Case vignette: A 42-year-old female presents at 10 pm with a throbbing right frontal headache associated with nausea, vomiting, photophobia, and phonophobia. The headache is severe, rated as “10” on a 0 to 10 triage pain scale. The headache began gradually while the patient was at work at 2 pm. Since 2 pm, she has taken 2 tablets of naproxen 500 mg and 2 tablets of sumatriptan 100 mg without relief.
The patient has a diagnosis of migraine without aura. She reports 12 attacks per month. The headache is similar to her previous migraine headaches. She is forced to present to an Emergency Department (ED) on average 2 times per month for management of migraine refractory to oral therapy. She reports a history of dystonic reactions and akathisia after receiving IV dopamine antagonists during a previous ED visit. The physical exam is non-contributory including a normal neurological exam, normal visual fields and fundoscopic exam, and no signs of a head or face infection. When you are done evaluating her, the patient reports that she usually gets relief with 3 doses of hydromorphone 2 mg + diphenhydramine 50 mg IM, and asks that you administer her usual treatment. What do you do?
Migraine is a neurological disorder characterized by recurrent painful headaches and abnormal processing of sensory input resulting in symptoms such as photophobia, phonophobia, and osmophobia . Central to disease pathogenesis is abnormal activation of nociceptive pathways . Disease severity ranges from mild to severe. Patients at one end of the spectrum have rare episodic headaches. On the other end are patients who have headaches on more days than not, patients who are functionally impaired by their headaches, and patients who frequently cannot participate fully in work or social activities. Chronic migraine, a sub-type of migraine defined by ≥15 days with headache for at least 3 consecutive months, is experienced by 1-3% of the general population .
ED use for treatment of migraine is common. 1.2 million patients present to U.S. ED’s annually for management of this primary headache disorder . Parenteral opioids are used to treat the acute headache in slightly more than 50% of all ED visits . Multiple authorities have cautioned against the use of opioids for migraine [5,6]. However, the frequent use of opioids has continued unabated, despite the publication in the EM, neurology, and headache literature of dozens of randomized controlled trials (RCTs) demonstrating safety and efficacy of parenteral alternatives, most notably dopamine antagonists and non-steroidal anti-inflammatory drugs .
Opioids have been associated with a variety of poor outcomes in migraine patients including:
- Progression of the underlying migraine disorder from episodic to chronic migraine 
- Increased frequency of return visits to ED 
- Less responsiveness to subsequent treatment with triptans 
- Less frequent headache relief than patients who received dihydroergotamine or dopamine antagonists 
In contrast, a high quality, ED-based RCT did not demonstrate more harm from 1 or 2 doses of meperidine than from dihydroergotamine . Hydromorphone, the parenteral opioid currently used most commonly in U.S. EDs , has never been studied experimentally in migraine patients. However, given the wide range of parenteral alternatives, the possibility that opioids may worsen the underlying migraine disorder, and the fact that they are less efficacious than other treatments, opioids should not be offered as first- or second-line therapy for patients who present de novo to an ED with an acute migraine (assuming no contraindications to alternative medications).
1) Other than opioids, what parenteral therapies can be offered to this patient?
The 3 classes of parenteral therapeutics with the most evidence supporting safety and efficacy for use as first-line therapy for migraine are the following :
- Dopamine antagonists
- Subcutaneous sumatriptan
However, this patient has relative contraindications to each of these. Other parenteral medications used for migraine are listed in the following table.
