Fluid balance control in critically ill patients: results from POINCARE-2 stepped wedge cluster-randomized trial.

BACKGROUND: In critically ill patients, positive fluid balance is associated with excessive mortality. The POINCARE-2 trial aimed to assess the effectiveness of a fluid balance control strategy on mortality in critically ill patients. METHODS: POINCARE-2 was a stepped wedge cluster open-label randomized controlled trial. We recruited critically ill patients in twelve volunteering intensive care units from nine French hospitals. Eligible patients were ≥ 18 years old, under mechanical ventilation, admitted to one of the 12 recruiting units for > 48 and ≤ 72 h, and had an expected length of stay after inclusion > 24 h. Recruitment started on May 2016 and ended on May 2019. Of 10,272 patients screened, 1361 met the inclusion criteria and 1353 completed follow-up. The POINCARE-2 strategy consisted of a daily weight-driven restriction of fluid intake, diuretics administration, and ultrafiltration in case of renal replacement therapy between Day 2 and Day 14 after admission. The primary outcome was 60-day all-cause mortality. We considered intention-to-treat analyses in cluster-randomized analyses (CRA) and in randomized before-and-after analyses (RBAA). RESULTS: A total of 433 (643) patients in the strategy group and 472 (718) in the control group were included in the CRA (RBAA). In the CRA, mean (SD) age was 63.7 (14.1) versus 65.7 (14.3) years, and mean (SD) weight at admission was 78.5 (20.0) versus 79.4 (23.5) kg. A total of 129 (160) patients died in the strategy (control) group. Sixty-day mortality did not differ between groups [30.5%, 95% confidence interval (CI) 26.2-34.8 vs. 33.9%, 95% CI 29.6-38.2, p = 0.26]. Among safety outcomes, only hypernatremia was more frequent in the strategy group (5.3% vs. 2.3%, p = 0.01). The RBAA led to similar results. CONCLUSION: The POINCARE-2 conservative strategy did not reduce mortality in critically ill patients. However, due to open-label and stepped wedge design, intention-to-treat analyses might not reflect actual exposure to this strategy, and further analyses might be required before completely discarding it. Trial registration POINCARE-2 trial was registered at ClinicalTrials.gov (NCT02765009). Registered 29 April 2016.

Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial.

BACKGROUND: Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20-40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE. METHODS: This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90. RESULTS: A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89-1.19); p = 0.58]. There were no between-group differences for secondary outcomes. CONCLUSIONS: VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15. TRIAL REGISTRATION NO: NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

Patient-Level Meta-Analysis of Low-Dose Hydrocortisone in Adults with Septic Shock.

Low-Dose Hydrocortisone and Septic ShockCorticosteroids have been evaluated as a therapy for septic shock for more than 50 years. However, uncertainty persists about their effects on mortality. Pirracchio and colleagues undertake a patient-level meta-analysis to answer this important question.

A three-step support strategy for relatives of patients dying in the intensive care unit: a cluster randomised trial.

BACKGROUND: In relatives of patients dying in intensive care units (ICUs), inadequate team support can increase the prevalence of prolonged grief and other psychological harm. We aimed to evaluate whether a proactive communication and support intervention would improve relatives' outcomes. METHODS: We undertook a prospective, multicentre, cluster randomised controlled trial in 34 ICUs in France, to compare standard care with a physician-driven, nurse-aided, three-step support strategy for families throughout the dying process, following a decision to withdraw or withhold life support. Inclusion criteria were relatives of patients older than 18 years with an ICU length of stay 2 days or longer. Participating ICUs were randomly assigned (1:1 ratio) into an intervention cluster and a control cluster. The randomisation scheme was generated centrally by a statistician not otherwise involved in the study, using permutation blocks of non-released size. In the intervention group, three meetings were held with relatives: a family conference to prepare the relatives for the imminent death, an ICU-room visit to provide active support, and a meeting after the patient's death to offer condolences and closure. ICUs randomly assigned to the control group applied their best standard of care in terms of support and communication with relatives of dying patients. The primary endpoint was the proportion of relatives with prolonged grief (measured with PG-13, score ≥30) 6 months after the death. Analysis was by intention to treat, with the bereaved relatives as the unit of observation. The study is registered with ClinicalTrials.gov, NCT02955992. FINDINGS: Between Feb 23, 2017, and Oct 8, 2019, we enrolled 484 relatives of ICU patients to the intervention group and 391 to the control group. 379 (78%) relatives in the intervention group and 309 (79%) in the control group completed the 6-month interview to measure the primary endpoint. The intervention significantly reduced the number of relatives with prolonged grief symptoms (66 [21%] vs 57 [15%]; p=0·035) and the median PG-13 score was significantly lower in the intervention group than in the control group (19 [IQR 14-26] vs 21 [15-29], mean difference 2·5, 95% CI 1·04-3·95). INTERPRETATION: Among relatives of patients dying in the ICU, a physician-driven, nurse-aided, three-step support strategy significantly reduced prolonged grief symptoms. FUNDING: French Ministry of Health.

