Continuous subcutaneous instillation of bupivacaine compared to saline reduces interleukin 10 and increases substance P in surgical wounds after cesarean delivery

Anesth Analg. 2010 Dec;111(6):1452-9. doi: 10.1213/ANE.0b013e3181f579de. Epub 2010 Sep 22.

Abstract

Background: Recent evidence suggests that locally delivered local anesthetics may exert tissue-damaging effects such as chondrolysis after intraarticular injection. Alteration of the inflammatory response is a potential mechanism for local anesthetic-induced tissue toxicity. In this study, we tested the effects of continuous local anesthetic infiltration on the release of inflammatory and nociceptive mediators in skin wounds after cesarean delivery.

Methods: Thirty-eight healthy women undergoing cesarean delivery with spinal anesthesia were enrolled in this study, and were randomized to receive subcutaneous surgical wound infiltration with bupivacaine 5 mg/mL or saline at 2 mL/h for 24 hours after cesarean delivery. Wound exudate was sampled at 1, 3, 5, 7, and 24 hours after cesarean delivery using a subcutaneous wound drain technique. Cytokines, chemokines, substance P, prostaglandin E(2), and nerve growth factor were assayed using multiplex Bio-Plex® (Bio-Rad, Hercules, CA) and enzyme-linked immunosorbent assays.

Results: Bupivacaine wound infusion resulted in a significant decrease of interleukin 10 and increase of substance P in wounds compared with saline infusion (area under the 24-hour concentration-time curve; P < 0.001). No statistically significant differences were detected for other cytokines, nerve growth factor, and prostaglandin E(2).

Conclusions: This study demonstrates that the continuous administration of clinically used doses of bupivacaine into wounds affects the local composition of wound mediators. Observed changes in interleukin 10 are compatible with a disruption of antiinflammatory mechanisms. Whether such modulation combined with the release of the proinflammatory mediator substance P results in an overall proinflammatory wound response will require future studies of wound healing.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Analgesia, Obstetrical*
  • Anesthetics, Local / administration & dosage*
  • Bupivacaine / administration & dosage*
  • California
  • Cesarean Section*
  • Dinoprostone / metabolism
  • Down-Regulation
  • Elective Surgical Procedures
  • Enzyme-Linked Immunosorbent Assay
  • Exudates and Transudates / drug effects*
  • Exudates and Transudates / immunology
  • Female
  • Humans
  • Inflammation Mediators / metabolism*
  • Infusions, Subcutaneous
  • Interleukin-10 / metabolism*
  • Nerve Growth Factor / metabolism
  • Pain Measurement
  • Pain, Postoperative / immunology
  • Pain, Postoperative / prevention & control
  • Pregnancy
  • Sodium Chloride / administration & dosage
  • Subcutaneous Tissue / drug effects*
  • Subcutaneous Tissue / immunology
  • Subcutaneous Tissue / surgery*
  • Substance P / metabolism*
  • Time Factors
  • Treatment Outcome
  • Up-Regulation

Substances

  • Anesthetics, Local
  • IL10 protein, human
  • Inflammation Mediators
  • NGF protein, human
  • Interleukin-10
  • Substance P
  • Sodium Chloride
  • Nerve Growth Factor
  • Dinoprostone
  • Bupivacaine