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

NCT04657107 | Unknown

• 1 other identifier: BeijingOGH
• Study Type: interventional
• Target: 402
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Anesthesia; Analgesia; Depression; Cesarean Section; Parturition

Keywords

S-ketamine; efficacy; safety; Postpartum depression

Outcome Measures

Primary Outcomes (3)

• Intraoperative anesthesia effect

  Anesthesia effect is graded I-IV. Level I means that it is very satisfactory, while Level IV means other anesthesia methods are needed to complete the operation. We expect to reach level I.

  Day 1

• Ramsay Sedation Scale score

  The Ramsay Sedation Scale (RSS) was the first scale to be defined for sedated patients and was designed as a test of rousability. The RSS scores sedation at six different levels, according to how rousable the patient is.

  Day 1

• Clock-in-the-Box(CIB)

  The Clock-in-the-Box (CIB) is a rapidly administered cognitive screening measure which has been previously validated with cognitive screening and neuropsychological assessments. The CIB is scored on a 0-8 point scale and the total score includes two separate subscale scores. The higher scores reflect better performance.

  Day 0 & Day 2

Secondary Outcomes (6)

• PHQ-9

  Day 0 & Day 3 & Day 8 & Day 43

• Edinburgh Postnatal Depression Scale(EPDS)

  Day 3 & Day 8 & Day 43

• Apgar score

  Day 0

• placental transfer of S-ketamine

  Day 0

• blood gas

  Day 0

Study Arms (3)

Saline group

PLACEBO COMPARATOR

Parturients were subsequently placed in a supine position with a left lateral tilt (15 ̊). Combined spinal-epidural anesthesia method (CSE) was performed at the L2-L3 or L3-L4 lumbar vertebral interspace, with 10～13mg 0.5% ropivacaine by a needle-through-needle technique. When adequate anesthesia to the T6 dermatome was achieved (Sensory and motor assessments were performed at 1 min intervals using pinprick testing and the modified Bromage score). Parturients received 10ml intravenous normal saline before surgery, If the anesthesia is inadequate, another 5ml 0.5% ropivacaine was given. Morphine hydrochloride 1 mg in saline 10 mL was injected by several times into the epidural space at the end of the operation. After the surgery, their PCA protocol consisted of 150 ug sufentanil and 24ml atropisetron diluted into 150 ml (2ml of basal infusion, a bolus of 0.5ml on demand, "lock-out" interval of 10 min, last for 48 h postoperatively);

Other: normal saline

K1 group

EXPERIMENTAL

Parturients were subsequently placed in a supine position with a left lateral tilt (15 ̊). Combined spinal-epidural anesthesia method (CSE) was performed at the L2-L3 or L3-L4 lumbar vertebral interspace, with 10～13mg 0.5% ropivacaine by a needle-through-needle technique. When adequate anesthesia to the T6 dermatome was achieved (Sensory and motor assessments were performed at 1 min intervals using pinprick testing and the modified Bromage score). Parturients received 10ml intravenous 0.2mg/kg before surgery, If the anesthesia is inadequate, another 5ml 0.5% ropivacaine was given. Morphine hydrochloride 1 mg in saline 10 mL was injected by several times into the epidural space at the end of the operation. After the surgery, their PCA protocol consisted of 150 ug sufentanil and 24ml atropisetron diluted into 150 ml (2ml of basal infusion, a bolus of 0.5ml on demand, "lock-out" interval of 10 min, last for 48 h postoperatively);

Drug: S-ketamine

K2 group

EXPERIMENTAL

Parturients were subsequently placed in a supine position with a left lateral tilt (15 ̊). Combined spinal-epidural anesthesia method (CSE) was performed at the L2-L3 or L3-L4 lumbar vertebral interspace, with 10～13mg 0.5% ropivacaine by a needle-through-needle technique. When adequate anesthesia to the T6 dermatome was achieved (Sensory and motor assessments were performed at 1 min intervals using pinprick testing and the modified Bromage score). Parturients received 10ml intravenous 0.3mg/kg before surgery, If the anesthesia is inadequate, another 5ml 0.5% ropivacaine was given. Morphine hydrochloride 1 mg in saline 10 mL was injected by several times into the epidural space at the end of the operation. After the surgery, their PCA protocol consisted of 150 ug sufentanil and 24ml atropisetron diluted into 150 ml (2ml of basal infusion, a bolus of 0.5ml on demand, "lock-out" interval of 10 min, last for 48 h postoperatively);

Drug: S-ketamine

Interventions

S-ketamine DRUG

K1 group: pregnant women received 0.2mg/kg S-ketamine, intravenous drip;

Also known as: esketamine

K1 group

normal saline OTHER

Saline group: pregnant women received saline, intravenous drip

Also known as: physiological saline

Saline group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Parturients undergoing elective cesarean section
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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);
• Those who have a history of stroke, cognitive dysfunction, and epilepsy;
• 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;
• Pregnancy with other diseases (malignant tumors, hypertension during pregnancy, abnormal thyroid function, etc.);
• In the non-oxygen state, the peripheral blood oxygen saturation (SpO2) \<92%;
• Subjects whose prolactin is greater than the upper limit of normal during the screening period;
• 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;
• The effect of combined spinal-epidural anesthesia is not good, and other anesthetics are needed;
• People with a history of allergies to various foods and drugs;
• 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;
• There is a history of drug abuse and/or alcohol abuse within 1 year before the screening;
• Participated in other drug or device trials within 3 months before the screening;
• Subjects judged by the investigator to be unsuitable to participate in this clinical study.

Sponsors & Collaborators

• Beijing Obstetrics and Gynecology Hospital: lead
• China Health Promotion Foundation: collaborator
• Beijing Haidian Maternal and Child Health Hospital: collaborator
• Obstetrics & Gynecology Hospital of Fudan University: collaborator
• The Fourth Hospital of Shijiazhuang: collaborator
• Changzhi Maternal and Child Health Hospital: collaborator
• Linfen Maternity&Child Healthcare Hospital: collaborator
• Maternal and Child Health Hospital, Jiading District: collaborator
• Tongzhou Maternal and Child Healthcare Hospital of Beijing: collaborator
• Beijing Chaoyang District Maternal and Child Health Care Hospital: collaborator

MeSH Terms

Conditions

Agnosia; Depression; Depression, Postpartum

Interventions

Esketamine; Saline Solution

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior; Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Lei Wang

  Beijing Haidian Maternal and Child Health Hospital

  PRINCIPAL INVESTIGATOR

• Shaoqiang Huang

  Obstetrics & Gynecology Hospital of Fudan University

  PRINCIPAL INVESTIGATOR

• Jin Zhang

  The Fourth Hospital of Shijiazhuang

  PRINCIPAL INVESTIGATOR

• Yingbin Ren

  Changzhi Maternal and Child Health Hospital

  PRINCIPAL INVESTIGATOR

• Yong Qin

  Linfen Maternity&Child Healthcare Hospital

  PRINCIPAL INVESTIGATOR

• Shenghua Li

  Maternal and Child Health Hospital, Jiading District

  PRINCIPAL INVESTIGATOR

• Zhenhuan Hou

  Tongzhou Maternal and Child Healthcare Hospital of Beijing

  PRINCIPAL INVESTIGATOR

• Shuyi Miao

  Beijing Chaoyang District Maternal and Child Health Care Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mingjun Xu

CONTACT

86-13701038959; snake650222@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Anesthesiology department

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: December 8, 2020
• Study Start: December 1, 2020
• Primary Completion: December 15, 2021
• Study Completion: July 1, 2022
• Last Updated: December 8, 2020

Record last verified: 2020-12