Nitrous Oxide Use in Minor Procedures
Condition: Laceration; Abscess
MeSH terms: Lacerations
Study type: Interventional

Summary: 
      Title:

      High-concentration continuous flow nitrous oxide use for procedural-induced pain or anxiety
      during pediatric minor procedures.

      Objective: To assess whether the use of high-concentration continuous flow nitrous oxide in
      addition to standard management increases the comfort level in pediatric patients undergoing
      minor procedures compared to standard management alone.
    

Detailed description: 
      Title:

      High-concentration continuous flow nitrous oxide use for procedural-induced pain or anxiety
      during pediatric minor procedures

      Brief Summary:

      Background: Over the past 10 years pediatric emergency departments (PED) throughout the
      country have adopted the concept of an "ouchless" PED, using both pharmacologic and
      non-pharmacologic methods to achieve this goal. There are a number of minor procedures
      performed routinely in a PED. Despite our interest in an "ouchless" PED, many of these
      procedures are performed without full attention to patient comfort. Some procedures, such as
      laceration repair, require local anesthesia, while others, such as intravenous catheter
      placement, are usually performed without local anesthesia. All of these minor procedures,
      however, are ones in which the risk of parenteral procedural sedation outweighs the benefit.

      Due to the awareness of trying to create as pain-free an experience as possible, the use of
      high-concentration nitrous oxide (>50%) in the pediatric outpatient setting has grown and is
      used in PEDs throughout the country. Nitrous oxide is a colorless, non-narcotic, analgesic
      gas. Its efficacy and safety have been well documented in anesthesia, pediatric and dental
      literature. Over the last 30 years, nitrous oxide has been incorporated in the outpatient
      pediatric setting for procedural analgesia. At Jacobi Medical Center (JMC), nitrous oxide has
      been successfully used for children undergoing a variety of minor procedures in the PED.

      Several studies have been published on the use of nitrous oxide in decreasing pain and
      anxiety in the pediatric emergency setting; however, previous studies using high
      concentration nitrous oxide have been either observational, have focused on a narrow age
      range, a single procedure type or procedures associated with moderate to severe pain, such as
      fracture reduction.

      This investigation, unlike previous studies, will include a wider age range of children, as
      well as a variety of painful or anxiety provoking minor procedures commonly performed in the
      PED. We are choosing to include a variety of pre-defined minor procedures, rather than a
      single procedure, in order to assess the feasibility and benefit of nitrous oxide for the
      many minor procedures performed routinely on a daily basis in a pediatric emergency
      department. It will allow us to quantify our rate of effectiveness in decreasing pain and/or
      anxiety with the use of high concentration (>50%) nitrous oxide and to expand the use of
      nitrous oxide if shown to be superior to standard management in the reduction of procedural
      pain and anxiety.

      Objective: To assess whether the use of high-concentration continuous flow nitrous oxide in
      addition to standard management increases the comfort level in pediatric patients undergoing
      minor procedures compared to standard management alone.

      Methods: This will be a prospective randomized controlled trial conducted in the JMC PED.
      Children 3-12 years of age presenting to the PED, who require a minor procedure will be
      assessed for eligibility. Minor procedures will be defined as any procedure in which the
      standard management may involve providing local anesthetic and/or holding the child in order
      to successfully accomplish the procedure. These are not procedures in which the patient would
      receive parenteral analgesics, anxiolytics or anesthetics, because they are minimally painful
      and do not warrant the potential risks associated with parenteral anesthesia. Examples of
      minor procedures include simple incision and drainage of an abscess, intravenous catheter
      placement, urinary catheter placement, paronychia incision, foreign body removal and simple
      laceration repair. A local anesthetic such as injectable lidocaine or a topical anesthetic
      such as Eutectic Mixture of Local Anesthetics (EMLA) is frequently used and their use will be
      at the discretion of the provider performing the procedure. The doses of the topical
      anesthetics used are uniform. The decision of whether topical anesthesia will be used will be
      made by the provider before group randomization of the patient. Exclusion criteria include
      patients with medical conditions in which nitrous oxide is contraindicated, who are unable to
      communicate reliable levels of pain or who have low-to-no anxiety levels demonstrable by a
      validated anxiety scale, scored in the examining room by a research assistant after the
      procedure is described by the provider. After obtaining parental consent/child assent,
      patients will be randomized using a random number table to group 1 (nitrous oxide plus
      standard management) or group 2 (standard management alone). Because younger children
      especially experience significant anxiety before and during procedures, which can negatively
      affect the success of the procedure, we will use block randomization by groups of 6 for two
      separate age groups in order to ensure equal representation in both groups. These groups will
      be divided into preschool age (3 years to <6 years) and school age (>6 years- 12 years)
      children. Patients in the nitrous oxide group will receive nitrous oxide up to 70%
      concentration using a nitrous oxide protocol previously developed for use in the PED
      (attached), along with standard management (+/- local anesthetic, +/- holding the child) as
      determined by the provider prior to randomization. Patients in Group 2 will receive standard
      management alone (+/-local anesthetic, +/- holding the child).

