Surviving Sepsis Campaign: Research Opportunities for Infection and Blood Purification Therapies

Abstract

OBJECTIVES: Patients with infection can develop sepsis, and their mortality can be high. An important aspect in the treatment of sepsis is adequate management of the infection. DATA SOURCES: Using a modified Delphi approach, the Surviving Sepsis Campaign research committee recently published a series of 26 priorities for sepsis and septic shock. STUDY SELECTION: Task force members with specific expertise were tasked with generating expanded reviews for all infection questions and a subset of adjunctive therapy questions from the larger list of sepsis priorities. Each question was addressed by one of the six task force members. DATA EXTRACTION: In-depth reviews were then edited by the group as a whole, with added input from the committee cochairs. DATA SYNTHESIS: Six questions were addressed: 1) should empiric antibiotic combination therapy be used in sepsis or septic shock? 2) does optimization of antimicrobial pharmacokinetics and pharmacodynamics impact patient outcomes in sepsis? 3) should viral reactivation resulting from sepsis-induced immunosuppression be treated with antiviral therapy in critically ill septic patients? 4) should rapid diagnostic tests be implemented in clinical practice? 5) what is the role of lung-protective ventilation in sepsis patients without acute respiratory distress syndrome? and 6) how do we determine the efficacy of “blood purification” therapies such as endotoxin absorbers, cytokine absorbers, and plasmapheresis. CONCLUSIONS: The research committee members for the Surviving Sepsis Campaign aimed to explore research questions in order to provide existing evidence and highlight areas of uncertainty and future directions.

Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup

“…In patients with SA-AKI for whom KRT is indicated and with explicit clinical (for example, shock) and/or biological (for example, the detection of damage-associated molecular patterns and pathogen-associated molecular patterns) criteria are recognized, EBP for immunomodulatory support might be considered in combination with KRT, either concurrently (for example, hybrid treatments) or following KRT (Box 5). EBP for immunomodulatory support can be considered in patients with sepsis as a stand-alone treatment if kidney support is not required 142 . Despite the biological rationale for using EBP approaches in SA-AKI, namely their potential to limit the pathophysiology of organ damage, mitigate homeostatic derangements and prevent multi-organ dysfunction in sepsis, the lack of robust data precludes definitive recommendations with regard to its use in patients with sepsis or SA-AKI, including its timing in the clinical course of the disease.…”

Hemoperfusion: technical aspects and state of the art

“…Blood purification in sepsis has been a key area of investigation because of the view that soluble mediators of injury are a major contributor to morbidity and mortality in septic patients [ 30 ]. Such mediators appear to span a wide array of molecular size and are potentially amenable to removal by hemoperfusion.…”

Extracorporeal therapy of sepsis by purified granulocyte concentrates: ex vivo circulation model

“…A wide range of new treatment modalities has been evaluated for sepsis and septic shock. However, none of these treatments has currently been granted approval 4 …”

“…However, none of these treatments has currently been granted approval. 4 Immune cell dysfunction is a central component of immune paralysis in sepsis. With regard to cellular immunocompetence, functional impairment of neutrophils and monocytes as well as lymphopenia is associated with increased mortality in advanced stages of sepsis.…”