title: Efficacy of selective mineralocorticoid and glucocorticoid agonists in canine septic shock.
abstract: OBJECTIVE
  Corticosteroid regimens that stimulate both mineralocorticoid and glucocorticoid pathways consistently reverse vasopressor-dependent hypotension in septic shock but have variable effects on survival. The objective of this study was to determine whether exogenous mineralocorticoid and glucocorticoid treatments have distinct effects and whether the timing of administration alters their effects in septic shock. DESIGN, SETTING, SUBJECTS, AND INTERVENTIONS: Desoxycorticosterone, a selective mineralocorticoid agonist; dexamethasone, a selective glucocorticoid agonist; and placebo were administered either several days before (prophylactic) or immediately after (therapeutic) infectious challenge and continued for 96 hrs in 74 canines with staphylococcal pneumonia.
  
  
  RESULTS
  Effects of desoxycorticosterone and dexamethasone were different and opposite depending on timing of administration for survival (p = .05); fluid requirements (p = .05); central venous pressures (p ≤ .007); indicators of hemoconcentration (i.e., sodium [p = .0004], albumin [p = .05], and platelet counts [p = .02]); interleukin-6 levels (p = .04); and cardiac dysfunction (p = .05). Prophylactic desoxycorticosterone treatment significantly improved survival, shock, and all the other outcomes stated, but therapeutic desoxycorticosterone did not. Conversely, prophylactic dexamethasone was much less effective for improving these outcomes compared with therapeutic dexamethasone with the exception of shock reversal. Prophylactic dexamethasone given before sepsis induction also significantly reduced serum aldosterone and cortisol levels and increased body temperature and lactate levels compared with therapeutic dexamethasone (p ≤ .05), consistent with adrenal suppression.
  
  
  CONCLUSIONS
  In septic shock, mineralocorticoids are only beneficial if given prophylactically, whereas glucocorticoids are most beneficial when given close to the onset of infection. Prophylactic mineralocorticoids should be further investigated in patients at high risk to develop sepsis, whereas glucocorticoids should only be administered therapeutically to prevent adrenal suppression and worse outcomes.
authors.affiliation: Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA. hicksc@ccf.org
authors.forename: Caitlin W
authors.initials: CW
authors.lastname: Hicks
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Sweeney
authors.forename: Robert L
authors.initials: RL
authors.lastname: Danner
authors.forename: Peter Q
authors.initials: PQ
authors.lastname: Eichacker
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Suffredini
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.forename: Junfeng
authors.initials: J
authors.lastname: Sun
authors.forename: Ellen N
authors.initials: EN
authors.lastname: Behrend
authors.forename: Steven B
authors.initials: SB
authors.lastname: Solomon
authors.forename: Charles
authors.initials: C
authors.lastname: Natanson
mesh_terms: D000818:Animals; D001810:Blood Volume / Q000187:drug effects / Q000502:physiology; D002496:Central Venous Pressure / Q000187:drug effects / Q000502:physiology; D003900:Desoxycorticosterone / Q000008:administration & dosage / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004285:Dogs; D005938:Glucocorticoids / Q000819:agonists*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008901:Mineralocorticoids / Q000819:agonists*; D010976:Platelet Count; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy; D012709:Serum Albumin / Q000032:analysis; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D012964:Sodium / Q000097:blood; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
chemical_list: D005938:Glucocorticoids; D015850:Interleukin-6; D008901:Mineralocorticoids; D012709:Serum Albumin; D003900:Desoxycorticosterone; D003907:Dexamethasone; D012964:Sodium