Clinical trial NCT00675909
Conditions: Anxiety
Keywords: Sedation Anxiety Minor procedures Emergency Department
Sponsor: Seattle Children's Hospital
Start date: 2006-11-01; Completion date: 2010-01-01
Enrollment: 180 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: Oral midazolam 0.5mg/kg arm 2: Intranasal midazolam 0.3mg/kg arm 3: Buccal midazolam 0.3mg/kg
Interventions: intervention 1: Aerosolized Intranasal midazolam intervention 2: Aerosolized Buccal Midazolam intervention 3: Oral midazolam
Intervention descriptions: intervention 1: Midazolam will be administered via aerosolization (using "atomizer") with half of dose in each nostril. Total dose is 0.3mg/kg. intervention 2: 0.3mg/kg total dose administered with aerosolization device ("atomizer") sprayed onto buccal mucosa inside the cheek on both sides of mouth. intervention 3: oral midazolam 0.5mg/kg

Protocol documents: