The intensive care medicine research agenda on septic shock

Perner, Anders; Gordon, Anthony; Angus, Derek C.; Lamontagne, François; Machado, Flávia Ribeiro; Russell, James A.; Timsit, Jean‐François; Marshall, John C.; Myburgh, John; Shankar-Hari, Manu; Singer, Mervyn

doi:10.1007/s00134-017-4821-1

Cited by 64 publications

(58 citation statements)

References 104 publications

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“…A 2017 research agenda by 11 international experts in septic shock listed 10 topics to undergo testing over the next 10 years [236]. A 2015 research roadmap by 13 international authors proposed research topics on a wide array of subjects ranging from epidemiology to molecular diagnostics [237].…”

Section: Resultsmentioning

confidence: 99%

Surviving sepsis campaign: research priorities for sepsis and septic shock

et al. 2018

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Objective: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock.Design: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations.Methods: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 -supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. Results:The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction?Conclusions: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

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Section: Resultsmentioning

confidence: 99%

Surviving sepsis campaign: research priorities for sepsis and septic shock

et al. 2018

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“…1 Among patients with sepsis in the ICU, evidence supports a fluid-sparing strategy. 1 Among patients with sepsis in the ICU, evidence supports a fluid-sparing strategy.…”

Section: Discussionmentioning

confidence: 99%

“…1 It also features prominently among the top research priorities identified by emergency physicians in the UK, Australia and New Zealand. 1 It also features prominently among the top research priorities identified by emergency physicians in the UK, Australia and New Zealand.…”

Section: Introductionmentioning

confidence: 99%

The Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In Emergency Department Sepsis, a multicentre observational study (ARISE FLUIDS observational study): Rationale, methods and analysis plan

Keijzers

Macdonald

Udy

et al. 2019

Emerg Medicine Australasia

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Objective There is uncertainty about the optimal i.v. fluid volume and timing of vasopressor commencement in the resuscitation of patients with sepsis and hypotension. We aim to study current resuscitation practices in EDs in Australia and New Zealand (the Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In Emergency Department Sepsis [ARISE FLUIDS] observational study). Methods ARISE FLUIDS is a prospective, multicentre observational study in 71 hospitals in Australia and New Zealand. It will include adult patients presenting to the ED during a 30 day period with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation. We will obtain data on baseline demographics, clinical and laboratory variables, all i.v. fluid given in the first 24 h, vasopressor use, time to antimicrobial administration, admission to intensive care, organ failure and in‐hospital mortality. We will specifically describe (i) the volume of fluid administered at the following time points: when meeting eligibility criteria, in the first 6 h, at 24 h and prior to vasopressor commencement and (ii) the frequency and timing of vasopressor use in the first 6 h and at 24 h. Screening logs will provide reliable estimates of the proportion of ED patients meeting eligibility criteria for a subsequent randomised controlled trial. Discussion This multicentre, observational study will provide insight into current haemodynamic resuscitation practices in patients with sepsis and hypotension as well as estimates of practice variation and patient outcomes. The results will inform the design and feasibility of a multicentre phase III trial of early haemodynamic resuscitation in patients presenting to ED with sepsis and hypotension.

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“…Efficacy may differ between tissue compartments and receptor subtypes involved, as a recent report by Proudfoot and colleagues demonstrates . In tailoring trials of novel agents, investigators should consider immunophenotyping patients before stratification into intervention arms to ensure the relevant cellular dysfunction is actually present before treating it . Finally, candidate therapies should resolve or limit organ dysfunction in preclinical studies as opposed to preventing it from occurring, as delivering therapies to patients pre‐illness is unlikely to be therapeutically tenable.…”

Section: Therapeutic Advances and Considerationsmentioning

confidence: 99%

“…Finally, candidate therapies should resolve or limit organ dysfunction in preclinical studies as opposed to preventing it from occurring, as delivering therapies to patients pre‐illness is unlikely to be therapeutically tenable. Careful attention to the above constraints is key for developing therapeutics in critical illness, and whilst laborious, is likely to meet with more success than previous efforts …”

Section: Therapeutic Advances and Considerationsmentioning

confidence: 99%

C5a anaphylatoxin and its role in critical illness‐induced organ dysfunction

Wood

Vassallo

Summers

et al. 2018

Eur J Clin Investigation

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Critical illness is an aetiologically and clinically heterogeneous syndrome that is characterised by organ failure and immune dysfunction. Mortality in critically ill patients is driven by inflammation-associated organ damage and a profound vulnerability to nosocomial infection. Both factors are influenced by the activated complement protein C5a, released by unbridled activation of the complement system during critical illness. C5a exerts deleterious effects on organ systems directly and suppresses antimicrobial functions of key immune cells. Whilst several recent reports have added key knowledge of the cellular signalling pathways triggered by C5a, there remain a number of areas that are incompletely understood and therapeutic opportunities are still being evaluated. In this review, we summarise the cellular basis for C5a-induced vulnerability to nosocomial infection and organ dysfunction. We focus on cells of the innate immune system, highlighting the major areas in need of further research and potential avenues for targeted therapies.

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The intensive care medicine research agenda on septic shock

Cited by 64 publications

References 104 publications

Surviving sepsis campaign: research priorities for sepsis and septic shock

Surviving sepsis campaign: research priorities for sepsis and septic shock

The Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In Emergency Department Sepsis, a multicentre observational study (ARISE FLUIDS observational study): Rationale, methods and analysis plan

C5a anaphylatoxin and its role in critical illness‐induced organ dysfunction

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