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

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT03085563
• Collaborator: (none)
• Enrollment: 63
• Location: 1
• Arms: 2
• Actual Duration (Months): 17.5
• Patients Per Site Per Month: 3.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Conscious Sedation; Simple Lacerations Less Than 4 cm; Lumbar Punctures; Minor Incision Drainage of Abscesses Not Requiring Extensive Debridement	Drug: Nitrous Oxide; Drug: Midazolam	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Comparison of Intranasal Midazolam and Nitrous Oxide (N2O) Minimal Sedation for Minor Procedures in a Pediatric Emergency Department
• Actual Study Start Date: May 24, 2017
• Actual Primary Completion Date: Nov 8, 2018
• Actual Study Completion Date: Nov 8, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. ED Length of Stay After Intranasal Midazolam or Nitrous Oxide Administration [From administration of intranasal midazolam or nitrous oxide, assessed over an estimated time of 2 hours.]

   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.

Secondary Outcome Measures

1. Patient/Parent and Provider Satisfaction With Sedation and Anxiolytic/Sedative. [Time of discharge, Approximately 2 hours]

   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".

2. Adverse Events. [Time of discharge, Approximately 2 hours]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

5. Minor procedures will include simple lacerations less than 4 cm

6. Lumbar punctures

7. Minor incision

8. Drainage of abscesses that do not require extensive debridement

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

10. Nitrous oxide up to 70% nitrous concentration will be allowed

11. 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:

13. pneumothorax,

14. air embolus,

15. pneumocephalus, or

16. craniotomy in the last 3 weeks,

17. intraocular surgery with retained gas,

18. pulmonary bullae,

19. severe emphysema, or

20. bowel obstruction.

21. Patients with significant co-morbidities:

22. severe pulmonary disease,

23. cardiac disease,

24. hematologic diseases associated with B12 deficiency,

25. sickle cell disease.

26. Patients with acute otitis media and/or sinusitis

27. History of paradoxical reaction to nitrous oxide

28. Known Methicillin-resistant Staphylococcus aureus (MRSA+) patients

29. Co-administration of additional sedation or analgesic medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Colorado	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 24, 2017

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT03085563
• Other Study ID Numbers: 16-1909
• First Posted: Mar 21, 2017
• Last Update Posted: May 10, 2022
• Last Verified: Apr 1, 2022

• 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
• Additional relevant MeSH terms: Emergencies; Lacerations; Midazolam; Nitrous Oxide

Study Results

Participant Flow

Pre-assignment Detail	Three patients were excluded prior to randomization (two withdrawals, one screen failure).

Arm/Group Title	Nitrous Oxide	Intranasal Midazolam
Arm/Group Description	Nitrous oxide will be delivered in one of two ways, using the titration method or rapid infusion method. 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%.	Intranasal midazolam with mucosal atomizer device administration will follow the Children's Hospital Colorado (CHCO) established policy 'Intranasal Administration (atomization) of Medications'. 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.
Period Title: Overall Study
STARTED	19	41
COMPLETED	19	41
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Nitrous Oxide	Intranasal Midazolam	Total
Arm/Group Description	Nitrous oxide will be delivered in one of two ways, using the titration method or rapid infusion method. 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%.	Intranasal midazolam with mucosal atomizer device administration will follow the Children's Hospital Colorado (CHCO) established policy 'Intranasal Administration (atomization) of Medications'. 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.	Total of all reporting groups
Overall Participants	19	41	60
Age (Count of Participants)
<=18 years	19 100%	41 100%	60 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	12 63.2%	13 31.7%	25 41.7%
Male	7 36.8%	28 68.3%	35 58.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	19 100%	41 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	ED Length of Stay After Intranasal Midazolam or Nitrous Oxide Administration
Description	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.
Time Frame	From administration of intranasal midazolam or nitrous oxide, assessed over an estimated time of 2 hours.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitrous Oxide	Intranasal Midazolam
Arm/Group Description	Nitrous oxide will be delivered in one of two ways, using the titration method or rapid infusion method. 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%.	Intranasal midazolam with mucosal atomizer device administration will follow the Children's Hospital Colorado (CHCO) established policy 'Intranasal Administration (atomization) of Medications'. 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.
Measure Participants	19	41
Time from intranasal midazolam or nitrous oxide administration to time of discharge readiness	24.5	18.5
Time from anxiolytic/sedative given to time of procedure completion	9	10
Total time for recovery	15.5	8.5

2. Secondary Outcome

Title	Patient/Parent and Provider Satisfaction With Sedation and Anxiolytic/Sedative.
Description	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 Frame	Time of discharge, Approximately 2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitrous Oxide	Intranasal Midazolam
Arm/Group Description	Nitrous oxide will be delivered in one of two ways, using the titration method or rapid infusion method. 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%.	Intranasal midazolam with mucosal atomizer device administration will follow the Children's Hospital Colorado (CHCO) established policy 'Intranasal Administration (atomization) of Medications'. 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.
Measure Participants	19	41
Parent/Patient	5	5
Provider	5	4.5

3. Secondary Outcome

Title	Adverse Events.
Description	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 Frame	Time of discharge, Approximately 2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitrous Oxide	Intranasal Midazolam
Arm/Group Description	Nitrous oxide will be delivered in one of two ways, using the titration method or rapid infusion method. 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%.	Intranasal midazolam with mucosal atomizer device administration will follow the Children's Hospital Colorado (CHCO) established policy 'Intranasal Administration (atomization) of Medications'. 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.
Measure Participants	19	41
hypoxia	0	3
need for administration of reversal agent	0	0
nausea, vomiting	0	0
paradoxical reaction	0	1
airway obstruction	0	0
laryngospasm	0	0
inadequate sedation	0	0
allergic reaction	0	0
cardiac arrest	0	0

Adverse Events

Time Frame	1 day
Arm/Group Title	Nitrous Oxide		Intranasal Midazolam
Arm/Group Description	Nitrous oxide will be delivered in one of two ways, using the titration method or rapid infusion method. 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%.		Intranasal midazolam with mucosal atomizer device administration will follow the Children's Hospital Colorado (CHCO) established policy 'Intranasal Administration (atomization) of Medications'. 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.
All Cause Mortality
	Nitrous Oxide		Intranasal Midazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/41 (0%)
Serious Adverse Events
	Nitrous Oxide		Intranasal Midazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/41 (0%)
Other (Not Including Serious) Adverse Events
	Nitrous Oxide		Intranasal Midazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		4/41 (9.8%)
Nervous system disorders
paradoxical reaction	0/19 (0%)	0	1/41 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
hypoxia	0/19 (0%)	0	3/41 (7.3%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.