Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock.
OBJECTIVE
To investigate the effect of low-dose hydrocortisone on time to shock reversal, the cytokine profile, and its relation to adrenal function in patients with early septic shock.


METHODS
Prospective, randomized, double-blind, single-center study.


METHODS
Medical intensive care unit of a university hospital.


METHODS
Forty-one consecutive patients with early hyperdynamic septic shock.


METHODS
After inclusion and a short adrenocorticotropic hormone test, all patients were randomized to receive either low-dose hydrocortisone (50-mg bolus followed by a continuous infusion of 0.18 mg/kg body of weight/hr) or matching placebo. After shock reversal, the dose was reduced to 0.06 mg/kg/hr and afterward slowly tapered. Severity of illness was estimated using Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score.


RESULTS
Time to cessation of vasopressor support (primary end point) was significantly shorter in hydrocortisone-treated patients compared with placebo (53 hrs vs. 120 hrs, p < .02). This effect was more profound in patients with impaired adrenal reserve. Irrespective of endogenous steroid production, cytokine production was reduced in the treatment group with lower plasma levels of interleukin-6 and a diminished ex vivo lipopolysaccharide-stimulated interleukin-1 and interleukin-6 production. Interleukin-10 levels were unaltered. Adverse events were not more frequent in the treatment group.


CONCLUSIONS
Treatment with low-dose hydrocortisone accelerates shock reversal in early hyperdynamic septic shock. This was accompanied by reduced production of proinflammatory cytokines, suggesting both hemodynamic and immunomodulatory effects of steroid treatment. Hemodynamic improvement seemed to be related to endogenous cortisol levels, whereas immune effects appeared to be independent of adrenal reserve.
Oppert
Michael
M
Department of Nephrology and Medical Intensive Care, Charite Universitätsmedizin Berlin, Humboldt University, Berlin, Germany.
Schindler
Ralf
R
Husung
Claudia
C
Offermann
Katrin
K
Gräf
Klaus-Jürgen
KJ
Boenisch
Olaf
O
Barckow
Detlef
D
Frei
Ulrich
U
Eckardt
Kai-Uwe
KU
D018806:APACHE; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012772:Shock, Septic / Q000097:blood / Q000145:classification / Q000188:drug therapy*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006854:Hydrocortisone