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PEM Pearls: Migraine Treatment for Pediatric EM Patients

migraine treatment for pediatric em patients © Can Stock Photo / SergiyNYou are working your evening shift at the pediatrics emergency department, and you walk into a darkened patient room with a distressed mother and her otherwise healthy 10-year old son who is curled in a ball, holding his head and crying. Her mother tells you that the around-the-clock ibuprofen has barely touched his 2-day headache.

After determining that your patient has no neurologic deficits and that this is most likely a primary headache, what can you do to break his symptoms?

The numbers

Headaches account for 1% of all pediatric emergency department visits. Of those presenting with headache, 40% of children are diagnosed with a primary headache, and 75% of these are migraines. Most research and medications have focused on children < 7 years ago as the average age of onset of migraines is 7 years old among boys and 11 years old among girls.1 The diagnosis of pediatric migraine can be challenging, especially in younger children (<7 yo) who may not be able to describe their symptoms.

Should you stick the kid?

Children may have been vomiting and have decreased oral intake. If you are feeling bad about placing an IV in your patient, just know that about half of patients with migraines will need IV therapy.2

Should you reach for that opioid?

According to the American Academy of Neurology, they recommend that opiate medications be avoided for the treatment of migraines in children. A study by DeVries found that among adolescents who received opioids, 28% had an emergency department revisit for their headache compared to only 14% who did not receive any opioids (P < 0.01).3 Dr. Amy Gelfand, a UCSF pediatric neurologist who specializes in pediatric headaches, says that by giving opioids, there is an associated decreased responsiveness to triptans in the future (See her Expert Peer Review comments below).

What should you try then?

By the time your patient present to the ED for migraines, they have been symptomatic for probably  24-72 hours already, and have taken some type of abortive medication, most often acetaminophen or ibuprofen.2,4 The addition of caffeine to ibuprofen may increase ibuprofen’s analgesic properties.4

Which dopamine-receptor antagonists to use?

Your choices of the phenothiazines for ages ≥7 years old include:

  • Prochlorperazine (1st choice)
  • Chlorpromazine
  • Metoclopramide

Pros:  Alleviates both pain and nausea/vomiting

Cons: Drowsiness, hypotension, and extrapyramidal reactions (EPS).

In a recent study in Pediatrics 2015, Bachur et al. performed a large retrospective study, using data collected on children aged 7-18 years from 35 pediatric EDs.5 They examined any revisits within 3 days of initial encounter as their primary outcome. Common medications included:

  1. Non-opioid analgesics (66%)
  2. Dopamine receptor antagonists (50%)
  3. Ddiphenhydramine (33%)

Of those discharged at the initial encounter, 5.5% of children had a return visit within 3 days.

They found that children treated with prochlorperazine had a 31% decreased odds of returning to the emergency department, compared to those treated with metoclopramide. Kanis et al. found that proclorperazine was more effective than chlopromazine, with less admission, need for rescue medications, shorter disposition times, and hypotensive events.6

Prophylactic diphenhydramine may be administered to patients receiving prochlorperazine to pre-treat akathisia and dystonic reactions. Diphenhydramine may cause additional sedation and drowsiness when co-administered with prochlorperazine. EPS may occur after ED discharge even in patients receiving prophylactic diphenhydramine, so parents should be cautioned about restlessness (akathesia)  and dystonia.8

Brousseau et al. showed better efficacy with a 50% reduction of pain at 1 hour in children who received prochlorperazine IV (84.8%) versus ketorolac IV (55.2%) though 30% of both groups had recurrences of some headache 48 hours after treatment.7 Per Dr. Gelfand,  prochlorperazine should be considered first-line over ketorolac.

Other regimens

Triptans may be administered via oral and subcutaneous routes, or via intranasal spray. In the ED, triptans may be useful in kids with migraines who do not take triptans as abortive therapy. In general, patients should not receive more than two doses of triptans in a 24-hour period. They work effectively at the earlier stages of the migraine when the symptoms are more mild compared to when there are more moderate or severe. Zolmitriptan nasal spray has recently been approved for children 12 years old and older, while sumitriptan nasal spray is available for children 5 years and older. When compared to placebo, triptans have a 2-hour efficacy for 42-86% of patients. Combination medications of triptans and naproxen have also been shown to have good efficacy.1,4 You can prescribe patients home with triptans, as long as there are no contraindications such as cardiac issues.  Keep in mind the cost impact of these medications. Many triptans are still non-generic and patients without insurance may not have access to them. There are four triptans that are FDA-approved for acute migraine treatment in the <18 age group (See below for the dosing table).

