Ketamine shortage during the funding period of the trial

In this proposal, the investigators will determine if a single dose of intravenous (IV) ketamine (in combination with midazolam) reduces pain severity, depressive symptoms and need for opiate analgesics both in the ED and in the acute recovery period after ED discharge. The investigators will compare the ketamine arm to an active placebo-controlled arm (with midazolam).

The investigators will enroll 120 medically stable adult patients who present to two Emergency Departments with a chief complaint of acute pain.

The investigators will randomly assign subjects using a blocked randomization schedule to either: 1) a single dose of IV ketamine (0.3 mg.kg) + midazolam, or 2) placebo + midazolam. ED providers and patients will be blind to treatment allocation.

All participants will complete measures of pain and mood scores every 30 minutes, and the investigators will record any analgesics administered in the ED until discharge. At 7-days and 14-days post- discharge, the investigators will measure summary reports of pain severity, mood, and analgesic medication used.

Inclusion Criteria:

1. Adults between the ages of 18-65
2. A chief complaint of painful condition (pain score ≥ 5 on the numeric rating scale [NRS] from 0-10 with anchors of 0 = "no pain" and 10 = "worst pain imaginable")
3. Expected to be in the ED for at least 2 hours

Exclusion Criteria:

1. Non-English speaking
2. Not medically suitable for ketamine per treating MD (e.g. medical condition where ketamine is contraindicated); ketamine or midazolam may be unsafe (e.g., known sensitivity, glaucoma, or other concerns)
3. Not alert and oriented
4. Active psychosis, self-injury, suicidal/homicidal intentions on initial evaluation by treating team
5. Seeking treatment due to a mental health or substance use disorder
6. History of chronic opioid use
7. Prescribed opioid use within the past 24 hours
8. Any use of recreational narcotics throughout lifetime
9. Sensitivity or allergy or intolerance to ketamine, opioids, and/or benzodiazepines
10. Weight > 170kg (375 lbs)
11. Current neurological disease (e.g., multiple sclerosis, stroke, brain tumor, seizure disorder, etc.)
12. Pregnancy
13. Prisoner

There is no plan in place yet because it is undecided whether the investigators will need to share the data with additional investigators/researchers not listed on the protocol.