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Rationale: Most vascular catheter-related infections (CRIs) occur extraluminally in patients in the intensive care unit (ICU). Chlorhexidine-impregnated and strongly adherent dressings may decrease catheter colonization and CRI rates. Objectives: To determine if chlorhexidine-impregnated and strongly adherent dressings decrease catheter colonization and CRI rates. Methods: In a 2:1:1 assessor-masked randomized trial in patients with vascular catheters inserted for an expected duration of 48 hours or more in 12 French ICUs, we compared chlorhexidine dressings, highly adhesive dressings, and standard dressings from May 2010 to July 2011. Coprimary endpoints were major CRI with or without catheter-related bloodstream infection (CR-BSI) with chlorhexidine versus nonchlorhexidine dressings and catheter colonization rate with highly adhesive nonchlorhexidine versus standard nonchlorhexidine dressings. Catheter-colonization, CR-BSIs, and skin reactions were secondary endpoints. Measurements and Main Results: A total of 1,879 patients (4,163 catheters and 34,339 catheter-days) were evaluated. With chlorhexidine dressings, the major-CRI rate was 67% lower (0.7 per 1,000 vs. 2.1 per 1,000 catheter-days; hazard ratio [HR], 0.328; 95% confidence interval [CI], 0.174-0.619; P = 0.0006) and the CR-BSI rate 60% lower (0.5 per 1,000 vs. 1.3 per 1,000 catheter-days; HR, 0.402; 95% CI, 0.186-0.868; P = 0.02) than with nonchlorhexidine dressings; decreases were noted in catheter colonization and skin colonization rates at catheter removal. The contact dermatitis rate was 1.1% with and 0.29% without chlorhexidine. Highly adhesive dressings decreased the detachment rate to 64.3% versus 71.9% (P < 0.0001) and the number of dressings per catheter to two (one to four) versus three (one to five) (P < 0.0001) but increased skin colonization (P < 0.0001) and catheter colonization (HR, 1.650; 95% CI, 1.21-2.26; P = 0.0016) without influencing CRI or CR-BSI rates. Conclusions: A large randomized trial demonstrated that chlorhexidine-gel-impregnated dressings decreased the CRI rate in patients in the ICU with intravascular catheters. Highly adhesive dressings decreased dressing detachment but increased skin and catheter colonization. Clinical trial registered with www.clinicaltrials.gov (NCT 01189682). [ABSTRACT FROM AUTHOR]

This retrospective study aimed to compare the mortality and burden of respiratory syncytial virus (RSV group), SARS-CoV-2 (COVID-19 group), non-H1N1 (Seasonal influenza group) and H1N1 influenza (H1N1 group) in adult patients admitted to intensive care unit (ICU) with respiratory failure. A total of 807 patients were included. Mortality was compared between the four following groups: RSV, COVID-19, seasonal influenza, and H1N1 groups. Patients in the RSV group had significantly more comorbidities than the other patients. At admission, patients in the COVID-19 group were significantly less severe than the others according to the simplified acute physiology score-2 (SAPS-II) and sepsis-related organ failure assessment (SOFA) scores. Using competing risk regression, COVID-19 (sHR = 1.61; 95% CI 1.10; 2.36) and H1N1 (sHR = 1.87; 95% CI 1.20; 2.93) were associated with a statistically significant higher mortality while seasonal influenza was not (sHR = 0.93; 95% CI 0.65; 1.31), when compared to RSV. Despite occurring in more severe patients, RSV and seasonal influenza group appear to be associated with a more favorable outcome than COVID-19 and H1N1 groups., (© 2024. The Author(s).)

