = 106) of cirrhosis patients listed for LT died in the ICU waiting for LT. In multivariable analysis, higher SOFA at 48 hours after admission was independently associated with lower probability of receiving LT (OR, 0.89; 95% CI, 0.82 to 0.97; P = 0.006). When including serum lactate and SOFA at 48 hours in the final model, elevated lactate (at 48 hours) was also significantly associated with lower likelihood of receiving LT (0.32; 0.17 to 0.61; P = 0.001)., Conclusions: SOFA appears poor at predicting 90-day survival in critically ill cirrhosis patients after LT, but higher SOFA score and elevated lactate 48 hours after ICU admission are associated with a lower probability receiving LT. Older critically ill cirrhosis patients (older than 60) receiving LT have worse 90-day survival and should be considered for LT with caution.

In mammalians, toll-like receptors (TLR) signal-transduction pathways induce the expression of a variety of immune-response genes, including inflammatory cytokines. It is therefore plausible to assume that TLRs are mediators in glial cells triggering the release of cytokines that ultimately kill DA neurons in the substantia nigra in Parkinson disease (PD). Accordingly, recent data indicate that TLR4 is up-regulated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in a mouse model of PD. Here, we wished to evaluate the role of TLR4 in the acute mouse MPTP model of PD: TLR4-deficient mice and wild-type littermates control mice were used for the acute administration way of MPTP or a corresponding volume of saline. We demonstrate that TLR4-deficient mice are less vulnerable to MPTP intoxication than wild-type mice and display a decreased number of Iba1+ and MHC II+ activated microglial cells after MPTP application, suggesting that the TLR4 pathway is involved in experimental PD.

Background: It is clear that patients with a severe traumatic brain injury (TBI) develop secondary, potentially lethal neurological deterioration. However, it is difficult to predict which patients with mild-to-moderate TBI (MM-TBI), even after intensive care unit (ICU) admission, will experience poor outcome at 6 months. Standard computed tomography (CT) imaging scans provide information that can be used to estimate specific gravity (eSG). We have previously demonstrated that higher eSG measurements in the standard CT reading were associated with poor outcomes after severe TBI. The aim of this study was to determine whether eSG of the intracranial content predicts 6-month outcome in MM-TBI., Methods: We analyzed admission clinical and CT scan data (including eSG) of 66 patients with MM-TBI subsequently admitted to our neurosurgical ICU. Primary outcome was defined as a Glasgow Outcome Scale score of 1 to 3 after 6 months. Discriminating power (area under the receiver operating characteristic curve [ROC-AUC], 95% confidence interval) of eSG to predict 6-month poor outcome was calculated. The correlation of eSG with the main ICU characteristics was then compared., Results: Univariate and stepwise multivariate analyses showed an independent association between eSG and 6-month poor outcome (P = 0.001). ROC-AUC of eSG for the prediction of 6-month outcomes was 0.87 (confidence interval: 0.77-0.96). Admission eSG values were correlated with the main ICU characteristics, specifically 14-day mortality (P = 0.004), length of mechanical ventilation (P = 0.01), length of ICU stay (P = 0.045), and ICU procedures such as intracranial pressure monitoring (P < 0.001)., Conclusions: In this MM-TBI cohort admitted to the ICU, eSG of routine CT scans was correlated with mortality, ICU severity, and predicted 6-month poor outcome. An external validation with studies that include the spectrum of TBI severities is warranted to confirm our results.

Introduction: Cerebral vasospasm is a well-documented complication of aneurismal subarachnoid hemorrhage but has not been extensively studied in brain arteriovenous malformations (BAVMs). Here, our purpose was to identify risk factors for cerebral vasospasm after BAVM rupture in patients requiring intensive care unit (ICU) admission., Methods: Patients admitted to our ICU from January 2003 to May 2010 for BAVM rupture were included in this observational study. Clinical, laboratory and radiological features from admission to ICU discharge were recorded. The primary endpoint was cerebral vasospasm by transcranial Doppler (TCD-VS) or cerebral infarction (CI) associated with vasospasm. Secondary endpoints included the Glasgow Outcome Scale (GOS) at ICU discharge., Results: Of 2,734 patients admitted to our ICU during the study period, 72 (2.6%) with ruptured BAVM were included. TCD-VS occurred in 12 (17%) and CI in 6 (8%) patients. All patients with CI had a previous diagnosis of TCD-VS. A Glasgow Coma Scale score <8 was a risk factor for both TCD-VS (relative risk (RR), 4.7; 95% confidence interval (95% CI), 1.6 to 26) and CI (RR, 7.8; 95% CI, 0.1 to 63). Independent risk factors for TCD-VS by multivariate analysis were lower Glasgow Coma Scale score (odds ratio (OR) per unit decrease, 1.38; 95% CI, 1.13 to 1.80), female gender (OR, 4.86; 95% CI, 1.09 to 25.85), and younger age (OR per decade decrease, 1.39; 95% CI, 1.05 to 1.82). The risk of a poor outcome (GOS <4) at ICU discharge was non-significantly increased in the patients with TCD-VS (RR, 4.9; 95% CI, 0.7 to 35; P = 0.09). All six patients with CI had poor outcomes., Conclusions: This is the first cohort study describing the incidence and risk factors for cerebral vasospasm after BAVM rupture. Larger studies are needed to investigate the significance of TCD-vasospasm and CI in these patients.

