The Effect of Analgesic Drugs on Respiratory Center

Opioids are commonly used in analgesic treatment of severe patients. Opioid receptors are divided into five types:,,, and.1 receptor is associated with analgesia and sedation above the spinal cord, while 2 receptor is associated with respiratory depression, bradycardia, euphoric sensation, pruritus, pupil contraction, inhibition of intestinal motility and other side effects.Κ receptors play a role of spinal analgesia, sedation and diuresis.Δ receptors associated with spinal analgesia and respiratory inhibition and regulate the activity of mu receptor.

Different opioid analgesics have different binding degree with different receptors, which determines the difference of analgesic effect and side effect, especially respiratory central inhibitory effect.Remifentanil is a pure opioid receptor agonist, mainly ACTS on the first and second receptors, binding to the second receptor is weak, in the analgesic, sedative effect, with opioid respiratory depression and hypotensive side effects, respiratory depression is dose dependent.Nalbuphine hydrochloride has strong analgesic effect, quick effect and long time by stimulating receptor, and has partial antagonistic effect on the receptor, so the incidence of respiratory depression is low in theory.The metabolic pathways of different opioids are also different. In particular, severe patients often need continuous opioid infusion for analgesia, which may lead to the accumulation of drugs and further affect the respiratory center.In the process of continuous application of different types of opioids to the analgesia of severe patients, the presence of respiratory center inhibition, the degree of inhibition and the dose-effect relationship have not been quantitatively evaluated.

Study Overview

• Status: Unknown
• Conditions: The Effect of Analgesic Drugs on Respiratory Center
• Intervention / Treatment: Drug: nalbuphine; Drug: remifentanil

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • Zhongda Hospital, Southeast University
      • Contact: Ling Liu, Dr; Phone Number: +8613851435472; Email: liulingdoctor@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients with tracheal intubation transferred to ICU after surgery;Stop the use of sedative drugs continue to pump more than 2h into the vein, anesthesia awake can cooperate with the command action;Can withstand PSV ventilation; need pain relief treatment

Exclusion Criteria:

Patients who cannot place transnasal gastric tube (EAdi catheter) beside the bed due to various reasons (such as massive gastrointestinal bleeding, esophagus and stomach surgery within the past 1 month, severe coagulation dysfunction);Patients with neuromuscular diseases: diseases that directly or indirectly inhibit respiratory centers and affect respiratory muscles;The patient is expected to die within 24 hours;Pregnant women, patients with malignant tumors;Patients with craniocerebral injury or ARDS who require deep sedation;Patients with agitated delirium.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nalbuphine	Drug: nalbuphine; Nalbuphine hydrochloride has strong analgesic effect, quick effect and long time by stimulating receptor, and has partial antagonistic effect on the receptor, so the incidence of respiratory depression is low in theory.; Other Names: remifentanil
Placebo Comparator: remifentanil	Drug: remifentanil; remifentanil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Richmond Agitation-Sedation Scale	1 week

Collaborators and Investigators

• Sponsor: Chun Pan
• Collaborators: Southeast University, China

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Anticipated): January 28, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: January 21, 2020
• First Submitted That Met QC Criteria: May 1, 2020
• First Posted (Actual): May 4, 2020

Study Record Updates

• Last Update Posted (Actual): May 4, 2020
• Last Update Submitted That Met QC Criteria: May 1, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil; Nalbuphine
• Other Study ID Numbers: Nalbuphine

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