Dexamethasone: benefit and prejudice for patients undergoing on-pump coronary artery bypass grafting: a study on myocardial, pulmonary, renal, intestinal, and hepatic injury.
OBJECTIVE
Cardiac surgery with cardiopulmonary bypass (CPB) results in perioperative organ damage caused by the systemic inflammatory response syndrome (SIRS) and ischemia/reperfusion injury. Administration of corticosteroids before CPB has been demonstrated to inhibit the activation of the systemic inflammatory response. However, the clinical benefits of corticosteroid therapy are controversial. This study was designed to document the effects of dexamethasone on cytokine release and perioperative myocardial, pulmonary, renal, intestinal, and hepatic damage, as assessed by specific and sensitive biomarkers.


METHODS
A prospective, double-blind, placebo-controlled, randomized trial for dexamethasone was conducted in 20 patients receiving either dexamethasone (1 mg/kg before anesthesia induction and 0.5 mg/kg after 8 h; n = 10) or placebo (n = 10). Different markers were used to assess the SIRS: interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), and tryptase; and organ damage: heart (plasma heart-type fatty acid binding protein, cardiac troponin I [cTnI], creatine kinase-MB), kidneys (N-acetyl-glucosaminidase [NAG], microalbuminuria), intestine (intestinal-type fatty acid binding protein [I-FABP]/liver-type fatty acid binding protein [L-FABP]), and liver (alpha-glutathione S-transferase).


RESULTS
Dexamethasone modulated the SIRS with lower proinflammatory (IL-6, IL-8) and higher antiinflammatory (IL-10) IL levels. CRP and tryptase were lower in the dexamethasone group. cTnI values were lower in the dexamethasone group at 6 h in the ICU (p = 0.009). Patients in the dexamethasone group had a longer time to tracheal extubation (18.86 +/- 1.13 h vs 15.01 +/- 0.99 h, p = 0.02 [mean +/- SEM]), with a lower oxygenation index at that time: Pa(O2)/fraction of inspired oxygen ratio, 37.17 +/- 1.8 kPa vs 29.95 +/- 2.1 kPa (p = 0.009). The postoperative glucose level (10.7 +/- 0.6 mmol/L vs 7.4 +/- 0.5 mmol/L, p = 0.005) was higher in the dexamethasone group. Serum glucose was independently associated with intestinal injury (urine I-FABP peak, R2 = 42.5%, beta = 114.4 +/- 31.4, significant at p = 0.002; urine L-FABP peak, R2 = 47.3%, beta = 7,714.1 +/- 1,920.9, significant at p = 0.001) and renal injury (urine NAG, R2 = 32.1%, beta = 0.21 +/- 0.07, significant at p = 0.009). Tryptase peaks correlated negatively with peaks of intestinal and renal injury biomarkers.


CONCLUSIONS
Even while inhibiting SIRS, dexamethasone treatment offered no protection against transient, subclinical, perioperative abdominal organ damage. Tryptase release could have a preconditioning effect, offering protection against perioperative intestinal and renal damage. Dexamethasone treatment resulted in more pronounced postoperative pulmonary dysfunction, prolonged time to tracheal extubation, and initiated postoperative hyperglycemia in patients undergoing elective on-pump coronary artery bypass graft surgery.
Morariu
Aurora M
AM
Department of BioMedical Engineering/Artificial Organs, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, Netherlands.
Loef
Berthus G
BG
Aarts
Leon P H J
LP
Rietman
Gerrit W
GW
Rakhorst
Gerhard
G
van Oeveren
Wim
W
Epema
Anne H
AH
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001026:Coronary Artery Bypass; D016207:Cytokines / Q000097:blood; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D006321:Heart / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D007422:Intestines / Q000187:drug effects; D007430:Intraoperative Care; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D010919:Placebos; D011183:Postoperative Complications / Q000453:epidemiology* / Q000517:prevention & control; D014947:Wounds and Injuries / Q000209:etiology / Q000517:prevention & control
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D010919:Placebos; D003907:Dexamethasone