Managing migraine headaches in complicated patients

2017-03-11T00:22:59+00:00

migraineCase vignette: A 42-year-old female presents at 10 pm with a throbbing right frontal headache associated with nausea, vomiting, photophobia, and phonophobia. The headache is severe, rated as “10” on a 0 to 10 triage pain scale. The headache began gradually while the patient was at work at 2 pm. Since 2 pm, she has taken 2 tablets of naproxen 500 mg and 2 tablets of sumatriptan 100 mg without relief.

The patient has a diagnosis of migraine without aura. She reports 12 attacks per month. The headache is similar to her previous migraine headaches. She is forced to present to an Emergency Department (ED) on average 2 times per month for management of migraine refractory to oral therapy. She reports a history of dystonic reactions and akathisia after receiving IV dopamine antagonists during a previous ED visit. The physical exam is non-contributory including a normal neurological exam, normal visual fields and fundoscopic exam, and no signs of a head or face infection. When you are done evaluating her, the patient reports that she usually gets relief with 3 doses of hydromorphone 2 mg + diphenhydramine 50 mg IM, and asks that you administer her usual treatment. What do you do?

Background

Migraine is a neurological disorder characterized by recurrent painful headaches and abnormal processing of sensory input resulting in symptoms such as photophobia, phonophobia, and osmophobia.1 Central to disease pathogenesis is abnormal activation of nociceptive pathways.2 Disease severity ranges from mild to severe. Patients at one end of the spectrum have rare episodic headaches. On the other end are patients who have headaches on more days than not, patients who are functionally impaired by their headaches, and patients who frequently cannot participate fully in work or social activities. Chronic migraine, a sub-type of migraine defined by ≥15 days with headache for at least 3 consecutive months, is experienced by 1-3% of the general population.3

ED use for treatment of migraine is common. 1.2 million patients present to U.S. ED’s annually for management of this primary headache disorder.4 Parenteral opioids are used to treat the acute headache in slightly more than 50% of all ED visits.4 Multiple authorities have cautioned against the use of opioids for migraine.5,6 However, the frequent use of opioids has continued unabated, despite the publication in the EM, neurology, and headache literature of dozens of randomized controlled trials (RCTs) demonstrating safety and efficacy of parenteral alternatives, most notably dopamine antagonists and non-steroidal anti-inflammatory drugs.7

Opioids have been associated with a variety of poor outcomes in migraine patients including:

  1. Progression of the underlying migraine disorder from episodic to chronic migraine8
  2. Increased frequency of return visits to ED9
  3. Less responsiveness to subsequent treatment with triptans10
  4. Less frequent headache relief than patients who received dihydroergotamine or dopamine antagonists11

In contrast, a high quality, ED-based RCT did not demonstrate more harm from 1 or 2 doses of meperidine than from dihydroergotamine.12 Hydromorphone, the parenteral opioid currently used most commonly in U.S. EDs,4 has never been studied experimentally in migraine patients. However, given the wide range of parenteral alternatives, the possibility that opioids may worsen the underlying migraine disorder, and the fact that they are less efficacious than other treatments, opioids should not be offered as first- or second-line therapy for patients who present de novo to an ED with an acute migraine (assuming no contraindications to alternative medications).

Questions:

1) Other than opioids, what parenteral therapies can be offered to this patient?

The 3 classes of parenteral therapeutics with the most evidence supporting safety and efficacy for use as first-line therapy for migraine are the following13:

  1. Dopamine antagonists
  2. NSAIDs
  3. Subcutaneous sumatriptan

However, this patient has relative contraindications to each of these. Other parenteral medications used for migraine are listed in the following table.

Table: Alternative parenteral migraine therapies

Agent Dose Adverse events Evidence supporting efficacy Notes
Acetaminophen (APAP)14,15 1 gm IV Well tolerated In one trial, IV APAP did no better than placebo. In another, IV APAP was comparable to an IV NSAID.
Dihydroergotamine16 0.5 mg -1 mg IV infusion Nausea is common. Pre-treat with anti-emetics. In one trial, DHE was less effective than sumatriptan at 2 hours but more effective by 4 and 24 hours. Use cautiously in patients with cardiovascular risk factors.
Ketamine17 0.08 mg/kg SC Fatigue, delirium In one low quality cross-over RCT, ketamine outperformed placebo.
Magnesium18–21 1-2 gm IV Flushing In RCTs of varying quality, IV mg did not consistently outperform placebo Efficacy data is most compelling for migraine with aura.
Octreotide22 0.1 mg SC Diarrhea, injection site reactions In a high quality RCT, octreotide did not outperform placebo
Propofol23,24 10 mg IV every 10 minutes as needed up to 80 mg Or 30-40 mg IV with 10-20 mg bolus every 3-5 minutes up to 120 mg Sedation, hypoxia In a low quality RCT, propofol outperformed dexamethasone. In another low quality trial, propofol outperformed sumatriptan. It is not clear whether the migraine returns after propofol administration has been completed. Previous ALiEM post on migraines and propofol.
Valproic acid28,29 1000 mg IV Well tolerated In a high quality RCT, valproate was outperformed by metoclopramide and ketorolac. In a lower quality RCT, valproate was comparable to IV aspirin.
APAP= acetaminophen; DHE= dihydroergotamine; Mg= magnesium

 

In some patients, greater occipital nerve blocks with a long-acting local anesthetic such as bupivaciane may play a role.25 While the above alternative parenteral therapies may benefit this patient, available evidence regarding risks and benefits does not dictate that these other therapies must be offered prior to use of opioids.