IV dihydroergotamine (DHE) is primarily used in the inpatient setting, but could be initiated in the ED for refractory cases, given that it typically takes several doses over several hours to administer. DHE can worsen nausea and lead to emesis,  therefore should be used in conjunction with an antiemetic or prochlorperazine (which also has anti-emetic properties). Avoid DHE and triptans together, especially for those patients with cardiovascular disease.1,4

If the history is consistent with migraine, the algorithm by Sheridan et al may be useful in your pocket for patients ≥7 years old:1

Flowchart adapted from: Sheridan, Headache (2014)

Flowchart adapted from: Sheridan, Headache (2014)

Bottom Line

  1. Give hydration either by oral or by parenteral route.
  2. Dim the lights and turn down any loud sounds or alarms.
  3. Break the habit… Avoid opioids!
  4. Give prochlorperazine instead of metoclopramide or chlopromazine.
  5. Try a triptan.
  6. Refer to a neurologist. If your patient has migraines that are bad enough to have them land in the ED, they should be evaluated by a specialist, ideally one that has experience with managing pediatric migraines.

Dosages

Medications Dosage
Simple analgesics
Acetaminophen 15 mg/kg PO or PR (max 1 g/dose or 4 g/day)
Ibuprofen 10 mg/kg PO (max dose 800 mg/dose or 2400 mg/day)
Ketorolac 0.5 mg/kg IV (max dose 15 mg/dose)
Dopamine antagonists
Prochlorperazine 0.15 mg/kg IV (max dose 10 mg/dose)
Metoclopramide 0.1 mg/kg IV ( max dose 10 mg/dose)
5HT receptor agonists
Sumatriptan 5-20 mg IN 50-100 mg PO 3-6 subQ
Almotriptan  6.25 or 12.5 mg PO for ages 12-17 years
Rizatriptan MLT 5 mg (<40 kg) or 10 mg (≥40 kg) for >6 years old
Zolmitriptan  2.5-5 mg IN for ages 12-17 years
Treximet: Sumatriptan/Naproxen combination For ages 12-17 years: 10 mg/60 mg PO 85 mg/500 mg PO (max dose)
Dihydroergotamine 0.5-1 mg SubQ, IM or IV
Other anti-emetics
Diphenhydramine 1 mg/kg (max dose 50 mg/dose)
Promethazine 0.25-1 mg/kg IV (max dose 25 mg/dose)
Table adapted from Sheridan, Bulloch and Dr. Gelfand’s comments below
1.
Sheridan D, Spiro D, Meckler G. Pediatric migraine: abortive management in the emergency department. Headache. 2014;54(2):235-245. [PubMed]
2.
Bulloch B, Tenenbein M. Emergency department management of pediatric migraine. Pediatr Emerg Care. 2000;16(3):196-201; quiz 203. [PubMed]
3.
DeVries A, Koch T, Wall E, Getchius T, Chi W, Rosenberg A. Opioid use among adolescent patients treated for headache. J Adolesc Health. 2014;55(1):128-133. [PubMed]
4.
Gelfand A, Goadsby P. Treatment of pediatric migraine in the emergency room. Pediatr Neurol. 2012;47(4):233-241. [PubMed]
5.
Bachur R, Monuteaux M, Neuman M. A comparison of acute treatment regimens for migraine in the emergency department. Pediatrics. 2015;135(2):232-238. [PubMed]
6.
Kanis J, Timm N. Chlorpromazine for the treatment of migraine in a pediatric emergency department. Headache. 2014;54(2):335-342. [PubMed]
7.
Brousseau D, Duffy S, Anderson A, Linakis J. Treatment of pediatric migraine headaches: a randomized, double-blind trial of prochlorperazine versus ketorolac. Ann Emerg Med. 2004;43(2):256-262. [PubMed]
8.
Coralic, PharmD Z. I am giving prochlorperazine. Should I give diphenhydramine too? ALiEM. https://www.aliem.com/2014/give-prochlorperazine-diphenhydramine/. Published September 3, 2014. Accessed October 29, 2016.

