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

Not Applicable
Conditions
Postoperative Cognitive Dysfunction
Postoperative Pain
Interventions
Registration Number
NCT04643132
Lead Sponsor
Tianjin Medical University General Hospital
Brief 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.

Detailed 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 & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
120
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.
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
S-ketamine at low dose in patientsS-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 at high dose in patientsS-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.
Normal saline in patientsNormal salineAfter the induction of anesthesia, normal saline is intravenously injected in a volume of 2ml, and then a continuous infusion of 20 ml/h normal saline until starting skin suture.
Primary Outcome Measures
NameTimeMethod
Mechanical hyperalgesia threshold on the palms of feet48 hours after surgery

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.

Secondary Outcome Measures
NameTimeMethod
Pain Score (NRS)48 hours after surgery

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.

Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm48 hours after surgery

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

Time of First Postoperative Analgesic Requirement1 hour after surgery

First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.

Total Dose of First Postoperative Analgesic Requirement1 hour after surgery

First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.

Cumulative Sufentanyl Consumption48 hours after surgery

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

Occurrence of Side Effects48 hours after surgery

Occurrence of side effects: nausea, vomiting, dizziness, headache, shivering, pruritus

Mini-Mental State Examination (MMSE)48 hours after surgery

Cognitive performance was assessed with Mini-Mental State Examination (MMSE).

Trial Locations

Locations (1)

Tianjin Medical University General Hospital

🇨🇳

Tianjin, China

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