Intravenous versus intrapulmonary administration of corticosteroids in combination with fluid infusion in experimental septic shock.
Three different routes of corticosteroid administration (intravenous (IV), intratracheal instillation (IT), and aerosol inhalation (AE)) were evaluated for the treatment of an experimental septic shock induced by E. coli, given intraperitoneally. The corticosteroids, dexamethasone and budesonide, were given alone and in combination with 3% albumin infusion. Shock induced a plasma volume loss to 69% of control levels. This was partially prevented by corticosteroids alone, and prevented completely by 3% albumin infusion. The two corticosteroids were identical with respect to prolongation of survival time and hematocrit changes, regardless of the route of administration. Plasma steroid concentrations of budesonide were similar after IT and IV administration. Increasing doses of corticosteroids up to 8 mg/kg significantly prolonged mean survival time from 9 to 13 hours. When antibiotics and 3% albumin infusions were combined, survival time increased to 15 hours. Corticosteroids added to antibiotics and 3% albumin increased 24-hour survival rate from 0 to 60% (p less than 0.001). Intrapulmonary administration of corticosteroids is as effective as the intravenous route, and offers an important alternative, with obvious clinical implications. Further pharmacological modifications of the corticosteroids are necessary in order to evaluate local pulmonary versus the systemic effects.
Ottosson
J
J
Department of Surgery, University of Texas Health Science Center, Dallas.
Dawidson
I J
IJ
Svensjö
E
E
Brattsand
R
R
Dahlbäck
M
M
D000280:Administration, Inhalation; D000418:Albumins / Q000008:administration & dosage; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D019819:Budesonide; D003907:Dexamethasone / Q000008:administration & dosage* / Q000097:blood; D004359:Drug Therapy, Combination; D006400:Hematocrit; D007275:Injections, Intravenous; D008297:Male; D011282:Pregnenediones / Q000008:administration & dosage* / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality; D014132:Trachea
D000418:Albumins; D000893:Anti-Inflammatory Agents; D011282:Pregnenediones; D019819:Budesonide; D003907:Dexamethasone