Terence J. McMurray

The choice of anesthetic maintenance technique influences the antiinflammatory cytokine response to abdominal surgery.

Outcome in some diseases is determined by the relationship between pro-and antiinflammatory cytokines. Surgery may also provoke a cytokine response, which has both pro- and antiinflammatory components. The aim of this study was to ascertain whether anesthetic technique can modify the balance of cytokines associated with abdominal surgery. Twenty patients scheduled to undergo elective abdominal hysterectomy were randomly allocated to receive maintenance of anesthesia with isoflurane (IH group) or propofol (IV group). Venous blood samples for measurement of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL-1ra) were taken before the induction of anesthesia and at set intervals until 24 h postoperatively. TNF-alpha levels remained low throughout the study; however, all patients showed a significant postoperative increase in IL-6, IL-10, and IL-1ra (P < 0.05). Levels of the proinflammatory cytokine IL-6 were similar in both groups, whereas the antiinflammatory cytokine IL-10 was higher in the IV group at 4 h postoperatively (P < 0.02). The difference between groups in terms of IL-1ra production just failed to reach significance (P < 0.06). We conclude that the cytokine response to abdominal surgery has both pro- and antiinflammatory components and that the choice of anesthetic may modify the balance of these cytokines. Implications: This study demonstrates that in addition to the widely reported proinflammatory cytokine response, elective abdominal surgery provokes an antiinflammatory response, which may be enhanced by total intravenous anesthesia. The ability of anesthetics to modify the cytokine response to surgery may have therapeutic potential. (Anesth Analg 1997;85:1394-8)

Plasma and Urinary Cytokine Homeostasis and Renal Dysfunction during Cardiac Surgery

BackgroundCardiac surgery induces changes in plasma cytokines. Proinflammatory cytokines have been associated with a number of renal diseases. The proinflammatory cytokines interleukin 8 (IL-8), tumor necrosis factor &agr; (TNF&agr;), and interleukin 1&bgr; (IL-1&bgr;) are smaller than the antiinflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra), and TNF soluble receptor 2 (TNFsr2), and thus undergo glomerular filtration more readily. Accordingly, this study investigated the relation between plasma and urinary cytokines and proximal renal dysfunction during cardiac surgery. MethodsTwenty patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) were studied. Blood and urine samples were analyzed for proinflammatory and antiinflammatory cytokines. Proximal tubular dysfunction was measured using urinary N-acetyl-&bgr;-d-glucosaminidase (NAG)/creatinine and &agr;1-microglobulin/creatinine ratios. ResultsPlasma IL-8, IL-10, IL-1ra, and TNFsr2 values were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated. Urinary NAG/creatinine and &agr;1-microglobulin/creatinine ratios were also elevated. Plasma TNF&agr; at 2 h correlated with urinary NAG/creatinine ratio at 2 and 6 h (P < 0.05) and with urinary IL-1ra at 2 h (P < 0.05). Plasma IL-8 at 2 h correlated with NAG/creatinine at 6 h (P < 0.05). Urinary IL-1ra correlated with urinary NAG/creatinine ratio after cross-clamp release and 2 and 6 h after CPB (P < 0.05). ConclusionsCardiac surgery using CPB leads to changes in plasma and urinary cytokine homeostasis that correlate with renal proximal tubular dysfunction. This dysfunction may be related to the renal filtration of proinflammatory mediators. Renal autoprotective mechanisms may involve the intrarenal generation of antiinflammatory cytokines.

