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.

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.

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.