Continuous epidural blockade arrests the postoperative decrease in muscle protein fractional synthetic rate in surgical patients

Background: 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. Methods: Twelve otherwise healthy patients scheduled for elective colorectal surgery, who were receiving a constant intake of nitrogen (0.1 g.kg(-1).day(-1)) and calories (20 kcal.kg(-1).day(-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 papaveretom 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 of C-13-labeled leucine (1 mg.kg(-1).h(-1)), and the C-13 enrichment in muscle biopsy specimens before surgery and 48 h after surgery was measured. Results: Plateau C-13 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. Conclusions: 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.