2) Does the fact that this patient makes frequent use of the ED indicate an unmet medical need?

As with congestive heart failure and asthma, frequent use of an ED for migraine is associated with worse underlying disease.26 These frequent users are more likely to have chronic migraines (> 15 headache days per month) and psychiatric co-morbidities.26 Concomitant medication overuse headache, a disorder defined by an upward spiral of increasing headache frequency in the setting of increased usage of analgesic or migraine medication, is also common.27 Management of complicated patients with migraines is exceedingly difficult, particularly during a busy ED shift, and may lead to frustration for both the healthcare practitioner and the patient. Ideally, outpatient healthcare practitioners with appropriate expertise should direct management of complicated patients with migraines.

3) Should the patient be administered 3 doses of hydromorphone 2 mg + diphenhydramine 50 mg IM as she wishes?

Management of chronic pain patients can be trying and demoralizing for emergency physicians because the underlying problem cannot be solved, and all avenues of treatment are flawed.  Allowing the patient to suffer without appropriate justification is cruel. Delaying opioid administration during good faith efforts to identify alternative effective therapeutic agents is reasonable. Withholding opioids on principle is problematic because for most patients in most circumstances, published data do not establish that the benefit of pain relief is outweighed by the potential for opioid induced harm. On the other hand, thoughtlessly acquiescing to repeated requests for opioids during multiple ED visits is a violation of good medical practice, because of the concern of exacerbating the underlying migraine disorder, which could result in more ED visits, increased number of headache days, and the potential to cause refractoriness to standard migraine medication. One might compare it to administering antibiotics for bronchitis.

Case Resolution

The best solution for the patient in the case vignette is to administer parenteral opioids only as rescue therapy for patients who adhere to an established outpatient plan of care. Acutely, the patient should not be allowed to suffer. However distasteful it may be, the harm arising from 3 isolated doses of parenteral opioids during one ED visit is unlikely to be either long-lasting or severe. But a prerequisite to treatment with opioids during a subsequent visit should be adherence to appropriate outpatient treatment: specifically, patients who require parenteral opioids for migraines should regularly attend outpatient appointments with an appropriate healthcare provider within the ED’s healthcare system.

Department-wide opioid policies are essential, as physician to physician variability in care may undermine a strict approach to opioids. Ideally, a committee with relevant expertise can monitor frequently presenting pain patients and develop patient-specific interventions that will be enforced by all practitioners during subsequent visits. If need be, the terms of treatment can be reinforced with a written document (example in the Appendix). This written document is not meant to be legally binding, but should be used to establish expectations. The last thing a busy emergency physician needs is a battle over opioids with a frequently presenting migraine patient. But before discharge, there should be a conversation about expectations during future ED visits. This will contribute to increased satisfaction for both the provider and the patient.

 

Top image: (c) Can Stock Photo

 

