PREMIX vs PREMED Intranasal Lidocaine and Midazolam

Columbia University

Status and phase: Completed; Phase 2

Conditions: Pain

Treatments: Drug: Midazolam; Drug: Lidocaine; Drug: Lidocaine and midazolam (PREMIX)

Study type: Interventional

Funder types: Other

Identifiers

NCT03054844

AAAQ6408

Details and patient eligibility

About

Intranasal (IN) midazolam is an anxiolytic that is commonly used in the pediatric population for procedural anxiolysis in the emergency department (ED) setting to facilitate painful and distressing procedures, such as laceration repairs. Intranasal midazolam is both effective and safe in children. However, due to the acidic nature of midazolam, there is a burning sensation that is associated with the intranasal administration of midazolam. The use of IN lidocaine has been shown to decrease the pain associated with the administration of IN midazolam and other acidic solutions. The IN lidocaine can be given as a premedication (PREMED), where it is sprayed in the nares first to provide topical anesthesia, and then followed by the administration of the IN midazolam. Lidocaine can also be given concurrently with the IN midazolam (PREMIX), where it is mixed with the midazolam and then the combined mixture administered. Both methods have been shown to be effective in decreasing the pain associated with the intranasal administration of acidic solutions, such as midazolam, although the PREMIX method could have the advantage of requiring less number of sprays, and be tolerated better by children. Although both methods have been shown to work, it is not known if the PREMIX method is non-inferior to the PREMED method for decreasing pain and distress associated with administering IN midazolam. Therefore, the investigators aim to determine if the PREMIX method is non-inferior to the PREMED method of using lidocaine to decrease the pain and distress associated with the administration of IN midazolam in children.

Full description

We will enroll 50 children to determine whether the PREMED method is non-inferior to the PREMIX method. We based our sample size on the outcome of pain and distress associated with the administration of IN midazolam, which will be measured using our primary outcome measure of the Observational Scale of Behavioral Distress-Revised (OSBD-R). The OSBD-R is an observational measure of distress that has been well validated in the pediatric population for evaluating painful and distressing procedures, and has been used in children as young as 1 year of age [1,2]. The sample size of 50 patients was determined based on a prestated margin of non-inferiority (delta) of 1.8 (SD 2.25). This value was based on the minimum clinically significant differences used in prior studies of painful procedures in children in the emergency department [3,4,5]. To determine noninferiority using a delta of 1.80 (SD 2.25), with a 1-tailed alpha of 0.025 and power of 80%, we would require 25 patients in each arm, for a total of 50 patients. OSBD-R scores will be determined independently by two blinded trained assessors who will review the videotapes of the study procedures. Interrater reliability of the OSBD-R between the two assessors will evaluated by determining the intraclass correlation coefficient. The period of administration of the midazolam alone in the PREMED group and the period of administration of the midazolam/lidocaine mixture in the PREMIX group are the two phases which will be compared to each other to determine our primary outcome.

Secondary outcome measures of pain and distress associated with IN midazolam administration will include the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS); the Faces-LegsActivity-Crying-Consolability (FLACC) scale; and cry duration. These are all continuous measures that will be analyzed using the independent samples t-test.We will also evaluate parental and provider satisfaction across various domains using a 5-point Likert scale (see attached document for questions to be asked). Responses will be dichotomized into "agree" (i.e. if respondent answers "agree" or "strongly agree") or "disagree" (i.e. if respondent responds "undecided", "disagree", or "strongly disagree") and analyzed using the chi square test.

Enrollment: 55 patients

Sex: All

Ages: 6 months to 7 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Between the age of ≥ 6 months or ≤ 7 years old
2. Undergoing a laceration repair
3. Treating physician has determined that patient requires intranasal midazolam to facilitate the laceration repair

Exclusion criteria

1. Weight < 5 kg
2. Known allergy to Lidocaine or Midazolam
3. Does not speak English or Spanish
4. Nasal injury precluding IN medication delivery
5. Presence of intranasal obstruction (mucous/blood) not easily cleared with suction or nose blowing
6. Baseline motor neurological abnormality (e.g. motor deficit, cerebral palsy)
7. Developmental delay, autism, autism spectrum disorder

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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55 participants in 2 patient groups

PREMED

Experimental group

Description:

Patients will receive 0.25 mL of IN 4% lidocaine (10 mg) in each naris (total of 0.5 mL/20 mg for both nares) preceding adminstration of IN midazolam.

Treatment:

Drug: Lidocaine

Drug: Midazolam

PREMIX

Experimental group

Description:

Patients will receive midazolam mixed with 0.5 mL of 4% lidocaine (20 mg).

Treatment:

Drug: Lidocaine and midazolam (PREMIX)