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Background: Vascular access for renal replacement therapy (RRT) is routine question in the intensive care unit. Randomized trials comparing jugular and femoral sites have shown similar rate of nosocomial events and catheter dysfunction. However, recent prospective observational data on RRT catheters use are scarce. We aimed to assess the site of RRT catheter, the reasons for catheter replacement, and the complications according to site in a large population of critically ill patients with acute kidney injury., Patients and Methods: We performed an ancillary study of the AKIKI study, a pragmatic randomized controlled trial, in which patients with severe acute kidney injury (KDIGO 3 classification) with invasive mechanical ventilation, catecholamine infusion or both were randomly assigned to either an early or a delayed RRT initiation strategy. The present study involved all patients who underwent at least one RRT session. Number of RRT catheters, insertion sites, factors potentially associated with the choice of insertion site, duration of catheter use, reason for catheter replacement, and complications were prospectively collected., Results: Among the 619 patients included in AKIKI, 462 received RRT and 459 were finally included, with 598 RRT catheters. Femoral site was chosen preferentially (n = 319, 53%), followed by jugular (n = 256, 43%) and subclavian (n = 23, 4%). In multivariate analysis, continuous RRT modality was significantly associated with femoral site (OR = 2.33 (95% CI (1.34-4.07), p = 0.003) and higher weight with jugular site [88.9 vs 83.2 kg, OR = 0.99 (95% CI 0.98-1.00), p = 0.03]. Investigator site was also significantly associated with the choice of insertion site (p = 0.03). Cumulative incidence of catheter replacement did not differ between jugular and femoral site [sHR 0.90 (95% CI 0.64-1.25), p = 0.67]. Catheter dysfunction was the main reason for replacement (n = 47), followed by suspected infection (n = 29) which was actually seldom proven (n = 4). No mechanical complication (pneumothorax or hemothorax) occurred., Conclusion: Femoral site was preferentially used in this prospective study of RRT catheters in 31 French intensive care units. The choice of insertion site depended on investigating center habits, weight, RRT modality. A high incidence of catheter infection suspicion led to undue replacement.

Background: Improving outcomes of older patients admitted into intensive care units (ICU) is a raising concern. This study aimed at determining which geriatric and ICU parameters were associated with in-hospital and long-term mortality in this population., Methods: We conducted a prospective multicentric observational cohort study, including patients aged 75 years and older requiring mechanical ventilation, admitted between September 2012 and December 2013 into ICU of 13 French hospitals. Comprehensive geriatric assessment at ICU admission and ICU usual parameters were registered in a standardized manner. Survival was recorded and comprehensive geriatric assessment was updated after 1 year during a dedicated home visit., Results: 501 patients were analyzed. 108 patients (21.6%) died during the hospital stay. One-year survival rate was 53.8% (IC 95% [49.2%; 58.2%]). Factors associated with increased in-hospital mortality were higher acute illness severity score, resuscitated cardiac arrest as primary ICU diagnosis, perception of anxiety and low quality of life by the proxy, and living in a chronic care facility before ICU admission. Among patients alive at hospital discharge, factors associated with increased 1-year mortality in multivariate analysis were longer duration of mechanical ventilation, all primary ICU diagnoses other than septic shock, a Katz-activities of daily living (ADL) score below 5 and living in a chronic care facility before ICU admission. Among the 163 survivors at 1 year who received a second comprehensive geriatric assessment, the ADL score (functional abilities) showed a significant but moderate decline over time, whereas the Mini-Zarit score (family burden) improved. No significant change in patients' place of life was observed after 1 year, and quality of life was reported as happy-to-very-happy in 88% of survivors., Conclusions: The mortality rate remains high among older ICU patients requiring mechanical ventilation. Factors associated with short- and long-term mortality combined geriatric and ICU criteria, which should be jointly evaluated in routine care. Clinical trial registration NCT01679171.

Aims: We aimed at assessing the effectiveness of renal replacement therapy in patients severely self-poisoned with baclofen and with normal kidney function., Methods: A population pharmacokinetic model was built using analytical data extracted from 26 baclofen poisoning cases reported to a French Poison Centre: 8 patients underwent renal replacement therapy (RRT), 18 did not. In the RRT group, 2 patients suffered from kidney failure. Mechanical ventilation was required for 20 patients with normal kidney function; 15 were not treated by RRT and 5 were. Pharmacokinetic profiles of baclofen were measured in 28 patients and further modelled by a non-parametric approach (PMetrics®). The total data set was divided into a building data set (26 patients, 57 observations) and a validation set (2 external patients, 6 observations). Then, the estimated elimination half-life of baclofen and the duration of intubation were compared in patients with or without RRT using Wilcoxon-Mann-Whitney test., Results: A model using three parameters plus a lag time and bioavailability was necessary to determine the pharmacokinetics of baclofen. Estimated elimination half-life in the 'RRT' group and the 'no RRT' group were respectively 3.1 [2.2-4.8] h (n = 6 patients) and 3.4 [1.4-5.5] h (n = 19 patients, p = 0.53). The median duration of intubation was not significantly different between groups (72 [48-72] h and 72 [24-96] h, respectively; p = 0.38)., Conclusion: Renal replacement therapy did not appear to significantly increase baclofen clearance in patients without kidney failure., (Copyright © 2020 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: Students' choice of medical specialties has evolved throughout year, with a growing interest in quality of life and in technological specialties. We investigated the repartition of such choices in the world and its influencing factors with a focus on the gender's influence, for helping policy-makers to deal with medical shortage and territorial to specialty disconnect., Methods: A systematic search was conducted on MEDLINE and Scopus from January 2010 to January 2020. Data extraction and analysis followed JBI and PRISMA recommendations. The selected articles had to focus on medical students, detail their choice of specialty, and look for factors influencing their choice. Articles were excluded if they only assessed the attractiveness of a specialty, or evaluated a public policy. This review was registered on PROSPERO, CRD 42020169227., Findings: 751 studies were screened, and fifty-four were included. Surgery and internal medicine were the most wanted specialties, both in occidental and non-occidental countries. The main factors influencing the choice of specialty were lifestyle, work-life balance and discipline interest, with variation across different countries. Gender clearly affected this choice with 63.7% of men willing radiology and 14.7% of men in obstetrics and gynecology., Interpretation: Influential factors vary with specialty and are affected by the country of residence. Gender has a great impact in students' willingness to work in specific specialties. Policymakers should adapt their appealing strategies according to the country and the medical discipline concerned., Funding: The authors have no support or funding to report., Competing Interests: We declare no competing interest, (© 2020 The Author(s).)

Purpose: Little is known on the incidence of discomfort during the end-of-life of intensive care unit (ICU) patients and the impact of sedation on such discomfort. The aim of this study was to assess the incidence of discomfort events according to levels of sedation., Methods: Post-hoc analysis of an observational prospective multicenter study comparing immediate extubation vs. terminal weaning for end-of-life in ICU patients. Discomforts including gasps, significant bronchial obstruction or high behavioural pain scale score, were prospectively assessed by nurses from mechanical ventilation withdrawal until death. Level of sedation was assessed using the Richmond Agitation-Sedation Scale (RASS) and deep sedation was considered for a RASS - 5. Psychological disorders in family members were assessed up until 12 months after the death., Results: Among the 450 patients included in the original study, 226 (50%) experienced discomfort after mechanical ventilation withdrawal. Patients with discomfort received lower doses of midazolam and equivalent morphine, and were less likely to have deep sedation than patients without discomfort (59% vs. 79%, p < 0.001). After multivariate logistic regression, extubation (as compared terminal weaning) was the only factor associated with discomfort, whereas deep sedation and administration of vasoactive drugs were two factors independently associated with no discomfort. Long-term evaluation of psychological disorders in family members of dead patients did not differ between those with discomfort and the others., Conclusion: Discomfort was frequent during end-of-life of ICU patients and was mainly associated with extubation and less profound sedation.

Purpose: Bereavement research has helped to improve end-of-life practices in the ICU. However, few studies have explored bereaved relatives experience of research participation in this context. We aimed to explore the experience of bereaved relatives' participation in the ARREVE study which included three telephone follow-up calls to complete several quantitative tools., Methods: Volunteer relatives who participated in the 12-month follow-up call completed a questionnaire about research participation that included ten open-ended questions so that respondents could use their own words and thoughts. These open-ended questions were analyzed using qualitative analysis that examines themes within the data., Results: 175/311 relatives completed the questionnaire. Three themes were derived from the thematic analysis: (1) struggling: reactivation of emotional distress associated with the ICU experience and the loss is frequent, specifically during the 1st follow-up call. (2) Resilience: as time goes by, research participation becomes increasingly positive. The calls are a help both in giving meaning to the relatives' experience and in accepting the loss. (3) Recognition: research calls can compensate for the absence of support during bereavement., Conclusion: Although some emotional difficulties must be acknowledged, bereavement research is overall associated with benefits, by facilitating emotional adjustments, meaning-making and resilience. Lack of support and social isolation during bereavement are frequent experiences, revealing that support strategies for bereaved relatives should be developed after the loss of a loved one in the ICU.

Our objective was to bridge the gap between gerontechnology developers and hospitalized frail elderly people, in order to promote open gerontechnology innovation in hospitals. We designed a hospital-based living lab that provides reflexive "idea incubator workshops" that gather both the users and the developers of technology, supplemented with an "experimental hospital room" for the testing of devices by older inpatients. The ALLEGRO living lab was delivered in 2018 at the Geriatric Department of Angers University Hospital, France. The workshops and experimental hospital room should help frail older inpatients to participate in the co-design and co-development of new technologies to improve hospital care and promote successful aging., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Increased renal resistive index (RI) measured by Doppler ultrasonography has been shown to be associated with acute kidney injury (AKI) in septic patients. However, its clinical use is limited by poor sensitivity and specificity which may be explained by its numerous determinants [in particular mean arterial pressure (MAP)]. We measured, in patients with septic shock, RI at different MAP levels over a short period of time on the admission day to ICU (D1) and every 3 days until day 10 (D10) to define the determinants of RI and study specifically the relationship between RI and MAP., Results: Consecutive patients with septic shock without preexisting chronic renal dysfunction were included in this prospective cohort study in two ICUs. Sixty-five patients were included in the study. Thirty-three (50.8%) and 15 (23.1%) patients had a history of chronic hypertension or diabetes, respectively. At D3, 35 patients presented AKI with AKIN 2 or 3 criteria (severe AKI, AKIN2-3 group) and 30 presented no AKIN or AKIN 1 criteria (AKIN0-1 group). As previously described, RI at D1 was higher in the AKIN2-3 group than in the AKIN0-1 group (0.73 interquartile range [0.67; 0.78] vs. 0.67 [0.59; 0.72], p = 0.001). A linear mixed model for predicting RI from D1 to D10 showed that an increase in pulse pressure, presence of severe AKI and additional day of ICU hospitalization were associated with an increase in RI. An increase in MAP and recovery from severe AKI were associated with a decrease in RI. In the presence of chronic hypertension or diabetes, an increase in MAP resulted in a lower decrease in RI, than in the absence of such factors. Presence of AKI at D3 did not impact the relationship between MAP and RI., Conclusions: Severe AKI was associated with a reversible increase in RI without significant interaction with the relationship between MAP and RI. Conversely, the presence of chronic hypertension and/or diabetes interacted with this relationship.

Purpose: We set out to summarize the current challenges in academic conflict of interest., Methods: This is a narrative review by a multidisciplinary, multinational panel of academic officers including deans of medical/pharmacy schools., Results and Conclusions: Disclosing conflict of interest has become the appropriate professional behavior since the 1990s in response to the necessity to fix moral and financial fences around medical activities. The nature of the conflict of interest is academic when either the conflict relates to academic duties and/or the nature of the interest is academic. People usually distinguish between real conflict of interest, when private interest overtly influences one's professional obligations; potential conflict of interest, when there is no obvious direct link between a person interests and current duties without ruling out that expected changes in duties cause a situation of conflict; and apparent conflict of interest, when the risk does not really exist, but serious doubts remain. Areas at risk of academic conflict of interest include peer review process for grant evaluation or journals, scientific communications such as elaborating and disseminating clinical guidelines, lecturing at meeting, advising decision-makers, teaching activities, and mentoring. The management of academic conflict of interest should consider actions in four domains, i.e., education, prevention, measures for enforcement and solving, and communication. Academic conflicts of interest are as frequent as financial conflicts but more difficult to identify and assess, and much less addressed in the literature. Generating more evidence from high-quality research is mandated to improve the management of academic and more generally non-financial conflicts of interest.

Purpose: Since renal biopsy is rarely performed for identifying acute tubular necrosis in ICU patients, there is little information on the real histopathological abnormalities observed in such situations., Materials and Methods: The clinical data of 27 patients with a confirmed diagnostic of acute tubular necrosis issued from two recent series gathering 125 patients who had renal biopsy during their ICU stay were reviewed. They were divided into sepsis (n = 14) and non-sepsis (n = 13) groups. Histopathologic lesions were reanalyzed and semi-quantitatively graded by a pathologist without knowledge of clinical characteristics of the patients., Results: SAPS2 and SOFA scores were identical in the two groups. Half of the patients had neither sepsis nor shock. The histopathological score was higher in the septic than in the non-septic group: 9 [IC; 9-11] vs 7 [IC 5.25-8.75]; p = 0.01. There was no striking histopathological difference between septic and non-septic patients. However, the cytotoxic edema score was higher (3 [1; 3] vs 1 [0; 1]; p = 0.006), and interstitial infiltration with polymorphonuclears was more frequent (p = 0.02) in septic than in non-septic patients., Conclusions: Septic and non-septic ICU patients with ATN had similar histopathologic features but lesions were more severe than in septic than in non-septic patients., (Copyright © 2018. Published by Elsevier Inc.)

Rationale: The optimal strategy for initiation of renal replacement therapy (RRT) in patients with severe acute kidney injury in the context of septic shock and acute respiratory distress syndrome (ARDS) is unknown., Objectives: To examine the effect of an early compared with a delayed RRT initiation strategy on 60-day mortality according to baseline sepsis status, ARDS status, and severity., Methods: Post hoc analysis of the AKIKI (Artificial Kidney Initiation in Kidney Injury) trial., Measurements and Main Results: Subgroups were defined according to baseline characteristics: sepsis status (Sepsis-3 definition), ARDS status (Berlin definition), Simplified Acute Physiology Score 3 (SAPS 3), and Sepsis-related Organ Failure Assessment (SOFA). Of 619 patients, 348 (56%) had septic shock and 207 (33%) had ARDS. We found no significant influence of the baseline sepsis status (P = 0.28), baseline ARDS status (P = 0.94), and baseline severity scores (P = 0.77 and P = 0.46 for SAPS 3 and SOFA, respectively) on the comparison of 60-day mortality according to RRT initiation strategy. A delayed RRT initiation strategy allowed 45% of patients with septic shock and 46% of patients with ARDS to escape RRT. Urine output was higher in the delayed group. Renal function recovery occurred earlier with the delayed RRT strategy in patients with septic shock or ARDS (P < 0.001 and P = 0.003, respectively). Time to successful extubation in patients with ARDS was not affected by RRT strategy (P = 0.43)., Conclusions: Early RRT initiation strategy was not associated with any improvement of 60-day mortality in patients with severe acute kidney injury and septic shock or ARDS. Unnecessary and potentially risky procedures might often be avoided in these fragile populations. Clinical trial registered with www.clinicaltrials.gov (NCT 01932190).

