Emergency Department

NeuroWiki

Acute Migraine: Emergency Department

Migraine accounts for approximately 3-5% of all ED visits. The goals of ED management are rapid pain relief, control of nausea/vomiting, and safe disposition. Evidence strongly supports dopamine antagonists and NSAIDs as first-line, while opioids should be avoided. Most patients can be treated and discharged; admission is reserved for refractory cases and status migrainosus.

Bottom Line

First-line: IV metoclopramide 10-20 mg or IV prochlorperazine 10 mg + diphenhydramine 25-50 mg (to prevent akathisia) — these are the most evidence-supported ED treatments
Add IV ketorolac 15-30 mg for additional analgesic effect
IV fluids: 1L NS bolus — most migraine patients are dehydrated
Avoid opioids — inferior efficacy, increase ED return visits, promote medication overuse headache
IV magnesium 2 g is useful in migraine with aura and as adjunctive therapy
Dexamethasone 10 mg IV reduces 24-72 hour headache recurrence (NNT ~9)
For triptan-ineligible patients: Gepants (ubrogepant, rimegepant) or lasmiditan are options if patient can take PO

Initial Management: IV Fluids

Many migraine patients presenting to the ED are dehydrated from nausea, vomiting, and reduced oral intake. IV fluid resuscitation is a standard first step.

1 liter normal saline bolus over 30-60 minutes
May provide modest symptomatic benefit independent of other medications
Required before chlorpromazine to prevent orthostatic hypotension
No RCT evidence that fluids alone abort migraine, but physiologically sound and standard practice

First-Line: Dopamine Antagonists

Dopamine antagonists (antiemetics) are the most effective acute migraine treatments in the ED setting. They address both pain and nausea through central dopaminergic blockade.

Agent	Dose	Route	Evidence	Notes
Metoclopramide	10-20 mg	IV over 15 min	Multiple RCTs; superior to placebo, comparable to sumatriptan	20 mg more effective than 10 mg; add diphenhydramine for akathisia
Prochlorperazine	10 mg	IV over 15 min	Largest evidence base; superior to hydromorphone (Friedman 2019)	Higher akathisia risk; always co-administer diphenhydramine 25-50 mg IV
Chlorpromazine	12.5-25 mg	IV (with NS bolus)	Effective but more sedating; orthostatic hypotension risk	Pre-treat with 500-1000 mL NS bolus; less commonly used
Haloperidol	2.5-5 mg	IV	Limited RCT data; effective in case series	Consider when other agents fail; QTc monitoring
Droperidol	2.5 mg	IV/IM	RCT data supports efficacy; black box warning limits use	QTc monitoring required; very effective but rarely used due to FDA warning

Akathisia Prevention

Akathisia (inner restlessness, inability to sit still) occurs in 15-40% of patients receiving IV dopamine antagonists
Always co-administer diphenhydramine 25-50 mg IV — reduces akathisia rates significantly
If akathisia occurs despite prophylaxis: benzodiazepine (midazolam 1-2 mg IV) or propranolol 10-20 mg PO
Slow infusion over 15-20 minutes (not IV push) also reduces risk

Ondansetron: A Note

Ondansetron (4-8 mg IV) is frequently used in EDs as an antiemetic but has less evidence for migraine pain relief compared to dopamine antagonists. It is useful:

As pretreatment before DHE (to prevent DHE-induced nausea)
When dopamine antagonists are contraindicated (e.g., Parkinson's disease, history of dystonic reaction)
For isolated nausea/vomiting control without expectation of headache relief

Ondansetron should not replace prochlorperazine or metoclopramide as first-line for migraine.

NSAIDs

Ketorolac

Dose: 15-30 mg IV or 60 mg IM
Note on dosing: The 2020 FDA label recommends 15 mg IV as the standard dose due to ceiling effect and renal risk; many EDs still use 30 mg. Use 15 mg in patients >65, <50 kg, or with renal impairment.
Effective as monotherapy but most commonly used as adjunct to dopamine antagonists
Comparable efficacy to sumatriptan in some trials
Limit to single dose to avoid contributing to medication overuse

IV Ibuprofen

800 mg IV over 5-10 minutes; emerging data as ED option
Not widely available; ketorolac remains the standard parenteral NSAID

IV Magnesium Sulfate

Dose: 1-2 g IV over 15-30 minutes
Best evidence in migraine with aura — may be effective specifically in patients with low serum magnesium (up to 50% of migraineurs)
Safe, well-tolerated; most common side effects are flushing and warmth during infusion
Reasonable as first-line adjunct, especially in migraine with aura
Avoid in renal failure; check for hypotension during infusion

IV Valproate Sodium

Dose: 500-1000 mg IV over 15-30 minutes
Mixed evidence: some trials show benefit, Friedman 2014 found inferior to metoclopramide for acute migraine
Reasonable second- or third-line option, particularly in patients with contraindications to first-line agents
Contraindicated in pregnancy, liver disease, and mitochondrial disease (POLG mutations)

Dexamethasone for Recurrence Prevention

Dexamethasone does not acutely treat the current migraine but prevents headache recurrence over the following 24-72 hours.

