Intranasal Ketamine for Anxiolysis in Pediatric Emergency Department Patients

Anxiolysis for Emergency Department Procedures in Pediatric Patients Using Intranasal Ketamine Compared With Intranasal Midazolam: A Randomized Controlled Trial

Investigators plan to conduct a randomized, double-blinded, controlled study among pediatric patients requiring minor procedures in the Emergency Department setting. Patients will be randomized to one of two arms of intranasal treatments: ketamine 1.0 mg/kg (K) or midazolam 0.3 mg/kg (M). The primary outcome will be change in anxiety using the Modified Yale Preoperative Anxiety Scale (mYPAS).

Study Overview

• Status: Terminated
• Conditions: Anxiety; Pediatric ALL; Procedural Anxiety
• Intervention / Treatment: Drug: Ketamine 100 MG/ML; Drug: Midazolam 5 MG/ML

Detailed Description

The intranasal route of drug delivery is commonly used in Emergency Departments (ED) in pediatric patients. Multiple trials have shown the safety of administration of intranasal ketamine, including studies performed in the ED to treat pain in pediatric patients. The use of ketamine for anxiolysis has not been directly studied; however, ketamine has been shown to have anxiolytic effect at low doses as secondary outcomes when studied. Midazolam has been established as an effective medication to provide analgesia and anxiolysis. Investigators plan to conduct a randomized, double-blinded, controlled study in the Emergency Department. Pediatric patients presenting to the ED with the need for minor procedures who meet the inclusion and exclusion criteria will be consented, and if amenable, will be enrolled. Patients will be randomized to one of two arms of intranasal treatments: ketamine 1.0 mg/kg (K) or midazolam 0.3 mg/kg (M). Patients will be tracked for symptom improvement within the Emergency Department. The primary outcome will be change in anxiety from initial measurement to measurement 5 minutes pre-procedure using the Modified Yale Preoperative Anxiety Scale (mYPAS). Secondary outcomes will include sedation level, adverse events, need for additional medications, change in pain rating, patient and/or parent/guardian satisfaction.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Fort Sam Houston, Texas, United States, 78234
      • San Antonio Military Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients age 2 to 12 years who present to the ED
• Requiring intravenous access
• Requiring laceration repairs
• Requiring incision and drainage of abscesses
• Requiring digital nerve blocks
• Requiring radiological imaging
• Requiring bladder catheterization
• Requiring foreign body removal.

Exclusion Criteria:

• Vital sign abnormalities greater than 20% deviation from age-normalized ranges
• Altered mental status/delirium or intoxication
• Patient or patient's parent/guardian are unwilling to participate or provide informed consent
• Any allergy to ketamine or midazolam
• Patient is female with history of menarche
• Presence of chronic oxygen-dependent pulmonary disease, liver cirrhosis, or renal disease requiring dialysis
• Presence of ischemic heart disease, heart failure, or a history of unstable dysrhythmias
• Presence of intracranial mass or vascular lesion.
• Presence of a history of psychosis or hallucinations
• Weight greater than 100kg
• History of increased intracranial pressure/ hypertensive hydrocephalus within the last 3 months
• Non-English speaking/reading parent/guardian and/or patients
• Patient is acutely psychotic
• Provider feels that patient currently or likely will require chemical and/or physical restraints
• History of prolonged QT-interval
• Nasal trauma
• Epistaxis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine; Ketamine 100 mg/mL concentration administered in a single 1.0 mg/kg dose with a maximum of 50mg intranasal via mucosal atomization device.	Drug: Ketamine 100 MG/ML; Administer ketamine via mucosal atomization device
Active Comparator: Midazolam; Midazolam 5 mg/mL concentration administered in a single administered in a single 0.3 mg/kg dose with a maximum of 5mg intranasal via mucosal atomization device.	Drug: Midazolam 5 MG/ML; Administer midazolam via mucosal atomization device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mYPAS	Modified Yale preoperative anxiety scale	Change in score between initial measurement versus 5 minutes pre-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in sedation scale	University of Michigan sedation scale	Change in score between initial measurement versus 5 minutes pre procedure, 5 minutes post procedure, and 5 minutes pre-discharge
Change in pain rating (Wong-Baker Pain Faces Rating Scale)	Wong-Baker Pain Faces Rating Scale	Change in score between initial measurement versus 5 minutes pre procedure, 5 minutes post procedure, and 5 minutes pre-discharge
Change in anxiety score (Visual analogue scale)	Visual analogue scale	Change in score between initial measurement versus 5 minutes pre procedure, 5 minutes post procedure, and 5 minutes pre-discharge

Collaborators and Investigators

• Sponsor: Brooke Army Medical Center
• Investigators: Principal Investigator: Nadia M Pearson, MD, Faculty Physician

Publications and helpful links

General Publications

• Hosseini Jahromi SA, Hosseini Valami SM, Adeli N, Yazdi Z. Comparison of the effects of intranasal midazolam versus different doses of intranasal ketamine on reducing preoperative pediatric anxiety: a prospective randomized clinical trial. J Anesth. 2012 Dec;26(6):878-82. doi: 10.1007/s00540-012-1422-6. Epub 2012 Jun 12.
• Roelofse JA, Shipton EA, de la Harpe CJ, Blignaut RJ. Intranasal sufentanil/midazolam versus ketamine/midazolam for analgesia/sedation in the pediatric population prior to undergoing multiple dental extractions under general anesthesia: a prospective, double-blind, randomized comparison. Anesth Prog. 2004;51(4):114-21.
• Narendra PL, Naphade RW, Nallamilli S, Mohd S. A comparison of intranasal ketamine and intranasal midazolam for pediatric premedication. Anesth Essays Res. 2015 May-Aug;9(2):213-8. doi: 10.4103/0259-1162.154051.
• Khatavkar SS, Bakhshi RG. Comparison of nasal Midazolam with Ketamine versus nasal Midazolam as a premedication in children. Saudi J Anaesth. 2014 Jan;8(1):17-21. doi: 10.4103/1658-354X.125904.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): April 1, 2023
• Study Completion (Actual): April 1, 2023

Study Registration Dates

• First Submitted: January 30, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimate): February 6, 2017

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 23, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease Attributes; Emergencies; Anxiety Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam
• Other Study ID Numbers: C.2016.021

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