Objectives: The objective of this study was to compare three different approaches for estimating 30-day survival in ICU studies, considering the issue of informative censoring that occurs when patients are lost to follow-up after discharge., Design: A comparative analysis was conducted to evaluate the effect of different approaches on the estimation of 30-day survival. Three methods were compared: the classical approach using the Kaplan-Meier (KM) estimator and Cox regression modeling, the competing risk approach using the Fine and gray model, considering censoring as a competing event, and the logistic regression approach., Setting: The study was conducted in a university ICU and data from patients admitted between 2010 and 2020 were included. Patient characteristics were collected from electronic records., Patients: A total of 10,581 patients were included in the study. The true date of death for each patient, obtained from a national registry, allowed for an absence of censoring., Interventions: All patients were censored at the time of discharge from the ICU, and the three different approaches were applied to estimate the mortality rate and the effects of covariates on mortality. Regression analyses were performed using five variables known to be associated with ICU mortality., Measurements and Main Results: The 30-day survival rate for the included patients was found to be 80.5% (95% CI, 79.7-81.2%). The KM estimator severely underestimated the 30-day survival (50.6%; 95% CI, 48.0-53.4%), while the competing risk and logistic regression approaches provided similar results, only slightly overestimating the survival rate (84.5%; 95% CI, 83.8-85.2%). Regression analyses showed that the estimates were not systematically biased, with the Cox and logistic regression models exhibiting greater bias compared with the competing risk regression method., Conclusions: The competing risk approach provides more accurate estimates of 30-day survival and is less biased compared with the other methods evaluated., Competing Interests: Dr. Friggeri received funding from Merck Sharp & Dohme. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose: The effect of renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in comatose patients with severe AKI., Methods: We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72 h and/or blood urea nitrogen higher than 112 mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140 mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale [RASS] < - 3), irrespective of sedation, at randomization. A multi-state model was built, defining five mutually exclusive states: death, coma (RASS < - 3), incomplete awakening (RASS [- 3; - 2]), awakening (RASS [- 1; + 1] two consecutive days), and agitation (RASS >  + 1). Primary outcome was the transition from coma to awakening during 28 days after randomization., Results: A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio [HR] = 0.36 [0.17-0.78]; p = 0.010). Time spent awake was 10.11 days [8.11-12.15] and 7.63 days [5.57-9.64] in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results., Conclusion: In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study aimed to assess the outcome and factors associated with mortality in patients who received urgent chemotherapy (CT) in the intensive care unit (ICU) in Lyon, France., Material and Methods: A total of 147 adult patients diagnosed with cancer and requiring urgent CT during ICU stay between October 2014 and December 2019 were included in this retrospective study., Results: Hematological cancer was found in 77% of patients, and acute respiratory failure was the leading cause of ICU admission (46.3%). The 6-month mortality rate was 69.4%; patients with solid cancer had a higher risk of mortality. Patients who died within 6 months had a poor performance score and a higher SOFA score at admission. The multivariate analysis showed that solid tumors, sepsis on the day of CT, and SOFA score on the day of CT were associated with 6-month mortality. Additionally, 95% of patients who survived the ICU resumed conventional CT, with a higher likelihood of resuming CT among those with hematological cancer., Conclusion: Urgent CT in the ICU is feasible in a specific subset of patients, mainly those with hematological cancer, with resumption of the curative treatment regimen after ICU discharge., Competing Interests: Declaration of Competing Interest J. BERNARD has no conflict of interest. C.H. VACHERON has no conflict of interest. N. VANTARD has no conflict of interest. E. BACHY has no conflict of interest. J.C. RICHARD has no conflict of interest. F. AUBRUN has no conflict of interest. M. COUR has no conflict of interest. AC. LUKASZEWICZ has no conflict of interest. J. BOHE has no conflict of interest. B. ALLAOUCHICHE has no conflict of interest. A. FRIGGERI has no conflict of interest. F. WALLET has no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Intra-Abdominal Candidiasis (IAC) is frequent and associated with high mortality in intensive care unit (ICU) patients. Antifungal treatments may be overused due to a lack of diagnostic tools to rule out IAC. Serum 1,3-Beta-D-Glucan (BDG) concentrations are used to diagnose Candida infections, its concentration in peritoneal fluid (PF) may help to confirm or invalidate the diagnosis of IAC. We performed a non-interventional, prospective, multicenter study, at the Hospices Civils de Lyon, France, in seven ICU located in three different hospitals from December 2017 to June 2018. IAC was defined as