Trial Outcomes & Findings for A Comparison of Intranasal Midazolam and Nitrous Oxide (N2O) Minimal Sedation for Minor Procedures in a Pediatric Emergency Department (NCT NCT03085563)

Last Updated: 2022-05-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

63 participants

Primary outcome timeframe

From administration of intranasal midazolam or nitrous oxide, assessed over an estimated time of 2 hours.

Results posted on

2022-05-10

Participant Flow

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

Participant milestones

Participant milestones
Measure	Nitrous Oxide 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 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.
Overall Study STARTED	19	41
Overall Study COMPLETED	19	41
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nitrous Oxide n=19 Participants 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 n=41 Participants 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 n=60 Participants Total of all reporting groups
Age, Categorical <=18 years	19 Participants n=19 Participants	41 Participants n=41 Participants	60 Participants n=60 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=19 Participants	0 Participants n=41 Participants	0 Participants n=60 Participants
Age, Categorical >=65 years	0 Participants n=19 Participants	0 Participants n=41 Participants	0 Participants n=60 Participants
Sex: Female, Male Female	12 Participants n=19 Participants	13 Participants n=41 Participants	25 Participants n=60 Participants
Sex: Female, Male Male	7 Participants n=19 Participants	28 Participants n=41 Participants	35 Participants n=60 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	19 participants n=19 Participants	41 participants n=41 Participants	60 participants n=60 Participants

PRIMARY outcome

Timeframe: From administration of intranasal midazolam or nitrous oxide, assessed over an estimated time of 2 hours.

Outcome measures

Outcome measures
Measure	Nitrous Oxide n=19 Participants 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 n=41 Participants 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.
ED Length of Stay After Intranasal Midazolam or Nitrous Oxide Administration Time from intranasal midazolam or nitrous oxide administration to time of discharge readiness	24.5 minutes Interval 15.5 to 33.5	18.5 minutes Interval 16.0 to 34.0
ED Length of Stay After Intranasal Midazolam or Nitrous Oxide Administration Time from anxiolytic/sedative given to time of procedure completion	9 minutes Interval 3.0 to 19.0	10 minutes Interval 6.0 to 16.0
ED Length of Stay After Intranasal Midazolam or Nitrous Oxide Administration Total time for recovery	15.5 minutes Interval 12.5 to 17.5	8.5 minutes Interval 7.0 to 18.0

SECONDARY outcome

Timeframe: 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".

Outcome measures

Outcome measures
Measure	Nitrous Oxide n=19 Participants 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 n=41 Participants 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.
Patient/Parent and Provider Satisfaction With Sedation and Anxiolytic/Sedative. Parent/Patient	5 score on a scale Interval 5.0 to 5.0	5 score on a scale Interval 4.0 to 5.0
Patient/Parent and Provider Satisfaction With Sedation and Anxiolytic/Sedative. Provider	5 score on a scale Interval 4.0 to 5.0	4.5 score on a scale Interval 4.0 to 5.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Nitrous Oxide n=19 Participants 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 n=41 Participants 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.
Adverse Events. hypoxia	0 Adverse Events	3 Adverse Events
Adverse Events. need for administration of reversal agent	0 Adverse Events	0 Adverse Events
Adverse Events. nausea, vomiting	0 Adverse Events	0 Adverse Events
Adverse Events. paradoxical reaction	0 Adverse Events	1 Adverse Events
Adverse Events. airway obstruction	0 Adverse Events	0 Adverse Events
Adverse Events. laryngospasm	0 Adverse Events	0 Adverse Events
Adverse Events. inadequate sedation	0 Adverse Events	0 Adverse Events
Adverse Events. allergic reaction	0 Adverse Events	0 Adverse Events
Adverse Events. cardiac arrest	0 Adverse Events	0 Adverse Events

Adverse Events

Nitrous Oxide

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Intranasal Midazolam

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Nitrous Oxide n=19 participants at risk 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 n=41 participants at risk 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.
Respiratory, thoracic and mediastinal disorders hypoxia	0.00% 0/19 • 1 day	7.3% 3/41 • Number of events 3 • 1 day
Nervous system disorders paradoxical reaction	0.00% 0/19 • 1 day	2.4% 1/41 • Number of events 1 • 1 day

Additional Information

Paul Szefler, MD, FAAP

Children's Hospital Colorado

Phone: 303-724-1111

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place