Dexmedetomidine-Esketamine Combination on Depression and Anxiety After Laparoscopic Ureteral Reconstruction

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 stuy is designed to test the hypothesis that perioperative administation of low-dose dexmedetomidine-esketamine combination may relieve postoperative depressive and anxiety symptoms in patients undergoing laparoscopic ureteral reconstruction for US.

Inclusion criteria

• Aged ≥ 18 years;
• Diagnosed with ureteral stricture and scheduled for elective laparoscopic ureteral reconstruction under general anesthesia;
• Requiring patient-controlled intravenous analgesia after surgery.

Exclusion criteria

• 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.