title: Postoperative subcutaneous instillation of low-dose ketorolac but not hydromorphone reduces wound exudate concentrations of interleukin-6 and interleukin-10 and improves analgesia following cesarean delivery.
abstract: The objectives of this study were to test the effects of low-dose ketorolac and hydromorphone added to continuous local anesthetic wound instillation on surgical-site inflammatory mediators, postoperative pain, and opioid consumption. Sixty healthy women undergoing cesarean delivery were enrolled in this randomized, double-blinded study. Patients were randomized to receive a subcutaneous wound instillation of bupivacaine .5% at 10 mg/hour (active control), bupivacaine .5% with ketorolac .6 mg/hour, or bupivacaine .5% with hydromorphone .04 mg/hour for 48 hours postcesarean. Wound exudate was sampled at 4, 24, and 48 hours postcesarean and assayed for interleukins IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-12, tumor necrosis factor (TNF-α), interferon (INF-γ), and granulocyte-macrophage colony stimulating factor (GM-CSF). The addition of ketorolac to bupivacaine significantly decreased IL-6 (P = .012) and IL-10 (P = .005) compared to plain bupivacaine. Ketorolac, but not hydromorphone, was associated with a decrease in pain (P = .018) and analgesic use (P = .020) following cesarean delivery. Our results are compatible with the view that significant analgesics effects are mediated through local modulation of inflammatory events. Low-dose ketorolac administered into surgical wounds exert significant anti-inflammatory and analgesic effects and may be a valuable analgesic alternative to systemic nonsteroidal anti-inflammatories (NSAIDs) but with potentially fewer side effects.
  
  
  CONCLUSIONS
  This article demonstrates that low-dose ketorolac administered into wounds modulates local inflammatory events, decreases postoperative pain, and reduces opioid consumption. These results suggest that administration of NSAIDs into surgical wounds may be an analgesic alternative to higher systemic dosing of NSAIDs.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305, USA. bcarvalho@stanford.edu
authors.forename: Brendan
authors.initials: B
authors.lastname: Carvalho
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Lemmens
authors.forename: Vicki
authors.initials: V
authors.lastname: Ting
authors.forename: Martin S
authors.initials: MS
authors.lastname: Angst
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000627:therapeutic use*; D000779:Anesthetics, Local / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use*; D002045:Bupivacaine / Q000627:therapeutic use; D002585:Cesarean Section; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D005122:Exudates and Transudates / Q000378:metabolism*; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage* / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D020910:Ketorolac / Q000008:administration & dosage* / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000517:prevention & control*; D011182:Postoperative Care; D011247:Pregnancy
chemical_list: D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D015850:Interleukin-6; D016753:Interleukin-10; D004091:Hydromorphone; D002045:Bupivacaine; D020910:Ketorolac