Severe Migraine: Options for Acute Therapy in the Emergency Department

A 36-year-old man with a 15-year history of episodic migraine presents to the emergency department (ED) at 5 AM with a right-sided throbbing headache of 4 hours' duration. The headache awakened him, which is typical of his more severe migraine attacks. Unfortunately, the patient forgot to refill his prescription for pain medication and did not "catch" this headache in time. He took an over-the-counter combination of aspirin( and caffeine(, which seemed to help for about 60 minutes, but the headache has returned full force. He has vomited twice-another characteristic typical of his migraine attacks. The patient complains of nausea, is anxious about missing work during the upcoming day, and demands a "pain shot." His most recent ED visits were 1 and 3 months ago. The records from these visits confirm the diagnosis of migraine.

THE DIALOGUE:
Clinician: This patient, who has an established diagnosis of migraine, appears to be overusing ED services. What is the most appropriate way to help him without encouraging repeated visits?

Headache specialist: If the headache pattern is typical and the physical examination is normal, the first step is to determine which medications the patient has previously used to control the headaches acutely and when he last took medication to abort a headache.

Clinician: How will that information help guide treatment?

Headache specialist: It can help you determine whether his therapeutic regimen is suboptimal and why headache control is less than ideal. For example, this patient may have used only nonspecific medications, such as narcotics or butalbital combinations. The goal is to find an option for this patient that will allow him to function well for the rest of the day.

Clinician: Why is it important to know when this patient last took medication for his headache?

Headache specialist: It can give you clues as to whether the patient is overusing an abortive medication, which can lead to rebound headache. This is a state of refractory, increasingly resistant headaches that recur as soon as the patient's blood level of the overused or abused agent decreases below a certain point.

You need to ascertain that this patient is not using abortive medications too frequently or inappropriately. You would not want to treat the patient with a medication that he has previously overused or with an agent incompatible with a drug that he has ingested recently.

Clinician: What are the most appropriate options for this patient?

Headache specialist: The best would be an agent that acts directly on the mechanism of migraine-ideally, a serotonin agonist. This type of drug is migraine-specific and acts directly on the 5-HT1B or 5-HT1D receptor sites on neural and vascular tissues to inhibit the nociceptive cycle, reverse abnormal meningeal blood vessel dilation, quiet perivascular inflammation, and relieve the neurologic and GI accompaniments of the migraine. The medications in this group include dihydroergotamine( (DHE), an ergotamine( derivative, and the triptans. Five triptans are currently available in the United States; however, only the nonoral formulations are appropriate in a patient who is vomiting and who also needs immediate pain relief.

Clinician: Are DHE and the triptans appropriate for any patient who presents with migraine in the ED?

Headache specialist: There are contraindications (Tables 1 and 2). Patients with uncontrolled hypertension are at risk because the vasoconstrictor effect of serotonin ago- nists can further increase blood pressure. Similarly, patients with coronary artery disease should not use ergotamines or triptans because these agents constrict coronary and cerebral blood vessels. Triptans are less likely than DHE to affect the coronary vessels; for example, subcutaneous (SC) sumatriptan( is associated with about a 15% decrease in coronary diameter. However, even a small reduction in coronary diameter could be fatal in a patient with significant coronary atherosclerosis or Prinzmetal angina.

Do not give serotonin agonists to:

• Patients with significant risk factors for coronary artery disease or stroke.
• Those who have complicated migraine with stroke-like symptoms.
• Persons older than 60 years.

DHE is contraindicated during pregnancy because of its oxytocic effects. Triptans have not been thoroughly evaluated for use during pregnancy. DHE should be avoided in patients with a history of deep venous thrombosis, significant liver disease, or concurrent infections.

Clinician: What regimen and route of administration do you recommend?

Headache specialist: DHE is probably most effective when given intravenously, preceded by an antiemetic. The initial test dose is 0.5 mg diluted in 50 mL of normal saline or dextrose( 5% in water, to be infused over 30 minutes. Subsequent doses can be increased to 1 mg. DHE can be administered via IV push, although this route increases the risk of nausea. DHE can also be given at a dose of 1 mg SC; 1 mg IM is even more effective. Possible side effects include leg cramps, joint aches, and diarrhea. Subcutaneous DHE is effective in 70% to 75% of patients.

Sumatriptan is used in the ED because it is the only triptan that can be given parenterally. The preferred dose in this setting is 6 mg SC, although the nasal spray, available in a 20-mg formulation, may also be effective quickly. The average time to onset for sumatriptan SC is about 10 minutes and for sumatriptan nasal spray about 15 minutes. The earlier in the attack sumatriptan is given, the greater the likelihood of pain relief.

Clinician: Can I safely use a triptan if the ergot does not work-or vice versa?

Headache specialist: No-an ergot and a triptan cannot be used within the same 24-hour period. This is one of the reasons that we need to inquire about medications the patient may have used before arriving at the ED.

Clinician: What if the patient has already failed to respond to a triptan or ergotamine that was self-administered at home, or if he or she is not a suitable candidate for either form of therapy?

Headache specialist: Several options are still available. For a patient who wants to remain alert after treatment, parenteral ketorolac(-an effective analgesic that is usually nonsedating-is an excellent alternative. The recommended doses are 30 mg IV or 60 mg IM. Occasionally, magnesium sulfate(, 1000 mg IV, will abort a severe headache without sedating effects. Val- proate acid, 1000 mg IV, administered fairly rapidly over 15 minutes, is another alternative.

Clinician: I see an occasional patient for whom none of these drugs are effective-and the rare patient who is allergic to all of these medications. What do you recommend in this setting?

Headache specialist: If your hospital pharmacy supplies it, parenteral orphenadrine(, 30 to 60 mg IM or IV, is highly effective in certain patients. This agent has an antihistamine effect that may be slightly sedating. Hydroxyzine(, 50 to 75 mg IM (without the narcotic component), may be effective, although this agent is also sedating.

The most sedating of the non-narcotic agents for aborting migraine are the phenothiazines, which are probably effective because they act on several neurotransmitters, including dopamine( and possibly serotonin. The phenothiazines are anxiolytic and some are potent antiemetics. Suggested agents and doses are listed in Table 3. The agents used most frequently in the ED are chlorpromazine and prochlorperazine(. Patients who receive intravenous chlorpromazine( must be monitored for hypotension and peripheral vein irritation. Alternatives are intravenous droperidol( or intramuscular haloperidol(. Adverse effects, such as muscle spasm or dystonic reaction, can be treated with benztropine mesylate, 1 to 2 mg IM, or diphenhydramine, 25 to 50 mg IV.

Clinician: I find that some patients become very "antsy" and uncomfortable following intravenous administration of a phenothiazine.

Headache specialist: Lorazepam(, 1 to 2 mg IM or IV, may provide relief. Of course, respiratory status must be monitored. Akathisias from phenothiazine treatment are extremely uncomfortable and must be treated promptly.

Clinician: What do you recommend if, in spite of everything that has been tried, the patient still says that his pain has not been relieved and demands a narcotic?

Headache specialist: If you feel that the patient is reliable, it is perfectly appropriate to administer a powerful analgesic on the rare occasion when all else fails. The longest-acting narcotic, methadone(, can be administered at a dose of 10 mg IM with an antiemetic. This drug has a 6-hour half-life. The short-acting narcotics (meperidine, nalbuphine(, and butorphanol) wear off almost before the patient is discharged from the ED. The problem with narcotics, of course, is the associated disability that prevents the patient from functioning fully. In order not to interfere with the primary physician's underlying treatment plan, do not give the patient a discharge prescription for more than 4 to 6 narcotic pills. Follow-up with the primary physician or appropriate referral physician is mandatory.

Clinician: What if I suspect a patient is overusing the ED for secondary purposes, such as obtaining narcotics?

Headache specialist: You have no obligation to provide treatment that you deem inappropriate simply because the patient requests it. I would suggest drug-dependence counseling. If you feel the patient may be addicted, consider admitting him for detoxification or refer him to a specialty headache clinic.

FOR MORE INFORMATION:

• Diamond S, Pepper BJ. Severe acute headache: step by step through the workup. Consultant. 2001;41:1329-1332.