Surgical trauma affects the proinflammatory status after cardiac surgery to a higher degree than cardiopulmonary bypass.

Prondzinsky R, Knupfer A, Loppnow H, Redling F, Lehmaan DW, Stabenow I, Witthaut R, Unverzagt S, Radke J, Zerkowski HR, Werdan K J Thorac Cardiovasc Surg 129:760-766, 2005.

Reviewer: Mark A. Chaney, MD
Associate Professor
University of Chicago˙

Abstract: Cytokines contribute to the development of the systemic inflammatory response syndrome or multiple-organ failure frequently observed after cardiopulmonary bypass-supported cardiac surgery. In order to quantify the contribution of bypass-induced versus trauma-induced inflammatory response after coronary artery bypass grafting, these investigators examined plasma cytokine levels in 120 patients with coronary artery disease who were treated with or without cardiopulmonary bypass-assisted procedures. Patients underwent either elective percutaneous coronary intervention without cardiopulmonary bypass (n=69), cardiopulmonary bypass-supported percutaneous coronary intervention (n=10), or cardiopulmonary bypass-supported coronary artery bypass grafting (n=41). Cytokine levels were measured by enzyme-linked immunosorbent assay from plasma samples obtained at various time points. Interleukin-6 was measured in blood samples from all three patient populations. The maximum interleukin-6 level was 13.6 ± 22.3 pg/ml in the percutaneous coronary intervention group, 170.4 ± 165.4 pg/ml in the cardiopulmonary bypass-percutaneous coronary intervention group, and 640.3 ± 285.7 pg/ml in the cardiopulmonary bypass-coronary artery bypass grafting group. Interleukin-6 levels were significantly different, and the 95% confidence intervals did not overlap. In the cardiopulmonary bypass-percutaneous coronary intervention group, bypass duration correlated well with interleukin-6 production ( r = 0.915; p < 0.001), whereas these parameters did not correlate in patients who underwent cardiopulmonary bypass-coronary artery bypass grafting (r = 0.307; p = 0.054). These investigators conclude that their findings support the suggestion that both surgical trauma and cardiopulmonary bypass contribute to the inflammatory response after cardiac surgery, although trauma may contribute to a higher degree.

Comments: The systemic inflammatory response associated with cardiac surgery is thought to directly lead to postoperative organ dysfunction. While the inflammatory response is multifaceted (and the best mediator to assess the stress response is controversial), release of cytokines represent an important component. Cytokine plasma levels peak during the immediate postoperative period following cardiac surgery. Patients with severely impaired preoperative left ventricular function and complicated postoperative courses demonstrate higher cytokine levels. However, it remains somewhat controversial whether cardiopulmonary bypass or surgical trauma itself plays the most important role in initiating the systemic inflammatory response. This study was designed to help distinguish the contribution of cardiopulmonary bypass from that of surgical trauma to the increase in inflammatory mediators after cardiac surgery. These investigators found that both cardiopulmonary bypass and surgical trauma contribute to the observed inflammatory response yet surgical trauma appears to be the more potent activator.

Cytokines are important modulators of immune function, infectious processes, and the inflammatory response. Elevated levels of cytokines are found in patients following exposure to cardiopulmonary bypass. The cytokine family is large. These investigators chose to assess interleukin-6 because this cytokine has been proposed by others as a prognostic proinflammatory marker in heart failure and following cardiac surgery assisted with cardiopulmonary bypass. While mildly controversial, most feel that an uninhibited stress response during the perioperative period (mostly immediate postoperative) increases morbidity and mortality. As previously stated, the best way to assess the stress response is unknown.

The recent resurgence of off-pump cardiac surgery is an attempt to avoid physiologic complications associated with cardiopulmonary bypass (neurologic, pulmonary, renal, bleeding, systemic inflammatory response, etc.). From emerging clinical studies, we are finding out that all of these complications do not go away entirely if cardiopulmonary bypass is avoided. These investigators provide evidence that the surgical procedure itself may be a more potent activator of the proinflammatory response than cardiopulmonary bypass. Perhaps cardiopulmonary bypass is not as bad as once thought.

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