Safety and Efficacy Evaluation of S（+）-Ketamine for Postoperative Acute Pain in Adults in Perioperative Settings: A Multicenter, Randomized, Open-label, Active Controlled Pragmatic Clinical Trial
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 12,000
- 主要终点
- Opioid consumption
研究概览
简要总结
A multicenter, randomized, open-label, active controlled pragmatic clinical trial that evaluates the safety and efficacy of S (+) -ketamine for postoperative acute pain in adults in perioperative settings.
详细描述
Patients often suffer acute pain after operation ，which may affect the recovery. Opioid such as morphine is the most commonly analgesic drugs, but opioid has many obviously adverse reactions ,for example respiratory depression,circulation inhibition,tolerance, addiction, nausea, vomiting, pruritus, etc. S (+) - ketamine has been described to decrease acute pain and opioid consumption,but it needs to confirm for chinese patients undergoing surgery.
Objective
Evaluate the efficacy and safety of S (+) - ketamine on acute perioperative pain for chinese adult patients,and look for the best dosage, mode of administration, timing, and compatibility ,as well explore the effect of S (+) - ketamine on postoperative delirium,anxiety ,depression and cognitive dysfunction.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years old;
- •Scheduled for elective digestive tract surgery, gynecological surgery, urological surgery, thoracic surgery, orthopedic limb surgery, orthopedic spine surgery or body surface surgery (thyroid surgery or breast surgery), head and neck surgery;
- •ASA score Ⅰ～Ⅲ;
- •The informed consent form was signed by the patients.
排除标准
- •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 a history of severe cardiovascular disease (congestive heart failure, severe angina attack, or unstable angina or myocardial infarction within 6 months);
- •Patients during pregnancy or lactation;
- •Patients with MMSE score <18 points;
- •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.
研究组 & 干预措施
S (+)-Ketamine group
Drug: Conventional therapy + S (+)-Ketamine 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:
- Bolus intravenous injection before skin incision, the dose is 0.1~0.5 mg/kg;
- Bolus intravenous injection (dose 0.1~0.5 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.
干预措施: Conventional therapy + S (+)-Ketamine (Drug)
Control group
Drug: Conventional therapy 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.
干预措施: Conventional therapy (Drug)
结局指标
主要结局
Opioid consumption
时间窗: Hour 0-48 after surgery
Total opioid consumption(conversion to equivalent morphine)
The area under the broken line of NRS score
时间窗: Hour 0-48 after surgery
The score of Numerical Rating Scale(NRS) is 0-10, the higher the score, the more severe the pain.
次要结局
- Simple Mental State Examination (MMSE) Scale score(Hour 48 after surgery)
- NRS pain scores(Hour 0-48 after surgery)
- Time of first rescue analgesia(Hour 0-48 after surgery)
- The incidence of rescue analgesia(Hour 0-48 after surgery)
- The Patient Efficacy Questionnaire (IPOQ ) scores(Hour 48 after surgery)
- The incidence of adverse events after surgery(Hour 0-48 after surgery)
- Recovery time(Day 0)
- The incidence of unexpected intraoperative events(Intraoperative)
- Pharmacoeconomic indicators(Hour 48 after surgery)
- Incidence of postoperative delirium(Hour 0-48 after surgery)
- Hospital Anxiety and Depression (HAD) Scale score(Hour 48 after surgery)
研究者
Weidong Mi
Director of the Department of Anesthesiology, Chinese PLA General Hospital
Chinese PLA General Hospital