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Background. Little is known about the epidemiology and the prognostic factors of Guillain—Barré syndrome (GBS) following primary infection with cytomegalovirus (CMV-GBS). Methods. We prospectively followed up 506 patients with cases of GBS who were admitted to our center from 1996 through 2006. We diagnosed 63 (12.4%) CMV-GBS cases by immunoglobulin (Ig) M detection and IgG avidity. Plasma CMV DNA was detected at hospital admission. Patient subgroups were compared using Fisher's exact test and the Wilcoxon rank-sum test. Temporal variations were analyzed with time series methods. Results. Patients with CMV-GBS were mostly young (median age, 32 years; sex ratio, 0.85), but we also identified a subpopulation of patients consisting of women aged >50 years. Sensory defects (in 72% of cases) and facial palsy (49%) were frequent, and test results positive for CMV DNA in plasma at hospital admission (found in 62% of cases) tended to be associated with objective sensory defect (P = .052). The main factors associated with long-term neurological sequelae (21%) were older age (P <.001) and assisted ventilation during hospitalization (P = .005). The number of CMV-GBS cases decreased between 1996 and 2006 (P = .019) and displayed an annual periodicity between the months of July and October. The incidence of CMV-GBS was estimated to be between 0.6 and 2.2 cases per 1000 cases of primary CMV infection (versus 0.25 to 0.65 cases per 1000 cases of Campylobacter jejuni infection). Conclusions. This study provides new insights about the epidemiology of CMV-GBS and shows that the risk of developing GBS is similar following primary CMV infection or C. jejuni infection. Our results also suggest a direct or indirect involvement of viral replication in the neuropathological processes of CMV-GBS.

Introduction Corticosteroids have been proposed to decrease morbidity and mortality in patients with septic shock. An impact on morbidity should be anticipated to be earlier and more easily detected than the impact on mortality. Methods Prospective, randomized, double-blind, placebo-controlled study of 28-day mortality in patients with septic shock for <72 h who underwent a short high-dose ACTH test in 52 centers in 9 European countries. Patients received 11-day treatment with hydrocortisone or placebo. Organ dysfunction/failure was quantified by the use of the sequential organ failure assessment (SOFA) score. Results From March 2002 to November 2005, 499 patients were enrolled (hydrocortisone 251, placebo 248). Both groups presented a similar SOFA score at baseline (hydrocortisone 10.8 ± 3.2 vs. placebo 10.7 ± 3.1 points). There was no difference in 28-day mortality between the two treatment groups (hydrocortisone 34.3% vs. placebo 31.5%). There was a decrease in the SOFA score of hydrocortisone-treated patients from day 0 to day 7 compared to the placebo-treated patients ( p  = 0.0027), driven by an improvement in cardiovascular organ dysfunction/failure ( p  = 0.0005) and in liver failure ( p  < 0.0001) in the hydrocortisone-treated patients. Conclusion Patients randomized to treatment with hydrocortisone demonstrated a faster decrease in total organ dysfunction/failure determined by the SOFA score, primarily driven by a faster improvement in cardiovascular organ dysfunction/failure. This organ dysfunction/failure improvement was not accompanied by a decreased mortality.

Background Delirium (acute brain dysfunction) is a potentially life threatening disturbance in brain function that frequently occurs in critically ill patients. While this area of brain dysfunction in critical care is rapidly advancing, striking limitations in use of terminology related to delirium internationally are hindering cross-talk and collaborative research. In the English literature, synonyms of delirium such as the Intensive Care Unit syndrome, acute brain dysfunction, acute brain failure, psychosis, confusion, and encephalopathy are widely used. This often leads to scientific \"confusion\" regarding published data and methodology within studies, which is further exacerbated by organizational, cultural and language barriers. Objective We undertook this multinational effort to identify conflicts in terminology and phenomenology of delirium to facilitate communication across medical disciplines and languages. Methods The evaluation of the terminology used for acute brain dysfunction was determined conducting communications with 24 authors from academic communities throughout countries/regions that speak the 13 variants of the Romanic languages included into this manuscript. Results In the 13 languages utilizing Romanic characters, included in this report, we identified the following terms used to define major types of acute brain dysfunction: coma , delirium , delirio , delirium tremens , délire , confusion mentale , delir , delier , Durchgangs-Syndrom , acute verwardheid , intensiv-psykose , IVA - psykos , IVA - syndrom , akutt konfusion / forvirring . Interestingly two terms are very consistent: 100 % of the selected languages use the term coma or koma to describe patients unresponsive to verbal and/or physical stimuli, and 100% use delirium tremens to define delirium due to alcohol withdrawal. Conversely, only 54% use the term delirium to indicate the disorder as defined by the DSM-IV as an acute change in mental status, inattention, disorganized thinking and altered level of consciousness. Conclusions Attempts towards standardization in terminology, or at least awareness of differences across languages and specialties, will help cross-talk among clinicians and researchers.