Expert Peer Review

Migraine is indeed a common reason for children and adolescents to present to the Emergency Department. Adolescents are particularly likely to present at those times of the year that their schedule is shifting—specifically September and January, right after returning from long vacations from school, (Kedia et. al., Cephalalgia 2013)

It is important to remember the treatment environment of the child or adolescent. They may be sensitive to lights and/or sounds, so keeping the room dim and trying to turn off any unnecessary alarms or sounds can be helpful.

Their hydration status may be low, due to either direct losses from nausea/vomiting, decreased PO intake from nausea, or increased micturition during the premonitory phase of the migraine attack. Therefore try to encourage PO hydration, and have a low threshold to provide IV fluids—particularly if you are going to provide parenteral treatment anyway.

Certainly opioids should be avoided. Opioids would not be considered evidence based therapy for acute migraine treatment in this age group (or any age group). Unfortunately recent research presented at the June 2015 American Headache Society meeting found five out of six children and teenagers are not receiving evidence based acute migraine therapy (Nicholson R, et. al., “Pediatric Migraine Treatment: Poor Adherence to Evidence Based Acute Medication Guidelines, AHS conference proceedings 2015). Nearly 1 in 6 is receiving an opioid and the risk of receiving an opioid is higher if they are a teen or being seen in the ED setting (Nicholson, R, et. al., “Opioid prescribing patterns in pediatric migraine 2009-2014\", AHS conference proceedings 2015). While no doubt it is a compassionate impulse that drives the clinician to prescribe an opioid to a child with migraine, it is important to remember that migraine is a chronic condition with episodic exacerbations. The child is going to have another migraine attack—and probably soon. Recent opioid use is associated with decreased responsiveness to triptans in the weeks ahead (Ho et. al., Headache 2009)—so by giving them an opioid today we might cause them more pain tomorrow when their triptans don’t work as well at home for their next headache.

In the only comparative effectiveness trial for pediatric acute migraine treatment in the ED setting to date (that I am aware of), prochlorperazine was clearly superior to ketorolac at 1 hour: 85% vs. 55% successfully treated (Brousseau et. al., Ann Emerg Med 2004). Therefore prochlorperazine should be considered first line over ketorolac. By using prochlorperazine first you are also well set up to give DHE later on if needed, as the anti-emetic effects of prochlorperazine will help prevent DHE associated nausea.

Triptans are another good treatment option. There are now four triptans FDA approved for acute migraine treatment in the <18 age group:

  1. almotriptan 6.25 or 12.5 mg PO for ages 12-17 years
  2. rizatriptan 5 mg MLT (<40 kg) or 10 mg (≥40 kg) is approved down to age 6</li?
  3. Treximet (a combination of sumatriptan/naproxen), at doses down to 10/60 mg and up to 85/500 mg (sumatriptan/naproxen) for ages 12-17 years
  4. Zomig 2.5-5 mg NS for ages 12-17 years

Sometimes people think triptans only work if they are taken early in an attack. It is actually that triptans are more likely to be effective if taken while pain is still mild, which tends to be earlier in an attack. This does not mean that triptans don\'t work if taken when pain is mod/severe, it is just that they work in a lower proportion of such attacks—in the Act When Mild study, the 2 hour pain free rate in attacks that were treated while mild was 53% vs. 38% in those treated at the moderate/severe phase. In general, in the ED setting it would be preferable to give a child (≥6 years) or adolescent a triptan than an opioid.

Arranging appropriate follow-up at ED discharge is quite important. Migraine is a chronic condition, and by virtue of having landed in the Emergency Department a child or teen has now demonstrated that their migraine condition is significant enough to merit evaluation by a neurologist—ideally one with experience in managing pediatric migraine.

Amy Gelfand, MD
Dr. Amy Gelfand directs the the pediatric headache program at UCSF. Her research interests are in the epidemiology and treatment of pediatric migraine and related disorders such as infant colic, cyclic vomiting syndrome and abdominal migraine
Delphine Huang, MD

Delphine Huang, MD

Resident
Department of Emegency Medicine (EM) UCSF-San Francisco General Hospital EM Residency Program
Steven Bin, MD

Steven Bin, MD

Associate Clinical Professor of Pediatrics and Emergency Medicine
Division of Pediatric Emergency Medicine
University of California, San Francisco
Zlatan Coralic, PharmD

Zlatan Coralic, PharmD

Assistant Clinical Professor
Emergency Department Clinical Pharmacist
University of California, San Francisco (UCSF)