the isolation of Candida in a sample collected from the intra-abdominal cavity under sterile conditions in patients displaying clinical evidence of intra-abdominal infection. Among the 113 included patients, 135 PF samples corresponding to 135 intra-abdominal infection episodes were collected and BDG concentrations were assessed. IAC accounted for 28 (20.7%) of the intra-abdominal infections. Antifungals were administered empirically to 70 (61.9%) patients; among them, 23 (32.9%) had an IAC. The median [IQR] BDG value was significantly higher in IAC (8100 [3000;15000] pg/mL) than in non-IAC samples (1961 [332;10650] pg/mL). BDG concentrations were higher in PF with Fecaloid aspect and in case of positive bacterial culture. For a BDG threshold of 125 pg/mL, the negative predictive value to assess IAC was 100%. In conclusion, low BDG PF concentrations could be used to rule out IAC. https://clinicaltrials.gov/ct2/show/NCT03469401., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: SARS-Cov-2 (COVID-19) has become a major worldwide health concern since its appearance in China at the end of 2019., Objective: To evaluate the intrinsic mortality and burden of COVID-19 and seasonal influenza pneumonia in ICUs in the city of Lyon, France., Design: A retrospective study., Setting: Six ICUs in a single institution in Lyon, France., Patients: Consecutive patients admitted to an ICU with SARS-CoV-2 pneumonia from 27 February to 4 April 2020 (COVID-19 group) and seasonal influenza pneumonia from 1 November 2015 to 30 April 2019 (influenza group). A total of 350 patients were included in the COVID-19 group (18 refused to consent) and 325 in the influenza group (one refused to consent). Diagnosis was confirmed by RT-PCR. Follow-up was completed on 1 April 2021., Main Outcomes and Measures: Differences in 90-day adjusted-mortality between the COVID-19 and influenza groups were evaluated using a multivariable Cox proportional hazards model., Results: COVID-19 patients were younger, mostly men and had a higher median BMI, and comorbidities, including immunosuppressive condition or respiratory history were less frequent. In univariate analysis, no significant differences were observed between the two groups regarding in-ICU mortality, 30, 60 and 90-day mortality. After Cox modelling adjusted on age, sex, BMI, cancer, sepsis-related organ failure assessment (SOFA) score, simplified acute physiology score SAPS II score, chronic obstructive pulmonary disease and myocardial infarction, the probability of death associated with COVID-19 was significantly higher in comparison to seasonal influenza [hazard ratio 1.57, 95% CI (1.14 to 2.17); P = 0.006]. The clinical course and morbidity profile of both groups was markedly different; COVID-19 patients had less severe illness at admission (SAPS II score, 37 [28 to 48] vs. 48 [39 to 61], P < 0.001 and SOFA score, 4 [2 to 8] vs. 8 [5 to 11], P < 0.001), but the disease was more severe considering ICU length of stay, duration of mechanical ventilation, PEEP level and prone positioning requirement., Conclusion: After ICU admission, COVID-19 was associated with an increased risk of death compared with seasonal influenza. Patient characteristics, clinical course and morbidity profile of these diseases is markedly different., (Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) are the two main RRT modalities in patients with severe acute kidney injury (AKI). Meta-analyses conducted more than 10 years ago did not show survival difference between these two modalities. As the quality of RRT delivery has improved since then, we aimed to reassess whether the choice of IHD or CRRT as first modality affects survival of patients with severe AKI., Methods: This is a secondary analysis of two multicenter randomized controlled trials (AKIKI and IDEAL-ICU) that compared an early RRT initiation strategy with a delayed one. We included patients allocated to the early strategy in order to emulate a trial where patients would have been randomized to receive either IHD or CRRT within twelve hours after the documentation of severe AKI. We determined each patient's modality group as the first RRT modality they received. The primary outcome was 60-day overall survival. We used two propensity score methods to balance the differences in baseline characteristics between groups and the primary analysis relied on inverse probability of treatment weighting., Results: A total of 543 patients were included. Continuous RRT was the first modality in 269 patients and IHD in 274. Patients receiving CRRT had higher cardiovascular and total-SOFA scores. Inverse probability weighting allowed to adequately balance groups on all predefined confounders. The weighted Kaplan-Meier death rate at day 60 was 54·4% in the CRRT group and 46·5% in the IHD group (weighted HR 1·26, 95% CI 1·01-1·60). In a complementary analysis of less severely ill patients (SOFA score: 3-10), receiving IHD was associated with better day 60 survival compared to CRRT (weighted HR 1.82, 95% CI 1·01-3·28; p < 0.01). We found no evidence of a survival difference between the two RRT modalities in more severe patients., Conclusion: Compared to IHD, CRRT as first modality seemed to convey no benefit in terms of survival or of kidney recovery and might even have been associated with less favorable outcome in patients with lesser severity of disease. A prospective randomized non-inferiority trial should be implemented to solve the persistent conundrum of the optimal RRT technique., (© 2022. The Author(s).)

