Perioperative GDNF as a Predictive Factor for Postoperative Delirium and Adverse Neurological Outcomes in Pediatric Surgery

Perioperative GDNF as a Predictive Factor for Postoperative Delirium and Adverse Neurological Outcomes in Pediatric Surgery:a Single-center, Prospective, Randomized Controlled Study

To observe the dynamic changes in serum levels of inflammatory cytokines (e.g., IL-6, TNF-α), Brain-Derived Neurotrophic Factor (BDNF), and Glial Cell Line-Derived Neurotrophic Factor (GDNF) during the perioperative period in pediatric patients undergoing Scheduled Laparoscopic Hernia Repair surgery, and to investigate their relationship with the occurrence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD),and to compare the different influence between propofol and sevoflurane . The aim is to provide insights into the neurobiological mechanisms underlying these complications and to identify potential biomarkers for risk stratification.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Delirium; Postoperative Cognitive Dysfunction
• Intervention / Treatment: Drug: Sevoflurane group; Drug: Propofol group

Detailed Description

Clarify the Correlation Between Perioperative Changes in Inflammatory Factors, BDNF, and GDNF Levels and Postoperative delirium (POD) Blood and urine samples were collected from pediatric patients at three time points: 5 minutes before anesthesia induction (T0), 1 hour after surgery began (T1), and on the first postoperative day (T2). Serum levels of inflammatory factors (such as IL-6 and TNF-α) as well as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were measured. The Richmond Agitation-Sedation Scale (RASS) was used to assess the children within 5-10 minutes after awakening from anesthesia. The RASS score ranges from +4 (combative agitation) to -5 (coma), comprising 10 levels, with higher scores indicating more agitated states and lower scores indicating deeper sedation. A score ≥+1 was defined as agitation. By comparing changes in inflammatory factors and neurotrophic factor levels across different time points, the association with the occurrence of postoperative agitation was analyzed.

Clarify the Correlation Between Perioperative Changes in Inflammatory Factors, BDNF, and GDNF Levels and Learning and Memory Abilities at Age 5 For the same cohort of children, based on blood and urine samples collected at the aforementioned time points (T0, T1, T2), concentrations of inflammatory factors (such as IL-6 and TNF-α), BDNF, and GDNF were measured. When the children reached 5 years of age, standardized neurocognitive assessment tools (such as the Wechsler Preschool and Primary Scale of Intelligence-IV [WPPSI-IV] or age-appropriate memory and learning function tests) were used to evaluate their learning and memory abilities. Statistical analysis was performed to explore the potential correlation between the dynamic changes in the aforementioned biomarkers during the perioperative period and cognitive function scores at age 5.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• (1) Aged 1-3 years; (2) American Society of Anesthesiologists (ASA) Physical Status Classification I-II; (3) Body Mass Index (BMI) 18-35 kg/m²; (4) Agreement to participate in the study and signed informed consent form.

Exclusion Criteria:

