Intensive Care Medicine

, Volume 38, Issue 12, pp 2063–2071

Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia

  • Caitlin W. Hicks
  • Daniel A. Sweeney
  • Robert L. Danner
  • Peter Q. Eichacker
  • Anthony F. Suffredini
  • Jing Feng
  • Junfeng Sun
  • Brad Moriyama
  • Robert Wesley
  • Ellen N. Behrend
  • Steven B. Solomon
  • Charles Natanson
Experimental

DOI: 10.1007/s00134-012-2735-5

Cite this article as:
Hicks, C.W., Sweeney, D.A., Danner, R.L. et al. Intensive Care Med (2012) 38: 2063. doi:10.1007/s00134-012-2735-5

Abstract

Purpose

The effects of stress-dose corticosteroid therapy were studied in a canine staphylococcal pneumonia model of septic shock.

Methods

Immediately following intrabronchial bacterial challenge, purpose-bred beagles were treated with stress doses of desoxycorticosterone (DOC), a mineralocorticoid agonist, and dexamethasone (DEX), a glucocorticoid agonist, or with placebo for 96 h. Oxacillin (30 mg/kg every 8 h) was started 4 h after infection onset. Bacterial dose was titrated to achieve 80–90 % lethality (n = 20) using an adaptive design; additional animals (n = 18) were investigated using the highest bacterial dose.

Results

Initial analysis of all animals (n = 38) demonstrated that the effects of DOC + DEX were significantly altered by bacterial dose (p = 0.04). The treatment effects of DOC + DEX were different in animals administered high or relatively lower bacterial doses in terms of survival (p = 0.05), shock reversal (p = 0.02), interleukin-6 levels (p = 0.02), and temperature (p = 0.01). DOC + DEX significantly improved the above parameters (p ≤ 0.03 for all) and lung injury scores (p = 0.02) after high-dose bacterial challenges, but not after lower challenges (p = not significant for all). Oxacillin trough levels were below the minimum inhibitory concentration of the infecting organism, and DOC + DEX increased the frequency of persistent staphylococcal bacteremia (odds ratio 3.09; 95 % confidence interval 1.05–9.11; p = 0.04).

Conclusions

Stress-dose corticosteroids were only beneficial in cases of sepsis with high risk for death and even short courses may interfere with host mechanisms of bacterial clearance.

Keywords

Shock: experimental studies SIRS/sepsis: experimental studies Antimicrobial agents Cardiopulmonary resuscitation Host defenses against pathogens Pulmonary nosocomial infections 

Supplementary material

134_2012_2735_MOESM1_ESM.doc (118 kb)
Supplementary material 1 (DOC 125 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2012

Authors and Affiliations

  • Caitlin W. Hicks
    • 1
    • 2
    • 3
  • Daniel A. Sweeney
    • 4
  • Robert L. Danner
    • 3
  • Peter Q. Eichacker
    • 3
  • Anthony F. Suffredini
    • 3
  • Jing Feng
    • 3
  • Junfeng Sun
    • 3
  • Brad Moriyama
    • 5
  • Robert Wesley
    • 6
  • Ellen N. Behrend
    • 7
  • Steven B. Solomon
    • 3
  • Charles Natanson
    • 3
  1. 1.Department of General SurgeryThe Johns Hopkins HospitalBaltimoreUSA
  2. 2.National Institutes of Health Research Scholars ProgramHoward Hughes Medical InstituteChevy ChaseUSA
  3. 3.Critical Care Medicine Department, Clinical CenterNational Institutes of HealthBethesdaUSA
  4. 4.Medical Intensivist ProgramWashington HospitalFremontUSA
  5. 5.Clinical Center Pharmacy DepartmentNational Institutes of HealthBethesdaUSA
  6. 6.Office of Deputy Director of Clinical Care, Clinical CenterNational Institutes of HealthBethesdaUSA
  7. 7.Department of Clinical Sciences, College of Veterinary MedicineAuburn UniversityAuburnUSA

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