ALICE: Anxiolysis for Laceration Repair in Children
Study Details
Study Description
Brief Summary
This is a 3-arm adaptive clinical trial to the optimal light sedative for reducing distress during laceration repair in children. The investigators will compare intranasal (IN) dexmedetomidine, IN midazolam, and nitrous oxide (N20). The primary outcome is the Observational Scale of Behavioral Distress - Revised (OSBD-R).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Accounting for almost half of all procedures performed, lacerations are the most common reason for an ED visit in children. There is consistent evidence that children experience considerable distress during laceration repair, despite routine application of topical anesthetic, lidocaine-epinephrine-tetracaine (LET). Certified child life specialists (CCLSs) can help children cope with distress but are not widely available. Untreated distress in childhood can lead to anxiety, needle phobia, and fear of medical care as adults. The American Academy of Pediatrics and American Academy of Pediatric Dentistry strongly recommend minimizing discomfort and controlling behavior and movement during procedures but there is no specific guidance on laceration repair. Many children require pharmacologic anxiolysis for laceration repair but evidence for the most effective agent is lacking. Although anxiolytics such as midazolam and nitrous oxide (N2O) are frequently used, there are drawbacks including variable efficacy and nasal irritation in the case of midazolam and lack of cooperation in younger children in the case of N2O. IN dexmedetomidine is a potentially effective anxiolytic for laceration repair that could overcome these limitations.
IN dexmedetomidine is a relatively new anxiolytic with sedative and analgesic properties. It is tasteless, non-irritative, and highly concentrated (100 mcg/mL). A maximum dose of 200 mcg/2 mL can be given with 2 pairs of 0.5 mL IN sprays. The investigator's team published a systematic review of IN dexmedetomidine for distressing procedures. It was well tolerated by more than 90% of children and provided adequate anxiolysis in more children (79%) versus conventional anxiolytics (midazolam, chloral hydrate) (60%). Only one trial investigated IN dexmedetomidine in children for laceration repair and 70% were deemed "not anxious" compared to IN midazolam (11%). However, the study focused on initial positioning rather than repair. For proof of concept and to identify the optimal dose and feasibility of IN dexmedetomidine, we completed a pilot of 55 children undergoing laceration repair. All children tolerated IN administration, the consent rate was 82%, and there were no serious adverse events (AE). A dose of 3 mcg/kg balanced efficacy with duration of sedation, in line with others' findings.
Oral midazolam is the most common anxiolytic for laceration repair in children. However, onset and duration of action and efficacy can be unreliable and its bitter taste leads to poor compliance. IN midazolam using a mucosal atomizer device (MAD) is increasingly popular because it overcomes these limitations. Compared to oral midazolam, IN midazolam has a shorter onset of action (28 vs 34 minutes) but causes nasal irritation in up to 40% of patients. In addition, IN midazolam has variable efficacy for laceration repair and more adverse effects compared to nitrous oxide or IN dexmedetomidine. The largest study of IN midazolam was a retrospective study of combination IN midazolam plus fentanyl. A lower dose of midazolam (0.2 mg/kg) resulted in fewer adverse effects (0.7%) than with higher doses (2-5%). Adding IN fentanyl provided superior efficacy where only 2.4% of patients experienced a treatment failure.
The second most common anxiolytic is inhaled N2O, a tasteless gas that is administered in a concentration of 30-70% with oxygen. N2O is safe and effective for minor painful procedures. Peak effect is rapid (2 minutes) and effects dissipate quickly (3 minutes) upon discontinuation. Minor adverse effects occur in less than 10% of patients. However, based on the United Kingdom National Clinical Guideline Centre, it's unclear whether uncooperative children will comply with N2O administration. The investigators' recently completed systematic review of 29 trials of N2O for painful procedures in children found 50% N2O was superior to subcutaneous lidocaine, placebo, and oral midazolam. Only 5 trials focused on laceration repair but they were small and limited by non-validated or no measures of anxiety .
Despite frequent use of anxiolytics such as midazolam and N2O, The investigators' national survey found that 80% of Canadian paediatric ED physicians strongly believed that "children experience significant enough distress to warrant anxiolysis" and it would "improve the patient care experience". To improve care, a rigorous trial of a novel anxiolytic, IN dexmedetomidine, and dissemination of the research findings is needed.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Intranasal dexmedetomidine IN dexmedetomidine 3 mcg/kg [100 mcg/mL (max 200 mcg or 2 mL)] |
Drug: Dexmedetomidine
Intranasal dexmedetomidine 3 mcg/kg [100 mcg/mL (max 200 mcg or 2 mL)
Other Names:
|
| Experimental: Intranasal midazolam IN midazolam 0.4 mg/kg [5 mg/mL (max 10 mg or 2 mL)] |
Drug: Midazolam Nasal Spray
Intranasal midazolam 0.4 mg/kg [5 mg/mL (max 10 mg or 2 mL)
Other Names:
|
| Experimental: Inhaled nitrous oxide 50% N2O in 50% oxygen by face mask or on-demand system |
Drug: Nitrous oxide
50% nitrous oxide in 50% oxygen by face mask or on-demand system
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Observational Scale of Behavioral Distress - Revised (OSBD-R) [During preparation, suturing, and recovery (20 minutes)]
Score ranges from 0 (no distress) to 23.5 (maximal distress) and will be scored for the time interval encompassing preparation, suturing, and recovery
Secondary Outcome Measures
- Adverse effects [From intervention to 72 hours post-discharge]
Will be based on the Quebec guidelines for sedation in children and include nausea and vomiting
- Need for additional sedation [During suturing (10 minutes)]
Need for additional sedation or anxiolysis unrelated to study interventions
- Pain during suturing [During suturing (10 minutes)]
Pain during suturing using the Faces, Legs, Arms, Activity, Cry (FLACC) scale. The FLACC is an observational scale, scored from 0 (no pain) to 10 (maximal pain)
- Need for physical restraint [During preparation and suturing (10 minutes)]
Need for restraint during preparation and suturing based on the Procedural Restraint Intensity in Children (PRIC) scale. The PRIC is scored in discrete integer values from 0=no restraint to 4=extreme forceful restraint. A higher score indicates more restraint is needed.