APPENDIX: Sample document to establish expectations for ED patients who require opioids
1.
Headache C. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629-808. [PubMed]
2.
Goadsby P. Pathophysiology of migraine. Ann Indian Acad Neurol. 2012;15(Suppl 1):S15-22. [PubMed]
3.
Lipton R. Chronic migraine, classification, differential diagnosis, and epidemiology. Headache. 2011;51 Suppl 2:77-83. [PubMed]
4.
Friedman B, West J, Vinson D, Minen M, Restivo A, Gallagher E. Current management of migraine in US emergency departments: an analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. [PubMed]
5.
Langer-Gould A, Anderson W, Armstrong M, et al. The American Academy of Neurology’s top five choosing wisely recommendations. Neurology. 2013;81(11):1004-1011. [PubMed]
6.
Loder E, Weizenbaum E, Frishberg B, Silberstein S, American H. Choosing wisely in headache medicine: the American Headache Society’s list of five things physicians and patients should question. Headache. 2013;53(10):1651-1659. [PubMed]
7.
Sumamo S, Dryden D, Pasichnyk D, et al. Acute Migraine Treatment in Emergency Settings. November 2012. http://www.ncbi.nlm.nih.gov/books/NBK115368/. [PubMed]
8.
Bigal M, Serrano D, Buse D, Scher A, Stewart W, Lipton R. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache. 2008;48(8):1157-1168. [PubMed]
9.
Colman I, Rothney A, Wright S, Zilkalns B, Rowe B. Use of narcotic analgesics in the emergency department treatment of migraine headache. Neurology. 2004;62(10):1695-1700. [PubMed]
10.
Burstein R, Collins B, Jakubowski M. Defeating migraine pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol. 2004;55(1):19-26. [PubMed]
11.
Friedman B, Kapoor A, Friedman M, Hochberg M, Rowe B. The relative efficacy of meperidine for the treatment of acute migraine: a meta-analysis of randomized controlled trials. Ann Emerg Med. 2008;52(6):705-713. [PubMed]
12.
Carleton S, Shesser R, Pietrzak M, et al. Double-blind, multicenter trial to compare the efficacy of intramuscular dihydroergotamine plus hydroxyzine versus intramuscular meperidine plus hydroxyzine for the emergency department treatment of acute migraine headache. Ann Emerg Med. 1998;32(2):129-138. [PubMed]
13.
Orr S, Aubé M, Becker W, et al. Canadian Headache Society systematic review and recommendations on the treatment of migraine pain in emergency settings. Cephalalgia. 2015;35(3):271-284. [PubMed]
14.
Turkcuer I, Serinken M, Eken C, et al. Intravenous paracetamol versus dexketoprofen in acute migraine attack in the emergency department: a randomised clinical trial. Emerg Med J. 2014;31(3):182-185. [PubMed]
15.
Leinisch E, Evers S, Kaempfe N, et al. Evaluation of the efficacy of intravenous acetaminophen in the treatment of acute migraine attacks: a double-blind, placebo-controlled parallel group multicenter study. Pain. 2005;117(3):396-400. [PubMed]
16.
Winner P, Ricalde O, Le F, Saper J, Margul B. A double-blind study of subcutaneous dihydroergotamine vs subcutaneous sumatriptan in the treatment of acute migraine. Arch Neurol. 1996;53(2):180-184. [PubMed]
17.
Nicolodi M, Sicuteri F. Exploration of NMDA receptors in migraine: therapeutic and theoretic implications. Int J Clin Pharmacol Res. 1995;15(5-6):181-189. [PubMed]
18.
Corbo J, Esses D, Bijur P, Iannaccone R, Gallagher E. Randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache. Ann Emerg Med. 2001;38(6):621-627. [PubMed]
19.
Shahrami A, Assarzadegan F, Hatamabadi H, Asgarzadeh M, Sarehbandi B, Asgarzadeh S. Comparison of therapeutic effects of magnesium sulfate vs. dexamethasone/metoclopramide on alleviating acute migraine headache. J Emerg Med. 2015;48(1):69-76. [PubMed]
20.
Cete Y, Dora B, Ertan C, Ozdemir C, Oktay C. A randomized prospective placebo-controlled study of intravenous magnesium sulphate vs. metoclopramide in the management of acute migraine attacks in the Emergency Department. Cephalalgia. 2005;25(3):199-204. [PubMed]
21.
Bigal M, Bordini C, Tepper S, Speciali J. Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study. Cephalalgia. 2002;22(5):345-353. [PubMed]
22.
Levy M, Matharu M, Bhola R, Meeran K, Goadsby P. Octreotide is not effective in the acute treatment of migraine. Cephalalgia. 2005;25(1):48-55. [PubMed]
23.
Soleimanpour H, Taheraghdam A, Ghafouri R, Taghizadieh A, Marjany K, Soleimanpour M. Improvement of refractory migraine headache by propofol: case series. Int J Emerg Med. 2012;5(1):19. [PubMed]
24.
Moshtaghion H, Heiranizadeh N, Rahimdel A, Esmaeili A, Hashemian H, Hekmatimoghaddam S. The Efficacy of Propofol vs. Subcutaneous Sumatriptan for Treatment of Acute Migraine Headaches in the Emergency Department: A Double-Blinded Clinical Trial. Pain Pract. 2015;15(8):701-705. [PubMed]
25.
Voigt C, Murphy M. Occipital nerve blocks in the treatment of headaches: safety and efficacy. J Emerg Med. 2015;48(1):115-129. [PubMed]
26.
Friedman B, Serrano D, Reed M, Diamond M, Lipton R. Use of the emergency department for severe headache. A population-based study. Headache. 2009;49(1):21-30. [PubMed]
27.
Kristoffersen E, Lundqvist C. Medication-overuse headache: epidemiology, diagnosis and treatment. Ther Adv Drug Saf. 2014;5(2):87-99. [PubMed]
28.
Leniger T, Pageler L, Stude P, Diener H, Limmroth V. Comparison of intravenous valproate with intravenous lysine-acetylsalicylic acid in acute migraine attacks. Headache. 2005;45(1):42-46. [PubMed]
29.
Friedman B, Garber L, Yoon A, et al. Randomized trial of IV valproate vs metoclopramide vs ketorolac for acute migraine. Neurology. 2014;82(11):976-983. [PubMed]

ALiEM Copyeditor, Dr. Matthew Zuckerman

>Concerned that this post tries to do a little too much. Includes background on migraine, recommendations for standard therapies, non-opioid therapies, when opioids are indicated, and pain contract. Perhaps focusing on less and decrease length of post by 25%.

  • Avoid cliché e.g. (“without blinking an eye”)
  • Reduce citations and focus on core references. Reference 22 is from a Serbian publication, did the authors have this translated?
  • Very concerned that this article cites numerous adjunctive therapies, many with little or poor evidence. Many of the references actually suggest therapies are not more effective than placebo (ref 20, 26, 27, 31).
  • Why IV acetaminophen rather than PO?
  • Not sure if data on opioids for headache is up to date. Haven’t seen Demerol used for pain in long time and anecdotally my department almost never uses opiates for headache. Is there more up to date data?
  • Is abstaining from medication overuse really “detoxification”? What toxin is being removed?
  • Table on ketamine refers to “feelings of insobriety”. Please clarify.
  • Happy to re-review post edits, great opportunity to talk about when how to use opiates in migraine or potential adjunctive meds for migraine.

