Headache Management: Best Current Evidence for the ED

Author: Sara Adibi, MD (@deebs_6, EM Attending Physician, Baylor Scott & White at Centennial/Baylor Medical Center-Frisco) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

This discussion will focus on managing headache symptoms in the ED. Red flags in the H&P, diagnostic testing, differential diagnoses, etc. are outside the scope of this review, as is a comprehensive review of the different types of headaches (both primary and secondary). If interested in further info, go here: http://www.emdocs.net/acute-headache-emergency-department/

Brief review of ACEP Clinical Policy

Critical Question 1. Does a response to therapy predict the etiology of an acute headache?


Level C Recommendation: Pain response to therapy should not be used as the sole diagnostic indicator of the underlying etiology of an acute headache.

Critical Question 2. Which patients with headache require neuroimaging in the ED?


Level B Recommendations

• Patients presenting to the ED with headache and new abnormal findings in a neurologic examination (eg, focal deficit, altered mental status, altered cognitive function) should undergo emergent non-contrast head CT.
• Patients presenting with new sudden-onset, severe headache should undergo an emergent head CT.
• HIV-positive patients with a new type of headache should be considered for an emergent neuroimaging study.

Level C Recommendation

• Patients who are older than 50 years and presenting with a new type of headache but with a normal neurologic examination should be considered for an urgent neuroimaging study.

Critical Question 3. Does lumbar puncture need to be routinely performed on ED patients being worked up for non-traumatic SAH whose non-contrast brain CT scans are interpreted as normal?

Level B Recommendation

• In patients presenting to the ED with sudden onset, severe headache and a negative non-contrast head CT scan result, lumbar puncture should be performed to rule out SAH.

Critical Question 4. In which adult patients with a complaint of headache can a lumbar puncture be safely performed without a neuroimaging study?

Level C Recommendation

• Adult patients with a headache and exhibiting signs of increased intracranial pressure should undergo a neuroimaging study before having a lumbar puncture.
• In the absence of clinical findings suggestive of increased intracranial pressure, a lumbar puncture can be performed without obtaining a neuroimaging study.

Critical Question 5. Is there a need for further emergent diagnostic imaging in the patient with sudden onset, severe headache who has negative findings in both CT and LP?

Level B Recommendations

Patients with a sudden onset, severe headache who have negative findings on a head CT, normal opening pressure, and negative findings in CSF analysis do not need emergent angiography and can be discharged in the ED with follow up recommended.

Introduction

Headaches account for up to 4.5% of emergency room visits per year³.  There are a wide range of causes of headaches, ranging from benign primary migraine disorders to those that are life threatening, such as seen with subarachnoid hemorrhage.

Our understanding of pain pathways in headaches are not well understood. Multiple hypotheses exist involving cerebral vessels, nerves, inflammation, intracranial pressure, meningeal irritation, and/or intracerebral serotonergic projections. Thus there are many different medical therapies available for symptomatic relief. Prior to managing headaches in the ER, it is often beneficial to ask “What therapies have you tried at home?” Some patients may have already tried NSAIDs or even oral triptans prior to arrival, while others may not have tried anything at all. Having this information at hand can alter your success at effectively treating headache pain in the ER.

With this in mind, it should go without saying that a full diagnostic evaluation should always be performed with the utmost emphasis on a thorough history and physical including a complete neurological exam (pearl: don’t forget the eye exam).

Medications:

– Intravenous Fluids: Liberal fluid replacement can help avoid postural hypotension or provide renal protection that may occur as a side effect of medications administered. Additionally, dehydration can often worsen headache pain and therefore IV fluids may provide an independent benefit. Use with caution in those with CHF and uncontrolled hypertension.

– Anti-dopaminergic agents: Have both analgesic and anti-emetic properties. Side effects due to anti-histaminic and anti-cholinergic effects include drowsiness. Other documented side effects include QT prolongation, dystonia, and akathisia. Concomitant administration of Benadryl may prevent dystonia and akathisia.

