emDocs Cases: Headache Management in the ED

Author: Brit Long, MD (@long_brit, EM Attending Physician, San Antonio, TX) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

Welcome back to emDocs Cases! Today we have case-based discussion on a core EM topic, with a look at some controversy and cutting-edge treatments.

A 28-year-old female presents with right sided headache and one episode of vomiting, but no abdominal pain. The headache is not sudden in onset, but has rather worsened gradually over the last several hours. She denies fever, neck stiffness/pain, trauma, ingestion, vision changes/eye pain, and any other complaints. She has had several headaches in the past similar to the present headache. Her VS and exam are normal, including gait, cerebellar system, motor/sensory, reflexes, gait, and cranial nerves.

How are headaches classified?

Headaches affect over 50% of patients annually, with close to 4% of ED visits for headache.^1-3 Women are more commonly affected.^4-6 In the ED, physicians must first evaluate for potentially life-threatening causes of headache, as well as treat patient symptoms.

Primary headaches are not life-threatening, but they can cause significant morbidity. These headaches include tension, migraine, cluster, paroxysmal hemicranias, hemicrania continua, trigeminal neuralgia, and medication overuse.^6-12

Secondary headaches are dangerous and may result in death if not diagnosed and treated. These include intracranial hemorrhage, sentinel bleed, meningitis, encephalitis, abscess, tumor, carotid/vertebrobasilar dissection, reversible cerebral vasoconstriction syndrome (RCVS), cerebral venous thrombosis, temporal arteritis, idiopathic intracranial hypertension, hypertensive encephalopathy, posterior reversible encephalopathy syndrome (PRES), acute hydrocephalus (e.g., colloid cyst obstructing third ventricle), pituitary apoplexy, acute angle closure glaucoma, and carbon monoxide poisoning.^6-12

What evaluation is necessary in the ED?

The most important component of the ED evaluation is focused history and physical exam (including HEENT and neurologic systems). This evaluation comes down to looking closely for “red flags”.^6-8 Patients with a benign headache should have no major change in headache pattern, no red flag on history and exam, and no high-risk comorbidity.^6-8,10

What is a primary, or benign, headache?

Most headaches managed in the ED are benign, with 90% of these headaches classified as tension, migraine, or cluster. These differ in symptoms, but our job in the ED is to not diagnose the specific type of primary headache, but rather exclude a secondary dangerous headache.^3,4,7-13

Migraines have several criteria for diagnosis, shown in the table below. Several factors increase the likelihood of migraine headache, including nausea/vomiting, photophobia, and limitation in work/daily function due to headache (2 of 3 of these criteria possess sensitivity over 80%).^3-5,12,13

What treatments are available, and which medications are efficacious?

Emergency physicians have another major role in the care of these patients by treating symptoms. This is one area where we can truly help patients. Treatment of nausea, vomiting, and pain should be a primary goal in ED care, no matter the headache etiology.^6-12 Over twenty different types of medications are available, many with different routes (parenteral, intranasal, subcutaneous, and oral). Many of these medications are provided in the “headache cocktail”, which varies based on the physician, institution, patient preferences, and other factors. The best medication should provide fast, sustained pain relief, while having little to no side effects. Unfortunately, there is no perfect medication, and over one third of patients managed in the ED for headache experience sustained pain relief.^10,14 Medication complications include vascular problems, extrapyramidal effects, and gastrointestinal issues such as gastritis or hemorrhage.^14,15 The American Headache Society released updated recommendations in 2016 for headache treatment.⁹

As you can see, clinicians have a large number of options…What should you choose?

Many studies have evaluated medication efficacy for benign headaches. The rest of this post will look at some of the more common medications used for headache treatment in the ED.

1. Antidopaminergic agents – This is one of the best classes for symptom management, including headache pain and nausea relief.^6-13 This class consists of phenothiazines and butyrophenones. Drowsiness is the most common side effect, and abnormal movements such as dystonia and akathisia may occur as well (more common with faster infusion rates).^6,9,10

Chlorpromazine, prochlorperazine, and promethazine are phenothiazines. Chlorpromazine is provided in 0.1 mg/kg IV, with studies suggesting improved pain, photophobia, and phonophobia in migraines, with NNT of 2 for pain relief at one hour.^16-21 Prochlorperazine is more commonly used in the U.S., with dosing 10 mg IV providing pain relief in up to 90% of patients.^22-30  This medication has been compared to magnesium, valproic acid, sumatriptan, octreotide, and ketorolac, with literature suggesting superiority of prochlorperazine.^22-30 Promethazine can be used in doses of 25 mg IM or IV (IV administration can produce soft tissue injury if the medication extravasates).^5,31-33  Fewer studies have evaluated its use in the ED.

Butyrophenones include droperidol and haloperidol. Droperidol possesses strong literature support as an analgesic and antiemetic in headaches, with doses ranging from 0.1-8.25 mg IM providing effective pain relief. It may be provided IV as well.^6-13,34-36  However, it possesses an FDA Black Box warning for QTc prolongation. Haloperidol provides analgesia that is comparable or better to other previously discussed medications.^9-11,38-40  When compared to placebo, haloperidol provides pain relief in 80% of patients. ³⁹

One of the most common medications used in a “headache cocktail” is metoclopramide, an antidopaminergic and serotonin receptor antagonist, often administered 10 mg IV or IM.^{9-11,24,26,40-45}  This medication has significant literature support, with one meta-analysis suggesting a NNT of 4 for pain reduction.⁴³  Akathisia is a potential side effect, which can be reduced with slower rate of infusion.^9-11,40-44

2. Triptans – These medications are serotonin receptor agonists (5HT_1B/1D), primarily used in the outpatient setting.^{8-13,21,23,46-48} One of the more common agents is sumatriptan 2.5-6 mg given subcutaneously, with an NNT of 2.5 for pain relief when compared to placebo.^9-13,47  It can also be administered intranasally (10-20 mg) or PO (100 mg).^10,11,46-48  Unfortunately, there are many potential side effects such as chest pain, shortness of breath, flushing, and worsening headache, with number needed to harm (NNH) of 4.⁴⁷ This medication should not be used for patients with cardiovascular disease, uncontrolled hypertension, or pregnancy.^9-13,47  To reduce the risk of overuse headache, patients should not use a triptan more than 2 days per week. Close to two thirds of patients may experience recurrent headache.⁴⁷ Triptans also demonstrate efficacy in cluster headaches, with sumatriptan 6 mg subcutaneously demonstrating pain relief in 75% of patients at 20 minutes and intranasal sumatriptan also beneficial.^49-51  Zolmitriptan is given in doses of 5-10 mg.^51,52  A maximum of two doses in 24 hours is recommended.

3. NSAIDs – This class can be used for a variety of conditions, with evidence strongly supporting use in headaches. Ketorolac in doses 30 mg IV or 60 mg IM is one of the most commonly evaluated medications.^6-13,53-55 IV and IM routes show up to 80% pain relief at 2 hours, with similar pain relief when compared to metoclopramide or chlorpromazine. ^9-11,27,54 Naproxen 500-550 mg two times per day can reduce pain if used for patients with headache, but does not decrease headache recurrence.⁵⁵ If taken daily, gastric protection is recommended, and extended use may cause chronic daily headaches.^9-13,55

4. Acetaminophen – This medication is useful for headache therapy, with recent studies evaluating IV dosing.^8-13,56,57 Studies have suggested equivalency to dexketoprofen 50 mg, with no adverse events. The medication outperforms the triptan class at 60 minutes in terms of pain relief, though not at 30 or 120 minutes.^56,57 More research is needed, but this class is promising.

5. Steroids – Though early studies demonstrated analgesic benefits for acute treatment,^58,59 more recent randomized studies do not suggest efficacy for acute pain treatment.^60-64 However, steroids can reduce risk of headache recurrence in 24-72 hours, with NNT 9.^9-13,65 Another meta-analysis and systematic review suggest similar results.^66,67 This must be balanced with potential risks of steroids, especially with older patients and diabetics. The most common steroid utilized is dexamethasone, in doses of 8-16 mg. The most prevalent dose and route evaluated is dexamethasone 10 mg IV.^9-13

6. Antihistamines – Diphenhydramine and promethazine are two medications from this class. This is a common component of the ED “headache cocktail”, based on studies suggesting elevated serum histamine and IgE levels in migraine patients, and patients with migraine may have higher prevalence of allergic rhinitis.^68-72 Unfortunately, these agents do not possess strong literature support, with one study comparing metoclopramide versus metoclopramide + diphenhydramine suggesting no difference in pain, akathisia, or length of stay.⁶⁸ This medication class may cause sedation, but likely do not assist in analgesia.^9-13

7. Intravenous Fluids – Over 40% of ED headache patients are given IV fluids.^4,5,9-13 Patients may have fluid loss from vomiting and decreased oral intake. However, concerning pain relief, a study evaluating IV fluids with metoclopramide versus metoclopramide alone found no difference in acute pain relief.⁷³ If the patient appears dehydrated, IV fluids are helpful, but they otherwise likely do not assist in pain relief.