    Matthew Zuckerman, MD
    Assistant Professor, Emergency Medicine
    University of Colorado, Anschutz Medical Campus

    Expert Peer Review, Dr. David Vinson

    The authors have done a fantastic job directing their case vignette and the following discussion straight to the issues that commonly complexify the emergency department (ED) management of refractory migraine. This patient’s situation is admittedly difficult: her migraines are frequent and disabling and fail about twice a month to respond to oral medications, precipitating ED visits in search of pain relief. The triad of first-line parenterals well known to the emergency physician (NSAIDs, triptans, and dopamine antagonists) is out of consideration (clever of our sly vignette writers). Our pain-afflicted patient has found high-dose opioids effective in the past and understandably solicits their aid. This forces the physician onto the horns of a familiar dilemma: concede to the request and resolve the pain but feel a pang of compunction while reinforcing the patient’s drug-requesting behavior, or refuse to comply and risk undertreating the pain and catalyzing an all-sides- lose confrontation (1).

    The solution the authors recommend is both highly sensible and far-sighted, avoiding the simplistic either-or dichotomy I just put forth. But it requires a high-level coordination of care on several fronts, first within the ED itself. A department-wide approach is essential so that with each of the patient’s visits she encounters the same expected treatment plan, regardless of the physician who happens to be on shift that day. What might such a plan include? A list recommended pharmacological interventions would be helpful. Select the better-performing agents from the authors’ table of second-tier therapies and create a patient-specific treatment plan that spells out the sequence of suggested parenteral medications for ED use. If the first medication were to fail at the first visit, the next parenteral on the list could be tried at the second visit, and so on, with careful documentation of each medication’s effects and side-effects. The process would continue until one drug was found that hit a home run with this patient—or at least a double. If the patient proved mostly resistant or intolerant to the whole lot, then the preferred agent might be the one that was only modestly effective; it could be employed as an adjunct treatment to help reduce the opioid need. Even that is progress.

    The second level of coordination the authors propose is between the ED and the patient’s primary care provider (thank goodness she has one!). Synchronizing efforts here is also vital. Ideally, her physician will serve as a supportive ally in patient care, designing a home management plan that complements our ED efforts. One pillar that is missing from this patient’s regimen is a prophylactic agent, recommended for patients with migraines of high frequency or disabling severity. Our migraineur qualifies on both counts. When effective, these medications can significantly reduce migraine frequency, duration, and attack severity. They can also improve responsiveness to abortive therapies and prevent progression or transformation of episodic migraine to chronic migraine. The American Academy of Neurology tops their list of prophylactics with specific antiepileptics and beta-blockers (2). The former agents need close follow-up, and some require monitoring. Propranolol, however, is less complicated and is more likely a drug that can be started out of the ED. The initial dose is 20 mg twice daily, which will need to be titrated up over time (3). Headache improvement may not be evident for several weeks. A higher dose should be maintained for at least three months before deeming the medication a failure.

    The third level of coordination the authors address is between the ED and the patient. This component is often overlooked, though it is crucial to the success of the treatment plan. Securing our patients’ understanding of what we’re doing—and why—is a minimum. If nothing else, communicating our objectives helps recalibrate expectations. This can go a long way to mitigate any unruly emotions that might emerge when a patient’s opioid ambitions are thwarted and may help preempt the unwarranted objection that we don’t care. On the contrary, it is precisely because we do care that we are going to these lengths to improve our management of patients with hard-to- control migraine.

    Management of a patient like this will vary across EDs as each works out a solution that seems most suitable to the several parties in play. Whatever the local variations, enlisting cooperation at these three levels—among the ED faculty, between the ED and the primary care provider, and with the ED and the afflicted patient—will help arrive at an approach that is thoughtful, sensible, and serviceable to the long- term interests of the patient and those who rally around to provide her the best care possible.

    I also have a few very minor editorial suggestions.

    • 42 year old should be hyphenated: 42-year- old
    • Emergency room might be better represented as emergency department
    • The first use of ED should be defined: emergency department (ED) and subsequent uses should follow the abbreviation
    • First or second line therapy might also benefit from hyphens: first- or second-line therapy
    • Does contra-indications need a hyphen?
    • Consider referencing the sentence on medication overuse headache so your readers can find supplemental information
    • The last sentence of the penultimate paragraph is a tad cumbersome. Consider breaking it up.
    • Department wide opioid practices in the last paragraph might be better written with a hyphen: department-wide opioid
    • References in the table should refer to the primary literature, and not just to summaries or guidelines. The propofol information will illustrate. Two studies are described: “In a low quality RCT, propofol outperformed dexamethasone. In another low quality trial, propofol outperformed sumatriptan.” Yet the only reference given is to a systematic review.
    1. Friedman BW, Vinson DR. Convincing the skeptic. How to fix emergency department headache management. Cephalalgia. 2015;35(8):641-3.
    2. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17):1337-45.
    3. Pringsheim T, Davenport WJ, Becker WJ. Prophylaxis of migraine headache. CMAJ 2010;182:E269-76.
    David R. Vinson, MD
    The Permanente Medical Group, Oakland, California
    Kaiser Permanente Sacramento Medical Center, Sacramento, California
    Co-chair, KP CREST Network
    Adjunct Investigator, Kaiser Permanente Division of Research, Oakland, California
    Volunteer Clinical Faculty, University of California, Davis, Department of Emergency Medicine, Sacramento, California

    Our thanks to Dr. Vinson for his typical thoughtful, helpful, and detailed review. We have incorporated all of his grammatical suggestions and included the recommended references.

