Preventing Postoperative Delirium with Intranasal Long-acting Insulin

Postoperative delirium (POD) often complicates the recovery of older adults undergoing major surgeries like radical esophagectomy. A groundbreaking study has identified intranasal long-acting insulin as a promising preventive measure against this cognitive decline. By delivering insulin directly to the brain, clinicians can target neuroinflammation without impacting systemic blood sugar levels. This method addresses the urgent need for effective delirium prevention in geriatric oncology.

The Neuroprotective Mechanism of Intranasal Long-acting Insulin

The research involved sixty elderly patients scheduled for elective esophageal cancer surgery. The intervention group received a single 30 U dose of intranasal long-acting insulin one day before their procedure. Consequently, the incidence of POD dropped from 46.7% in the control group to just 16.7% in the insulin group. This significant reduction highlights the efficacy of preconditioning the brain against surgical stress.

Specifically, the study explored the NLRP3/caspase-1/IL-1β inflammatory pathway. Postoperative surgery often triggers a surge in these inflammatory markers, leading to neural dysfunction. However, patients receiving the insulin pretreatment showed significantly lower levels of peripheral IL-1β. Furthermore, their mRNA expression of NLRP3 and caspase-1 remained suppressed. These findings suggest that long-acting insulin provides sustained protection by inhibiting the inflammasome activation that usually drives delirium.

Clinical Advantages and Safety

Moreover, the researchers emphasized the benefits of long-acting formulations over rapid-acting ones. Long-acting insulin ensures continuous exposure of the central nervous system to neuroprotective signals throughout the critical perioperative window. Additionally, the intranasal route avoids common side effects like systemic hypoglycemia. Therefore, this approach offers a safe, simple, and targeted strategy for enhancing postoperative recovery in high-risk elderly populations.

Frequently Asked Questions

Why is the intranasal route preferred for insulin delivery?

The intranasal route allows insulin to bypass the blood-brain barrier via olfactory and trigeminal nerve pathways. This direct access ensures higher concentrations in the brain while minimizing systemic absorption and the risk of low blood sugar.

How does insulin reduce postoperative delirium?

Insulin acts as a potent anti-inflammatory agent in the brain. It specifically inhibits the NLRP3 inflammasome and reduces the production of pro-inflammatory cytokines like IL-1β, which are major contributors to postoperative cognitive impairment.

Disclaimer: This content is for informational and educational purposes only. It does not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

Zhang Y et al. Effects of intranasal long-acting insulin pretreatment on postoperative delirium and the NLRP3/caspase-1/IL-1β pathway in older patients with esophageal cancer. Inflamm Regen. 2026 Apr 18. doi: 10.1186/s41232-026-00418-4. PMID: 41998765.

Zhang H et al. Intranasal insulin and postoperative delirium in adult surgical patients: a meta-analysis and systematic review of randomized controlled trials. Frontiers in Medicine. 2025;12:1543210.

Amin AM et al. The Role of Perioperative Intranasal Insulin Administration in Preventing Postoperative Delirium: A Systematic Review. American Journal of Geriatric Psychiatry. 2026;34(2):112-115.