Necrotizing autoimmune myopathy (NAM) is a relatively newly recognized subgroup of idiopathic inflammatory myopathies. The common histopathologic features are myocyte necrosis without significant inflammation. Necrotizing autoimmune myopathy can be associated with connective tissue disorders but can also be triggered by viral infections such as human immunodeficiency virus or malignancy, be statin-induced NAM, or be idiopathic. Here, the authors present the case of a 58-year-old man who was referred to our PET unit for a suspected paraneoplastic syndrome in a context of NAM. Complementary contrast-enhanced CT and 3-dimensional T1-weighted MRI were carried out subsequently in order to resolve the PET/CT abnormalities.

Background: Little is known about the causes, clinical course and long-term outcome of comatose patients with prolonged hypoglycemic encephalopathy., Methods: In a multicenter retrospective study conducted in patients hospitalized from July 1, 2004, to July 1, 2014, we investigated functional long-term prognosis and identified prognosis factors of patients admitted in an intensive care unit (ICU) with prolonged neurological manifestations related to hypoglycemia. Eligible patients were adults admitted to the ICU with a Glasgow Coma Score <8 due to hypoglycemia and persistent consciousness disorders after normalizing blood glucose levels. Patients with possible other causes of consciousness disorders, previous cognitive disorders, hypothermia <35 °C or circulatory arrest within 24 h after ICU admission, were excluded. Follow-up phone call was used to determine patients' functional outcome using modified Rankin Scale (mRS) at a minimum of 1-year follow-up with mRS 0-3 defining good and mRS 4-6 poor outcomes., Results: Forty-nine patients were included. Causes of hypoglycemia were various, mainly including insulin or oral antidiabetic drugs abuse (65%) and neuroendocrine carcinoma (16%). Twenty (41%) patients died in the ICU, two (4%) patients further died and nine (18%) patients had a poor outcome at long-term follow-up. Five patients discharged from the ICU with mRS > 3 improved enough to be in the good outcome group 1 year later. Twenty-two (45%) patients underwent therapeutic limitation, mainly related to no expected hope for improvement. On multivariate analysis, only low mRS prior to ICU admission (OR 2.6; 95% CI 1.1-6.3; P = 0.03) and normal brain imaging (OR 7.1; 95% CI 1.1-44; P = 0.03) were significantly predictive of a good outcome. All patients (n = 15) who remained hypoglycemic >480 min had a poor outcome., Conclusion: Poor outcome was observed in about 60% of this population of hypoglycemic encephalopathy. However, some patients can recover satisfactorily over time.

Correction to: Intensive Care Med (2017) DOI 10.1007/s00134-017-4891-0.

Purpose: Data for ANCA-associated vasculitis (AAV) patients requiring intensive care are scarce., Methods: We included 97 consecutive patients with acute AAV manifestations (new onset or relapsing disease), admitted to 18 intensive care units (ICUs) over a 10-year period (2002-2012). A group of 95 consecutive AAV patients with new onset or relapsing disease, admitted to two nephrology departments with acute vasculitis manifestations, constituted the control group., Results: In the ICU group, patients predominantly showed granulomatosis with polyangiitis and proteinase-3 ANCAs. Compared with the non-ICU group, the ICU group showed comparable Birmingham vasculitis activity score and a higher frequency of heart, central nervous system and lungs involvements. Respiratory assistance, renal replacement therapy and vasopressors were required in 68.0, 56.7 and 26.8% of ICU patients, respectively. All but one patient (99%) received glucocorticoids, 85.6% received cyclophosphamide, and 49.5% had plasma exchanges as remission induction regimens. Fifteen (15.5%) patients died during the ICU stay. The following were significantly associated with ICU mortality in the univariate analysis: the need for respiratory assistance, the use of vasopressors, the occurrence of at least one infection event in ICU, cyclophosphamide treatment, sequential organ failure assessment at admission and simplified acute physiology score II. After adjustment on sequential organ failure assessment or infection, cyclophosphamide was no longer a risk factor for mortality. Despite a higher initial mortality rate of ICU patients within the first hospital stay (p < 0.0001), the long-term mortality of hospital survivors did not differ between ICU and non-ICU groups (18.6 and 20.4%, respectively, p = 0.36). Moreover, we observed no renal survival difference between groups after a 1-year follow-up (82.1 and 80.5%, p = 0.94)., Conclusion: This study supports the idea that experiencing an ICU challenge does not impact the long-term prognosis of AAV patients.

The French Intensive Care Society organized its yearly Paris International Conference in intensive care on June 18-19, 2015. The main purpose of this meeting is to gather the best experts in the field in order to provide the highest quality update on a chosen topic. In 2015, the selected theme was: "Acute Renal Failure in the ICU: from injury to recovery." The conference program covered multiple aspects of renal failure, including epidemiology, diagnosis, treatment and kidney support system, prognosis and recovery together with acute renal failure in specific settings. The present report provides a summary of every presentation including the key message and references and is structured in eight sections: (a) diagnosis and evaluation, (b) old and new diagnosis tools,, ((c) old and new treatments, (d) renal replacement therapy and management, (e) acute renal failure witness of other conditions, (f) prognosis and recovery, (g) extracorporeal epuration beyond the kidney, (h) the use of biomarkers in clinical practice http://www.srlf.org/5th-paris-international-conference-jeudi-18-et-vendredi-19-juin-2015/ .)

Background: According to international guidelines, volume expansion with crystalloids is the first-line treatment for hemodynamic management in patients with severe sepsis or septic shock. Compared to balanced crystalloids, 0.9% sodium chloride (0.9% NaCl) induces hyperchloremia and metabolic acidosis and may alter renal hemodynamics and function. We compared the effects of 0.9% NaCl to a less chloride-concentrated fluid, PlasmaLyte ® (PL) in targeted fluid resuscitation in a randomized, double-blind controlled study in an experimental model of severe sepsis in rats., Results: A sepsis with hypotension was induced by cecal ligature and puncture (CLP) in 40 male Wistar rats (20 for each crystalloid). Rats received fluid resuscitation over a period of 200 min for a targeted mean arterial pressure of 90 mm Hg. Animals received similar volumes of 0.9% NaCl or PL. Unlike PL-resuscitated rats, 0.9% NaCl-resuscitated rats experienced hyperchloremia and metabolic acidosis, whereas systemic hemodynamics, renal hemodynamics and renal function were not significantly different between both groups., Conclusion: In our model of rats with severe sepsis resuscitated with large amounts of crystalloids, 0.9% NaCl-induced hyperchloremic acidosis, but balanced crystalloid did not improve systemic and renal hemodynamics or renal function.

