title: Effects of anaesthesia based on high versus low doses of opioids on the cytokine and acute-phase protein responses in patients undergoing cardiac surgery.
abstract: BACKGROUND
  Cardiac surgery with cardiopulmonary bypass (CPB) evokes a systemic inflammatory response involving the proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha), 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anaesthesia and Intensive Care, Aarhus University Hospital, Kommunehospitalet, Aarhus C, Denmark.
authors.forename: V
authors.initials: V
authors.lastname: Brix-Christensen
authors.forename: E
authors.initials: E
authors.lastname: Tønnesen
authors.forename: I J
authors.initials: IJ
authors.lastname: Sørensen
authors.forename: T V
authors.initials: TV
authors.lastname: Bilfinger
authors.forename: R G
authors.initials: RG
authors.lastname: Sanchez
authors.forename: G B
authors.initials: GB
authors.lastname: Stefano
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis*; D000368:Aged; D015360:Analgesia, Epidural; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000494:pharmacology; D000769:Anesthesia, Inhalation; D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000494:pharmacology; D002097:C-Reactive Protein / Q000032:analysis; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D016207:Cytokines / Q000097:blood*; D015536:Down-Regulation; D017558:Elective Surgical Procedures; D004797:Enzyme-Linked Immunosorbent Assay; D005283:Fentanyl / Q000008:administration & dosage* / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007122:Immunoelectrophoresis; D018836:Inflammation Mediators / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D000683:Serum Amyloid P-Component / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000209:Acute-Phase Proteins; D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D000683:Serum Amyloid P-Component; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002097:C-Reactive Protein; D005283:Fentanyl