Propofol-Fentanyl Anesthesia: A Comparison With Isoflurane-Fentanyl Anesthesia in Coronary Artery Bypass Grafting and Valve Replacement Surgery

The hemodynamic effects of propofol-fentanyl and isoflurane-fentanyl anesthesia during the prebypass period were compared in 42 patients undergoing coronary artery bypass grafting (CABG) and 22 patients undergoing valve replacement (VR) for stenotic lesions. Anesthesia was induced with fentanyl, 25 micrograms/kg, and pancuronium, 0.1 mg/kg, and was maintained with a propofol infusion commenced at 4 mg/kg/h (range 1 to 10 mg/kg/h) or with isoflurane commenced at 1% (range 0 to 2%). Additional fentanyl, 7.5 micrograms/kg, was given before sternotomy. Hemodynamic measurements were made before induction of anesthesia and at various times in the prebypass period. In the VR group, there were no significant differences between the two anesthetics in any hemodynamic variables during the study. Significant decreases (P < 0.05) in mean arterial pressure (MAP 14%), left ventricular stroke work index (LVSWI 29%), and stroke volume index (SVI 24%) occurred after 15 minutes of propofol anesthesia in the CABG group. With isoflurane MAP was well maintained with reductions in LVSWI and SVI of 22% and 20%, respectively. Isoflurane was, however, associated with a significant increase in heart rate (HR) in the CABG group (P < 0.05), whereas no significant change in HR occurred in CABG or VR patients receiving propofol. With both techniques there were no significant changes in right-sided or left-sided filling pressures or in systemic vascular resistance index in the CABG or VR groups, except for a decrease in pulmonary artery occlusion pressure in the propofol VR group and isoflurane CABG group at the time of aortic cannulation. Propofol produced similar hemodynamic changes in the CABG and VR groups. Both anesthetic techniques caused myocardial depression and effectively controlled the autonomic responses to sternotomy in both groups. The study suggests that propofol-fentanyl anesthesia is an acceptable technique for CABG surgery and for VR in patients with stenotic valvular heart disease.

The effect of methylprednisolone on cytokine concentration and leukocyte adhesion molecule expression in an isolated cardiopulmonary bypass system

This study examines the effect of methylprednisolone on cytokine balance and adhesion molecule expression within an isolated cardiopulmonary bypass (CPB) system. This isolated CPB system is an in vitro model which simulates the pro-inflammatory immune response. Whole blood from 10 volunteers was obtained in two equal amounts. Heparin and saline were added to the control group while heparin and methylprednisolone were added to the methylprednisolone group. The blood was added to two identical CPB circuits and bypass commenced by a trained perfusionist. Samples were taken at blood donation (Sample 0), 10 min after the addition of drugs (Sample 1) and after 30, 60 and 90 min of CPB (Samples 2, 3 and 4, respectively). Cytokines interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1ra) and tumour necrosis factor soluble receptor 2 (TNFsr2) and the leucocyte adhesion molecules L-selectin, HLA DR, CD18 and CD11b were determined. IL-8 increased in both groups. This increase was significantly less in the methylprednisolone group. Increases in granulocyte CD11b and CD18 expression were less in the methylprednisolone group than in the control group but did not reach statistical significance. These results indicate that methylprednisolone significantly reduces the production of IL-8 in an isolated CPB system. This effect occurs in the absence of IL-10.

A clinical ,renal and immunological assessment of Surface-Modifying Additive treated (SMART) cardiopulmonary bypass circuits

Biocompatible cardiopulmonary bypass (CPB) circuits aim to reduce contact activation and its physiological consequences. We investigated the hypothesis that use of Surface Modifying Additive (SMA)-treated circuits (Sorin Group Ltd) compared with non-SMA circuits would be associated with preservation of blood pressure during CPB and modulation of perioperative subclinical renal function (urinary α-1-microglobulin (α-1-m)) and plasma and urinary cytokine changes. In a study of low-risk CABG patients (n=40), randomized to SMA (n=20) versus non-SMA circuits (n=20), we found better preserved blood pressure at CPB initiation in SMA patients (p <0.05), particularly in ACE-inhibited SMA patients (n=11) versus ACE-inhibited non-SMA patients (n=10) (p <0.05). Plasma anti-inflammatory IL-10, as well as urinary α-1-m, were elevated 48 hours postoperatively (p <0.05). SMA patients also had lower blood loss (p <0.05). SMA circuits have some clinical benefit, especially in ACE-inhibited patients.