    We agree with his comments about initiating migraine preventive medication in the ED. Some may argue that initiating chronic medication is not within the purview of emergency medicine. We believe that it is the responsibility of the emergency physician to provide evidence-base care if the ED patient is not receiving appropriate treatment in the outpatient setting. This is particularly true for frequent ED visitors. Hopefully, this can be coordinated with the outpatient provider. Of all the evidence-based migraine preventive therapies, propranolol or metoprolol are the ones with which emergency physicians may be most comfortable. The target dose for propranolol is 80-160 mg per day [1]. Metoprolol should be dosed at 100-200 mg daily [1].

    References:

    1. Pringsheim, T., et al., Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci, 2012. 39(2 Suppl 2): p. S1-59.
    Cindy Prettypaul
    Medical Student
    Lake Erie College of Osteopathic Medicine
    Seton Hill

    Cindy Prettypaul

    Cindy Prettypaul

    Medical Student
    Lake Erie College of Osteopathic Medicine
    Seton Hill
    Cindy Prettypaul

    Latest posts by Cindy Prettypaul (see all)

    Benjamin Friedman, MD MS

    Benjamin Friedman, MD MS

    Department of Emergency Medicine
    Montefiore Medical Center
    Albert Einstein College of Medicine
    Benjamin Friedman, MD MS

    Latest posts by Benjamin Friedman, MD MS (see all)

    • Steve

      This is certainly a though situation but I disagree with the final outcome. Barring contraindications, I would rather give the patient full procedural sedation with propofol (1mg/kg IV) or ketamine (1-2 mg/kg) rather than go to opoids with the goal of complete sedation. The patient will wake up after essentially pressing the “reset” button on their pain. While labor intensive, small case series have shown good results and actually lower ED LOS with propofol versus typical migraine patients. I would only do this on ASA 1 and 2 patients and they would get the same consent, monitoring, and airway prep as any other procedural sedation gets. While an ED visit may not be significant in the long view- I would worry about perpetuating a cycle. What happens when the next neuro appointment is not for a month? Does the patient get multiple weekly doses of hydromirphone? I think you are already at that point where opoids would only be given in conjunction with a neurologist and a plan for admission. What the authors are suggesting is not completely unreasonable- I just think more intervention should be attempted before going to opiates. My current practice is to attempt all of the above. If those fail then the patient gets admitted for status and neurology can guide their further therapy

      • We agree! Although lately we’ve had some success using greater occipital nerve blocks with bupivacaine, we agree that the most compelling therapeutics in our table are propofol and ketamine. For the patient in the case vignette, it is very reasonable to try either or both of these agents prior to administering opioids. However, (wearing our evidence based cap), we pose the following question: Among patient with migraine (or any recurrent pain disorder) who present frequently to the ED for treatment of pain, are there fewer downstream adverse events among patients who receive ketamine (or propofol) than among those who receive opioids? Before we all jump on the ketamine (or propofol) bandwagon, it is important to answer this question.

        We also agree that many ED frequent flyers are complicated. The headache patients often have concomitant chronic migraine + medication overuse headache. For some of these patients, admission for “detoxification” of the offending overused medication is very reasonable.

        And what about in limited resources areas, where patients can’t get in to see a specialist in a timely matter? There needs to be some compromise so that patients who adhere to established plans of care can be treated with opioids when they really need pain relief.

    • Henry

      I agree with Steve. There is a whole discussion here of alternatives and poor justification for why you would just resort to opioids. The patient would be better served by finding an alternative treatment for the headache than giving a couple rounds of meds that do nothing but cover up the pain.

      • We agree: it is preferable to identify an effective alternative agent such as magnesium, IV APAP, ketamine, or greater occipital nerve blocks. But in the end, if nothing else works, it is cruel to make a patient suffer unnecessarily–particularly if it is a patient who adheres to established plans of care.

    • Chris Tidwell

      12 migraines a month and requesting a specific narcotic regimen?
      These are red flags for me. Here is my approach:
      (1) Consult Neurology and ensure prompt follow up
      (2) one Liter bolus of Normal Saline, 30mg IV toradol and 25mg Benadryl IV

      It is ok to say no to narcotics in this case, in fact it is essential with the rebound effects they have with migraines.

      Ideally, I would have added Reglan but with her reported allergies it is problematic.

      • i too like ketorolac but this patient has already taken 1000mg of naproxen in the last 8 hours. Too much NSAIDs you think? I admit, I do sometimes use ketorolac in this scenario, particularly in young, large, healthy patients.

        While I love my neurology consultants dearly, they always recommend IV valproic acid, which we know is less likely to work (PMID 12764341)

    • Sergey Motov, Lewis Nelson

      We appreciate author’s attempt to tackle the issue
      of ED management of migraine headache in complex patients by providing an
      overview of variety of analgesic modalities. However, we are concerned with
      several statements and recommendations mentioned in this review that, if accepted
      into clinical practice, could be detrimental and potentially dangerous.

