Frontiers in Medicine · Oct 31, 2026
Preoperative Hypertonic Sodium Chloride Hydroxyethyl Starch Infusion for Delayed Neurocognitive Recovery in Elderly Hip Fracture Patients: A Randomized Controlled Trial Protocol
By Long Wu, Jia Huang, Siyu Chen et al.
Introduction: Delayed neurocognitive recovery (dNCR) is a common neurological complication in elderly patients following hip fracture surgery and is associated with poor prognosis and reduced quality of life.. Hypertonic sodium chloride hydroxyethyl starch (HSH) has both volume-expanding and immunomodulatory properties. Our previous animal studies demonstrated that HSH exerts neuroprotective effects by stabilizing the blood-brain barrier, with greater efficacy than hypertonic saline or hydroxyethyl starch alone. However, high-quality clinical evidence regarding its cognitive protective effect in elderly hip fracture patients is lacking. This trial aims to evaluate the preventive effect and mechanisms of preoperative prophylactic HSH infusion on dNCR in elderly patients with hip fracture.The findings are expected to provide high-quality evidence for optimizing perioperative fluid management strategies and offer a novel, practical approach for perioperative cognitive protection in this vulnerable population. Methods and analysis: This is a single-center, prospective, randomized, double-blind, placebo-controlled, superiority trial. A total of 148 elderly patients aged ≥65 years with ASA physical status I–III scheduled for hip fracture surgery will be randomly assigned in a 1:1 ratio to the HSH group (4 ml/kg HSH40 infused 30 min before anesthesia induction) or the control group (equal volume of normal saline). The primary outcome is the incidence of dNCR at postoperative day 7, defined as a ≥2-point decrease in Montreal Cognitive Assessment score from baseline. Secondary outcomes include exploratory cognitive function at 1 and 3 months postoperatively assessed by the Telephone Interview for Cognitive Status–Modified, days alive and at home within 30 days postoperatively, quality of recovery assessed by the QoR-15 scale, serum biomarkers of blood-brain barrier injury and inflammation (S100β, MMP-9, IL-6), incidence of postoperative delirium, and postoperative complications. Safety indicators include electrolytes, coagulation function, and liver and kidney function. Ethics and dissemination: This study has been approved by the Ethics Committee of Chongqing Traditional Chinese Medicine Hospital (Ethics Approval No. 2025-KY-HY66). Clinical trial registration: www.chictr.org.cn, identifier: ChiCTR2600122105