Articles: sepsis.
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Am. J. Respir. Crit. Care Med. · Apr 2019
Randomized Controlled TrialTranscriptomic Signatures in Sepsis and a Differential Response to Steroids: From the VANISH Randomized Trial.
There remains uncertainty about the role of corticosteroids in sepsis with clear beneficial effects on shock duration, but conflicting survival effects. Two transcriptomic sepsis response signatures (SRSs) have been identified. SRS1 is relatively immunosuppressed, whereas SRS2 is relatively immunocompetent. ⋯ Transcriptomic profile at onset of septic shock was associated with response to corticosteroids. Those with the immunocompetent SRS2 endotype had significantly higher mortality when given corticosteroids compared with placebo. Clinical trial registered with www.clinicaltrials.gov (ISRCTN 20769191).
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Critical care medicine · Apr 2019
Randomized Controlled TrialTreatment With Acetylsalicylic Acid Reverses Endotoxin Tolerance in Humans In Vivo: A Randomized Placebo-Controlled Study.
To investigate immunostimulatory effects of acetylsalicylic acid during experimental human endotoxemia and in sepsis patients. ⋯ Treatment, but not prophylaxis, with low-dose acetylsalicylic acid, partially reverses endotoxin tolerance in humans in vivo by shifting response toward a proinflammatory phenotype. This acetylsalicylic acid-induced proinflammatory shift was also observed in septic monocytes, signifying that patients suffering from sepsis-induced immunoparalysis might benefit from initiating acetylsalicylic acid treatment.
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Randomized Controlled Trial Multicenter Study
Permissive versus restrictive temperature thresholds in critically ill children with fever and infection: a multicentre randomized clinical pilot trial.
Fever improves pathogen control at a significant metabolic cost. No randomized clinical trials (RCT) have compared fever treatment thresholds in critically ill children. We performed a pilot RCT to determine whether a definitive trial of a permissive approach to fever in comparison to current restrictive practice is feasible in critically ill children with suspected infection. ⋯ Uncertainty around the optimal fever threshold for antipyretic intervention is relevant to many emergency PICU admissions. A more permissive approach was associated with a modest increase in mean maximum temperature. A definitive trial should focus on the most seriously ill cases in whom antipyretics are rarely used for their analgesic effects alone.
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Randomized Controlled Trial Multicenter Study
A protocol for a phase 3 multicentre randomised controlled trial of continuous versus intermittent β-lactam antibiotic infusion in critically ill patients with sepsis: BLING III.
β-Lactam antibiotics display a time-dependent mechanism of action, with evidence suggesting improved outcomes when administering these drugs via continuous infusion compared with standard intermittent infusion. However, there is no phase 3 randomised controlled trial (RCT) evidence to support one method of administration over another in critically ill patients with sepsis. ⋯ The BLING III study will compare the effect on 90-day mortality of β-lactam antibiotics administered via continuous versus intermittent infusion in 7000 critically ill patients with sepsis.
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Randomized Controlled Trial Multicenter Study
A double-blind, placebo-controlled, randomised, multicentre, proof-of-concept and dose-finding phase II clinical trial to investigate the safety, tolerability and efficacy of adrecizumab in patients with septic shock and elevated adrenomedullin concentration (AdrenOSS-2).
Sepsis remains a major health problem with an increasing incidence, high morbidity and high mortality. Apart from treatment with antibiotics and organ support, no approved specific adjunct therapies currently exist. Adrenomedullin (ADM) is a vasoactive peptide. High plasma concentrations of ADM correlate with worse outcome in sepsis patients. Preclinical work with the non-neutralising ADM-binding antibody adrecizumab showed promising effects in animal models of septic shock, including improved vascular barrier function, reduced vasopressor demand and organ dysfunction and increased survival. Therapeutic use of adrecizumab may therefore improve outcome in critically ill patients with septic shock and high ADM plasma concentrations. Phase I studies in healthy volunteers did not reveal any safety concerns. In this biomarker-guided trial, the safety and efficacy of adrecizumab will be investigated in patients with septic shock. ⋯ This study is approved by relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, the European Medicines Agency guidelines of Good Clinical Practice and all other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal.