Intravenous Ketorolac and Metoclopramide for Pediatric Migraine in the Emergency Department
Condition: Probable Migraine; Migraine With Aura; Migraine Without Aura
MeSH terms: Migraine Disorders; Migraine without Aura; Migraine with Aura; Emergencies
Study type: Interventional
Phase: Phase 4

Summary: 
      Migraine headaches are a common problem for children. When treatment at home fails, children
      may benefit from intravenous treatment administered in a hospital setting like the Emergency
      Department. Most treatments used however have only been tested in adults and the best
      treatment strategy for children is not always clear. The combination of more than one
      medication is frequently prescribed in Canadian Emergency Departments. The purpose of this
      study is to investigate whether the combination of ketorolac (an anti-inflammatory pain
      medication) and metoclopramide (an anti-nauseant that may also relieve migraine headaches) is
      better than metoclopramide by itself.
    

Detailed description: 
      Migraine headache is a painful condition of recurrent moderate to severe head pain associated
      with nausea, vomiting, photophobia, and phonophobia. The condition is highly prevalent and a
      significant community health problem with considerable impact on the health care system. To
      alleviate the pain and morbidity associated with a migraine attack, drug therapies are often
      employed including simple analgesics like ibuprofen and migraine-specific medications like
      sumatriptan. When these treatments fail or in severe, intractable cases, patients and
      families may present to the Emergency Department (ED).

      Ketorolac in combination with metoclopramide or prochlorperazine was the most common
      multi-drug combination used in 36% of ED presentations for migraine across Canada in our
      national practice variation study. The scientific rationale for combining a non-selective
      non-steroidal anti-inflammatory drug (NSAID) with inhibition of both the cyclooxygenase (COX)
      1 and 2 isoenzymes with other migraine therapies is enticing; however, no studies have
      specifically examined the relative efficacy of the practice. Why would the combination of a
      non-selective NSAID like ketorolac with other migraine therapies improve treatment outcomes?
      The benefit of multi-target combinations may be relate to the duration of the migraine and
      the multiple brain areas involved in sustained pain. It has long been recognized that
      patients who treat their migraine headaches early at the onset have a better response. The
      underlying mechanism for this phenomenon has now been identified. The initiation of migraine
      pain requires activation of the trigeminal (5th cranial nerve) nociceptive (pain) system.
      Activation of these sensory fibers within the arachnoid membrane on the surface of the brain
      produces the first and most common painful manifestation of migraine - the pulsatile
      headache. With each heartbeat, minor dilation of the cerebral blood vessels produces stretch
      and a painful activation of the trigeminal fibers known as peripheral sensitization. The
      second phase in the maintenance of a migraine attack over several hours is the sensitization
      of trigeminal pain pathways leading to higher brain centers known as central sensitization.
      The efficacy of medications like the triptans is greater early in the course of a migraine
      attack when there is only peripheral sensitization and before the onset of central
      sensitization. Non-selective NSAIDs like naproxen sodium and ketorolac may be uniquely
      effective in the reduction of central sensitization in the animal model of migraine and the
      reduction of migraine pain in adult patients late in the course of a migraine headache.

      The population of patients in the ED is uniquely different from outpatients in that most have
      developed their migraine headache hours or days before presenting. In our practice variation
      study, the mean duration of the migraine prior to presenting to the ED was 2 days. Including
      an NSAID when treating a prolonged migraine in the ED may thus increase the therapeutic
      window and improve outcomes. While many Canadian ED physicians have adopted the practice of
      combining ketorolac with other migraine therapies, the gold standard assessment of efficacy
      and safety in a randomized clinical trial has not been applied.
    

Intervention name(s): Ketorolac Tromethamine; Metoclopramide
Intervention type(s): Drug; Drug
Intervention description(s): Ketorolac 0.5 mg/kg (max 30 mg) IV; Metoclopramide 0.2 mg/kg (max 10 mg) IV
Other intervention name(s): Toradol; 74103-07-4; Maxeran; Reglan; 364-62-5
Intervention MeSH terms: Ketorolac; Ketorolac Tromethamine; Metoclopramide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: migraine; pediatric; childhood; emergency department; ketorolac; metoclopramide; intravenous