Ch. 2 - Migraine

David H. Cisewski, MD, MS | Icahn School of Medicine at Mount Sinai
Benjamin W. Friedman, MD, MS | Albert Einstein College of Medicine

Current estimates suggest more than 1 million patients visit the ED annually for acute migraine attacks.¹ Not only are these attacks debilitating, but the management is also complicated by a wide range of analgesic regimens, none of which offer guaranteed relief.

More than 20 different migraine medications are currently used. Yet, less than 25% of patients achieve sustained headache relief (> 48 hrs), indicating we still fall well short of optimal management.² Additionally, many of the analgesic options we currently use cause debilitating side effects such as drowsiness, dizziness, restlessness, akathisia, and dry mouth. What we need is an analgesic regimen that is not only quick and efficacious but also contains minimal side effects to return the patient to their baseline quality of life.

DEFINING MIGRAINES

Migraine is a clinical disorder that lacks definitive laboratory or neuroimaging findings. Migraines are defined as recurrent headaches (at least five life-time headaches), not associated with another disease pathology, lasting 4-72 hours with at least 2 of the following characteristics:³

• Unilateral location
• Pulsating quality
• Moderate/severe intensity
• Aggravated by physical activity

Additionally, the diagnosis of migraine must include either photophobia/phonophobia or nausea/vomiting.³

To effectively manage pain, we must recognize the individual, subjective nature of each patient's pain presentation and treat it safely and effectively using available research data. Additionally, an accurate diagnosis will allow patients to access appropriate care as an outpatient and at future ED visits. A common question is whether there is a need to distinguish migraine-specific headaches from alternative headache subtypes in the emergency setting. Though migraine is not synonymous with "severe headache," patients with moderate to severe headaches often respond to a similar analgesic regimen. When the diagnosis is unclear and severe causes of headache have been safely ruled out, a migraine regimen may be considered for all moderate to severe headaches.

MIGRAINE DIFFERENTIAL DIAGNOSIS

Although anchoring bias may focus attention on a classic migraine presentation, particularly in patients with a history of migraines, consideration must be given to other benign and life-threatening causes of migraine-mimics.

Benign: Along with migraines, benign causes of headache include tension headaches, cluster headaches, trigeminal neuralgia, post-lumbar puncture headaches, sinusitis, coital headaches, medication overuse headache, and low/ high CSF pressure headaches such as post-dural puncture headache.

Deadly: More dangerous and potentially life-threatening causes of headaches (along with associated can't-miss red flags) include: carbon monoxide toxicity (family with headaches), temporal arteritis (temporal tenderness, jaw claudication, age > 50 years), subarachnoid and other forms of intracranial hemorrhage ('worst headache of my life,' maximal at the onset, anticoagulant use), cervical artery dissection (neck trauma, unilateral face pain, ptosis & miosis), cerebral venous sinus thrombosis (thromboembolic risk factors, recent brain/ face surgery), idiopathic intracranial hypertension (obesity, transient visual obscurations, papilledema), preeclampsia (current/recent pregnancy), meningitis/encephalitis (fever and neck stiffness, altered mental status, immunocompromised state, and space-occupying lesion such as malignancy (weight loss, history of malignancy).

TREATING MIGRAINES

A migraine is often a debilitating form of headache. It may be resistant to first-line oral medications used for mild/moderate pain such as acetaminophen (975 mg PO) and ibuprofen (400 mg PO). For migraines resistant to oral acetaminophen/ibuprofen combinations, several non-opioid alternatives exist. The optimal migraine medication should have a safe, quick-onset, maximal efficacy, limited side effects, and allow for sustained headache relief. To date, this optimal combination does not exist. Of the 1 million patients presenting to the ED each year for migraine treatment, opioids are still being used in the majority of treatment plans, with hydromorphone being the analgesic of choice in approximately one-fourth of the cases.¹ However, research has demonstrated superior analgesic relief with non-opioid alternatives^4, and several other alternatives have been shown to treat migraines safely and effectively. The following is an evidence-based list of migraine treatment options that may be utilized in the emergency setting:^5,6

Standard first-line migraine treatment options for moderate to severe pain include metoclopramide (10 mg IV), prochlorperazine (10 mg IV), chlorpromazine (12.5 mg IV), haloperidol (5 mg IV), or droperidol (2.5 mg IV or IM). Though the specific frontline analgesic depends on the patient's past success and current presentation, metoclopramide (10 mg IV) is considered an optimal, evidence-based first-line agent.^7,8 Prochlorperazine has also demonstrated superiority over opioids for acute migraine relief but should be administered with 25 mg diphenhydramine to avoid extrapyramidal side effects.^9,10 Both metoclopramide and prochlorperazine should be administered slowly over a 15-minute infusion to avoid akathisia.⁹ Chlorpromazine (12.5 mg IV) has also been shown to be as effective as metoclopramide. It should also be administered slowly over 20-30 min.^11,12 Among patients with a normal cardiac QT length, the antidopaminergics haloperidol and droperidol may also be considered first-line options. Droperidol (2.5 mg IV) has been shown to be at least as effective as prochlorperazine for acute pain reduction of benign acute headaches in the emergency setting.^13,14 Haloperidol (5 mg IV) has also been shown to be as efficacious as metoclopramide (10 mg IV) for acute headaches in the emergency setting though with increased restlessness.⁸