Table: Alternative parenteral migraine therapies
|Agent||Dose||Adverse events||Evidence supporting efficacy||Notes|
|Acetaminophen (APAP) [17, 18]||1 gm IV||Well tolerated||In one trial, IV APAP did no better than placebo. In another, IV APAP was comparable to an IV NSAID.|
|Dihydroergotamine ||0.5 mg -1 mg IV infusion||Nausea is common. Pre-treat with anti-emetics.||In one trial, DHE was less effective than sumatriptan at 2 hours but more effective by 4 and 24 hours.||Use cautiously in patients with cardiovascular risk factors.|
|Ketamine ||0.08 mg/kg SC||Fatigue, delirium||In one low quality cross-over RCT, ketamine outperformed placebo.|
|Magnesium [21-24]||1-2 gm IV||Flushing||In RCTs of varying quality, IV mg did not consistently outperform placebo||Efficacy data is most compelling for migraine with aura.|
|Octreotide ||0.1 mg SC||Diarrhea, injection site reactions||In a high quality RCT, octreotide did not outperform placebo|
10 mg IV every 10 minutes as needed up to 80 mg
30-40 mg IV with 10-20 mg bolus every 3-5 minutes up to 120 mg
|Sedation, hypoxia||In a low quality RCT, propofol outperformed dexamethasone. In another low quality trial, propofol outperformed sumatriptan.||It is not clear whether the migraine returns after propofol administration has been completed. Previous ALiEM post on migraines and propofol.|
|Valproic acid [28,29]||1000 mg IV||Well tolerated||In a high quality RCT, valproate was outperformed by metoclopramide and ketorolac. In a lower quality RCT, valproate was comparable to IV aspirin.|
APAP= acetaminophen; DHE= dihydroergotamine; Mg= magnesium
In some patients, greater occipital nerve blocks with a long-acting local anesthetic such as bupivaciane may play a role . While the above alternative parenteral therapies may benefit this patient, available evidence regarding risks and benefits does not dictate that these other therapies must be offered prior to use of opioids.
2) Does the fact that this patient makes frequent use of the ED indicate an unmet medical need?
As with congestive heart failure and asthma, frequent use of an ED for migraine is associated with worse underlying disease . These frequent users are more likely to have chronic migraines (> 15 headache days per month) and psychiatric co-morbidities . Concomitant medication overuse headache, a disorder defined by an upward spiral of increasing headache frequency in the setting of increased usage of analgesic or migraine medication, is also common . Management of complicated patients with migraines is exceedingly difficult, particularly during a busy ED shift, and may lead to frustration for both the healthcare practitioner and the patient. Ideally, outpatient healthcare practitioners with appropriate expertise should direct management of complicated patients with migraines.
3) Should the patient be administered 3 doses of hydromorphone 2 mg + diphenhydramine 50 mg IM as she wishes?
Management of chronic pain patients can be trying and demoralizing for emergency physicians because the underlying problem cannot be solved, and all avenues of treatment are flawed. Allowing the patient to suffer without appropriate justification is cruel. Delaying opioid administration during good faith efforts to identify alternative effective therapeutic agents is reasonable. Withholding opioids on principle is problematic because for most patients in most circumstances, published data do not establish that the benefit of pain relief is outweighed by the potential for opioid induced harm. On the other hand, thoughtlessly acquiescing to repeated requests for opioids during multiple ED visits is a violation of good medical practice, because of the concern of exacerbating the underlying migraine disorder, which could result in more ED visits, increased number of headache days, and the potential to cause refractoriness to standard migraine medication. One might compare it to administering antibiotics for bronchitis.
The best solution for the patient in the case vignette is to administer parenteral opioids only as rescue therapy for patients who adhere to an established outpatient plan of care. Acutely, the patient should not be allowed to suffer. However distasteful it may be, the harm arising from 3 isolated doses of parenteral opioids during one ED visit is unlikely to be either long-lasting or severe. But a prerequisite to treatment with opioids during a subsequent visit should be adherence to appropriate outpatient treatment: specifically, patients who require parenteral opioids for migraines should regularly attend outpatient appointments with an appropriate healthcare provider within the ED’s healthcare system.
Department-wide opioid policies are essential, as physician to physician variability in care may undermine a strict approach to opioids. Ideally, a committee with relevant expertise can monitor frequently presenting pain patients and develop patient-specific interventions that will be enforced by all practitioners during subsequent visits. If need be, the terms of treatment can be reinforced with a written document (example in the Appendix). This written document is not meant to be legally binding, but should be used to establish expectations. The last thing a busy emergency physician needs is a battle over opioids with a frequently presenting migraine patient. But before discharge, there should be a conversation about expectations during future ED visits. This will contribute to increased satisfaction for both the provider and the patient.
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