Purpose An optimal target for glucose control in ICU patients remains unclear. This prospective randomized controlled trial compared the effects on ICU mortality of intensive insulin therapy (IIT) with an intermediate glucose control. Methods Adult patients admitted to the 21 participating medico-surgical ICUs were randomized to group 1 (target BG 7.8–10.0 mmol/L) or to group 2 (target BG 4.4–6.1 mmol/L). Results While the required sample size was 1,750 per group, the trial was stopped early due to a high rate of unintended protocol violations. From 1,101 admissions, the outcomes of 542 patients assigned to group 1 and 536 of group 2 were analysed. The groups were well balanced. BG levels averaged in group 1 8.0 mmol/L (IQR 7.1–9.0) (median of all values) and 7.7 mmol/L (IQR 6.7–8.8) (median of morning BG) versus 6.5 mmol/L (IQR 6.0–7.2) and 6.1 mmol/L (IQR 5.5–6.8) for group 2 ( p  < 0.0001 for both comparisons). The percentage of patients treated with insulin averaged 66.2 and 96.3%, respectively. Proportion of time spent in target BG was similar, averaging 39.5% and 45.1% (median (IQR) 34.3 (18.5–50.0) and 39.3 (26.2–53.6)%) in the groups 1 and 2, respectively. The rate of hypoglycaemia was higher in the group 2 (8.7%) than in group 1 (2.7%, p  < 0.0001). ICU mortality was similar in the two groups (15.3 vs. 17.2%). Conclusions In this prematurely stopped and therefore underpowered study, there was a lack of clinical benefit of intensive insulin therapy (target 4.4–6.1 mmol/L), associated with an increased incidence of hypoglycaemia, as compared to a 7.8–10.0 mmol/L target. (ClinicalTrials.gov # NCT00107601, EUDRA-CT Number: 200400391440).

International guidelines for management of septic shock recommend that dopamine or norepinephrine are preferable to epinephrine. However, no large comparative trial has yet been done. We aimed to compare the efficacy and safety of norepinephrine plus dobutamine (whenever needed) with those of epinephrine alone in septic shock. This prospective, multicentre, randomised, double-blind study was done in 330 patients with septic shock admitted to one of 19 participating intensive care units in France. Participants were assigned to receive epinephrine (n=161) or norepinephrine plus dobutamine (n=169), which were titrated to maintain mean blood pressure at 70 mm Hg or more. The primary outcome was 28-day all-cause mortality. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00148278. There were no patients lost to follow-up; one patient withdrew consent after 3 days. At day 28, there were 64 (40%) deaths in the epinephrine group and 58 (34%) deaths in the norepinephrine plus dobutamine group (p=0·31; relative risk 0·86, 95% CI 0·65–1·14). There was no significant difference between the two groups in mortality rates at discharge from intensive care (75 [47%] deaths vs 75 [44%] deaths, p=0·69), at hospital discharge (84 [52%] vs 82 [49%], p=0·51), and by day 90 (84 [52%] vs 85 [50%], p=0·73), time to haemodynamic success (log-rank p=0·67), time to vasopressor withdrawal (log-rank p=0·09), and time course of SOFA score. Rates of serious adverse events were also similar. There is no evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock.

Purpose The blood glucose target range and optimal method to reach this range remain a matter of debate in the intensive care unit (ICU). A computer decision support system (CDSS) might improve the outcome of ICU patients through facilitation of a tighter blood glucose control. Methods We conducted a multi-center randomized trial in 34 French ICU. Adult patients expected to require treatment in the ICU for at least 3 days were randomly assigned without blinding to undergo tight computerized glucose control with the CDSS (TGC) or conventional glucose control (CGC), with blood glucose targets of 4.4–6.1 and <10.0 mmol/L, respectively. The primary outcome was all-cause death within 90 days after ICU admission. Results Of the 2,684 patients who underwent randomization to the TGC and CGC treatment groups, primary outcome was available for 1,335 and 1,311 patients, respectively. The baseline characteristics of these treatment groups were similar in terms of age (61 ± 16 years), SAPS II (51 ± 19), percentage of surgical admissions (40.0 %) and proportion of diabetic patients (20.3 %). A total of 431 (32.3 %) patients in the TGC group and 447 (34.1 %) in the CGC group had died by day 90 (odds ratio for death in the TGC 0.92; 95 % confidence interval 0.78–1.78; p  = 0.32). Severe hypoglycemia (<2.2 mmol/L) occurred in 174 of 1,317 patients (13.2 %) in the TGC group and 79 of 1,284 patients (6.2 %) in the CGC group ( p  < 0.001). Conclusions Tight computerized glucose control with the CDSS did not significantly change 90-day mortality and was associated with more frequent severe hypoglycemia episodes in comparison with conventional glucose control.