      We agree with author’s statement that “published
      data do not establish that the benefit of pain relief is outweighed by the
      potential for opioid induced harm ince the benefit does not clearly exceed the
      harm, and we know that the harm is extensive, this treatment should be
      relegated to the rarest of uses. This is consistent with the Choosing Wisely
      campaign and with the American Academy of Neurology
      position on opioid use (1).There are clear unfavorable short and long-term
      consequences associated with opioids use for migraine HA as mentioned in
      beginning of the article: progression of the underlying migraine
      disorder from episodic to chronic migraine, increased frequency of return
      visits to ED, less responsiveness to subsequent treatment with triptans, less
      frequent headache relief than patients who received dihydroergotamine or
      dopamine antagonists. And this does not include all the risks associated with chronic
      opioid use, such as abuse, addiction, overdose, and death. Furthermore,
      teaching patients that the only successful treatment for their particular pain
      syndrome is an opioid leads to difficult patient interactions and bidirectional
      dissatisfaction with nearly every visit.

      However, and surprisingly, the author’s statement
      that “the harm arising from 3 isolated doses of parenteral opioids during
      one ED visit is unlikely to be either long-lasting or severe” is quite misleading
      especially in the context of hydromorphone use. Hydromorphone use in the ED is associated with
      significant rates of respiratory depression and excessive sedation, nearly 7-8
      times higher dosing than morphine, and significantly greater potential for
      abuse and misuse due to its high likeability, abuse liability, and profound euphoric
      effect. (2-4).

      Most importantly, the equinanalgesic dosing of
      hydromorphone with respect to morphine milligram equivalent (1mg of
      hydromorphone equals 7 mg of morphine) has not been elaborated. In fact, if
      used as suggested, this dosing would lead to the administration of what amounts
      to 42 mg of morphine intravenously during the patients stay in the ED. Since
      equianalgesic doses of all opioids carry essentially the same adverse effects
      and risks, the consequences of this dosing regimen, especially in opioid –naïve
      patient, are extremely SEVERE and
      may result in fulminant respiratory depression and even death. Th illusion that the smaller milligram dosing
      of hydromorphone means that smaller functional amount of opioid is being
      administered has led to significant hydromorphone overdosing in the ED. This
      has resulted in significant rates of respiratory depression and the need for
      rescue naloxone. (4-6) For example, a single dose of 2 mg of hydromorphone
      resulted in hypoxia in 33% of patients with acute pain and “1+1” hydromorphone
      titration dosing resulted in respiratory depression in 30% of patients.(7,8)

      We strongly oppose author’s recommendation of hydromorphone
      use for migraine headache in the ED even as a rescue analgesic. If an opioid
      must be administered, morphine is less euphoric and more familiar to most
      clinicians. If hydromorphone is considered, the maximal single and total doses
      administered should be placed in the context of the more familiar morphine
      dosing (as noted, 1 mg hydromprhone is equivalent to 7 mg of morphine. Thus a
      typical dose of 0.5 mg of hydromorphone seems most reasonable). We urge the authors to revise their statement
      by better discussing harms associated with supranalgesic dosing of all opioids,
      especially hydromorphone, in the ED and the lack of adequate evidence to
      support its use.

      Sergey Motov, MD, Lewis Nelson, MD

      References:

      1. Franklin GM.
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      2. Gulur P, Koury K, Arnstein P, Lee H et al. Morphine versus
      Hydromorphone: Does Choice of Opioid Influence Outcomes? Pain Res Treat. 2015;2015:482081. doi:
      10.1155/2015/482081. Epub 2015 Nov 1.

      3. Bryson EO.The anesthetic
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      4. Adverse Drug
      Events with HYDROmorphone: How Preventable are They? Pa Patient Saf Advis 2010 Sep;7(3):69-75 http://patientsafetyauthority.org/ADVISORIES/AdvisoryLibrary/2010/Sep7(3)/Pages/69.aspx ( accessed on 5/18/16)

      5. O’Connor AB, Lang VJ, Quill TE. Underdosing of
      morphine in comparison with other parenteral opioids in an acute hospital: a
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      Beaudoin FL, Merchant RC, Janicki A, McKaig DM, et al. Preventing iatrogenic
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      events and medication errors. Ann Emerg Med. 2015 Apr;65(4):423-31.

      7. Chang AK, Bijur PE, Napolitano A, Lupow J, et al Two milligrams i.v.
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      • thanks for the detailed and thoughtful critique.

        seems like we agree on a lot: 1) Published data do not support the use of opioids as first or second line treatment of acute migraine in the ED and 2) Opioids, when used for acute exacerbations of chronic pain, should be used judiciously. These two statements probably encompass 95% of all individuals who present to the ED with headache.

        It seems like we disagree on how to manage the frequent ED user presented in our case vignette: acquiesce to her request or fight it. From our perspective, it is cruel to make a patient suffer unnecessarily. If this patient knows what treatment is effective, then one needs a strong rationale to deny her effective treatment. Now often, one does have a strong rationale. If the patient does not play by the rules (ie, does not adhere to established plans of care or uses healthcare resources inappropriately) then treatment with potent, high dose opioids is withheld justifiably. However, if the patient adheres to established plans of care, making her suffer unnecessarily is unreasonable.

        We also disagree with your interpretation of the accumulated works of AK Chang et.al, who have enrolled over 1000 patients in various hydromorphone versus morphine RCTs and similarly designed studies (PMIDs: 26074387, 23846749, 2369480, 23406078, 21507527, 19560838, 18996618, 16857467). To our reading, hydromorphone 2mg IV is safe if administered in an ED, where O2 supplemetation is readily available. This is supported by the fact that, in all their studies, these investigators have never had to use naloxone to counteract the effects of hydromorphone.

