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Early depletion of contact system in patients with sepsis : a prospective matched control observational study

Berkestedt, Ingrid LU ; Andersson, Pia LU ; Herwald, Heiko LU ; Valik, John Karlsson; Sörensen, Ola and Bodelsson, Mikael LU (2018) In APMIS p.892-898
Abstract

Activation of the contact system generates bradykinin from high-molecular-weight kininogen and has been suggested to participate in the pathophysiology of sepsis. To test this, we prospectively measured bradykinin and high-molecular-weight kininogen levels in a cohort of sepsis patients requiring intensive care. From 29 patients meeting criteria for sepsis or septic shock according to Sepsis-3, blood was sampled within 24 h and on the fourth day following admittance to intensive care. Patients planned for neurosurgery served as matched controls. Sequential organ failure assessment score and 90-day mortality was registered. Bradykinin levels (median [interquartile range]) were lower in sepsis patients (79 [62–172] pg/ml) compared to... (More)

Activation of the contact system generates bradykinin from high-molecular-weight kininogen and has been suggested to participate in the pathophysiology of sepsis. To test this, we prospectively measured bradykinin and high-molecular-weight kininogen levels in a cohort of sepsis patients requiring intensive care. From 29 patients meeting criteria for sepsis or septic shock according to Sepsis-3, blood was sampled within 24 h and on the fourth day following admittance to intensive care. Patients planned for neurosurgery served as matched controls. Sequential organ failure assessment score and 90-day mortality was registered. Bradykinin levels (median [interquartile range]) were lower in sepsis patients (79 [62–172] pg/ml) compared to controls (130 [86–255] pg/ml, p < 0.025) and did not correlate with mortality or severity of circulatory derangement. High-molecular-weight kininogen levels were lower in sepsis patients (1.6 [0.8–4.8] densitometry units) compared to controls (4.4 [2.9–7.7] densitometry units, p < 0.001), suggesting previous contact system activation. High-molecular-weight kininogen levels were lower in non-survivors than survivors (p = 0.003) and negatively correlated to severity of circulatory derangement. We conclude that a role for bradykinin in later stages of severe sepsis must be challenged. Low high-molecular-weight kininogen concentrations suggest that the decrease in bradykinin is due to substrate depletion.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bradykinin, contact system, high-molecular-weight, kininogen, sepsis
in
APMIS
pages
892 - 898
publisher
John Wiley & Sons
external identifiers
  • scopus:85056146994
ISSN
0903-4641
DOI
10.1111/apm.12898
language
English
LU publication?
yes
id
0dccf2e2-92e5-4a68-b0ce-1bd366760b7e
date added to LUP
2018-11-23 09:20:48
date last changed
2019-09-04 02:21:23
@article{0dccf2e2-92e5-4a68-b0ce-1bd366760b7e,
  abstract     = {<p>Activation of the contact system generates bradykinin from high-molecular-weight kininogen and has been suggested to participate in the pathophysiology of sepsis. To test this, we prospectively measured bradykinin and high-molecular-weight kininogen levels in a cohort of sepsis patients requiring intensive care. From 29 patients meeting criteria for sepsis or septic shock according to Sepsis-3, blood was sampled within 24 h and on the fourth day following admittance to intensive care. Patients planned for neurosurgery served as matched controls. Sequential organ failure assessment score and 90-day mortality was registered. Bradykinin levels (median [interquartile range]) were lower in sepsis patients (79 [62–172] pg/ml) compared to controls (130 [86–255] pg/ml, p &lt; 0.025) and did not correlate with mortality or severity of circulatory derangement. High-molecular-weight kininogen levels were lower in sepsis patients (1.6 [0.8–4.8] densitometry units) compared to controls (4.4 [2.9–7.7] densitometry units, p &lt; 0.001), suggesting previous contact system activation. High-molecular-weight kininogen levels were lower in non-survivors than survivors (p = 0.003) and negatively correlated to severity of circulatory derangement. We conclude that a role for bradykinin in later stages of severe sepsis must be challenged. Low high-molecular-weight kininogen concentrations suggest that the decrease in bradykinin is due to substrate depletion.</p>},
  author       = {Berkestedt, Ingrid and Andersson, Pia and Herwald, Heiko and Valik, John Karlsson and Sörensen, Ola and Bodelsson, Mikael},
  issn         = {0903-4641},
  keyword      = {Bradykinin,contact system,high-molecular-weight,kininogen,sepsis},
  language     = {eng},
  pages        = {892--898},
  publisher    = {John Wiley & Sons},
  series       = {APMIS},
  title        = {Early depletion of contact system in patients with sepsis : a prospective matched control observational study},
  url          = {http://dx.doi.org/10.1111/apm.12898},
  year         = {2018},
}