      Data Collection:

      Data collection occurs at three time points: pre- procedure, intra-procedure and
      post-procedure. The pre-procedural data collection will include: 1) a pain score using a
      standard number scale ranging from 0-10 for children >6 years or 10-point Wong-Baker faces
      pain scale for children < 6 years measured at the time of triage by the triage nurse and 2)
      demographics including age, gender, procedure type, adjunctive pain medication (including the
      use of local anesthesia) and anxiety score using the Modified Yale Preoperative Anxiety Scale
      (M-YPAS) performed by a research assistant (medical student or college student who will be
      trained in data collection) in the treatment room after the provider has described the
      procedure to the patient and parent. Intra-procedural data collection will include: comfort
      score measured on the Face, Legs, Activity, Cry, Consolability (FLACC) Pain Scale and anxiety
      score measured on the M-YPAS. The FLACC Scale is a 10 point scoring system with 10 indicating
      the highest level of pain. Both scoring scales are validated scales of pain (FLACC) and
      anxiety (M-YPAS). The FLACC score and the M-YPAS score will be documented by a research
      assistant (medical student or college student who will be trained in data collection). The
      post-procedure data collection will include: mask tolerance, level of holding the child
      required in order to complete the procedure, length of procedure, highest nitrous oxide
      concentration used, patient recovery time back-to-baseline, adverse events, and independent
      rating of the success of the procedure by both the provider performing the procedure and the
      provider administering the nitrous oxide. At the end of the visit, a research assistant
      blinded to the patient's group assignment will document the parent's satisfaction with the
      encounter.

      Outcomes:

      The primary outcome will be the FLACC Pain Scale score measured intra-procedure. Secondary
      outcomes will be the M-YPAS Anxiety Score, length of the procedure, parent satisfaction
      score, and provider rating of success of the procedure. To assess inter-relator reliability,
      a second provider will complete the provider survey for 75% of the participants.

      Sample Size:

      Based on a pre-study sample of children undergoing minor procedures, the mean FLAAC Pain
      Scale score was 7.25/10. We determined that a 25% difference in the mean FLACC scores between
      the two groups would be clinically relevant. In various published articles a clinical
      significant change in pain score was noted with the use of nitrous oxide between 20% and 40%.
      At an alpha of .05 and a power of 80%, we estimate a sample size of 42 patients in each arm
      (21 patients in each of the two age ranges per arm).

      Statistics:

      Data will be collected and analyzed using Statistical Package for the Social Sciences (SPSS)
      version 19 with the FLACC Pain Scale being the primary outcome measure. The mean FLACC score
      will be compared between the two groups. Ordinal variables will be analyzed using the
      Mann-Whitney -U test and categorical values using the Chi Square test. Associations between
      the intra-procedure FLACC Pain Scale score with patient age (preschool and school age),
      pre-procedural pain and pre-procedural anxiety scores will be analyzed using Spearman
      correlation and the Chi Square test. The kappa statistic will be used to assess agreement
      between the two providers' rating of the success of the procedure. Since the randomization is
      stratified and the sample size calculation is based on stratified analysis, we will analyze
      both groups separately to test this hypothesis. An interim review of the data will be done
      effectiveness of the treatment. Any adverse events will be reported by the principal
      investigator in writing to the The Committee on Clinical Investigations (CCI) and the
      institutional review board (IRB).

      Additional Response:

      Although lack of blinding may be seen as a potential weakness concerning objectivity of the
      main outcome, we are intentionally not blinding the study in order to mimic PED practice. Our
      goal is to determine whether nitrous oxide will benefit the child in terms of reducing pain
      and/or anxiety during a minor procedure. The method of delivery, however, may be in itself
      noxious to some children (face mask). Introducing this aspect to the standard arm may unduly
      increase the FLACC Pain Scale score in this group. Additionally, in the sense that we may be
      introducing a noxious stimulus without any possibility of benefit seems unethical.

      In both arms, the administration of local anesthetic and/or the degree to which a child is
      held in order to perform the procedure will be at the discretion of the treating physician.
      The practice, however, for a specific minor procedure is similar between all providers. For
      example, a child receiving sutures will have a topical anesthetic placed at triage and then
      injectable lidocaine administered at the time of the suturing. The doses for topical
      anesthetics are uniform and the decision by the provider whether to use topical anesthesia
      will be made before group randomization. In order for our data to be clinically meaningful,
      we again want to mimic PED practice. The details of all aspects of adjuvant care, such as
      local anesthetic use and holding a child, will be documented.

      Risks:

      The adverse effects of nitrous oxide occur very infrequently. However, in the literature, the
      following adverse effects have been described: vomiting, oxygen desaturation, dizziness,
      euphoria, abdominal pain and hallucinations.

      Benefits:

      The subjects may or may not experience a decreased pain and anxiety level, potential for
      shorter procedure time due to compliance, and increased parent/child satisfaction. A positive
      procedural experience may reduce long-term procedural traumatic distress.
    

Intervention name(s): Nitrous Oxide
Intervention type(s): Drug
Intervention description(s): Patients randomized to the intervention arm will receive nitrous oxide plus standard management for their minor procedure.
Other intervention name(s): nitronox
Intervention MeSH terms: Nitrous Oxide
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: nitrous oxide; pediatric pain and anxiety