Assessing physicians' and nurses' experience of dying and death in the ICU: development of the CAESAR-P and the CAESAR-N instruments.

BACKGROUND: As an increasing number of deaths occur in the intensive care unit (ICU), studies have sought to describe, understand, and improve end-of-life care in this setting. Most of these studies are centered on the patient's and/or the relatives' experience. Our study aimed to develop an instrument designed to assess the experience of physicians and nurses of patients who died in the ICU, using a mixed methodology and validated in a prospective multicenter study. METHODS: Physicians and nurses of patients who died in 41 ICUs completed the job strain and the CAESAR questionnaire within 24 h after the death. The psychometric validation was conducted using two datasets: a learning and a reliability cohort. RESULTS: Among the 475 patients included in the main cohort, 398 nurse and 417 physician scores were analyzed. The global score was high for both nurses [62/75 (59; 66)] and physicians [64/75 (61; 68)]. Factors associated with higher CAESAR-Nurse scores were absence of conflict with physicians, pain control handled with physicians, death disclosed to the family at the bedside, and invasive care not performed. As assessed by the job strain instrument, low decision control was associated with lower CAESAR score (61 (58; 65) versus 63 (60; 67), p = 0.002). Factors associated with higher CAESAR-Physician scores were room dedicated to family information, information delivered together by nurse and physician, families systematically informed of the EOL decision, involvement of the nurse during implementation of the EOL decision, and open visitation. They were also higher when a decision to withdraw or withhold treatment was made, no cardiopulmonary resuscitation was performed, and the death was disclosed to the family at the bedside. CONCLUSION: We described and validated a new instrument for assessing the experience of physicians and nurses involved in EOL in the ICU. This study shows important areas for improving practices.

Influence of deprivation on initial severity and prognosis of patients admitted to the ICU: the prospective, multicentre, observational IVOIRE cohort study.

BACKGROUND: The influence of socioeconomic status on patient outcomes is unclear. We assessed the impact of socioeconomic deprivation on severity of illness at intensive care unit (ICU) admission, and on the risk of death at 3 months after ICU admission. METHODS: The IVOIRE study was a prospective, observational, multicentre cohort study in the ICU of 8 participating hospitals in France, including patients aged ≥ 18 years admitted to the ICU and receiving at least one life support therapy for organ failure. The primary outcomes were severity at admission (assessed by SAPSII score), and mortality at 3 months. Socioeconomic data were obtained from interviews with patients or family. Deprivation was assessed using the EPICES score. RESULTS: Among 1294 patents included between 2013 and 2016, 629 (48.6%) were classed as deprived and differed significantly from non-deprived subjects in terms of sociodemographic characteristics and pre-existing conditions. The mean SAPS II score at admission was 50.1 ± 19.4 in deprived patients and 52.3 ± 17.3 in non-deprived patients, with no significant difference by multivariable analysis (ß = - 1.85 [95% CI - 3.86; + 0.16, p = 0.072]). The proportion of death was 31.1% at 3 months, without significant differences between deprived and non-deprived patients, even after adjustment for confounders. CONCLUSIONS: Deprivation is frequent in patients admitted to the ICU and is not associated with disease severity at admission, or with mortality at 3 months between deprived and non-deprived patients. Trial registration The IVOIRE cohort is registered with ClinicalTrials.gov under the identifier NCT01907581, registration date 17/7/2013.

Viscerotropic disease and acute uveitis following yellow fever vaccination: a case report.

BACKGROUND: Yellow fever vaccine exists for over 80 years and is considered to be relatively safe. However, in rare cases it can produce serious neurotropic and viscerotropic complications. We report a case of a patient who presented both viscerotropic and neurological manifestations after yellow fever vaccination. CASE PRESENTATION: We describe the case of a 37 years old man who developed after the yellow fever vaccination a yellow fever vaccine-associated viscerotropic disease followed by acute uveitis. Prolonged detection of yellow fever RNA in blood and urine was consistent with yellow fever vaccine-associated adverse event. The final outcome was good, although with persistent fatigue over a few months. CONCLUSIONS: Even if the yellow fever vaccine is relatively safe, physicians should be aware of its possible serious adverse effects.

