Community EM

Extra dry or up with a twist? A take on the ‘migraine cocktail’

You’re seeing a patient in the community emergency department with a primary headache disorder. Based on your history & physical examination skills, you have considered and ruled out all dangerous secondary headache causes such as intracranial hemorrhage, sentinel bleed, meningoencephalitis, abscess, tumor, temporal arteritis, hypertensive encephalopathy, acute angle closure glaucoma, etc. With many classes of treatments available, providers have typically used some form of a ‘migraine cocktail’ including IV prochlorperazine, IV ketorolac, IV diphenhydramine, IV dexamethasone, and/or IV normal saline.[1]

There are several considerations with the above typical ‘headache cocktail’ that I would like to discuss. Ideally, the treatment regimen implemented in the ED will be efficacious in providing modest headache relief, while also being safe (few side effects) and fast. Depending on other considerations for the department at that time, the nurse may be limited with time and unable to obtain IV access and initiate the typical multimodal intravenous components of the ‘migraine cocktail’. Furthermore, most headache patients will not need labs drawn. While not advocating for a one-size fits all approach, my goal is to discuss the evidence on the utility of commonly used therapeutics as well as providing you with additional time-efficient modalities to add to your armamentarium in effectively treating patients with primary headache disorder.

Antidopaminergics:

Any of the typical medications, whatever available readily, will work, including: metoclopramide 10 mg IM, prochlorperazine 10 mg IM, or promethazine 25 mg IM. The onset of action of all three medications via the IM route is between 10-20 minutes.[2-4]

Diphenhydramine:

Routine co-administration with metoclopramide has not been shown to improve migraine outcomes or prevent metoclopramide-induced akathasia.[5,6] Additionally, the sedative side effects will potentially keep the patient in the ED for a lengthier time frame.

IV Fluids:

In a post hoc analysis of 4 ED-based migraine clinical trials utilizing IV metoclopramide as well as IV fluids at the discretion of the treating physician, the patients receiving IV fluids had a lower improvement in pain scale after one hour and their use was not associated with sustained headache freedom.[7] Universal addition of this modality to patients with primary headache disorder similarly will likely add to a lengthier ED visit as the fluids trickle in.

NSAIDs:

Typical treatment is with ketorolac 60 mg IM, and has been proven to be effective for migraine treatment in comparison to many antidopaminergics.[8] It may also be fruitful to maximize the patient’s appropriate use of acetaminophen and ibuprofen/naproxen upon discharge.

Steroids:

Dexamethasone 10-25 mg IM can be administered to help prevent headache recurrence.[9]

Sumatriptan:

Frequently forgotten are triptains and anecdotally do not seem to be the go-to for many ED providers, but 6 mg subcutaneous has shown benefit in treating patient with primary headache disorder.[10]

For patients with primary headache disorder, it is vitally important to do several things:

  • Rule out dangerous secondary causes, as above, first and foremost

  • Set expectations with the patient, that their headache may not be completely resolved, but we hope to be aggressive up front

  • Delineate return precautions to the ED and close Neurology followup or referral

Faculty Reviewer: Dr. Kristina McAteer

References:

  1. Long B, Koyfman A. Headache management in the ED. emDocs Cases. http://www.emdocs.net/emdocs-cases-headache-management-ed/. Accessed June 2019.

  2. Promethazine: drug information. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/promethazine-drug-information?search=promethazine&source=panel_search_result&selectedTitle=1~79&usage_type=panel&kp_tab=drug_general&display_rank=1#F214058. Accessed June 2019.

  3. Metoclopramide: drug information. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/metoclopramide-drug-information?search=metoclopramide&source=panel_search_result&selectedTitle=1~149&usage_type=panel&kp_tab=drug_general&display_rank=1. Accessed June 2019.

  4. Prochlorperazine: drug information. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/prochlorperazine-drug-information?search=prochlorperazine&source=panel_search_result&selectedTitle=1~72&usage_type=panel&kp_tab=drug_general&display_rank=1. Accessed June 2019.

  5. Friedman BW, Cabral L, Adewunmi V, et al. Diphenhydramine as adjuvant therapy for acute migraine: an emergency department-based randomized clinical trial. Ann Emerg Med. 2016 Jan:67(1):32-39.

  6. Erdur B, Tura P, Aydin B, et al. A trial of midazolam vs diphenhydramine in prophylaxis of metoclopramide-induced akathisia. Am J Emerg Med. 2012 Jan;30(1):84-91.

  7. Balbin JE, Nerenberg R, Baratloo A, et al. Intravenous fluids for migraine: a post hoc analysis of clinical trial data. Am J Emerg Med. 2016 Apr;34(4):713-6.

  8. Taggart E, Doran S, Kokotillo A, et al. Ketorolac in the treatment of acute migraine: a systematic review. Headache 2013;53:277.'

  9. Does the addition of dexamethasone to standard therapy for acute migraine headache decrease the incidence of recurrent headache for patients treated in the emergency department? A meta-analysis and systematic review of the literature. Acad Emerg Med. 2008 Dec;15(12):1223-33.

