Pain Reduction With Intranasal Medications for Extremity Injuries

Study Overview
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Brief Summary
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This study compares the analgesic effect of intranasal sub-dissociative dosing of ketamine and intranasal fentanyl in children presenting to the Emergency Department with acute extremity injuries.

Detailed Description
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Inadequate pain control, especially in the emergency department (ED), is a major public health concern. Despite increased awareness, pain continues to be underdiagnosed and undertreated, particularly in the pediatric population. Children often encounter long delays in medication administration, possibly due to the time required to obtain intravenous access. The intranasal administration route offers a more efficient alternative for faster and noninvasive delivery of pain medication. This route is gaining popularity secondary to its rapid onset of active, minimal discomfort and relative simplicity. Opioids are the most commonly used class of analgesic pain medication for children presenting in severe pain due to traumatic injuries. Despite their potential effectiveness, opioids have several concerning adverse effects, particularly when administered prior to procedural sedation in children. Administration of pre-procedural sedation opioids is associated with an increased risk of serious adverse events (oxygen desaturation, apnea, and hypotension) as well as the need for significant interventions, such as bag-mask ventilation, intubation, and pharmacologic blood pressure support. In addition, due to genetic variations that may lead to increased or diminished opioid sensitivity, ideal dosing to adequately control severe pain yet avoid adverse medication-related side effects is difficult to ascertain. Many children in severe pain do not receive opioids, receive doses that are below those recommended or experience long delays in receiving opioids. The reasons for this are unclear, but the investigators speculate that this may be due in part to fear of adverse effects of opioids, provider inexperience with opioid use in children or fear of contributing to opioid tolerance or abuse. For all of these reasons, providers often seek non-opioid alternatives for pediatric patients with acute, severe pain. Ketamine, in sub-dissociative doses administered by the intravenous or intranasal route, is emerging as an alternative medication for the treatment of moderate to severe pain in multiple settings. In adults, low dose ketamine is well tolerated and has been used successfully as an adjuvant and an alternative to opioids to provide rapid pain relief in the ED. As a dissociative anesthetic, ketamine is the most commonly used agent to facilitate painful procedures in the pediatric emergency department. At lower doses, it has been used in children to provide analgesia in a variety of acute and chronic pain settings, including terminal diagnoses, sickle cell disease, perioperative pain, traumatic injuries, extensive burns and conditions where opioids are contraindicated. Similar to adults, ketamine has been used via the intranasal route to provide adequate analgesia and sedation in children in the pre-hospital setting and in those undergoing procedures. The objective of this study is to compare intranasal sub-dissociative ketamine with intranasal fentanyl for treatment of acute pain associated with traumatic limb injuries in children presenting to the ED and to document an objective respiratory side effect profile utilizing noninvasive capnometry. If found to be an effective analgesic, intranasal ketamine would be particularly useful in children who experience adverse effects with opioids, have developed opioid tolerance as a result of chronic painful conditions, have poor opioid sensitivity due to their genetic predisposition or in pediatric trauma patients with the potential for hypotension. Additionally, for patients that require procedural sedation for fracture reduction, avoiding opioids early in the emergency department visit may decrease sedation recovery time and the risk of serious adverse events during sedation.

Official Title
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A Randomized Controlled Trial of Intranasal Sub-dissociative Dosing of Ketamine Compared to Intranasal Fentanyl for Treatment of Pain Associated With Acute Extremity Injuries in Children

Conditions
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Pain, Traumatic Limb Injury

Intervention / Treatment
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* Drug: Ketamine
* Drug: Fentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 8 years to 17 years (up to the 18th birthday) Presenting to emergency department with one or more extremity injuries Visual analog scale score 35 mm or greater Parent or legal guardian present and willing to provide written consent Exclusion Criteria: Received narcotic pain medication prior to arrival Evidence of significant head, chest, abdomen, or spine injury Glasgow coma score less than 15 or unable to self report pain score Nasal trauma or aberrant nasal/airway anatomy Active epistaxis Allergy to ketamine, fentanyl or meperidine Non-English speaking parent and/or child History of psychosis Postmenarchal female without a urine or serum assay documenting the absence of pregnancy Brought in my juvenile detention center or in police custody Pregnancy

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine<br>Ketamine 1.5 mg/kg intranasally for one dose | Drug: Ketamine<br> <br> * Other names: Ketalar;|
| Active Comparator: Fentanyl<br>Fentanyl 2 mcg/kg intranasally for one dose | Drug: Fentanyl<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference From Baseline in Visual Analog Scale Pain Score | A VAS score is a self reported pain score of 0-100 millimeters (0 = no pain; 100 = worst possible pain). A decrease in a VAS score indicates a decrease in pain severity. | 30 minutes after study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference From Baseline in Visual Analog Scale Pain Score | A VAS score is a self reported pain score of 0-100 millimeters (0 = no pain; 100 = worst possible pain). A decrease in a VAS score indicates a decrease in pain severity. | 15 minutes after study medication | 
| Difference From Baseline in Visual Analog Scale Pain Score | A VAS score is a self reported pain score of 0-100 millimeters (0 = no pain; 100 = worst possible pain). A decrease in a VAS score indicates a decrease in pain severity. | 60 minutes after study medication | 
| Highest Achieved University of Michigan Sedation Scale (UMSS) Score | The University of Michigan Sedation Scale is a valid and reliable tool that allows for rapid assessment of the depth of sedation in children. It is a simple observational tool that assesses the level of alertness on a five-point scale. It has been validated in children and has shown to have significant inter-rater reliability. Score is 0-4 (0 = awake and alert; 1= minimally sedated; 2 = moderately sedated; 3 = deeply sedated; 4 = unarousable) | 15, 30, and 60 minutes after study medication administration | 
| Rescue Analgesia | Documentation of additional pain medication after study medication administration | Within the first 60 minutes after study medication | 
| Heart Rate |  | 15 minutes after study medication | 
| Heart Rate |  | 30 minutes after study medication | 
| Heart Rate |  | 60 minutes after study medication | 
| Respiratory Rate |  | 15 minutes after study medication | 
| Respiratory Rate |  | 30 minutes after study medication | 
| Respiratory Rate |  | 60 minutes after study medication | 
| Systolic Blood Pressure |  | 15 minutes after study medication | 
| Systolic Blood Pressure |  | 30 minutes after study medication | 
| Systolic Blood Pressure |  | 60 minutes after study medication | 
| Diastolic Blood Pressure |  | 15 minutes after study medication | 
| Diastolic Blood Pressure |  | 30 minutes after study medication | 
| Diastolic Blood Pressure |  | 60 minutes after study medication | 
| Oxygen Saturation |  | 15 minutes after study medication | 
| Oxygen Saturation |  | 30 minutes after study medication | 
| Oxygen Saturation |  | 60 minutes after study medication | 
| Capnometry Value |  | 15 minutes after study medication | 
| Capnometry Value |  | 30 minutes after study medication | 
| Capnometry Value |  | 60 minutes after study medication |