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. DESIGN:Prospective, randomized, double-blind clinical study of cardiac surgical patients. SETTING:Operating room and inpatient care facility of a university medical center. SUBJECTS:Sixty elective cardiac surgical patients scheduled for coronary artery bypass graft, cardiac valve replacement, or both. INTERVENTIONS: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. MEASUREMENTS AND MAIN 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 μg/dL before surgery to a mean of 43 μg/dL by 4 hrs after surgery. A dose of hydrocortisone (4 μg/kg/min for 6 hrs) that maintained plasma cortisol between 40 and 50 μg/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 μg/kg/min, although the mean peak plasma interleukin-10 concentration increased further compared with the group that received the 4 μg/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.