Purpose: To evaluate the in vivo accuracy of the new Pressio(®) device for intraparenchymal monitoring of intracranial pressure (ICP) versus the Codman(®) device and intraventricular measurement external ventricular drainage (EVD)., Methods: Data were collected retrospectively for 30 consecutive patients admitted into a 25-bed neurosurgical intensive care unit of a university hospital between January and December 2009. Patients received both intraventricular and intraparenchymal ICP monitoring with Pressio(®) (n = 15) or Codman(®) (n = 15)., Results: We obtained 3,089 data points from the 30 patients. Mean difference between intraparenchymal and EVD pressure (bias) was -0.6 mmHg, and limits of agreement (1.96 SD of the bias) were -8.1 to 6.9 mmHg with Pressio(®) and 0.3 mmHg with limits of agreement of -6.7 to 7.1 mmHg with Codman(®) (NS). The temporal difference was -0.7 ± 1.6 mmHg/100 h of monitoring with Pressio(®) and 0.1 ± 1.6 mmHg/100 h of monitoring with Codman(®) over the study period (NS)., Conclusions: Intraparenchymal pressure measured with both transducers approximates intraventricular cerebrospinal fluid pressure with an accuracy of ±7 mmHg.

Recent evidence supports a crucial role for matrix metalloproteinase-9 (MMP-9) in blood-brain barrier (BBB) disruption and vasogenic edema formation after traumatic brain injury (TBI). Although the exact causes of MMP-9 upregulation after TBI are not fully understood, several arguments suggest a contribution of the enzyme poly(ADP-ribose)polymerase (PARP) in the neuroinflammatory response leading to MMP-9 activation. The objectives of this study were to evaluate the effect of PARP inhibition by 3-aminobenzamide (3-AB) (1) on MMP-9 upregulation and BBB integrity, (2) on edema formation as assessed by magnetic resonance imaging (MRI), (3) on neuron survival as assessed by (1)H magnetic resonance spectroscopy ((1)H-MRS), and (4) on neurological deficits at the acute phase of TBI. Western blots and zymograms showed blunting of MMP-9 upregulation 6 h after TBI. BBB permeability was decreased at the same time point in 3-AB-treated rats compared to vehicle-treated rats. Cerebral MRI showed less "free" water in 3-AB-treated than in vehicle-treated rats 6 h after TBI. MRI findings 24 h after TBI indicated predominant cytotoxic edema, and at this time point no significant differences were found between 3-AB- and vehicle-treated rats with regard to MMP-9 upregulation, BBB permeability, or MRI changes. At both 6 and 24 h, neurological function was better in the 3-AB-treated than in the vehicle-treated rats. These data suggest that PARP inhibition by 3-AB protected the BBB against hyperpermeability induced by MMP-9 upregulation, thereby decreasing vasogenic edema formation 6 h after TBI. Furthermore, our data confirm the neuroprotective effect of 3-AB at the very acute phase of TBI.