Purpose: Several remarks have been raised regarding the variables and cut-points used in the Sequential Organ Failure Assessment (SOFA) score. This study revisited the SOFA score and created a new simplified and accurate sa-SOFA score., Methods: The study grouped four prospective cohorts (2005-2016) of patients with Systemic Inflammatory Response Syndrome. It collected 28-day mortality, sociodemographic characteristics, and the SOFA score with all variable values at Day 1. A logistic regression analysis was used to select the most relevant variables and a minimum p value approach with a 10-fold cross-validation were used to find the optimal partition of selected variables. The minimum number of cut-points (2, 3, or 4) was also tested by comparing the distributions of areas under receiver operating characteristic (AUROC) curves., Results: Among the 1436 participants, 416 died within 28 days (28.9%). The sa-SOFA kept one variable per dimension and two cut-points per variable. The AUROC curves that investigated the abilities of the sa-SOFA and SOFA scores to predict 28-day mortality were 0.739 [0.712-0.768] and 0.687 [0.656-0.717], respectively (p-value of DeLong test <0.001)., Conclusion: Keeping the conventional SOFA dimension variables, the new sa-SOFA proved to be simpler and more accurate in predicting 28-day mortality., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To compare the assessment of decision-making capacity of ICU patients by attending clinicians (physicians, nurses, and residents) with a capacity score measured by the Mini-Mental Status Examination, completed by Aid to Capacity Evaluation if necessary. The primary outcome was agreement between physicians' assessments and the score. Secondary outcomes were agreement between nurses' or residents' assessments and the score and identification of factors associated with disagreement., Design: A 1-day prevalence study., Setting: Nineteen ICUs in France., Subjects: All patients hospitalized in the ICU on the study day and the attending clinicians., Interventions: The decision-making capacity of patients was assessed by the attending clinicians and independently by an observer using the score., Measurements and Main Results: A total of 206 patients were assessed by 213 attending clinicians (57 physicians, 97 nurses, and 59 residents). Physicians designated more patients as having decision-making capacity (n = 92/206 [45%]) than score (n = 34/206 [17%]; absolute difference 28% [95% CI, 20-37%]; p = 0.001). There was a high disagreement between assessments of all clinicians and score (Kappa coefficient 0.39 [95% CI, 0.29-0.50] for physicians; 0.39 [95% CI, 0.27-0.52] for nurses; and 0.46 [95% CI, 0.35-0.58] for residents). The main factor associated with disagreement was a Glasgow Coma Scale score between 10 and 15 (odds ratio, 2.92 [1.18-7.19], p = 0.02 for physicians; 4.97 [1.50-16.45], p = 0.01 for nurses; and 3.39 [1.12-10.29], p = 0.03 for residents) without differentiating between the Glasgow Coma Scale scores from 10 to 15., Conclusions: The decision-making capacity of ICU patients was largely overestimated by all attending clinicians as compared with a score. The main factor associated with disagreement was a Glasgow Coma Scale score between 10 and 15, suggesting that clinicians confused consciousness with decision-making capacity.

There is considerable physiological and clinical evidence of harm and increased risk of death associated with dysglycemia in critical care. However, glycemic control (GC) currently leads to increased hypoglycemia, independently associated with a greater risk of death. Indeed, recent evidence suggests GC is difficult to safely and effectively achieve for all patients. In this review, leading experts in the field discuss this evidence and relevant data in diabetology, including the artificial pancreas, and suggest how safe, effective GC can be achieved in critically ill patients in ways seeking to mimic normal islet cell function. The review is structured around the specific clinical hurdles of: understanding the patient's metabolic state; designing GC to fit clinical practice, safety, efficacy, and workload; and the need for standardized metrics. These aspects are addressed by reviewing relevant recent advances in science and technology. Finally, we provide a set of concise recommendations to advance the safety, quality, consistency, and clinical uptake of GC in critical care. This review thus presents a roadmap toward better, more personalized metabolic care and improved patient outcomes.

Glucose management in intensive care unit (ICU) patients has been a matter of debate for almost two decades. Compared to intermittent monitoring systems, continuous glucose monitoring (CGM) can offer benefit in the prevention of severe hyperglycemia and hypoglycemia by enabling insulin infusions to be adjusted more rapidly and potentially more accurately because trends in glucose concentrations can be more readily identified. Increasingly, it is apparent that a single glucose target/range may not be optimal for all patients at all times and, as with many other aspects of critical care patient management, a personalized approach to glucose control may be more appropriate. Here we consider some of the evidence supporting different glucose targets in various groups of patients, focusing on those with and without diabetes and neurological ICU patients. We also discuss some of the reasons why, despite evidence of benefit, CGM devices are still not widely employed in the ICU and propose areas of research needed to help move CGM from the research arena to routine clinical use.

Background: Intensive care unit (ICU) patients require dialysis catheters (DCs) for renal replacement therapy (RRT). They carry a high risk of developing end-stage renal disease, and therefore their vascular access must be preserved. Guidewire exchange (GWE) is often used to avoid venipuncture insertion (VPI) at a new site. However, the impact of GWE on infection and dysfunction of DCs in the ICU is unknown. Our aim was to compare the effect of GWE and VPI on DC colonization and dysfunction in ICU patients., Methods: Using data from the ELVIS randomized controlled trial (RCT) (1496 ICU adults requiring DC for RRT or plasma exchange) we performed a matched-cohort analysis. Cases were DCs inserted by GWE (n = 178). They were matched with DCs inserted by VPI. Matching criteria were participating centre, simplified acute physiology score (SAPS) II +/-10, insertion site (jugular or femoral), side for jugular site, and length of ICU stay before DC placement. We used a marginal Cox model to estimate the effect of DC insertion (GWE vs. VPI) on DC colonization and dysfunction., Results: DC colonization rate was not different between GWE-DCs and VPI-DCs (10 (5.6 %) for both groups) but DC dysfunction was more frequent with GWE-DCs (67 (37.6 %) vs. 28 (15.7 %); hazard ratio (HR), 3.67 (2.07-6.49); p < 0.01). Results were similar if analysis was restricted to DCs changed for dysfunction., Conclusions: GWE for DCs in ICU patients, compared with VPI did not contribute to DC colonization or infection but was associated with more than twofold increase in DC dysfunction., Trial Registration: This study is registered with ClinicalTrials.gov, number NCT00563342 . Registered 2 April 2009.

