Effectiveness of IV Therapy in the Headache Clinic for Refractory Migraines ABSTRACT
The future of aggressive headache treatment is in the specialty clinic,
a far more cost- and time-effective mode of treating intractable headaches, Jane Cagle, LVN, John Claude Krusz PhD, MD including refractory and chronic migraines. Compared with the emergencydepartment, the headache clinic can offer a wider range of effective anddefinitive treatments and offer headache patients maximum degree ofsuccess for control of migraines. We have used IV treatment in the clinicsince 1994 and presented initial data regarding its effectiveness in 1998. Thisstudy continues in documenting the degree of success of outpatient IVtreatment of headaches.
Our total treated patients number over 1700. Of these, 874 were treated for refractory migraines or headaches; the rest were for pain flare- Outpatient aggressive
therapy of refractory headaches
and migraines with IV therapies is highly efficacious with a very
dexamethasone, valproate sodium, lidocaine, droperidol, dihydroergotamine, low need for re-treatment.
promethazine, propofol, tramadol, levetiracetam and ketamine.
Results are measured on the basis of successful resolution of 2. Our series successfully treated refractory migraine and other
symptoms, defined by at least a 50% decrease in severity of the presenting headaches 97.5% of the time [852 of 874 patients].
headache or migraine, or by return to work or regular activity. On this basis,62 patients from the total pool, and 22 from the headache pool (22/874) [ Treatment
2.5%] had unsuccessful treatment that required re-treatment in the clinic, productivity, most importantly in the workplace, at home and in
hospital ED or inpatient. This represents a 97.5% rate of effective treatment personal life for the migraine sufferer.
4. We would urge headache specialists and physicians interested in
headaches and migraines is highly successful with a very low need for re- the acute management of headache disorders to explore these
treatment. It contributes to productivity, most importantly in the workplaceand also at home and in personal life.
options in their practices.
IV steroids
IV propofol
There is very little published literature on the use of corticosteroids t Sometimes, interesting results are found serendipitously, as Some headache and pain practitioners have a sense (and the at migraines, although there is more data in the cluster headache field o occurred in the case of the pre-anesthetic agent, propofol. We use this experience) that aggressive management of headache and pain flareups can treatment of status migrainosus or analgesic rebound headaches. We us agent routinely in the clinic as a mild sedative prior to epidural steroid be easily and effectively managed in an outpatient clinic setting, rather than xamethasone in the clinic fairly often for refractory migraines, for helpin and other nerve blocks in a conscious sedation manner. We noted that in the traditional mode utilizing hospitalization or simply treatment in theemergency department (ED). Of course this is predicated upon having a clinic h detoxification regimens and for pain flare-ups. This is not necessari some patients who had migraines at the time of their blocks would that can adequately perform the various treatments in the first place. Our owed by an oral taper. Most often, I give it along with IV MgSO4 as the comment on betterment of the migraine before the block was belief is that this method of treatment is far more effective for the patient, e both compatible in the same IV bag (unpublished observations). Othe performed but after propofol was given in conscious sedation doses.
far less costly and allows for a greater range of IV medications to be thors have published results from their own clinics, showing tha After researching the literature, we found no other mention of this administered than would occur in the ED. This is based on our experience xamethasone was indeed effective in their migraine and status migrain agent in treating migraines and undertook a formal open-label study in and out patients' satisfaction with treatment. Based on the results presented pulations. Other than very rare transient elevations in blood sugar and the headache clinic to treat refractory migraines unresponsive to usual here, we urge headache and pain practitioners to incorporate these IV dency to be hungry and have more energy, I see very little in the way o treatment techniques when they are seeing a patient with refractory gative effects from a single IV dose of dexamethasone in my headach We treated a cohort of 77 patients and the results were nothing short of spectacular. Propofol was the most effective IV agent that wehad ever employed, with a 95.4% success rate in reducing ongoing IV Dihydroergotamine (DHE)
migraine headaches. The total dose was only 120mg, given slowly byIV push 20mg at a time. The most fascinating element in this study This outpatient IV treatment approach requires nursing was the specific pharmacologic effect of propofol, which has sole staff trained in IV therapy to start and monitor IV lines; pulse oximetry dihydroergotamine (DHE), a compound similar to, but very different effects on subtypes of the GABAA receptor. It had me speculating as to monitoring is desirable in many cases, and even necessary for some of pharmacologically from, ergotamine. Many people forget that the the role that this receptor system might play in the maintenance of the medications. A comfortable room or rooms where patients can be migraine headaches. Indeed, topiramate has been approved for treated, hopefully where lights can be dimmed, would also be ideal.
