Intranasal Medications for Anxiety During Pediatric Procedures

Overseen By Gavely Toor, DO

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Oklahoma

Must not be taking: Beta blockers

Disqualifiers: Cardiac, Respiratory, Renal, Liver, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day

90 Participants Needed

Trial Summary

What is the purpose of this trial?

Pain in young children has been universally under-recognized due to their inability to describe or localize pain. Improvements in pharmacological interventions are necessary to optimize patient and family experience and allow for successful and efficient procedure completion. This is the first study that will compare three intranasal medications (Intranasal Midazolam, Dexmedetomidine, and Ketamine) to evaluate the length of stay after medication administration along with patient and provider satisfaction. The objective of this study is to demonstrate superior intranasal anxiolysis for pediatric laceration repairs with the shortest emergency department stay and highest patient and provider satisfaction. Based on previous studies and medication pharmacokinetics, we hypothesize that Intranasal Ketamine will have the shortest Emergency Department (ED) stay followed by Midazolam and then Dexmedetomidine with the longest stay; however, Dexmedetomidine will have the highest patient and provider satisfaction followed by Ketamine and then Midazolam.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are taking beta blockers or any other blood pressure lowering agents, you cannot participate in the trial.

What data supports the effectiveness of the drug for reducing anxiety during pediatric procedures?

Research shows that intranasal dexmedetomidine and intranasal ketamine can effectively reduce anxiety in children before medical procedures, making them calmer and more cooperative. These drugs have been compared to other medications like oral midazolam and have shown promising results in reducing anxiety and improving sedation. ^{1 2 3 4 5}

Is intranasal medication safe for children during procedures?

Research shows that intranasal medications like dexmedetomidine, midazolam, and ketamine are generally safe for children when used for sedation during procedures, with studies focusing on their use in dental and cardiac settings. ^{2 3 4 6 7}

How is the intranasal drug for anxiety during pediatric procedures different from other treatments?

This treatment is unique because it uses the intranasal route to deliver a combination of dexmedetomidine, ketamine, and midazolam, which can provide faster and more predictable sedation compared to traditional oral medications. The intranasal method is non-invasive and can be more comfortable for children, making it a novel approach for managing anxiety during procedures. ^{1 3 4 7 8}

Research Team

Ryan Mckee, MD

Principal Investigator

University of Oklahoma

Eligibility Criteria

This trial is for children aged 1-5 who need stitches for small cuts (up to 5cm) and are in the emergency department. Their parents or caregivers must speak English. It's not clear what conditions exclude someone from participating.

Inclusion Criteria

I am between 1 and 5 years old.

I need stitches for a cut that is 5cm or shorter.

Exclusion Criteria

I have had injuries or issues with my eyes, nose, mouth, or face.

My heart rate or blood pressure is not normal for my age.

Known or anticipated difficult airway

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive intranasal Midazolam, Dexmedetomidine, or Ketamine for anxiolysis during minimal procedures in the pediatric emergency department

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including anxiety levels and satisfaction

1 day

1 visit (in-person)

Treatment Details

Interventions

• Intranasal Dexmedetomidine
• Intranasal Ketamine
• Intranasal Midazolam

Trial Overview The study compares three nose-spray medications—Midazolam, Dexmedetomidine, and Ketamine—to see which one helps kids feel less anxious during minor procedures, gets them home fastest, and makes both families and doctors happiest with the process.

Participant Groups

Group I: Intranasal Midazolam Experimental Treatment 1 Intervention

Dose/Concentration: 5mg/ml of 0.4mg/kg Midazolam (max dose 10mg). Adverse side effects include respiratory depression and hypotension. Intranasal Midazolam is standard of care for minimal procedures in pediatric ED.

Group II: Intranasal Ketamine Experimental Treatment 1 Intervention

Dose/Concentration: 100mg/ml of 3mg/kg Ketamine (max dose 100mg). Adverse side effect include Laryngospasm. IV Ketamine is FDA approved and widely used in procedural sedation in pediatric EDs. IN form isn't FDA approved in pediatric population; however, it has also been approved to conduct research studies especially in combination with other medications. Gutherie et al conducted a study demonstrating intranasal Ketamine providing safe and successful anxiolysis in pediatric patients in an ED setting.

