Impact of Perioperative Dexmedetomidine and Esketamine on Postoperative Quality of Recovery

Peking University

Status and phase: Not yet enrolling; Phase 4

Conditions: Quality of Recovery; Esketamine; Dexmedetomidine; Surgery; General Anesthesia

Treatments: Drug: Dexmedetomidine; Drug: Esketamine; Drug: Placebo; Drug: Dexmedetomidine-esketamine

Study type: Interventional

Funder types: Other

Identifiers

NCT07308756

2025-0455

Details and patient eligibility

About

For patients after surgery, quality of recovery has significant impacts on the prognosis, quality of life, and rational allocation of medical resources. Dexmedetomidine and esketamine have each been used during the perioperative period and improved postoperative analgesia and subjective sleep quality. This 2x2 factorial trial is designed to explore the effects of dexmedetomidine, esketamine, and their combination on the quality of recovery in patients recovering from surgery under general anesthesia.

Full description

Surgical operation is an important therapeutic modality for surgical patients; quality of postoperative recovery has significant impacts on the prognosis, quality of life, and rational allocation of medical resources. Postoperative recovery is a complex process involving return of patients from surgery to baseline physiological and psychological status. Traditional indicators evaluating postoperative recovery mainly focus on physiological markers, length of hospital stay (LOS), and incidences of adverse events and complications. Recently, the quality of recovery (QoR) is increasingly used. QoR is subjectively reported by patients and includes multidimensional assessments on postoperative pain, cognitive function, sleep quality, and emotional stability.

Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, has anxiolytic, sedative, and analgesic effects. By activing α2-adrenergic receptors in the locus coeruleus, it activates the endogenous sleep pathways, and produce a state mimicking non-rapid eye movement (NREM) sleep. Clinical studies showed that perioperative use of low-dose dexmedetomidine improves sleep architecture, increases sleep efficiency, and prolongs total sleep time in non-mechanically ventilated patients. Furthermore, when used as an analgesic adjuvant, dexmedetomidine improves analgesia, reduces opioid consumption, and reduces opioid-related adverse events.

Ketamine, a non-competitive N-Methyl-D-aspartic (NMDA) receptor antagonist, exerts analgesic and anti-hyperalgesic effects by reducing transmission of noxious stimuli to the spinal cord. It is characterized by minimal respiratory and circulatory depression and excellent analgesic efficacy. In recent years, multiple studies confirmed that ketamine has antidepressant properties. Ketamine is a racemic mixture composed of S-ketamine (esketamine) and R-ketamine. Esketamine exhibits a stronger affinity for the NMDA receptor, with an effect approximately twice that of racemic ketamine. In clinical practice, esketamine has stronger analgesic effects and a lower incidence of adverse psychomimetic reactions. When used in combination with opioids, esketamine improved postoperative analgesia.

Previous studies showed that combined use of dexmedetomidine and esketamine might produce synergetic effects in improving sedation and analgesia. A recent trial found that low-dose dexmedetomidine-esketamine combination improved pain relief and subjective sleep quality in patients after scoliosis corrective surgery, without increasing side effects. It is therefore hypothesized that co-administration of dexmedetomidine and esketamine may enhance efficacy and optimize the quality of postoperative recovery. This 2x2 factorial trial is designed to explore the effects of dexmedetomidine, esketamine, and their combination on the quality of recovery in patients recovering from surgery under general anesthesia.

Enrollment: 316 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged 18 years or over;
• Scheduled to undergo surgery under general anesthesia, with an expected surgical duration of at least 1 hour;
• Required patient-controlled intravenous analgesia after surgery.

Exclusion criteria

• Unable to communicate preoperatively due to visual, auditory, or verbal barriers or other reasons;
• Severe bradycardia (heart rate <50 bpm), sick sinus syndrome, or grade 2 or higher atrioventricular block without pacemaker;
• History of hyperthyroidism or pheochromocytoma;
• History of schizophrenia, epilepsy, Parkinson's disease, myasthenia gravis, or intracranial hypertension;
• Intracranial tumor or neurosurgery;
• Severe liver dysfunction (Child-Pugh class C), renal failure (requiring renal replacement therapy), or American Society of Anesthesiologists class IV or higher;
• Enrolled in other clinical studies.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

---

316 participants in 4 patient groups, including a placebo group

Dexmedetomidine

Experimental group

Description:

A loading dose of dexmedetomidine (0.2 ug/kg) is administered after anesthesia induction, followed by a continuous infusion of dexmedetomidineat a rate of 0.2 ug/kg/h until 30 minutes before the end of surgery. Self-controlled analgesia is established with dexmedetomidine 100 ug and sufentanil 100 ug, diluated with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a lock-out interval of 10 minutes and a background infusion rate at 1 ml/h for a duration of 48 hours.

Treatment:

Drug: Dexmedetomidine

Esketamine

Experimental group

Description:

A loading dose of esketamine (0.1 mg/kg) is administered after anesthesia induction, followed by a continuous infusion of esketamineat a rate of 0.1 mg/kg/h until 30 minutes before the end of surgery. Self-controlled analgesia is established with esketamine 50 mg and sufentanil 100 ug, diluated with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a lock-out interval of 10 minutes and a background infusion rate at 1 ml/h for a duration of 48 hours.

Treatment:

Drug: Esketamine

Dexmedetomidine-esketamine

Experimental group

Description:

A loading dose of dexmedetomidine (0.2 ug/kg) and esketamine (0.1 mg/kg) is administered after anesthesia induction, followed by a continuous infusion of dexmedetomidine at a rate of 0.2 ug/kg/h and esketamine at a rate of 0.1 mg/kg/h until 30 minutes before the end of surgery. Self-controlled analgesia is established with dexmedetomidine 100 ug, esketamine 50 mg, and sufentanil 100 ug, diluated with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a lock-out interval of 10 minutes and a background infusion rate at 1 ml/h for a duration of 48 hours.

Treatment:

Drug: Dexmedetomidine-esketamine

Control

Placebo Comparator group

Description:

A loading dose of placebo (normal saline) is administered after anesthesia induction, followed by a continuous infusion of placebo at a rate same as above until 30 minutes before the end of surgery. Self-controlled analgesia is established with sufentanil 100 ug, diluated with normal saline to 100 ml, and programmed to deliver 2-ml boluses with a lock-out interval of 10 minutes and a background infusion rate at 1 ml/h for a duration of 48 hours.

Treatment:

Drug: Placebo