Intranasal Remimazolam for Premedication in Pediatric Patient

Intranasal Remimazolam for Premedication in Pediatric Patients: a Double-blinded Randomized Clinical Trial

Anesthetic inhalation induction could be one of the most stressful experiences for children during the perioperative period, with almost 50% of them showing anxiety. It is an essential challenge for pediatric anesthesiologists on how to decrease anxiety for children in the operating room (OR) environment and to facilitate a smooth induction of anesthesia. Various factors like parental separation, unfamiliar surroundings, fear of physicians and needle injections can increase their preoperative anxiety. The researchers conducted the current study to investigate whether intranasal remimazolam can reduce anxiety in children before surgery.

Study Overview

• Status: Completed
• Conditions: Sedative; Anxiety Disorder
• Intervention / Treatment: Drug: Dexmedetomidine; Other: Distilled water for injection; Drug: Remimazolam

Detailed Description

children aged 2-5 years old were randomly allocated into three equal groups based on the premedication routes: Group R with intranasal remimazolam, Group D with intranasal dexmedetomidine and Group P with intranasal placebo, respectively.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China
      • The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. with American Society of Anesthesiologists (ASA) physical status I or II；
2. aged 2-5 years；
3. children with weight for age within the normal range
4. were scheduled surgery with general anesthesia

Exclusion Criteria:

1. Children who had gastrointestinal,Cardiovascular or endocrine dysfunction;
2. contraindication to preoperative sedation or had a known allergy or hypersensitive reaction to either dexmedetomidine or remimazolam;
3. with any nasal pathology,organ dysfunction;
4. recently respiratory infection, mental disorder;
5. other reasons that researchers hold it is not appropriate to participate in this trial.-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: group P (Placebo group); intranasal placebo about 30min before anesthesia induction	Other: Distilled water for injection; intranasal distilled water for injection
Experimental: group R (remimazolam group); intranasal remimazolam about 30min before anesthesia induction	Drug: Remimazolam; intranasal remimazolam
Active Comparator: group D (Dexmedetomine group); intranasal dexmedetomidine about 30min before anesthesia induction	Drug: Dexmedetomidine; Intranasal dexmedetomidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The level of anxiety	The Modified Yale Preoperative Anxiety Scale: The 22-item measure has five behavioural categories: activity, emotional expressivity, alertness and arousal, vocalizations, and interaction with parents. Total scores range from 23.33 through 100 with higher scores indicating greater anxiety.	up to 30 minutes after study drug given

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The degree of cooperation during inhalation anesthesia induction	Induction Compliance Checklist range from 0 through 10,and lower scores indicate the higher degree of cooperation during inhalation anesthesia induction	intraoperative, (During inhalation anesthesia induction)
Mask acceptance scale，MAS	Mask acceptance scale，MAS; terrified, crying, agitated; moderate fear, not calmed with reassurance; slight fear of mask, easily calmed; unafraid, cooperative, accepts mask readily The scores of 3 and 4 signified satisfactory mask acceptable whereas scores of 1 and 2 were classified as poor mask acceptable.	intraoperative, (During inhalation anesthesia induction)
Pediatric anesthesia emergence delirium scale，PAEDs	The pediatric anesthesia emergence delirium scale consists of four items. Each item is scored 0-4 yielding a total between 0 and 20. The degree of emergence delirium increased directly with the total score.pediatric anesthesia emergence delirium scale ≥12 at any time indicates presence of emergence delirium.	Within up to 15-30 minutes after child's first eye opening in the postoperative period
Recovery times	The time from discontinuation of sevoflurane to the first open eye of the children and to achieve aldrete≥9	Within up to 30 minutes after child's first eye opening in the postoperative period
Number of children with adverse effects	Number of children with adverse effects; Bradycardia and/or hypotension need for hemodynamic support; Desaturation is defined as Oxygen desaturation <90%; Any adverse effects requiring interventions	Up to 24 hours including preoperative, intraoperative, and postoperative periods
The level of sedation	Ramsay score; Patient anxious or agitated or both; Patient cooperative, oriented and tranquil; Patient responds to commands only; A brisk response to a light glabellar tap; A sluggish response to a light glabellar tap; No response higher scores mean a higher levels of sedation.	up to 30 minutes after study drug given
the compliance of study drug given	behavior score; Clam and cooperative；; Anxious but reassurable;; Anxious but not reassurable;; Crying, or resisting The scores of 1 and 2 signified satisfactory compliance, whereas scores of 3 and 4 were classified as poor compliance.	up to 30 minutes before anesthesia induction
Parental separation anxiety scale	A four-point parental separation anxiety scale as follows: Easy separation,; Whimpers, but is easily reassured, not clinging,; Cries and cannot be easily reassured, but not clinging to parents,; Crying and clinging to parents. The scores of 1 and 2 signified acceptable separation whereas scores of 3 and 4 were classified as difficult separation.	up to 30 minutes after study drug given

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Wenzhou Medical University
• Investigators: Study Chair: Huacheng Liu, Second Affiliated Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2021
• Primary Completion (Actual): February 28, 2022
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: January 11, 2021
• First Submitted That Met QC Criteria: January 21, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: remimazolam
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety 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: SAHoWMU-CR2020-03-114

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