Circulating inflammatory mediators and organ dysfunction after cardiovascular surgery with cardiopulmonary bypass: a prospective observational study

Abstract

Introduction: Cardiovascular surgery with cardiopulmonary bypass (CPB) has improved in past decades, but inflammatory activation in this setting is still unpredictable and is associated with several postoperative complications. Perioperative levels of macrophage migration inhibitory factor (MIF) and other inflammatory mediators could be implicated in adverse outcomes in cardiac surgery.

Methods: Serum levels of MIF, monocyte chemoattractant protein (MCP)-1, soluble CD40 ligand, IL-6 and IL-10 from 93 patients subjected to CPB were measured by enzyme-linked immunosorbent assay and compared with specific and global postoperative organ dysfunctions through multiple organ dysfunction score (MODS) and sequential organ failure assessment (SOFA).

Results: Most of the cytokines measured had a peak of production between 3 and 6 hours after CPB, but maximum levels of MIF occurred earlier, at the cessation of CPB. Among specific organ dysfunctions, the most frequent was hematological, occurring in 82% of the patients. Circulatory impairment was observed in 73.1% of the patients, and 51% of these needed inotropics or vasopressors within the first 24 hours after surgery. The third most frequent dysfunction was pulmonary, occurring in 48.4% of the patients. Preoperative levels of MIF showed a relevant direct correlation with the intensity of global organ dysfunction measured by SOFA (rho = 0.46, p < 0.001) and MODS (rho = 0.50, p < 0.001) on the third day after surgery. MCP-1 production was associated with postoperative thrombocytopenia, and MIF was related to the use of a high dose of vasopressors in patients with cardiovascular impairment and also to lower values of the ratio of partial arterial oxygen tension (PaO2) to fraction of inspired oxygen (FiO2) registered in the first 24 hours after CPB.

Conclusion: Despite the multifactorial nature of specific or multiple organ dysfunctions, MIF should be explored as a predicting factor of organ dysfunction, or even as a potential therapeutic target in decreasing postoperative complications.

Figure 1

Kinetics of inflammatory mediators at anesthesia induction and after cardiopulmonary bypass. (a) Macrophage migration inhibitory factor; (b) IL-6, (c) monocyte chemoattractant protein-1; (d) soluble CD40 ligand. AI, anesthesia induction; CPB, cardiopulmonary bypass.

Figure 2

Correlation of preoperative levels of macrophage migration inhibitory factor (MIF) with postoperative organ failure scores. (a) Sequential Organ Failure Assessment (SOFA) at day 3 after surgery. (b) Multiple Organ Dysfunction Score (MODS) at day 3 after surgery. Data are shown graphically as a linear regression with 95% confidence intervals.