Management of Emergency HeadacheCHAPTER 1

A theoretical model of emergency use for migraine has been proposed: patients present to an emergency with their ‘first or worst’ headache or their ‘last straw’ headache.¹² The severe ‘first or worst’ headache is generally believed to require a thorough diagnostic evaluation in the emergency.¹³ The ‘last straw’ syndrome refers to an unbearable or unremitting exacerbation of a chronic episodic headache disorder. However, there is some variability in what constitutes the last straw—a consistent and substantial minority of emergency headache users present to emergency without taking any analgesic, not even acetaminophen, before presenting to the emergency.^14,15 In general, emergency solution-use for headache is most closely associated with emergency use for other chief complaints; thus patients who rely on emergency as a source of medical care will use it for manage-ment of their headache as well.^11,16 Other important predictors for emergency use are lower socio-economic status and increased severity of the underlying recurrent headache disorder.^11,16

Migraine attack typically occurs as a recurring unilateral headache with attacks 4 to 72 hours, if not treated. Classical attacks are of moderate to severe intensity, throbbing, aggravated by physical activity, and associated with nausea, vomiting, photophobia, phonophobia, and olfactophobia.⁵ Because the standard criteria require ten questions to diagnose migraine, various screening instruments have been developed to help clinicians identify migraine. Migraine is the headache type with a many of evidence-based treatment options. Using a headache expert's clinical gestalt as the gold standard, brief instruments such as ID Migraine can help identify migraine with a high degree of sensitivity.¹⁷ ID Migraine incorporates three questions (nausea, photophobia, and headache-related functional disability), requires two to be positive, and is focused on typical attacks, rather than the acute attack. A systematic review identified the following clinical features to be most useful for discriminating migraine from nonmigraine recurrent headaches: pounding headache, duration of headache lasting four to 72 hours, unilateral pain, nausea, and headache-related functional disability; the presence of any four made it highly likely that the headache was indeed a migraine; fewer than three decreased the odds of migraine.¹⁸ These instruments have yet to be validated in the emergency setting, but may provide a useful frame of reference for the emergency physician.

An emergency history and physical exam should focus on excluding secondary causes of headache, then determining which therapeutic agent is most appropriate. Physicians should be vigilant not to dismiss a diagnosis of migraine because of the presence of a coexisting illness, such as sinusitis.^19,20 This condition, amongst others, may exacerbate an acute attack of migraine. It is well-recognized that acute sinusitis can indeed cause headache, though it is less clear that chronic sinusitis does the same.¹⁹ The role of imaging in sinus headache, and how to interpret the findings is not clear because findings on CT imaging of the sinuses may not correlate with a patient's symptomatology.^21,22 Surprisingly, a sizable number of patients who are either self-diagnosed with sinus headache or referred to an otolaryngology practice with this working diagnosis actually meet criteria for migraine and respond appropriately to migraine-specific medications.^23-25

3Similarly, the pain associated with a migraine headache may cause an elevation in blood pressure. Care should be taken not to mistakenly diagnose this occurrence as a ‘hypertensive’ headache. Whether and how often hypertension causes headache is uncertain-even more, so at levels of hypertension that are considered moderate. We believe that known migraineurs who present with an acute migraine attack and associated moderate hypertension should be treated with an analgesic medication prior to an antihypertensive agent if there is no evidence of end-organ damage. Physicians should be careful not to cause an unnecessary precipitous drop in blood pressure. Once the headache has been controlled the blood pressure can be reassessed and a more thorough history obtained and examination undertaken.

Diagnostic testing is of limited value in patients with a well-established diagnosis of migraine. Concomitant infection or associated dehydration can be diagnosed clinically. Depending on the choice of therapeutic agent, pregnancy may need to be excluded before initiating therapy. In the absence of a concerning alteration in a patient's typical chronic headache pattern, emergent neuroimaging is unlikely to be helpful.

Routine intravenous fluids may be of benefit to patients with acute migraine, though this has not been well-established. For patients with persistent gastrointestinal symptoms intravenous rehydration is unlikely to be harmful. In general, parenteral treatment is preferred because gastric stasis and delayed absorption of medication occur during an acute migraine attack.²⁶

