Safety and Efficacy Evaluation of S (+) - Ketamine in Children

Study Overview
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Brief Summary
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A multicenter, randomized, open-label, active controlled pragmatic clinical trial that evaluates the safety and efficacy of S (+) -ketamine for postoperative acute pain in children in perioperative settings.

Detailed Description
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Children often suffer acute pain,awakening delirium, anxiety and depression after operation which may affect the recovery of children. S (+) - ketamine has been described to decrease acute pain and opioid consumption,but it needs to confirm for chinese children undergoing surgery. Objective: To evaluate the analgesic effect of perioperative administration of S (+) - ketamine on postoperative acute pain in children undergoing surgery, and explore the effects of S (+) - ketamine on postoperative awakening delirium, postoperative anxiety and depression mood ,as well find the best usage, including dose, timing, compatibility, and type of operation.

Official Title
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Safety and Efficacy Evaluation of S (+) -Ketamine for Postoperative Acute Pain in Children in Perioperative Settings: A Multicenter, Randomized, Open-label, Active Controlled Pragmatic Clinical Trial

Conditions
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S-ketamine, Esketamine, Acute Pain, Postoperative Pain, Analgesia, Hyperalgesia, Delirium, Depression, Anxiety, Children

Intervention / Treatment
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* Drug: Conventional therapy + S (+)-Ketamine
* Drug: Conventional therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≤17 years; Scheduled for elective digestive tract surgery, orthopedic surgery, urological surgery or ear surgery under general anesthesia; ASA physical status I～Ⅲ; The informed consent form was signed by the patients or the guardians. Exclusion Criteria: The expected length of hospital stay of the patient is less than 48h; Patients expected to be admitted to the ICU after surgery; Patients expected to return to the ward with tracheal catheter after surgery; Be allergic to S (+) - ketamine; Patients with severe disorder of consciousness or mental system diseases (schizophrenia, mania, bipolar disorder, psychosis, etc.) or cognitive dysfunction; Patients with congenital heart disease or severely developmental retardation; Patients with any of the following contraindications of S (+) - ketamine: Patients with risk of serious rise of blood pressure or intracranial pressure; Patients with high intraocular pressure (glaucoma) or penetrating ocular trauma; Patients with poorly controlled or untreated hypertension (Resting systolic blood pressure greater than 180 mmHg, or resting diastolic blood pressure greater than 100mmHg); Patients with untreated or undertreated hyperthyroidism.

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Experimental group : Control group=2:1
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S (+)-Ketamine group<br>Patients who undergo general anesthesia using S(+)-ketamine hydrochloride for anesthesia induction, maintenance or postoperative analgesia. | Drug: Conventional therapy + S (+)-Ketamine<br>* In principle, there are no specific restrictions on the dosage, mode of administration, timing, and compatibility of S-ketamine hydrochloride injection, but the recommended dosage is given, which is lower than the dosage specified in the instructions. Recommended use and dosage of S (+)-Ketamine: Intravenous injection：Bolus intravenous injection before skin incision, the dose is 0.1 0.25 mg/kg; Bolus intravenous injection (dose 0.1 0.25 mg/kg) before skin incision + continuous intravenous infusion (dose of 0.1 0.25 mg/kg/h) during operation; Continuous intravenous infusion after surgery with a dose of 0.02 0.1 mg/kg/h for 24 48 h. Intramuscular injection：The dose is 2 4 mg/kg.<br>* Other names: Conventional therapy + Esketamine;|
| Active Comparator: Control group<br>Patients who undergo conventional therapy without S (+)-Ketamine hydrochloride injection during perioperative period. | Drug: Conventional therapy<br>* Receiving conventional therapy without S (+)-Ketamine hydrochloride injection. There is no restrictions in drugs, doses and incompatibility, the researchers can choose appropriate medication regimens based on clinical practice, but other NMDA receptor antagonists are not be allowed to use, such as dextromethorphan and amantadine.<br>* Other names: Routine treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the broken line of FLACC scale score | Only for children aged 0 7 years. The score of FLACC Scale is 0-10, the higher the score, the more severe the pain. | Hour 0-48 after surgery | 
| The area under the broken line of Numerical Rating Scale score | Only for children aged 8 17years. The score of Numerical Rating Scale(NRS) is 0-10, the higher the score, the more severe the pain. | Hour 0-48 after surgery | 
| Opioid consumption | Total opioid consumption(conversion to equivalent morphine) | Hour 0-48 after surgery |