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

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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.

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Authors and Affiliations

  1. Department of General Surgery, The Johns Hopkins Hospital, Baltimore, MD, 21287, USA

    Caitlin W. Hicks

  2. National Institutes of Health Research Scholars Program, Howard Hughes Medical Institute, Chevy Chase, MD, USA

    Caitlin W. Hicks

  3. Critical Care Medicine Department, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bldg 10, Room 2C145, Bethesda, MD, 20892, USA

    Caitlin W. Hicks, Robert L. Danner, Peter Q. Eichacker, Anthony F. Suffredini, Jing Feng, Junfeng Sun, Steven B. Solomon & Charles Natanson

  4. Medical Intensivist Program, Washington Hospital, Fremont, CA, 94538, USA

    Daniel A. Sweeney

  5. Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD, 20892, USA

    Brad Moriyama

  6. Office of Deputy Director of Clinical Care, Clinical Center, National Institutes of Health, Bethesda, MD, 20892, USA

    Robert Wesley

  7. Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL, 36849, USA

    Ellen N. Behrend

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  1. Caitlin W. Hicks
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Corresponding author

Correspondence to Caitlin W. Hicks.

Additional information

The study was supported by NIH intramural funds, but the opinions expressed herein do not necessarily represent the opinions of the US Government.

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Hicks, C.W., Sweeney, D.A., Danner, R.L. et al. Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia. Intensive Care Med 38, 2063–2071 (2012). https://doi.org/10.1007/s00134-012-2735-5

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  • DOI: https://doi.org/10.1007/s00134-012-2735-5

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