Effect of Preoperative Intervention With Folic Acid and Vitamin B12 on Postoperative Neurobehavioral Changes in Children

Comparison of preoperative folic acid and VitB12 intervention on postoperative delirium and long-term neurobehavioral changes in children under general anesthesia

Study Overview

• Status: Recruiting
• Conditions: Delirium
• Intervention / Treatment: Dietary supplement: Folic acid and vitamin B12; Dietary supplement: brown sugar aqueous

Detailed Description

Folic acid, as a one-carbon unit transferase coenzyme, participates in the synthesis of purine and thymine, and is an important element of the nervous system. Vitamin B12 participates in methyl conversion and folate metabolism in the body, promoting the conversion of 5-methyltetrahydrofolate to tetrahydrofolate. It has been reported that the lack of serum folic acid and B12 is associated with an increased risk of cognitive impairment. The explanation mechanism of the relationship between folic acid deficiency and cognitive dysfunction may be that folic acid deficiency leads to impaired central nervous system methylation, resulting in insufficient methyl synthesis of myelin sheaths, neurotransmitters, membrane phospholipids and deoxyribonucleic acid. Our previous studies showed that preoperative folic acid supplementation can alleviate myelin damage and cognitive impairment in young rats caused by sevoflurane anesthesia. Therefore, this study further explored the preoperative folic acid and coenzyme B12 supplementation for children's delirium and long-term neurobehavioral changes after general anesthesia.

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: lei zhang, Doctor; Phone Number: 0086-18717822662; Email: weiymzhl@126.com
• Study Contact Backup: Name: hong jiang, Doctor; Phone Number: 0086-021-23271699; Email: jianghongjiuyuan@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200001
      • Recruiting
      • China
      • Contact: lei zhang, doctor; Phone Number: +86-18717822662; Email: weiymzhl@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 2 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ASA grade is Ⅰ ~ Ⅱ;
2. Children aged 6 months to 2 years old;
3. It is planned to undergo head, neck and maxillofacial surgery under general anesthesia with anesthesia for less than 6 hours

Exclusion Criteria:

1. Children with a history of respiratory tract infection within 1 week;
2. Children with congenital malformations such as congenital heart disease;
3. Children with central nervous system diseases or mental disorders or mental disorders;
4. Children with long-term use of sedative or analgesic drugs;
5. Children with severe liver and kidney dysfunction;
6. Received folic acid and VitB12 supplement treatment or taken related derivatives;
7. Have taken drugs that affect absorption within the past month, such as sulfonamides, aspirin, etc .;
8. Those who have participated in other relevant clinical research in the past 3 months;
9. Children with stunting

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Intervention group; Before the operation, the patient took 20ml of brown sugar aqueous solution containing folic acid and VitB12 for 3 days (folic acid concentration is 0.4mg / d for 2 year old children + 1.2μg / d of VitB12, dissolved in 20ml brown sugar water once a day). Postoperatively, PAED scores were performed at the time of awakening, extubation and every 10min within 30min after extubation. 10 points is defined as delirium during the recovery period). Long-term neurobehavioral changes were evaluated using the Gesell scale, followed up every six months until the age of three	Dietary supplement: Folic acid and vitamin B12; Take folic acid and VitB12 for 3 consecutive days before surgery
PLACEBO_COMPARATOR: Placebo group; The patients in the placebo group took 20 ml of brown sugar aqueous solution with the same concentration as the intervention group 3 days before the operation. Postoperatively, PAED scores were performed at the time of recovery, extubation, and every 10 minutes within 30 minutes after extubation. The PAED scores of all children were measured by the same person. (The total score is 0-20, and the score ≥10 is defined as delirium during the recovery period). Long-term neurobehavioral changes were evaluated using the Gesell scale, followed up every six months until the age of three	Dietary supplement: brown sugar aqueous; take 20 ml of brown sugar aqueous solution with the same concentration as the intervention group 3 days before the operation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PAED scale	Observe whether the index will cause delirium during the recovery period.The evaluation range of the PAED scale is 0-20 points, If the score exceeds 10 points, Then it is considered delirium.	10 minutes after surgery
Gesell scale	Through the gesell scale, 5 tests are carried out on children: gross motor ability, fine movement, physical ability, verbal ability, and human ability.The evaluation range of the Gesell scale is 0-100 points. If the score is higher, it means good. If the score is low, it means that the result is not good. If the result is not good, it may be caused by anesthesia, so we conducted this evaluation.	2 day after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate	Observe heart rate through a monitor	During the induction period of anesthesia, intubation, and the operation period；immediately after entering the resuscitation room (T1), 5 minutes before extubation (T2), immediately after extubation (T3), and 2 minutes after extubation (T4);
Mean Blood Pressure	Observe and calculated mean blood pressure through a monitor	During the induction period of anesthesia, intubation, and the operation period；immediately after entering the resuscitation room (T1), 5 minutes before extubation (T2), immediately after extubation (T3), and 2 minutes after extubation (T4);
Extubation time	Extubation time	immediately after surgery
Ramsay sedation score	Ramsay sedation score after recovery, extubation and every 10min within 30min after extubation，Ramsay sedation score is 1-6 points. If the score is 2-4 points，That result is satisfactory, 5-6 points are excessive sedation.	10 minutes after extubation
Postoperative pain CHEOPs scores	The postoperative pain CHEOPs scores were taken at the time of extubation and every 10 minutes within 30 minutes after extubation (the total score was less than 6 points, there was no pain, and ≥10 points for corresponding analgesia treatment). The total score is 46 points, if the total score is less than 6 points, it is judged as no pain	20 minutes after extubation
Narcotic drugs	The use of narcotic drugs (eg pentazocine, propofol)	During the surgery
Other adverse events during the recovery period	Other adverse events during the recovery period (eg nausea and vomiting, bronchospasm, respiratory depression, etc.)	Immediately after the surgery
recovery time	recovery time	immediately after recovery

Collaborators and Investigators

• Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
• Investigators: Study Director: hong jiang, Doctor, Director of Anesthesiology

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2020
• Primary Completion (ANTICIPATED): June 30, 2025
• Study Completion (ANTICIPATED): June 30, 2025

Study Registration Dates

• First Submitted: June 14, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (ACTUAL): July 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 7, 2020
• Last Update Submitted That Met QC Criteria: June 29, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Folic Acid; Vitamin B 12; Hydroxocobalamin
• Other Study ID Numbers: SH9H-2020-T57-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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