Thursday, May 9, 2013

Milking It: Propofol for Migraine Headache

An 18-year-old female patient presents to your emergency department with complaints of having "the worst migraine headache ever." She states that the migraine headache with associated photophobia started about three days ago, and symptoms have gotten progressively worse ever since. She has a history of migraine headaches, and as an outpatient, she is on sumatriptan at home, which she states she has not used in the past year. Prior to her arrival, she took ibuprofen and her prescription of sumatriptan at home, but to no avail. Her expectation now is for you, the ED attending, to give her "the best stuff you've got for migraines," and preferably something injectable so that its onset is immediate and "will take care of her migraine headache yesterday."

Your EM resident turns to you and states, "You know, I just read an article that looked at using propofol for migraine headaches. Apparently, it worked in the pediatric population. Maybe we can give it a try for our patient?"

Propofol has been evaluated in a number of studies for the treatment of migraine headache due to its agonist properties on the gamma aminobutyric acid (GABA) receptor, which has been purported to relieve pain associated with migraine headache. It is thought that propofol may also reduce central sensitization and cortical spreading depression that is associated with migraine headache as well (1, 2).

One of the earliest studies that evaluated propofol for intractable headaches was conducted in an open-label study in 77 patients in an outpatient clinic by Krusz and colleagues. Propofol was administered as an IV bolus dose in increments of 20 to 30 mg every 3 to 5 minutes. Patients received an average of 110 mg of propofol, which was considered to be a subanesthetic dose. 63 of the 77 (82%) patients had complete resolution of pain associated with headache at 30 minutes. In terms of adverse effects, some patients experienced transient drowsiness and slurred speech, with 8 patients experiencing spontaneous movements in the fingers. Otherwise, no other significant adverse effects occurred. After a period of 20 to 30 minutes, patients reported a reduction in headache intensity by 95.4%.

The use of propofol for this indication has been analyzed in a retrospective study of pediatric patients who presented to the emergency department, and was compared to matched control patients who received other standard abortive therapies (which included nonsteroidal anti-inflammatory drugs [NSAIDs], diphenhydramine, and prochlorperazine) used in the emergency department. Patients received a mean total dose of 1.71 mg/kg IV of propofol administered over approximately three boluses. Patients in the propofol group had greater reductions in pain scores compared to those in the matched control group (80.1% versus 61.1%, respectively [p < 0.05]) as well as a shorter length of stay in the emergency department (122 minutes versus 203 minutes, respectively). Hypotension, hypoxia, and respiratory depression were not experienced by patients in either group.

A recently published study also compared the effects propofol to intravenous dexamethasone for pain relief associated with migraine headache in a randomized, double-blinded fashion. 90 adult patients who presented to the emergency department with signs and symptoms that were consistent with a clinical diagnosis of migraine headaches were randomized to receive either propofol at an initial dose of 10 mg IV that was titrated upward every 5 to 10 minutes as needed for pain relief to a maximum dose of 80 mg or dexamethasone at a dose of 0.15 mg/kg to a maximum dose of 16 mg. Pain scores based on a visual analog scale were recorded at the time of presentation and at 5, 10, 20, 30, and 45 minutes after administration of either agent. Patients in the propofol group had lower pain scores and more rapid resolution of migraine headache pain compared to those in the dexamethasone group. In addition, there were no significant differences observed among patients in both groups in hemodynamic stability (heart rate, blood pressure, and oxygen saturation).

It seems pretty clear that based on the studies described above, propofol is a reasonable option for patients who present to the emergency department with migraine headache. However, there are a couple of caveats I would like to highlight before you grab that vial of propofol for your patient with migraine headache:
  • These patients essentially have to be treated as if they were undergoing conscious sedation. That is, patients have to be closely monitored by physicians and nurses for adverse effects associated with propofol. 
    • Although patients in the studies described above received considerably lower doses of propofol than those typically used for conscious sedation, that is not to say that the number of resources should be minimized to ensure that adverse effects associated with hemodynamic status are properly managed, should any occur.
  • In terms of the "appropriate patient" in which to use propofol for migraine headache, I would probably resort to propofol as a last-line option if all other standard therapies used in your emergency department have been exhausted and failed to minimize the pain associated with migraine headache in your patient. 
Alternatively, we may be able to select specific patients in which propofol may be beneficial in reducing pain associated headache, such as those patients who experience headache after undergoing a lumbar puncture procedure. This is especially relevant since intravenous caffeine sodium benzoate, which is typically used for this reason, has been on shortage for quite some time. In addition, these patients are typically closely monitored after the procedure, which would make it ideal for administering propofol for this purpose. Any willing study collaborators out there?

1. Dhir A, Lossin C, Rogawski MA. Propofol hemisuccinate suppresses cortical spreading depression. Neurosci Lett 2012; 514:67-70.
2. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 2009; 10:895-926.

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