1) Prochlorperazine (Compazine): Often recommended as a first line agent. Dosed at 10mg IV or IM. Had a positive outcome in all patients at 2 hours in small double blind randomized trial (i.e. 90% had at least partial relief)⁸.  Rectal suppository form also available. Multiple studies have demonstrated superiority to Magnesium, Depakote, Ketorolac, Metoclopramide, and SC Sumatriptan.

2) Chlorpromazine (Thorazine): Dosed at 0.1mg/kg to 25 mg, IV or IM. One study demonstrated that 83% of patients had symptomatic relief at 1 hour⁸.  Has also been shown to have significantly reduced rate of headache relapse at 24 hours².

3) Promethazine (Phenergan): Dosed at 25mg IM or IV. Caution with IV administration as extravasation can cause soft tissue injury. While often used as an adjunct in the ED, there have not been any independent studies for efficacy in treatment of acute headaches.

4) Droperidol (Inapsine): Dosed at 2.5mg to 5mg IM or IV. The black box warning for QT prolongation is controversial, as dosing of droperidol approached 30 mg in the studies with adverse outcomes. With the lower doses of droperidol used for headache treatment, QT prolongation is unlikely. Per institutional guidelines, an ECG may still be required before droperidol is administered. There have been randomized controlled studies that have both demonstrated greater efficacy than Compazine and superiority to placebo⁸.  However, can have high rate of adverse effects such as dystonia.

5) Haloperidol (Haldol): Dosed at 5mg IV or IM. Placebo controlled studies demonstrate efficacy.

6) Metoclopramide (Reglan): Dosed at 10mg IV. One study demonstrated efficacy in 46% of patients at 1 hour⁸.  Also has serotonin receptor antagonist properties.

– Serotonin receptor agonist (5HT 1B/1D), Triptans: Contraindications: cardiovascular disease, uncontrolled HTN and pregnancy. These drugs will not precipitate serotonin syndrome in someone taking an SSRI or SNRI as they do not interact with 5H2 receptor. There are few to no trials that compare triptans head to head.

1) Sumatriptan: Dosed at 6mg SC, 10-20mg intranasal, or 100mg PO (can be repeated x1 if no improvement after 1 hour). When used for headaches whose duration is less than 6 hours the efficacy has been shown to be as high as 91%. SQ Sumatriptan has been shown to be more effective than oral formulations, however all formulations have demonstrated superiority to placebo. Additionally, in combination with an NSAID has proven to be more effective than either agent alone⁸. Treximet is an FDA approved formulation of Sumatriptan and Naproxen sodium in a combination pill.

2) Other triptans demonstrated to be effective for treatment of migraine pain and FDA approved for such: Almotriptan (Axert) 12.5mg, Eletriptan (Relpax) 20-40mg, and Rizatriptan (Maxalt) 10mg.

– Dihydroergotamine: Dosed at 0.5 to 1mg IM or IV (for maximum of 3mg). One study demonstrated 60% reduction in mean pain scores at 1 hour with 0.75mg IV use and 72% with 1mg IM. Contraindications include cardiovascular disease, uncontrolled HTN and pregnancy. In multiple studies when combined with antiemetic, usually Reglan, was as effective as or more effective than Demerol, Depakote, and/or Toradol^2,8.

– NSAIDs:

1) Ketorolac (Toradol): Dosed at 30mg IV or 60mg IM. Studies demonstrated a 57% decrease in pain scores at 1 hour using 30 mg IV and 80% at 2 hours using 60 IM⁸. Can be combined with triptans for increased efficiency. Contraindications include active PUD, renal insufficiency, severe asthma, and pregnancy during 3rd trimester. No placebo controlled trials, but in a 2013 systematic review of 8 randomized trials demonstrated efficacy compared to other standard migraine therapies².

2) Naproxen: Dosed at 500-550mg BID. In 4 placebo controlled studies was noted to have a positive effective¹². Consider adding a PPI for gastric protection. Moderate usage is protective against conversion to chronic migraine.

