The Effect of Corticosteroids on Quality of Life Following Total Hip Arthroplasty: HIPSTER Study

Total hip arthroplasty (THA) is a successful and cost-effective treatment for end-stage osteoarthritis and other degenerative hip conditions. It is one of the most frequently performed surgical procedures worldwide and continues to increase in volume each year, largely due to the growing population of older adults. Despite its effectiveness, THA is associated with significant surgical trauma that induces a pronounced inflammatory response, leading to postoperative pain, fatigue, postoperative nausea and vomiting (PONV), prolonged hospital stays, and delayed functional recovery. Prevention of postoperative inflammation can be a crucial cornerstone to optimize recovery and enhance outcomes after THA.

Dexamethasone, a potent and long-acting glucocorticoid with strong anti-inflammatory properties, is widely used in orthopedic surgery. It suppresses prostaglandin synthesis by downregulating cyclooxygenase-2 expression, thereby inhibiting cell adhesion factor expression and cytokine gene transcription. Dexamethasone also reduces neutrophil and macrophage exudation and activity at inflammatory sites, decreasing cellular adhesion and aggregation along vascular endothelium. Although dexamethasone has a short half-life of approximately 36-72 hours, by modulating the surgical stress response and its multiple downstream effects on inflammation, acute pain, nausea, and fatigue, it may also influence longer-term outcomes. Due to these mechanisms, dexamethasone has become an integral component of perioperative management in various surgical disciplines, including THA.

Previous studies have demonstrated that perioperative dexamethasone administration can attenuate inflammatory responses, reduce PONV, and acute postoperative pain and fatigue in patients undergoing THA. These short-term benefits translate into improved early postoperative recovery, which can be quantified using validated instruments such as the Quality of Recovery-15 (QoR-15) score. Consequently, dexamethasone is now commonly incorporated into Enhanced Recovery After Surgery (ERAS) protocols for THA. Intermediate glucocorticoid doses - equivalent to 25 mg of dexamethasone - are generally considered safe and are part of the standard of care in many arthroplasty centers performing primary THA.

While the short-term benefits of dexamethasone on postoperative inflammation, acute pain control, PONV reduction, early recovery, and hospital length of stay are well established in THA, concerns remain regarding its long-term safety profile. Several studies have reported potential adverse effects associated with intermediate to high doses, such as impaired sleep quality, immunosuppression, and possible wound-healing complications. Although glucocorticoids at the implemented doses have demonstrated efficacy in reducing acute postoperative pain, their role in preventing chronic postsurgical pain (CPSP) remains unclear, with some studies suggesting even a trend to persistent wound pain with higher doses of dexamethasone. Furthermore, the long-term effects of perioperative dexamethasone on health-related quality of life (HRQoL) following THA have not yet been systematically investigated.

As health-related quality of life, assessed by EQ-5D, is an important patient-reported outcome following anaesthesia and surgery, as emphasised in the StEP-COMPAC initiative, the effect of different doses of dexamethasone on health-related quality of life needs further investigation.

Therefore, the main objective of the HIPSTER trial is to evaluate the effect of different doses of a single intraoperative intravenous dose of dexamethasone (5 mg versus 25 mg) on health-related quality of life up to three months after surgery.

• Quality of Recovery (QoR) [Time frame: Preoperative and postoperative day 1, day 3 and day 5]
• Health-related quality of life (EQ-VAS) [Time frame: Preoperative and postoperative day 30, day 60 and day 90]
• Oxford Hip Score (OHS) [Time frame: Postoperative day 30, day 60 and day 90]
• Brief Pain Inventory (BPI) [Time frame: Preoperative and postoperative day 30, day 60 and day 90]
• Chalder fatigue questionnaire (CFQ) [Time frame: Preoperative and postoperative day 30, day 60 and day 90]