Counteraction of early circulatory derangement by administration of low dose steroid treatment at the onset of established endotoxemic shock is not directly mediated by TNF-α and IL-6.
BACKGROUND
Once a septic condition is progressing, administration of steroids in the pro-inflammatory phase of septic shock ought to yield maximal effect on the subsequent, devastating inflammatory response. Recently, a retrospective study showed that early initiation of corticosteroid therapy improved survival in septic shock. We aimed to prospectively evaluate effects of early administrated hydrocortisone therapy on physiologic variables in a porcine model of septic shock.


METHODS
Eight anesthetized pigs were given a continuous infusion of endotoxin during this 6 h prospective, randomized, parallel-grouped placebo-controlled experimental study. At the onset of endotoxemic shock, defined as the moment when the mean pulmonary arterial pressure reached the double baseline value, the pigs were either given a single intravenous dose of hydrocortisone (5 mg kg(-1)) or the corresponding volume of saline.


RESULTS
Mean arterial pressure and systemic vascular resistance index were significantly higher (both p<0.05), and heart rate was significantly lower (p<0.05), in the endotoxin+hydrocortisone group as compared to the endotoxin+saline group. Body temperature and blood hemoglobin levels increased significantly in the endotoxin+saline group (both p<0.05). Urinary hydrocortisone increased significantly in both groups (p<0.05). There were no significant differences in the plasma levels of TNF-alpha, IL-6 or nitrite/nitrate between the groups.


CONCLUSIONS
Early treatment with hydrocortisone ameliorates some endotoxin mediated circulatory derangements, fever response and microvascular outflow. Our results suggest that these effects are not directly mediated by the pro-inflammatory cytokines TNF-alpha or IL-6, nor by NO.
Section of Anaesthesiology & Intensive Care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. ewa.soderberg@surgsci.uu.se
Ewa
E
Söderberg
Miklós
M
Lipcsey
Jan
J
Sjölin
Anders
A
Larsson
Mats B
MB
Eriksson
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D062186:Arterial Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004334:Drug Administration Schedule; D004731:Endotoxins; D006339:Heart Rate / Q000187:drug effects; D006854:Hydrocortisone / Q000008:administration & dosage*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008297:Male; D010919:Placebos; D011897:Random Allocation; D055502:Secondary Prevention; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D015850:Interleukin-6; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D006854:Hydrocortisone