TY - JOUR
T1 - Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia
AU - Hicks, Caitlin W.
AU - Sweeney, Daniel A.
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
PY - 2012/12
Y1 - 2012/12
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.
AB - 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.
KW - Antimicrobial agents
KW - Cardiopulmonary resuscitation
KW - Host defenses against pathogens
KW - Pulmonary nosocomial infections
KW - SIRS/sepsis: experimental studies
KW - Shock: experimental studies
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U2 - 10.1007/s00134-012-2735-5
DO - 10.1007/s00134-012-2735-5
M3 - Article
C2 - 23111805
AN - SCOPUS:84872074252
SN - 0342-4642
VL - 38
SP - 2063
EP - 2071
JO - Intensive Care Medicine
JF - Intensive Care Medicine
IS - 12
ER -