Clinical trial NCT05924854: The Influence of Electroacupuncture on Postoperative Agitation of Pediatrics Undergoing Sevoflurane General Anesthesia
Official title: The Influence of Electroacupuncture on Postoperative Agitation of Sevoflurane Inhalation Combined With Intravenous Anesthesia in Pediatrics: an Experimental, Single-center Clinical Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: General Anesthetics Toxicity
Postoperative Cognitive Dysfunction
Electroacupuncture
Keywords: Electroacupuncture
Sevoflurane
Postoperative agitation
pediatrics
Lead sponsor: The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine
Sponsor class: OTHER
First posted: 2023-06-29
Enrollment: 80
Sex: ALL
Minimum age (years): 4
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization according to center will be used. Subjects were randomly assigned to the sevoflurane general anesthesia group（S group） and the electroacupuncture group（E group） at a ratio of 1:1.
Primary purpose: TREATMENT

Brief summary: Postoperative agitation is a common complication in pediatric anesthesia, with an incidence ranging from 10% to 80%. Common surgical procedures in children include tonsillectomy, adenoidectomy, insidious penis prolongation and circumcision, etc. Postoperative delirium and agitation is a clinical emergency, and can have detrimental effects on the child's health. The primary clinical manifestations include disorganized movements, moaning, incoherent speech, confusion and paranoid characters, inability to be concentrated, and irritability, obstinacy or uncooperative; all these would increase the risks of falling out of bed, possible fractures, and all kinds of tube loss. These symptoms would sustain postoperative recovery significantly and pose a possible long-term neurological dysfunction. As a result, an extended hospitalization, elevated in-hospital mortality rate, escalated medical expenses, heightened risk of cognitive impairment, reduced quality of life, and increased incidence of postoperative complications.

Traditional acupuncture has been shown to improve cerebral micro-circulation, correct energy metabolism disorders, alleviate chronic pain and regulate visceral function, lessen fatigue and modulate immune. Moreover, acupuncture is a simple, effective and safe therapy. Electroacupuncture therapy is produced and developed on the basis of acupuncture therapy, which has a regulatory effect on multiple systems of the body and can play a regulatory effect that is consistent with normal physiological regulation. Modern medicine believes that the anterior cingulate gyrus, hippocampus, and other regions of the limbic system are the possible center control of emotion and cognition. Electroacupuncture treatment can help accelerate the recovery of central nervous system function, which plays a protective role on the central nerve system, especially the brain, within 24-72 hours after electroacupuncture treatment. At the same time, electroacupuncture is beneficial to the recovery of immune function postoperatively, it can promote the release of central neurotransmitters and improve receptor activity, so as to play a role in postoperative analgesia, reduce the dosage of anesthetics, brain protection, neurological function rehabilitation, and so on. According to scientific research, it also posses a certain effect on the prevention and treatment of postoperative delirium. Sevoflurane is an inhale anesthetic which is widely used in clinics for pediatric general anesthesia. Due to the high incidence of postoperative delirium and agitation, it has been given rise to great concern on pediatric clinical anesthesia. In order to reduce delirium and agitation incidence, the investigators apply electroacupuncture in pediatric for sevoflurane combined with intravenous general anesthesia, aim to target a safe way to lessen postoperative brain complications on pediatric.

This is a single-center experimental study that employs randomization, triple-blinding, and control study. Pediatric patients were randomly assigned to two groups, sevoflurane general anesthesia group (S group) and electroacupuncture group (E group), 40 patients, respectively. Anesthesia induction, maintenance, and monitoring be performed identically in both groups, the S group will not receive electroacupuncture treatment, the E group will receive electroacupuncture therapy. Electroacupuncture intervention will be performed by blinded acupuncture physicians, visitor who is blind to collect preoperative, intraoperative and postoperative data while visiting patients, data statisticians, who are blind to the intervention, data collection, conducted statistical analyses on the data electronically.

Detailed description: Pediatric patients who meet the screening criteria were randomly divided into two groups,sevoflurane general anesthesia group (S group) and electroacupuncture group (E group), 40 patients in each group, respectively. Anesthesia induction, maintenance, and monitoring performed identically in both groups, the S group will not receive electroacupuncture treatment, the E group will receive electroacupuncture therapy. All patients have a regular preoperative fasting, monitoring of vital signs after the patient was admitted to the operating room, Preoxygenation was performed by face mask oxygen with oxygen flow set to 8 L/min for 3 minutes to each patient, and anesthesia induced with 8% sevoflurane inhalation while oxygen flow rate will set to 2 L/min. After the patient slept and accessing successful venipuncture, intravenous drugs were administered with midazoline 0.03-0.05 mg/kg, propofol 0.3-0.5 mg/kg, sufentanil 0.4-0. 5 mg/ kg, and cisatracurium 0.15 mg/kg for induction of anesthesia. After the patient's muscle relaxation, tracheal intubation was performed, and the patient's airway pressure was monitored by connecting an airway pressure detection device, and then IPPV-controlled ventilation was performed by connecting a Drager Fabius GS anesthesia machine (Drager Germany), with oxygen flow rate set to 1 L/min, initial tidal volume set to 6-8 ml/kg, and initial respiratory rate set to 15-20 bpm, adjusted to PaCO2 was maintained at about 36-40 mmHg. The patient's depth of anesthesia was also detected with the EEG dual frequency index, and the BIS was about 45-50.

