The Intractable Migraneous Headache

Migraine headaches results from dysfunction of brainstem pathways that normally modulate sensory input, with disordered activity of blood vessels. This leads to neurogenic inflammation in pain-sensitive arteries, the dura, and meningeal tissues, and promotes local vasodilatation. Medications such as sumatriptan and ergot derivatives cause vasoconstriction and relieve the symptoms. These triggers stimulate trigeminovascular axons causing pain and the release of vasoactive neuropeptides from perivascular axons. 

Clinical Presentation

• Headache that lasts from 4 to 72 hours
• Aggravation by routine physical activity
• Classically unilateral and pulsating (May not be unilateral)
• a/w Nausea, vomiting, and photophobia or photophobia 
• May have Scalp Tenderness 
• Aura (most common are visual auras with flashes of lights)

Key Q - Is your headache similar to your usual migraine headaches? If the news is no, then a different cause should be suspected. 

Treatment Options for Migraine

• Acetaminophen - Patients with diagnosed migraine often try paracetamol before arriving to the EDs. There is no harm in adding Paracetamol to routine migraine therapy.
• Fluids - Dehydration is a known trigger of migraine. Persistent nausea and vomiting further exacerbates the migraine. Adequate hydration might improve patient malaise and help those who are dehydrated.
• Anti-emetics - Parenteral metoclopramide, chlorpromazine, and prochlorperazine (Stemetil) all have demonstrated efficacy in randomized trials as monotherapy for acute migraine. Antiemetic medications are efficacious and are recommended for acute migraine in the ED. To reduce the risk of akathisia, diphenhydramine should be included. (Diphenhydramine does not prevent Metoclopramide induced dystonia)
• Oxygen - "High-flow" oxygen has been studied in migraine headaches. When compared with placebo, oxygen used for 15 min was more effective in pain relief with no significant adverse events.
• Steroids - Steroids prevent the lingering of attacks and recurrence as well. Everyone with a migraine attack should receive dexamethasone 10mg IV/IM or a 3 day course of presdqisolone unless there is an obvious contraindication. 
• NSAIDs - NSAIDs are effective in treating acute migraine. Ketorolac is a potent pain killer which often works for migraine.

• Triptans - Evidence suggests that SC delivery is fastest and most effective route. Common side effects include injection site reactions, dizziness, and paresthesias. Triptans are contraindicated in cardiovascular disease, pregnancy, basilar migraines, Prinzmetal angina, and ischemic stroke, and with the use of ergotamines within the previous 24 hours. Studies have also suggested that triptan therapy is less effective in patients with prolonged and severe migraine. Triptans are best reserved for patients who present within 1-2 hours of headache. Given the side effect profile, lack of efficacy in severe migraine, and relative contraindications, triptan use in the ED is of limited value. 
• Butyrophenones - (haloperidol and droperidol). RCTs have demonstrated efficacy of haloperidol and droperidol mono therapy. However, these drugs have been associated with frequent side effects (somnolence, akathisia, anxiety) and also prolong QTc interval. These are generally reserved for rescue therapy in refractory migraine. 
• Ergot Alkaloids - Dihydroergotamine (DHE), a 5-HT_1B/1D serotonin receptor agonist which highly effective in relieving headaches. However, DHE causes vomiting in a significant proportion of patients. Patients therefore should be pretreated with an antiemetic such as metoclopramide or prochlorperazine.
• Opioids - Use opioids only as the last sort for refractory headache. When compared with NSAIDs, DHE, and antiemetic medications, opioids are less effective for migraine. The frequent use of opioids in chronic and recurrent headache conditions may lead to adverse effects and may even exacerbate headaches.
• Propofol - Evidence for using propofol is not robust but it is again something to consider when everything else fails. Follow the procedural sedation protocol and doe as 10-20 mg IVP every 3-4 minutes up to 1 mg/kg. Our aim is mild sedation, not apnea.
• Magnesium - Magnesium is ideally used for refractory migraine, migraine patients with true aura, those with hypoMg. Administer 2 g IV Mg over 20min. Evidence for the use of Migraine is still conflicting though. 

• Sphenopalatine Ganglion Block

Bottomline: It is reasonable to start with fluids/O2, Metoclopramide. Do not forget to add steroids. Add Acetaminophen/NSAIDs if symptoms persist. Other  potential options (Ergot Alkaloids/Mg/Propofol, Ganglion Blocks) are all based on your comfort and local protocols. Opioids are your last option. 

References:

• Singhal AB, Maas MB, Goldstein JN, et al. High-flow oxygen therapy for treatment of acute migraine: A randomized crossover trial. Cephalalgia. 2016 May 20.
• Balbin JE, Nerenberg R, Baratloo A, Friedman BW. Intravenous fluids for migraine: a post hoc analysis of clinical trial data. Am J Emerg Med. 2016 Apr;34(4):713-6.
• Bigal ME, Bordini CA, Tepper SJ, Speciali JG. Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study. Cephalalgia. 2002 Jun;22(5):345-53.
• Colman I, Friedman BW, Brown MD, Innes GD, Grafstein E, Roberts TE, Rowe BH. Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence. BMJ. 2008 Jun 14;336(7657):1359-61.
• Colman I, Rothney A, Wright SC, Zilkalns B, Rowe BH. Use of narcotic analgesics in the emergency department treatment of migraine headache. Neurology. 2004 May 25;62(10):1695-700.
• Friedman BW, Bender B, Davitt M, Solorzano C, Paternoster J, Esses D, Bijur P, Gallagher EJ. A randomized trial of diphenhydramine as prophylaxis against metoclopramide-induced akathisia in nauseated emergency department patients. Ann Emerg Med. 2009 Mar;53(3):379-85.
• Friedman BW, Greenwald P, Bania TC, Esses D, Hochberg M, Solorzano C, Corbo J, Chu J, Chew E, Cheung P, Fearon S, Paternoster J, Baccellieri A, Clark S, Bijur PE, Lipton RB, Gallagher EJ. Randomized trial of IV dexamethasone for acute migraine in the emergency department. Neurology. 2007 Nov
• Regan LA, Hoffman RS, Nelson LS. Slower infusion of metoclopramide decreases the rate of akathisia. Am J Emerg Med. 2009 May;27(4):475-80.
• Soleimanpour H, Taheraghdam A, Ghafouri RR, Taghizadieh A, Marjany K, Soleimanpour M. Improvement of refractory migraine headache by propofol: case series. Int J Emerg Med. 2012 May 15;5(1):19.
• Taggart E, Doran S, Kokotillo A, Campbell S, Villa-Roel C, Rowe BH. Ketorolac in the treatment of acute migraine: a systematic review. Headache. 2013 Feb;53(2):277-87.