EFFECTS OF METHYLPREDNISOLONE ON PLASMA LEVELS OF C3a, PGE2, AND PAF IN PATIENTS UNDERGOING CABG AND EARLY EXTUBATION

Abstract

Introduction. Cardiopulmonary bypass (CPB) triggers the production and release of numerous chemotactic and vasoactive substances. [1,2] It remains controversial whether or not pretreatment with methylprednisolone (METHYL) may attenuate these changes. Furthermore, no investigation has examined use of the drug in the setting of early extubation (with substantially lower amounts of intraoperative opioids). This study investigates the effects of METHYL on plasma levels of complement 3a (C3a), prostaglandin E2 (PGE2), and platelet activating factor (PAF) in patients undergoing coronary artery bypass grafting (CABG) and early extubation. Methods. After IRB approval and informed consent, 60 patients scheduled for elective CABG were studied. Prior to anesthesia induction, patients were randomized to receive either intravenous METHYL (30 mg/kg at sternotomy and 30 mg/kg at initiation of CPB) or intravenous PLACEBO (normal saline) at the same two times. All patients received a standardized anesthetic technique consisting of fentanyl (20 mcg/kg), midazolam (10 mg, total), and vecuronium. Blood samples were obtained at five times perioperatively: ten minutes after intubation (Time A), ten minutes after sternotomy (Time B), twenty minutes after CPB initiation (Time C), ten minutes after sternal wires (Time D), and sixty minutes after intensive care unit (ICU) arrival (Time E). C3a, PGE2, and PAF levels were determined from each blood sample via radioimmunoassay. Results. 30 patients were randomized to each group. Mean crossclamp time (79 +/- 21 min, 84 +/- 22 min) and mean CPB time (98 +/- 28 min, 102 +/- 24 min) were similar in the PLACEBO and METHYL groups, respectively. C3a, PGE2, and PAF levels are listed below. (Table 1)Table 1Both groups exhibited significant increases in C3a levels (p < 0.0002 for each group) following exposure to CPB. Although PGE2 and PAF levels also increased in both groups, the changes were not statistically significant. No significant differences existed between groups. Discussion. CPB-induced increases in C3a, PGE2, and PAF may cause detrimental physiologic changes in patients following cardiac surgery (increased vascular permeability, vasodilation, platelet and leukocyte aggregation, etc.). [1,2] Previous clinical studies, although controversial, suggest METHYL may be beneficial in attenuating these changes. No investigation has examined use of the drug in the setting of early extubation (with substantially lower amounts of intraoperative opioids). We found that pretreatment with METHYL had no effect on plasma levels of C3a, PGE (2), and PAF and was unable to prevent significant increases in C3a levels following exposure to CPB in patients undergoing elective CABG and early extubation.