Clinical trial NCT04873479: Effect of S-ketamine Anesthetic on Inflammatory Response in Septic Patients Undergoing Abdominal Surgery
Official title: Effect of S-ketamine Anesthetic on Inflammatory Response in Septic Patients Undergoing Abdominal Surgery:a Single Center, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sepsis
Acute Lung Injury
Keywords: sepsis
acute lung injury
S-ketamine
Inflammation
Lead sponsor: Tianjin Nankai Hospital
Sponsor class: OTHER
First posted: 2021-05-05
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: the incidence of postoperative pulmonary complications
timeFrame: an average of 1 week
Secondary outcomes:
measure: Inflammatory indicators: leukocyte, CRP, PCT levels
timeFrame: an average of 1 day
measure: Inflammatory factors
timeFrame: an average of 1 day
measure: imaging diagnosis
timeFrame: an average of 1 week
measure: therapies for respiratory insufficiency
timeFrame: an average of 1 week
measure: Incidence of postoperative adverse reactions
timeFrame: an average of 1 week
measure: Length of stay in ICU
timeFrame: an average of 1 month
measure: Opioid consumption
timeFrame: an average of 1 day
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Nankai Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Nankai Hospital
name: Jianbo Yu MD PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.