Purpose: The relative merits of immediate extubation versus terminal weaning for mechanical ventilation withdrawal are controversial, particularly regarding the experience of patients and relatives., Methods: This prospective observational multicentre study (ARREVE) was done in 43 French ICUs to compare terminal weaning and immediate extubation, as chosen by the ICU team. Terminal weaning was a gradual decrease in the amount of ventilatory assistance and immediate extubation was extubation without any previous decrease in ventilatory assistance. The primary outcome was posttraumatic stress symptoms (Impact of Event Scale Revised, IES-R) in relatives 3 months after the death. Secondary outcomes were complicated grief, anxiety, and depression symptoms in relatives; comfort of patients during the dying process; and job strain in staff., Results: We enrolled 212 (85.5%) relatives of 248 patients with terminal weaning and 190 relatives (90.5%) of 210 patients with immediate extubation. Immediate extubation was associated with airway obstruction and a higher mean Behavioural Pain Scale score compared to terminal weaning. In relatives, IES-R scores after 3 months were not significantly different between groups (31.9 ± 18.1 versus 30.5 ± 16.2, respectively; adjusted difference, -1.9; 95% confidence interval, -5.9 to 2.1; p = 0.36); neither were there any differences in complicated grief, anxiety, or depression scores. Assistant nurses had lower job strain scores in the immediate extubation group., Conclusions: Compared to terminal weaning, immediate extubation was not associated with differences in psychological welfare of relatives when each method constituted standard practice in the ICU where it was applied. Patients had more airway obstruction and gasps with immediate extubation., Trial Registration: ClinicalTrials.gov identifier: NCT01818895.

Background: Bevacizumab, an anti-VEGF monoclonal antibody, has recently emerged as a new option for severe forms of hereditary hemorrhagic telangiectasia (HHT). Its utilization in this orphan disease has rapidly spread despite the lack of randomized trials and international guidelines. The objective of this study is to report the main clinical data (baseline characteristics, dose schedule, efficacy, adverse events and deaths) of HHT patients treated by intravenous bevacizumab in France., Methods: Retrospective observational study of HHT patients treated with bevacizumab for a severe form of the disease in the 14 centers of the French HHT network., Results: Forty-six patients (median age: 68 years) were treated between March 2009 and May 2015. Ten patients were treated for high output cardiac failure, 20 patients for severe hemorrhages and 16 for both indications. The standard protocol (6 infusions of 5mg/kg every 2 weeks) was initially used in 89% of the cases but diverse strategies were subsequently applied. A clinical improvement was noted by the referent physician for 74% of the patients with a median effect's duration of 6 months. Wound healing complications led to 2 amputations. Arthralgia/arthritis and arterial hypertension occurred in 5 patients each. One third of the patients were dead at the time of the final update, coherently with age and the poor prognosis of these highly symptomatic patients., Conclusion: Intravenous bevacizumab seems to provide a clinical benefice in severe HHT patients. Precautions concerning wound healing and vascular pathologies must be respected. Prospective double blinded versus placebo trials are needed.

Background: An extended course of tetanus (up to 6 weeks) requiring ICU admission and protracted mechanical ventilation (MV) may have a significant impact on short- and long-term survival. The subject is noteworthy and deserves to be discussed., Methods: Twenty-two ICUs in France performed tetanus screenings on patients admitted between January 2000 and December 2014. Retrospective data were collected from hospital databases and through the registers of the town hall of the patients., Results: Seventy patients were included in 15 different ICUs. Sixty-three patients suffered from severe or very severe tetanus according to the Ablett classification. The median age was 80 years [interquartile range 73-84], and 86% of patients were women. Ninety per cent of patients (n = 63) required MV for a median of 36 days [26-46], and 66% required administration of a neuromuscular-blocking agent for 23 days [14-29]. A nosocomial infection occurred in 43 patients (61%). ICU and 1-year mortality rates were 14% (n = 10) and 16% (n = 11), respectively. Forty-five per cent of deaths occurred during the first week. Advanced age, a higher SAPS II, any infection, and the use of vasopressors were significantly associated with a lower number of days alive without ventilator support by day 90. Age was the only factor that significantly differed between deceased and survivors at 1 year (83 [81-85] vs. 79 [73-84] years, respectively; p = 0.03). Sixty-one per cent of survivors suffered no impairment to their functional status., Conclusion: In a high-income country, tetanus mainly occurs in healthy elderly women. Despite prolonged MV and extended ICU length of stay, we observed a low 1-year mortality rate and good long-term functional status.

Aims: Baclofen has gained interest in treating alcohol use disorder patients. These patients are at risk of voluntary drug intoxications. Understanding the context of baclofen's widespread use for alcohol use disorder, a recent evaluation of the epidemiology, morbidity and mortality of baclofen self-poisoning episodes is necessary., Methods: All baclofen self-poisoning reported to the Western France Poison Control Centre between January 2008 and December 2015 were included for analysis in this retrospective study. Baclofen poisoning cases were compared to the 31,859 non-baclofen voluntary poisoning cases declared over the same period., Results: Number of baclofen poisoning grew from 8 cases in 2008 to 91 cases in 2015, attributable to patients purposely treated for alcohol use disorder. Overall, 190 cases were considered: 111 patients (59%) had Glasgow coma score (GCS) ≤12 at hospital admission and 77 had GCS > 12 (41%). Eighty patients required mechanical ventilation (42.6%). Neurological severity (GCS ≤ 12) was associated with seizures (n = 24, 22% vs. n = 2, 3%, P < 0.001). Two patients were deceased at first medical evaluation and three died in the hospital (mortality rate 2.6%). Non-baclofen cases had lower rate of endotracheal intubation (n = 1833, 6%, P < 0.001) and mortality rate (n = 299, 0.1%, P = 0.02)., Conclusions: Baclofen self-poisoning cases has risen in recent years due to baclofen intake for alcohol use disorder therapies. The risk-benefit ratio may be evaluated before baclofen is safely prescribed., (© The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Introduction: IgA vasculitis is a systemic small vessel leukocytoclastic vasculitis characterized by skin purpura, arthritis, abdominal pain and nephritis. Most of the abdominal complications are due to edema and hemorrhage in the small bowel wall, but rarely to acute secondary pancreatitis., Case Report: Here, we report a 53-year-old woman who presented with acute pancreatitis and, secondarily, developed skin purpura and arthritis at the seventh day of the clinical onset. Biological tests and computed tomographic scan allowed to rule out another cause of pancreatitis and IgA vasculitis was diagnosed as its etiology. The outcome was favorable without any relapse on glucocorticoids., Conclusion: Despite its rarity, pancreatitis is a potential life-threatening complication of IgA vasculitis in which the role of glucocorticoids and immunosuppressive drugs remains uncertain. A prompt elimination of other usual pancreatitis etiologies is mandatory to improve the management of the patients., (Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Acute kidney injury (AKI) is common in critically ill patients and associated with grim short- and long-term outcome. Although in the vast majority of cases AKI is multifactorial, with sepsis, shock and nephrotoxicity accounting for most episodes, specific causes of AKI are not uncommon. Despite remaining uncertainties regarding their prevalence in the ICU, prompt recognition of specific aetiologies of AKI is likely to ensure timely management, limit worsening of renal dysfunction, and ultimately limit renal and systemic consequences of AKI. The ability to recognize conditions that may be associated with specific aetiologies and the appropriate use of clinical imaging, biological and immunological tests, along with optimal assessment of the need for renal biopsies, should be part of routine ICU care. In this review, we summarize uncertainties, current knowledge and recent advances regarding specific types of AKI. We describe the most common specific causes as well as rare aetiologies requiring urgent management, and outline available tools that may be used during the diagnostic work-up along with their limitations.

Acute kidney injury is frequently encountered in patients in intensive care units and is associated with higher risk of mortality and chronic renal failure. Even small increases in serum creatinine are associated with adverse outcomes. Many interventions have been proposed to prevent or treat acute kidney injury in patients in intensive care units. However, no intervention has proved its efficacy in large randomized control trials. This review presents the various attempts aiming at acute kidney injury improvement in patients in intensive care units published over the recent years: hemodynamic interventions, "usual" drugs used in intensive care units, modulation of inflammation and hemostasis, remote ischemic conditioning, drugs specifically dedicated for acute kidney injury, and stimulation of renal recovery., (Copyright © 2017 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.)

