PREMIX vs PREMED Intranasal Lidocaine and Midazolam
Condition: Pain
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed 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.
    

Intervention name(s): Lidocaine; Lidocaine and midazolam (PREMIX); Midazolam
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Lidocaine will be administered before administration of midazolam.; Lidocaine will be administered as a mixture with midazolam.; Midazolam will be administered either after lidocaine, or as a mixture with lidocaine.
Other intervention name(s): PREMED; PREMIX
Intervention MeSH terms: Lidocaine; Midazolam
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Intranasal; Pain; Lidocaine; Midazolam; Emergency department