Glucocorticoid effects on the inflammatory and clinical responses to cardiac surgery.
OBJECTIVE
To measure the effects of glucocorticoids on the systemic inflammatory response and clinical recovery after cardiac surgery.


METHODS
Randomized, prospective, double-blind, placebo-controlled clinical trial with concurrent comparison groups.


METHODS
University medical center.


METHODS
Patients scheduled for elective coronary artery bypass graft surgery using normothermic cardiopulmonary bypass (CPB) and a standardized anesthetic.


METHODS
Participants randomly received either methylprednisolone, 15 mg/kg intravenously 1 hour before surgery and 0.3 mg/kg intravenously every 6 hours x 4 doses, or placebo. Comparison groups included cardiac surgical patients who received etomidate to lower endogenous cortisol during surgery and healthy volunteers who received methylprednisolone only.


RESULTS
Patients who received methylprednisolone had a significant reduction in circulating interleukin (IL)-6 at 60 minutes after CPB (p < 0.05) and on the morning of the 1st (p < 0.01) and 3rd (p < 0.05) postoperative days and a significant increase in circulating IL-10 at 60 minutes after CPB (p < 0.01) compared with the placebo group. Etomidate, given to lower cortisol during surgery, was associated with significantly decreased IL-6 and IL-10 responses to surgery compared with the placebo group, whereas methylprednisolone alone, given to healthy nonsurgical volunteers, had no effect on these cytokines. After adjusting for age, there were no significant differences in postoperative length of hospital stay between the methylprednisolone-treated (4.6 days) and placebo (6.1 days) groups or in the duration of mechanical ventilation (9.9 hours and 15.6 hours). No patient treated with methylprednisolone had nausea and vomiting on the 1st postoperative day compared with 33% of placebo-treated patients (p = 0.02). Glucose was significantly higher after methylprednisolone treatment at 1 hour after CPB (276 mg/dL v 210 mg/dL; p = 0.001) and at 2 hours (289 mg/dL v 213 mg/dL; p = 0.009) and 8 hours (247 mg/dL v 196 mg/dL; p = 0.02) after surgery. There were no differences in pain scores and no significant intergroup differences in lung peak expiratory flow rate or alveolar-arterial oxygen gradients after surgery.


CONCLUSIONS
This study shows significant effects of glucocorticoids on the production of IL-6 and IL-10 in response to cardiac surgery but only minor effects on clinical recovery.
Fillinger
Mary P
MP
Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Rassias
Athos J
AJ
Guyre
Paul M
PM
Sanders
John H
JH
Beach
Michael
M
Pahl
Janice
J
Watson
R Brad
RB
Whalen
P Kate
PK
Yeo
Kiang-Teck J
KT
Yeager
Mark P
MP
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005045:Etomidate / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008775:Methylprednisolone / Q000494:pharmacology*; D008875:Middle Aged; D011183:Postoperative Complications; D020250:Postoperative Nausea and Vomiting; D011446:Prospective Studies; D015656:Respiratory Mechanics / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D018836:Inflammation Mediators; D015850:Interleukin-6; D016753:Interleukin-10; D006854:Hydrocortisone; D008775:Methylprednisolone; D005045:Etomidate