Spinal SurgeryPhase 4NCT07523321
Dexmedetomidine-esketamine Combination and Moderate-to-severe Pain After Spinal Surgery
A Phase 4 study testing Combined dexmedetomidine-esketamine administration in people with Spinal Surgery and Pain Intensity, run by Peking University First Hospital at 1 site in China.
Trial summary
Spinal surgery is generally followed by severe postoperative pain, and poor pain control may cause adverse outcomes such as cardiovascular events, neurocognitive disorders, and chronic postsurgical pain (CPSP). Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Spinal Surgery, Pain Intensity, Dexmedetomidine
- What is being tested?
- Combined dexmedetomidine-esketamine administration
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 274 participants
- Where
- 1 siteChina
- Study dates
- Apr 2026to May 2027
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged >= 40 years but < 80 years;
- Scheduled to undergo elective posterior cervical, thoracic, or lumbar spine surgery with an expected duration >= 2 hours under general anesthesia;
- Required patient-controlled intravenous analgesia (PCIA) after surgery.
Who cannot join
- Uncontrolled preoperative hypertension (ward systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg);
- Severe bradycardia (heart rate <= 50 bpm), sick sinus syndrome, atrioventricular block of grade II or higher without pacemaker implantation, a history of myocardial infarction within one year, or presence of rapid ventricular arrhythmia;
- History of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis, or prresence of intracranial hypertension;
- Uncontrolled hyperthyroidism or pheochromocytoma;
- Inability to communicate due to coma, severe dementia, or language barrier;
- Severe cardiac insufficiency (preoperative left ventricular ejection fraction < 30% or New York Heart Association Functional classification IV), severe hepatic dysfunction (Child-Pugh class C), severe renal dysfunction (preoperative dialysis), or American Society of Anesthesiologists physical status >= IV;
- Other conditions that are considered unsuitable for study participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Huai-Jin Li, MD contact
China1 site
Peking University First Hospital
Beijing, Beijing Municipality, 100034
Huai-Jin Li, MD, 01083572784, sophie.lee.coffee@gmail.com
About this study
Official title: Effect of Perioperative Use of Dexmedetomidine-esketamine Combination on Incidence of Moderate-to-severe Pain After Spinal Surgery: a Randomized Controlled Trial
Spinal surgery is generally followed by severe postoperative pain, and poor pain control may cause adverse outcomes such as cardiovascular events, neurocognitive disorders, and chronic postsurgical pain (CPSP). In previous studies, perioperative use of dexmedetomidine or esketamine is each associated with improved analgesia after surgery. Recent studies suggest that combined use of dexmedetomidine and esketamine may produce synergetic effects in improving analgesia. This trial is designed to test the hypothesis that perioperative combined use of dexmedetomidine and esketamine may improve analgesia and reduce moderate-to-severe pain in patients after spinal surgery.
Read the detailed description
Spinal surgery is genrally followed by severe pain due to extensive trauma. The reported rate of moderate-to-severe pain ranged from 30% to 63%. Uncontrolled postoperative pain is associated with worse outcomes including cardiovascular events, neurocognitive complications, and chronic postsurgical pain. Opioids are the main stay of analgesia after spinal surgery. However, high dose opioids provoke side effects such as nausea and vomiting, delirium, and even respiratory depression. Multimodel analgesia is suggested for these patients.
Dexmedetomidine is a highly selective alpha 2 adrenergic receptor agonist with sedative, analgesic, and anxiolytic effects. A meta-analysis suggest that, for patients undergoing spinal surgery, intraoperative dexmedetomidine improved early postoperative analgesia, but the effect did not persist beyond 6 hours. Ketamine is a noncompetitive N-Methyl-D-aspartic acid (NMDA) receptor antagonist and has been used as an anesthetic and analgesic for decades. Esketamine is the S-enantiomer of ketamine and has an analgesic potent of approximately 2 times of that of ketamine. Small sample size studies in patients undergoing spinal surgery showed that intra- or postoperative use of subanesthetic dose esketamine improved analgesia and reduced rescue analgesics.