migraine prophylaxis last year and one of its mechanisms of action is Many of my IV rooms are multi-use so that the psychologists or other ergotamine is a pure arterial vasoconstrictor. DHE can be given IV or clinicians can use them as well. We have a room that we use for IM and has a 10-14 half-life. The original IV DHE protocol to treat cervical and lumbar traction, a fluoroscopy room and an EEG room refractory migraine headaches was introduced in 1986 by Professor that can be used for IV treatments. Some of these rooms already have IV levetiracetam (Keppra™)
metochlopramide, 10mg, for 2-3 days. In retrospect, metochlopramide Our data with the oral form of this neuronal stabilizing agent was probably also has a migraine blocking effect as discussed under the the first available anywhere in the treatment of refractory migraine LIST OF MEDICATION OPTIONS
headaches, and this agent has a unique mechanism of action thatblocks high-voltage calcium channels, another major activity of many We utilized the following treatments (listed alphabetically): treatment with meperidine and promethazine showed similar efficacy with significantly fewer side effects in the DHE/metochlopramide Subsequently, we developed an IV form of the same agent with ketamine, levetiracetam, magnesium sulfate, propofol, group, making it very useful for office-based treatment of migraines.
a compounding pharmacy and evaluated levetiracetam IV in the tramadol, steroids, and valproate sodium. (see Table 1). These One of the authors [JCK] introduced the DHE45 protocol to treatment of refractory migraines. More recently, cluster headache treatment protocols, and their specifics, will be described in more Dallas in 1987. We have switched to an outpatient protocol where we flare-ups and trigeminal neuralgia have also been treated in the clinic.
give two or even three doses of IV or IM DHE/metochlopramide perday for up to three days. The third dose, if needed, can be given at Call it somewhat proprietary for now, but this is a powerful, non-toxicform of treatment for many difficult pain and headache flare-ups. The antinauseants
home by the patient or a family member. This results in a tremendous manufacturer is working on an IV preparation for commercial use to promethazine, prochlorperazine, and ondansetron)
cost and time savings for the patient and for the clinical staff. Thepatient can also continue a short protocol (3-5 days) of 2 IM doses at Antinauseants have long been used along with acute opiate home each day to break a bad cycle of migraines. This is especially therapy for headaches and for pain treatment, on the notion that use useful for peri-menstrual or seasonal migraine flareups.
of both agents was somehow synergistic. Animal experiments seemed IV tramadol
to support this idea, but human studies are not at all conclusive on this IV Valproate sodium
point. We've looked for evidence of this, but it is almost non-existent.
Tramadol has been available in the US for a number of years and Nevertheless, ED treatment of headache most often uses both opiates Sodium valproate (divalproex sodium as an enteric-coated has been used in Europe for over 30 years. 0.5 billion people with antinauseants. In a very large study of ED treatment patterns in preparation) was approved in 1994 for oral use in the prophylaxis of worldwide have been treated for pain with this agent, whose Canada and the US for headache, analysis of 811,419 migraine migraines in the United States. It was the first anticonvulsant molecule pharmacologic activity includes opiate-like effects on the mu receptor, treatments in l998 showed that adjunct anti-emetics were most often to be found useful in treating migraines in a prophylaxis manner. After as well as weak presynaptic reuptake inhibition of norepinephrine and given with opiates. Promethazine was used six times more often than a time, an IV version of the valproate sodium was developed and has serotonin (like venlafaxine or duloxetine).
been used for treatment of seizures. In our search for additional IV tramadol has been available in Europe but not the US. We metochlopramide. Our preference is to use metochlopramide, both IV agents to use in the clinic intravenously for intractable migraines and decided to formulate a sterile IV preparation to treat headaches. An IV and IM as a first-line antinauseant in the clinic. A very recent paper in other headaches, we turned to this compound and presented an initial form is available in Europe and has a fairly extensive literature in Neurology, described an ED study showing superior effectiveness of IV treating pain. The IV preparation of tramadol turned out to be very metochlopramide, 20mg, against 6mg of SQ sumatriptan. Better Our IV study was a sample of 85 intractable migraineurs and the efficacious, very well-tolerated and treated refractory migraines and decreased pain intensity scores and pain-free rates were found in this response to IV valproate sodium was a 88 % reduction in severity of mixed headaches with pain flareups. We use 50mg IV every 5-15 migraine, patient-rated on a 0-10 numeric rating scale. The average minutes given in the clinic. If it has efficacy, we place the patient on dose of valproate was 720 mg, given IV over about 50 minutes (100- There is a growing body of evidence that blockade of central IV ketamine
dopamine receptor systems can enhance anti-nociception or reduce We have recently gone back over our initial study data and the migraine severity itself. One of the initial studies using IV extracted 23 cases of bona fide HIS-criteria status migrainosus from droperidol10 used quite high doses (mean = 5.6mg) and reported our initial published study sample treated with IV valproate sodium in neuropathic pain, chronic daily headaches and migraines are quite nearly all of their patients being sedated and over 50% with the headache clinic. This very difficult-to-treat migraine population similar in their biochemical mechanisms or underpinnings. The fields of extrapyramidal symptoms 24 hours after treatment. We repeated a responded to almost the same degree as the refractory migraineurs, pain and headache management have become more confluent and series of patients in our clinic using up to ¼-1/5th the dose of IV but needed a higher dose of valproate sodium (1017mg) and a longer droperidol with only 3% side effects and over 80% success rate in treatment time (73 minutes vs 50 minutes). 13 of the 23 patients nociceptive pain, peripheral and central sensitization, windup, long- reducing or eliminating refractory migraines. A recent double-blind rated their migraines as 0/10 in severity after treatment (57%) 37.
