IMPORTANCE Norepinephrine, the first-line vasopressor for septic shock, is not always effective and has important catecholaminergic adverse effects. Selepressin, a selective vasopressin V1a receptor agonist, is a noncatecholaminergic vasopressor that may mitigate sepsis-induced vasodilatation, vascular leakage, and edema, with fewer adverse effects.OBJECTIVE To test whether selepressin improves outcome in septic shock. DESIGN, SETTING, AND PARTICIPANTSAn adaptive phase 2b/3 randomized clinical trial comprising 2 parts that included adult patients (n = 868) with septic shock requiring more than 5 μg/min of norepinephrine. Part 1 used a Bayesian algorithm to adjust randomization probabilities to alternative selepressin dosing regimens and to trigger transition to part 2, which would compare the best-performing regimen with placebo. The trial was conducted between July 2015 and August 2017 in 63 hospitals in Belgium, Denmark, France, the Netherlands, and the United States, and follow-up was completed by May 2018.INTERVENTIONS Random assignment to 1 of 3 dosing regimens of selepressin (starting infusion rates of 1.7, 2.5, and 3.5 ng/kg/min; n = 585) or to placebo (n = 283), all administered as continuous infusions titrated according to hemodynamic parameters. MAIN OUTCOMES AND MEASURESPrimary end point was ventilator-and vasopressor-free days within 30 days (deaths assigned zero days) of commencing study drug. Key secondary end points were 90-day mortality, kidney replacement therapy-free days, and ICU-free days. RESULTS Among 868 randomized patients, 828 received study drug (mean age, 66.3 years; 341 [41.2%] women) and comprised the primary analysis cohort, of whom 562 received 1 of 3 selepressin regimens, 266 received placebo, and 817 (98.7%) completed the trial. The trial was stopped for futility at the end of part 1. Median study drug duration was 37.8 hours (IQR,). There were no significant differences in the primary end point (ventilator-and vasopressor-free days: 15.0 vs 14.5 in the selepressin and placebo groups;

Objective Precise measurements of fluid status lack valid methods. Bioimpedance is an attractive diagnostic tool because it is noninvasive, quick, and relatively cheap. This systematic review aims to assess the existing evidence of bioimpedance as an accurate measure of fluid status in critically ill patients. Data sources PubMed and Embase up till March 2021 were systematically searched (PROSPERO: CRD42020157436). Study selection Eligibility criteria were studies reporting original data from cohorts of adult patients in intensive care units and doing at least one whole‐body bioimpedance and one reference test. In addition, studies assessing internal reproducibility were included. Data extraction An extraction form was designed for the purpose. Data synthesis Nine hundred five studies were screened for eligibility, and 28 studies, comprising 1482 individual patients, were included in the final analysis. Eight studies compared bioimpedance with a gold standard, and two of those reported the results adequate. We found a low mean difference, but the 95% limits of agreements had wide limits. The remaining studies applied different surrogates as reference tests. Correlations ranged from 0.05 to 0.99. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty of evidence for all outcomes was very low. Conclusions The accuracy of bioimpedance as a measure for fluids in critically ill patients in the intensive care unit cannot be determined. Due to the lack of a gold standard, numerous studies compared bioimpedance with surrogate outcomes with great variability in both designs and results. Assessing the internal reproducibility of bioimpedance had the same limitations, but the studies overall reported good internal reproducibility.

We have found seven new variants of the BCHE, which seem to reduce the activity of BChE in patients undergoing anaesthesia involving succinylcholine or mivacurium.