Nalbuphine in ARDS Patients After Surgery

Analgesic Effect and Safety Analysis of Nalbuphine in ARDS Patients After Surgery

Critically ill patients need reasonable and moderate analgesic and sedative treatment to eliminate or reduce pain, anxiety and restlessness, improve patient comfort and cooperation, reduce patients' stress response, protect organ function and optimize prognosis. As a semi-synthetic opioid receptor agonist-antagonist, nalbuphine can bind to μ, κand δ receptors, has partial antagonistic effect on μ receptor, and is fully activated on κreceptor, with very weak δ receptor activity. Results of a study on the efficacy and safety of nalbuphine for analgesia in ICU patients showed that nalbuphine has sustained and stable analgesic effect for patients with mild to moderate analgesic needs in ICU, the onset time is comparable to sufentanil, and excessive sedation caused by sufentanil can be avoided, and the effect on hemodynamics is small. It can be used as a new choice of analgesic drugs in ICU.

A single-center, randomized, single-blind, prospective study was designed to compare nalbuphine and sufentanil in patients with ARDS after surgery. Sixty patients with ARDS after surgery to be admitted to ICU were randomly divided into experimental group (Nalbuphine group) and control group (Sufentanil group). This study aims to determine the analgesic efficacy and safety of nalbuphine hydrochloride in patients with Acute Respiratory distress syndrome (ARDS) after surgery. The successful development of this study will provide more theoretical basis for the individualized analgesic sedation program for surgical patients.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Nalbuphine; Drug: Sufentanil

Detailed Description

Severe patients need reasonable and moderate analgesic sedation to eliminate or reduce pain, anxiety and agitation, improve comfort and cooperation, reduce stress response, protect organ function and improve prognosis. As a semi-synthetic opioid receptor agonist-antagonist, nalbuphine can bind to μ, κand δ receptors, has partial antagonistic effect on μ receptor, and is fully activated on κreceptor, with very weak δ receptor activity. Nalbuphine exerts powerful analgesic and sedative effects at the spinal cord level, with rapid analgesic effect and long duration, almost no cardiovascular adverse reactions, mild respiratory depression and capping effect, low incidence of nausea, vomiting and skin pruritus, and low addiction. Results of a study on the efficacy and safety of nalbuphine for analgesia in ICU patients showed that nalbuphine has sustained and stable analgesic effect for patients with mild to moderate analgesic needs in ICU, the onset time is comparable to sufentanil, and excessive sedation caused by sufentanil can be avoided, and the effect on hemodynamics is small. It can be used as a new choice of analgesic drugs in ICU. Moreover, nalbuphine theoretically has no σ-receptor excitability, is not hallucinogenic, and the chance of inducing delirium is lower. Studies have shown that nalbuphine can reduce postoperative inflammation and oxidative stress and has a lung protective effect.

This study aims to determine the analgesic efficacy and safety of nalbuphine hydrochloride in patients with Acute Respiratory distress syndrome (ARDS) after surgery, and to explore the effects of nalbuphine hydrochloride on respiratory function, gastrointestinal function and cognitive function. To provide more theoretical basis for individualized analgesic and sedation program for surgical patients. Sixty patients were included and randomly divided into 1:1 groups, with 30 patients in each group. All patients were included according to strict inclusion criteria.

The experimental group was given nalbuphine analgesia and the control group was given sufentanil analgesia. The number of patients reaching the target level of analgesia and sedation at each time node, invasive mechanical ventilation time, oxygenation index change, mortality and other indicators were compared between the two groups.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Quanzhen Wang, doctor; Phone Number: 15562570205; Email: wangquanzhen1986@163.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250014
      • Recruiting
      • Department of Intensive Care Medicine
      • Contact: Quanzhen Wang, doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Had undergone surgical treatment within 7 days before enrollment;
• Meet the diagnostic criteria for ARDS proposed at the 2011 Berlin ARDS Definition Conference;
• Age ≥18 years old, gender unlimited;
• Patients admitted to ICU with CPOT score ≥3;
• Stay in ICU ≥48h;
• Sign the informed consent form.

