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Epidural anesthesia with local anesthetics is associated with postoperative attenuation of nitrogen loss. The protein-sparing effect could be the result of either a decreased protein breakdown or increased protein synthesis. Although the role of epidural local anesthetics in effectively limiting the increase in postoperative protein breakdown is established at the whole-body level, it is necessary to determine whether the muscle protein fractional synthetic rate is directly modulated when nociceptive stimuli are blocked.Twelve otherwise healthy patients scheduled for elective colorectal surgery, who were receiving a constant intake of nitrogen (0.1 g [center dot] kg sup -1 [center dot] day sup -1) and calories (20 kcal [center dot] kg sup -1 [center dot] day sup -1) before and after surgery, were randomly assigned to receive either general anesthesia (with thiopentone, vecuronium, fentanyl, or enflurane; control group, n = 6) or epidural anesthesia (T3-S5 sensory block with 0.75% bupivacaine) and general anesthesia (epidural group, n = 6). In the control group, postoperative analgesia was achieved with papaveretum given subcutaneously, whereas a continuous epidural bupivacaine infusion (T8-L5 sensory block) was maintained for 48 h in the epidural group. The postabsorptive muscle protein fractional synthetic rate was determined using a 6-h continuous infusion of13 C-labeled leucine (1 mg [center dot] kg sup -1 [center dot] h sup -1), and the13 C enrichment in muscle biopsy specimens before surgery and 48 h after surgery was measured.Plateau13 C enrichment of plasma alpha-ketoisocaproate (taken to represent the intracellular leucine precursor pool enrichment for protein synthesis) was achieved during the 6-h infusion (mean coefficient of variation was 2.8%). Muscle protein synthesis at 48 h after operation compared with preoperative levels decreased significantly in the control group (P = 0.03). In contrast, it increased by 25% in the epidural group. Although this was not significantly (P = 0.15) different from preoperative levels, it was significantly greater than in the control patients.Epidural infusion of local anesthetics begun before surgery and continued during the first 48 h after operation significantly attenuates the decrease in the postabsorptive muscle protein synthesis rate associated with surgical injury. Effective block of nociceptive stimuli thus preserves tissue protein synthesis.