Triptans—Despite twenty years of clinical experience with the serotonin 1B/1D receptor agonists, this class of medication still has not enjoyed widespread use in an emergency setting.²⁷ One explanation for this is the lack of parenteral options—to this day, sumatriptan remains the only injectable triptan available in the US. Another likely cause of its infrequent use is the perception of cardiovascular risk. Though cardiac events have been infrequent, the difficulty of risk stratifying migraine patients in acute pain may cause practitioners to choose alternates.²⁸ Side effects, which are often short-lived, occurred in 50% of patients receiving subcutaneous sumatriptan in the emergency setting. This rate is twice that of placebotreated patients.²⁹ Cheaper alternatives are available, as sumatriptan will soon be available as a generic medication. Nevertheless, when it is effective, subcutaneous sumatriptan can rapidly and completely relieve migraine headache, allowing patients to return promptly to their usual daily activities. Data from a meta-analysis demonstrate that subcutaneous sumatriptan was almost three times as likely to relieve headache as placebo.³⁰ By two hours, 60% of sumatriptan subjects were pain free, versus 12% of placebo subjects. Sustained headache response (attaining headache relief and maintaining it for 24 hours) 4was achieved in 49% of sumatriptan subjects, almost three times as many as placebo. In the emergency setting, the median time to headache relief with subcutaneous sumatriptan was 34 minutes.²⁹ However, a large proportion of those who respond to sumatriptan will suffer a headache recurrence within 24 hours of emergency discharge.²⁹ When choosing a suitable population for subcutaneous sumatriptan, the most reasonable candidates include those who report previous response to sumatriptan. Recent literature describes a phenomenon referred to as cutaneous allodynia which may be associated with migraine headaches.³¹ Cutaneous allodynia is defined as the sensation of pain in response to normally non-noxious touch stimuli, such as brushing one's hair, taking a hot shower, or putting one's hair back in a ponytail. This phenomenon is an expression of involvement of ascending pain pathways.³² The presence of cutaneous allodynia has been associated with reduced sensitivity to subcutaneous sumatriptan.³³ This phenomenon has not been well studied outside of headache subspecialty populations and may be confounded by chronicity of the underlying headache disorder. Inadvertent administration of sumatriptan during pregnancy has not resulted in a marked increase in birth defects, though safety cannot yet be assured.³⁴ Therefore, in pregnant patients, alternate therapies should be used. Triptan nasal sprays are available but do not yet have a well-defined role in emergency set-up. Summarizing, subcutaneous sumatriptan may be used for the treatment of acute migraine as a single 6 mg dose. Further doses are unlikely to be more relieving.³⁵ Subcutaneous sumatriptan should be considered a first-line therapy for patients who are known to reespond to triptans previously. The emergency first dose triptan prescription may not be the most effective treatment option for triptan naïve patients.

Dihydroergotamine—Ergotamine has been prescribed for the treatment of migraine for several years. Its hydrogenated derivative, dihydroergotamine has been available for over 50 years as a parenteral option and is better tolerated than its precursor.³⁶ Though largely replaced by the triptans because of the latter's greater selectivity for serotonin receptors, dihydroergotamine may still play a useful second-line role for some emergency patients. When compared head-to-head, sumatriptan has greater initial efficacy, though dihydroergotamine is less likely to allow recurrence of headache, and so it may be useful in patients with a history of recurrence after treatment.³⁷ Dihydroergotamine is often administered with an anti-emetic, because it commonly induces nausea. When choosing an antiemetic, one of the antimigraine antiemetics, discussed below, would be preferred. Dihydroergotamine, when administered as monotherapy, is less likely than sumatriptan to relieve the pain or the functional disability associated with an acute migraine attack.³⁸ Both these medications are associated with an mixture of adverse events, including chest pain (sumatriptan), nausea (dihydroergotamine), drowsiness, flushing, neck tightness, dizziness, fatigue, and injection local site reactions.³⁸ Compared to chlorpromazine, dihydroergotamine as a single drug was more preferentially used as a rescue drug.³⁸ Dihydroergotamine can be administered in doses of 0.5 to 1 mg, infused as a slow intravenous drip. It is commonly coadministered with intravenous metoclopramide 10 mg. It is not recommended for use in patients with uncontrolled hypertension, vascular disease, and in pregnancy.

The antiemetic dopamine-antagonists—Recent concepts and increasing evidence suggests that this class of medication can be the most appropriate first line medications for the treatment of acute migraine in the emergency setting. Although not demonstrated, dopamine receptor blockade is being postulated. The efficacy of various drugs has 5been studied in multiple clinical trials for chlorpromazine,³⁹ metoclopramide,^14,40 prochlorperazine,⁴¹ and droperidol.⁴² Advantages being that these are inexpensive, well-tolerated and at least as efficacious, sometimes more than the agent to which they have been compared with. Hence, these medications can be considered as first-line medications for acute migraine in the emergency department. Amongst the above four agents above, chlorpromazine is least preferred because of profound orthostasis that may occur. Among the rest, droperidol is preferably the most effective, with two hour headache relief rates reaching almost 100% with an ideal dose of 2.5 mg.⁴² This is commonly used and is considered safe, although reports of QT prolongation has been observed, hence an ECG prior to administration is advised.

