The efficacy and safety of two low-dose peri-operative dexamethasone on pain and recovery following total hip arthroplasty: a randomized controlled trial

Since the discovery of glucocorticoids in the 1940s and the recognition of their anti-inflammatory effects, they have been amongst the most widely used and effective treatments to control inflammatory and autoimmune diseases. However, their clinical efficacy is compromised by the metabolic effects of long-term treatment, which include osteoporosis, hypertension, dyslipidaemia and insulin resistance/type 2 diabetes mellitus. In recent years, a great deal of effort has been invested in identifying compounds that separate the beneficial anti-inflammatory effects from the adverse metabolic effects of glucocorticoids, with limited effect. It is clear that for these efforts to be effective, a greater understanding is required of the mechanisms by which glucocorticoids exert their anti-inflammatory and immunosuppressive actions. Recent research is shedding new light on some of these mechanisms and has produced some surprising new findings. Some of these recent developments are reviewed here.

Dexamethasone is frequently administered in the perioperative period to reduce postoperative nausea and vomiting. In contrast, the analgesic effects of dexamethasone are not well defined. The authors performed a meta-analysis to evaluate the dose-dependent analgesic effects of perioperative dexamethasone. We followed the PRISMA statement guidelines. A wide search was performed to identify randomized controlled trials that evaluated the effects of a single dose systemic dexamethasone on postoperative pain and opioid consumption. Meta-analysis was performed using a random-effect model. Effects of dexamethasone dose were evaluated by pooling studies into three dosage groups: low (less than 0.1 mg/kg), intermediate (0.11-0.2 mg/kg) and high (≥ 0.21 mg/kg). Twenty-four randomized clinical trials with 2,751 subjects were included. The mean (95% CI) combined effects favored dexamethasone over placebo for pain at rest (≤ 4 h, -0.32 [0.47 to -0.18], 24 h, -0.49 [-0.67 to -0.31]) and with movement (≤ 4 h, -0.64 [-0.86 to -0.41], 24 h, -0.47 [-0.71 to -0.24]). Opioid consumption was decreased to a similar extent with moderate -0.82 (-1.30 to -0.42) and high -0.85 (-1.24 to -0.46) dexamethasone, but not decreased with low-dose dexamethasone -0.18 (-0.39-0.03). No increase in analgesic effectiveness or reduction in opioid use could be demonstrated between the high- and intermediate-dose dexamethasone. Preoperative administration of dexamethasone appears to produce a more consistent analgesic effect compared with intraoperative administration. Dexamethasone at doses more than 0.1 mg/kg is an effective adjunct in multimodal strategies to reduce postoperative pain and opioid consumption after surgery. The preoperative administration of the drug produces less variation of effects on pain outcomes.

Fatigue is a frequent symptom in several inflammatory diseases, particularly in rheumatic diseases. Elements of disease activity and cognitive and behavior aspects have been reported as causes of fatigue in patients with rheumatoid arthritis. Fatigue could be associated with activity of inflammatory rheumatism. Indeed, biologic agents targeting inflammatory cytokines are effective in fatigue. Fatigue is also associated with pain and depressive symptoms. Different pathways could be involved in fatigue and interact: the immune system with increased levels of pro-inflammatory cytokines (interleukin-1 and −6 and tumor necrosis factor alpha), dysregulation of the hypothalamic-pituitary-adrenal axis and neurological phenomena involving the central and autonomic nervous systems. A pro-inflammatory process could be involved in pain and behavioral symptoms. Inflammation could be a common link between fatigue, pain, and depression.