Effects of anaesthesia based on high versus low doses of opioids on the cytokine and acute-phase protein responses in patients undergoing cardiac surgery

Background: Cardiac surgery with cardiopulmonary bypass (CPB) evokes a systemic inflammatory response involving the proinflammatory cytokines tumor necrosis factor-α (TNFα), interleukin (IL)-1, IL-6, IL-8 and anti- inflammatory cytokines such as IL-10. Like IL-10, opioids downregulate the immune responses in vivo and in vitro, including the activity of the cytokine-producing monocytes and granulocytes. The proinflammatory cytokines are potent inducers of the hepatic acute-phase protein synthesis. The aim of the present study was to investigate if choice of anaesthesia, based on high- dose opioids (fentanyl) versus low-dose opioids influenced the release of IL- 6, IL-8, and IL-10. Secondly, it was investigated whether serum amyloid P- component (SAP) is an acute-phase protein in man such as C-reactive protein (CRP), with which it is physically and structurally related. Methods: Sixteen patients submitted to elective coronary artery bypass grafting (CABG) surgery were randomized to either low-dose opioid anaesthesia consisting of thoracic epidural analgesia combined with inhalational anaesthesia (group I) or high- dose fentanyl anaesthesia (group II). From each patient 18 blood samples were taken perioperatively. Cytokine analyses were performed with ELISA, CRP and SAP mere measured with rocket immunoelectrophoresis (RIE). Results: Surgery and CPB elicited a marked, transient and almost simultaneous proinflammatory and anti-inflammatory cytokine response with no differences between the groups. The cytokine levels returned to preoperative levels 1-3 d after operation. Anaesthesia and surgery did not affect SAP plasma levels while patients showed a major increase in CRP concentrations preceding the cytokine responses. Conclusion: CABG performed during two different anaesthetic techniques, high-dose fentanyl versus low-dose opioid anaesthesia, elicited a well-defined cytokine response with minor variation in the time course of each cytokine. The cytokine production was not modified by type of anaesthesia. Finally, SAP is not an acute-phase protein in men.