An Exploratory Study of Esketamine in Patients After Thoracoscopic Surgery

Thoracic surgery can produce severe postoperative acute pain, which can easily lead to cough weakness, atelectasis, respiratory restriction, pneumonia, hypoxemia, secretion retention, respiratory failure and other adverse events. Esketamine can reduce the demand of analgesic opioids, reduce the respiratory depression caused by opioids, improve ventilation, significantly reduce postoperative pain and prolong the analgesic time after thoracic surgery. Therefore, the application of esketamine in postoperative analgesia of patients undergoing thoracoscopic surgery may help to improve the respiratory function of clinical patients and further improve the postoperative analgesia effect, so as to achieve the purpose of accelerating the surgical rehabilitation of patients undergoing thoracoscopic surgery. Esketamine is rarely used in perioperative period in China, and the development of its safe and reasonable application methods and potential role in perioperative anesthesia needs further research and verification. Generally speaking, at present, there is still a lack of evaluation of ketamine in improving respiratory function, pain, anxiety and depression after thoracoscopic surgery, and there is no direct clinical evidence.

At present, sufentanil is the most commonly used drug for postoperative analgesia in patients undergoing clinical surgery. As a strong opioid, although sufentanil can provide good analgesic effect, the respiratory depression caused by sufentanil is not conducive to the recovery of postoperative lung function in patients undergoing thoracic surgery. The action sites of esketamine include N- methyl-aspartic acid (NMDA) receptor, opioid receptor, monoamine receptor, M cholinergic receptor, sodium channel, calcium channel, etc., which can relieve respiratory depression caused by opioids, stimulate respiration, relax airway smooth muscle, prevent hyperalgesia caused by opioids, reduce the dosage of postoperative analgesics and prolong the duration of postoperative analgesia. Therefore, esketamine is likely to improve postoperative respiratory function of patients after thoracoscopic surgery and play a good role. To sum up, this study is intended to include patients undergoing elective thoracoscopic surgery. Through a prospective randomized controlled double-blind clinical trial, different analgesic drugs of intravenous patient-controlled analgesia and simple conventional opioid analgesic sufentanil are used as the control. Combined with the investigation of preoperative and postoperative tidal volume, oxygenation index, postoperative pain and postoperative recovery outcome, the effects of esketamine on postoperative respiratory function, postoperative pain and overall rehabilitation of these patients are compared, so as to provide direct clinical evidence for improving postoperative lung function of patients undergoing elective thoracoscopic surgery, and at the same time, provide a choice for thoracoscopic surgery.

To explore the effect of esketamine on improving postoperative respiratory function, pain, depression and anxiety and overall rehabilitation of patients undergoing thoracoscopic surgery. Compound esketamine is used for postoperative analgesia, thus providing direct clinical evidence for improving postoperative pulmonary function of patients undergoing elective thoracoscopic surgery, and providing reference for improving postoperative pain, anxiety and depression of patients undergoing elective thoracoscopic surgery.

Study Overview

• Status: Completed
• Conditions: Thoracoscopic Surgery; Esketamine
• Intervention / Treatment: Drug: Esketamine

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: duan; Phone Number: (+86)18323376014; Email: duangy@hospital.cqmu.edu.cn

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University
    • Chongqing, Chongqing, China, 400010
      • The Second Affiliated Hospital, Chongqing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients undergoing thoracoscopic surgery are required to use PCIA for analgesia;
2. ASA grade I-III;
3. The patient's age is 18-75 years old; 4、18.5 < BMI < 28；

5. Obtain the informed consent of patients and their families;

Exclusion Criteria:

