Intranasal Midazolam vs Intranasal Dexmedetomidine vs Intranasal Ketamine During Minimal Procedures in Pediatric Emergency Department

Sponsor

University of Oklahoma (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05934669

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Laceration of Skin Anxiety Discharge Time	Drug: Intranasal Midazolam Drug: Intranasal Dexmedetomidine Drug: Intranasal Ketamine	Phase 4

Detailed Description

Children commonly present to ED with injuries requiring procedures that can be painful or require a child to be absolutely still. Pain in young children has been universally under-recognized due to their inability to describe or localize pain. Multiple surveys of parents and families have showed that ED satisfaction is highly dependent on the degree of pain a patient experiences and the efforts made to alleviate the pain. Therefore, improvements in pharmacological interventions are necessary to optimize patient and family experience and allow for successful and efficient procedure completion.

Intranasal Midazolam is widely used for minimal procedural anxiolysis in pediatric population. Intranasal medication delivery has the highest parent and provider satisfaction with the advantage of avoiding painful needle stick and faster absorption compared to oral or intramuscular medication. Midazolam is a gamma-aminobutyric acid (GABA) receptor agonist that can provide anxiolysis and amnesia but no analgesia. Intranasal Midazolam has a rapid onset of 5-10 minutes with peak at 30 minutes. There have been limited studies evaluating the length of stay or time to discharge after medication administration with an average length of stay of about 30 minutes. It has been shown to be safe and effective in children for minor procedures; however, intranasal Midazolam is notoriously noxious and irritating to nasal mucosa and requires larger volumes for intranasal dosing. Main side effects include respiratory depression and hypotension. It is also known to cause paradoxical reaction with hyperactivity, agitation, and restlessness especially in developmentally delayed or children with Autism or behavioral concerns. Therefore, several new studies have evaluated other newer intranasal medications for minor procedures including intranasal Dexmedetomidine and intranasal Ketamine.

Dexmedetomidine is an alpha 2 agonist that mirrors sleep in children and can provide anxiolysis and minimal analgesia. Intranasal dosages that have provided adequate minimal sedation is 2-4mcg/kg (max dosage 100-200mcg) with wide range of onset 10-45 mins with average 30 minutes and peak at 90 minutes. Unlike Midazolam, it preserves airway reflexes without clinically significant hemodynamic instability in children. Studies have also shown that it is well tolerated by children and preferred in children with Autism and behavioral concerns.

Ketamine is an N-methyl-D-aspartate (NMDA) antagonist that provides both anxiolysis and analgesia. It is widely used in ED settings for intravenous procedural sedation; however, intranasal route provides non-invasive method of medication administration. Gutherie et al conducted a study demonstrating intranasal Ketamine providing safe and successful anxiolysis and analgesia in pediatric patients in an ED setting. Intranasal dosage of 3-5mg/kg (max dosage 100-200mg) provides optimal onset of action within 10 minutes with peak at 15-20 minutes and duration of 45-60 minutes. It has few significant side effects including the rare laryngospasm and recovery agitation, however, it preserves airway reflexes and favorable in hemodynamic instability.

Previous Studies:

Limited studies have demonstrated anxiolysis with patient and provider satisfaction or time to discharge after medication administration comparing intranasal Midazolam to intranasal Dexmedetomidine or intranasal Ketamine in a pediatric emergency medicine setting. Neville et al conducted a study comparing intranasal Dexmedetomidine and intranasal Midazolam prior to laceration repair in a pediatric emergency department and concluded that patients who received Dexmedetomidine had less anxiety at the time of positioning for the procedure. Several other studies have demonstrated similar outcomes with better patient and provider satisfaction in pre-operative settings, imaging, and dental settings. Surendar et al is the only study that compared all three intranasal medications. The study included uncooperative pediatric patients in a dental setting. Although overall differences were not statistically significant, the onset of sedation was rapid among Intranasal Ketamine and Midazolam groups but overall success was highest in Dexmedetomidine group.

Objective/Aims/Hypothesis:

This is the first study that will compare all three intranasal medications 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. The primary outcome will measure the time to discharge after medication administration. Other measurements with include patient's anxiety using previously validated scale Modified Yale Preoperative Anxiety Scale (mYPAS) and physician and parent satisfaction using 5 point Likert scale. Based on previous studies and medication pharmacokinetics, we hypothesize that Ketamine will have the shortest 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

After patient enrollment, a nurse will assign a chronological number from 1 to 90. The pharmacist will randomly divide all 90 subjects into 3 even groups to receive either medication A, B, or C. The pharmacist will dispense the medication in a 1ml syringe to the chronological number provided in the order. The nurse will fill out a mYPAS scale to assess the patient's anxiety level and then administer the medication. After 30 minutes, the physician will determine subject readiness and perform laceration repair. The patient's vitals will be monitored every 5 minutes. At the end of the procedure, both the physician and the parent will answer a question using a Likert scale and the nurse will fill out another mYPAS scale. After the procedure, the patient will be monitored in the ED for any adverse effects and will be discharged home once the patient meets established discharge criteria. The nurse will document the time the patient is discharged.After patient enrollment, a nurse will assign a chronological number from 1 to 90. The pharmacist will randomly divide all 90 subjects into 3 even groups to receive either medication A, B, or C. The pharmacist will dispense the medication in a 1ml syringe to the chronological number provided in the order. The nurse will fill out a mYPAS scale to assess the patient's anxiety level and then administer the medication. After 30 minutes, the physician will determine subject readiness and perform laceration repair. The patient's vitals will be monitored every 5 minutes. At the end of the procedure, both the physician and the parent will answer a question using a Likert scale and the nurse will fill out another mYPAS scale. After the procedure, the patient will be monitored in the ED for any adverse effects and will be discharged home once the patient meets established discharge criteria. The nurse will document the time the patient is discharged.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

A double blind randomized study. Except for the pharmacist, all treating ED physicians, nurses, patients, patients' caregivers/guardians, ancillary staff, and data analysts will be blinded to the medication administered to the patient. The medication will be dispensed in a 1ml syringe and the barrel of the syringe will be covered by the pharmacist. All the syringes sent from the pharmacy will appear the same, regardless of the volume of the medication.

