CLINICAL QUESTION: Does intranasal insulin administration reduce postoperative delirium in older patients undergoing hip fracture surgery?
BACKGROUND: Cerebral hypometabolism may be a therapeutic target for the management of delirium in older, hospitalized patients. Insulin delivered via the intranasal route acts directly on the central nervous system and has been shown to enhance cerebral metabolism and improve cognition in people with dementia, without hypoglycemic episodes. This study looked at the effective intranasal insulin dose for patients undergoing hip surgery.
STUDY DESIGN: Randomized, double-blinded, placebo-controlled trial
SETTING: Single academic hospital in China
SYNOPSIS: Patients over the age of 65 undergoing unilateral hip arthroplasty or closed reduction and intramedullary nailing under spinal anesthesia were randomly assigned to receive intranasal saline (control group), 20 units of intranasal detemir insulin (I-20 group), or 40 units of intranasal detemir insulin (I-40 group). Cohorts received their respective medication the day before surgery, 50 minutes before surgery, and at 7 p.m. on the day of surgery. The primary outcome was the incidence of postoperative delirium. Pertinent exclusion criteria include body mass index greater than 24, insulin allergy, and inability to communicate. 144 patients were initially enrolled, 14 were excluded due to transfer to the ICU, and four were excluded due to conversion from spinal analgesia to general anesthesia, surgery greater than three hours, or refusal of spinal analgesia. 130 patients were included in the analysis. All patients received 8 to 10 mg of dexamethasone in the operative setting.
Patients were evaluated for post-op delirium daily, within three days of surgical intervention. Prior to delirium, patients were evaluated for sedation using the Richmond Agitation-Sedation Scale. If the patient was deeply sedated or unarousable, the assessment was terminated. If not, the patient underwent scoring with the Confusion Assessment Method.
Compared to the control group, the I-20 and I-40 groups showed significantly lower incidence of post-op delirium within the first three days, with the control group at 39.5% versus 11.4% and 14.3% in the I-20 and I-40 groups, respectively. While the incidence of post-op delirium tended to be lower in the I-20 group than in the I-40 group, the difference was not statistically significant. There were no hypoglycemic episodes reported.
BOTTOM LINE: Given that current medication options for delirium often have significant risks and side effects, intranasal insulin may be a safe prophylactic strategy to minimize post-op delirium in patients undergoing hip surgery with spinal anesthesia.
CITATION: Li Y, et al. Optimal dose of intranasal insulin administration for reducing postoperative delirium incidence in older patients undergoing hip fracture surgery. Am J Geriatr Psychiatry. 2025;33(8):891-900. doi: 10.1016/j. jagp.2025.03.009.
Dr. Childers
Dr. Childers is an associate clinical professor in the division of hospital medicine and a hospitalist at UC San Diego Health in San Diego.