Steroids to reduce the impact on delirium (STRIDE): a double‐blind, randomised, placebo‐controlled feasibility trial of pre‐operative dexamethasone in people with hip fracture

• Published in: Anaesthesia Vol. 76; no. 8; pp. 1031 - 1041
• Main Authors: Kluger, M. T., Skarin, M., Collier, J., Rice, D. A., McNair, P. J., Seow, M.Y., Connolly, M. J.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-08-2021
• Subjects: Adverse events; Age Factors; Aged; Aged, 80 and over; Cognition; Cognitive ability; Delirium; Dexamethasone; Dexamethasone - therapeutic use; Double-Blind Method; Double-blind studies; Emergence Delirium - prevention & control; Emergency medical care; Emergency medical services; Feasibility Studies; Female; Fractures; Geriatric Assessment - methods; Glucocorticoids - therapeutic use; Hip; hip fracture; Hip Fractures - surgery; Hip joint; Humans; Inflammation; Male; Mental disorders; Pain; Pathogenesis; Patients; Placebos; prevention; Recruitment; Steroid hormones; Steroids; Surgery; Treatment Outcome; dexamethasone; hip fracture; delirium; prevention
• ISSN: 0003-2409; 1365-2044
• DOI: 10.1111/anae.15465

Summary
Neuro‐inflammation may be important in the pathogenesis of postoperative delirium following hip fracture surgery. Studies have suggested a potential role for steroids in reducing postoperative delirium; however, the potential efficacy and safety of pre‐operative high‐dose dexamethasone in this specific population is largely unknown. Conducting such a study could be challenging, considering the multidisciplinary team involvement and the emergency nature of the surgery. The aim of this study was to assess feasibility and effectiveness of dexamethasone given as early as possible following hospital admission for hip fracture, to inform whether a full‐scale trial is warranted. This single‐centre, randomised, double‐blind, placebo‐controlled study randomly allocated 79 participants undergoing hip fracture surgery to dexamethasone 20 mg or placebo pre‐operatively. Eligibility and recruitment rates, timing of the intervention and adverse events were recorded. Incidence and severity of postoperative delirium were assessed using the 4AT delirium screening tool and the Memorial Delirium Assessment Scale. Postoperative pain, length of stay and mortality were also assessed. The eligibility rate for inclusion was 178/527 (34%), and 57/178 (32%) of eligible patients presented to hospital when no researcher was available (e.g. after‐hours, weekends, public holidays). Recruitment was limited mainly by ethical limitations (not including patients with impaired cognition) and lack of weekend staffing. Median (IQR [range]) time from emergency department admission to drug administration was 13.3 (5.9–17.6 [1.8–139.6]) hours. There was a significant difference in delirium severity scores, favouring the dexamethasone group: median (IQR [range]) 5 (3–6 [3–7]) vs. 9 (6–13 [5–14]) in the placebo group, with the probability of superiority effect size being 0.89, p = 0.010. Delirium incidence did not differ between groups: 6/40 (15%) in the dexamethasone group vs. 9/39 (23%) in the placebo group, relative risk (95%CI) 0.65 (0.22–1.65), p = 0.360). A larger randomised controlled trial is feasible and ideally this should include people with existing cognitive impairment, seven days‐a‐week cover and a multicentre design.