Though not as effective as droperidol, Prochlorperazine in doses of 10 mg is also a highly effective option.^43,44 Metoclopramide as a 10 mg intravenous dose provides good results but has shown maximal responses when administered as repeated successive doses of 20 mg.^14,45 The troublesome side effect accompanied with these agents include extrapyramidal symptoms, chiefly akathisia. Prior administration of diphenhydramine can effectively reduce the side effects, as will a slower intravenous drip rates.^46,47 The anti-emetic trimethobenzamide⁴⁸ and the antipsychotic haloperidol⁴⁹ have also demonstrated efficacy and tolerability for acute migraine attacks, though as of this writing, fewer data are available to determine the relative efficacy of these two agents. Metoclopramide is preferred in pregnancy and considered the most suitable parenteral agent for treating acute migraine.

Nonsteroidal anti-inflammatory drugs—NSAIDs are a main-stay of stable patients with lesser intensity. Ketorolac, parenteral NSAID, has shown favorable responses for the acute treatment of migraine. Its overall efficacy is comparable to meperidine,^50-52 though less than the antiemetics.^53-55 In patients without contraindications to nonsteroidals, such as peptic ulcer disease or chronic kidney disease, this medication dosed at 30 mg IV or 60 mg IM is a reasonable treatment option, either as primary treatment or as adjuvant therapy for acute migraine.

Opioids—Opioids, particularly meperidine, are still the most widely used medications for the treatment of acute migraine in western countries (North America).^27,56 Standard critiques of opioid use for migraine include the following: decreased efficacy, high rate of adverse effects, increased rate of recurrence of migraine within the short term, increased rate of emergency recidivism, and association with chronic migraine, though specific data for all of these is underwhelming. A recent meta-analysis demonstrated that meperidine is less efficacious for the treatment of acute migraine and burdened by more side effects than regimens containing DHE.⁵⁷ Additionally, meperidine is probably less efficacious than the antiemetics while allowing a higher rate of return visits to the emergency, though a lower rate of extrapyramidal side effects. Finally meperidine is no better than ketorolac, with a similar side effect profile.⁵⁷ Some data suggest that meperidine is associated with an increased rate of return visit to the emergency^56,58 and may be associated with decreased responsiveness to triptans.⁵⁹ In short, there are ample reasons to recommend avoidance of meperidine as a first-line treatment of migraine. In patients with infrequent episodic migraine and a history of excellent response to this medication, it still may be a reasonable option. When choosing among opioids, scant data are available to help guide a clinician. Parenteral morphine and hydromorphone have not been subjected to comparative clinical 6trials. Intramuscular butorphanol is more efficacious than meperidine and is as efficacious and well-tolerated as DHE + metoclopramide.⁶⁰ Opioids should not be withheld on principle—in general, this class of medication is highly effective, safe, and well-tolerated for the management of acute pain. However, for this one ailment, better agents are available.

Valproic acid—A more recent addition to the antimigraine armamentarium, this antiepileptic medication has seemed beneficial in open-label studies,^61-63 though it has performed less well in randomized trials.⁶⁴ It is not an unreasonable choice as a final treatment prior to admission, and should not be considered a first line medication. Valproic acid is often administered in doses between 500 mg and 1 gm as a slow intravenous drip over thirty minutes.

Recurrence of migraine after emergency discharge—No matter the treatment used, migraines frequently recur after emergency discharge. Almost 66% of patients report back to the emergency department with recurrence of moderate to severe intensity headache within 24 hours. Almost half of the patients report with functional disability within 24 hours.^65,66 It is hard to foresee who will suffer headache after discharge. Risk factors include a history of headache recurrence, longer duration of headache, more severe pain at baseline or persistent pain at discharge. It is a reasonable to educate all patients as to the likelihood of recurrence. A recent meta-analysis demonstrated that one dose of parenteral dexamethasone administered in the emergency can decrease the rate of recurrence of headache after emergency discharge, with a number needed to treat of nine.⁶⁷ Dexamethasone may begin to be effective within several hours. Doses of dexamethasone demonstrating efficacy have ranged from 10 mg to 24 mg, without a clear dose-response curve. In general, one dose of dexamethasone was very well-tolerated, and may now be considered first-line therapy to decrease the recurrence of headache after emergency discharge.