        We are also intrigued by the concept of euphoria, its relation to the various opioids, and whether or not it is on the causal pathway between parenteral opioid use for acute exacerbations of chronic recurrent pain disorders and frequent ED visits. As far as we know, there are no high quality data to support this contention, though it does have a fair amount of face validity. We are currently conducting an RCT in migraine patients in which we compare prochlorperazine IV to hydromorphone IV. We are collecting data on euphoria and long-term outcomes, so we hope to be able to answer this question definitively. Similarly, with what frequency does use of parenteral opioids in ED for chronic recurrent pain cause abuse, addiction, overdose, and death? Tough to answer this question in an RCT. But before we can have a rationale discussion, we need data on NNH and NNT.

        Thanks again for the comments. We are looking forward to reading more on this topic in your forthcoming textbook.

        • Sergey Motov

          We are absolutely agree with the statement that patient should not be suffering. On case-by-case basis when multiple analgesics fail to provide appropriate pain relief, opioids might be considered as a rescue despite the lack of evidence to support their use for migraine HA. The pressing issue is the dosing of hydromorphone in the vignette that does not honor equianalgesic dosing conversion. As we stated in the earlier post, patient is to receive 42 mg of morphine milligram equivalents during her stay in the ED. That is a huge dose of an opioid that carries extremely severe risk of respiratory depression. It is hard to conceive that patient’s headache warrants such a large hydromorphone dosing.
          Why not to start with 0.2-0.5 mg dose and titrate until pain is optimized? Purdue Pharma recommends the initial IV Hydromorphone dosing to be 0.2mg-1mg per dose. Chang et al clearly demonstrated that 32% of patients receiving 2mg IVP of hydromorphone became hypoxic. That is not safe. In addition, administration of even 1 mg of IVP Hydromorphone ( Chang et al) resulted in 5% patients to be hypoxic, 10% to be bradycardic, 13% to have nausea and 7% to have vomiting. That is not safe either despite the fact that none of the patients required naloxone. There should not be a need for supplemental oxygen and a monitor if opioids are properly titrated with lowest effective dose.

          • 1) Agree that titration is the way to go, if feasible. But don’t you worry that in a busy ED a titration plan will get lost by the wayside and the patient will continue to suffer? PCAs are great but have not yet been widely adopted for use in EDs.

            2) I don’t want the conclusion from this discussion to be that high dose opioids are unsafe. In an ED, an EP should feel comfortable using high dose opioids if required because we have the tools to deal with hypoxia, bradycardia, and nausea.My take home lesson from the Chang et al series is that hydromorphone is safe in an ED–there were no irreversible or long-lasting adverse events.

            3) What about parenteral diphenhydramine? Should we encourage use because, at least theoretically, it is opioid sparing? or discourage use because it induces euphoria, which is not our goal? ( I favor the former)

            • Lewis Nelson

              Thanks for the interesting and frank discussion. This is obviously an important issue for all to consider, and there are no right answers, though there are a few wrong ones. I have several concerns based on the preceding discussion.

              Probably the most important one is that the dosing of hydromorphone that is suggested is potentially extraordinarily dangerous. Though your concerns for some excess pain while titration occurs in a busy, distracted ED, are real, the alternative is far worse. A distracted physician and nurse who miss hypoxia (which unfortunately occurs quite commonly) may leave a patient with hypoxic encephalopathy or dead. As Sergey suggested, the dosing of hydromorphone must be respected, and perhaps if we dosed it in micrograms, like we do with fentanyl, rather than milligrams, it would be more obvious how potent this opioid really is.

              Do not forget the “long lasting effects” of teaching the patient that only opioids are good analgesics, as it sets up both conflict and unrealistic expections on subsequent visits. We have all had those interactions, and they are quite uncomfortable for both patients and providers. And the “long lasting effects” of addiction and abuse that are often initiated by well intended physicians, both in the ED and in follow up. Every person with iatrogenic opioid addiction started with an opioid from some prescriber. The only thing that we can say for 100% sure is that if you never receive an opioid from your doctor you cannot develop iatrogenic addiction. This of course does not mean that people cannot go out on their own and find opioids…of course they can, and many do. Unfortunately, that is another issue for which we (physicians and other prescribers) are partially responsible – the widespread availability of these pills on the street.

              The role of diphenhydramine, or acetaminophen for that matter, as being opioid sparing is virtually unproven and probably unable to be proven. Given the psychoactive and other effects of diphenhydramine, finding an adequate control will be severely limiting. Admittedly its generally benign, and not cost prohibitive as with IV APAP, but it teaches the wrong lesson to both patients and physicians.

              Given the limited to nonexistent data on the benefit of opioids for migraine headache and the clear destructive potential of this class of medications, as you said in the initial post, the risk benefit falls solidly on the side of “do not use.” There may be the rarest of times that it is necessary to give an opioid (and morphine is a much better option than hydromorphone), but I believe we are doing our patients a disservice to use them rather than, as we seem to assume, being passionate caregivers.

