Perioperative Use of Dexmedetomidine-esketamine Combination on Depression and Anxiety in Patients Undergoing Laparoscopic Ureteral Reconstruction: a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 658
- 试验地点
- 1
- 主要终点
- Prevalence of depressive symptoms at postoperative day 3 / before discharge
研究概览
简要总结
Anxiety and depressive symptoms are prevalent in patients undergoing surgical repair for ureteral stricture, driven by chronic pain, renal function concerns, and surgical uncertainty. Dexmedetomidine has anxiolytic and antidepressant effects but may increase bradycardia and hypotension; esketamine provides rapid antidepressant efficacy but may cause psychiatric side effects. Preliminary studies showed that combined use of low-dose dexmedetomidine and esketamine reduced the prevalence of postoperative depressive symptoms without increasing adverse events. This study is designed to test the hypothesis that perioperative use of low-dose dexmedetomidine-esketamine combination may relieve postoperative depressive symptoms and anxiety in patients undergoing laparoscopic ureteral reconstruction.
详细描述
Ureteral stricture (US) is characterized by narrowing of the ureteral lumen, which can lead to upper urinary tract obstruction and subsequent renal impairment. The primary therapeutic goal of US is to relieve obstruction and preserve renal function. Current treatment methods include endoscopic balloon dilation, endoureterotomy, ureteral dilation, and ureteral reconstruction surgery. Among these, ureteral reconstruction surgery is highly effective, especially for complex strictures exceeding 2 cm in length.
Patients with US often endure prolonged symptom burden and substantial medical costs, and are prone to emotional disturbances such as anxiety and depression. A multicenter prospective study reported that the preoperative prevalence of anxiety and depressive syndromes in US patients scheduled for surgery was 31.3% and 20.7%, respectively, with iatrogenic US and urinary symptoms being the strongest predictors of increased levels of anxiety and depression. Perioperative stress may further exacerbate the severity of anxiety and depressive symptoms, leading to increased intraoperative anesthetic and analgesic requirements, delayed emergence from anesthesia, and higher risks of postoperative delirium and sleep disturbances.
Dexmedetomidine is a highly selective α2-adrenergic receptor agonist with sedative, analgesic, and anxiolytic properties. It also exerts antidepressant effects through multiple mechanisms. Clinical studies have confirmed its efficacy in alleviating postoperative anxiety and depression across various surgical populations. Esketamine, the S-enantiomer of ketamine, is an N-methyl-D-aspartate (NMDA) receptor antagonist with anesthetic, analgesic, and rapid-onset antidepressant effects. Perioperative studies also confirmed the efficacy of esketamine in relieving postoperative depressive symptoms.
Routine dose esketamine may cause psychiatric side effects such as dissociative symptoms and hallucinations; administration of low-dose esketamine attenuates these side effects but may weaken the antidepressant efficacy. The sedative properties of dexmedetomidine can mitigate the side effects of esketamine. Furthermore, the combined use of low-dose dexmedetomidine and esketamine may offer synergistic anxiolytic and antidepressant effects with a favorable safety profile.
This study is designed to test the hypothesis that perioperative administration of low-dose dexmedetomidine-esketamine combination may relieve postoperative depressive and anxiety symptoms in patients undergoing laparoscopic ureteral reconstruction for US.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Aged ≥ 18 years;
- •Diagnosed with ureteral stricture and scheduled for elective laparoscopic ureteral reconstruction under general anesthesia;
- •Requiring patient-controlled intravenous analgesia after surgery.
排除标准
- •Preoperative inability to communicate due to coma, delirium, severe dementia, or language barrier;
- •History of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis;
- •Presence of preexisting left ventricular ejection fraction (LVEF) < 30%, sick sinus syndrome, severe sinus bradycardia (heart rate < 50 beats/min), or atrioventricular block above grade II without pacemaker implanted;
- •Uncontrolled hyperthyroidism or history of pheochromocytoma;
- •Severe hepatic insufficiency (Child-Pugh Class C), severe renal insufficiency (required preoperative dialysis), or American Society of Anesthesiologists (ASA) physical status classification ≥ IV;
- •Allergy to dexmedetomidine and/or esketamine;
- •Other conditions deemed unsuitable for study participation by the investigators.
研究组 & 干预措施
Combined dexmedetomidine-esketamine group
During anesthesia, a loading dose (0.8 ml/kg/h) of dexmedetomidine-esketamine (DEX-ESK) combination (DEX 1 ug/ml; ESK 0.5 mg/ml) will be infused after anesthesia induction for 30 min (DEX 0.4 ug/kg; ESK 0.2 mg/kg), followed by a continuous infusion at 0.1 ml/kg/h (DEX 0.1 ug/kg/h; ESK 0.05 mg/kg/h) until 1 hour before the expected end of surgery.
After surgery, patient-controlled intravenous analgesia will be established with dexmedetomidine (DEX 1.5 ug/ml), esketamine (ESK 0.25 mg/ml), and sufentanil (1.0 ug/ml), programmed to deliver 2-ml boluses (DEX 3.0 ug, ESK 0.5 mg, and sufentanil 2.0 ug) with an 8-minute lockout interval and a 1-ml/h (DEX 1.5 ug/h, ESK 0.25 mg/h, and sufentanil 1.0 ug/h) background infusion, and used for up to 48 hours.
干预措施: Combined dexmedetomidine-esketamine administration (Drug)
Placebo group
During anesthesia, a loading dose (0.8 ml/kg/h) of normal saline will be infused after anesthesia induction for 30 min, followed by a continuous infusion at 0.1 ml/kg/h until 1 hour before the expected end of surgery.
After surgery, patient-controlled intravenous analgesia will be established with sufentanil (1.0 ug/ml), programmed to deliver 2-ml boluses (sufentanil 2.0 ug) with an 8-minute lockout interval and a 1-ml/h (sufentanil 1.0 ug/h ) background infusion, and used for up to 48 hours.
干预措施: Placebo administration (Drug)
结局指标
主要结局
Prevalence of depressive symptoms at postoperative day 3 / before discharge
时间窗: At postoperative day 3 or before hospital discharge.
Depressive symptoms will be screened using the Patient Health Questionnaire-9 (PHQ-9; total scores range from 0 to 27, with higher scores indicating more severe symptoms). A PHQ-9 score ≥5 is defined as presence of depressive symptoms.
Prevalence of depressive symptoms on postoperative day 7
时间窗: On postoperative day 7.
Depressive symptoms will be screened using the Patient Health Questionnaire-9 (PHQ-9; total scores range from 0 to 27, with higher scores indicating more severe symptoms). A PHQ-9 score ≥5 is defined as presence of depressive symptoms.
次要结局
- Incidence of moderate-to-severe catheter-related bladder discomfort (CRBD) within 24 hours after surgery(Up to 24 hours after surgery.)
- Prevalence of anxiety symptoms at postoperative day 3 / before discharge(At postoperative day 3 or before hospital discharge.)
- Prevalence of depressive symptoms at 30 days after surgery(At 30 days after surgery.)
- Prevalence of anxiety symptoms on postoperative day 7(On postoperative day 7.)
- Prevalence of depressive symptoms 30 days after surgery(At 30 days postoperatively.)
研究者
Dong-Xin Wang
Professor and Chairman, Department of Anesthesiology
Peking University First Hospital