Dose: 10 mg IV (single dose)
Meta-analysis (Colman 2008): NNT ~9 to prevent one recurrence; absolute risk reduction ~10-12%
Should be considered for all ED migraine patients, especially those with prolonged attacks or history of recurrence
No benefit for the acute headache itself — always combine with first-line abortive therapy

Dihydroergotamine (DHE)

Dose: 1 mg IV or IM, preceded by an antiemetic (metoclopramide 10 mg or ondansetron 4 mg) 30 minutes prior
Highly effective, particularly for prolonged migraine (>48 hours) approaching status migrainosus
The DHE IV for Intractable Migraine trial showed 89% of patients became headache-free within 48 hours with repetitive IV DHE
Contraindicated: Within 24 hours of triptan use, pregnancy, uncontrolled hypertension, coronary/peripheral vascular disease, hemiplegic or basilar migraine
Can be repeated every 8 hours (max 3 mg/24 hours)
Consider as second-line when dopamine antagonist + NSAID combination fails

Options for Triptan-Ineligible Patients

Patients with cardiovascular disease, uncontrolled hypertension, or history of stroke/MI cannot receive triptans or DHE. Newer agents provide alternatives:

Gepants (Oral CGRP Antagonists)

If the patient can tolerate oral medications:

Ubrogepant: 50-100 mg PO; can repeat once after 2 hours if needed (max 200 mg/24h)
Rimegepant: 75 mg ODT (dissolves on tongue without water)
The Ubrogepant for Acute Migraine trial showed 2-hour pain freedom of 19-21% vs 12% placebo
No vasoconstrictive effects — safe in cardiovascular disease
Can be used even if patient has taken a triptan in the past 24 hours (unlike DHE)
Side effects: nausea (4%), somnolence (2.5%), dry mouth (2%)
Avoid with strong CYP3A4 inhibitors

Lasmiditan (5-HT_1F Agonist)

Dose: 50, 100, or 200 mg PO (100 mg is standard starting dose)
The SAMURAI and SPARTAN trials showed 2-hour pain freedom of 28-32% vs 15% placebo
No vasoconstrictive effects — binds selectively to 5-HT_1F receptors (not 5-HT_1B)
Major limitation: Causes CNS depression (dizziness 15-17%, somnolence 6-8%)
Patient cannot drive or operate machinery for 8 hours after dosing — critical counseling point
Schedule V controlled substance
Useful for ED patients who will not be driving themselves home

When to Use Gepants or Lasmiditan in the ED

Patient has cardiovascular contraindication to triptans/DHE
Patient can tolerate oral intake (not actively vomiting)
First-line IV therapy has failed and patient remains in moderate pain
Patient prefers to avoid IV medications
Practical consideration: Most EDs do not stock these medications; patient may need to use their own prescription or receive a new prescription for outpatient use

Nerve Blocks

Greater Occipital Nerve Block

2-3 mL bupivacaine 0.5% (or lidocaine 2%) injected at the greater occipital nerve (medial to occipital artery at superior nuchal line)
Several RCTs show benefit for acute migraine and cluster headache in ED
Onset within 15-30 minutes; can be bilateral
Minimal side effects; can be combined with any other treatment

Sphenopalatine Ganglion Block

Performed via intranasal approach using a cotton-tipped applicator or specialized catheter (Tx360, SphenoCath) soaked in lidocaine 4% or bupivacaine 0.5%
Emerging evidence supports efficacy for acute migraine; relatively simple to perform
No systemic side effects; can cause brief nasal discomfort
Useful adjunct when first-line therapies provide incomplete relief

Treatments to Avoid

🔴 Opioids in Acute Migraine

Do not use opioids as first-line treatment for migraine in the ED
Friedman 2019 RCT: prochlorperazine + diphenhydramine was superior to IV hydromorphone for migraine relief
Opioid use in ED is associated with higher 7-day return rates (17% vs 7% with standard therapy)
Single ED opioid exposure increases risk of chronic opioid use and medication overuse headache
Choosing Wisely (AAN/AHS): "Don't use opioid or butalbital-containing medications as first-line treatment for recurrent headache disorders"
Exception: severe nausea preventing oral intake when IV access is unobtainable — even then, prefer IM ketorolac + IM metoclopramide over opioids

ED Migraine Protocol

Suggested Protocol

Immediate: 1 liter NS bolus (while preparing medications)
First-line: Prochlorperazine 10 mg IV + diphenhydramine 25 mg IV + ketorolac 15-30 mg IV (all can run simultaneously)
Add: Dexamethasone 10 mg IV (for recurrence prevention)
If migraine with aura: Add magnesium sulfate 2 g IV
Reassess at 30-60 minutes
- If significant improvement → discharge with rescue plan
- If partial response → consider DHE 1 mg IV (if no triptan in prior 24h and no CV contraindication) or nerve block
- If no response → reassess diagnosis; consider DHE, valproate IV, or admission
For triptan/DHE-ineligible patients: If able to take PO, consider ubrogepant 100 mg or lasmiditan 100 mg (counsel re: driving restriction for lasmiditan)

Status Migrainosus and Admission Criteria

Status migrainosus is a debilitating migraine attack lasting >72 hours with pain and/or associated symptoms of severe intensity. These patients may require admission for aggressive parenteral treatment.

