Stress Doses Of Glucocorticoid Therapy In Children With Adrenal Insufficiency After Pediatric Cardiac Surgey

Objective:1) To measure plasma Cortisol level after pediatric cardiac surgery withcardiopulmonary bypass (CPB) and analyze risk factors for adrenal insufficiency(AI)after surgery.2) To evaluate the effect of stress doses of glucocorticoid in a predefined riskgroup of children after cardiac surgery with CPB.3) To detect the expression of glucocorticoid-receptor (GR) mRNA inperipheral blood white cell and analyze the effect of cardiac surgery on GRmRNA andpossible mechanism with stress doses of glucocorticoid treatment.Methods:1) In a prospective study, 80 children with congenital heart disease undergoingCPB were enrolled from March to October in 2006．Possible preoperative andintraoperative risk factors were recorded. The plasma levels of Cortisol weredetermined by radioimmunoassay. The plasma levels of ACTH were detected byChemiluminescence.2) We enrolled 40 children with risk factors into a prospective randomized trial.Patients were divided into treatment group (n=20) and control group (n=20) . Thetreatment group received intravenous stress doses of hydrocortisone sodium succinate,2mg/kg every 8 h on the surgery day, then 1mg/kg every 8 h on the first day aftersurgery, and then 0．5 mg/kg every 8 h on the second day after surgery. The placebowas 0．9% saline in control group. The plasma levels of Cortisol were determined byradioimmunoassay. The plasma levels of ACTH were detected byChemiluminescence. The plasma IL-6 concentration were measured by ELISA.Postoperative datum were collected. GRαmRNA and GR?mRNA levels in peripheralblood white cell were deteced by real-time fluorescence quantitative polymerase chainreaction technology(RT-PCR).Results:1) Plasma Cortisol concentration was significantly increased immediately and 6 hrs after surgery, compared with preoperation P<0．05．Plasma Cortisol concentrationwas significantly decreased 24, 48 and 72 hrs after surgery. Plasma ACTHconcentration decreased significantly 24 and 48 hrs after surgery, compared withpreoperation P<0．05．The incidence of AI was 41．25%. In AI children, means of age,cardiopulmonary bypass time, aortic cross-clamp time and pulse oxygen saturation(SPO₂) were significantly different from the means in children without AI. Ageand cardiopulmonary bypass time are independent risk factors.2) In treament group, plasma Cortisol concentration maintained high level,decreased a little from 24 hours after surgery, but still above the preoperative level.Plasma Cortisol concentration in control group was increased immediately and 6 hrsafter surgery, but significantly decreased 24,48 hs after surgery, compared withtreatment group P<0．05．The change of plasma ACTH concentration was nosignificant difference between two groups. Plasma IL-6 concentration was lower intreatment group 24,48, and 72hrs, compared with the control group P<0．05．, Intreatment group, postoperative PaO₂/FiO₂ was higher and the duration on mechanicalventilation was shorter. Inotrope score in treatment group was lower 24 hrs aftersurgery, compared with control group(4．70±2．13 vs 6．38±3．90, P<0．05) . C-reactiveprotein levels in treatment group was lower 24 and 48hrs after surgery, comparedwith the control group. The complication and mortality rate within the first 30 daysafter the operation did not differ significantly in our study. GRαmRNA levels washigher in treatment group 6, 24, and 48hrs, compared with the control group P<0．05．GRβmRNA levels was no difference between two groups.Conclusion:1) Plasma Cortisol concentration increases early after pediatric cardiac surgerywith CPB, followed by markedly decreasing 24 hrs postoperatively. AI may occur in anumber of patients after surgery.2) Age≤3m, CPB time≥90min are independent risk factors for AI after pediatriccardiac surgery with CPB.3) Stress doses of glucocorticoid seem to attenuate systemic inflammation in apredefined risk group of patients after pediatric cardiac surgery with CPB andimprove early outcome.4) Stress doses of glucocorticoid increase expression of GRαmRNA afterpediatric cardiac surgery with CPB . Elevated GRαlevel as a result of GRαmRNA expression is a possible therapeutic mechanisms with steroid supplementation.