EVERE SEPSIS, A SYNDROME OF acute infection complicated by organ dysfunction, is caused by a dysregulated systemic inflammatory response. Sepsis can progress to systemic hypotension (septic shock), Importance Eritoran is a synthetic lipid A antagonist that blocks lipopolysaccharide (LPS) from binding at the cell surface MD2-TLR4 receptor. LPS is a major component of the outer membrane of gram-negative bacteria and is a potent activator of the acute inflammatory response. Objective To determine if eritoran, a TLR4 antagonist, would significantly reduce sepsis-induced mortality. Design, Setting, and Participants We performed a randomized, double-blind, placebo-controlled, multinational phase 3 trial in 197 intensive care units. Patients were enrolled from June 2006 to September 2010 and final follow-up was completed in September 2011. Interventions Patients with severe sepsis (n=1961) were randomized and treated within 12 hours of onset of first organ dysfunction in a 2:1 ratio with a 6-day course of either eritoran tetrasodium (105 mg total) or placebo, with n=1304 and n=657 patients, respectively. Main Outcome Measures The primary end point was 28-day all-cause mortality. The secondary end points were all-cause mortality at 3, 6, and 12 months after beginning treatment. Results Baseline characteristics of the 2 study groups were similar. In the modified intent-to-treat analysis (randomized patients who received at least 1 dose) there was no significant difference in the primary end point of 28-day all-cause mortality with 28.1% (366/1304) in the eritoran group vs 26.9% (177/657) in the placebo group (P=.59; hazard ratio, 1.05; 95% CI, 0.88-1.26; difference in mortality rate, Ϫ1.1; 95% CI, Ϫ5.3 to 3.1) or in the key secondary end point of 1-year all-cause mortality with 44.1% (290/657) in the eritoran group vs 43.3% (565/1304) in the placebo group, Kaplan-Meier analysis of time to death by 1 year, P=.79 (hazard ratio, 0.98; 0.85-1.13). No significant differences were observed in any of the prespecified subgroups. Adverse events, including secondary infection rates, did not differ between study groups. Conclusions and Relevance Among patients with severe sepsis, the use of eritoran, compared with placebo, did not result in reduced 28-day mortality.

ClinicalTrials.gov (ID: NCT03134807).

Quality of life differed on diagnostic category but, overall, critically ill patients had a lower quality of life than an age- and gender-matched population. A minority of studies met the predefined methodologic quality criteria. Results concerning the influence of the patients' characteristics and illnesses on long-term quality of life were conflicting.

Premorbid conditions affect prognosis of acutely-ill aged patients. Several lines of evidence suggest geriatric syndromes need to be assessed but little is known on their relative effect on the 30-day survival after ICU admission. The primary aim of this study was to describe the prevalence of frailty, cognition decline and activity of daily life in addition to the presence of comorbidity and polypharmacy and to assess their influence on 30-day survival.Methods: Prospective cohort study with 242 ICUs from 22 countries. Patients 80 years or above acutely admitted over a six months period to an ICU between May 2018 and May 2019 were included. In addition to common patients' characteristics and disease severity, we collected information on specific geriatric syndromes as potential predictive factors for 30-day survival, frailty (Clinical Frailty scale) with a CFS > 4 defining frail patients, cognitive impairment (informant questionnaire on cognitive decline in the elderly (IQCODE) with IQCODE ≥ 3.5 defining cognitive decline, and disability (measured the activity of daily life with the Katz index) with ADL ≤ 4 defining disability. A Principal Component Analysis to identify co-linearity between geriatric syndromes was performed and from this a multivariable model was built with all geriatric information or only one: CFS, IQCODE or ADL. Akaike's information criterion across imputations was used to evaluate the goodness of fit of our models. Results:We included 3920 patients with a median age of 84 years (IQR: 81-87), 53.3% males). 80% received at least one organ support. The median ICU length of stay was 3.88 days (IQR: 1.83-8). The ICU and 30-day survival were 72.5% and 61.2% respectively. The geriatric conditions were median (IQR): CFS: 4 (3-6); IQCODE: 3.19 (3-3.69); ADL: 6 (4-6); Comorbidity and Polypharmacy score (CPS): 10 (7-14). CFS, ADL and IQCODE were closely correlated. The multivariable analysis identified predictors of 1-month mortality (HR; 95% CI): Age (per 1 year increase): 1.02 (1.-1.03, p = 0.01), ICU admission diagnosis, sequential organ failure assessment score (SOFA) (per point): 1.15 (1.14-1.17, p < 0.0001) and