Ketamine for Pain in the Emergency Department

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).

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

Eligibility Criteria:
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