Group III: Intranasal Dexmedetomidine Experimental Treatment 1 Intervention

Dose/Concentration: 100mcg/ml of 2mcg/kg Dexmedetomidine (max dose 100mcg). Adverse side effects include Hypotension and Bradycardia at high dosages. IV Dexmedetomidine is FDA approved and widely used in sedation. IN form isn't FDA approved; however, it has been approved to conduct research studies that have showed its efficacy in pre-operative settings, imaging-CT or MRI, dental procedures, and much more. Specifically, in a pediatric ED setting, Neville et al conducted a study comparing intranasal Dexmedetomidine and intranasal Midazolam prior to laceration repair in a pediatric emergency department and showed safe administration of Dexmedetomidine.

Intranasal Dexmedetomidine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Precedex for:

• Sedation of adult patients requiring monitored anesthesia care in outpatient settings
• Sedation of adult patients requiring sedation prior to diagnostic or surgical procedures
• Sedation of pediatric patients requiring sedation for diagnostic or therapeutic procedures

Approved in European Union as Dexdor for:

• Sedation of adult intensive care unit (ICU) patients requiring a sedation level not deeper than arousal in response to verbal command
• Sedation of adult patients requiring sedation prior to diagnostic or surgical procedures

Approved in Canada as Precedex for:

• Sedation of adult patients requiring monitored anesthesia care in outpatient settings
• Sedation of adult patients requiring sedation prior to diagnostic or surgical procedures

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Findings from Research

In a study of 60 children aged 1 to 8 undergoing surgery, intranasal ketamine provided significantly better sedation and mask acceptance compared to intranasal dexmedetomidine, with a p-value of < 0.0001.

However, while dexmedetomidine was less effective for sedation, it resulted in fewer cases of emergence delirium and postoperative nausea and vomiting, suggesting it may be safer for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Study of Intranasal Dexmedetomidine Versus Intranasal Ketamine as Premedicant in Children. Arun, N., Choudhary, A., Kumar, M.[2022]

In a study of 75 children aged over 5 years requiring general anesthesia, intranasal dexmedetomidine resulted in significantly better sedation during parental separation compared to oral midazolam, with 69.4% of dexmedetomidine patients achieving satisfactory sedation versus 40.5% for midazolam.

Intranasal dexmedetomidine was well-tolerated and did not cause significant changes in heart rate or blood pressure, indicating it is a safe option for pre-medication in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-medication before dental procedures: A randomized controlled study comparing intranasal dexmedetomidine with oral midazolam. Sathyamoorthy, M., Hamilton, TB., Wilson, G., et al.[2020]

In a study of 108 children aged 2-12, intranasal dexmedetomidine was found to significantly reduce preoperative anxiety compared to oral midazolam, with lower anxiety levels observed at 60 minutes, during induction, and in recovery phases.

Dexmedetomidine reduced the risk of anxiety by 28%, with a number needed to treat of 4, indicating that for every four children treated with dexmedetomidine, one case of anxiety could be prevented, while showing no serious side effects like bradycardia or hypotension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pre-anesthetic medication with intranasal dexmedetomidine and oral midazolam as an anxiolytic. A clinical trial]. Linares Segovia, B., García Cuevas, MA., Ramírez Casillas, IL., et al.[2022]

The combination of intranasal ketamine and intranasal dexmedetomidine significantly reduced sedation induction time to 13.5 minutes compared to 35 minutes with the standard combination of intranasal dexmedetomidine and oral midazolam, indicating a faster onset of action.