Rationale: Ethanol rapidly eradicated experimental biofilm. Clinical studies of ethanol lock to prevent catheter-related infections (CRIs) suggest preventive efficacy. No such studies have been done in intensive care units (ICU)., Objectives: To determine whether ethanol lock decreases the risk of major CRI in patients with short-term dialysis catheters (DCs)., Methods: A randomized, double-blind, placebo-controlled trial was performed in 16 ICUs in seven university hospitals and one general hospital in France between June 2009 and December 2011. Adults with insertion of a nontunneled, nonantimicrobial-impregnated double-lumen DC for an expected duration greater than 48 hours, to perform renal-replacement therapy or plasma exchange, were randomly allocated (1:1) to receive a 2-minute catheter lock with either 60% wt/wt ethanol solution (ethanol group) or 0.9% saline solution (control group) at the end of DC insertion and after each renal-replacement therapy or plasma exchange session. The main outcome was major CRI defined as either catheter-related clinical sepsis without bloodstream infection or catheter-related bloodstream infection during the ICU stay., Measurements and Main Results: The intent-to-treat analysis included 1,460 patients (2,172 catheters, 12,944 catheter-days, and 8,442 study locks). Median DC duration was 4 days (interquartile range, 2-8) and was similar in both groups. Major CRI incidence did not differ between the ethanol and control groups (3.83 vs. 2.64 per 1,000 catheter-days, respectively; hazard ratio, 1.55; 95% confidence interval, 0.83-2.87; P = 0.17). No significant differences occurred for catheter colonization (P = 0.57) or catheter-related bloodstream infection (P = 0.99)., Conclusions: A 2-minute ethanol lock does not decrease the frequency of infection of DCs in ICU patients. Clinical trial registered with www.clinicaltrials.gov (NCT 00875069).

Objectives: Active treatment withholding and withdrawing decisions in the emergency room (ER) must be taken collegially according to ethical and juridical statements. Specific tools can support this process and our main goal was to create and validate such a tool., Method: We created a first version of a tool to help for treatment withholding and withdrawing decisions inspired by similar documents from literature. Every item of this tool was then assessed by a group of experts (ER physicians and nurses) using the Delphi method to reach a consensus., Results: Thirty-four experts from eleven ER (academic, regional centre) were included and participate to the first round and twenty-seven to the second round. From the eighty-two-item tool, sixty-five items reach a consensus during these two rounds and were kept to constitute the final version of the tool., Conclusion: We have been able to create a tool to help for treatment withholding and withdrawing decisions adapted to the guidelines for end of life patient's management in the ER. This tool has been validated using a Delphi method by a group of experts from different centres. This multicentre validation will help for the diffusion and use of this tool in the different ER of the Rhône-Alpes region., (Copyright © 2014 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Rationale: When subclavian access is not possible, controversy exists between the internal jugular and femoral sites for the choice of central-venous access in intensive care unit patients., Objectives: To compare infection and colonization rates of short-term jugular and femoral catheters., Methods: Using data from two multicenter studies, we compared femoral and internal jugular for the risks of catheter-related bloodstream infection, major catheter-related infection, and catheter-tip colonization. We also compared the rates of dressing disruption and skin colonization. We used marginal structural models with inverse probability of treatment weighting to adjust on indication bias., Measurements and Main Results: We included 2,128 patients (2,527 catheters and 19,481 catheter-days). We found no difference in catheter-related bloodstream infection (internal jugular 1.0 vs. femoral 1.1 per 1,000 catheter-days; hazard ratio [HR], 0.63 [0.25-1.63]; P = 0.34), major catheter-related infection (internal jugular 1.8 vs. femoral 1.4 per 1,000 catheter-days; HR, 0.91 [0.38-2.18]; P = 0.34), and colonization (internal jugular 11.6 vs. femoral 12.9 per 1,000 catheter-days; HR, 0.80 [0.25-1.63]; P = 0.15). However, colonization was higher with femoral for female (HR, 0.39 [0.24-0.63]; P < 0.001) and, at the significance limit, catheter maintained for more than 4 days (HR, 0.73 [0.53-1.01]; P = 0.05). The absence of benefit of internal jugular before Day 5 was related to a higher skin colonization at the internal jugular site for catheters removed before Day 5. After the fourth day, dressing disruption became more frequent with femoral catheters and may explain the subsequent risk of catheter colonization. Differences in cutaneous and catheter colonization between internal jugular and femoral was suppressed by the use of chlorhexidine-impregnated dressings., Conclusions: Femoral and internal jugular accesses lead to similar risks of catheter infection. Internal jugular might be preferred for female, nonchlorhexidine-impregnated dressings users, and when catheters are left in place more than 4 days. Both sites are acceptable when a subclavian approach is not feasible. Clinical trial registered with www.clinicaltrials.gov (NCT00417235 and NCT01189682).