– Sodium Valproate (Depakote): Dosed at 300-1200mg IV. Has been demonstrated to be effective in 75% of patients at 50 minutes. No placebo controlled studies for intravenous use in acute migraine, but there is evidence to support its use for migraine prophylaxis⁸. Contraindications include pregnancy, liver disease, and urea cycle defects.

– Diphenhydramine (Benadryl): Dosed at 25-50mg IV, IM, or PO. In a January 2016 article in the Annals of EM a randomized double blind clinical trial compared administering 50mg IV Benadryl with Reglan 10mg IV versus 10mg IV Reglan with placebo⁷. There was no difference in outcome when comparing sustained relief at 48 hours, length of stay, and adverse effects. Furthermore, when looking specifically at a subset of patients with “allergic symptoms” there was no difference in outcome of efficacy, however it appears there was greater patient satisfaction as noted from an increased desire to receive the Benadryl combination again in the case of recurrence of headache symptoms.

Pearls and Pitfalls

• Opioids should NOT be routinely used for acute migraine headaches. There are multiple side effects that have been noted including addictive potential. Additionally, opioids have a high association with medication overuse headaches/rebound headaches and therefore can increase the risk of relapse and subsequent bounce back to ER. Can also promote chronic migraines.
• Magnesium. Studies have shown that routine serum studies do not reflect true total magnesium stores⁶. Migraine sufferers may have magnesium deficiency (hypothesized to be due to genetic defect resulting inability to properly absorb magnesium, increased renal wasting with excretion of excessive amounts, and/or low nutritional intake, etc). While double-blind placebo controlled trials have mixed results, researchers believe this may be due to involvement of both magnesium deficient and non-deficient patients. Since both oral and intravenous formulations are widely available and relatively safe this can provide a significant benefit to those patients with chronic migraines who may be magnesium deficient (reportedly up to half of migraine patients).
• There is controversy surrounding use of steroids (typically dexamethasone at 10-25mg IM or IV).
  • Up to date does recommend use to reduce risk of early relapsing headache².
  • Up to 49% of patients will have a recurrence of headache within 72 hours¹. While recurrence is dependent on choice of abortive agent, sex, age, and severity of migraine at presentation there is evidence (meta-analysis of 7 randomized trials) that dexamethasone may decrease the frequency of such recurrences in up to 10% of patients (number needed to treat was 9)⁸. Additionally, dexamethasone does not provide an immediate benefit for relief of symptoms. Thus it is important to weight the benefits versus the risk of administering this medication. While one dose of dexamethasone has been shown to have no increased adverse effects compared to placebo, it is important to note that repeated exposure is associated with significant side effects including avascular necrosis of bone.
• Abortive treatments for migraine are usually more effective if they are given early in the course of the headache; a large single dose tends to work better than repetitive small doses.

Special Circumstances

• Pregnancy

  1. 50-75% of patients will have a reduction in the frequency of attacks, while 8% will have increased frequency or intensity of attacks.
  2. There are multiple high risk causes of headache that have an increased occurrence during pregnancy such as pre-eclampsia, central venous thrombosis, pituitary apoplexy, subarachnoid hemorrhage, arterial dissection, etc.

• Children

  1. Obesity and physical inactivity have been linked to headache disorders.
  2. Clinical trials have shown a high placebo effect in pediatric migraine disorders⁵.
  3. FDA approved triptans include Axert, Maxalt (in children aged 6-17), Zomig Nasal Spray, and Treximet (in those 12 years of age or older).
  4. Ergotamines are generally not used in children 6 or younger due to side effects.
  5. Over-the-counter analgesics such as acetaminophen and NSAIDs are particularly effective in the pediatric population.