Feasibility, reproducibility and diagnostic usefulness of right ventricular strain by 2-dimensional speckle-tracking echocardiography in ARDS patients: the ARD strain study.

BACKGROUND: Right ventricular (RV) function evaluation by echocardiography is key in the management of ICU patients with acute respiratory distress syndrome (ARDS), however, it remains challenging. Quantification of RV deformation by speckle-tracking echocardiography (STE) is a recently available and reproducible technique that provides an integrated analysis of the RV. However, data are scarce regarding its use in critically ill patients. The aim of this study was to assess its feasibility and clinical usefulness in moderate-severe ARDS patients. RESULTS: Forty-eight ARDS patients under invasive mechanical ventilation (MV) were consecutively enrolled in a prospective observational study. A full transthoracic echocardiography was performed within 36 h of MV initiation. STE-derived and conventional parameters were recorded. Strain imaging of the RV lateral, inferior and septal walls was highly feasible (47/48 (98%) patients). Interobserver reproducibility of RV strain values displayed good reliability (intraclass correlation coefficients (ICC) > 0.75 for all STE-derived parameters) in ARDS patients. ROC curve analysis showed that lateral, inferior, global (average of the 3 RV walls) longitudinal systolic strain (LSS) and global strain rate demonstrated significant diagnostic values when compared to several conventional indices (TAPSE, S', RV FAC). A RV global LSS value > - 13.7% differentiated patients with a TAPSE < vs > 12 mm with a sensitivity of 88% and a specificity of 83%. Regarding clinical outcomes, mortality and cumulative incidence of weaning from MV at day 28 were not different in patients with normal versus abnormal STE-derived parameters. CONCLUSIONS: Global STE assessment of the RV was highly achievable and reproducible in moderate-severe ARDS patients under MV and additionally correlated with several conventional parameters of RV function. In our cohort, STE-derived parameters did not provide any incremental value in terms of survival or weaning from MV prediction. Further investigations are needed to evaluate their theranostic usefulness. Trial registration NCT02638844: NCT.

Corticosteroids for treating sepsis in children and adults.

BACKGROUND: Sepsis occurs when an infection is complicated by organ failure. Sepsis may be complicated by impaired corticosteroid metabolism. Thus, providing corticosteroids may benefit patients. The original review was published in 2004 and was updated in 2010 and 2015 prior to this update. OBJECTIVES: To examine the effects of corticosteroids on death in children and adults with sepsis. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, ISRCTN, and the WHO Clinical Trials Search Portal, on 25 July 2019. In addition, we conducted reference checking and citation searching, and contacted study authors, to identify additional studies as needed. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of corticosteroids versus placebo or usual care (antimicrobials, fluid replacement, and vasopressor therapy as needed) in children and adults with sepsis. We also included RCTs of continuous infusion versus intermittent bolus of corticosteroids. DATA COLLECTION AND ANALYSIS: All review authors screened and selected studies for inclusion. One review author extracted data, which was checked by the others, and by the lead author of the primary study when possible. We obtained unpublished data from the authors of some trials. We assessed the methodological quality of trials and applied GRADE to assess the certainty of evidence. Review authors did not contribute to assessment of eligibility and risk of bias, nor to data extraction, for trials they had participated in. MAIN RESULTS: We included 61 trials (12,192 participants), of which six included only children, two included children and adults, and the remaining trials included only adults. Nine studies are ongoing and will be considered in future versions of this review. We judged 19 trials as being at low risk of bias. Corticosteroids versus placebo or usual care Compared to placebo or usual care, corticosteroids probably slightly reduce 28-day mortality (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.84 to 0.99; 11,233 participants; 50 studies; moderate-certainty evidence). Corticosteroids may result in little to no difference in long-term mortality (RR 0.97, 95% CI 0.91 to 1.03; 6236 participants; 7 studies; low-certainty evidence) and probably slightly reduce hospital mortality (RR 0.90, 95% CI 0.82 to 0.99; 8183 participants; 26 trials; moderate-certainty evidence). Corticosteroids reduced length of intensive care unit (ICU) stay for all participants (mean difference (MD) -1.07 days, 95% CI -1.95 to -0.19; 7612 participants; 21 studies; high-certainty evidence) and resulted in a large reduction in length of hospital stay for all participants (MD -1.63 days, 95% CI -2.93 to -0.33; 8795 participants; 22 studies; high-certainty evidence). Corticosteroids increase the risk of muscle weakness (RR 1.21, 95% CI 1.01 to 1.44; 6145 participants; 6 studies; high-certainty evidence). Corticosteroids probably do not increase the risk of superinfection (RR 1.06, 95% CI 0.95 to 1.19; 5356 participants; 25 studies; moderate-certainty evidence). Corticosteroids increase the risk of hypernatraemia (high-certainty evidence) and probably increase the risk of hyperglycaemia (moderate-certainty evidence). Moderate-certainty evidence shows that there is probably little or no difference in gastroduodenal bleeding, stroke, or cardiac events, and low-certainty evidence suggests that corticosteroids may result in little to no difference in neuropsychiatric events. Continuous infusion of corticosteroids versus intermittent bolus We are uncertain about the effects of continuous infusion of corticosteroids compared with intermittent bolus administration. Three studies reported data for this comparison, and the certainty of evidence for all outcomes was very low. AUTHORS' CONCLUSIONS: Moderate-certainty evidence indicates that corticosteroids probably reduce 28-day and hospital mortality among patients with sepsis. Corticosteroids result in large reductions in ICU and hospital length of stay (high-certainty evidence). There may be little or no difference in the risk of major complications; however, corticosteroids increase the risk of muscle weakness and hypernatraemia, and probably increase the risk of hyperglycaemia. The effects of continuous versus intermittent bolus administration of corticosteroids are uncertain.

