Effect of combination of multiple anti-inflammatory drugs strategy on postoperative delirium among older patients undergoing hip fracture surgery: a pilot randomized controlled trial.

Summary

In a dual-center, double-blind pilot RCT (n=132 randomized; 123 analyzed), a perioperative anti-inflammatory bundle (dexmedetomidine, glucocorticoid, ulinastatin, NSAIDs) reduced postoperative delirium from 44% to 15% (RR 0.33; P=0.001) without major adverse events. Lower postoperative CRP partially mediated the effect, supporting inflammation as a causal pathway.

Key Findings

• Postoperative delirium was reduced from 44% (27/61) to 15% (9/62) with the anti-inflammatory bundle (RR 0.33; 95% CI 0.17–0.64; P=0.001).
• No major adverse events occurred in either group, supporting safety of the bundled approach.
• Postoperative CRP levels were significantly lower with the bundle, and mediation analysis implicated systemic inflammation in the protective effect.

Clinical Implications

If replicated, anesthesiologists could adopt protocolized anti-inflammatory bundles to prevent delirium in high-risk geriatric fracture surgery, integrating dexmedetomidine sedation, a single perioperative steroid dose, ulinastatin, and NSAIDs with careful patient selection and monitoring.

Limitations

• Pilot sample size and two-center setting limit generalizability
• Bundle design precludes disentangling the contribution of individual drugs; short (3-day) delirium follow-up

Future Directions

Conduct adequately powered, multicenter RCTs to confirm efficacy, optimize dosing/timing, assess long-term cognitive and functional outcomes, and evaluate cost-effectiveness and safety in broader populations.