Cardiovascular Protection Conservative Effects of Esketamine Versus µ-opioid Receptor Agonists in General Anesthesia

NCT04553536 | Unknown

• 1 other identifier: ZGuo20200826
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

Pain is 'a double-edged sword', disturbing daily life of the sufferers and activating the intrinsic protective mechanisms. Transient receptor potential vanilloid 1 (TRPV1), play such role as 'a double agent', transmitting the pain signals and initiating the cardio-protective mechanism via release protective neuropeptides. Surgery-related pain is mostly so severe and disturbing that must be medically treated. Unfortunately, the beneficial aspect of pain is commonly ignored in daily clinical practice. Does it matter to the patients' outcomes? We don't know yet! What we have been seeing is the shocking outcomes of patients underwent surgery, which shows about 0.8% and 7% of mortalities in the period of 48 hours and 30 days after surgery, respectively (https://www.rcplondon.ac.uk/projects/outputs/national-hip-fracture-database-annual-report-2016; Injury. 2017; 48(10): 2180-2183). What causes the disaster? Piles of evidence demonstrate that deep anesthesia or deep sedation is related to the high mortality of the patients (Anesthesiology. 2012; 116:1195-1203; Crit Care. 2014; 18(4):R156 ). What about the effect of analgesia, especially the over-analgesia, on the patients' outcome in and after surgery? Opioids are the most commonly used drugs in the treatment of moderate and sever pain including intra- and postoperative pain. The µ-opioid receptor agonists induce analgesic effect via inhibition of the transduction and the transmission of pain signals, by suppression of the release of CGRP and SP from the nerve terminals. The protective effects on cardiovascular system mediated by CGRP and SP can be inhibited, if the same effect is produced by the action of opioids in the peripheral nerve terminals innervating the heart and the vasculature. Our previous research shows that intrathecal administration of morphine or epidural administration of ropivacaine (1%, in 20 μL) significantly attenuates the increases of CGRP and its coding mRNA in ventricular myocardium and the innervating dorsal root ganglion neurons following occlusion of coronary artery in experimental animals. We design this study to investigate the potential adverse effect of anesthesia with opioid as the main analgesic.

Conditions

Opioid Analgesic Adverse Reaction

Outcome Measures

Primary Outcomes (2)

• Perioperative adverse cardiac events

  It includes intra- and post-operative adverse cardiac events.

  72 hours

• Cardiac protection related molecules, including transient receptor potential vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP) and substance P.

  The molecules exist in myocardium participating in carioprotection.

  24 hours

Study Arms (2)

Opioid analgesics

ACTIVE COMPARATOR

Mu-opioid receptor agonists (remifentanil, sulfentanil) will be used as the only analgesic(s) in the surgery.

Drug: Esketamine, Sulfentanil or/and Remifentanil

Ketamine

EXPERIMENTAL

Esketamine will be used as the only anagesic in the surgey.

Drug: Esketamine, Sulfentanil or/and Remifentanil

Interventions

Esketamine, Sulfentanil or/and Remifentanil DRUG

The esketamine or the opioids will be intravenously injected or infused to the patients with propofol and one of the muscle relaxants to induce and maitain general anesthesia.

Also known as: Propofol, Atracurium Besilate or Cisatracurium besylate or Rocuronium Bromide

Ketamine; Opioid analgesics

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing general anesthesia

You may not qualify if:

• Patients with diabetes and neuropathy

Sponsors & Collaborators

• Second Hospital of Shanxi Medical University: lead

Study Sites (1)

Zheng Guo

Taiyuan, Shanxi, 030001, China

RECRUITING

MeSH Terms

Interventions

Esketamine; Propofol; Atracurium; cisatracurium; Rocuronium

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzylisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 3, 2020
• First Posted: September 17, 2020
• Study Start: November 2, 2020
• Primary Completion: June 30, 2023
• Study Completion: January 31, 2024
• Last Updated: January 25, 2024

Record last verified: 2024-01

Locations

CN (1)