Rationale: A decade after drotrecogin alfa (activated) (DAA) was released on the market worldwide, its benefit-to-risk ratio remains a matter of debate., Objectives: The current investigator-led trial was designed to evaluate the efficacy and safety of DAA, in combination with low-dose steroids, in adults with persistent septic shock., Methods: This was a multicenter (24 intensive care units), placebo-controlled, double-blind, 2 × 2 factorial design trial in which adults with persistent septic shock and no contraindication to DAA were randomly assigned to DAA alone (24 μg/kg/h for 96 h), hydrocortisone and fludrocortisone alone, their respective combinations, or their respective placebos. Primary outcome was mortality rate on Day 90., Measurements and Main Results: On October 25, 2011, the trial was suspended after the withdrawal from the market of DAA. The Scientific Committee decided to continue the trial according to a two parallel group design comparing low-dose steroids with their placebos and to analyze the effects of DAA on patients included before trial suspension. At the time trial was suspended, 411 patients had been recruited, 208 had received DAA, and 203 had received its placebo. There was no significant interaction between DAA and low-dose steroids (P = 0.47). On Day 90, there were 99 deaths (47.6%) among the 208 patients receiving DAA and 94 deaths (46.3%) among the 203 patients receiving placebo (P = 0.79). There was no evidence of a difference between DAA and its placebo for any secondary outcomes or serious adverse events., Conclusions: In adults with established and severe septic shock, DAA showed no evidence of benefit or harm. Clinical trial registered with www.clinicaltrials.gov (NCT00625209).

Although it is known that septic shock induces immunosuppression, the mechanism for this phenomenon is not well understood. Monocytes play a central role in septic shock pathophysiology, which is also characterized by an increased proportion of natural regulatory T (Treg) cells. We therefore investigated whether Treg could be involved in the decreased monocyte expression of CD14 and HLA-DR observed during septic shock. We demonstrated that human Treg inhibit LPS-induced retention of monocyte CD14. Because loss of CD14 is a hallmark of monocyte apoptosis, this suggests that Treg inhibit monocyte survival. This effect was largely mediated through the release of a soluble mediator that was not identical with either IL-10 or IL-4. The Fas/FasL pathway participated in the effect as it was blocked by anti-FasL Abs and reproduced by Fas agonist and recombinant soluble FasL. Furthermore, expression of FasL was much higher on Treg than on their CD25(-) counterparts. Collectively, these results indicate that Treg act on monocytes by inhibiting their LPS-induced survival through a proapoptotic mechanism involving the Fas/FasL pathway. This may be an important mechanism for septic shock-induced immunosuppression and may offer new perspectives for the treatment of this deadly disease.

Objective: Immunoparalysis has recently emerged as a possible cause explaining the failure of clinical trials in septic shock. Because human peripheral blood CD4+CD25+ T cells have been characterized as suppressor T cells, we hypothesized they might be increased in sepsis-induced immunoparalysis., Design: Prospective, observational, clinical study., Setting: Adult intensive care units in a university hospital., Subjects: Patients with septic shock (n = 16) and healthy individuals (n = 36)., Interventions: None., Measurements and Main Results: In patients with septic shock (mortality rate at 28 days, 56%; mean admission Simplified Acute Physiology Score II, 47), we first illustrated immunoparalysis by showing a severe diminished monocytic human leukocyte antigen (HLA)-DR expression. Afterward, compared with control values, we found in these patients a marked elevation of circulating CD4+CD25+ T cells that were also CD45RO+ and CD69- and overexpressed CTLA-4. Importantly, nonsurvivors (n = 9) presented prolonged lower monocytic HLA-DR expression and higher percentage of CD4+CD25+ T-suppressor T cells., Conclusions: These data support the concept that the persistence of a pronounced immunoparalysis after septic shock is associated with a poor outcome. Whether CD4+CD25+ T cells directly participate in sepsis-induced immunoparalysis remains to be investigated.