Indications for Admission

Refractory to ED treatment: No significant improvement after full ED protocol including DHE
Status migrainosus >72 hours: Especially if dehydration, intractable vomiting, or unable to tolerate oral intake
Comorbidities: Uncontrolled hypertension, pregnancy complications, severe psychiatric distress
Concern for secondary headache: Diagnostic uncertainty requiring inpatient workup
Social factors: Unable to safely manage at home, no reliable follow-up

Inpatient DHE Protocol (Raskin Protocol)

Premedication: Metoclopramide 10 mg IV or ondansetron 4 mg IV, 30 minutes before each DHE dose
DHE: 0.5-1 mg IV every 8 hours for 2-3 days (max 3 mg/24h)
The DHE IV for Intractable Migraine trial showed 89% headache-free at 48 hours with mean hospital stay of 3.8 days
Monitoring: Blood pressure, nausea, chest discomfort; reduce dose if significant nausea despite antiemetics
Transition to outpatient: Bridge with naproxen 500 mg BID and ensure preventive therapy is in place

🔴 DHE Contraindications (Critical for Inpatient Protocol)

Coronary artery disease, prior MI, angina
Peripheral vascular disease
Uncontrolled hypertension
Pregnancy or breastfeeding
Triptan use within 24 hours
Hemiplegic or basilar-type migraine (relative)
Severe hepatic or renal impairment
Concurrent use of potent CYP3A4 inhibitors

Discharge Planning

Rescue prescription: Provide an oral triptan, gepant (ubrogepant, rimegepant), or lasmiditan if the patient does not already have one
Short-term bridge: Naproxen 500 mg BID for 3-5 days if prolonged attack (limit to avoid MOH)
Referral to headache specialist if: frequent ED visits (≥2/year), no established preventive therapy, suspected medication overuse
Headache diary recommended for all patients discharged from ED for migraine
Return precautions: worst headache of life, new neurologic symptoms, fever, altered consciousness, headache not responding to rescue medication within 24-48 hours

Trial Comparison Table

Trial	Year	Comparison	Population	Key Outcome
Friedman (Neurology)	2019	Prochlorperazine + diphenhydramine vs hydromorphone	ED migraine	Prochlorperazine superior; lower return visits
Friedman (Neurology)	2014	IV valproate vs metoclopramide	ED migraine	Metoclopramide superior (pain-free 40% vs 20%)
Colman (BMJ meta-analysis)	2008	Dexamethasone vs placebo (added to acute tx)	ED migraine	Dexamethasone reduced recurrence; NNT ~9
DHE IV for Intractable Migraine	1986	Repetitive IV DHE vs IV diazepam	Intractable migraine	89% vs 13% headache-free at 48h
Ubrogepant for Acute Migraine	2019	Ubrogepant 50/100 mg vs placebo	Acute migraine	2h pain-free: 19-21% vs 12%; p<0.001
SAMURAI/SPARTAN	2019	Lasmiditan 100-200 mg vs placebo	Acute migraine	2h pain-free: 28-32% vs 15%; p<0.001
Lasmiditan Phase 3	2019	Lasmiditan 50-200 mg vs placebo	Acute migraine (incl. CV risk)	Effective in patients with CV risk factors
Bigal (Cephalalgia)	2002	IV magnesium vs placebo	Migraine with aura	Magnesium superior in migraine with aura

References

Friedman BW, et al. Randomized trial of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for acute migraine. Neurology. 2019;92(20):e2349-e2357.
Orr SL, et al. Management of adults with acute migraine in the emergency department: the American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2016;56(6):911-940.
Colman I, et al. Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence. BMJ. 2008;336(7657):1359-1361.
Friedman BW, et al. A randomized, double-blind, placebo-controlled trial of IV valproate sodium for acute migraine. Neurology. 2014;82(11):976-983.
Bigal ME, et al. Intravenous magnesium sulphate in the acute treatment of migraine with and without aura. Cephalalgia. 2002;22(5):345-353.
Raskin NH. Repetitive intravenous dihydroergotamine as therapy for intractable migraine (DHE IV for Intractable Migraine). Neurology. 1986;36(7):995-997.
Dodick DW, et al. Ubrogepant for the treatment of migraine (Ubrogepant trial). N Engl J Med. 2019;381(23):2230-2241.
Goadsby PJ, et al. Trial of lasmiditan for acute treatment of migraine (SAMURAI/SPARTAN). JAMA Neurol. 2019;76(9):1025-1034.
Choosing Wisely: American Academy of Neurology — Five things physicians and patients should question. 2013.