Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department*

Gaieski, David F.; Mikkelsen, Mark E.; Band, Roger A.; Pines, Jesse M.; Massone, Richard; Furia, Frances F.; Shofer, Frances S.; Goyal, Munish

doi:10.1097/ccm.0b013e3181cc4824

Cited by 820 publications

(581 citation statements)

References 16 publications

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“…Although these results require additional testing and further confirmation, they suggest that small but distinct variations in basal TIE2 expression can interact with the environmental stress of infection to influence risk in critical illness. Whether these same polymorphisms influence outcomes, such as ventilator duration or overall survival, may require a more complex analysis that accounts for variation in major treatment variables, such as time to antibiotic initiation or frequency with which lungprotective ventilation was used (27)(28)(29). It remains to be determined whether genetic variants that lower TIE2 expression contribute to worse survival outcomes, whereas variants that raise expression are associated with better outcomes.…”

Section: Discussionmentioning

confidence: 99%

Gene control of tyrosine kinase TIE2 and vascular manifestations of infections

Ghosh

David

Zhang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Ligands of the endothelial-enriched tunica interna endothelial cell kinase 2 (Tie2) are markedly imbalanced in severe infections associated with vascular leakage, yet regulation of the receptor itself has been understudied in this context. Here, we show that TIE2 gene expression may constitute a novel vascular barrier control mechanism in diverse infections. Tie2 expression declined rapidly in wide-ranging models of leak-associated infections, including anthrax, influenza, malaria, and sepsis. Forced Tie2 suppression sufficed to attenuate barrier function and sensitize endothelium to permeability mediators. Rapid reduction of pulmonary Tie2 in otherwise healthy animals attenuated downstream kinase signaling to the barrier effector vascular endothelial (VE)-cadherin and induced vascular leakage. Compared with wild-type littermates, mice possessing one allele of Tie2 suffered more severe vascular leakage and higher mortality in two different sepsis models. Common genetic variants that influence TIE2 expression were then sought in the HapMap3 cohort. Remarkably, each of the three strongest predicted cis-acting SNPs in HapMap3 was also associated with the risk of acute respiratory distress syndrome (ARDS) in an intensive care unit cohort of 1,614 subjects. The haplotype associated with the highest TIE2 expression conferred a 28% reduction in the risk of ARDS independent of other major clinical variables, including disease severity. In contrast, the most common haplotype was associated with both the lowest TIE2 expression and 31% higher ARDS risk. Together, the results implicate common genetic variation at the TIE2 locus as a determinant of vascular leak-related clinical outcomes from common infections, suggesting new tools to identify individuals at unusual risk for deleterious complications of infection.Tie2 | endothelium | infection | angiopoietin | permeability

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Section: Discussionmentioning

confidence: 99%

Gene control of tyrosine kinase TIE2 and vascular manifestations of infections

Ghosh

David

Zhang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Further, several studies show an adverse effect on secondary end points (e.g., LOS [75], acute kidney injury [76], acute lung injury [77], and organ injury assessed by Sepsis-Related Organ Assessment score [78] with increasing delays. Despite a meta-analysis of mostly poor-quality studies that failed to demonstrate a benefit of rapid antimicrobial therapy, the largest and highest-quality studies support giving appropriate antimicrobials as soon as possible in patients with sepsis with or without septic shock [57,74,[79][80][81]. The majority of studies within the meta-analysis were of low quality due to a number of deficiencies, including small study size, using an initial index time of an arbitrary time point such as emergency department arrival, and indexing of outcome to delay in time to the first antimicrobial (regardless of activity against the putative pathogen) [82,83].…”

Section: Rationalementioning

confidence: 99%

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

et al. 2017

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Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods:The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable.

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“…Gaieski y cols. 22 encontraron que el principal determinante de mortalidad en pacientes con sepsis severa y shock séptico, en quienes la reanimación precoz guiada por objetivos se inició en el departamento de emergencia, fue precisamente el retardo en la administración de un adecuado esquema antimicrobiano. Un análisis desarrollado por Barochia y cols.…”

Section: Administración Precoz De Antibióticos De Amplio-espectrounclassified

Actualización del bundle de reanimación inicial y monitorización integral de la perfusión tisular en la sepsis severa

P¹,

P²

2013

Rev. méd. Chile

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Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department*

Abstract: Elapsed times from triage and qualification for early goal-directed therapy to administration of appropriate antimicrobials are primary determinants of mortality in patients with severe sepsis and septic shock treated with early goal-directed therapy.

Cited by 820 publications

References 16 publications

Gene control of tyrosine kinase TIE2 and vascular manifestations of infections

Gene control of tyrosine kinase TIE2 and vascular manifestations of infections

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

Actualización del bundle de reanimación inicial y monitorización integral de la perfusión tisular en la sepsis severa

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