Intranasal Ketamine for Acute Traumatic Pain

Study Overview
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Brief Summary
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Introduction: Ketamine has been well studied for its efficacy as an analgesic agent. However, intranasal (IN) administration of ketamine has only recently been studied in the emergency setting. Objective: To elucidate the efficacy and adverse effects of a sub-dissociative dose of IN Ketamine compared to IV and IM morphine. Methods: A single-center, randomized, prospective, parallel clinical trial of efficacy and safety of IN ketamine compared to IV and IM morphine for analgesia in the emergency department (ED). A convenience sample of 90 patients aged 18-70 experiencing moderate-severe acute traumatic pain (≥80mm on 100mm Visual Analog Scale [VAS]) were randomized to receive either 1.0mg/kg IN ketamine, 0.1mg/kg IV MO or 0.15mg/kg IM MO. Pain relief and adverse effects were recorded for 1 hour post-administration. Primary Outcomes: The primary outcome was efficacy of IN ketamine compared to IV and IM MO, measured by time-to-onset (defined as a ≥15mm pain decrease on VAS), as well as time to and degree of maximal pain reduction.

Official Title
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Intranasal Ketamine for Acute Traumatic Pain in the Emergency Department: A Prospective, Randomized Clinical Trial of Efficacy and Safety

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: Ketamine Hydrochloride
* Drug: Morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18-70 years, with mild to moderate blunt trauma (sustained in road, workplace and home accidents) causing moderate to severe pain (≥ 80mm score on a 100mm Visual Analog Scale=VAS) were eligible for participation in the study. Inclusion criteria also included a Glasgow Coma Score (GCS) of 15, body weight of 50-110 kg, systolic blood pressure of 90-160 mmHg, heart rate <100 bpm. Patients were also required to have an American Society of Anesthesiologists (ASA) score of 1 or 2, deny head injury, and deny regular use or use of opiates. Exclusion Criteria: Any analgesia received within the prior 3 hours, allergic sensitivity to morphine or ketamine, a large meal ingested within the previous hour, pregnancy, deviated nasal septum or trauma to the nose, and a history of a psychiatric condition. Despite evidence that ketamine does not exacerbate intracranial hemorrhage in patients with head trauma, patients with head injury complaining of loss of consciousness, dizziness, vomiting, or nausea were excluded as well.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IN Ketamine<br>A single administration of 1 mg/kg ketamine hydrochloride delivered in an intranasal route using an atomizer | Drug: Ketamine Hydrochloride<br>* Delivered intranasally using an atomizer<br>|
| Active Comparator: IM Morphine<br>A single administration of 0.15 mg/kg intramuscular morphine | Drug: Morphine<br>* Delivered either as an IM injection or a slow IV bolus<br>|
| Active Comparator: IV Morphine<br>A single administration of 0.1 mg/kg slow intravascular bolus of morphine. | Drug: Morphine<br>* Delivered either as an IM injection or a slow IV bolus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of intranasal ketamine in decreasing pain intensity [patient assessed - VAS pain score] | Time to achieve a clinically meaningful pain reduction was defined as the first time-point at which the patient reported 15mm of pain reduction or more. Maximal pain reduction was defined as the lowest VAS score reported by the patient over the course of follow-up. Time to maximal pain reduction was defined as the time at which the patient has the lowest VAS score over the course of the hour follow-up. | 1 hour post administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse effects [Opiate Related Symptom Distress Scale] | Adverse effects were recorded at the end of one hour using the 'Opiate Related Symptom Distress Scale' and included measurements of the presence, frequency, intensity and disruptiveness of 12 common opiate side-effects. Among these were nausea, vomiting, urinary retention, constipation, difficulty concentrating, dizziness, confusion, and others. | 1 hour post administration | 
| patient satisfaction [Interview] | patients were asked to provide subjective comments | 1 hour post administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intranasal Ketamine, Analgesia, Trauma, Morphine, Mass Casualty