Going beyond the standard “headache cocktail”…

8. Oxygen – Supplemental oxygen is efficacious in cluster headaches and is recommended by headache guidelines.^74,75 If cluster headache is suspected on clinical evaluation, oxygen should be given, though other headaches do not demonstrate a similar response to oxygen.^6-13,74,75 In migraine or tension type headaches, oxygen is likely not helpful.

9. Valproic Acid – Though most commonly used for seizures, this medication has been used for headache management in doses of 300-1200 mg IV.^9-13,54,76 Randomized controlled trials (RCTs) demonstrate varied efficacy for symptom improvement when compared to ketorolac, metoclopramide, and prochlorperazine.^54,76-82 Contraindications include pregnancy, liver disease, and metabolic disorders such as urea cycle defects.

10. Propofol – Propofol demonstrates efficacy in analgesia for refractory headaches.^9-13,83-85 Studies have evaluated varying doses of propofol. One study found propofol in 30-40 mg IV boluses (with 10-20 mg boluses every 3-5 minutes) had better pain relief and decreased adverse events when compared with sumatriptan. ⁸⁵ Another study evaluated propofol 10 mg IV every 5-10 minutes up to 80 mg, finding this strategy was effective in analgesia.⁸⁶ Propofol is useful in refractory pain relief, though close monitoring for hypotension and respiratory depression is recommended.

11. Ketamine – Finally to the NMDA antagonist that is changing emergency medicine, first in procedural sedation and now analgesia.^6,9-13,86-90 Analgesic doses of 0.1-0.3 mg/kg IV as slow push have found ability to decrease pain, though one study suggests feelings of fatigue and insobriety were more common with ketamine.⁸⁹  Ketamine in 100 mL of NS with slower infusion over 15 minutes may reduce these feelings, versus faster infusion over 5 minutes.⁹¹

 12. Magnesium – Severe asthma/COPD, preeclampsia/eclampsia, atrial fibrillation…this medication possesses a variety of uses in the ED. For patients with headache, it can be given in doses of 1-2 g IV. However, RCT’s evaluating magnesium are not high quality, and the literature suggests magnesium does not consistently provide analgesia for severe headaches.^92-95

13. Nerve Block – This includes several different blocks with an anesthetic, including the occipital nerve block and sphenopalatine ganglion block. The occipital nerve block has been studied in open label trials and observational cohorts, and studies suggest the block is effective in over 65% of patients.^9-13,96

Another option is the sphenopalatine ganglion block, which reduces parasympathetic outflow and pain.^97-99  Academic Life in EM has a great post on this procedure with video. Several studies suggesting benefit against placebo, though the studies are not well designed. Another study comparing bupivacaine versus saline placebo found no difference in pain relief at 15 minutes,⁹⁹ though others suggest improved pain at 15 minutes, 30 minutes, and 24 hours.^98,100 

Intranasal lidocaine is helpful in patients with cluster headaches and should be used if this is suspected.^101-105

14. Opioids – You can’t really talk about analgesia without discussing opioids. These are used in over 50% of patients in the ED for headache.^9-13 However, we have a significant number of alternative agents. Plus, several societies recommend against opioids for headaches, as these medications may cause headache progression, increase frequency of revisit, and decrease efficacy of other headache treatments. ^9-11,106-114 Opioids can also increase depression, anxiety and disability.¹¹⁶ If patients ask specifically for opioids, counseling on the risks of this treatment is recommended.

So when it comes down to it, what medications should you provide?

As discussed, you have many choices. Antidopaminergics in combination with an NSAID, acetaminophen, and dexamethasone will reduce pain and nausea. If ketorolac is chosen, recent literature suggests reduced dosing (10 or 15 mg) is as efficacious as 30 mg, with reduced risk of side effects.¹²³  Triptans can be used, but only if there are no contraindications. If no response to first line agents, then nerve block, ketamine, or propofol can be used. Nerve block is useful for rapid pain relief.

Case Conclusion:

The patient feels improved with metoclopramide 10 mg IV, ketorolac 15 mg IV, acetaminophen 975 mg PO, and dexamethasone 10 mg IV. She desires discharge and will follow up with her primary care physician.

Key Points:

– Headache is divided into benign, primary causes and dangerous, secondary etiologies. Focused history and examination are recommended.

– Benign headaches include migraine, tension, cluster, and several others, but a specific diagnosis is not required in the ED.

– Management should also focus on symptom treatment for pain and nausea.

– A combination of medications is advised.

– Antidopaminergics have the strongest literature support. These should be used with NSAIDs and/or acetaminophen.

– Steroids likely decrease headache recurrence.

– Other treatments include ketamine, propofol, and nerve blocks. These are options for refractory headaches to other treatments.

References/Further Reading:

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