Rationale: During noninvasive ventilation (NIV) for chronic obstructive pulmonary disease (COPD) exacerbations, helium/oxygen (heliox) reduces the work of breathing and hypercapnia more than air/O 2 , but its impact on clinical outcomes remains unknown., Objectives: To determine whether continuous administration of heliox for 72 hours, during and in-between NIV sessions, was superior to air/O 2 in reducing NIV failure (25-15%) in severe hypercapnic COPD exacerbations., Methods: This was a prospective, randomized, open-label trial in 16 intensive care units (ICUs) and 6 countries. Inclusion criteria were COPD exacerbations with Pa CO 2  ≥ 45 mm Hg, pH ≤ 7.35, and at least one of the following: respiratory rate ≥ 25/min, Pa O 2  ≤ 50 mm Hg, and oxygen saturation (arterial [Sa O 2 ] or measured by pulse oximetry [Sp O 2 ]) ≤ 90%. A 6-month follow-up was performed., Measurements and Main Results: The primary endpoint was NIV failure (intubation or death without intubation in the ICU). The secondary endpoints were physiological parameters, duration of ventilation, duration of ICU and hospital stay, 6-month recurrence, and rehospitalization rates. The trial was stopped prematurely (445 randomized patients) because of a low global failure rate (NIV failure: air/O 2 14.5% [n = 32]; heliox 14.7% [n = 33]; P = 0.97, and time to NIV failure: heliox group 93 hours [n = 33], air/O 2 group 52 hours [n = 32]; P = 0.12). Respiratory rate, pH, Pa CO 2 , and encephalopathy score improved significantly faster with heliox. ICU stay was comparable between the groups. In patients intubated after NIV failed, patients on heliox had a shorter ventilation duration (7.4 ± 7.6 d vs. 13.6 ± 12.6 d; P = 0.02) and a shorter ICU stay (15.8 ± 10.9 d vs. 26.7 ± 21.0 d; P = 0.01). No difference was observed in ICU and 6-month mortality., Conclusions: Heliox improves respiratory acidosis, encephalopathy, and the respiratory rate more quickly than air/O 2 but does not prevent NIV failure. Overall, the rate of NIV failure was low. Clinical trial registered with www.clinicaltrials.gov (NCT 01155310).

Rationale: Encephalitis caused by anti-N-methyl-d-aspartate receptor (NMDAR) antibodies is the leading cause of immune-mediated encephalitis. There are limited data on intensive care unit (ICU) management of these patients., Objectives: To identify prognostic factors of good neurologic outcome in patients admitted to an ICU with anti-NMDAR encephalitis., Methods: This was an observational multicenter study of all consecutive adult patients diagnosed with anti-NMDAR encephalitis at the French National Reference Centre, admitted to an ICU between 2008 and 2014. The primary outcome was a good neurologic outcome at 6 months after ICU admission, defined by a modified Rankin Scale score of 0-2., Measurements and Main Results: Seventy-seven patients were included from 52 ICUs. First-line immunotherapy consisted of steroids (n = 61/74; 82%), intravenous immunoglobulins (n = 71/74; 96%), and plasmapheresis (n = 17/74; 23%). Forty-five (61%) patients received second-line immunotherapy (cyclophosphamide, rituximab, or both). At 6 months, 57% of patients had a good neurologic outcome. Independent factors of good neurologic outcome were early (≤8 d after ICU admission) immunotherapy (odds ratio, 16.16; 95% confidence interval, 3.32-78.64; for combined first-line immunotherapy with steroids and intravenous immunoglobulins vs. late immunotherapy), and a low white blood cell count on the first cerebrospinal examination (odds ratio, 9.83 for <5 vs. >50 cells/mm 3 ; 95% confidence interval, 1.07-90.65). Presence of nonneurologic organ failures at ICU admission and occurrence of status epilepticus during ICU stay were not associated with neurologic outcome., Conclusions: The prognosis of adult patients with anti-NMDAR encephalitis requiring intensive care is good, especially when immunotherapy is initiated early, advocating for prompt diagnosis and early aggressive treatment.

Acute kidney injury (AKI) is a syndrome that has progressed a great deal over the last 20 years. The decrease in urine output and the increase in classical renal biomarkers, such as blood urea nitrogen and serum creatinine, have largely been used as surrogate markers for decreased glomerular filtration rate (GFR), which defines AKI. However, using such markers of GFR as criteria for diagnosing AKI has several limits including the difficult diagnosis of non-organic AKI, also called "functional renal insufficiency" or "pre-renal insufficiency". This situation is characterized by an oliguria and an increase in creatininemia as a consequence of a reduction in renal blood flow related to systemic haemodynamic abnormalities. In this situation, "renal insufficiency" seems rather inappropriate as kidney function is not impaired. On the contrary, the kidney delivers an appropriate response aiming to recover optimal systemic physiological haemodynamic conditions. Considering the kidney as insufficient is erroneous because this suggests that it does not work correctly, whereas the opposite is occurring, because the kidney is healthy even in a threatening situation. With current definitions of AKI, normalization of volaemia is needed before defining AKI in order to avoid this pitfall.

Context: Routine biological tests are frequently ordered in self-poisoning patients, but their clinical relevance is poorly studied., Materials and Methods: This is a prospective multicentric observational study conducted in the emergency departments and intensive care units of 5 university and nonuniversity French hospitals. Adult self-poisoning patients without severely altered vital status on admission were prospectively included., Results: Routine biological test (serum electrolytes and creatinine, liver enzymes, bilirubin, blood cell count, prothrombin time) ordering and results were analyzed. A total of 1027 patients were enrolled (age, 40.2 ± 14 years; women, 61.5%); no patient died during the hospital stay. Benzodiazepine was suspected in more than 70% of cases; 65% (range, 48%-80%) of patients had at least 1 routine biological test performed. At least 1 abnormal test was registered in 23% of these patients. Three factors were associated with abnormal test results: age older than 40 years, male sex, and poisoning with a drug known to alter routine tests (ie, acetaminophen, NSAIDs, metformine, lithium). Depending on these factors, abnormal results ranged from 14% to 48%. Unexpected severe life-threatening conditions were recorded in 6 patients. Only 3 patients were referred to the intensive care unit solely because of abnormal test results., Conclusion: Routine biological tests are commonly prescribed in nonsevere self-poisoning patients. Abnormal results are frequent but their relevance at bedside remains limited., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Terminal extubation (TE) and terminal weaning (TW) are the methods available for withdrawing mechanical ventilation. Perceptions of TE and TW by intensive care unit (ICU) staff may influence bedside practices and the feasibility of studies comparing these methods., Methods: From January to June 2013, 5 nurses and 5 physicians in each of 46 (out of 70, 65.7 %) French ICUs completed an anonymous self-questionnaire. Clusters of staff members defined by perceptions of TE and TW were identified by exploratory analysis. Denominators for computing percentages were total numbers of responses to each item; cases with missing data were excluded for the relevant item., Results: Of the 451 (98 %) participants (225 nurses and 226 physicians), 37 (8.4 %) had never or almost never performed TW and 138 (31.3 %) had never or almost never performed TE. A moral difference between TW and TE was perceived by 205 (45.8 %) participants. The exploratory analysis identified three clusters defined by personal beliefs about TW and TE: 21.2 % of participants preferred TW, 18.1 % preferred TE, and 60.7 % had no preference. A preference for TW seemed chiefly related to unfavorable perceptions or insufficient knowledge of TE. Staff members who preferred TE and those with no preference perceived TE as providing a more natural dying process with less ambiguity., Conclusion: Nearly two-fifths of ICU nurses and physicians in participating ICUs preferred TW or TE. This finding suggests both a need for shared decision-making and training before performing TE or TW and a high risk of poor compliance with randomly allocated TW or TE.

Non-pharmaceutical forms of Artemisia annua (a Chinese plant containing artemisinin) are used by some travellers who believe these products are safer than anti-malarial drugs. We report two cases of severe Plasmodium falciparum malaria requiring hospitalization in an Intensive Care Unit following prophylaxis with non-pharmaceutical A. annua in French travellers., (© International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of debate., Methods: In this multicenter randomized trial, we assigned patients with severe acute kidney injury (Kidney Disease: Improving Global Outcomes [KDIGO] classification, stage 3 [stages range from 1 to 3, with higher stages indicating more severe kidney injury]) who required mechanical ventilation, catecholamine infusion, or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of renal-replacement therapy. With the early strategy, renal-replacement therapy was started immediately after randomization. With the delayed strategy, renal-replacement therapy was initiated if at least one of the following criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter, or oliguria for more than 72 hours after randomization. The primary outcome was overall survival at day 60., Results: A total of 620 patients underwent randomization. The Kaplan-Meier estimates of mortality at day 60 did not differ significantly between the early and delayed strategies; 150 deaths occurred among 311 patients in the early-strategy group (48.5%; 95% confidence interval [CI], 42.6 to 53.8), and 153 deaths occurred among 308 patients in the delayed-strategy group (49.7%, 95% CI, 43.8 to 55.0; P=0.79). A total of 151 patients (49%) in the delayed-strategy group did not receive renal-replacement therapy. The rate of catheter-related bloodstream infections was higher in the early-strategy group than in the delayed-strategy group (10% vs. 5%, P=0.03). Diuresis, a marker of improved kidney function, occurred earlier in the delayed-strategy group (P<0.001)., Conclusions: In a trial involving critically ill patients with severe acute kidney injury, we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients. (Funded by the French Ministry of Health; ClinicalTrials.gov number, NCT01932190.).

Purpose: On a regular basis, the intensivist encounters the patient who is difficult to wean from mechanical ventilatory support. The causes for failure to wean from mechanical ventilatory support are often multifactorial and involve a complex interplay between cardiac and pulmonary dysfunction. A potential application of point of care ultrasonography relates to its utility in the process of weaning the patient from mechanical ventilatory support., Methods: This article reviews some applications of ultrasonography that may be relevant to the process of weaning from mechanical ventilatory support., Results: The authors have divided these applications of ultrasonography into four separate categories: the assessment of cardiac, diaphragmatic, and lung function; and the identification of pleural effusion; which can all be evaluated with ultrasonography during a dynamic process in which the intensivist is uniquely positioned to use ultrasonography at the point of care., Conclusions: Ultrasonography may have useful application during the weaning process from mechanical ventilatory support.

Purpose: Reversibility and impact of diaphragmatic dysfunction (DD) are unknown. The principal aim was to describe diaphragmatic function as assessed by ultrasonography during weaning trials., Materials and Methods: The present study is a 6-month single-center prospective study. All patients under mechanical ventilation for more than 7 days and eligible for a spontaneous breathing trial (SBT) were enrolled prospectively., Intervention: Two blinded ultrasonographers evaluated each hemidiaphragm during SBT. Prevalence of DD among weaning failure and death and interobserver reproducibility have been evaluated., Results: The 34 included patients had a mean Simplified Acute Physiology Score version II of 55.7 ± 14 and a median intensive care unit (ICU) stay length of 17 days (13-30). Diaphragmatic dysfunction was found in 13 (38%) patients, on both sides in 8. Bilateral DD resolved before ICU discharge in 5 of the 7 reevaluated patients. No weaning failures were recorded. The ICU mortality was higher in patients with DD (37% vs 5%, P = .048). Mean interobserver agreement rate was 91%. Reproducibility was better with M-mode., Conclusion: The ICU-acquired DD usually improves before ICU discharge but might constitute a marker for greater disease severity. The present preliminary results require confirmation in a larger prospective multicenter study., (© The Author(s) 2015.)

Objectives: To better select for patients who most likely will benefit from cardiac surgery among those with infective endocarditis (IE), we aimed to identify preoperative markers associated with poor outcome after cardiac surgery for IE, and to evaluate the accuracy of European System for Cardiac Operative Risk Evaluation (EuroSCORE) II to predict mortality., Methods: We enrolled all adult patients who underwent cardiac surgery during the acute phase of definite IE (Duke Criteria) in two referral centres for cardiac surgery. Patients were identified through intensive care unit (ICU) electronic databases, and data were collected from medical charts on standardized questionnaire., Results: Between 2002 and 2013, 149 patients (117 males), with a median age of 64 years [interquartile range 52-73], fulfilled the inclusion criteria. Main complications before surgery were left ventricular dysfunction (23%), central nervous system symptomatic events (34%) and septic shock (24%). Most patients (95%) presented with valve regurgitation, and 49% had perivalvular abscess. Surgery was performed with a median delay of 12 days [5-24] after IE diagnosis, and mean EuroSCORE II was 15.8 (13.4-18.1). In-hospital mortality was 21%. Preoperative variables associated with mortality in multivariate analysis were obesity [odds ratio (OR) 3.67 [1.10-12.19], P = 0.03], vegetation >15 mm (OR 6.72 [1.46-30.98], P = 0.01), septic shock (OR 4.87 [1.67-14.28], P = 0.004) and mechanical prosthetic valve IE (OR 4.99 [1.72-28.57], P = 0.007). EuroSCORE II underestimated mortality in patients with predicted mortality over 10%., Conclusion: Factors independently predictive of mortality after cardiac surgery for IE are obesity, septic shock, large vegetation and a mechanical prosthetic valve IE. EuroSCORE II underestimates post-cardiac surgery mortality in patients with IE., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Somatic severity of a self-poisoning episode varies widely between patients., Aims: To determine the correlates (psychiatric profiles, long-term outcome) of mechanical ventilation used as a proxy to define somatic severity during a self-poisoning., Method: All patients who required mechanical ventilation were pair-matched with ones who did not for age, gender and presence of psychiatric history. One year after the self-poisoning episode, patients were interviewed using the Hospital Anxiety and Depression Scale (HADS) and a quality-of-life assessment questionnaire (Short-Form 12 Health Survey)., Results: The ventilation group (n = 99) more frequently had mood disorders and less frequently had adjustment disorders (P = 0.007), with a higher depression score on the HADS (P = 0.01) than those in the non-ventilation group (n = 97). Survival curves showed lower survival in the ventilation group (P = 0.03)., Conclusions: Requirement for mechanical ventilation following self-poisoning is associated with a high prevalence of mood disorders and poor long-term outcome., (© The Royal College of Psychiatrists 2016.)

