• Department of Anaesthesiology and Orthopaedic Surgery, Hvidovre University Hospital; Section for Surgical Pathophysiology, Rigshospitalet - Copenhagen University Hospital and The Lundbeck Centre for Fast-Track Hip and Knee Arthroplasty, Copenhagen, Denmark.
• Acta Anaesthesiol Scand. 2013 Oct 1;57(9):1207-9.

BackgroundTotal hip and knee arthroplasty (THA and TKA) are frequently performed surgical procedures with excellent long-term functional outcomes. However, pain is pronounced in the early post-operative phase, especially after TKA. Glucocorticoids have proven to relieve post-operative pain, but a higher dose might be needed, as compared with the lower dose recommended to reduce post-operative nausea and vomiting (PONV). Prior to this PhD study, procedure-specific data were limited on the effects of high-dose glucocorticoid on post-operative pain and recovery in THA and TKA. So, the following question remained to be answered: does high-dose glucocorticoid added to a multimodal analgesic regime reduce pain and improve recovery after THA and TKA?MethodsThe thesis is based upon two randomised controlled trials, one in TKA (paper I) and one in THA (paper II), and one qualitative literature review in hip and knee surgery (paper III), starting from the CONSORT and the PRISMA recommendations, respectively. It was hypothesised that methylprednisolone (MP), 125 mg intravenously (IV), would improve acute post-operative analgesia during walk (5 m) 24 h after TKA (paper I) and reduce time to meet well-defined functional discharge criteria after THA (paper II). Paper III aimed to evaluate the overall benefit vs. harm of perioperative glucocorticoids in patients undergoing hip or knee surgery and to assess, whether the recent years of research has led us closer to clinical recommendations.ResultsIn TKA (paper I), pain during walk (5 m) 24 h after surgery was lower in the MP vs. the placebo group, as were overall pain for the first 48 h for all pain assessments (during walk, at rest, upon passive hip flexion, upon passive knee flexion). Also, the C-reactive protein (CRP) response 24 h after surgical incision, the number of patients requiring rescue sufentanil in the post-anaesthesia care unit, cumulative rescue oxycodone requirement from 0 to 24 h, combined nausea score and cumulative ondansetron requirement from 0 to 48 h, and fatigue throughout the day of surgery were lower. However, sleep quality was worse on the first post-operative night. In THA (paper II), no difference was observed in time to meet functional discharge criteria in the MP vs. the placebo group. However, overall pain for the first 24 h after surgery was lower in the MP vs. the placebo group for all pain assessments (during walk, upon rise from chair, at rest, upon passive hip flexion). Also, the CRP response 24 h after surgical incision was lower in the MP vs. the placebo group. In the literature review (paper III), PONV was reduced with systemic glucocorticoid. Pain was reduced with high-dose systemic and local glucocorticoid, but not with low-dose systemic glucocorticoid. Systemic inflammatory markers were reduced with low-dose and high-dose systemic glucocorticoid and with local glucocorticoid. Functional recovery was improved with local glucocorticoid. All studies were small-sized and underpowered to meaningfully evaluate uncommon adverse events. Most of the local administration studies had poor scientific quality (high risk of bias).ConclusionsThis PhD thesis render new knowledge by demonstrating - for the first time - detailed procedure-specific beneficial effects of a single pre-operative dose of MP, 125 mg IV, on acute post-operative analgesia in THA, and on acute post-operative analgesia and on other immediate recovery aspects in TKA. Noteworthy, these benefits were observed with MP added to a comprehensive multimodal oral analgesic regime consisting of paracetamol, celecoxib and gabapentin - and in TKA also to an intra-operative local infiltration analgesia regimen. However, current data in hip and knee surgery preclude firm safety conclusions, and call for large-scale studies to definitively clarify the risk-benefit ratio, before final recommendations can be made. Also, the shortage of dose-finding data calls for studies to define the minimal effective dose to provide post-operative analgesia.© 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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