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Randomized controlled trial of intra‐articular ketorolac on pain and inflammation after minor arthroscopic knee surgery
Author(s) -
Solheim N.,
Gregersen I.,
Halvorsen B.,
Bjerkeli V.,
Stubhaug A.,
Gordh T.,
Rosseland L. A.
Publication year - 2018
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/aas.13104
Subject(s) - ketorolac , medicine , analgesic , anesthesia , placebo , prostaglandin , microdialysis , ketorolac tromethamine , surgery , pathology , alternative medicine , central nervous system
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 E 2 and chondroitin sulphate in vitro. Results Intra‐articular ketorolac (5 mg) administration did not reduce pain or synovial pro‐inflammatory cytokines CXCL 1, 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 CXCL 1 and IL ‐8 in prostaglandin E 2 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.