term potentiation and neuroplasticity are concepts basic to the trial of intramuscular droperidol, again using high doses of the IV methocarbamol
pathophysiology, expression and maintenance of these disorders.
medication, showed efficacy; however, the placebo response rate was On the treatment side of things, why is it that medications with 57% vs 84% for droperidol. Once again, anxiety, akathisia and completely different structures and similar mechanisms of action (ie, somnolence were rated as severe in 30% of patients, presumably due Although methocarbamol is an older muscle relaxant preparation propofol and topiramate, each of which act on GABAA receptors) can to the high doses employed. Thus, keeping doses quite low (around 2 with an uncertain pharmacologic mechanism(s) of action, it is one of both reduce migraines and other headaches and pain as well? mg total) can be very effective and we have quite a number of the very few available in an IV form and, for this reason, I sometimes One antagonist of NMDA-type glutamate receptors shown to patients who use droperidol IM as rescue medication for their utilize it in the clinic to treat migraines and other headaches especially decrease migraine attacks when given subcutaneously is ketamine.
migraines, either with migraine-specific therapy or to avoid a trip to if accompanied by a lot of neck spasm. We know of no published This anesthetic agent has been little studied thus far but may have the emergency room. We begin with 0.625mg of IM droperidol, studies looking at effectiveness of this agent intravenously to treat theoretical implications for preventing chronic migraines. A recent repeated after 20-30 minutes, and once again if needed.
headaches. All our information is anecdotal and rarely do we use it study administered ketamine intranasally to migraine patients who had alone, it is often used after or with the above other agents. We have pronounced and disabling aura, but less than 50% had successful about 60 patients over the last 4-5 years for whom addition of methocarbamol is a positive element in their overall headache andmuscle spasm relief.
In the headache clinic, this treatment is a sort of "opening shot" for intractable headaches, both migraines and not. It can be given IV lidocaine
TABLE 1 - Medications for Use in the headache clinic
promethazine, prochlorperazine or droperidol) or with IV steroids.
Lidocaine is an indiscriminate blocker of sodium (Na+) channels Medication
and blockade of this system has definite implications for reducing monitoring Factor
intravenously for migraines and cluster headaches. The original studies neuropathic pain disorders. Many of the so-called anti-convulsants by Mauskop and colleagues utilized ion-sensitive Mg++ electrodes to (better termed neuronal stabilizing agents) have this mechanism of measure ionized magnesium, a technique not commonly available.
action, at least, in their pharmacology. We have used IV lidocaine, Magnesium has primary effects as a physiologic antagonist to calcium.
with pulse oximetry monitoring, in the clinic for years in the treatment It also blocks NMDA-type glutamate excitatory amino acid activity, and of headache and pain flare-ups. The paradigm is to treat very slowly, nitric oxide synthesis and release, all of which are factors in migraine so as to saturate the Na+ channels and obtain the best possible pathophysiology or maintenance. It augments serotonin which may be blockade. Often, the response is short-lived (12-48 hours) and buys a direct means of blocking migraines. Multiple types of headaches, time for other treatments to be put in place. This is not a first-line including migraines, migrainous headaches, tension-type headache choice for migraines, but IV lidocaine may be part of a regimen of daily and cluster headaches respond to intravenous magnesium therapy.
or nearly-daily IV treatments to break a cycle of headache. IV We have found that although 1-2 grams of IV Mg++ given over lidocaine and Ca+ channel blockade (via IV MgSO4) can be particularly 30 minutes was very well tolerated and resulted in an almost 85% effective, along with IV dexamethasone.
reduction of intractable migraine, we are sometimes prepared to Combinations
increase the dose for a very refractory headache. In addition, Mg++ is the gold standard for muscle relaxation so it will relax muscle spasm in It seems like virtually every combination of IV medications at the neck area that accompanies refractory headache quite well. It also our disposal has been tried or given in my clinic at one time or another works very well to relax muscle spasm from any source, making it for refractory migraines, headaches or a combination of these with a very useful for flareups of pain with muscle spasm and cramping. In pain flareup. Of course, we make every effort to use one medication at all, this is a very easy IV to do or have done for your patient in the ED a time and to document carefully the percentage reduction to that successfully, perhaps many times before, might not work in the next *ACLS trained staff and crash cart is recommended on the premises particular situation and so we always have the next potentialtreatment "game plan". For example, one flareup may have muchmore accompanying muscle spasm, or burning pain. One must be flexibleand individualized in each treatment paradigm.


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