The effects of epidural anesthesia on the neuroendocrine response to major surgical stress: a randomized prospective trial

Abstract

It has long been held that the acute-phase and neuroendocrine response to stress requires afferent neural input for its propagation. To further clarify the role of afferent neural impulses in this process and to determine the ability of epidural anesthesia to attenuate the normal perioperative stress response, 39 patients undergoing uncomplicated abdominal aortic replacement were randomized to receive either general anesthesia with postoperative patient-controlled intravenous morphine (n = 19) or combined regional/general anesthesia with intraoperative epidural catheter anesthesia using Bupivacaine to the T4 dermatome level followed by postoperative epidural morphine (n = 20). The stress response was quantitated by blinded measurement of baseline and postoperative (0, 12, 24, 48, and 72 hours) serum cortisol, epinephrine norepinephrine, total catecholamines, interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP). Total operative time (4.2 +/- 0.3 vs 4.3 +/- 0.4 hours), 72-hour fluid requirement (7.0 +/- 0.6 vs 6.8 +/- 0.71 mL), and length of hospitalization (7.8 +/- 1.4 vs 8.1 +/- 1.2 days) were not different between groups. All patients showed a significant increase in cortisol, epinephrine, norepinephrine, total catecholamines, CRP, and IL-6 in the postoperative period (P < 0.05). IL-1beta and TNF-alpha were less predictable and undetectable in most patients. There was no difference in any of the stress response indices between those patients receiving patient-controlled or epidural catheter anesthesia. In fact, the only parameter that was predictive of increased activation of the stress response was the length of operation, irrespective of anesthetic method. Those patients with operative times greater than 5 hours (n = 10) developed significantly higher CRP, IL-1beta, IL-6, and TNF-alpha levels (P < 0.05) at 12 and 24 hours postoperatively than those with total operative times less than 4 hours (n = 16). The neuroendocrine response to major surgical stress is propagated normally despite epidural blockade and is intensified with prolonged operative times. The inflammatory cytokines appear to play a major role in this process.