Effect of a Single Pre-operative 125 Mg Dose of Methylprednisolone on Postoperative Delirium in Hip Fracture Patients; a Randomised, Double-blind, Placebo-controlled Trial

Postoperative delirium is common after hip fracture surgery, and may have a neuro-inflammatory cause. We conducted a single-centre, randomised, double-blind, placebo-controlled trial of 117 older hip fracture patients to see if a single, pre-operative intravenous dose of 125 mg methylprednisolone could reduce the severity and/or incidence of postoperative delirium, assessed using the Confusion Assessment Method delirium severity score. Modified intention-to-treat analysis found no significant difference in our primary outcome, median (IQR [range]) cumulative Confusion Assessment Method delirium severity score over the first three postoperative days between the methylprednisolone and placebo groups (1 (0-6 [0-39]) vs. 2 (0-10 [0-32]), p = 0.294). Both the prevalence of postoperative delirium (Confusion Assessment Method delirium severity score ≥ 5, 10/59 vs. 19/58, p = 0.048) and the median (IQR [range]) cumulated postoperative (by day 3) fatigue scores (5 (2-6 [0-11]) vs. 6 (4-8 [0-16]), p = 0.008) were significantly lower in the methylprednisolone compared with the placebo group. There were no significant between-group differences in the rate of completing physiotherapy, postoperative pain, the administration of antipsychotic drugs, infection, length of inpatient stay or 30- and 90-day mortality. No major adverse reactions related to methylprednisolone were recorded. We conclude that a single, pre-operative dose of 125 mg methylprednisolone does not reduce the severity of postoperative delirium, but may reduce both the prevalence of delirium and the severity of fatigue after hip fracture surgery in older patients, enabling remobilisation and recovery.