Improving Sedation of Children Undergoing Procedures in the Emergency Department
Condition: Anxiety
MeSH terms: Emergencies
Study type: Interventional

Summary: 
      Lacerations (deep cuts) are a frequent cause of visits to emergency departments and
      laceration repair is one of the most common procedures performed in that setting. Children
      are often anxious when they visit the emergency department, and visits where they anticipate
      needing painful procedures can be particularly stressful. Though we can manage the pain
      associated with many minor procedures, we are frequently unable to adequately support the
      child and treat their problem if we don't manage their anxiety as well. Methods of calming
      that do not require medication (e.g. distraction, parental support) can help, but many
      patients still require sedative medications.

      The goal of sedation in the pediatric emergency department is to relieve the child's anxiety
      while minimizing the risk of adverse events. Unfortunately, when sedative medications are
      used in doses that do not slow breathing, they often fail to manage the child's anxiety
      adequately. In addition, many sedative agents require the placement of an intravenous line,
      which is itself a painful procedure that can create, rather than relieve, anxiety.

      Currently, there is no ideal sedative agent that is safe, effective, and easy to administer.
      Oral midazolam is one of the most commonly used sedative medications for laceration repair in
      children. In a dose of 0.5mg/kg it has been shown to be safe. Unfortunately, it provides
      adequate sedation in only about two thirds of patients and has a delayed onset of up to 20
      minutes. The remaining children must either endure the procedure in an agitated state or
      suffer placement of an intravenous line to administer additional sedative medications.

      We aim to find a method of providing sedation for laceration repair that has a higher success
      rate than oral midazolam as currently prescribed without increasing the risk of
      complications. We would like to evaluate new methods for administering midazolam using
      alternate routes and dosages. Previous studies have looked at the use of midazolam absorbed
      directly by mucous membranes such as inside the nose (intranasal) and inside the mouth
      (buccal). The use of intranasal midazolam has had some success especially given its rapid
      onset of action (about 5 minutes), but has been limited by the irritant effects of the drug.
      When placed in the mouth, many children swallow the drug or spit it out rather than allowing
      it to be absorbed by the mucous membrane. There has been some improved success when the drug
      was placed under the tongue, but this is typically difficult for young children. However, a
      new device called an "atomizer" has been developed that allows for improved intranasal and
      buccal administration. The "atomizer" has a small adapter placed on the end of a syringe,
      which spreads the medication out in a fine mist over a wide area. It can be sprayed in the
      mouth inside the cheek (buccal), avoiding the need to keep the medication under the tongue.
      While some pediatric institutions have already started giving midazolam with the atomizer,
      and are reporting anecdotal success with these methods, its safety and effectiveness have not
      been rigorously studied.

      We propose to compare three approaches to sedation: commonly used doses of oral midazolam,
      atomized intranasal midazolam and atomized intraoral midazolam. Children under the age of 7
      requiring sedation for wound repair will be eligible for enrollment. After informed consent,
      children will be randomized to one of the three methods described above. Their level of
      sedation will be determined using two scores validated for use in children (the sedation
      score and the modified CHEOPS score). Physician, nurse and parent impressions of sedation
      will also be compared.

      By comparing our current approach to these new methods, we will be able to determine which
      method is best. If we can identify a method for administering the sedative drug midazolam
      that is safe, well tolerated, and more effective, we will have made a valuable and important
      contribution to the care of injured children in the emergency department.
    

Detailed description: 
      The goal of this study is to improve sedation of children undergoing laceration repair in the
      emergency department. Currently, children who require sedation for laceration repair most
      often receive short acting benzodiazepines (i.e.,midazolam) orally (by mouth). Studies on the
      effectiveness of oral midazolam for minor procedures cite a 50-75% success rate. Oral
      midazolam has variable effectiveness and onset of action, and due to first pass hepatic
      metabolism, oral midazolam has a bioavailability of only 27% in children (Blumer 1998). Given
      the low success rate of oral midazolam, administration via mucous membranes has also been
      attempted. When administered intranasally or buccally, midazolam has a much higher
      bioavailability (Walberg 1991) and more rapid onset of action. Unfortunately, when given by
      these routes in previous studies, it was dripped into the nose or placed under the tongue.
      This leads to either swallowing the liquid drug, or expelling it, leading again to suboptimal
      bioavailability. Moreover, intranasal midazolam is irritating to the nasal mucosa and has
      therefore not always been well tolerated. When given to cooperative adults, midazolam dripped
      onto mucosal surfaces can have a bioavailability of approximately 75% (Schwagmeier 1998).

      It has been hypothesized that better distribution of midazolam on mucosal surfaces would
      improve the reliability and effectiveness of this route of administration. A device called an
      atomizer has been developed for just this purpose (Wolfe Tory Medical, Inc., Salt Lake City,
      UT). The atomizer is an attachment on the end of a small syringe that causes the medication
      to be propelled over a larger surface area in a spray (see Figure below). This allows a
      greater percentage of the medication to be absorbed via the mucosal surface with a direct
      route to the blood stream leading to faster and more reliable onset of action, while avoiding
      the problem of hepatic metabolism that occurs with enterally absorbed midazolam.

      We propose a study to determine if changes in the mode of administration and dosing of
      midazolam can provide improved sedation for children undergoing anxiety-producing procedures,
      without adversely effecting safety, length of stay, or patient/family and staff satisfaction.

      To study this, we propose a randomized clinical trial to compare three methods of
      administering midazolam for sedation: oral midazolam 0.5 mg per kg, buccal midazolam 0.3 mg
      per kg and intranasal midazolam 0.3 mg per kg. The subject population will be children under
      the age of 7 who require sedation for laceration repair in the Emergency Department of
      Children's Hospital and Regional Medical Center. Patients will be excluded if they have:
      closed head injury with loss of consciousness, abnormal neurologic exam relative to baseline
      status, severe developmental delay or baseline neurologic deficits, severe trauma with
      suspected internal injuries, acute or chronic respiratory conditions, or renal, cardiac or
      hepatic abnormalities.

      Variables of interest will include level of sedation prior to and during the procedure (using
      an activity scale and a modified CHEOPS scale) (McGrath 1985), time to adequate sedation,
      procedure length, length of ED stay, parental, MD, and RN satisfaction using a Likert scale,
      and complications such as respiratory depression and vomiting as well as measures needs to
      ameliorate those complications. For adequate power, we anticipate enrolling 180 patients (60
      in each treatment group) during the 24-month duration of the study.
    

Intervention name(s): Aerosolized Intranasal midazolam; Aerosolized Buccal Midazolam; Oral midazolam
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Midazolam will be administered via aerosolization (using "atomizer") with half of dose in each nostril. Total dose is 0.3mg/kg.; 0.3mg/kg total dose administered with aerosolization device ("atomizer") sprayed onto buccal mucosa inside the cheek on both sides of mouth.; oral midazolam 0.5mg/kg
Other intervention name(s): Versed; Versed; Versed
Intervention MeSH terms: Midazolam
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Sedation; Anxiety; Minor procedures; Emergency Department