A Comparison of Intranasal Midazolam and Nitrous Oxide (N2O) Minimal Sedation for Minor Procedures in a Pediatric Emergency Department

The objective of this project is to compare the sedative effects of intranasal midazolam versus inhaled nitrous oxide (N2O) for minor procedures in the pediatric emergency department. The primary outcome will be length of stay (LOS) in the emergency department (ED) stay for minor procedures. Secondarily the investigators will compare patient/family and provider satisfaction while using either intranasal midazolam or N2O for minimal sedation. The investigators hypothesize that the total length of stay for children undergoing minor procedures in the ED will be lower for N2O, as compared to intranasal midazolam. The investigators also hypothesize that patient/family and provider satisfaction will be higher with N2O and adverse effects will not differ between N2O and intranasal midazolam. Patients will receive either intranasal midazolam or N2O for minor procedures. Following the enrollment period, data will be analyzed and the two will be compared. Total length of stay, patient/family and provider satisfaction will be studied.

Study Overview

• Status: Completed
• Conditions: Conscious Sedation; Simple Lacerations Less Than 4 cm; Lumbar Punctures; Minor Incision Drainage of Abscesses Not Requiring Extensive Debridement
• Intervention / Treatment: Drug: Nitrous Oxide; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients ≥2 years of age and <18 years of age, and
2. Parent/legal guardian age ≥18 years of age to <80 years of age
3. Patients with an American Society of Anesthesiologists (ASA) Physical Status Classification System level 1, 2, and 3

4. Patients requiring anxiolysis and mild sedation for minor procedures

   1. Minor procedures will include simple lacerations less than 4 cm
   2. Lumbar punctures
   3. Minor incision
   4. Drainage of abscesses that do not require extensive debridement

5. Must receive the standard of care dosing for either nitrous oxide or intranasal midazolam.

   1. Nitrous oxide up to 70% nitrous concentration will be allowed
   2. Intranasal Midazolam 0.4mg/kg with a max dose of 10mg

Exclusion Criteria:

1. Nasal injury, nasal obstruction or significant congestion
2. Laceration that involves the nose and ears or come into contact with the scavenger device or nitrous oxide tubing
3. Allergy to benzodiazepines
4. Benzodiazepine dosing for any reason 24 hours prior to procedure
5. Excessive Epistaxis
6. Facial or nasal deformity
7. Copious mucous
8. Recent (less than 1 week) tympanic membrane graft or middle ear surgery
9. Recent bleomycin therapy
10. Patients known to be pregnant at time of enrollment
11. Patients with severe behavior problems, personality disorders or other mind-altering conditions as determined by administering provider.

12. Closed space situations such as:

    1. pneumothorax,
    2. air embolus,
    3. pneumocephalus, or
    4. craniotomy in the last 3 weeks,
    5. intraocular surgery with retained gas,
    6. pulmonary bullae,
    7. severe emphysema, or
    8. bowel obstruction.

13. Patients with significant co-morbidities:

    1. severe pulmonary disease,
    2. cardiac disease,
    3. hematologic diseases associated with B12 deficiency,
    4. sickle cell disease.
14. Patients with acute otitis media and/or sinusitis
15. History of paradoxical reaction to nitrous oxide
16. Known Methicillin-resistant Staphylococcus aureus (MRSA+) patients
17. Co-administration of additional sedation or analgesic medications

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nitrous Oxide; Nitrous oxide will be delivered in one of two ways, using the titration method or rapid infusion method.	Drug: Nitrous Oxide; Nitrous oxide will be delivered in one of two ways, using the titration method or rapid infusion method. Which ever method is used will be recorded. When using the titration method, starting at 20%, nitrous oxide will be added in 10% increments every 60 seconds until the ideal level of sedation has been met (not to exceed 70% nitrous oxide). Using the rapid infusion method, after the proper flow rate has been achieved with oxygen, the flowmeter will be increased to obtain 50% concentration of nitrous oxide. After 2-3 minutes if the patient does not have adequate sedation, nitrous oxide concentration will be increased to 70%.; Other Names: N2O
Active Comparator: Intranasal Midazolam; Intranasal midazolam with mucosal atomizer device administration will follow the Children's Hospital Colorado (CHCO) established policy 'Intranasal Administration (atomization) of Medications'.	Drug: Midazolam; Intranasal midazolam with mucosal atomizer device administration will follow the Children's Hospital Colorado (CHCO) established policy 'Intranasal Administration (atomization) of Medications'. As per standard of care, each patient will receive a standardized dose of 0.4mg/kg (maximum dose of 10mg) of intranasal midazolam with the mucosal atomizer device for all procedures.; Other Names: Versed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ED Length of Stay After Intranasal Midazolam or Nitrous Oxide Administration	The total length of Emergency Department (ED) stay will be defined as time from intranasal midazolam or nitrous oxide administration to time of discharge readiness, collected by the research assistants. Additional time periods measured will include: time from anxiolytic/sedative given to time of procedure completion, and total time for recovery.	From administration of intranasal midazolam or nitrous oxide, assessed over an estimated time of 2 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient/Parent and Provider Satisfaction With Sedation and Anxiolytic/Sedative.	Patient/parent satisfaction will be assessed for all patients; child satisfaction will be assessed for patients over 12 years of age. Satisfaction will be measured on a scale of 1 to 5 (1 being not satisfied and 5 being very satisfied). Specifically, parents (and children when applicable) will be asked "how satisfied with the means of sedation were you for the procedure performed". Research assistants will then ask the ED providers on a scale of 1 to 5 (1 being not satisfied and 5 being very satisfied) "how satisfied with the means of sedation were you for the procedure performed".	Time of discharge, Approximately 2 hours
Adverse Events.	Number of adverse events observed. Adverse events will be classified and defined as hypoxia, need for administration of reversal agent, nausea, vomiting, paradoxical reaction, airway obstruction, laryngospasm, inadequate sedation, allergic reaction, and cardiac arrest.	Time of discharge, Approximately 2 hours

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Paul A Szefler, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2017
• Primary Completion (Actual): November 8, 2018
• Study Completion (Actual): November 8, 2018

Study Registration Dates

• First Submitted: October 21, 2016
• First Submitted That Met QC Criteria: March 14, 2017
• First Posted (Actual): March 21, 2017

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: April 14, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Wounds and Injuries; Disease Attributes; Emergencies; Lacerations; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anesthetics, Inhalation; Midazolam; Nitrous Oxide
• Other Study ID Numbers: 16-1909

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.: No