    • Zack Repanshek

      I think the issue is a lack a familiarity with second line agents.
      Many of us may have never given mag or VPA for an acute headache. But we are all comfortable giving an opioid.
      In my opinion, opioids for migranous HA should be a never event.
      It’s up to us to stay educated on the best next line agents in a difficult situation such as this. Thanks to ALIEM for raising such a good discussion.

      • Amen to that: thanks to ALiEM for this awesome forum.

        My approach to acute migraine (assuming no contra-indications): First, metoclopramide 10mg IV (or prochlorperazine 10mg IV or droperidol 2.5mg IV). Then more metoclopramide 10mg IV + ketorolac 30mg IV (though based on abstract just presented by Motov et al at SAEM, this should just be 10mg IV). Then metoclopramide 10mg IV + dihydroergotamine 1mg IV. Then greater occipital nerve block with bupivacaine. Then opioids. Dexamethasone 10mg IV should probably be administered to all acute migraineurs to prevent recurrence of headache after ED discharge (NNT=9) Data supporting magnesium and VPA are less robust.

        • Brian

          The above example of step care (first this, then that, then this) may be less effective then stratified care (based on severity, your treatment regimen will be this or this plus that) according to a RCT published in JAMA in 2000.

          Admittedly, this is an outpatient based study however the tenant to therapy remains the same. Assuming the patient is appropriately utilizing ED resources, the migraine is likely severe.

          An alternative to the above may be initial therapy with anti dopaminergic (prochlorperazine seems to have best evidence) plus ketorolac plus IV fluids. To provide fastest resolution of therapy, it makes sense to me to administer multiple mechanisms up front instead of waiting. If this fails, step wise escalation from here would be appropriate.

          In a completely unrelated side note, administration of DHE within 24 hours of any triptan is considered a relative contraindication owing to additive vasocaontrictive side effects. It is imperative to find out what your patient took prior to presentation!

          Thank you for reviewing this subject!

          Brian Melhart, PharmD

          (Litpton et al. Stratified Care vs Step Care Strategies for Migraine
          The Disability in Strategies of Care (DISC) Study: A Randomized Trial. JAMA 2000; 284: 2599-2605)

      • M. Pius, MD

        I have been using valproic acid for migraines in the ED for several years now – including patients who report never having relief from triptans and patients who report previous requirement for opiates. My usual first-line drugs are ketorolac + metoclopramide IV. If no relief after those, 500mg IV valproic acid. I really can’t recall any patients that required further intervention after that. Although, it’s possible that the time delay (60 min) while the valproate runs in is really just giving the first round of drugs more time to work.

    • Gabe

      C6 Paracervical trigger-point Injections with Bupivacaine 0.5% 1.5ml each side with a 27-gauge 1.5-inch needle followed by trigger point pressure/massage I’ve found to be quite successful; this is different than occipital Bupivicaine which was mentioned about.

      Considering the substantial risks of several of the meds mentioned, this procedure is low risk and high benefit; I’ve had great success provided patients are amenable (some say they are open to anything that will get rid of this pain; others don’t want a needle anywhere near their neck).

      Mellick et al. Treatment of headaches in the ED with lower cervical intramuscular bupivacaine injections; a 1-year retrospective review of 417 patients. Headache. 2006 Oct;46(9):1441-9.

    • Dr Smiley

      I give what the customer (oops, I meant the patient) wants. Otherwise my satisfaction scores would go down.

      • Alas, it is certainly true that external pressures often force us to practice sub-optimally. This is also true with regard to antibiotics for bronchitis and head CTs for minor head trauma. With regard specifically to the question of opioids for migraine in complicated patients, we think the best solution is to manage these patients between shifts rather than during shifts. “Complicated patient” committees, made up of clinicians and administrators with appropriate expertise, can help determine the ideal short and long-term treatment plan for each patient, which can then be enforced by monitoring frequent visitor lists and utilizing patient care contracts. Department-wide policies can insulate individual EPs from complaints and (more importantly) can be used to design and deliver appropriate and high quality care to each individual patient. Most likely, patients will interpret well-intentioned interventions as beneficial, particularly when they begin to see actual outcome benefits.

    • Tradomedical Healer

      I’m here to tell everyone who are suffering from migraine headache that there is a treatment for it, I was ones a migraine sufferers for over 13 years, I always had migraine headaches 2 to 3 times in a week to an extent i lost one of my eye site for days, it was really hell for me, i visited different doctor for the treatment but all were singing the same song of no treatment for migraine, and I have taken different types of drugs, i spent all my money in drugs and health care centres, but still there were no avail, and I keep on praying to God to heal me from migraine headaches, but one day i was online doing research on how i can get treated on my headache and i found a testimony on how someone was been treated from migraine headache by Dr muzack of Africa with natural herbal products, at first i couldn’t believe him, but i was dying in pain and now I have no option again than to gives this same man a trial but i never knew it’s going to be the end of my headache i has been living with for years, the God who has done this for me will be praised for ever, that was how i contacted Dr muzack and he was humble and very understanding man, the way he spoke politely with me, that was when I knew that my problems is over, that’s was how he sends the drugs which was made from herbal products over to me here in Canada, I took the drugs as I was directed to, it’s over 7 months now and haven’t feel any pain like headache and I’m even stronger than ever and it has no side effect. Feel free to contact him directly on his email address tradomedicalhealer@gmail.com or call; +2347037791346