Conclusion

After reviewing the evidence, the following recommendations for treating mild to moderate headache pain include oral over-the-counter analgesics (Excedrin, Naproxen, Tylenol) +/- an anti-emetic. Other alternatives are Treximet for patients who have already tried these therapies at home or subcutaneous Sumatriptan. For patients with moderate to severe headache pain, try starting with oral triptan. If one form of triptan does not provide relief of symptoms, an alternative triptan may be used. For patients refractory to oral medications, first line agent is Compazine. This may be used in conjunction with intravenous fluids, Benadryl, and/or Toradol. Alternative therapies include DHE with Reglan or Droperidol in conjunction with intravenous fluids, Benadryl, and/or Toradol. As noted earlier, there are multiple different medical therapies available to treat headache pain and many may be used in combination. Each patient will respond differently to “cocktail” combinations and therefore it is important to have a broad knowledge of the different medications available in order to have a wide array of treatment plans.

References / Further Reading

1. Giuliano, C., Smalligan, R., Mitchon, G., & Chua, M. (2012, May). Role of dexamethasone in the prevention of migraine recurrence in the acute care setting: A review. Retrieved March 12, 2016, from http://www.ncbi.nlm.nih.gov/pubmed/22691905
2. Bajwa, Z. H., MD, & Smith, J. H., MD. (2016, February). Acute treatment of migraine in adults. Retrieved March 12, 2016, from http://www.uptodate.com/contents/acute-treatment-of-migraine-in-adults#H342443188
3. Cutrer, F., MD. (2015, May 11). Evaluation of the adult with headache in the emergency department. Retrieved March 12, 2016, from http://www.uptodate.com/contents/evaluation-of-the-adult-with-headache-in-the-emergency-department
4. ACEP Clinical policy: Headache. <http://www.acep.org/Clinical—Practice-Management/ACEP-Current-Clinical-Policies/>
5. Lopez, I., MD, Bechtel, K. A., MD, & Rothrock, J. F., MD. (2015, June 23). Pediatric Headache Treatment & Management. Retrieved March 14, 2016, from http://emedicine.medscape.com/article/2110861-treatment#d8
6. Mauskop, A., & Varughese, J. (2012, May). Why all migraine patients should be treated with magnesium. Retrieved March 16, 2016, from http://www.ncbi.nlm.nih.gov/pubmed/22426836
7. Friedman, B. W., MD, Cabral, L., MD, Adewunmi, V., MD, Solorazano, C., Esses, D., MD, Bijur, P. E., PhD, & Gallagher, J., MD. (2016). Diphenhydramine as Adjuvant Therapy for Acute Migraine: An Emergency Department-Based Randomized Clinical Trial. Annals of Emergency Medicine, 67(1), 32-39.
8. Gelfand, A. A., MD, & Goadsby, P. J., MD. (2012). A Neurologist’s Guide to Acute Migraine Therapy in the Emergency Room. The Neurohospitalist, 2(2), 51-59.
9. Schoen, J. C., MD, Sadosty, A. T., MD, & Campbell, R. L., MD. (2015). Headache in Pregnancy: An Approach to Emergency Department Evaluation and Management. Western Journal of Emergency Medicine, XVI(2), 291-301.
10. Edlow, J. A., MD, Panagos, P. D., MD, Godwin, S. A., MD, Thomas, T. L., MD, & Decker, W. W., MD. (2008). Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Acute Headache. Annals of Emergency Medicine, 52(4), 407-436.
11. Edlow, J., MD, & Bounes, V., MD. (2010). Current Guidelines for the Management of Headache in the Emergency Department. EM Practice, 2(9), 1-10.
12. Suthisisang, Chuthamanee C., PHD, Nalinee Poolsup, PHD, Naeti Suksomboon, PHD, Vorachart Lertpipopmetha, BSC, and Bhakanit Tepwitukgid, BSC. “Meta-analysis of the Efficacy and Safety of Naproxen Sodium in the Acute Treatment of Migraine.” Meta-analysis of the Efficacy and Safety of Naproxen Sodium in the Acute Treatment of Migraine. N.p., n.d. Web. 09 May 2016. <http://www.medscape.com/viewarticle/722947>.