The CHECK Trial: A Comparison of Headache Treatment in the ED: Compazine Versus Ketamine

After enrollment, each patient will randomized either to the standard treatment arm to receive prochlorperazine 10 mg IV along with diphenhydramine 25 mg IV, OR to the study arm to receive Ketamine 0.3 mg/kg along with ondansetron 4 mg IV. The diphenhydramine or ondansetron will be administered first, and immediately afterward the prochlorperazine or Ketamine will be administered. The prochlorperazine or Ketamine will be diluted in saline so that the total volume is 5 mL, and will be administered over 2 minutes. The diphenhydramine will be diluted in saline so that it is 2 mL (the same volume as the ondansetron). Both groups will also receive a 500 mL normal saline bolus after the study medications are administered. The ED pharmacist will be responsible for preparing the medications, using a double-blind protocol. He or she will record which arm the patient was randomized to. Only the pharmacist will have access to the randomization records and will not reveal the randomization until the end of the study. Emergency providers will be instructed not to administer any rescue medications for at least 30 minutes. The electronic medical record order will read "randomized study medication" (for the Ketamine or prochlorperazine) and "randomized add-on medication" (for the ondansetron or diphenhydramine).

Inclusion criteria

• Age 18 to 65 years
• Temperature < 100.4° F
• Diastolic Blood Pressure <104 mm Hg
• Normal neurological exam and mormal mental status

Exclusion criteria

• Pregnant or breastfeeding.
• Meningeal signs are present
• Acute angle closure glaucoma is suspected.
• Head trauma within the previous two weeks
• Lumbar puncture within the previous two weeks
• Thunderclap onset of the headache
• Weight more than 150 kg or less than 40 kg.
• Known allergy to one of the study drugs.
• History of schizophrenia or bipolar disorder.
• History of intracranial hypertension.
• Is a prisoner
• Patient declined informed consent
• Non-English speaking patient.
• Attending provider excludes patient