Continuous subcutaneous instillation of bupivacaine compared to saline reduces interleukin 10 and increases substance P in surgical wounds after cesarean delivery.
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.
Carvalho
Brendan
B
Department of Anesthesia, H3580, Stanford University School of Medicine, Stanford, CA 94305, USA. bcarvalho@stanford.edu
Clark
David J
DJ
Yeomans
David C
DC
Angst
Martin S
MS
D000328:Adult; D016362:Analgesia, Obstetrical; D000779:Anesthetics, Local / Q000008:administration & dosage*; D002045:Bupivacaine / Q000008:administration & dosage*; D002140:California; D002585:Cesarean Section; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation; D017558:Elective Surgical Procedures; D004797:Enzyme-Linked Immunosorbent Assay; D005122:Exudates and Transudates / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D055104:Infusions, Subcutaneous; D016753:Interleukin-10 / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism; D010147:Pain Measurement; D010149:Postoperative Pain / Q000276:immunology / Q000517:prevention & control; D011247:Pregnancy; D012965:Sodium Chloride / Q000008:administration & dosage; D040521:Subcutaneous Tissue / Q000187:drug effects* / Q000276:immunology / Q000601:surgery*; D013373:Substance P / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
D000779:Anesthetics, Local; C508609:IL10 protein, human; D018836:Inflammation Mediators; C502240:NGF protein, human; D016753:Interleukin-10; D013373:Substance P; D012965:Sodium Chloride; D020932:Nerve Growth Factor; D015232:Dinoprostone; D002045:Bupivacaine