Wound Infusion of 0.35% Levobupivacaine Reduces Mechanical Secondary Hyperalgesia and Opioid Consumption After Cesarean Delivery: A Prospective, Randomized, Triple-Blind, Placebo-Controlled Trial
Authors: Gómez-Ríos Manuel Á. , Codesido-Barreiro Pastora , Seco-Vilariño Carmen , Calvín-Lamas Marta , Curt-Nuño Federico , Nieto-Serradilla Laura , Rabuñal-Álvarez María T. , Fernández-Rodríguez Fernando , Peteiro-Cartelle Javier , Pensado-Boo Ramón , Bou Germán , Pensado-Castiñeiras Alberto , Casans-Francés Rubén 
Published: January 2022

BACKGROUND:
Some patients still report moderate-to-severe postoperative pain after cesarean delivery. Local anesthetic wound infusion improves acute pain and might act on peripheral and central sensitization mechanisms; however, no studies have proved this hypothesis. We evaluated the potential benefits of continuous wound infusion of levobupivacaine after cesarean delivery on secondary hyperalgesia (primary end point) and primary hyperalgesia, pain relief, persistent pain, and inflammatory and metabolic stress response.

METHODS:
Healthy women scheduled for elective cesarean delivery participated in this prospective, randomized, triple-blind, placebo-controlled trial (NCT01458431). All patients received spinal anesthesia with 0.5% hyperbaric bupivacaine with fentanyl and a multiholed wound catheter placed under the fascia. Women were randomized to receive continuous wound infusion (0.35% levobupivacaine 7 mL/h for 48 hours; group L) or an equal volume of saline (group S). Secondary hyperalgesia to punctate mechanical stimuli was evaluated using dynamic tests, and primary hyperalgesia was evaluated using an electronic von Frey anesthesiometer; both were assessed at 24, 48, and 72 hours. The following variables were collected: intensity of postoperative parietal and visceral pain at rest and on movement rated on a visual analog scale >72 hours, time to first bolus of patient-controlled analgesia (PCA), cumulative dose of rescue morphine (PCA) and acetaminophen, ability to sleep and sleep quality, and patient satisfaction. Persistent postoperative pain was evaluated during a telephone interview at 1, 3, 6, and 12 months after surgery. C-reactive protein, acid glycoprotein, preprandial glucose, insulin, cortisol, prolactin, growth hormone, and interleukin-6 were measured before cesarean delivery and at 8, 24, and 48 hours. Adverse events and patient outcomes were recorded.

RESULTS:
Seventy women were included. In group L, the area of secondary hyperalgesia was significantly reduced (43.4 [18.5–80] vs 68.4 [39.0–136] cm2 and 45.1 [0.9–89.8] vs 67.3 [31.3–175] cm2 at 24 and 48 hours, respectively; group:time interaction P value < .001), the mechanical pain threshold was significantly higher at 24 hours (633 [441–802] vs 417 [300–572] g.mm−2; P = .001), and morphine consumption was significantly lower at 24 hours (4 [2–11] vs 11[6–23]; P = .003) compared with group S. Levobupivacaine had no effect on persistent postoperative pain at 1, 3, 6, and 12 months. Plasma insulin levels in the immediate postoperative period and at 8, 24, and 48 hours were significantly lower in group L (P < .001). There were no significant differences in other biochemical parameters of inflammatory and endocrine-metabolic response.

CONCLUSIONS:
Levobupivacaine wound infusion provides adequate analgesia and might be an effective antihyperalgesic adjunct.