Dexamethasone (10 mg IV) reduces headache recurrence within 72 hours of ED discharge (NNT = 9)^15, as well as decrease the need for repeated analgesic use during the emergency presentation.¹⁶ Additionally, magnesium (1 g IV) may offer similar effect to decrease current and repeat migraines, though the evidence is mixed and most suggestive in treating migraine with aura.^17,18

A nerve block may also be considered in patients with moderate to severe occipital headaches. Nerve blocks have been used for migraines for years with the greater occipital nerve (GON) being a major target.^19,20 The GON is composed of sensory fibers that derive from the C2 spinal nerve, providing cutaneous innervation to the majority of the posterior scalp.²¹ The theoretical rationale for the GON block (GONB) for migraines derives from the convergence of its neurons with trigeminal nerve fibers, which have been implicated in migraine.^21,22 (Note: This convergence pattern also accounts for the location of pain distribution with migraines, which often includes both anterior and posterior regions of the head/upper neck.) The greater occipital nerve innervates the posterior scalp bilaterally. The following 3-step landmark technique can be used to identify the greater occipital nerve on each side of the scalp:²³

1. Place index finger on the occipital protuberance.
2. Place thumb on the mastoid process (either right or left side).
3. Measure one-third the distance between two points extending from the occipital protuberance.

This is the approximate location of the greater occipital nerve as it extends up from its exit from the semispinalis capitis muscle at approximately the C1/C2 position (*GON often noted as the point of maximal tenderness).

Once identified, 3–5 mL of 1% to 2% lidocaine or 2–4 mL of 0.25% to 0.5% bupivacaine is injected using a 27-gauge needle to infiltrate the GON.²¹ The optimal technique involves a "fanning technique" in which 1 cc of anesthetic is injected immediately adjacent to the GON, 1 cc medial to the GON, and 1 cc lateral to the GON for maximal infiltration. The "fanning technique" can be repeated bilaterally to cover both GONs.^17,18 If continued symptoms, despite 1 hour of assessment, proceed to step five.

Among patients with an unremitting headache following a 30- to 60-minute reassessment, full consideration should be given to alternative diagnoses, particularly the deadly can't-miss diagnosis. For further analgesic relief, consider an alternative first-line analgesic option from those listed above. Additionally, ketorolac (15-30 mg IV)may be added among patients who do not have contraindications to nonsteroidal anti-inflammatories.⁷ Intravenous fluids may be considered among patients who appear dehydrated or who have been vomiting but have not been shown to increase migraine relief when used as an adjunct with other first-line regimens.²⁴

Among patients who show refractory migraines following repeated attempts at the first-line options, second-line alternatives may be considered, such as valproate, sumatriptan, and acetylsalicylic acid. Valproate (1 g IV) may be considered among patients who have previously had a favorable response. However, research has shown decreased efficacy compared to other first-line options (metoclopramide).⁷ Sumatriptan may also be considered. Although sumatriptan is considered a first-line migraine treatment option in the outpatient setting, it causes many adverse effects (chest tightness, flushing, potentially worse headache) and an increased rate of short-term headache recurrence.²⁵ Additionally, the first-line antidopaminergics have increased efficacy and improved tolerability compared to triptans.^26,27 Nevertheless, sumatriptan (6 mg SQ) may be considered among patients who do not have cardiovascular risk factors and who have received a benefit from it during previous migraine attacks. Although ketamine (0.15-0.3 mg/kg IV, 15 min infusion) is not recommended for migraine headaches as it has been shown to be ineffective,²⁸ and also inferior to prochlorperazine for benign headaches,²⁹ it may be considered as a non-opioid alternative for refractory headache pain. If available, addition of acetylsalicylic acid (0.5-1 g IV) may also be considered with efficacy comparable to sumatriptan but with less of a side effect profile.^30,31

Propofol (sub-anesthetic dosing – 30–40 mg IV) with repeat boluses of 10 mg every 3-5 min up to 120 mg may be considered as a last resort for refractory migraines.³² The use of propofol is limited by the need for cardiac monitoring and provider observation to avoid over-sedation.

MIGRAINE DISPOSITION

It is essential to set realistic expectations for patients presenting for migraine management. Though many patients will have a defined analgesic regimen that works best for their migraine flairs, most will not and will require trial periods of the above stepwise approach. Dexamethasone (10 mg IV) may assist with prevention, yet up to two-thirds patients will still have migraine relapse in the days following ED visit.² Be sure to establish outpatient primary care follow up for management and ensure close ED return precautions for warning signs that may suggest an alternative diagnosis such as continued headache suffering, fever, or vomiting with an inability to tolerate oral fluids. Among patients without contraindications, naproxen (500 mg PO) or sumatriptan (100 mg PO) may be prescribed to treat a short-term recurrence of headache after ED discharge.³³ A sumatriptan auto-injector (Imitrex) is also available as an easy-to-use administration during an acute headache attack.³⁴ Additionally, acetaminophen or acetaminophen/aspirin/caffeine combination (Excedrin) may be effective in treating the pain and associated side effects of migraine headaches.^35,36 The combination acetaminophen/butalbital/caffeine (Fioricet) should be avoided due to the increased adverse effect profile, medication overuse headaches, and rebound headaches.³⁷

References

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