  10. Sumatriptan (subcutaneous route of administration) for acute migraine attacks in adults. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD009665.

Brown EM Whit-ticisms: Epinephrine Auto-Injectors

You are in the middle of woods when your hiking partner is stung by a bee. Anaphylaxis! You whip out and use an epinephrine auto-injector. Your companion has some relief, but quickly becomes more short of breath. You only had that one dose of epinephrine. Or do you? Watch our latest Whit-ticism video by faculty member Dr. Whit Fisher to learn how to make the most out of an epinephrine auto-injector.

Feeling Faint: Reflex Syncope

Case

The patient is 70-year-old female presenting with an episode of loss of consciousness at home. While eating dinner with her husband, the patient stated, “I don’t feel well,” and subsequently lost consciousness for 15 seconds. Per her husband, she spontaneously returned to baseline and vomited once. The patient denied any preceding symptoms including chest pain, shortness of breath, dizziness, nausea. There was no seizure-like activity. She stated that this has occurred 5-6 times previously, but she has had unremarkable Holter monitoring.

She has stable vital signs with a normal physical exam. Her symptoms are not reproducible upon sitting or standing. Laboratory testing, including CBC, BMP, troponin, D-Dimer, and urinalysis, are all within normal limits.  A routine EKG demonstrates normal sinus rhythm with mild PR prolongation and no acute ST changes.

While discussing disposition, the patient states she feels unwell and develops sinus bradycardia on telemetry. Without complete loss of consciousness, she returns to her baseline after 20 seconds. Repeat EKG demonstrates rebound sinus tachycardia without any ischemic or interval changes. She is admitted to cardiology for further monitoring.

While admitted, the patient has an uneventful hospital course. Her echocardiogram demonstrates an ejection fraction of 70% with no underlying structural heart defects. Serial troponins and EKG trending is unremarkable. She tolerates a trial of metoprolol 25mg BID and is discharged home with instructions to follow up for tilt testing.

Diagnosis: Reflex Syncope

Syncope: A transient loss of consciousness with spontaneous return to baseline

Reflex syncope, or neurally-mediated syncope, is thought to present in three ways:

  1. Vasodepressive- primary loss of sympathetic function, presenting as hypotension (1)

  2. Cardioinhibitory- increased parasympathetic function, presenting as bradycardia or asystole (1)

  3. Mixed type- The majority of reflex syncope is mixed (1)

Reflex syncope is thought to result from a trigger causing orthostasis, decreased venous return, thereby decreased cardiac output, and a transient lack of cerebral perfusion inducing transient loss of consciousness. (2)

Syncope can be vasovagal, during high emotional states, or situational, such as post-micturition, while eating, coughing, sneezing, and post-exercise. Carotid sinus syncope and atypical forms, without trigger or prodromes, can also be forms of reflex syncope.(3) It is important to distinguish reflex syncope from other causes of syncope, such as arrhythmogenic or ischemic, orthostatic syncope, and non-syncopal mimics such as stroke, seizure, hemorrhage, etc.(3) Patient history can help guide this differentiation.

 

Demographics

Approximately 40% population have had one or more episodes of syncope. Reflex syncope is the most common type of syncope in any age group; it has been suggested that it may follow a bimodal age distribution.(1) Atypical reflex syncope, without trigger or cause, is more common amongst older patients. However, the rate of cardiac syncope also rises with age and elderly patients are more likely to have concomitant cardiovascular disease or orthostasis induced by medication.(4)

Prognosis

Reflex syncope is generally considered benign and portends a low risk of mortality. However, frequent episodes, particularly in the elderly may predispose to trauma and injury. These patients may benefit from treatment. Researchers have concluded that the number of events in the preceding year is a better predictor of recurrent syncope rather than the total number of lifetime events.(5)

Treatment

The mainstay of treatment is the of avoidance of triggers. Other non-pharmacologic therapies may also help, such as volume support, from increased fluid intake or a high-salt diet, compression shorts or stockings to support venous return, counter-pressure maneuvers, and tilt training.(4) Counter pressure maneuvers are exercises such as muscle tensing, grip squeezing, leg crossing, squatting, bending forward. Patients can try these maneuvers when they feel a prodrome. Ideally this delays symptoms until patients can lay supine, improving venous return and delaying or preventing syncope.(6) The PC trial investigated this in 2006 and showed a lower recurrence of syncope 31.6% compared to 50.9% at 14 months using counter pressure.(7) However, the ISSUE 3 trial demonstrated no difference in syncope prevention between groups.(6) Given the low cost and low risk associated with these maneuvers with the potential for benefit, patients can try these.