• (1) Surgical duration exceeding 4 hours; (2) Patients with language or hearing impairments hindering effective communication; (3) Patients with postoperative infections or perioperative cardiopulmonary complications; (4) Patients with preoperative psychiatric disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sevoflurane Group; Anesthesia was maintained with sevoflurane (Inhalation Sevoflurane, Brand: Kaiteli, Specification: 120 mL, Approval Number: National Drug Approval H20070172, Manufacturer: Shanghai Hengrui Pharmaceutical) combined with continuous intravenous infusion of remifentanil.	Drug: Sevoflurane group; Patients fasted for 6 hours and abstained from clear fluids for 3 hours preoperatively. Upon entering the operating room, oxygen was administered via an appropriately sized face mask at a flow rate of 6-8 L/min. Anesthesia was induced by sequential intravenous injection of remimazolam, sufentanil, and rocuronium. A laryngeal mask was inserted after the disappearance of the eyelash reflex. Anesthesia was maintained with sevoflurane (Inhalation Sevoflurane, Brand: Kaiteli, Specification: 120 mL, Approval Number: National Drug Approval H20070172, Manufacturer: Shanghai Hengrui Pharmaceutical) combined with continuous intravenous infusion of remifentanil. During surgery, vital signs and body movement responses were closely monitored, and the inhaled concentration of sevoflurane was adjusted as needed (maintained at 1%-3%). Administration of anesthetics was discontinued 5 minutes before the end of surgery.
Active Comparator: Propofol Group; Anesthesia was maintained with remifentanil combined with continuous intravenous infusion of propofol at a maintenance dose of 0.5 mg/(kg·h).	Drug: Propofol group; Preoperative preparation was identical to that of the Sevoflurane Group. Anesthesia induction was performed using the same sequence of intravenous injections of remimazolam, sufentanil, and rocuronium, followed by laryngeal mask insertion after the disappearance of the eyelash reflex. Anesthesia was maintained with remifentanil combined with continuous intravenous infusion of propofol at a maintenance dose of 0.5 mg/(kg·h). The infusion rate was dynamically adjusted based on intraoperative vital signs. Administration of anesthetics was stopped 5 minutes before the end of surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between Perioperative Inflammatory Factors and Neurotrophic Factor Levels with Postoperative Delirium	The levels of inflammatory factors IL-1β, IL-6, and TNF-α in pediatric patients will be measured using ELISA before surgery, 30 minutes during surgery, and one day after surgery. Simultaneously, the levels of neurotrophic factors BDNF and GDNF will be detected using ELISA. The RASS scale was employed to assess the level of emergence agitation in the children. A t-test will be used to compare whether the inflammatory factor levels between the two groups were correlated with the occurrence of emergence agitation, to determine whether the pre- and postoperative changes in neurotrophic factors are statistically significant, and to evaluate whether these changes is correlated with the incidence of emergence agitation.	Preoperative to postoperative day 1
Correlation between Perioperative Inflammatory Factors and Neurotrophic Factor Levels with Neurodevelopmental Outcomes at 5 Years of Age	The levels of inflammatory factors IL-1β, IL-6, and TNF-α in pediatric patients will be measured using ELISA before surgery, 30 minutes during surgery, and one day after surgery. Simultaneously, the levels of neurotrophic factors BDNF and GDNF will be detected using ELISA. The Wechsler Scale II will be employed to assess the learning and memory abilities of the children at five years of age. A t-test was used to compare whether the inflammatory factor levels between the two groups will be correlated with the development of long-term learning and memory function, and to evaluate whether changes in these levels were associated with the occurrence of long-term learning and memory function.	Preoperative until the child reaches 5 years of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between Surgical Type on the Expression of Inflammatory Factors with Neurotrophic Factors	We will categorize the surgeries into upper abdominal, lower abdominal, and limb procedures based on human anatomical structure. Correlation analysis will performe between these surgical categories and the levels of inflammatory factors and neurotrophic factors measured by ELISA. This analysis aim to evaluate whether the type of surgery will correlate with changes in inflammatory factor levels, as well as to examine the association between surgical categories and the occurrence of postoperative delirium.	Intraoperative to postoperative day 1
Correlation between Surgical Duration on the Expression of Inflammatory Factors with Neurotrophic Factors	We will classify the surgeries into two categories based on a 2-hour duration threshold and performed correlation analysis with the levels of inflammatory factors and neurotrophic factors measured by ELISA. This analysis aimed to evaluate whether the duration of surgery was correlated with changes in inflammatory factor levels, as well as to examine the association between surgical duration and the occurrence of emergence delirium and long-term neurological function.	Intraoperative to postoperative day 1
Collection between Anesthetic Drugs on the Expression of Inflammatory Factors with Neurotrophic Factors	We will categorize the surgeries into propofol-based maintenance group and sevoflurane-based maintenance group. Correlation analysis will be performed between these two anesthetic approaches and the levels of inflammatory factors and neurotrophic factors measured by ELISA. This analysis aim to evaluate whether the choice of anesthetic agent was correlated with alterations in inflammatory factor levels.	Intraoperative to postoperative day 1

Collaborators and Investigators

• Sponsor: General Hospital of Ningxia Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): September 15, 2025
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: September 10, 2025
• First Submitted That Met QC Criteria: September 17, 2025
• First Posted (Estimated): September 25, 2025

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Cognition Disorders; Delirium; Cognitive Dysfunction; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Postoperative Cognitive Complications; Emergence Delirium
• Other Study ID Numbers: Hui Wang-2025.9

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No