Exclusion Criteria:

• APACHE II score ≥23 points;
• Patients with esophageal reflux disease and severe gastrointestinal injury have AGI score ≥3;
• Long-term use of narcotic analgesics, hypnotics and psychotropic drugs;
• Alcohol withdrawal symptoms;
• Severe liver dysfunction (Child-Pugh grade C);
• Patients with bronchial asthma and myasthenia gravis;
• Patients with severe craniocerebral injury, brain tumor, and increased intracranial pressure are prone to respiratory depression;
• Patients undergoing cardiac surgery under cardiopulmonary bypass;
• Patients who have been enrolled in other clinical trials;
• Study patients with drug allergy or other contraindications;
• Pregnant or lactating women;
• The patient himself or his legally authorized representative is unwilling to sign the informed consent;

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: Nalbuphine group; 40 mg of nalbuphine was diluted into 50 mL solution, the load dose was 0.1mg/kg, the maintenance dose was 0.04-0.08mg/kg/h, the CPOT score was <2, and the daily maximum dose was 160mg.	Drug: Nalbuphine; Nalbuphine was injected intravenously. The target CPOT score was <2, and the target RASS score was -2 ~ 1. 40 mg of nalbuphine was diluted into 50 mL solution, the load was 0.1mg/kg, the maintenance dose was 0.04-0.08mg/kg/h, the CPOT score was <2, and the maximum daily dose was 160mg.; Other Names: Nalbuphine Hydrochloride Injection
Active Comparator: Sufentanil group; 0.1mg of sufentanil was diluted into 50 mL solution, the loading dose was 0.2-0.5μg/kg, the maintenance dose was 0.2-0.3μg/kg/h, and the CPOT score was <2 points.	Drug: Sufentanil; Sufentanil was injected intravenously, and the target CPOT score was <2, and the target RASS score was -2 ~ 1. 0.1mg of sufentanil was diluted into 50 mL solution, the loading dose was 0.2-0.5μg/kg, the maintenance dose was 0.2-0.3μg/kg/h, and the CPOT score was <2 points; Other Names: Sufentanil citrate Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number 1 of patients who achieved the target level of analgesia and sedation	The number of patients in the two groups who reached the target level of analgesia and sedation within 30 minutes after the administration of analgesic drugs was compared	30 minutes after the analgesic is administered
Number 2 of patients who achieved the target level of analgesia and sedation	The number of patients in the two groups who reached the target level of analgesia and sedation within 60 minutes after the administration of analgesic drugs was compared	60 minutes after the analgesic is administered
Number 3 of patients who achieved the target level of analgesia and sedation	The number of patients in the two groups who reached the target level of analgesia and sedation within 4 hours after the administration of analgesic drugs was compared	4 hours after the analgesic is administered
Number 4 of patients who achieved the target level of analgesia and sedation	The number of patients in the two groups who reached the target level of analgesia and sedation within 8 hours after the administration of analgesic drugs was compared	8 hours after the analgesic is administered
Number 5 of patients who achieved the target level of analgesia and sedation	The number of patients in the two groups who reached the target level of analgesia and sedation within 12 hours after the administration of analgesic drugs was compared	12 hours after the analgesic is administered
Number 6 of patients who achieved the target level of analgesia and sedation	The number of patients in the two groups who reached the target level of analgesia and sedation within 24 hours after the administration of analgesic drugs was compared	24 hours after the analgesic is administered
Comparison of invasive mechanical ventilation time	Invasive mechanical ventilation time was compared between the two groups	The time from the start of the tracheal intubation to the withdrawal of the ventilator, assessed up to 28 days

Collaborators and Investigators

• Sponsor: Hairong Chen
• Investigators: Study Director: Hairong Chen, doctor, Qianfo Mountain Hospital, Shandong Province

Publications and helpful links

General Publications

• Zacny JP, Conley K, Galinkin J. Comparing the subjective, psychomotor and physiological effects of intravenous buprenorphine and morphine in healthy volunteers. J Pharmacol Exp Ther. 1997 Sep;282(3):1187-97.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): April 28, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: August 17, 2023
• First Submitted That Met QC Criteria: September 7, 2023
• First Posted (Actual): September 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Nalbuphine; Sufentanil; Dsuvia
• Other Study ID Numbers: QFSYXLL-KY-2022(092)

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