The analgesic effects of dexmedetomidine and esketamine are dose-dependent. However, routine dose dexmedetomidine may increase bradycardia and hypotension, and even subanethetic dose esketamine may produce neuropsychiatric symptoms. Combined use of dexmedetomdine and esketamine may augment analgesic and sedative effects while decreasing side effects. In a previous study, using low-dose dexmedetomidine (1 ug/ml) and esketamine (0.25 mg/ml) as supplements to self-controlled sufentanil analgesia improved pain relief and sleep quality after spinal surgery, but the rate of moderate-to-severe pain remained high. In a recent study, when used as a supplement to sufentanil analgesia, increasing esketamine dose to 0.5 mg/ml did not significantly improve analgesia, whereas increasing esketamine dose to 0.75 mg/ml increased nausea and vomiting.
In available studies, use of dexmedetomidine and/or esketamine were mostly limited to either intra- or postoperative period. Introperative use of the combination only improve early postoperative analgesia. Whereas postoperative use of the combination did not have effects on peak intraoperative stress. It is reasonable to hypothesize that using dexmedetomidine-esketamine combination during both the intra- and postoperative periods may provide better analgesia in patients after spinal surgery.
- Being tested
- Combined dexmedetomidine-esketamine administration, Placebo administration
- Keywords
- Spinal surgery, Pain intensity, Dexmedetomidine, Esketamine, Postoperative analgesia
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combined dexmedetomidine-esketamine administrationDrug
Also called Dexmedetomidine and esketamine
During anesthesia, a loading dose (0.2 ml/kg) of dexmedetomidine-esketamine (DEX-ESK) combination (DEX 2 ug/ml; ESK 1 mg/ml) will be infused after anesthesia induction (DEX 0.4 ug/kg; ESK 0.2 mg/kg), followed by a continuous infusion at 0.1 ml/kg/h (DEX 0.2 ug/kg/h; ESK 0.1 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 0.5 mg/ml), and sufentanil (1.25 ug/ml), programmed to deliver 2-ml boluses (DEX 3.0 ug, ESK 1 mg, and sufentanil 2.5 ug) with a 8-10-minute lockout interval and a 1-ml/h (DEX 1.5 ug/h, ESK 0.5 mg/h, and sufentanil 1.25 ug/h) background infusion, and used for up to 48 hours.
Placebo administrationDrug
Also called Placebo (normal saline)
During anesthesia, a loading dose (0.2 ml/kg) of normal saline will be infused after anesthesia induction, 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 (1.25 ug/ml), programmed to deliver 2-ml boluses (sufentanil 2.5 ug) with a 8-10-minute lockout interval and a 1-ml/h (sufentanil 1.25 ug/h) background infusion, and used for up to 48 hours.
| Study group | Role | What they receive |
|---|---|---|
| Combined dexmedetomidine-esketamine group | Experimental | During anesthesia, a loading dose (0.2 ml/kg) of dexmedetomidine-esketamine (DEX-ESK) combination (DEX 2 ug/ml; ESK 1 mg/ml) will be infused after anesthesia induction (DEX 0.4 ug/kg; ESK 0.2 mg/kg), followed by a continuous infusion at 0.1 ml/kg/h (DEX 0.2 ug/kg/h; ESK 0.1 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 0.5 mg/ml), and sufentanil (1.25 ug/ml), programmed to deliver 2-ml boluses (DEX 3.0 ug, ESK 1 mg, and sufentanil 2.5 ug) with a 8-10-minute lockout interval and a 1-ml/h (DEX 1.5 ug/h, ESK 0.5 mg/h, and sufentanil 1.25 ug/h) background infusion, and used for up to 48 hours. Receives: Drug: Combined dexmedetomidine-esketamine administration |
| Placebo group | Placebo comparator | During anesthesia, a loading dose (0.2 ml/kg) of normal saline will be infused after anesthesia induction, 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 (1.25 ug/ml), programmed to deliver 2-ml boluses (sufentanil 2.5 ug) with a 8-10-minute lockout interval and a 1-ml/h (sufentanil 1.25 ug/h) background infusion, and used for up to 48 hours. Receives: Drug: Placebo administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of moderate-to-severe pain within 72 hours after surgery
Pain intensity will be assessed at 1 and 6 hours, and then twice daily (8:00-10:00, 18:00-20:00) until 72 hours after surgery, using the Numerical Rating Scale (NRS; an 11-point scale where 0=no pain and 10=the worst pain) both at rest and with movement (e.g., bed turning, walking). NRS pain scores 1-3 points indicate mild pain, 4-6 points indicate moderate pain, and 7-10 points indicate severe pain.