Background: Acute dissection of the aorta during myocardial infarction is exceptional. In such cases, fibrinolysis can be fatal., Case Reports: A 63-year-old woman with a history of hypertension was referred to our intensive care unit with the diagnosis of early stage inferior myocardial infarction. Thrombolysis was instituted and the patient rapidly developed cardiovascular collapse with global heart failure. Coronarography was attempted to revascularize the occluded coronary artery but the coronary arteries could not be catheterized. An aortography was performed and gave the diagnosis of De Bakey type I dissection of the aorta. The patient died from cardiac arrest after a phase of low cardiac output., Discussion: This case illustrates how myocardial infarction can complicate or mask acute dissection of the aorta. It also raises the question of transthoracic echocardiography prior to institution of fibrinolysis.

The objective of this randomized study was to compare the occurrence of nosocomial pneumonia in nasotracheally intubated patients who were randomly allocated either to a systematic search of sinusitis by CT scan (study group) or not (control group). A total of 399 patients were included: 272 male and 127 female; mean age, 61 +/- 17 yr; SAPS: 12.6 +/- 4.9. The study group consisted of 199 patients and the control group consisted of 200. In the study group, sinus CT scans were performed in case of fever at Days 4 and 8 and then every 7 d. Nosocomial sinusitis was defined as follows: fever of >/= 38 degrees C, radiographic (sinusal air-fluid level or opacification on CT scan) signs, and presence of purulent aspirate from the involved sinus puncture with >/= 10(3) cfu/ml. Patients with sinusitis received sinus lavage and intravenously administered antibiotics. In the study group, 80 patients experienced nosocomial sinusitis. In the control group, no patient was treated for a sinusitis. Ventilator-associated bronchopneumonia (VAP) was observed in 88 patients: 37 in the study group (1 mo Kaplan-Meier estimate, 34%) versus 51 in the control group (1 mo Kaplan-Meier estimate, 47%); (p = 0.02, log-rank test; relative risk [RR] = 0.61; 95% confidence interval [CI], 0.40 to 0.93). Two months overall mortality was estimated at 36% in the study group versus 46% in the control group (p = 0.03, log-rank test; RR = 0.71; 95% CI, 0.52 to 0.97). We conclude that the occurrence of VAP in patients undergoing prolonged mechanical ventilation via a nasotracheal intubation can be prevented by the systematic search and treatment of nosocomial sinusitis. The effect on mortality should be confirmed.

Thrombolytic treatment of acute myocardial infarction (MI) is limited by the time elapsed since onset, accuracy of the diagnosis and the presence of contra-indications. These factors were prospectively investigated in 173 consecutive patients with proven acute MI, admitted to a city hospital between July and December 1986. Fifty-eight patients (35%) were admitted within three hours of onset of symptoms. Delay in calling a doctor or ambulance was significant: 50% of patients waited for more than two hours after onset of symptoms, 40% more than three hours. Duration of transport to hospital averaged 30 min. Infarct-typical angina of at least 30 min had been present in 143 patients (83%). Atypical symptoms and silent MI was more frequent in the older patients. Diagnostic ST segment elevation of 2 to 3 mm on admission was present in 59 (34%) patients. After consideration of contraindications, present in 120 patients with altogether 165 potential factors, thrombolytic treatment was possible in only seven (4%) of those with the greater ST elevations within three hours after onset of symptoms and 13 (7.5%) within six hours. The most frequent contraindications were age (over 75 years), hypotension, re-infarction at the same site, intramuscular injections (unspecified drugs) within the preceding seven days, or resuscitation with cardiac massage before admission.