Effect of S-ketamine Anesthetic on Inflammatory Response in Septic Patients Undergoing Abdominal Surgery

Effect of S-ketamine Anesthetic on Inflammatory Response in Septic Patients Undergoing Abdominal Surgery:a Single Center, Randomized, Controlled Trial

This study is a randomized, double-blinded, controlled design. In this study, low doses of S-ketamine were selected for surgury treatment in septic patients under general anesthesia , Meanwhile, activity of HO-1 protein , oxidative stress and inflammatory markers in serum are measured to evaluating the effects of S-ketamine Anesthetic on inflammatory response in septic patients undergoing abdominal surgury. In addition,It is very necessary to make use of the advantages of low-dose S-ketamine in anti-inflammation, and avoid the side effects of mental symptoms, so as to guide the new direction of perioperative clinical application of S-ketamine.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Acute Lung Injury
• Intervention / Treatment: Drug: S-ketamine; Other: saline

Detailed Description

1. Title: Effect of S-ketamine Anesthetic on Inflammatory Response in Septic Patients Undergoing Abdominal Surgery
2. Research center: Single Center
3. The Design of the study: Randomized,double-blind, Controlled Trial
4. The population of the study: The main inclusion criteria are 18 years old or above,Patients with sepsis who need surgical treatment under general anesthesia and should be transferred to ICU for further treatment after surgery
5. Sample size: Enroll 50 patients (25 patients in each group)

6. Interventions: Participants in the test group received midazolam 0.05-0.1mg /kg, sufentanil 0.1-0.2ug/kg,Etomidate 0.1-0.2mg/kg, cisatracurium 0.15-0.3mg/kg, S-ketamine 0.125mg/kg (low dose) for Anesthesia induction, followed by an infusion of remifentanil 0.05-0.15ug/kg/min and S-Ketamine 0.125mg/kg/h (low dose) and continuous inhalation of sevoflurane at 2-3%.

   while participants in the control group was the same as the test group except for received the same volume of saline instead of S-ketamine.

   Intraoperative cisatracurium and sufentanil were added according to the circumstances.Bispectral index (BIS) was used to monitor the depth of anesthesia in two groups, and the BIS value was controlled to be 40-60, and the dose was adjusted according to the depth of anesthesia.

7. The aim of the research: To investigate the effect of S-ketamine Anesthetic on Inflammatory Response in Septic Patients Undergoing Abdominal Surgery
8. Outcome# 1) Primary outcome# the incidence of postoperative pulmonary complications 2)Secondary outcome#Inflammatory indicators: leukocyte, CRP, PCT levels;Inflammatory factors: IL-6, TNF-α, CC-16,activity of HO-1;Imaging diagnosis,such as chest X-ray,ultrasound;therapies for respiratory insufficiency,such as nasal cannula,face mask,postoperative noninvasive ventilation, re-intubation with postoperative mechanical ventilation;Incidence of postoperative adverse reactions such as restlessness, delirium, salivation, nausea, vomiting, respiratory depression, dizziness, etc;Length of stay in ICU
9. The estimated duration of the study#1-2years

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jianbo Yu MD PhD; Phone Number: 86-22-27435873; Email: yujianbo11@126.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300000
      • Recruiting
      • Tianjin Nankai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with sepsis requiring surgical treatment under general anesthesia should be transferred to ICU with endotracheal intubation for further treatment after surgery
• 18≤ age ≤85, gender and nationality is not limited
• Agree to participate in this study and sign the informed consent

Exclusion Criteria:

• Declined to participate in this study
• Patients in pregnancy or with drug allergy in this study
• Patient had chronic or acute respiratory ailments
• long-term preoperative continuous ventilatory support or oxygen dependency
• Patients are now being included in another study
• In the opinion of the attending physician or researcher, there are other conditions that are not appropriate for the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: test group; Participants in the test group received midazolam 0.05-0.1mg /kg, sufentanil 0.1-0.2ug/kg,Etomidate 0.1-0.2mg/kg, cisatracurium 0.15-0.3mg/kg, S-ketamine 0.125mg/kg (low dose) for Anesthesia induction, followed by an infusion of remifentanil 0.05-0.15ug/kg/min and S-Ketamine 0.125mg/kg/h (low dose) and continuous inhalation of sevoflurane at 2-3%.	Drug: S-ketamine; Participants in the test group received midazolam 0.05-0.1mg /kg, sufentanil 0.1-0.2ug/kg,Etomidate 0.1-0.2mg/kg, cisatracurium 0.15-0.3mg/kg, S-ketamine 0.125mg/kg (low dose) for Anesthesia induction, followed by an infusion of remifentanil 0.05-0.15ug/kg/min and S-Ketamine 0.125mg/kg/h (low dose) and continuous inhalation of sevoflurane at 2-3%.
Other: control group; Participants in the control group received midazolam 0.05-0.1mg /kg, sufentanil 0.2-0.3ug/kg,Etomidate 0.2-0.3mg/kg, cisatracurium 0.15-0.3mg/kg, saline 0.125ml/kg for Anesthesia induction, followed by an infusion of remifentanil 0.1-0.3ug/kg/min and saline 0.125ml/kg/h and continuous inhalation of sevoflurane at 2-3%.	Other: saline; Participants in the control group received midazolam 0.05-0.1mg /kg, sufentanil 0.1-0.2ug/kg,Etomidate 0.1-0.2mg/kg, cisatracurium 0.15-0.3mg/kg, saline 0.125ml/kg for Anesthesia induction, followed by an infusion of remifentanil 0.05-0.15ug/kg/min and saline 0.125ml/kg/h and continuous inhalation of sevoflurane at 2-3%.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of postoperative pulmonary complications	such as pneumonia,atelectasis ,pleural effusion,respiratory insufficiency,etc	an average of 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory indicators: leukocyte, CRP, PCT levels	leukocyte, CRP, PCT levels	an average of 1 day
Inflammatory factors	IL-6, TNF-α, CC-16,activity of HO-1	an average of 1 day
imaging diagnosis	chest X-ray,ultrasound	an average of 1 week
therapies for respiratory insufficiency	nasal cannula,face mask,postoperative noninvasive ventilation, re-intubation with postoperative mechanical ventilation	an average of 1 week
Incidence of postoperative adverse reactions	such as restlessness, delirium, salivation, nausea, vomiting, respiratory depression, dizziness, etc	an average of 1 week
Length of stay in ICU	The time from the patient's surgery to leave the ICU	an average of 1 month
Opioid consumption	consumption of sufentanil and remifentanil	an average of 1 day

Collaborators and Investigators

• Sponsor: Tianjin Nankai Hospital
• Investigators: Study Chair: Jianbo Yu MD PhD, Tianjin Nankai Hospital

Publications and helpful links

General Publications

• Trimmel H, Helbok R, Staudinger T, Jaksch W, Messerer B, Schochl H, Likar R. S(+)-ketamine : Current trends in emergency and intensive care medicine. Wien Klin Wochenschr. 2018 May;130(9-10):356-366. doi: 10.1007/s00508-017-1299-3. Epub 2018 Jan 10. Erratum In: Wien Klin Wochenschr. 2018 Sep;130(17-18):557.
• Fernandez-Bustamante A, Frendl G, Sprung J, Kor DJ, Subramaniam B, Martinez Ruiz R, Lee JW, Henderson WG, Moss A, Mehdiratta N, Colwell MM, Bartels K, Kolodzie K, Giquel J, Vidal Melo MF. Postoperative Pulmonary Complications, Early Mortality, and Hospital Stay Following Noncardiothoracic Surgery: A Multicenter Study by the Perioperative Research Network Investigators. JAMA Surg. 2017 Feb 1;152(2):157-166. doi: 10.1001/jamasurg.2016.4065.
• Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, Pereira EFR, Albuquerque EX, Thomas CJ, Zarate CA Jr, Gould TD. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev. 2018 Jul;70(3):621-660. doi: 10.1124/pr.117.015198. Erratum In: Pharmacol Rev. 2018 Oct;70(4):879.
• Welters ID, Feurer MK, Preiss V, Muller M, Scholz S, Kwapisz M, Mogk M, Neuhauser C. Continuous S-(+)-ketamine administration during elective coronary artery bypass graft surgery attenuates pro-inflammatory cytokine response during and after cardiopulmonary bypass. Br J Anaesth. 2011 Feb;106(2):172-9. doi: 10.1093/bja/aeq341. Epub 2010 Dec 7.

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): October 30, 2023

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: April 30, 2021
• First Posted (Actual): May 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 31, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Inflammation; S-ketamine; sepsis; acute lung injury
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Thoracic Injuries; Acute Lung Injury; Lung Injury; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Psychotropic Drugs; Antidepressive Agents; Ketamine; Esketamine
• Other Study ID Numbers: ASLAT20210430

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No