Adjunctive treatments for the management of septic shock – a narrative review of the current evidence

Abstract

Summary Septic shock is a leading cause of death and morbidity worldwide. The cornerstones of management include prompt identification of sepsis, early initiation of antibiotic therapy, adequate fluid resuscitation and organ support. Over the past two decades, there have been considerable improvements in our understanding of the pathophysiology of sepsis and the host response, including regulation of inflammation, endothelial disruption and impaired immunity. This has offered opportunities for innovative adjunctive treatments such as vitamin C, corticosteroids and beta‐blockers. Some of these approaches have shown promising results in early phase trials in humans, while others, such as corticosteroids, have been tested in large, international, multicentre randomised controlled trials. Contemporary guidelines make a weak recommendation for the use of corticosteroids to reduce mortality in sepsis and septic shock. Vitamin C, despite showing initial promise in observational studies, has so far not been shown to be clinically effective in randomised trials. Beta‐blocker therapy may have beneficial cardiac and non‐cardiac effects in septic shock, but there is currently insufficient evidence to recommend their use for this condition. The results of ongoing randomised trials are awaited. Crucial to reducing heterogeneity in the trials of new sepsis treatments will be the concept of enrichment, which refers to the purposive selection of patients with clinical and biological characteristics that are likely to be responsive to the intervention being tested.

COVID-19 Infection and Circulating Microparticles—Reviewing Evidence as Microthrombogenic Risk Factor for Cerebral Small Vessel Disease

“…Additionally, the evidences on the use corticosteroids in the treatment for COVID-19 rest mainly on their high efficacy as an anti-inflammatory agent and therapy (i.e., in chronic inflammatory disease) [ 260 ]. Recent study also suggested the beneficial role of corticosteroids to reduce mortality in sepsis, alongside with the likely anti-inflammatory actions to reduce the detrimental effects of MPs-mediated inflammation [ 276 ]. Hence, corticosteroids may indirectly aid in reducing the peripherals MPs level which in turn could prevent undesirable progression and/or further adverse effect of the infection particularly towards the onset of CSVD.…”

Effect of β-blockers on mortality in patients with sepsis: A propensity-score matched analysis

“…The current therapeutics for sepsis mainly focus on early empiric antibiotics, fluid resuscitation, and the use of vasoactive drugs, as well as temporary organ support such as mechanical ventilation and renal replacement therapy. Given the lack of high-quality evidence, many treatments based on dysregulation of the host immune response are not routinely applied in clinical practice ( Donovan et al., 2021 ).…”

Circulating Microvesicle-Associated Inducible Nitric Oxide Synthase Is a Novel Therapeutic Target to Treat Sepsis: Current Status and Future Considerations

“…As the sepsis pathology progresses, organ dysfunction often occurs and deteriorates into multiple organ failure and death (18,19,20). Sepsis is estimated to be involved in up to 50% of all hospital deaths, and morbidity and mortality remain unacceptably high in septic patients mainly due to the lack of a specific and targeted treatment (21,22,23). Also, mortality has been reported to increase approximately 5% per year for the first five years after discharge due to the long-term health complications of sepsis (24,25).…”