Effect of fluid balance control in critically ill patients: Design of the stepped wedge trial POINCARE-2.

A high number of recent studies have shown that a positive fluid balance is independently associated with impaired prognosis in specific populations of patients hospitalized in intensive care unit (ICU): acute kidney injury, acute respiratory distress syndrome (ARDS), sepsis, high risk surgery. However, to date, there is no evidence that control of fluid overload reduces mortality in critically ill patients. The main objective is to assess the efficacy of a strategy limiting fluid overload on mortality in unselected critically ill patients hospitalized in ICU. We hypothesized that a strategy based on a weight-driven recommendation of restricted fluid intake, diuretics, and ultrafiltration initiated from 48 h up to 14 days after admission in critically ill patients would reduce all-cause mortality as compared to usual care. We use a stepped wedge cluster randomized controlled trial combined with a quasi-experimental (before-and-after) study. Patients under mechanical ventilation, admitted since >48 h and < 72 h in ICU, and with no discharge planned for the next 24 h are eligible. A total of 1440 patients are expected to be enrolled in 12 ICUs. Sociodemographic and clinical data are collected at inclusion, and outcomes are collected during the follow-up. Primary outcome is all-cause mortality at 60 days after admission. Secondary outcomes are patients weight differences between admission and day7 (or day 14), 28-day, in-hospital, and 1-year mortality, end-organ damages, and unintended harmful events. Analyses will be held in intention-to-treat. If POINCARE-2 strategy proves effective, then guidelines on fluid balance control might be extended to all critically ill patients. Trial registration: ClinicalTrials.govNCT02765009.

Quality of life assessment following amputation for septic shock: a long-term descriptive survey after symmetric peripheral gangrene.

PURPOSE: To assess health-related quality of life (HRQOL) following rehabilitation of amputees suffering symmetric peripheral gangrene (SPG) after septic shock. MATERIAL AND METHODS: A retrospective cohort study was conducted in nine French specialized rehabilitation centers. Thirty-two ICU adult patients hospitalized between 2005 and 2015 for septic shock who additionally presented with SPG resulting in at least two major amputations were enrolled. HRQOL was assessed by EQ-5D-3 L questionnaire. RESULTS: All patients (mean ICU length of stay 39 ±â€¯22d, SAPS II 58 ±â€¯18) had both lower limbs amputated and 84% were quadruple amputees. HRQOL, assessed 4.8 ±â€¯2.8 years after amputation, was inferior to the French reference. However, patients' self-rated health status was similar to the reference at the time of HRQOL assessment. The main factor of impaired HRQOL was intense phantom pain, not the mobility or self-care dimensions of EQ-5D. All patients except one preferred to be treated again for SPG despite disability. CONCLUSION: ICU survivors referred to rehabilitation centers after SPG-related amputations had impaired HRQOL. At the time of HRQOL assessment, they considered themselves in good health and preferred to be treated again despite disability. Appraisal of long-term functional outcome should not be used to guide end-of-life decision-making in this situation.