Importance: Acetazolamide has been used for decades as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis, but no large randomized placebo-controlled trial is available to confirm this approach., Objective: To determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with COPD and metabolic alkalosis., Design, Setting, and Participants: The DIABOLO study, a randomized, double-blind, multicenter trial, was conducted from October 2011 through July 2014 in 15 intensive care units (ICUs) in France. A total of 382 patients with COPD who were expected to receive mechanical ventilation for more 24 hours were randomized to the acetazolamide or placebo group and 380 were included in an intention-to treat analysis., Interventions: Acetazolamide (500-1000 mg, twice daily) vs placebo administered intravenously in cases of pure or mixed metabolic alkalosis, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days., Main Outcomes and Measures: The primary outcome was the duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy. Secondary outcomes included changes in arterial blood gas and respiratory parameters, weaning duration, adverse events, use of noninvasive ventilation after extubation, successful weaning, the duration of ICU stay, and in-ICU mortality., Results: Among 382 randomized patients, 380 (mean age, 69 years; 272 men [71.6%]; 379 [99.7%] with endotracheal intubation) completed the study. For the acetazolamide group (n = 187), compared with the placebo group (n = 193), no significant between-group differences were found for median duration of mechanical ventilation (-16.0 hours; 95% CI, -36.5 to 4.0 hours; P = .17), duration of weaning off mechanical ventilation (-0.9 hours; 95% CI, -4.3 to 1.3 hours; P = .36), daily changes of minute-ventilation (-0.0 L/min; 95% CI, -0.2 to 0.2 L/min; P = .72), or partial carbon-dioxide pressure in arterial blood (-0.3 mm Hg; 95% CI, -0.8 to 0.2 mm Hg; P = .25), although daily changes of serum bicarbonate (between-group difference, -0.8 mEq/L; 95% CI, -1.2 to -0.5 mEq/L; P < .001) and number of days with metabolic alkalosis (between-group difference, -1; 95% CI, -2 to -1 days; P < .001) decreased significantly more in the acetazolamide group. Other secondary outcomes also did not differ significantly between groups., Conclusions and Relevance: Among patients with COPD receiving invasive mechanical ventilation, the use of acetazolamide, compared with placebo, did not result in a statistically significant reduction in the duration of invasive mechanical ventilation. However, the magnitude of the difference was clinically important, and it is possible that the study was underpowered to establish statistical significance., Trial Registration: clinicaltrials.gov Identifier: NCT01627639.

Background: Compared to many other cardiovascular diseases, there is a paucity of data on the characteristics of successfully resuscitated cardiac arrest (CA) patients with human immunodeficiency virus (HIV) infection. We investigated causes, clinical features and outcome of these patients, and assessed the specific burden of HIV on outcome., Methods: Retrospective analysis of HIV-infected patients admitted to 20 French ICUs for successfully resuscitated CA (2000-2012). Characteristics and outcome of HIV-infected patients were compared to those of a large cohort of HIV-uninfected patients admitted after CA in the Cochin Hospital ICU during the same period., Results: 99 patients were included (median CD4 lymphocyte count 233/mm(3), viral load 43 copies/ml). When compared with the control cohort of 1701 patients, HIV-infected patients were younger, with a predominance of male, a majority of in-hospital CA (52%), and non-shockable initial rhythm (80.8%). CA was mostly related to respiratory cause (n=36, including 23 pneumonia), cardiac cause (n=33, including 16 acute myocardial infarction), neurologic cause (n=8) and toxic cause (n=5). CA was deemed directly related to HIV infection in 18 cases. Seventy-one patients died in the ICU, mostly for care withdrawal after post-anoxic encephalopathy. After propensity score matching, ICU mortality was not significantly affected by HIV infection. Similarly, HIV disease characteristics had no impact on ICU outcome., Conclusions: Etiologies of CA in HIV-infected patients are miscellaneous and mostly not related to HIV infection. Outcome remains bleak but is similar to outcome of HIV-negative patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The objective of the study to is to determine the characteristics associated with endotracheal intubation in septic shock patients., Methods: This is a post hoc analysis of the database of the SEPSISPAM study, including patients with septic shock., Results: Among the 776 patients, 633 (82%) were intubated within 12 hours of study inclusion (early intubation), 113 (15%) were never intubated, and 30 (4%) had delayed intubation. Intensive care units (ICUs) were classified according to frequency of early intubation: early intubation less than 80% of patients (lowest frequency: 7 ICUs, 254 patients), 80% to 90% (middle frequency: 5 ICUs, 170 patients), and greater than 90% (highest frequency: 6 ICUs, 297 patients). Type of ICU, pulmonary infection, lactate greater than 2 mmol/L, lower Pao2/fraction of inspired oxygen ratio, lower Glasgow score, and absence of immunosuppression were independently associated with early intubation. Patients never intubated had a lower initial severity and a low mortality rate. In comparison to patients intubated early, patients with delayed intubation had had fewer days alive without organ support by day 28. Intensive care units with the highest frequency of early intubation had a higher mortality rate in comparison to ICUs with middle frequency of early intubation. A nonsignificant increased mortality was observed in ICU with lowest frequency of early intubation., Conclusions: Practices regarding the place of endotracheal intubation in septic shock may impact outcome., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Some HIV controllers (HICs) experience CD4+T cell count loss and/or lose their ability to control HIV. In this study, we investigated the rate of immunologic and/or virologic progression (ImmP/VirP) and its determinants in the ANRS CO21/CODEX cohort. Immunologic progression was defined as a lasting fall in CD4+T cell count below 350/mm(3) or more than 200/mm(3) with a baseline count below 600/mm(3). Virologic progression was defined as a HIV viral load (VL) above 2000 copies/mL on two consecutive determinations. Clinical characteristics, immune activation, ultrasensitive HIV VL and total HIV DNA were analyzed. Disease progression was observed in 15 of the 217 patients followed up between 2009 and 2013 (ImmP, n = 10; VirP, n = 5). Progressors had higher ultrasensitive HIV RNA levels at inclusion (i.e. 1-2 years before progression) than non-progressors. ImmP had also lower CD4+T cell nadir and CD4+T cell count at inclusion, and VirP had higher HIV DNA levels in blood. T cell activation and IP10 levels at inclusion were significantly higher in ImmP than in non-progressors. In summary, the lasting loss of CD4+T cells, residual HIV replication and basal levels of immune activation appear to be major determinants of progression in HICs. These factors should be considered for adjusting their follow-up.

Because human immunodeficiency virus (HIV)-infected patients control Epstein-Barr virus (EBV) replication poorly, we hypothesized that reactive hemophagocytic syndrome (HS) in these patients may be associated with poor control of EBV. The files of 314 patients with a suspected diagnosis of HS were retrospectively reviewed. EBV viral load at the time of HS was compared between HIV-positive and -negative patients. A confirmed diagnosis of HS was made in 162 patients [109 males, median age 48 (35-62) years]. Among them, 61 (38%) were HIV positive [median HIV viral load 3.2 (1.6-5.5) log/ml, median CD4 count 94 (28-190)/mm(3)]. The median EBV viral load was significantly higher in HIV-positive than in HIV-negative patients [4.0 (2.9-4.6) vs 2.5 (0-4.2) log/ml, p = 0.002]. It was higher both in patients with hematological malignancy-associated HS [4.0 (2.9-4.4) vs 2.9 (0-4.9) log/ml, p = 0.03] and in patients with infection-associated HS [3.9 (0-4.9) vs 0 (0-4.1) log/ml, p = 0.14]. However, EBV viral load was not significantly higher in HIV-infected patients with confirmed HS than in HIV-infected patients for whom HS was unlikely [4.0 (2.9-4.6) vs 3.9 (2.6-4.1) log/ml, p = 0.48].The high EBV viral load observed in HIV-infected patients with HS may be more likely to reflect the chronic HIV infection than to be the direct trigger of HS.

Introduction: To characterize etiology, clinical course and outcomes of patients in prolonged refractory status epilepticus (PRSE) and looking for prognostic factors., Methods: Retrospective study conducted in patients hospitalized from January 1, 2001 to December 31, 2011 in 19 polyvalent intensive care units in French university and general hospitals. Patients were adults with a generalized convulsive refractory status epilepticus that lasted more than seven days, despite treatment including an anesthetic drug and mechanical ventilation. Patients with anoxic encephalopathy were excluded. Follow-up phone call was used to determine functional outcome using modified Rankin Scale (mRS) with mRS 0-3 defining good and mRS 4-6 poor outcome., Results: 78 patients (35 female) were included. Median age was 57 years. Causes of status epilepticus were various, mainly including prior epilepsy (14.1%), CNS infection (12.8%), and stroke (12.8%). No etiology was found in 27 (34.6%) patients. PRSE was considered controlled in only 53 (67.9%) patients after a median duration of 17 (IQR 12-26) days. The median length of ICU stay was 28 (19-48) days. Forty-one (52.5%) patients died in the ICU, 26 from multiple organ failure, 8 from care withdrawal, 2 from sudden cardiac arrest, 1 from brain death and 4 from unknown causes. PRSE was previously resolved in 20 patients who died in the ICU. At one-year follow-up, there were 12 patients with good outcome and 58 with poor outcome and 8 lost of follow-up. On multivariate analysis, only vasopressor use was a predictor of poor outcome (OR 6.54; 95%CI 1.09-39.29; p = 0.04)., Conclusion: Poor outcome was observed in about 80% of this population of PRSE. Most patients died from systemic complications linked to their ICU stay. Some patients can recover satisfactorily over time though we did not identify any robust factor of good outcome.

Background: There is currently no validated strategy for the timing of renal replacement therapy (RRT) for acute kidney injury (AKI) in the intensive care unit (ICU) when short-term life-threatening metabolic abnormalities are absent. No adequately powered prospective randomized study has addressed this issue to date. As a result, significant practice heterogeneity exists and may expose patients to either unnecessary hazardous procedures or undue delay in RRT., Methods/design: This is a multicenter, prospective, randomized, open-label parallel-group clinical trial that compares the effect of two RRT initiation strategies on overall survival of critically ill patients receiving intravenous catecholamines or invasive mechanical ventilation and presenting with AKI classification stage 3 (KDIGO 2012). In the 'early' strategy, RRT is initiated immediately. In the 'delayed' strategy, clinical and metabolic conditions are closely monitored and RRT is initiated only when one or more events (severity criteria) occur, including: oliguria or anuria for more than 72 hours after randomization, serum urea concentration >40 mmol/l, serum potassium concentration >6 mmol/l, serum potassium concentration >5.5 mmol/l persisting despite medical treatment, arterial blood pH <7.15 in a context of pure metabolic acidosis (PaCO2 < 35 mmHg) or in a context of mixed acidosis with a PaCO2 ≥ 50 mmHg without possibility of increasing alveolar ventilation, acute pulmonary edema due to fluid overload despite diuretic therapy leading to severe hypoxemia requiring oxygen flow rate >5 l/min to maintain SpO2 > 95% or FiO2 > 50% under invasive or noninvasive mechanical ventilation. The primary outcome measure is overall survival, measured from randomization (D0) until death, regardless of the cause. The minimum follow-up duration for each patient will be 60 days. Two interim analyses are planned, blinded to group allocation. It is expected that there will be 620 subjects in all., Discussion: The AKIKI study will be one of the very few large randomized controlled trials evaluating mortality according to the timing of RRT in critically ill patients with AKI classification stage 3 (KDIGO 2012). Results should help clinicians decide when to initiate RRT., Trial Registration: ClinicalTrials.gov NCT01932190.

Introduction: The thrombin generation test (TGT) describes the ability of the plasma to generate thrombin. Its usefulness in septic patients has yet to be assessed., Methods: Patients admitted for severe sepsis in a medical intensive care unit were sampled for TGT on day 0, 3, 6, and 10. TGT data were compared to "classical" hemostastic tests and to outcome parameters, notably disseminated intravascular coagulation (DIC) according to International Society for Thrombosis and Hemostasis criteria as well as survival., Results: A total of 102 patients were recruited of whom 11 received therapeutic anticoagulation and showed profoundly-altered TGT parameters. In comparison to healthy subjects, the 67 septic patients without DIC exhibited longer Lag times, higher Rate Indices, no change in peak or amount of thrombin generated, although the return to baseline was prolonged. In the 24 DIC patients, Lag time and Rate Index did not differ from healthy subjects (Rate Index being significantly lower than in Sepsis patients). The decreases in peak and amount of thrombin generated were not significant. Return to baseline was prolonged comparatively to Sepsis patients. Due to a large overlap of TGT values between groups, the ability of TGT parameters to diagnose DIC or predict survival was respectively poor or absent., Conclusion: The thrombin Generation Test displayed particular patterns in septic patients and in septic DIC patients. The wide overlap between patients in TGT values prevents the usefulness of this test in clinical practice., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Posaconazole (PSC) is currently recommended as primary prophylaxis in neutropenic patients with acute myeloid leukaemia (AML) and in allogenic haematopoietic stem cell transplantation (AHSCT) recipients with graft-versus-host disease (GVHD). Studies focusing on breakthrough invasive fungal disease (IFD) upon PSC prophylaxis show disparate results. In order to evaluate the incidence of IFD in patients on PSC prophylaxis and identify IFD risk factors, we carried out a retrospective study of all consecutive patients on PP from January 2007 to December 2010 in our hospital. Breakthrough IFDs were identified from the database of the central pharmacy and the French administrative database (PMSI), registering final medical diagnoses of hospitalized patients. Medical data were reviewed to study proven or probable IFD, according to EORTC/MSG definition. PSC plasma concentrations (PPC) were also retrieved. Poisson models were used for statistical analysis. Two hundred and seventy-nine patients received PSC prophylaxis for a median duration of 1.4 months (range 0.2-17.9). Proven (n=6) or probable (n=3) IFDs were diagnosed in nine cases (3.2%). IFD incidence rate per 100 person-month was 1.65 (95% CI, 0.79-2.97). IFDs were candidaemia (Candida glabrata, n=2), pulmonary invasive aspergillosis (n=3), disseminated fusariosis (n=2) and pulmonary mucormycosis (n=2). Seven deaths were reported, directly related to IFD in three patients (33.3%). First dosage of PPC under 0.3 mg/L was the single significant risk factor for IFD (RR, 7.77; 95% CI, 1.30-46.5; p 0.025). Breakthrough IFD in patients receiving PSC prophylaxis is rare but associated with a poor outcome. Low PSC plasma concentrations are associated with an increased risk of IFD., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Background: It is unknown whether the amount of care deployed in the intensive care unit population divided by the number of survivors, that is, amount of care per survivor including the care performed for nonsurvivors, differs between patients older and younger than 75 years of age., Methods: Data were extracted from the computerized files of all 2,220 patients admitted in a medical intensive care unit between January 2009 and December 2010. Patients ≥75 and <75 years old were compared. The Omega score per survivor (OMEGA/S) was calculated in both age groups by dividing the total amount of Omega points, a score of cumulated care load calculated over intensive care unit stay, by the number of survivors in each group., Results: OMEGA/S was 26% higher in elderly versus younger patients when considering intensive care unit mortality and 40% higher when considering hospital mortality. The absence of difference in raw Omega values between the two groups implies that OMEGA/S differences were related to differences in mortality rate. Simplified Acute Physiology Score II (without age-related points) strata analysis (<20, 20-39, 40-59, 60-79, and ≥80) showed that OMEGA/S in the elderly patients was significantly higher in the first three Simplified Acute Physiology Score II strata only. When calculating by main diagnosis categories, a major increase in the difference of OMEGA/S between elderly and younger patients was observed in cardiac arrest patients due to a major difference in mortality rate., Conclusions: Elderly patients required a significantly higher care load per survivor in comparison to younger patients. This excess was mainly due to patients with low initial severity., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)