A tilt test can be used to reproduce symptoms in patients whom the cause of syncope is less clear. Patients follow a protocol which is dependent upon steep tilting, with additional provocative medications such as isoproterenol or nitroglycerin as needed. Results are interpreted by patient response, vital sign measurements, and timing of symptoms. While there a high sensitivity is reported, it is at the cost of lowered specificity and many false positives. Additionally, patient assignment is important because factors such as home medications and structural heart disease may impact findings. If positive, it may help guide treatment.(8)

Similarly, it has been suggested that patients can perform tilt training as treatment. First discussed in 1998, tilt training consists of in-hospital sessions of suspended tilting, followed by at home training of standing against a wall for several minutes several times per day. While a meta-analysis has suggested benefit to tilt training, this was not sustained when evaluating only randomized studies. Patient noncompliance can also negatively impact outcomes, and lessen efficacy.(6)

Several medications have been proposed to lessen reflex syncope recurrence including: beta blocker, alpha adrenergic, SSRI, fludrocortisone, and theophylline. Many of these have small data sets of evidence or fail to succeed over placebo and are not routinely recommended.(6)

Since our patient was started on metoprolol, we will examine this more specifically. Physiologically, beta blockers are theorized to reduce overall sympathetic response and prevent vagal “overshooting”.(1) While observational data showed promise, many randomized trials have thus far failed to show benefit in decreasing syncope recurrence over placebo.(4)

The data to support beta blockade is largely driven by the POST trial. While initial study results demonstrated no benefit, a subset analysis of adults >42 years old demonstrated improvement with beta blockers in older patients.(9) Two smaller studies by Natale and Leor also showed an age-related distribution of benefit.(9) A randomized prospective trial, POST 5, is currently underway to further examine this conclusion. Results are expected December 2020.(10) As of the 2018 European Society of Cardiology guidelines, beta blockers are not currently routinely supported.(3) Given upcoming trial results these recommendations may change in the future.

Take Away Summary

  • Reflex syncope, or neurally-mediated syncope can be cardioinhibitory, vasodepressive, or mixed

  • Nonpharmacologic interventions such as counter pressure or tilt training may be beneficial for some patients

  • Pharmacologic interventions are broad; beta blockade has shown some initial promise in a subset of older patients, but is not yet routinely recommended across the board

  • Reflex syncope is in general benign, but patients at high risk of trauma or injury may benefit from further care. Young, healthy patients can be given reassurance of a good prognosis. 

Faculty Reviewer: Dr. Kristina McAteer

References

  1. Aydin, M. A., Salukhe, T. V., Wilke, I., & Willems, S. (2010, October 26). Management and therapy of vasovagal syncope: A review. Retrieved May 21, 2019, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2998831/

  2. Brignole, M., MD. (2016, July 5). Finally, A Drug That Proves to Be Effective Against Vasovagal Syncope! But Not in All Patients. Retrieved May 19, 2019, from http://www.onlinejacc.org/content/accj/68/1/10.full.pdf

  3. Brignole, M., Moya, A., De Lange, F. J., Deharo, J. C., Elliot, P. M., Fanciulli, A., . . . Van Dijk, J. (2018, March 19). 2018 ESC Guidelines for the diagnosis and management of syncope. Retrieved May 21, 2019, from https://academic.oup.com/eurheartj/article/39/21/1883/4939241#13420039

  4. Benditt, D. (n.d.). Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation. Retrieved May 21, 2019, from https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation?search=vasodepressor syncope&source=search_result&selectedTitle=1~84&usage_type=default&display_rank=1

  5. Sumner, G. L., Rose, M. S., Koshman, M. L., Ritchie, D., Sheldon, R. S., & Prevention, I. N. (2010, December). Recent history of vasovagal syncope in a young, referral-based population is a stronger predictor of recurrent syncope than lifetime syncope burden. Retrieved May 21, 2019, from https://www.ncbi.nlm.nih.gov/pubmed?term=20662990

  6. Ravielle, A. (2017, August 09). Update on treatment strategies for vasovagal syncope. Retrieved May 21, 2019, from https://cardiacrhythmnews.com/update-treatment-strategies-vasovagal-syncope/

  7. Van Dijk, N., Quartieri, F., Blanc, J., Garcia-Civera, R., Brignole, M., Moya, A., & Wieling, W. (2006, October 17). Effectiveness of physical counterpressure maneuvers in preventing vasovagal syncope: The Physical Counterpressure Manoeuvres Trial (PC-Trial). Retrieved May 21, 2019, from https://www.ncbi.nlm.nih.gov/pubmed/17045903

  8. Benditt, D. (n.d.). Upright tilt table testing in the evaluation of syncope. Retrieved May 21, 2019, from https://www.uptodate.com/contents/upright-tilt-table-testing-in-the-evaluation-of-syncope?search=vasodepressor syncope&source=search_result&selectedTitle=4~84&usage_type=default&display_rank=4#H11

  9. Sheldon, R., Morillo, C., Klingenheben, T., Krahn, A., Sheldon, A., & Rose, M. (2012, October 1). Age-Dependent Effect of β-Blockers in Preventing Vasovagal Syncope. Retrieved May 21, 2019, from https://www.ahajournals.org/doi/10.1161/CIRCEP.112.974386

  10.  Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects - Full Text View. (n.d.). Retrieved May 21, 2019, from https://clinicaltrials.gov/ct2/show/NCT02123056