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

Caitlin 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

Research output: Contribution to journalArticle

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: Stressdose 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.

Original languageEnglish (US)
Pages (from-to)2063-2071
Number of pages9
JournalIntensive Care Medicine
Volume38
Issue number12
DOIs
StatePublished - Dec 1 2012

Fingerprint

Staphylococcal Pneumonia
Desoxycorticosterone
Dexamethasone
Canidae
Adrenal Cortex Hormones
Oxacillin
Therapeutics
Mineralocorticoids
Microbial Sensitivity Tests
Lung Injury
Septic Shock
Bacteremia
Glucocorticoids
Shock
Interleukin-6
Sepsis
Odds Ratio
Placebos
Confidence Intervals
Temperature

Keywords

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

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Hicks, C., Sweeney, D. A., Danner, R. L., Eichacker, P. Q., Suffredini, A. F., Feng, J., ... Natanson, C. (2012). Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia. Intensive Care Medicine, 38(12), 2063-2071. https://doi.org/10.1007/s00134-012-2735-5

Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia. / Hicks, Caitlin; Sweeney, Daniel A.; Danner, Robert L.; Eichacker, Peter Q.; Suffredini, Anthony F.; Feng, Jing; Sun, Junfeng; Moriyama, Brad; Wesley, Robert; Behrend, Ellen N.; Solomon, Steven B.; Natanson, Charles.

In: Intensive Care Medicine, Vol. 38, No. 12, 01.12.2012, p. 2063-2071.

Research output: Contribution to journalArticle

Hicks, C, Sweeney, DA, Danner, RL, Eichacker, PQ, Suffredini, AF, Feng, J, Sun, J, Moriyama, B, Wesley, R, Behrend, EN, Solomon, SB & Natanson, C 2012, 'Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia', Intensive Care Medicine, vol. 38, no. 12, pp. 2063-2071. https://doi.org/10.1007/s00134-012-2735-5
Hicks, Caitlin ; Sweeney, Daniel A. ; Danner, Robert L. ; Eichacker, Peter Q. ; Suffredini, Anthony F. ; Feng, Jing ; Sun, Junfeng ; Moriyama, Brad ; Wesley, Robert ; Behrend, Ellen N. ; Solomon, Steven B. ; Natanson, Charles. / Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia. In: Intensive Care Medicine. 2012 ; Vol. 38, No. 12. pp. 2063-2071.
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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: Stressdose 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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AU - Danner, Robert L.

AU - Eichacker, Peter Q.

AU - Suffredini, Anthony F.

AU - Feng, Jing

AU - Sun, Junfeng

AU - Moriyama, Brad

AU - Wesley, Robert

AU - Behrend, Ellen N.

AU - Solomon, Steven B.

AU - Natanson, Charles

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N2 - 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: Stressdose 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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