International Symposium on the Pathophysiology of Cardiopulmonary Bypass
- Meeting abstract
Aprotinin does not influence the inflammatory reaction to cardiopulmonary bypass in humans
Critical Care volume 3, Article number: P10 (1999)
Cardiopulmonary bypass (CPB) is associated with a significant inflammatory reaction which has been related to complement activation, and release of various inflammatory mediators and proteolytic enzymes . Aprotinin, a low molecular-weight peptide inhibitor of trypsin, kallikrein and plasmin has been proposed to influence whole body inflammatory response inhibiting kallikrein formation, complement activation and neutrophil activation [2,3]. The present study was designed to determine whether aprotinin is able to reduce the inflammatory reaction to CPB in humans.
After institutional approval and written informed consent, 60 male patients, scheduled for primary coronary artery bypass grafting, were enrolled in this prospective double-blinded study. The patients were randomized into three groups: Group high dose aprotinin (HD) received 2 × 106 KIU followed by 0.5 × 106 KIU/h and 2 × 106 KIU added to the pump prime; group low dose (LD) received half that dose and the control group (CTRL) received no aprotinin. No corticosteroids were given. Anesthesia consisted of a high dose sufentanil infusion. The CPB circuit was primed with gelatin and the flow rate was maintained at 2.4 l/min/m2 using a non-pulsatile flow. An anterograde, cold, crystalloid cardioplegic solution was used and mild hypothermia (30°C) was maintained during CPB. We measured tumor necrosis factor (TNF), interleukin 6, 8, 10 (IL6, IL8, IL10), endotoxin, prekallikrein, and prostaglandin D2 (PGD2) at the following time points: 30 min after study drug loading, 10min after beginning of CPB, before end of CPB, 4h after CPB, 1st postoperative day (POD1) and 2nd postoperative day (POD2). Data were analyzed using an analysis of variance for repeated measurements after logarithmic transformation to achieve normalization. There was no significant difference between groups in number of anastomosis, duration of CPB and aortic clamping. All three groups showed a significant inflammatory reaction characterized by an increase of TNF up to 46 pg/ml, IL6 up to 600 pg/ml, IL8 up to 27 pg/ml with no difference between the treatment and the placebo groups. This inflammatory reaction started at the beginning of CPB, was maximal 4 h post-CPB and resolved on POD1 and POD2. Endotoxin levels at end of CPB as well as the maximum increase were slightly lower in the treated than in the CTRL group. However, this difference was essentially due to one CTRL patient with very high endotoxin levels. The proinflammatory reaction was accompanied by a significant increase in the anti-inflammatory cytokine IL10. No group has a significant activation of the complement system. Prekallikrein decreased all groups and PGD2 increased in all groups up to 100 pg/ml. Prekallikrein was significantly lower and PGD2 was significantly higher in the CTRL group only 10 min after beginning of CPB.
Our data show that aprotinin has no significant influence on the inflammatory reaction to CPB in men.
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Schmartz, D., Tabardel, Y., Preiser, J. et al. Aprotinin does not influence the inflammatory reaction to cardiopulmonary bypass in humans. Crit Care 3, P10 (1999). https://doi.org/10.1186/cc321
- Endotoxin Level
- CTRL Group
- High Dose Aprotinin