Younger children showed a higher success rate and shorter induction times for sedation, suggesting that age may influence the effectiveness of these sedation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal dexmedetomidine and intranasal ketamine association allows shorter induction time for pediatric sedation compared to intranasal dexmedetomidine and oral midazolam. Cossovel, F., Trombetta, A., Ramondo, A., et al.[2022]

Intranasal atomised dexmedetomidine was found to provide significantly better sedation in children undergoing spinal dysraphism surgery compared to intranasal atomised ketamine, as measured by the University of Michigan Sedation Score.

Both medications showed similar effectiveness in terms of ease of parental separation, intravenous cannulation, and mask acceptance, with no adverse effects reported, indicating that dexmedetomidine is a safe and effective premedication option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy of intranasal atomised dexmedetomidine versus intranasal atomised ketamine as a premedication for sedation and anxiolysis in children undergoing spinal dysraphism surgery: A randomized controlled trial. Hebbar K, C., Reddy, A., Luthra, A., et al.[2023]

In a study involving 84 uncooperative pediatric dental patients aged 4-14, intranasal Dexmedetomidine showed the highest overall success rate for sedation at 85.7%, compared to Midazolam (61.9%) and Ketamine (66.7%), although differences were not statistically significant.

All three medications (Dexmedetomidine, Midazolam, and Ketamine) were found to be safe, with no significant adverse effects reported, but Dexmedetomidine caused a notable reduction in pulse rate and systolic blood pressure compared to the other drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative evaluation of intranasal dexmedetomidine, midazolam and ketamine for their sedative and analgesic properties: a triple blind randomized study. Surendar, MN., Pandey, RK., Saksena, AK., et al.[2022]

In a study of 60 children aged 3-6 years undergoing cardiac catheterization, intranasal dexmedetomidine provided significantly better sedation and reduced anxiety compared to intranasal midazolam.

Dexmedetomidine also facilitated better parental separation during the premedication phase, indicating its potential as a preferred option for preanesthetic sedation in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Intranasal Dexmedetomidine Compared to Midazolam as a Premedication in Pediatrics with Congenital Heart Disease Undergoing Cardiac Catheterization. Messeha, MM., El-Morsy, GZ.[2022]

In a study of 60 children undergoing surgery, intranasal dexmedetomidine was found to significantly reduce sedation scores and anxiety levels compared to intranasal midazolam, indicating it may be a more effective premedication option.

Children receiving dexmedetomidine also experienced easier separation from their parents before surgery, suggesting it not only provides better sedation but also improves the overall experience for both the child and the parents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Intranasal Dexmedetomidine and Midazolam as Premedication in Pediatric Surgical Patients: A Prospective, Randomized Double-Blind Study. Diwan, G., Bharti, AK., Rastogi, K., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Comparative Study of Intranasal Dexmedetomidine Versus Intranasal Ketamine as Premedicant in Children. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pre-medication before dental procedures: A randomized controlled study comparing intranasal dexmedetomidine with oral midazolam. [2020]

3. Spain pubmed.ncbi.nlm.nih.gov

[Pre-anesthetic medication with intranasal dexmedetomidine and oral midazolam as an anxiolytic. A clinical trial]. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Intranasal dexmedetomidine and intranasal ketamine association allows shorter induction time for pediatric sedation compared to intranasal dexmedetomidine and oral midazolam. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy of intranasal atomised dexmedetomidine versus intranasal atomised ketamine as a premedication for sedation and anxiolysis in children undergoing spinal dysraphism surgery: A randomized controlled trial. [2023]

6. Singapore pubmed.ncbi.nlm.nih.gov

A comparative evaluation of intranasal dexmedetomidine, midazolam and ketamine for their sedative and analgesic properties: a triple blind randomized study. [2022]

7. India pubmed.ncbi.nlm.nih.gov

Comparison of Intranasal Dexmedetomidine Compared to Midazolam as a Premedication in Pediatrics with Congenital Heart Disease Undergoing Cardiac Catheterization. [2022]

8. India pubmed.ncbi.nlm.nih.gov

Comparison of Intranasal Dexmedetomidine and Midazolam as Premedication in Pediatric Surgical Patients: A Prospective, Randomized Double-Blind Study. [2022]