It is less clear what additional medications should be offered to treat the recurrence of headache after emergency discharge. Nonsteroidals, such as naproxen, or triptans, such as sumatriptan, are reasonable options, though data are not available. A substantial proportion of migraine patients who use the emergency continue to suffer from their underlying headache disorder over the months after emergency discharge.⁶⁶ It is reasonable practice to start patients who suffer from episodic migraines on an oral medication for use during their next migraine attack, particularly, if neurology or headache specialty appointments will be difficult to obtain. If nonsteroidals, acetaminophen, or aspirin have not proved sufficient for the patient previously, consider starting the patient on a triptan medication, assuming low cardiovascular risk, or a combination of metoclopramide taken with a nonsteroidal drug or salicylate. An evidence-based approach to outpatient care stratifies patients based on headache related disability at baseline.⁶⁸ Thus patients with substantial headache-related functional disability at baseline (i.e. frequently miss work or social activities) benefit from a triptan and patients without as much functional disability can be started on cheaper alternatives, such as a prescription nonsteroidal with or without metoclopramide. Though baseline headache-related functional disability scores are less useful in the emergency setting, this model is a useful framework to approach migraine care at the time of discharge.

Frequent emergency migraine visitors—Frequent visitors of migraine include 10% to the mergency department and up to 50% revisit the outpatient department.⁶⁹ Though it may be mistaken as ‘drug-seeking’ behavior, it may indicate poorly treated migraine. Well 7aware patients who observe their responses to specific medications often request for those medications, which includes opioids. Although effective urgency-based approaches to the frequent visitor have not been reported in the headache literature, individual emergencies should develop a uniform departmental approach to the chronic pain patient, so that the pain and social needs of the patient can be addressed appropriately. Physician to physician variability in management leads to unpleasant confrontations for the physician and uncomfortable situations for the patients, who at times are forced to beg for analgesia within the throes of an acute migraine. Multidisciplinary care and headache education have shown to reduce the frequency of visits to the hospital.^70-72 This approach reduced the burden of illness and healthcare expenses in patients with chronic headaches, though only a few patients were able to profit from these programs. We could not find any evidence-based emergency-appropriate strategies for addressing a patient's opioid for migraine requirements from the perspective of the individual clinician. This is a difficult problem for an emergency clinician in the middle of a busy shift. Potential strategies include offering a nonopioid therapy in conjunction with a lower opioid dose, referring to an appropriate outpatient clinician, and initiating a preventative therapy at the time of discharge. It is not clear how best to handle infrequent emergency users who report complete and persistent relief after one dose of opioid. On the one hand, one should not deny effective analgesics to patients who respond well to a particular therapy. On the other hand, there is an association between this particular class of therapy, chronic migraine, and emergency recidivism.

Special concerns for a pediatric population—Incidence of migraine in pediatric population peaks in early adolescence and as early as 5–6 year olds.⁶ The presentation of pediatric migraine is atypical, as they may present with bilateral headache of shorter duration and often without photo-and phonophobia.⁷³ Because of the higher placebo response rate there is smaller evidence base for treatment in pediatric populations. Management includes prescription of simple analgesics like ibuprofen, which seems to be as efficacious as triptans.^74,75 The antiemetic dopamine antagonists are commonly used,⁷⁶ though efficacy data is inferential and to date, limited to prochlorperazine.⁵³ The pediatric population also suffers several variants of cyclical pediatric pain and vomiting syndromes linked to migraine. These are particularly difficult to diagnose because they lack associated headache. Other presentations, such as cyclical vomiting, benign paroxysmal vertigo of childhood, and abdominal migraine are related with increased incidences of migraine in adulthood.⁵

