uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Counteraction of early circulatory derangement by administration of low dose steroid treatment at the onset of established endotoxemic shock is not directly mediated by TNF-α and IL-6
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function. (Klinisk kemi)
Show others and affiliations
2012 (English)In: Steroids, ISSN 0039-128X, E-ISSN 1878-5867, Vol. 77, no 11, 1101-1106 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Once a septic condition is progressing, administration of steroids in the pro-inflammatory phase of septic shock ought to yield maximal effect on the subsequent, devastating inflammatory response. Recently, a retrospective study showed that early initiation of corticosteroid therapy improved survival in septic shock. We aimed to prospectively evaluate effects of early administrated hydrocortisone therapy on physiologic variables in a porcine model of septic shock.

EXPERIMENT:

Eight anesthetized pigs were given a continuous infusion of endotoxin during this 6h prospective, randomized, parallel-grouped placebo-controlled experimental study. At the onset of endotoxemic shock, defined as the moment when the mean pulmonary arterial pressure reached the double baseline value, the pigs were either given a single intravenous dose of hydrocortisone (5 mg kg−1) or the corresponding volume of saline.

RESULTS:

Mean arterial pressure and systemic vascular resistance index were significantly higher (both p<0.05), and heart rate was significantly lower (p<0.05), in the endotoxin+hydrocortisone group as compared to the endotoxin+saline group. Body temperature and blood hemoglobin levels increased significantly in the endotoxin+saline group (both p<0.05). Urinary hydrocortisone increased significantly in both groups (p<0.05). There were no significant differences in the plasma levels of TNF-alpha, IL-6 or nitrite/nitrate between the groups.

CONCLUSION:

Early treatment with hydrocortisone ameliorates some endotoxin mediated circulatory derangements, fever response and microvascular outflow. Our results suggest that these effects are not directly mediated by the pro-inflammatory cytokines TNF-alpha or IL-6, nor by NO.

Place, publisher, year, edition, pages
2012. Vol. 77, no 11, 1101-1106 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-181444DOI: 10.1016/j.steroids.2012.06.001ISI: 000309021700010PubMedID: 22705410OAI: oai:DiVA.org:uu-181444DiVA: diva2:556128
Available from: 2012-09-24 Created: 2012-09-24 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Experimental septic shock – Effects of endotoxemia with special reference to pathophysiological responses in the pig
Open this publication in new window or tab >>Experimental septic shock – Effects of endotoxemia with special reference to pathophysiological responses in the pig
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Sepsis and septic shock are conditions, with severe outcome or in many cases death. Sepsis is a systemic inflammatory response trigger by bacteraemia but systemic inflammatory response can also be triggered by major trauma, major surgery, pancreatitis, severe burns etc.

The systemic inflammatory reaction initiating the evolvement of septic organ dysfunction can be modelled using endotoxin, a Gram-negative bacterial lipopolysaccharide. This thesis used a porcine experimental sepsis model to examine timing of the inflammatory response due to endotoxin infusion (Paper I) and the influence of steroid treatment on the inflammatory response in endotoxemic pigs (Paper II). Timing of steroid treatment and the role of neutrophil granulocyte activation was evaluated with pig specific NGAL assessing neutrophil activation (Paper III). A clinical observational study was performed with the aim to differentiate between sepsis and other inflammatory conditions (e.g. trauma due to major surgery) evaluated by calprotectin as a marker of neutrophil activation (Paper IV).

There was a dose-dependency in endotoxin tolerance which was measured with TNF-a. Pre-exposure to endotoxin did not reduce the pulmonary response to endotoxemic challenge. In fact, both PaO2 / FiO2 and static pulmonary compliance were reduced in this group when pre-treated with endotoxin at low dose.

Endotoxemic animals treated with hydrocortisone were more stable in circulatory variables than those without such treatment. This was not explained by an ability of steroids to modulate the production of NO (Nitric oxide), which has been suggested to be a mechanism of steroids in this aspect.

Pre-treatment with hydrocortisone attenuated the neutrophil granulocyte response and consequently diminished the release of NGAL in plasma. Circulatory derangement was associated with high plasma NGAL levels. Urine NGAL levels did not differ among the four groups.

Plasma calprotectin levels on ICU admission is a sensitive marker of systemic inflammation and are markedly increased in patients with sepsis and patients with systemic inflammatory response. Plasma Calprotectin performed better than any of the other inflammatory variables in predicting mortality at 30 days, except from the composite mortality prediction score, SAPS 3.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 59 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1256
Keyword
Endotoxin, inflammatory response, animal model, timing, steroid treatment, NGAL, Calprotectin
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-303822 (URN)978-91-554-9700-2 (ISBN)
Public defence
2016-10-28, Hedstrandsalen, Akademiska sjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-10-03 Created: 2016-09-24 Last updated: 2016-10-11

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Söderberg, EwaLipcsey, MiklósSjölin, JanLarsson, AndersEriksson, Mats B

Search in DiVA

By author/editor
Söderberg, EwaLipcsey, MiklósSjölin, JanLarsson, AndersEriksson, Mats B
By organisation
Anaesthesiology and Intensive CareInfectious DiseasesBiochemial structure and function
In the same journal
Steroids
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 516 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf