Vasoplegia in septic shock: Do we really fight the right enemy?

Sharawy, Nivin

doi:10.1016/j.jcrc.2013.08.021

Cited by 44 publications

(29 citation statements)

References 84 publications

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“…A drop in blood pressure associated with incipient or ongoing infection, manifested by fever, chills and prostration, represents a hallmark of sepsis, prompting vigorous resuscitation measures and rapid administration of empiric antimicrobial therapy until the infectious agent is identified . Hypotension in the setting of sepsis reflects endothelial instability manifested by hyporesponsiveness to catecholamines . Production of NO by endothelial NO synthase (eNOS), and especially inducible NO synthase (iNOS), and generation of prostacyclin by cyclooxygenase (COX) 2 are proposed as the main triggers of hypotension in sepsis.…”

Section: Persistent Hypotension (Vasoplegia) and Microvascular Leak Imentioning

confidence: 99%

New paradigms in sepsis: from prevention to protection of failing microcirculation

Hawiger

Veach

Zienkiewicz

2015

Journal of Thrombosis and Haemostasis

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SummarySepsis, also known as septicemia, is one of the 10 leading causes of death worldwide. The rising tide of sepsis due to bacterial, fungal and viral infections cannot be stemmed by current antimicrobial therapies and supportive measures. New paradigms for the mechanism and resolution of sepsis and consequences for sepsis survivors are emerging. Consistent with Benjamin Franklin's dictum ‘an ounce of prevention is worth a pound of cure’, sepsis can be prevented by vaccinations against pneumococci and meningococci. Recently, the NIH NHLBI Panel redefined sepsis as ‘severe endothelial dysfunction syndrome in response to intravascular and extravascular infections causing reversible or irreversible injury to the microcirculation responsible for multiple organ failure’. Microvascular endothelial injury underlies sepsis‐associated hypotension, edema, disseminated intravascular coagulation, acute respiratory distress syndrome and acute kidney injury. Microbial genome products trigger ‘genome wars’ in sepsis that reprogram the human genome and culminate in a ‘genomic storm’ in blood and vascular cells. Sepsis can be averted experimentally by endothelial cytoprotection through targeting nuclear signaling that mediates inflammation and deranged metabolism. Endothelial ‘rheostats’ (e.g. inhibitors of NF‐κB, A20 protein, CRADD/RAIDD protein and microRNAs) regulate endothelial signaling. Physiologic ‘extinguishers’ (e.g. suppressor of cytokine signaling 3) can be replenished through intracellular protein therapy. Lipid mediators (e.g. resolvin D1) hasten sepsis resolution. As sepsis cases rose from 387 330 in 1996 to 1.1 million in 2011, and are estimated to reach 2 million by 2020 in the US, mortality due to sepsis approaches that of heart attacks and exceeds deaths from stroke. More preventive vaccines and therapeutic measures are urgently needed.

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Section: Persistent Hypotension (Vasoplegia) and Microvascular Leak Imentioning

confidence: 99%

New paradigms in sepsis: from prevention to protection of failing microcirculation

Hawiger

Veach

Zienkiewicz

2015

Journal of Thrombosis and Haemostasis

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“…13 This capillary leakage and migration of intravascular fluid to interstitial space lead to relative hypovolemia, tissue hypoperfusion, and organ dysfunction. 14 In animal studies, during sepsis, degradation of the glycocalyx has been accompanied by elevated serum level of glycocalyx degradation by-product (syndecan-1 and hyaluronic acid). The degree of elevation is correlated with worse outcomes.…”

Section: Sepsis and Glycocalyxmentioning

confidence: 99%

Glycocalyx in Sepsis Resuscitation

Chen

2016

Critical Care Nursing Quarterly

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Starling's forces are fundamental to our understanding of physiology. Based on his findings, hydrostatic pressure and oncotic pressure are crucial factors in the movement of intravascular and extravascular fluid. However, new literatures on endothelial glycocalyx, a layer of protective glycoprotein within the vasculature that was first discovered in the 1980s, are reshaping our standard models of Starling's forces. This article examines the nature of the endothelial glycocalyx and why understanding it may change the way we resuscitate patients with sepsis.

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“…As a consequence of the central role for AVP in regulation of hemodynamics, there has been several studies on AVP relating to vasodilatory shock and vasoplegia. Septic shock has been described as a relative AVP deficiency and it has been speculated that conditions with severe vasoplegic syndrome are linked to arginine-vasopressin dysfunction 6,7 . This has made AVP into an important tool in treating patients with both septic and non-septic critical vasoplegic conditions 6 .…”

Section: Introductionmentioning

confidence: 99%