Objective To assess the effect on survival of macrolides or fluoroquinolones in intubated patients admitted to the intensive care unit (ICU) with severe community-acquired pneumonia (severe CAP). Methods Prospective, observational cohort, multicenter study conducted in 27 ICUs of 9 European countries. Two hundred eighteen consecutive patients requiring invasive mechanical ventilation for an admission diagnosis of CAP were recruited. Results Severe sepsis and septic shock were present in 165 (75.7%) patients. Microbiological documentation was obtained in 102 (46.8%) patients. ICU mortality was 37.6% ( n  = 82). Non-survivors were older (58.6 ± 16.1 vs. 63.4 ± 16.7 years, P  < 0.05) and presented a higher score on the simplified Acute Physiology Score II at admission (45.6 ± 15.4 vs. 50.8 ± 17.5, P  < 0.05). Monotherapy was given in 43 (19.7%) and combination therapy in 175 (80.3%) patients. Empirical antibiotic therapy was in accordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines in 100 (45.9%) patients (macrolides in 46 patients and fluoroquinolones in 54). In this cohort, a Cox regression analysis adjusted by severity identified that macrolide use was associated with lower ICU mortality (hazard ratio, HR 0.48, confidence intervals, 95% CI 0.23–0.97, P  = 0.04) when compared to the use of fluoroquinolones. When more severe patients presenting severe sepsis and septic shock were analyzed ( n  = 92), similar results were obtained (HR 0.44, 95% CI 0.20–0.95, P  = 0.03). Conclusions Patients with severe community-acquired pneumonia had a low adherence with the 2007 IDSA/ATS guidelines. Combination therapy with macrolides should be preferred in intubated patients with severe CAP.

Introduction Although hyperbaric oxygen therapy (HBO) is broadly used for carbon monoxide (CO) poisoning, its efficacy and practical modalities remain controversial. Objectives To assess HBO in patients poisoned with CO. Design Two prospective randomized trial on two parallel groups. Setting Critical Care Unit, Raymond Poincaré Hospital, Garches, France. Subjects Three hundred eighty-five patients with acute domestic CO poisoning. Intervention Patients with transient loss of consciousness (trial A, n  = 179) were randomized to either 6 h of normobaric oxygen therapy (NBO; arm A0, n  = 86) or 4 h of NBO plus one HBO session (arm A1, n  = 93). Patients with initial coma (trial B, n  = 206) were randomized to either 4 h of NBO plus one HBO session (arm B1, n  = 101) or 4 h of NBO plus two 2 HBO sessions (arm B2, n  = 105). Primary endpoint Proportion of patients with complete recovery at 1 month. Results In trial A, there was no evidence for a difference in 1-month complete recovery rates with and without HBO [58% compared to 61%; unadjusted odds ratio, 0.90 (95% CI, 0.47–1.71)]. In trial B, complete recovery rates were significantly lower with two than with one HBO session [47% compared to 68%; unadjusted odds ratio, 0.42 (CI, 0.23–0.79)]. Conclusion In patients with transient loss of consciousness, there was no evidence of superiority of HBO over NBO. In comatose patients, two HBO sessions were associated with worse outcomes than one HBO session.

Rationale Use of etomidate in the critically ill is controversial due to its links with an inadequate response to corticotropin and potential for excess mortality. In a septic shock population, we tested the hypotheses that etomidate administration induces more non-responders to corticotropin and increases mortality and that hydrocortisone treatment decreases mortality in patients receiving etomidate. Methods An a-priori sub-study of the CORTICUS multi-centre, randomised, double-blind, placebo-controlled trial of hydrocortisone in septic shock. Use and timing of etomidate administration were collected. Endpoints were corticotropin response and all-cause 28-day mortality in patients receiving etomidate. Measurements and main results Five hundred patients were recruited, of whom 499 were analysable; 96 (19.2%) were administered etomidate within the 72 h prior to inclusion. The proportion of non-responders to corticotropin was significantly higher in patients who were given etomidate in the 72 h before trial inclusion than in other patients (61.0 vs. 44.6%, P  = 0.004). Etomidate therapy was associated with a higher 28-day mortality in univariate analysis ( P  = 0.02) and after correction for severity of illness (42.7 vs. 30.5%; P  = 0.06 and P  = 0.03) in our two multi-variant models. Hydrocortisone administration did not change the mortality of patients receiving etomidate (45 vs. 40%). Conclusions The use of bolus dose etomidate in the 72 h before study inclusion is associated with an increased incidence of inadequate response to corticotropin, but is also likely to be associated with an increase in mortality. We recommend clinicians demonstrate extreme caution in the use of etomidate in critically ill patients with septic shock.

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