Automated measurement of neutrophil CD64 expression for diagnosing sepsis in critically ill patients.

BACKGROUND: Although early identification of sepsis improves outcome, prompt and correct diagnostic remains often challenging. The expression of the high affinity immunoglobulin-Fc fragment receptor I CD64 on neutrophils is upregulated during acute inflammation. We here aimed at determining the usefulness of its rapid measurement in diagnosing sepsis. METHODS: Seventy-two consecutive patients were enrolled upon admission to Intensive Care Unit within a two-month period. Sequential determination of serum C-reactive protein (CRP) and procalcitonin (PCT) concentrations was obtained. The neutrophil CD64 index was measured using Accellix-CD64® device, an in vitro diagnosis system allowing for an automatic and standardized measure. RESULTS: Serum concentrations of CRP and PCT as well as the neutrophil CD64 index were higher in septic patients compared to all others (P<0.05 for the three markers). Only CD64 index was an independent predictor of sepsis, though with modest sensitivity and specificity (78% and 70%, respectively). Repeat determination of CD64 index at day 2 correctly classified 85% of patients. CONCLUSIONS: This prospective study demonstrates the moderate performance of the neutrophil CD64 index, assessed through the Accellix-CD64® device, in diagnosing sepsis in the critically ill patient. However, repeat measurements improve its accuracy and may help to predict ICU-acquired infections.

Functional outcome of patients with prolonged hypoglycemic encephalopathy.

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.

Patients with ANCA-associated vasculitis admitted to the intensive care unit with acute vasculitis manifestations: a retrospective and comparative multicentric study.

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.

Long-term impact after fulminant Guillain-Barré syndrome, case report and literature review.

A 47-year-old man was admitted to the intensive care unit a few hours after presenting to emergency department with acute diplopia and dysphonia. Swallowing disorders and respiratory muscular weakness quickly required invasive ventilation. On day 3, the patient was in a "brain-death"-like state with deep coma and absent brainstem reflexes. Electroencephalogram ruled out brain death diagnosis as a paradoxical sleep trace was recorded. Cerebrospinal fluid analysis, electrophysiologic studies, and a recent history of diarrhea led to the diagnosis of Campylobacter jejuni-related fulminant Guillain-Barré syndrome (GBS) mimicking brain death. The outcome was favorable after long Intensive Care Unit and inpatient rehabilitation stays, despite persistent disability at 9 years follow-up. This case and the associated literature review of 34 previously reported fulminant GBS patients emphasize the importance of electrophysiological investigations during clinical brain-death states with no definite cause. Fulminant GBS has a worse outcome than "standard" GBS with higher rates of severe disability (about 50%). Long-term physiotherapy and specific rehabilitation programs appear essential to improve recovery.

CAESAR: a new tool to assess relatives' experience of dying and death in the ICU.

PURPOSE: To develop an instrument designed specifically to assess the experience of relatives of patients who die in the intensive care unit (ICU). METHODS: The instrument was developed using a mixed methodology and validated in a prospective multicentre study. Relatives of patients who died in 41 ICUs completed the questionnaire by telephone 21 days after the death, then completed the Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised and Inventory of Complicated Grief after 3, 6, and 12 months. RESULTS: A total of 600 relatives were included, 475 in the main cohort and 125 in the reliability cohort. The 15-item questionnaire, named CAESAR, covered the patient's preferences and values, interactions with/around the patient and family satisfaction. We defined three groups based on CAESAR score tertiles: lowest (≤59, n = 107, 25.9 %), middle (n = 185, 44.8 %) and highest (≥69, n = 121, 29.3 %). Factorial analysis showed a single dimension. Cronbach's alpha in the main and reliability cohorts was 0.88 (0.85-0.90) and 0.85 (0.79-0.89), respectively. Compared to a high CAESAR score, a low CAESAR score was associated with greater risks of anxiety and depression at 3 months [1.29 (1.13-1.46), p = 0.001], post-traumatic stress-related symptoms at 3 [1.34 (1.17-1.53), p < 0.001], 6 [OR = 1.24 (1.06-1.44), p = 0.008] and 12 [OR = 1.26 (1.06-1.50), p = 0.01] months and complicated grief at 6 [OR = 1.40 (1.20-1.63), p < 0.001] and 12 months [OR = 1.27 (1.06-1.52), p = 0.01]. CONCLUSIONS: The CAESAR score 21 days after death in the ICU is strongly associated with post-ICU burden in the bereaved relatives. The CAESAR score should prove a useful primary endpoint in trials of interventions to improve relatives' well-being.

Corticosteroids for treating sepsis.

BACKGROUND: Sepsis occurs when an infection is complicated by organ failures as defined by a sequential organ failure assessment (SOFA) score of two or higher. Sepsis may be complicated by impaired corticosteroid metabolism. Giving corticosteroids may benefit patients. The original review was published in 2004 and was updated in 2010 and again in 2015. OBJECTIVES: To examine the effects of corticosteroids on death at one month in patients with sepsis, and to examine whether dose and duration of corticosteroids influence patient response to this treatment. SEARCH METHODS: We searched the Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE (October 2014), EMBASE (October 2014), Latin American Caribbean Health Sciences Literature (LILACS; October 2014) and reference lists of articles, and we contacted trial authors. The original searches were performed in August 2003 and in October 2009. SELECTION CRITERIA: We included randomized controlled trials of corticosteroids versus placebo or supportive treatment in patients with sepsis. DATA COLLECTION AND ANALYSIS: All review authors agreed on the eligibility of trials. One review author extracted data, which were checked by the other review authors, and by the primary author of the paper when possible. We obtained some missing data from trial authors. We assessed the methodological quality of trials. MAIN RESULTS: We identified nine additional studies since the last update, for a total of 33 eligible trials (n = 4268 participants). Twenty-three of these 33 trials were at low risk of selection bias, 22 were at low risk of performance and detection bias, 27 were at low risk of attrition bias and 14 were at low risk of selective reporting.Corticosteroids reduced 28-day mortality (27 trials; n = 3176; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.76 to 1.00; P value = 0.05, random-effects model). The quality of evidence for this outcome was downgraded from high to low for imprecision (upper limit of 95% CI = 1) and for inconsistency (significant heterogeneity across trial results). Heterogeneity was related in part to the dosing strategy. Treatment with a long course of low-dose corticosteroids significantly reduced 28-day mortality (22 trials; RR 0.87, 95% CI 0.78 to 0.97; P value = 0.01, fixed-effect model). The quality of evidence was downgraded from high to moderate for inconsistency (owing to non-significant effects shown by one large trial). Corticosteroids also reduced mortality rate in the intensive care unit (13 trials; RR 0.82, 95% CI 0.68 to 1.00; P value = 0.04, random-effects model) and at the hospital (17 trials; RR 0.85, 95% CI 0.73 to 0.98; P value = 0.03, random-effects model). Quality of the evidence for in-hospital mortality was downgraded from high to moderate for inconsistency and imprecision (upper limit of 95% CI for RR approaching 1). Corticosteroids increased the proportion of shock reversal by day seven (12 trials; RR 1.31, 95% CI 1.14 to 1.51; P value = 0.0001) and by day 28 (seven trials; n = 1013; RR 1.11, 95% CI 1.02 to 1.21; P value = 0.01) and reduced the SOFA score by day seven (eight trials; mean difference (MD) -1.53, 95% CI -2.04 to -1.03; P value < 0.00001, random-effects model) and survivors' length of stay in the intensive care unit (10 trials; MD -2.19, 95% CI -3.93 to -0.46; P value = 0.01, fixed-effect model) without inducing gastroduodenal bleeding (19 trials; RR 1.24, 95% CI 0. 92 to 1.67; P value = 0.15, fixed-effect model), superinfection (19 trials; RR 1.02, 95% CI 0.87 to 1.20; P value = 0.81, fixed-effect model) or neuromuscular weakness (three trials; RR 0.62, 95% CI 0.21 to 1.88; P value = 0.40, fixed-effect model). Corticosteroid increased the risk of hyperglycaemia (13 trials; RR 1.26, 95% CI 1.16 to 1.37; P value < 0.00001, fixed-effect model) and hypernatraemia (three trials; RR 1.64, 95% CI 1.28 to 2.09; P value < 0.0001, fixed-effect model). AUTHORS' CONCLUSIONS: Overall, low-quality evidence indicates that corticosteroids reduce mortality among patients with sepsis. Moderate-quality evidence suggests that a long course of low-dose corticosteroids reduced 28-day mortality without inducing major complications and led to an increase in metabolic disorders.