Cortisol antiinflammatory effects are maximal at postoperative plasma concentrations.
OBJECTIVE
To determine the plasma concentration of cortisol that is needed for maximal suppression of the systemic inflammatory response to cardiac surgery with cardiopulmonary bypass.


METHODS
Prospective, randomized, double-blind clinical study of cardiac surgical patients.


METHODS
Operating room and inpatient care facility of a university medical center.


METHODS
Sixty elective cardiac surgical patients scheduled for coronary artery bypass graft, cardiac valve replacement, or both.


METHODS
Patients were randomized to receive one of three different hydrocortisone doses, by intravenous infusion, for 6 hrs before, during, and immediately after surgery while also receiving etomidate to suppress endogenous cortisol production.


RESULTS
Serial determinations of plasma interleukin-6 were studied as a marker of systemic inflammation. Measurements of interleukin-10 were used as a marker of the compensatory antiinflammatory response. Plasma cortisol concentrations in an untreated control group rose from 17 microg/dL before surgery to a mean of 43 microg/dL by 4 hrs after surgery. A dose of hydrocortisone (4 microg/kg/min for 6 hrs) that maintained plasma cortisol between 40 and 50 microg/dL, starting 60-90 mins before surgery, significantly suppressed plasma interleukin-6 after surgery compared with control while significantly increasing plasma interleukin-10 during surgery. Plasma interleukin-6 after surgery was not suppressed further by increasing the dose of hydrocortisone to 8 microg/kg/min, although the mean peak plasma interleukin-10 concentration increased further compared with the group that received the 4 microg/kg/min hydrocortisone dose.


CONCLUSIONS
At the doses studied, cortisol-induced suppression of plasma interleukin-6 during and after cardiac surgery appears to be a saturable phenomenon at the concentration of plasma cortisol that is normally achieved after surgery in untreated patients.
Department of Anesthesiology, Dartmouth Medical School, Hanover, NH, USA.
Mark P
MP
Yeager
Athos J
AJ
Rassias
Mary P
MP
Fillinger
Anthony W
AW
Discipio
Kelly E
KE
Gloor
Janice A
JA
Gregory
Paul M
PM
Guyre
D000368:Aged; D000893:Anti-Inflammatory Agents / Q000037:antagonists & inhibitors / Q000097:blood* / Q000627:therapeutic use*; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005045:Etomidate / Q000008:administration & dosage; D005260:Female; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D006854:Hydrocortisone / Q000037:antagonists & inhibitors / Q000097:blood* / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood / Q000209:etiology; D011446:Prospective Studies; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D005045:Etomidate; D006854:Hydrocortisone; D016753:Interleukin-10; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors