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Indices of Inflammatory and Oxidative Stress Following Antifibrinolytic Therapy in Cardiac Surgical Patients
Basel Ramlawi, Hasan Otu, Shigetoshi Mieno, Neel R Sodha, Munir Boodhwani, Shu-Hua Xu, Frank W Sellke
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
Objective: Recently, there has been controversy regarding the use of Aprotinin and adverse clinical outcomes following cardiac surgery. We studied the role of Aprotinin and ε-aminocaproic acid, on clinical outcomes and the attenuation of post-CPB inflammatory response at the protein and gene expression levels.
Design: Prospective cohort study.
Setting: Tertiary-care academic hospital
Patients: Thirty nine patients undergoing coronary revascularization (CABG) and/or valve procedures using cardiopulmonary bypass (CPB)
Interventions: Half-Hammersmith dose Aprotinin (1 x 106 KIU preoperatively) or ε-aminocaproic acid (100 mg/kg load, 5g pump prime and 30 mg/kg/h infusion) were administered to patients.
Main Outcome Measures: C-reactive protein(CRP), C3a, interleukin-1β (IL-1β), IL-6, IL-10 and total peroxide were all quantified from serum using high sensitivity immunoassay technique preoperatively and postoperatively at 6 hours (6h) and 4 days (POD4). Gene expression (mRNA) analysis of whole blood was also carried out using Affymetrix microarray Genechip U133+2.0 (>50,000 genes) to compare the two groups. Cytokine values were calculated and analyzed in a blinded fashion using parametric statistics.
Results: Preoperative baseline characteristics were similar in both characteristics with respect to age, sex, re-operative status and type of operation. We did not observe any significant difference in inflammatory mediators between the two groups for either the 6h or POD4 time points as in table below. There was no difference in the gene expression pathways between the groups. None of the patients developed postoperative stroke, myocardial infarction or systemic infections.
Conclusions: Aprotinin and ε-aminocaproic acid have an equal impact on the inflammatory and oxidative responses following CPB. | Mediator | Time point | Aprotinin
N=15 (38%) | ε-aminocaproic acid
N=24 (62%) | p Value | CRP
(mg/l) | 6h | 30.63±12.1 | 22.09±4.4 | 0.26 | | POD4 | 153.05±10.0 | 145.739.2 | 0.30 | C3a
(µg/ml) | 6h | 207.26±20.9 | 210.75±18.3 | 0.45 | | POD4 | 190.68±22.9 | 199.59±18.3 | 0.38 | IL-1β
(pg/ml) | 6h | 1.55±0.3 | 1.81±0.3 | 0.25 | | POD4 | 5.30±3.2 | 2.49±0.6 | 0.20 | IL-6
(pg/ml) | 6h | 17.35±0.3 | 16.08±0.8 | 0.07 | | POD4 | 9.74±1.8 | 10.30±1.3 | 0.40 | IL-10
(pg/ml) | 6h | 18.59±4.6 | 21.22±3.2 | 0.32 | | POD4 | 4.37±1.2 | 6.89±2.0 | 0.14 | Total Peroxide
(µmol/l) | 6h | 487.04±52.4 | 594.06±61.1 | 0.10 | | POD4 | 472.70±101.4 | 466.42±63.8 | 0.48 |
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