After general anesthesia induction, the acupuncturist used a Huatuo brand copper milli-needle (Suzhou Medical Supplies Factory) and selected Baihui point（DU20）, Shenting point (DU24), bilateral Zulinqi (GB41) and bilateral Taichong (LR3) point, for acupuncture. The acupuncture points are located 5 inches straight up from the middle of the front hairline of the head, and 0.3-0.5 inches from the midpoint of the front and back hairline of the patient's head in a 1-inch deviation. The TaiChong (LR3) point is located on the back of the patient's foot between the 1st and 2nd metatarsal bones, in the depression in front of the union of the metatarsal bones, or when the patient's foot artery is pulsating, the point is taken from the patient's 1st and 2nd metatarsal bones and pushed backward to the bottom, with a vertical puncture of 0.5-0.8 inch; the foot Linobu (GB41) point is located on the back of the patient's foot, in front of the union of the 4th and 5th metatarsal bones, on the outside of the 5th toe extensor tendon, with a vertical stab of 0.3-0.5 inch.

Then,the acupuncturist check the EA device ( SDZ-Ⅱ,Suzhou Medical Supplies Factory)before use, the EA device is set to zero at the beginning, then connect the acupuncture needle to the EA device and fixed, output frequency of EA from weak to strong (50-100hz) ,use sparse and dense mode,after 20 minutes intervention, pause the EA output, turn off the electric power ,and pulled out the needle. all the acupoint pressed by the Cotton swabs until there is no bleeding.

Maintenance of anesthesia: Patients were given continuous intraoperative inhalation of 1% sevoflurane combined with continuous intravenous propofol 5 mg.kg-1h-1 sevoflurane inhalation will be discontinued 30 minutes before the end of surgery, and propofol was stopped immediately after surgery. The inhalation concentration of sevoflurane adjusting according to the depth of anesthesia, intermittent intraoperative injection of sufentanil and cisatracurium, and other anesthetic drugs stopped at the end of surgery. All the pediatric anesthesia will be carried out by the anesthesiologists. Intraoperative BP, HR, MAP, RR, SpO2, infusion fluid and bleeding volume, total anesthetic dosage all keep record in time by the anesthesiologists. The anesthesia depth measures by Bispro (BeliveA2) and maintains between 40-60.

All patients are transferred to the PACU at the end of surgery, the patient's ECG, HR, MAP, RR, and SpO2 are monitored all the time. The tracheal tube is removed after the patient was fully awake, and recovery and extubation time keeps in record, PAED scale, Wong-bank facial expression scale, Ramsay sedation score recorded, adverse events of anesthesia like nausea, and vomiting all recorded 2 hours, 24 hours, 72 hours postoperatively; as well as anal exhaust time and defecate time. Venous blood sampling for inflammatory factors is carried out preoperative, 24 hours and 72 hours postoperatively.

In this experiment, the blinded investigator (acupuncturist) will perform the electroacupuncture intervention on the patients, the blinded investigator (assess visitor) will collect the data, and the blinded data statistician will analyze the data by computer and perform the statistical analysis. It will be performed using SPSS 17.0 statistical analysis software. All statistical tests were performed using a two-sided test, and a p-value less than or equal to 0.05 was considered a statistically significant difference.

Eligibility criteria: Inclusion Criteria:

1. Age 4-13 years old, both sexes;
2. Tonsillectomy, adenoidectomy, concealed penis, and circumcision were planned under sevoflurane intravenous inhalation combined general anesthesia;
3. The weight of the children was 10-60kg;
4. The child had no history of allergy or mental disease.
5. No respiratory tract infection within two weeks;
6. No infection at the puncture site;
7. There was no significant difference in body weight, age and operation time between the electroacupuncture group (E group) and the sevoflurane general anesthesia group（S group）.
8. The informed consent was signed by the legal guardian of the patient before surgery.

Exclusion Criteria:

1. Age \< 4 years old, age \> 13 years old;
2. Body weight \< 10kg, body weight \> 60kg;
3. The child has a history of heart disease, asthma, mental disease, and major surgery;
4. A history of respiratory infection in the past two weeks;
5. Non-electroacupuncture indications;
6. Infection at the acupuncture site;
7. Patients with liver and kidney insufficiency, cardiopulmonary insufficiency;
8. Those with allergic constitution (allergic to two or more substances);
9. Persons with legal disabilities;
10. Refusal to sign the consent form;

Primary outcomes:
measure: Pediatric Anesthesia Emergence Delirium Scale
timeFrame: 24 hours before surgery,
measure: Pediatric Anesthesia Emergence Delirium Scale
timeFrame: 2 hours after extubation in PACU
measure: Pediatric Anesthesia Emergence Delirium Scale
timeFrame: 24 hours after surgery
measure: Pediatric Anesthesia Emergence Delirium Scale
timeFrame: 72 hours after surgery
Secondary outcomes:
measure: Wong-bank(FPS-R)
timeFrame: 24 hours before surgery, 2 hours after extubation in PACU, and 24 hours and 72 hours after surgery.
measure: visual analogue scale (VAS)
timeFrame: 24 hours before surgery, 2 hours after extubation in PACU, and 24 hours and 72 hours after surgery
measure: Inflammatory markers in venous blood
timeFrame: 24 hours before surgery, 2 hours after extubation in PACU, and 24 hours and 72 hours after surgery.
measure: Sequencing analysis of the gut microbiota
timeFrame: 24 hours before surgery, 2 hours after extubation in PACU, and 24 hours and 72 hours after surgery.
Other outcomes:
measure: The wake recovery time of the patient after the operation
timeFrame: the patient is transfer to the pacu and observe 2 hours after the extubation.
Locations:
city: Changsha
country: China
facility: The First Affiliated Hospital of Hunan University of Chinese Medicine
state: Hunan
Study officials:
affiliation: Hunan University of Traditional Chinese Medicine
name: Feng Zhong, Doctor
role: PRINCIPAL_INVESTIGATOR
References: