The Efficacy and Safety of S-ketamine in Elective Cesarean Section

The Efficacy and Safety of S-ketamine in Elective Cesarean Section: a Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Study

During the past years, a large number of clinical trials have investigated the use of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist racemic ketamine as an adjunct to local anaesthetics, opioids, or other analgesic agents for the management and prevention of postoperative pain. Actually racemic ketamine not only abolishes peripheral afferent noxious stimulation, but can also prevent the central nociceptor sensitization. S-ketamine, one of two enantiomers of racemic ketamine, has twice the analgesic potency of the racemate. Moreover, S-ketamine shows smaller nervous system and less psychotropic effects than racemic ketamine , which may make the drug more suitable for clinical use. Recently, S-ketamine has been approved to treat refractory depression (TRD) and major depressive disorder (MDD) by the FDA .S-ketamine may have greater clinical significance due to the high rate of maternal depression. Therefore, we plan to explore whether clinical use of S-ketamine can optimize anesthesia protocol and improve maternal prognosis.

Inclusion Criteria:

1. ASA II;
2. Parturients voluntarily sign an informed consent form, fully understands the purpose and significance of the study, and voluntarily abides by the clinical study procedure;
3. Subjects who plan to be elected to undergo cesarean section under continuous combined spinal-epidural anesthesia;
4. Age 18 to 40 years;
5. The expected duration of surgery was less than 2h;
6. Prenatal body mass index (BMI) was less than 35kg/m2。

Exclusion Criteria:

1. Parturients with contraindications to continuous combined spinal-epidural anesthesia (such as history of central nervous system infection, spinal cord or spinal canal disease or surgery history, systemic infection, skin or soft tissue infection at the puncture site, coagulation dysfunction);
2. Those who have a history of stroke, cognitive dysfunction, and epilepsy;
3. Patients with a history of myocardial infarction, angina pectoris, or a serious arrhythmia such as second-degree and above-degree atrioventricular block within 6 months before screening;
4. Pregnancy with other diseases (malignant tumors, hypertension during pregnancy, abnormal thyroid function, etc.);
5. In the non-oxygen state, the peripheral blood oxygen saturation (SpO2) <92%;
6. Subjects whose prolactin is greater than the upper limit of normal during the screening period;
7. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamine transferase (GGT)> 1.5 times than the normal value, and total bilirubin is higher than the upper limit of normal value, and blood creatinine (Cr)>1.2 times than the upper limit of normal value;
8. The effect of combined spinal-epidural anesthesia is not good, and other anesthetics are needed;
9. People with a history of allergies to various foods and drugs;
10. Continuous taking for any reason within 3 months before the screening, including but not limited to: ketamine, non-steroidal anti-inflammatory drugs (aspirin, acetaminophen, indomethacin, diclofenac, ibuprofen, parecoxib) Sodium, etc.), alpha adrenergic receptor agonists (dexmedetomidine hydrochloride, clonidine, etc.), glucocorticoids (dexamethasone hydrochloride, hydrocortisone, methylprednisolone, etc.), antiepileptic ( Carbamazepine, sodium valproate, etc.), sedation (diazepam, estazolam, midazolam, alprazolam, barbital, phenobarbital and chloral hydrate, etc.), Chinese herbal medicine or Chinese patent medicine with pain and sedative effect;
11. There is a history of drug abuse and/or alcohol abuse within 1 year before the screening;
12. Participated in other drug or device trials within 3 months before the screening;
13. Subjects judged by the investigator to be unsuitable to participate in this clinical study.