385 Ketamine vs Metoclopramide for the Treatment of Primary Headache in the Emergency Department

Abstract

Headache is a significant problem in the emergency setting comprising approximately 2 million emergency department (ED) visits in the United States annually, leading to a significant health care burden. Although the impact of headache is large in the US, current treatment strategies are limited to several medications. Despite the fact that several commonly utilized treatments are currently recommended by the American Academy of Neurology, these, like any medication come with several notable adverse events such as somnolence, sedation and akathisia. Recently, several have been subject to drug shortages. Additionally, although opiates are discouraged in the treatment of headache in the ED setting they still remain as a back up medication for refractory headache. Given the adverse events, current state of medication shortages, and the opiod/opiate crisis in the US, it is desirable to discover safe and effective alternative treatments for pain disorders such as headache. With this in mind, we hypothesize that the dissociative anesthetic ketamine represents an alternative to current therapy for primary headache in the ED in comparison to standard treatment with metoclopramide alone. Prior trials have demonstrated that the Benadryl that is often utilized to reduce akathisia has no benefit when added to a standard 10 mg dose of metoclopramide and can safely be excluded for testing the efficacy of metoclopramide alone vs ketamine. We intend to conduct a single center randomized double blind intention to treat clinical trial comparing weight-based ketamine (0.3 mg/kg) to metoclopramide (10mg). Patients will be randomized using a Web-based randomization and allocated in permuted blocks of 4. Treating pharmacists will receive the patient’s sequence number and weight. Only the treating pharmacist will have access to the assigned treatment group and will then mix the blinded study drug into 250 ml of normal saline which will be be administered over 15 minutes. The primary outcome will be a change in the VAS score at 60 minutes from baseline. Power analysis with an assumed drop-out rate of 10% indicates that 37 patients per arm should be included. A change of 25 mm will be considered significant assuming a power of 0.80 and an alpha of 0.05. Secondary objectives include adverse events, hospital admission, and 48-hour ED return. Analysis of the primary outcome will be conducted using a between factors repeated measures ANOVA. We hypothesize that ketamine administered as an infusion over 15 minutes for primary headache in the emergency department is superior to metoclopramide. Our intent is to provide clinicians with an affordable alternative treatment with a wide therapeutic window and minimal adverse events thus avoiding the need to utilize medications that have higher side effect profiles or addictive potential.