Pharmacological management of acute migraine attacks in children and adolescents presenting to the emergency department

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Background

Headaches are common in the emergency department (ED), with migraine accounting for 30% of paediatric headache visits and frequent revisits^[1][2]. About 15% of these patients are hospitalized for symptom control^[3]. Migraine affects 10% of children and adolescents, with a mean onset age of 12 years and a female predilection^[4]-[8]. Migraine significantly impacts social, school, and home life^[9]-[11].

Despite their prevalence, evidence for managing migraine attacks in the paediatric ED is limited, with substantial practice variation among centres^[8][12].

The scope of this practice point includes pharmacological ED management of moderate to severe migraine attacks in children and adolescents unresponsive to home therapy (acetaminophen, ibuprofen, and/or triptan).

Definition

The International Classification of Headache Disorders (ICHD, 3rd edition) diagnostic criteria for migraine without aura in children and adolescents^[13] are:

1. At least five attacks fulfilling criteria B-D
2. Headache attacks lasting 2 to 72 hours (untreated or unsuccessfully treated)
3. Headache has at least two of the following four characteristics:
   • unilateral location or bilateral frontotemporal location
   • pulsating quality
   • moderate or severe pain intensity
   • aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)
4. During headache, experiencing at least one of the following:
   1. nausea or vomiting (or both)
   2. photophobia and phonophobia
5. Not better accounted for by another ICHD-3 diagnosis.

Evidence for the treatment of pain in acute migraine attacks

Dopamine antagonists

Metoclopramide improves both pain scores and symptoms of nausea and vomiting in acute migraine attacks^[14]. In a paediatric ED setting, one randomized control trial (RCT, n=53) assessed intravenous (IV) metoclopramide for migraine attacks in children, comparing monotherapy with a combination with IV ketorolac^[15]. The study found no significant difference in pain reduction between the two. A double-blind crossover RCT in two paediatric EDs (n=62) found IV prochlorperazine effective in 84.4% of patients, compared with 55.2% with IV ketorolac^[16]. Metoclopromide and prochlorperazine have not been compared head-to-head in youth but both appear to be effective in relieving pain. Prochlorperazine IV is not available for use in Canada.

Ketorolac

In trials, IV ketorolac did not show superiority over IV prochlorperazine^[14] or when combined with metoclopramide for pain relief improvement^[15]. A paediatric double-blind non-inferiority trial (n=53) found no difference in pain reduction at 60 minutes between intranasal and IV administration of ketorolac^[17]. There are no trials comparing ketorolac with placebo.

IV crystalloid solutions

A post-hoc analysis of four ED-based migraine trials with 570 patients treated with IV metoclopramide found that adding IV fluid did not improve pain outcomes for migraine attacks^[18].

A single-blind RCT in a paediatric ED (n=47) tested a 10 mL/kg normal saline bolus for migraine treatment^[19]. Neither drug treatment expectation nor the pain reduction with IV fluid alone were clinically significant.

Ibuprofen and acetaminophen

Two paediatric double-blind RCTs have addressed the use of these agents for acute migraine attacks in children and adolescents^[20][21]. Ibuprofen at a dose of 7.5 mg/kg was superior to placebo at reducing pain scores at 120 minutes^[21]. A crossover RCT with ibuprofen 10 mg/kg, acetaminophen 15 mg/kg, and placebo found that ibuprofen was superior at reducing pain scores in children compared with acetaminophen^[20].

Triptans

There is consistent evidence that triptans are superior to placebo, although most paediatric trials were conducted with outpatients or based on small numbers^[22]-[25]. Multiple trials have shown that triptans are less effective after the first 2 hours of the attack or when the pain has reached higher severity^[25]-[27]. Therefore, most ED patients are unlikely to meet treatment criteria.

Intranasal lidocaine

A pilot study (n=32) of atomized intranasal lidocaine for acute migraine attacks in children indicated tolerability and possibility for ED use but was underpowered to confirm efficacy^[28]. A meta-analysis of six RCTs in adults showed that intranasal lidocaine reduced pain severity at 5 and 15 minutes, improved success rates, and decreased the need for rescue medication. However, these benefits diminished when an antiemetic was administered^[29].

Valproic acid (VPA)

A meta-analysis including seven RCTs evaluated the role of IV VPA in adults and found that it was inferior to prochlorperazine, metoclopramide, and ketorolac^[30]. Observational studies in children have demonstrated tolerability and pain reduction with the use of IV VPA as a second-line agent for paediatric migraine^[31]-[33]. IV VPA is regulated by Health Canada’s Special Access Program (SAP). IV VPA is not approved for the indication of migraine attacks and not recommended in an ED setting.

Magnesium

A systematic review of seven adult RCTs demonstrated that IV magnesium improved pain control, reduced aura duration, and decreased the need for rescue analgesia in migraine attacks^[34]. However, one RCT showed that IV magnesium sulfate reduced the effectiveness of IV metoclopramide when they were used together^[35]. In a paediatric ED case series, IV magnesium sulfate had minimal side effects, but its efficacy in reducing migraine symptoms remained inconclusive^[36].

