The Theory is Out There: The Use of ALPHA-2 Agonists in Treatment of Septic Shock

The Theory is Out There: The Use of ALPHA-2 Agonists in Treatment of Septic Shock ABSTRACTThe sympathetic nervous system plays an important role in the initial response to sepsis. This response enables the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become detrimental in the septic patient has fueled interest in the role and impact of sympathetic manipulation, including the selective inhibition of sympathetic tone to return and augment vascular reactivity. While conventional understanding of alpha 2 agonists activity is depletion of sympathetic outflow, novel evidence suggests mitigation rather than depletion. The mechanism by which these agents exert these properties remains controversial and appears to be condition-specific. The hypothesis by which alpha agonists affect the pathology of sepsis is multifactorial, but includes influence on inflammatory regulation, coagulopathy, dynamic flow, as well as vascular responsiveness and integrity. Theory and basic science evidence supports the use of α agonists in the septic population. The clinical evidence shedding light on this topic is limited and confounded by intention or trial design. Future evidence should focus on adjuvant therapy in patients progressing to or at high risk of shock development. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches Wolters Kluwer Health

The Theory is Out There: The Use of ALPHA-2 Agonists in Treatment of Septic Shock

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Publisher
Wolters Kluwer
Copyright
Copyright © 2017 by the Shock Society
ISSN
1073-2322
eISSN
1540-0514
D.O.I.
10.1097/SHK.0000000000000979
Publisher site
See Article on Publisher Site

Abstract

ABSTRACTThe sympathetic nervous system plays an important role in the initial response to sepsis. This response enables the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become detrimental in the septic patient has fueled interest in the role and impact of sympathetic manipulation, including the selective inhibition of sympathetic tone to return and augment vascular reactivity. While conventional understanding of alpha 2 agonists activity is depletion of sympathetic outflow, novel evidence suggests mitigation rather than depletion. The mechanism by which these agents exert these properties remains controversial and appears to be condition-specific. The hypothesis by which alpha agonists affect the pathology of sepsis is multifactorial, but includes influence on inflammatory regulation, coagulopathy, dynamic flow, as well as vascular responsiveness and integrity. Theory and basic science evidence supports the use of α agonists in the septic population. The clinical evidence shedding light on this topic is limited and confounded by intention or trial design. Future evidence should focus on adjuvant therapy in patients progressing to or at high risk of shock development.

Journal

SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical ApproachesWolters Kluwer Health

Published: Apr 1, 2018

References

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