Primary Purpose:

Supportive Care

Official Title:

Randomized Controlled Trial of Intranasal Midazolam vs Intranasal Dexmedetomidine vs Intranasal Ketamine Evaluating Length of Stay After Medication Administration and Anxiolysis During Minimal Procedures in Pediatric Population in Pediatric Emergency Department

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intranasal Midazolam 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.	Drug: Intranasal Midazolam Using a computer-generated randomization schedule by the research pharmacist, all 90 subjects will be divided into 3 even groups to receive either medication A (intranasal Midazolam), B (intranasal Dexmedetomidine), or C (intranasal Ketamine). Based on the randomization schedule, the pharmacist will dispense medication A, B, or C to the chronological number provided in the order. The total amount of the medication will be based on the patient's charted weight. Small volumes of less than 1ml per nostril are preferred for reliable absorption; therefore, the medication will be dispensed in a 1ml syringe and the barrel of the syringe will be covered by the pharmacist. All the syringes sent from the pharmacy will appear the same, regardless of the volume of the medication. Other Names: Intranasal Versed
Experimental: Intranasal Dexmedetomidine 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.	Drug: Intranasal Dexmedetomidine See above Other Names: Intranasal Precedex
Experimental: Intranasal Ketamine 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.	Drug: Intranasal Ketamine See above

Arm

Intervention/Treatment

Experimental: Intranasal Midazolam

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.

Drug: Intranasal Midazolam

Using a computer-generated randomization schedule by the research pharmacist, all 90 subjects will be divided into 3 even groups to receive either medication A (intranasal Midazolam), B (intranasal Dexmedetomidine), or C (intranasal Ketamine). Based on the randomization schedule, the pharmacist will dispense medication A, B, or C to the chronological number provided in the order. The total amount of the medication will be based on the patient's charted weight. Small volumes of less than 1ml per nostril are preferred for reliable absorption; therefore, the medication will be dispensed in a 1ml syringe and the barrel of the syringe will be covered by the pharmacist. All the syringes sent from the pharmacy will appear the same, regardless of the volume of the medication.

Other Names:

Intranasal Versed

Experimental: Intranasal Dexmedetomidine

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.

Drug: Intranasal Dexmedetomidine

See above

Other Names:

Intranasal Precedex

Experimental: Intranasal Ketamine

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.

Drug: Intranasal Ketamine

See above

Outcome Measures

Primary Outcome Measures

The primary outcome will measure the time to discharge after intranasal medication administration [Day 1]
The nurse will document the time the medication is administered and the time of discharge once the patient meets AAP criteria of discharge. AAP discharge criteria includes cardiovascular function and airway potency satisfactory; arousable and protective reflexes are intact; able to talk appropriately for age; able to sit up appropriately for age; and state of hydration is adequate

Secondary Outcome Measures

The secondary outcome will measure patient's anxiety using the previously validated scale mYPAS and physician and parent satisfaction using a 5-point Likert scale [Day 1]
Once the pharmacy dispenses the medication, the nurse will fill out an 18-point scale survey (Modified Yale Preoperative Anxiety Scale [mYPAS]) to assess the patient's anxiety level. At the end of the procedure, both the physician and the parent will answer a question using a 5-point Likert scale and the nurse will fill out the same mYPAS survey utilized prior to medication administration. The mYAS scale evaluates four domains including activity, vocalizations, emotional expressivity, and state of apparent arousal. The scoring is combined into a total anxiety score between 23.3 and 100 with a patient scoring less than or equal to 30 being categorized as not anxious. The scores on 5-point Likert scale are categorized into very satisfied, satisfied, no difference, unsatisfied, very unsatisfied for 5, 4, 3, 2, and 1, respectively.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 5 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age 1-5 years old
Presents to the ED for suture repair for lacerations less than or equal to 5cm in length
Parent(s)/Caregiver(s) speak English

Exclusion Criteria:

Younger than 12 months of age or older than 5 years old
Suture repair needed for lacerations are greater than 5cm in length
Known allergy or adverse effect to Midazolam, Dexmedetomidine, Ketamine, or any other sedatives
Any abnormal vital signs for age, especially heart rate and blood pressure
History of Cardiac, respiratory, renal, or liver disease
Known electrolyte abnormalities
Any ocular trauma, nasal injury, nasal deformity, significant nasal congestion, abnormalities in the nasal or oral mucosa, facial deformity, or facial injury
Home medications include beta blockers or any other blood pressure lowering agents Classified ASA III and above
Known or anticipated difficult airway
Abnormal neurological exam
Parent(s)/Caregiver(s) do not speak English

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University of Oklahoma

Investigators

Principal Investigator: Ryan Mckee, MD, University of Oklahoma

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

University of Oklahoma

ClinicalTrials.gov Identifier:

NCT05934669

Other Study ID Numbers:

15872

First Posted:

Jul 7, 2023

Last Update Posted:

Jul 7, 2023

Last Verified:

Jun 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 7, 2023