Greater occipital nerve (GON) blocks

GON blocks are weakly recommended in adult migraine guidelines for treating chronic migraine (>15 headache days/month)^[37]. A recent double-blind RCT (n=64) compared bilateral GON blocks with lidocaine versus saline in children and adolescents with severe migraine attacks unresponsive to usual therapies^[38]. The lidocaine group reported a mean pain decrease of 2.3 points (out of 10) , while the saline group reported a mean decrease of 1.1 points (p=0.01) at 30 minutes, demonstrating superiority over placebo.

Opioids

A study of adult headache treatment in the ED found that there was a significant increase in the use of opioids from 2001 (20.6%) to 2010 (35%)^[39] despite their lacking effectiveness in treatment of acute migraine attacks^[40]. Opioids are still used to treat children and adolescents presenting to the ED with migraine attacks but are associated with longer lengths of stay, readmissions, and ED re-visits^[41]-[43]. Opioids are not recommended due to inefficacy and potential for harm.

Evidence for the treatment of nausea and vomiting in acute migraine attacks

A retrospective cohort study found that ondansetron may be useful for treatment of nausea and vomiting in acute migraine attacks and performs similarly to dopamine antagonists such as metoclopramide^[44]. However, no studies have identified that the addition of ondansetron to metoclopramide in the treatment of acute migraine improves nausea over treatment with metoclopramide alone. There is unlikely to be any benefit in adding ondansetron to treat nausea when using metocompramide for headache pain.

Prevention

Steroids

The use of steroids to prevent migraine recurrence post-acute treatment in children and adolescents is controversial. One large adult systematic review supported its use in outpatient and ED settings^[45], and other systematic reviews endorse dexamethasone as a well-tolerated and effective option for migraine recurrence prevention^[46]-[49]. A retrospective study in paediatric patients with intractable migraine demonstrated that adding steroids to the acute treatment did not significantly reduce migraine recurrence^[50].

Nutraceuticals

Riboflavin, coenzyme Q10, and magnesium are recommended in adult migraine prevention guidelines^[51]. All have some low quality supportive evidence for use in migraine prevention among children and adolescents^[52]-[60].

Best practice points

• Initial management of acute migraine might include ibuprofen, a triptan (if presenting within 2 hours of onset of attack) and oral antiemetic (ondansetron) depending on the initial patient presentation.
• Clinicians should administer intravenous (IV) fluids based on hydration status.
• IV metoclopramide is the recommended approach for paediatric patients with acute migraine attack presenting in the ED.
• Based on limited paediatric evidence, ketorolac may not provide added benefit to metoclopramide monotherapy.
• Greater occipital nerve blocks and intranasal lidocaine are potential second-line treatment options, and their use is based on clinical expertise and the patient’s preferences.
• IV valproic acid, IV magnesium sulfate, and opioids are not recommended therapies for migraine attacks.
• There is inadequate data on the use of dexamethasone to prevent recurrence of migraine, but riboflavin, coenzyme Q10, and oral magnesium can be used for prophylaxis in young patients with frequent attacks.

Conclusion

Migraine attacks are common in children and adolescents visiting the ED. Due to sparse paediatric-specific evidence, treatments are often based on adult data. High-quality evidence is needed to improve treatment for young patients presenting with migraine.

Figure 1. Algorithm of treatment

IN Intranasal, NSAID Non-steroidal anti-inflammatory drug, ODT Orally disintegrating tablets

Information for health care providers:

TREKK: Medication Dosing Recommendations: Migraine

Information for parents:

English: Migraine Canada

French: Migraine Québec

Acknowledgement

This practice point was reviewed by the Drug Therapy and Community Paediatrics Committees, and the Hospital Paediatrics and Paediatric Emergency Medicine Section Executives, of the Canadian Paediatric Society. It was also reviewed by representatives of the Canadian Headache Society (CHS), and reviewed and endorsed by representatives of the Canadian Association of Child Neurology (CACN).

CANADIAN PAEDIATRIC SOCIETY ACUTE CARE COMMITTEE (2024-2025)

Members: Kevin Chan MD MPH MBA BSC (Chair), Tricia Feener MD (Board Representative), Jonathan Sniderman MD, Troy Turner MD, Brigitte Parisien MD, Tanvi Agarwal MD, Patrick Seitzinger MD (Resident Member)
Liaisons: Melanie Buba MD (CPS Hospital Paediatrics Section), April Kam MD (CPS Paediatric Emergency Medicine Section)
Principal authors: Sarah Rogers MDCM, Serena L. Orr MD, Brigitte Parisien MD, Laurel Chauvin-Kimoff MD

Potential Conflict of Interest
Dr. Serena Orr reported receiving book royalties from Cambridge University Press and is on the Editorial Boards of Neurology, Headache, and the American Migraine Foundation. She has PI funding on two active Canadian Institutes of Health Research (CIHR) grants and an American Headache Society grant, and is the lead on a clinical trial on the management of migraine in the emergency department, funded by CIHR. Dr. Orr receives investigational devices from Theranica, Inc. Theranica has no other role in the study and no payments have been received from them. No other disclosures were reported.

Funding
There is no funding to declare.

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Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.