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

• Published in: Acta anaesthesiologica Scandinavica Vol. 42; no. 1; pp. 63 - 70
• Main Authors: Brix-Christensen, V., Tønnesen, E., Sørensen, I. J., Bilfinger, T. V., Sanchez, R. G., Stefano, G. B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-01-1998; Blackwell
• Subjects: acute-phase proteins; Acute-Phase Proteins - analysis; Aged; Analgesia, Epidural; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacology; Anesthesia; Anesthesia depending on type of surgery; Anesthesia, Inhalation; Anesthesia, Intravenous; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; anesthetics; Anesthetics, Intravenous - administration & dosage; Anesthetics, Intravenous - pharmacology; Biological and medical sciences; C-Reactive Protein - analysis; cardiac; Cardiopulmonary Bypass; Coronary Artery Bypass; cytokines; Cytokines - blood; Down-Regulation; Elective Surgical Procedures; Enzyme-Linked Immunosorbent Assay; epidural; fentanyl; Fentanyl - administration & dosage; Fentanyl - pharmacology; Granulocytes - drug effects; Granulocytes - immunology; Humans; Immune response; Immunoelectrophoresis; Inflammation Mediators - blood; Interleukin-1 - blood; Interleukin-10 - blood; Interleukin-6 - blood; Interleukin-8 - blood; intravenous; Male; Medical sciences; Middle Aged; Monocytes - drug effects; Monocytes - immunology; Serum Amyloid P-Component - analysis; surgery; Thoracic and cardiovascular surgery. Cardiopulmonary bypass; Tumor Necrosis Factor-alpha - analysis; Human; Immune response; Intravenous administration; Cytokine; Fentanyl; General anesthesia; Cardiovascular disease; Opiates; Narcotic analgesic; Posology; Cardiopulmonary bypass; Acute phase protein; Surgery
• ISSN: 0001-5172; 1399-6576
• DOI: 10.1111/j.1399-6576.1998.tb05082.x

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 (REI).
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.