SGEM#66: King of Pain (Migraine Headaches)

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Date: March 14, 2014

Case Scenario: A thirty-two year-old woman presents with her usual migraine headache.

Background: More than 10% of people (6% men and 18% women) suffer from migraines. This condition represents a significant source of both medical costs and lost productivity. Direct costs are estimated at ~17 billion dollars a year. There are also indirect costs of about 15 billion dollars a year mainly due to missed work.

Up to half of patients presenting to the ED with their migraines will “bounce-back” to the ED in a few days. Dexamethasone has been tried in randomized control trials to prevent bounce-backs. Giuliano et al did a good review on this topic in Postgraduate Medicine last year.

SGEM#28: Bang Your Head talked about the paper by Coleman et al in BMJ on the subject of migraine bounce backs. It showed that a single parenteral dose of dexamethasone ≥15mg for successfully aborted migraine will significantly reduce early recurrences (NNT=9) with no significant side effects.

Question: Does ketorolac work well for acute migraine headache treatment?

Reference: Taggart E et al. Ketorolac in the Treatment of Acute Migraine: A Systematic Review. Headache 2013; 53: 277-287

Population: Eight studies of adult patients (n=321) presenting to the emergency department with acute severe migraine headache
Intervention: Ketorolac parental alone or in combination with other migraine abortive therapies
Comparison: Placebo or other standard therapy
Outcome: Efficacy (pain relief) and safety

Authors’ Conclusions: “Overall, ketorolac is an effective alternative agent for the relief of acute migraine headache in the emergency department. Ketorolac results in similar pain relief, and is less potentially addictive than meperidine and more effective than sumatriptan; however, it may not be as effective as metoclopramide/phenothiazine agents.”

Quality Check List for Systematic Reviews and Meta-Analyses:

Sensible and answerable – Yes
Detailed and exhaustive search – Yes
High methodological quality – Yes
Studies reproducible – Yes
Outcomes clinically relevant – Yes
Low heterogeneity – Yes
Large and Precise – Yes

Results: Pooled estimates showed no difference in pain relief at 60 minutes between ketorolac alone or in combination compared to placebo or other standard therapy. For meperidine WMD=0.44 (95% CI= – 0.49 to 1.38) and heterogeneity was low (I2=0%).

Only one trial compared ketorolac to sumatriptan and demonstrated significant reduction in migraine pain at 60 minutes (WMD -4.07, 95%CI -6.02—2.12).

Only two trials compared ketorolac to phenothiazine with no significant benefit noted on the summary estimate (WMD 0.82, 95%CI 0.82, 95% CI -1.33- 2.98), though significant heterogeneity was identified (I2 = 70%).

Commentary: There is a wide variety of practice variations in the treatment of acute migraine. This may be because no single approach has been shown to be clinically superior. This study attempted to review what role ketorolac can play in the treatment of these common and painful presentations to the emergency department.

This SR started with some difficulty because while diagnostic criteria for migraine exist, they are often not used in the emergency department. This made it unclear if patients meet criteria for the diagnosis of migraine. The SR included studies that gave ketorolac IM in 6/8 studies with 5/6 studies using 60mg IM. Giving any medication IM vs. oral increases the placebo effect and could have influenced the results in some of these studies.

The quality of the primary studies was moderate to high quality on the Jadad score (3). However, the bias was either “high” or unclear.

The conclusion of ketorolac being more effective than sumatriptan was based on one RCT from 2003 of only 29 patients and should be viewed with caution.

The discussions of ketorolac +/- meperidine seem a bit irrelevant because most departments no longer have meperidine on their formulary. Ketorolac would be the preferred treatment in the ED due to the potential for abuse and addiction with meperidine.

There was very inconsistent information on rescue medications and no reporting on relapse rates. Previous BEEM review has demonstrated a single dose of dexamethasone can decrease migraine headache recurrence and bounce backs to the ED following an acute migraine (NNT=9).

This SR was of moderate quality, included small studies, high/unclear bias, inconsistent outcome reporting, and lack of data on relapse.

Bottom Line: Ketorolac is a reasonable second-line agent in the treatment of acute migraine.

Clinical Application: I will tend to use ketorolac only as a second-line agent in the treatment of acute migraine.

Case Resolution? I can see you are in pain and that is important to me. We will try some standard treatments first that have been shown to work. I will check back with you in 30-60 minutes to see how you are doing. If your pain is not controlled there is a plan B.

Keener Kontest: Last weeks winner was Jaime Davis from Florida. He correctly answered the riddle of the Sphinx “What goes on four feet in the morning, two feet at noon, and three feet in the evening?”

Listen to this weeks’ episode of the SGEM for the Keener Kontest? If you know the answer send an email to TheSGEM@gmail.com with “keener” in the subject line. The first person will receive a skeptical prize.