Measured: Up to 72 hours after surgery
Secondary outcomes (2)
Incidence of delayed neurocognitive recovery at postoperative day 5
Cognitive function will be assessed with the Montreal Cognitive Assessment (MoCA; scores range from 0 to 30, with higher scores indicating better function) at baseline and on the 5th day or before hospital discharge after surgery. Delayed neurocognitive recovery is defined as a decline of MoCA score of >= 1 stndard deviation (SD) from baseline.
Measured: Up to 5 days after surgery
Incidence of cardiovascular events within 30 days after surgery
Cardiovascular events include myocardial injury after non-cardiac surgery (MINS; including myocardial infarction), non-fatal cardiac arrest, stroke, and all-cause mortality. The diagnosis of MINS will strictly follow the consensus of the American Heart Association (AHA).
Measured: Up to 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2026
- Study startApr 2026 (estimated)
- Primary completionApr 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (48)Papers the sponsor has linked to this study.
- Other trials for Spinal SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 274 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University First Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dong-Xin Wang, Peking University First Hospital
- Investigators
- Dong-Xin Wang, Principal investigator, Peking University First Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07523321
- Sponsor's protocol ID
- 2026-0136
- Status last verified
- Apr 2026
- First submitted
- 4 Apr 2026
- Last updated
- 14 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011 May;46(3):399-424. doi: 10.1080/00273171.2011.568786. Epub 2011 Jun 8.
PubMed 21818162Ruetzler K, Smilowitz NR, Berger JS, Devereaux PJ, Maron BA, Newby LK, de Jesus Perez V, Sessler DI, Wijeysundera DN. Diagnosis and Management of Patients With Myocardial Injury After Noncardiac Surgery: A Scientific Statement From the American Heart Association. Circulation. 2021 Nov 9;144(19):e287-e305. doi: 10.1161/CIR.0000000000001024. Epub 2021 Oct 4.
PubMed 34601955Weir S, Samnaliev M, Kuo TC, Ni Choitir C, Tierney TS, Cumming D, Bruce J, Manca A, Taylor RS, Eldabe S. The incidence and healthcare costs of persistent postoperative pain following lumbar spine surgery in the UK: a cohort study using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES). BMJ Open. 2017 Sep 11;7(9):e017585. doi: 10.1136/bmjopen-2017-017585.
PubMed 28893756Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, Cohen M, Evers S, Finnerup NB, First MB, Giamberardino MA, Kaasa S, Kosek E, Lavand'homme P, Nicholas M, Perrot S, Scholz J, Schug S, Smith BH, Svensson P, Vlaeyen JWS, Wang SJ. A classification of chronic pain for ICD-11. Pain. 2015 Jun;156(6):1003-1007. doi: 10.1097/j.pain.0000000000000160. No abstract available.
PubMed 25844555Rodrigues NB, McIntyre RS, Lipsitz O, Lee Y, Cha DS, Shekotikhina M, Vinberg M, Gill H, Subramaniapillai M, Kratiuk K, Lin K, Ho R, Mansur RB, Rosenblat JD. A simplified 6-Item clinician administered dissociative symptom scale (CADSS-6) for monitoring dissociative effects of sub-anesthetic ketamine infusions. J Affect Disord. 2021 Mar 1;282:160-164. doi: 10.1016/j.jad.2020.12.119. Epub 2020 Dec 29.
PubMed 33418362Busse JW, Bartlett SJ, Dougados M, Johnston BC, Guyatt GH, Kirwan JR, Kwoh K, Maxwell LJ, Moore A, Singh JA, Stevens R, Strand V, Suarez-Almazor ME, Tugwell P, Wells GA. Optimal Strategies for Reporting Pain in Clinical Trials and Systematic Reviews: Recommendations from an OMERACT 12 Workshop. J Rheumatol. 2015 Oct;42(10):1962-1970. doi: 10.3899/jrheum.141440. Epub 2015 May 15.
PubMed 25979719Zhang Y, Cui F, Ma JH, Wang DX. Mini-dose esketamine-dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial. Br J Anaesth. 2023 Aug;131(2):385-396. doi: 10.1016/j.bja.2023.05.001. Epub 2023 Jun 9.
PubMed 37302963Junior AB Jr, Bendazzoli PS, Ferreira Melo FW Jr, Porto Franco RM, de Sousa Rocha EM, Matos Lima RD, Brondi EB. Efficacy and Safety of the Ketamine-Dexmedetomidine Combination in Adult Sedation and Anesthesia: A Systematic Review and Single-Arm Meta-Analysis of Randomized Controlled Trials. Cureus. 2025 Nov 21;17(11):e97432. doi: 10.7759/cureus.97432. eCollection 2025 Nov.
PubMed 41431543Raymond BL, Allen BFS, Freundlich RE, McEvoy MD, Parrish CG, Ruble SR, Scharfman KH, Wanderer JP, Gao Y, Choi L, Dear ML, Master H, Rice TW, Kertai MD; Vanderbilt Learning Healthcare System Platform Investigators. IMpact of PerioperAtive KeTamine on Enhanced Recovery After abdominal Surgery (IMPAKT ERAS): a pragmatic randomised single-cluster trial. Br J Anaesth. 2025 Dec;135(6):1770-1778. doi: 10.1016/j.bja.2025.08.001. Epub 2025 Sep 3.
PubMed 40903379Verret M, Le JBP, Lalu MM, Jeffers MS, McIsaac DI, Nicholls SG, Turgeon AF, Ramchandani R, Li H, Hutton B, Zivkovic F, Graham M, Le M, Geist A, Berube M, O'Hearn K, Gilron I, Poulin P, Daudt H, Martel G, McVicar J, Moloo H, Fergusson DA. Effectiveness of dexmedetomidine on patient-centred outcomes in surgical patients: a systematic review and Bayesian meta-analysis. Br J Anaesth. 2024 Sep;133(3):615-627. doi: 10.1016/j.bja.2024.06.007. Epub 2024 Jul 16.
PubMed 39019769Brinck ECV, Virtanen T, Makela S, Soini V, Hynninen VV, Mulo J, Savolainen U, Rantakokko J, Maisniemi K, Liukas A, Olkkola KT, Kontinen V, Tarkkila P, Peltoniemi M, Saari TI. S-ketamine in patient-controlled analgesia reduces opioid consumption in a dose-dependent manner after major lumbar fusion surgery: A randomized, double-blind, placebo-controlled clinical trial. PLoS One. 2021 Jun 7;16(6):e0252626. doi: 10.1371/journal.pone.0252626. eCollection 2021.
PubMed 34097713Hou NN, Zhang MY, Zhang YW, Wu HJ, Luo H, Yang H. Safety and efficacy of low-dose esketamine weakly opioidized anesthesia in elderly patients with lumbar spinal stenosis undergoing surgery: a prospective, double-blind randomized controlled trial. BMC Anesthesiol. 2025 Feb 5;25(1):57. doi: 10.1186/s12871-025-02908-3.
PubMed 39910473Liu J, Wang T, Song J, Cao L. Effect of esketamine on postoperative analgesia and postoperative delirium in elderly patients undergoing gastrointestinal surgery. BMC Anesthesiol. 2024 Feb 1;24(1):46. doi: 10.1186/s12871-024-02424-w.
PubMed 38302882O'Sullivan R, Inouye SK, Meagher D. Delirium and depression: inter-relationship and clinical overlap in elderly people. Lancet Psychiatry. 2014 Sep;1(4):303-11. doi: 10.1016/S2215-0366(14)70281-0. Epub 2014 Aug 10.
PubMed 26360863Elsamadicy AA, Adogwa O, Lydon E, Sergesketter A, Kaakati R, Mehta AI, Vasquez RA, Cheng J, Bagley CA, Karikari IO. Depression as an independent predictor of postoperative delirium in spine deformity patients undergoing elective spine surgery. J Neurosurg Spine. 2017 Aug;27(2):209-214. doi: 10.3171/2017.4.SPINE161012. Epub 2017 Jun 2.
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