Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia
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- Hicks, C.W., Sweeney, D.A., Danner, R.L. et al. Intensive Care Med (2012) 38: 2063. doi:10.1007/s00134-012-2735-5
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The effects of stress-dose corticosteroid therapy were studied in a canine staphylococcal pneumonia model of septic shock.
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.
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).
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.