Acceptable Hemodynamic Changes in Dexmedetomidine for Single Intravenous Bolus Injection

Determination of ED50 and ED95 of Single Bolus Dexmedetomidine in General Anesthesia Patients to Produce Acceptable Hemodynamic Outcomes

Dexmedetomidine（DEX）is a potent and highly selective α 2 adrenergic receptor agonist. It has the pharmacological effects of sedation, hypnosis, analgesia, anti-sympathetic and neuroprotective. Its sedative effect is similar to normal sleep, and easy to wake up. DEX is widely used clinically because of its advantages and acceptable side effects. The best clinical use of DEX is uncertain, including intravenous, intramuscular, oral, intralnasal and sublingual administration. Its clinical recommended use is intravenous load infusion for more than 10 minutes, followed by continuous infusion. However, the clinical recommended usage is inconvenient, time-consuming and other shortcomings, for the growing popularity of daytime surgery, will inevitably affect the operation process and turnover. If a suitable dose range of DEX can be found for a single intravenous injection to achieve clinical efficacy quickly without significant hemodynamic effects, this will improve the patient's postoperative recovery. We will speed up the utilization and turnover of medical resources. The aim of this study was to investigate the optimal dosage of DEX for single intravenous injection.

Study Overview

• Status: Unknown
• Conditions: Mental Disorders; Pathologic Processes; Postoperative Complications; Delirium; Neurocognitive Disorders; Dexmedetomidine; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Analgesics; Hypnotics and Sedatives
• Intervention / Treatment: Drug: Dexmedetomidine

Detailed Description

Patients undergoing thyroidectomy under general anesthesia were treated with routine anesthesia induction and maintenance, and DEX was injected intravenously 30 minutes before the end of operation. Single bolus is for more than 1 minute. In the first case, the dosage of DEX was 0.1 ug/kg. If the cardiovascular reaction was positive (MAP or heart rate was more than 20% before intravenous injection), the dosage of DEX in the next patient decreased by a gradient (0.05ug/kg). If the cardiovascular response was negative, the next patient increased the dose of DEX by a gradient (0.1ug/kg); if a patient withdrew from the study, the next patient received the same dose as the patient who withdrew. There were 8 turning points of cardiovascular reaction and the test was completed. The changes of blood pressure and heart rate per minute in 10min were recorded after single bolus. The dosimetric map of patients with DEX was drawn, and the ED50 and ED95 were calculated by probit probabilistic unit regression (Bills method).

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325027
      • Recruiting
      • The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University
      • Contact: Jie Chen; Phone Number: 0577-88002560; Email: feykjkcy@126.com
      • Contact: Xueqiong Zhu; Phone Number: 0577-88002560; Email: feykjkcy@126.com
      • Principal Investigator: Chengyu Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. volunteer to participate in the study and sign the informed consent;
2. selective operation of thyroid gland whose anesthesia time is less than 2 hours ;
3. aged 18-55 years;
4. ASA I - II;
5. BMI 18~28kg/m2.

Exclusion Criteria:

1. Mallampati grade Ⅲ or Ⅳ;
2. opening degree < 2.5 cm;
3. taking analgesic or sedative drugs for a long time before operation;
4. a history of arrhythmia, bronchial and cardiovascular diseases, abnormal liver function and so on;
5. allergic to dexmedetomidine, similar active ingredients or excipients;
6. G-6-PD deficiency;
7. a history of use of alpha 2 receptor agonists or antagonists.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Dexmedetomidine; Drug: Dexmedetomidine dexmedetomidine, 0.1ug/kg up or down Other Name: precedex

Drug: Dexmedetomidine; Dexmedetomidine was injected intravenously 30 minutes before the end of operation. Single bolus is for more than 1 minute. In the first case, the dosage of dexmedetomidine was 0.1 ug/kg. If the cardiovascular reaction was positive (mean arterial pressure or heart rate was more than 20% before intravenous injection), the dosage of Dexmedetomidine in the next patient decreased by a gradient (0.05ug/kg). If the cardiovascular response was negative, the next patient increased the dose of dexmedetomidine by a gradient (0.1ug/kg); if a patient withdrew from the study, the next patient received the same dose as the patient who withdrew.; Other Names: see arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate(HR)	HR changes per minutes in 10 minutes after single injection of DEX	10min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of operation	Duration of operation	intraoperative, from the beginning of the cut to the end of the seam
Anaesthesia time	Anaesthesia time	intraoperative, from initiation of anesthesia induction to cessation of anesthetic use
Recovery time of anesthesia	Recovery time of anesthesia	within 24 hours
Mean arterial pressure(MAP)	MAP changes per minutes in 10 minutes after single injection of DEX	10min

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Wenzhou Medical University
• Investigators: Study Director: Jun Li, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 23, 2018
• Primary Completion (ANTICIPATED): March 23, 2020
• Study Completion (ANTICIPATED): April 23, 2020

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: August 30, 2018
• First Posted (ACTUAL): August 31, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 25, 2019
• Last Update Submitted That Met QC Criteria: September 23, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Disease; Mental Disorders; Postoperative Complications; Pathologic Processes; Neurocognitive Disorders; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: LCKY2018-32

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be available.
• IPD Sharing Time Frame: Data will be available within 6 months of study complettion.
• IPD Sharing Access Criteria: Data access request will be reviewed by an external independent review panel.Requestors will be required to sign a Data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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