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Postoperative Subcutaneous Instillation of Ketorolac but not Hydromorphone Reduces Pain, Analgesic Use and Wound Exudate Concentrations of Interleukin-6 and Interleukin-10 Following Cesarean Delivery
Abstract Number: BP-4
Abstract Type: Original Research
Background: Low doses of drugs delivered locally into surgical wounds may provide effective anti-inflammatory effects, while evoking minimal systemic side effects.(1,2) The primary objective of this study was to test the effects of ketorolac and hydromorphone added to continuous local anesthetic wound instillation on the release of key inflammatory mediators following cesarean delivery.
Methods: Sixty healthy women undergoing cesarean delivery with spinal anesthesia were enrolled in this randomized, double-blinded study. Patients were randomized to receive a subcutaneous surgical wound instillation of either plain bupivacaine 0.5% at 10 mg/h (Active control; Group B) or bupivacaine 0.5% with hydromorphone 0.04 mg/h (Group H) or bupivacaine 0.5% with ketorolac 0.6 mg/h (Group K) for 48 hours post-cesarean delivery. Wound exudate was sampled at 4, 24, and 48 h post-cesarean delivery using a subcutaneously implanted catheter and assayed for interleukin (IL) 1β, IL-2, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (INFγ), and granulocyte-macrophage colony stimulating factor (GM-CSF).
Results: Analytes were detectable at variable rates (47-100%) and all changed significantly over the 48-hour study period. The addition of ketorolac to bupivacaine significantly decreased IL-6 (P=0.0121) and IL-10 (P=0.0046) compared to plain bupivacaine. Postoperative subcutaneous instillation of ketorolac but not hydromorphone was associated with a decrease in pain (P=0.018) and analgesic use (P=0.02) following cesarean delivery (Figure). The anti-inflammatory and nociceptive effects of peripherally administered hydromorphone were less apparent.
Conclusions: In addition to a reducing post-cesarean delivery pain and analgesic use, a low daily dose of peripherally administered ketorolac exerted significant anti-inflammatory effects in postoperative cesarean wounds. These results suggest a significant benefit to adding a low dose of ketorolac into surgical wounds. These anti-inflammatory and nociceptive benefits demonstrated at very low daily doses offer potential side effect advantages over higher systemic doses used routinely post-cesarean delivery.