N Solheim1,2, I Gregersen2,3, B Halvorsen2,3, V Bjerkeli2,3, A Stubhaug2,4, T Gordh5, L A Rosseland2,6. 1. Lovisenberg Diakonal Hospital, Oslo, Norway. 2. Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 3. Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway. 4. Division of Emergencies and Critical Care, Department of Pain Medicine and Research, Oslo University Hospital, Oslo, Norway. 5. Department of Surgical Sciences, Pain Medicine, Uppsala University, Uppsala, Sweden. 6. Division of Emergencies and Critical Care, Department of Research and Development, Oslo University Hospital, Oslo, Norway.
Abstract
BACKGROUND:Ketorolac is an effective non-steroidal anti-inflammatory drug, commonly used with local anaesthetics as part of local infiltration analgesia protocols following orthopaedic surgery. However, systemic uptake and drug action may be the major mechanism after local infiltration. The aims of this project were to study the effects of a small, systemically ineffective dose of ketorolac given intra-articularly for post-operative pain and also to study synovial inflammatory biomarkers. We investigated whether ketorolac affects pro-inflammatory biomarkers in an in vitro model, as well. METHODS: In this placebo-controlled, blind, randomized study, we analysed intra-articular ketorolac (5 mg) in ambulatory minor knee surgery patients with moderate or severe pain (n = 44). We assessed post-operative pain intensity (n = 44) and analysed microdialysis samples taken from knee synovial tissue every 20 min (n = 34). We also tested cyclooxygenase-independent effects of ketorolac in synovial cells stimulated by prostaglandin E2 and chondroitin sulphate in vitro. RESULTS:Intra-articular ketorolac (5 mg) administration did not reduce pain or synovial pro-inflammatory cytokines CXCL1, IL-8, and MCP-1, 0-120 min after knee arthroscopy. Female gender was a risk factor for moderate or severe pain (relative risk 1.45, 95% confidence interval 1.04-2.01). Paradoxically, ketorolac increased the release of CXCL1 and IL-8 in prostaglandin E2 and chondroitin sulphate-stimulated synovial cells in vitro. CONCLUSION:Ketorolac prescribed at a low dose intra-articularly does not produce any detectable analgesic effect after minor knee surgery.
RCT Entities:
BACKGROUND:Ketorolac is an effective non-steroidal anti-inflammatory drug, commonly used with local anaesthetics as part of local infiltration analgesia protocols following orthopaedic surgery. However, systemic uptake and drug action may be the major mechanism after local infiltration. The aims of this project were to study the effects of a small, systemically ineffective dose of ketorolac given intra-articularly for post-operative pain and also to study synovial inflammatory biomarkers. We investigated whether ketorolac affects pro-inflammatory biomarkers in an in vitro model, as well. METHODS: In this placebo-controlled, blind, randomized study, we analysed intra-articularketorolac (5 mg) in ambulatory minor knee surgery patients with moderate or severe pain (n = 44). We assessed post-operative pain intensity (n = 44) and analysed microdialysis samples taken from knee synovial tissue every 20 min (n = 34). We also tested cyclooxygenase-independent effects of ketorolac in synovial cells stimulated by prostaglandin E2 and chondroitin sulphate in vitro. RESULTS:Intra-articularketorolac (5 mg) administration did not reduce pain or synovial pro-inflammatory cytokines CXCL1, IL-8, and MCP-1, 0-120 min after knee arthroscopy. Female gender was a risk factor for moderate or severe pain (relative risk 1.45, 95% confidence interval 1.04-2.01). Paradoxically, ketorolac increased the release of CXCL1 and IL-8 in prostaglandin E2 and chondroitin sulphate-stimulated synovial cells in vitro. CONCLUSION:Ketorolac prescribed at a low dose intra-articularly does not produce any detectable analgesic effect after minor knee surgery.