TITLE: INTERLEUKIN BALANCE FOLLOWING MAJOR SURGERY IN GERIATRIC PATIENTS

AUTHORS: Eileen Shyong, BA¹, Michael Zaugg, MD², Thomas M. Tagliente, MD, PhD¹, Jeffrey H. Silverstein, MD¹
AFFILIATION: ¹Mount Sinai School of Medicine, New York, NY; ²Universitat Zurich, Zurich, Switzerland.

Sickness behavior refers to the nonspecific symptoms that accompany the response to infection. Increasing evidence suggests that these symptoms are part of an organized defense response mediated by the neural effects of cytokines such as interleukin 1.¹ In a recent experiment, we demonstrated a decrease in postoperative pain and morphine utilization associated with the use of two anesthetic regimens including atenolol. An evaluation of SF-36 (health related quality of Life) assessments showed a 46% decline in the psychologic composite score for patients in the control group as compared to 25 and 26% declines in the beta-blocker group. We hypothesized that alteration in interleukin balance would explain the difference in postoperative well being.
METHODS: From Jan to Jan 98, 63 patients were randomized to receive either: fentanyl, isoflurane in N2O/O2 (FINO), pre and postoperative atenolol plus FINO, or limited fentanyl (,2 ug/kg/ hr) and isoflurane (0.4%). Blood samples were acquired at baseline, induction, incision, 1 hour, PACU, 24 hrs and 72 hrs. Samples were analyzed for the proinflammatory cytokines (IL-6 and IL-1b) and the antiinflammatory cytokines (IL-10 and IL- 1ra) All assays were based on commercially available elisa kits (IL-6 and IL-1b Human Enzyme Immunoassay Kit by Cayman Chemical, Ann Arbor MI, and IL-1ra and IL-10 Human Enzyme Immunoassay Kit provided by R&D Systems, Minneapolis, Mn).
RESULTS: Evaluation of the IL-6 data demonstrated the greatest increase from baseline at PACU (median:34.5pg/ml max:457.9pg/ml min:245 pg/ml) and 24 hour (median:35.7pg/ml max:457.9pg/ml min:-260pg/ml), consistent with previous literature. Data for IL-1b showed minimal change across the time course. Both IL-1ra and IL-10 had the most change from baseline at PACU (median: 2333pg/ml, 32.1pg/ml max:7170 pg/ml, 68pg/ ml min:-1127.7pg/ml, -51.6pg/ml respectively). There was no significant difference between patients of the 3 groups as measured by the Wilcoxon Signed Rank, Friedman, and Wilcoxon 2-.
DISCUSSION: Neither pro-inflammatory nor the anti- inflammatory cytokines appear to be related to the alteration of the sense of well-being experienced by the patients who received beta blockade. No consensus exists as to alteration in interleukin response in aging. Our data are similar to previous reports using younger patient population.² Studies of cultured leukocytes may provide more detailed information on inflammatory responsiveness in surgical patients.³ Further research is necessary to determine the mechanism underlying altered well being following perioperative beta blockade.
REFERENCES:

1. Trends.Pharmacol.Sci. 1992; 13: 24-8.

2. Anesthesiology 1992; 77: 426-31.

3. J Int Fed Clin Chem 1993; 5: 216-9.