Magnetic resonance imaging (MRI) is widely used to evaluate the consequences of traumatic brain injury (TBI) in both experimental and clinical studies. Improved assessment of experimental TBI using the same methods as those used in clinical investigations would help to translate laboratory research into clinical advances. Here our goal was to characterize lateral fluid percussion-induced TBI, with special emphasis on differentiating the contused cortex from the pericontusional subcortical tissue. We used both in vivo MRI and proton magnetic resonance spectroscopy ((1)H-MRS) to evaluate adult male Sprague-Dawley rats 24 h and 48 h and 7 days after TBI. T2 and apparent diffusion coefficient (ADC) maps were derived from T2-weighted and diffusion-weighted images, respectively. Ratios of N-acetylaspartate (NAA), choline compounds (Cho), and lactate (Lac) over creatine (Cr) were estimated by (1)H-MRS. T2 values were high in the contused cortex 24 h after TBI, suggesting edema development; ADC was low, consistent with cytotoxic edema. At the same site, NAA/Cr was decreased and Lac/Cr elevated during the first week after TBI. In the ipsilateral subcortical area, NAA/Cr was markedly decreased and Lac/Cr was elevated during the first week, although MRI showed no evidence of edema, suggesting that (1)H-MRS detected "invisible" damage. (1)H-MRS combined with MRI may improve the detection of brain injury. Extensive assessments of animal models may increase the chances of developing successful neuroprotective strategies.

Traumatic brain injury (TBI) occurs abruptly, involves multiple specialized teams, calls on the health-care system in its emergency dimension, and engages the well-being of the patient and his relatives for a lifetime period. Clinicians in charge of these patients are faced with issues of uppermost importance: medical issues such as predicting the long-term neurological outcome of the comatose patient; ethical issues because of the influence of intensive care on the long-term survival of patients in a vegetative and minimally conscious state; legal issues because of the law that has set the concept of proportionality of care as the legal rule; and social issues as the result of the very high cost of these pathologies. Today's larger availability of magnetic resonance imaging (MRI) in ventilated patients and the recent improvements in hardware and in imaging techniques that have made the last-developed imaging techniques such as diffusion tensor imaging and magnetic resonance spectroscopy available in brain-trauma patients, are changing the paradigm in neurointensive care regarding outcome prediction. The old paradigm that no individual prognosis could be made at the subacute phase in TBI patients does not hold true anymore. This major change opens new challenging ethical questions. This review focuses on the brain explorations that are required, such as MRI, magnetic resonance spectroscopy, and diffusion tensor imaging, to provide the clinician with a multimodal assessment of the brain state to predict outcome of coma. Such an assessment will become mandatory in the near future to answer the crucial question of proportionality of care in these patients.

Purpose of Review: The review provides key points and recent advances regarding the treatments of intracranial hypertension as a consequence of traumatic brain injury. The review is based on the pathophysiology of brain edema and draws on the current literature as well as clinical bedside experience., Recent Findings: The review will cite baseline literature and discuss emerging data on cerebral perfusion pressure, sedation, hypothermia, osmotherapy and albumin as treatments of intracranial hypertension in traumatic brain-injured patients., Summary: One of the key issues is to consider that traumatic brain injury is more likely a syndrome than a disease. In particular, the presence or absence of a high contusional volume could influence the treatments to be implemented. The use of osmotherapy and/or high cerebral perfusion pressure should be restricted to patients without major contusions. Some physiopathological, experimental and clinical data, however, show that corticosteroids and albumin--therapies that have been proven deleterious if administered systematically--are worth reconsidering for this subgroup of patients. The current Pitié-Salpêtrière algorithm, where treatments are stratified according to their potential side effects, will be added at the end of the review as an example of an integrated strategy.

Objective: At the acute phase of traumatic brain injury (TBI), brain swelling contributes substantially to the development of secondary neurological lesions. Elucidating the pathophysiology of brain swelling is crucial to improve TBI management. In a previous study, specific gravity (SG) of the noncontused hemisphere, as estimated by computed tomography (CT), was higher in patients with high Marshall CT scores and severe brain swelling. The aim of this study was to investigate the relationship between estimated specific gravity (eSG) and clinical variable suggestive of brain swelling., Design: Retrospective study of data from a prospectively established database., Setting: Neurology ICU in a teaching hospital in Paris, France., Participants: We studied 20 patients with severe traumatic brain injury (TBI), 20 patients with high-grade subarachnoid hemorrhage (SAH) presenting similar brain-swelling criteria, 20 patients with low-grade SAH, and 20 healthy controls., Interventions: None., Measurements and Results: Estimated brain specific gravity was acquired from CT images obtained at ICU admission. eSG was estimated in the overall intracerebral content and in a region-of-interest composed of white matter and the diencephalon. eSG in the region of interest was significantly higher in the TBI patients than in the high-grade SAH patients (1.0350 +/- 0.0041 vs. 1.0310 +/- 0.0019 g/ml, P < 0.05). eSG was similar in the high-grade SAH, low-grade SAH, and control groups., Conclusions: Our findings do not support a causal link between brain swelling and eSG elevation. The eSG increase in severe TBI patients is not due to brain swelling.