Headache is classically unilateral and the side affected usually is consistent for every attack and every cluster period (defined as the interval of time which includes subsequent attacks). Most commonly pain occurs in and around the eye and temporal locations, the pain may frequently radiate in to the adjacent areas such ipsilateral neck, ear, cheek, jaw, upper and lower teeth, and nose.⁸⁵ Pain in these adjacent areas are common causes of being misdiagnosed as other forms of facial pain. The pain is agonizing and severe in intensity and is classically described as a stabbing or boring sensation. A typical attack starts abruptly and quickly intensifies, attaining a climax of pain within 5 to 15 minutes. Pain stops suddenly and the patient often is left feeling fatigued. The presence of at least one supplementary cranial autonomic symptom is required for a definite diagnosis of cluster headache.⁵ Autonomic symptoms such as conjunctival injection, lacrimation, congestion of nose, conjunctiva, rhinorrhea, edema of eyelid, forehead and sweating in face, ptosis, and miosis are the most common manifestations. These signs tend to occur invariably ipsilateral to the side of the pain. Another typical feature of this pattern of headache is its short duration. Untreated attacks classically lasts from 15 to 180 minutes, with more than 3/4th of attacks lasts less than 60 minutes. Because of the shortness of each attack, a partial or complete recovery may be observed while examining in the ED; which can obscure the accurate diagnosis. Rarely cluster attacks may last longer than 3 hours. Most commonly 1–3 attacks per day are observed, although up to 8 attacks can occur. 9The cluster period usually last for 2 to 3 months. The headaches then resolve suddenly, only to reappear again as another cluster of headaches several months to years later.⁸⁶ There is usually a not able expectedness to the timing of the such attacks and the cluster period, a phenomenon that differentiates cluster headache from other primary headache. On careful questioning, circadian rhythm and circannual periodicity can be observed which typically occur the same time each year. There is a diurnal variation where the attacks frequently tend to occur at night and awakens the patient 90 minutes after falling asleep, which corresponds to the onset of the first phase of rapid eye movement (REM) sleep. Sleep deprivation often is a manifestation of these repeated attacks and may also serve a catalyst for further attacks. Consumption of alcoholic beverages and vasodilator medications also may trigger an attack during the cluster period.⁸⁴ Seasonal periodicity is observed often, with the highest incidence occurring in the spring and autumn. Patients with cluster headache are agitated, restless and choose to be erect and to move about, a symptom that is in contrast to migraineurs where patients with migraine prefer to rest quietly and abstain themselves in a dark room. The severe intensity of the pain may sometimes cause some patients to scream loudly which may push patients to engage in destructive activities, such as banging their heads against the wall, in an attempt to relieve themselves of pain, sometimes pushing patients to extent to committing suicide.⁸⁶ Emergency treatment should be directed at relieving the acute attack and aborting the entire cluster of headaches. Abortive agents for cluster headache must work quickly and effectively. For most patients suffering from an acute cluster attack, the use of oxygen inhalation is the treatment of choice since it is easily administered, has an excellent safety profile, and works rapidly.^87,88 Based on our experience, oxygen is considered the most effective when administered with the patient positioned bent forward in a seated position. 100% oxygen is delivered through a loose-fitting, nonrebreathing facial mask at a flowrate of 7–10 L/min for 15 minutes. The response usually is quick and visibly appreciable, helping approximately 70% of patients within 15 minutes of administration. Although it is unclear why flow rate should matter when breathing 100% oxygen from a nonrebreather device, increasing the flow rate of oxygento 15 L/minute has been reported to help those refractory to the initial intervention.⁸⁹ Administering oxygen at the pinnacle of the attack may reduce the pain significantly; delivering it close to the onset of the attack may abort the pain completely. Subcutaneous sumatriptan in doses up to 12 mg SQ is highly effective at relieving cluster headache, though because of increased adverse effects, 6 mg is a more appropriate dose.⁹⁰ Subcutaneous sumatriptan has a rapid onset and is considered to be the most effective abortive agent for acute cluster attacks, often producing a benefit in 5–7 minutes after administration. A 6 mg subcutaneous dose maybe repeated at least 1 hour later but not more than twice daily. Dihydroergotamine (DHE) at doses of 0.5–1.0 mg given intravenously or intramuscularly is also useful as an abortive agent for cluster headache, though evidence supporting this medication is lacking. Anti-emetic dopamine receptor antagonists may be useful for acute attacks.^91,92 Subcutaneous octreotide (somatostatin) dosed at 100 micrograms can abort the acute attack, with a number needed to treat of five for complete relief of headache by 30 minutes.⁹³ After abortive therapy the patients must be educated and referred to a qualified specialist, because of its propensity to be of relatively long duration, follow-up and prophylaxis are essential to improve the quality of life for the patients. They will have to be reassured that there is no organic pathology involved and they must educated to avoid potential triggers. Prevention of 10consumption of alcohol, daytime naps avoidance of vasodilator medications can reduce the frequency of cluster attacks during the cluster period. Because of its nature to recur in 24 hours patients should be started on transitional and maintenance therapy. They must educated to help abort attacks at home using oxygen and subcutaneous sumatriptan. Corticosteroids are the recommended transitional treatment for cluster headache, though the evidence for this treatment is minimal.^94,95 Verapamil has been demonstrated to be an effective alternative prophylactic agent.⁹⁶ If rapid follow-up cannot be ensured as with most of Indian population, these medications should be initiated in the beginning which would significantly make an impact in the patients quality of life.