Ketamine for Pain in the Emergency Department

Study Overview
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Brief Summary
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This study will prospectively compare the mean Numerical Rating Scale (NRS) pain score reduction amongst three recommended dosing strategies of intravenous ketamine (0.1 mg/kg, 0.2 mg/kg, and 0.3mg/kg) for acute pain in the emergency department (ED).This study will also examine the frequency of adverse events secondary to ketamine including fatigue, dizziness, nausea, headache, feeling of unreality, changes in hearing or vision, mood changes, generalized discomfort, and hallucinations, changes in vital signs. Subgroups for exploratory analysis based on the need for rescue analgesia within two hours of ketamine administration, adequate pain relief, previous opioid tolerance, and age (adults < 65 years old and > 65 years old).

Detailed Description
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A literature review was performed that searched for randomized clinical trials involving ketamine IV boluses for acute pain in the Emergency Department. Studies involving continuous infusions or intranasal routes of ketamine administration were not included. Thirteen randomized clinical trials were identified meeting this criteria. None of these trials directly compared ketamine doses within the 0.1-0.3 mg/kg range for pain score reduction and adverse events. Many of these trials concluded with the recommendation that further studies were needed to evaluate the optimal dosing of ketamine for acute pain and determine which populations are most ideal for its use. This study will be the first to evaluate ketamine for acute pain in the emergency department at standard of care doses (0.1 mg/kg, 0.2 mg/kg, and 0.3 mg/kg IV) to determine which dose correlates with the most efficacy and safety. This study will include the following procedures: Patient consent, screening, and enrollment will be performed by the treating resident or attending who will remain blinded Patient will be assigned a subject number Treating resident or attending will notify the ED pharmacist that a patient has been enrolled in the trial ED pharmacist will notify the IV room and place the study drug order Either the ED pharmacist or a pharmacy supervisor will randomize the subject based on the predetermined randomization list Study drug will be prepared as 0.1 mg/kg, 0.2 mg/kg, or 0.3 mg/kg IV dose in a 100 mL solution of dextrose 5% or sodium chloride 0.9% ED pharmacist will promptly deliver the study drug to the ED Baseline vital signs will be assessed prior to starting the study drug infusion Study drug will be administered via IV infusion over 20 minutes Treating resident or attending will reassess the patient at 15 minutes from the end of infusion, at 30 minutes from the end of infusion, and then every 30 minutes for up to 120 minutes or until discharge, whichever is sooner

Official Title
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Comparison of Ketamine 0.1 mg/kg, 0.2 mg/kg, and 0.3 mg/kg Intravenous Doses for Acute Pain in the Emergency Department: A Prospective, Randomized, Double-blind, Active-controlled, Clinical Trial

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: Ketamine Injectable Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute pain (including acute on chronic pain) Pain score of moderate to severe (> 4/10) on the Numerical Rating Scale Provider determines the patient requires intravenous ketamine for analgesia Exclusion Criteria: History of hypersensitivity to ketamine Altered mental status Psychiatric illness Known history of renal or hepatic insufficiency Acute head or eye injury Suspected intracranial hypertension or mass Headache as the chief complaint Alcohol or drug abuse Received an analgesic within the last four hours History of congestive heart failure History of aortic or brain aneurysm Active Chest Pain Porphyria Active methadone treatment Pregnant or breastfeeding Signs of respiratory, hemodynamic, or neurologic compromise Systolic blood pressure < 90 mmHg or > 180 mmHg Heart rate < 50 beats per minute or > 150 beats per minute Respiratory rate < 10 breaths per minute or > 30 breaths per minute Glasgow Coma Score < 15 Previously received ketamine < 0.3 mg/kg IV for acute pain in the emergency department

Ages Eligible for Study
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Minimum Age: 21 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
Interventional Model Description: 3 arms each arm getting a different dose of ketamine
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1: 0.1 mg/kg ketamine<br>0.1 mg/kg in a 100 mL solution of dextrose 5% or sodium chloride 0.9% will be give after patient consent and enrollment in the study, vitals are followed (heart rate, systolic blood pressure and respiratory rate) for 2 hours following completion of ketamine infusion. Evaluated for side effects for 2 hours following completion of ketamine infusion. | Drug: Ketamine Injectable Product<br>* Three different doses of ketamine will be administered.<br>|
| Active Comparator: Arm 1: 0.2 mg/kg ketamine<br>0.2 mg/kg in a 100 mL solution of dextrose 5% or sodium chloride 0.9% will be give after patient consent and enrollment in the study, vitals are followed (heart rate, systolic blood pressure and respiratory rate) for 2 hours following completion of ketamine infusion. Evaluated for side effects for 2 hours following completion of ketamine infusion. | Drug: Ketamine Injectable Product<br>* Three different doses of ketamine will be administered.<br>|
| Active Comparator: Arm 1: 0.3 mg/kg ketamine<br>0.3 mg/kg in a 100 mL solution of dextrose 5% or sodium chloride 0.9% will be give after patient consent and enrollment in the study, vitals are followed (heart rate, systolic blood pressure and respiratory rate) for 2 hours following completion of ketamine infusion. Evaluated for side effects for 2 hours following completion of ketamine infusion. | Drug: Ketamine Injectable Product<br>* Three different doses of ketamine will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Score | Pain score using Numerical Rating Scale (NRS) post ketamine infusion. The Numerical Rating Scale (NRS) ranges from 0-to-10 with 0 being no pain and lower numbers representing less pain, so in this case lower numbers will represent better outcomes. Pain scores were reported at baseline and then at 15 min/30 min/60 min/90 min and 120 minutes post-infusion. | Within 2 hours post infusion completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Frequency of adverse events secondary to ketamine including fatigue, dizziness, nausea, headache, feeling of unreality, changes in hearing or vision, mood changes, generalized discomfort, and hallucinations, changes in vital signs. Adverse events were reported at baseline and then at 15 min/30 min/60 min/90 min and 120 minutes post-infusion. | Within 2 hours post infusion completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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moderate to severe pain, emergency department patient, ketamine