title: Steroid administration in heart and heart-lung transplantation: is the timing adequate?
abstract: BACKGROUND
  The release of cytokines after cardiopulmonary bypass may play an important role in postoperative morbidity. The release of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin (IL)-6 and IL-8, is even greater in patients undergoing heart transplantation (HTx) than coronary artery grafting. We tested the hypothesis that in HTx patients the earlier administration of steroids, before rather than after cardiopulmonary bypass as usual, can reduce the inflammatory response.
  
  
  METHODS
  In 20 consecutive patients who underwent HTx or heart-lung transplantation (HLTx), plasma levels of tumor necrosis factor alpha, IL-6, IL-8, and anti-inflammatory cytokine IL-10 were measured before heparin administration, at aortic cross-clamping and declamping, and 0.5, 1, 1.5, 2, 4, 12, and 24 hours after aortic declamping. In 10 patients (group I, 6 HTx and 4 HLTx), 500 mg of methylprednisolone was first given as usual at 1.5 hours after aortic declamping (at the end of cardiopulmonary bypass). In the next 10 patients (group II, 6 HTx and 4 HLTx), the first doses of methylprednisolone were given 1 hour before operation. In both groups, 125 mg of methylprednisolone were given every 8 hours thereafter during the first postoperative day.
  
  
  RESULTS
  The ischemic time and cardiopulmonary bypass time were similar in the two groups (166 +/- 16 minutes versus 157 +/- 13 minutes, and 192 +/- 21 minutes versus 186 +/- 20 minutes, respectively, mean +/- standard error of the mean). At 30 minutes after aortic declamping and throughout the next 4 hours, tumor necrosis factor alpha levels were significantly lower in group II than in group I (all p < 0.03). Interleukin-8 values 1 hour after declamping were also lower in group II than in group I (49 +/- 15 pg/mL versus 130 +/- 38 pg/mL, p < 0.02). Interleukin-10 levels were significantly higher in group II than in group I from 30 minutes after declamping through 2 hours after (all p < 0.03). Interleukin-6 levels were similar in the two groups.
  
  
  CONCLUSIONS
  Earlier steroid administration in the immunosuppressive protocol for HTx or HLTx may be preferable to reduce the inflammatory response to cardiopulmonary bypass, as reflected by a lower production of tumor necrosis factor alpha and IL-8, and a greater release of IL-10.
authors.affiliation: Department of Cardiac Surgery, University Hospital Erasme, Free University of Brussels, Belgium, USA.
authors.forename: S
authors.initials: S
authors.lastname: Wan
authors.forename: J M
authors.initials: JM
authors.lastname: DeSmet
authors.forename: M
authors.initials: M
authors.lastname: Antoine
authors.forename: M
authors.initials: M
authors.lastname: Goldman
authors.forename: J L
authors.initials: JL
authors.lastname: Vincent
authors.forename: J L
authors.initials: JL
authors.lastname: LeClerc
mesh_terms: D000328:Adult; D000368:Aged; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D016207:Cytokines / Q000097:blood*; D004334:Drug Administration Schedule; D005260:Female; D016027:Heart Transplantation; D016041:Heart-Lung Transplantation; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D011182:Postoperative Care; D011292:Premedication
chemical_list: D016207:Cytokines; D006493:Heparin; D008775:Methylprednisolone