Other Outcome Measures
- Compliance with intervention administration [From drug administration through suturing (40 minutes)]
Compliance (percent of calculated IN volume given and acceptance of face mask or on-demand system)
- Caregiver satisfaction with anxiolysis during laceration repair [At discharge (1 minute)]
Caregiver satisfaction with anxiolysis (5-item Likert scale ranging from 1=very unsatisfied to 5=very satisfied). A higher score indicates greater satisfaction.
- Child satisfaction with anxiolysis during laceration repair [At discharge (1 minute)]
Child (7-12 years) satisfaction with anxiolysis (5-item Likert scale ranging from 1=very unsatisfied to 5=very satisfied). A higher score indicates greater satisfaction.
- Healthcare provider (physician, nurse, respiratory therapist) satisfaction with anxiolysis during laceration repair [During recovery (1 minute)]
Nurse, physician, parent, and child 7-12 years satisfaction with anxiolysis (5-item Likert scale ranging from 1=very unsatisfied to 5=very satisfied). A higher score indicates greater satisfaction.
- Number of healthcare personnel required during repair [During suturing (10 minutes)]
Maximum number of healthcare personnel required at bedside during repair to provide physical restraint or patient care
- Delayed maladaptive behaviors [From discharge to 72 hours post-discharge]
Delayed maladaptive behaviors up to an including 72 hours post discharge using the Post-Hospital Behavior Questionnaire. The scale consists of 27 items concerning sleep, eating, anxiety, etc. where each item is scored from 1-5. The minimum score is 27 and the maximum score is 135 with higher scores indicating greater severity of behaviors.
- Total ED length of stay [During emergency department visit (2 hours)]
ED length of stay
- Duration of procedure [During suturing (10 minutes)]
Duration of laceration repair
- Post-intervention length of stay [From drug administration to discharge (80 minutes)]
Length of stay due to anxiolytic
- Nasal irritation [During IN intervention administration (1 minute)]
Nasal irritation due to IN intervention using the Faces, Legs, Arms, Activity, Cry (FLACC) scale. The FLACC is an observational scale, scored from 0 (no pain) to 10 (maximal pain)
- Post-procedure length of stay [From suturing to discharge (40 minutes)]
Post-procedure length of stay
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age 2-12.99 years (maximum 65 kg to avoid underdosing of intranasal interventions)
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Single laceration requiring simple interrupted sutures alone
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No concomitant fracture or dislocation
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Repair to be performed by the emergency physician or their designate
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Child or caregiver desires anxiolysis for laceration repair
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Local anesthesia planned to involve only topical LET and/or infiltrated lidocaine
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American Society of Anesthesiologists (ASA) Class I (healthy) or II (mild to moderate systemic disease that is medically well controlled, e.g. asthma or type II diabetes mellitus)
Exclusion Criteria:
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Opioid, sedative, or anxiolytic medication administered < 24 hours prior to procedure
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History of hypersensitivity to dexmedetomidine, midazolam, or nitrous oxide
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Occlusion of at least one nare due to mucus, polyps, septal deviation, or foreign body
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Bradycardia or hypotension below two standard deviations (SD) of age-related normal value
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Pre-existing renal insufficiency, uncorrected mineralocorticoid deficiency (e.g. congenital adrenal hyperplasia), pulmonary hypertension, uncorrected cyanotic congenital heart disease, cardiac conduction disorder, pulmonary hypertension, pulmonary edema, vitamin B12 (cobalamin) or folate deficiency or disorders, phenylketonuria, or psychotic disorder
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Impaired level of consciousness (e.g. due to head injury, toxin ingestion, or post-ictal state)
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Conditions associated with potential accumulation of gas within body spaces
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Suspected cardiorespiratory instability or cardiac ischemia,
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Suspected pregnancy
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Inability to vocalize pain due to motor deficits
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Caregiver in attendance unable to read or understand English or French in the absence of a native language interpreter
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Lawson Health Research Institute
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DFS05081977