S-ketamine Prevents Postoperative Pain and Cognitive Dysfunction After Tibial Fracture

Postoperative Pain Clinical Trial

Official title:

S-ketamine Prevents Tibial Fracture-associated Postoperative Pain and Cognitive Dysfunction After Orthopedic Surgery in Patients: a Randomized Double-blind Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04643132
• Other study ID #: GWang011
• Status: Recruiting
• Phase: N/A
• Start date: December 15, 2020
• Est. completion date: December 15, 2021

Study information

• Verified date: August 2021
• Source: Tianjin Medical University General Hospital
• Contact: Guolin Wang, MD
• Phone: +8615822855556
• Email: wangguolinghad[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Purpose:

To explore effects of S-ketamine on postoperative pain and cognitive dysfunction after tibial fracture and orthopedic surgery.

To evaluate and examine the incidence of adverse effects with the purpose of selecting the optimum dose.

Description:

With the increase in human life span, orthopedic injuries and subsequent repair surgery have become a major health problem which impairs the life quality of patients and burdens healthcare systems worldwide. Poor post-surgical pain control is a leading factor that hinders the physical rehabilitation and musculoskeletal functional recovery, and causes acute cognitive impairment and chronic pain syndrome. Also, existing treatments of opioids and non-steroidal anti-inflammatory drugs have potential drawbacks, which may in turn interfere with bone healing. Therefore, prophylaxis of fracture-associated pain is indispensable to postoperative comfort and satisfaction.

There is no denying the fact that pathologic pain is related to central glutaminergic system and N-methyl-d-aspartate (NMDA) receptor activation induced central sensitization. Also, we previously reported that neuroinflammation is associated with pain development and cognitive dysfunction. Ketamine, a NMDA receptor antagonist, is effective in reversing NMDA receptor activation underlying pain states. But the side effects of ketamine limit its clinical application, such as Delirium, gibberish and agitation. It is clarified that S-ketamine has lower side effects than ketamine and that antinociception of S-ketamine is stronger than ketamine. The following study is carried out to evaluate whether S-ketamine can prevent postoperative pain and cognitive impairment after tibial fracture and orthopedic surgery in patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 15, 2021
• Est. primary completion date: November 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Subject is scheduled to undergo tibial fracture with orthopedic surgery under a short general anesthesia of less than 2 hours

2. Subject's American Society of Anesthesiologists physical status is I-II.

3. The subject's parent/legally authorized guardian has given written informed consent to participate.

Exclusion Criteria:

1. Subject has a diagnosis of bronchial asthma, coronary heart disease, severe hypertension, renal failure or liver failure.

2. Subject has a diagnosis of Insulin dependent diabetes.

3. Subject is allergy and contraindication to S-ketamine.

4. Subject has a history of chronic pain, a history of alcohol or opioid abuse, pre- existing therapy with opioids.

5. Subject has any contraindication for the use of patient-controlled analgesia (PCA).

6. Subject is pregnant or breast-feeding.

7. Subject is obese (body mass index >30kg/m^2).

8. Subject is incapacity to comprehend pain assessment and cognitive assessment.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Pain, Postoperative
• Postoperative Cognitive Dysfunction
• Postoperative Pain
• Tibial Fractures

Intervention

Drug:
• Normal saline
After the induction of anesthesia, normal saline is intravenously injected in a volume of 2ml, and then a continuous infusion of 20ml/h normal saline until starting skin suture.
• S-ketamine (low-dose)
After the induction of anesthesia, S-ketamine is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h S-ketamine until starting skin suture.
• S-ketamine (high-dose)
After the induction of anesthesia, S-ketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h S-ketamine until starting skin suture.

Locations

Country	Name	City	State
China	Tianjin Medical University General Hospital	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Tianjin Medical University General Hospital

Country where clinical trial is conducted

China, 

References & Publications (2)

Cui W, Li Y, Wang Z, Song C, Yu Y, Wang G, Li J, Wang C, Zhang L. Spinal caspase-6 regulates AMPA receptor trafficking and dendritic spine plasticity through netrin-1 in postoperative pain after orthopedic surgery for tibial fracture in mice. Pain. 2021 Jan;162(1):124-134. doi: 10.1097/j.pain.0000000000002021. — View Citation

Zhang L, Terrando N, Xu ZZ, Bang S, Jordt SE, Maixner W, Serhan CN, Ji RR. Distinct Analgesic Actions of DHA and DHA-Derived Specialized Pro-Resolving Mediators on Post-operative Pain After Bone Fracture in Mice. Front Pharmacol. 2018 May 1;9:412. doi: 10.3389/fphar.2018.00412. eCollection 2018. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mechanical hyperalgesia threshold on the palms of feet	The mechanical hyperalgesia threshold was defined as the lowest force (g) necessary to bend a Von Frey filament, which was perceived to be painful by the patient and measured by Von Frey filament.	48 hours after surgery
Secondary	Pain Score (NRS)	The pain score at rest or after movement was evaluated by pain 11-point numerical rating scale (NRS): 0 = no pain, 10 = greatest imaginable pain.	48 hours after surgery
Secondary	Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm	The mechanical hyperalgesia threshold was defined as the lowest force (g) necessary to bend a Von Frey filament, which was perceived to be painful by the patient and measured by Von Frey filament	48 hours after surgery
Secondary	Time of First Postoperative Analgesic Requirement	First postoperative pain (NRS=5) is initially controlled by titration of sufentanyl.	1 hour after surgery
Secondary	Total Dose of First Postoperative Analgesic Requirement	First postoperative pain (NRS=5) is initially controlled by titration of sufentanyl.	1 hour after surgery
Secondary	Cumulative Sufentanyl Consumption	Each patient was administered analgesics using a PCA (Patient-controlled analgesia) pump containing sufentanil (100µg) in normal saline at a total volume of 100 ml after leaving PACU (Postanesthesia care unit). This device was set to deliver a basal infusion of 2 ml/h and bolus doses of 0.5 ml with a 15-min lockout period. Sufentanyl cumulative consumption is recorded 48 hours postoperatively	48 hours after surgery
Secondary	Occurrence of Side Effects	Occurrence of side effects: nausea, vomiting, dizziness, headache, shivering, pruritus	48 hours after surgery
Secondary	Mini-Mental State Examination (MMSE)	Cognitive performance was assessed with Mini-Mental State Examination (MMSE).	48 hours after surgery