1. Patients with previous history of thoracic surgery or combined history of thoracic trauma;
2. Patients with severe hypertension and poor control;
3. Patients with hyperthyroidism and poor control;
4. Patients at risk of increased intracranial pressure;
5. Patients with mental illness;
6. Patients who are allergic to any drug in the test;
7. Patients who take anti-inflammatory drugs, opioids or related diseases for a long time;
8. Pregnant or lactating patients;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esketamine arm; Self-controlled intravenous analgesia pump was used for continuous injection, and it was prepared according to sufentanil 1.5ug/ml+ esketamine 0.75ug/ml+16mg ondansetron. After the operation, the analgesic pump was connected, and sufentanil 0.1ug/kg/h+ e sketamine 0.05mg/kg/h was pumped continuously for 24 hours. The continuous infusion of analgesia pump is (kg body weight/15) ml/h. (e.g. 60kg, pump speed 4ml/h, total amount 96ml).	Drug: Esketamine; Self-controlled intravenous analgesia pump was used for continuous injection, and it was prepared according to sufentanil 1.5ug/ml+ esketamine 0.75ug/ml+16mg ondansetron. After the operation, the analgesic pump was connected, and sufentanil 0.1ug/kg/h+ esketamine 0.05mg/kg/h was pumped continuously for 24 hours. The continuous infusion of analgesia pump is (kg body weight/15) ml/h. (e.g. 60kg, pump speed 4ml/h, total amount 96ml).
No Intervention: Sufentanil arm; Continuous pumping with self-controlled intravenous analgesia pump. According to sufentanil 1.5ug/ml+16mg ondansetron. At the end of the operation, connect the analgesic pump, and pump it with sufentanil at 0.1ug/kg/h for 24 hours. The continuous infusion of analgesia pump is (kg body weight/15) ml/h. (e.g. 60kg, pump speed 4ml/h, total amount 96ml).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minute ventilation volume 0	Minute ventilation volume before anesthesia induction	Before anesthesia induction
Minute ventilation volume 1	Minute ventilation volume after extubation	Within 5 minutes after extubation
Tidal volume 0	Tidal volume before anesthesia induction	Before anesthesia induction
Tidal volume 1	Tidal volume after extubation	Within 5 minutes after extubation
Respiratory rate 0	Respiratory rate before anesthesia induction	Before anesthesia induction
Respiratory rate 1	Respiratory rate after extubation	Within 5 minutes after extubation
Minute ventilation volume 2	Minute ventilation volume on the first morning	postoperative day 1 (POD1) morning
Minute ventilation volume 3	Minute ventilation volume on the first afternoon	postoperative day 1 (POD1) afternoon
Minute ventilation volume 4	Minute ventilation volume on the next morning	postoperative day 2 (POD2) morning
Minute ventilation volume 5	Minute ventilation volume on the next afternoon	postoperative day 2 (POD2) afternoon
Tidal volume 2	Tidal volume on the first morning after surgery	Day1 （The first morning after surgery）
Tidal volume 3	Tidal volume on the first afternoon after surgery	Day1（The afternoon of the first day after surgery）
Tidal volume 4	Tidal volume on the next morning after surgery	day 2 ( second morning after surgery)
Tidal volume 5	Tidal volume on the next afternoon after surgery	day 2 ( second afternoon after surgery)
Respiratory rate 2	Respiratory rate on the first morning after surgery	Day1 （The first morning after surgery）
Respiratory rate 3	Respiratory rate on the first afternoon after surgery	Day1 （The afternoon of the first day after surgery）
Respiratory rate 4	Respiratory rate on the next morning after surgery	day 2 ( second morning after using surgery)
Respiratory rate 5	Respiratory rate on the next afternoon after surgery	day 2 ( second afternoon after surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vas score 1	The higher the score, the more painful it is.	Within 5 minutes after extubation
Vas score 2	The higher the score, the more painful it is.	postoperative day 1 (POD1) morning
Vas score 3	The higher the score, the more painful it is.	postoperative day 1 (POD1) afternoon
Vas score 4	The higher the score, the more painful it is.	postoperative day 2 (POD2) morning
Vas score 5	The higher the score, the more painful it is.	postoperative day 2 (POD2) afternoon
Oxygenation index 0	Oxygenation index (calculated as PaO2/FiO2) before anesthesia induction	Before anesthesia induction
Oxygenation index 1	Oxygenation index (calculated as PaO2/FiO2) after extubation	Within 5 minutes after extubation
Oxygenation index 3	Oxygenation index (calculated as PaO2/FiO2) on the first morning	postoperative Day 1
Incidence of postoperative pulmonary complications during hospitalization	postoperative pulmonary complications during hospitalization was assessed using the Melbourne Group Scale, whcih reached four or more of the 8 criteria would be diagnosed with postoperative pulmonary complications.	From end of the surgery to hospital discharge with about mean of 7 days after surgery
incidence of hypoxemia during the first and second day after surgery	hypoxemia is defined as SpO2<92% during the first and second day after surgery	from end of the surgery to the second day after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression scale 0	PHQ-9， The higher the score, the more depressed.	Before anesthesia induction
Depression scale 2	PHQ-9，The higher the score, the more depressed.	Day 1(the first morning after using PCIA)
anxiety score 0	GAD-7，The higher the score, the more anxious.	Before anesthesia induction
Depression scale 4	PHQ-9，The higher the score, the more depressed.	day 2 ( second morning after using PCIA)
anxiety score 2	GAD-7，The higher the score, the more anxious.	Day1(the first morning after using PCIA)
anxiety score 4	GAD-7，The higher the score, the more anxious.	day 2 ( second morning after using PCIA)
sleep quality during the first two days after surgery	assessed by Richards-Campbell sleep score, which higher socre represents better sleep quality	from end of the surgery to the second day after surgery

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2022
• Primary Completion (Actual): February 20, 2023
• Study Completion (Actual): February 28, 2023

Study Registration Dates

• First Submitted: July 1, 2022
• First Submitted That Met QC Criteria: July 12, 2022
• First Posted (Actual): July 14, 2022

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 15, 2023
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: Esketamine and thoracoscopic

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The individual participant data for this study is available from the sponsor on reasonable request through email.
• IPD Sharing Time Frame: Within one year
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No