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10 Articles in Volume 17, Issue #5
Cross-Linked Hyaluronic Acid Injection for Neuropathic Pain
Discussing Migraine: What to Try When Nothing Is Working
IV Propofol for Treatment of Chronic Intractable Cluster Headache: A Case Series
Letters to the Editor: Rapid Opioid Metabolizer, Intractable Pain, Adrenal Suppression, Traumatic Brain Injury
Migraine Treatment: What’s Old, What’s New
Schizophrenia Spectrum and Chronic Pain: Is Pain Insensitivity a Myth?
Spinal Fluid Flow and Pain Management
Step-by-Step Technique for Targeting Superficial Radial Nerve Pain
The Primary Care Provider’s Role in Diagnosing and Treating Rheumatoid Arthritis
What is the appropriate use of phone texting between physicians and patients?

IV Propofol for Treatment of Chronic Intractable Cluster Headache: A Case Series

Employing an IV anesthetic agent may be highly effective in reducing otherwise unresponsive refractory migraines, making it worthy of consideration as a self-administration option for appropriate patients.

Sometimes, you serendipitously stumble upon interesting results. I had that experience with the intravenous (IV) anesthetic agent propofol. I use this agent routinely in the clinic as a mild conscious sedative prior to epidural steroid, facet, and other nerve blocks. Some patients who had concomitant migraines at the time of their blocks would comment that their migraine went away before the block was actually performed. This occurred after propofol was given via IV in low conscious sedation doses.

After researching the literature, I found no other mention of this agent in treating migraines or pain. Therefore, I undertook a formal open-label study in the headache clinic to treat refractory migraines unresponsive to usual abortive approaches. A cohort of 77 patients was treated, and the results were dramatic.1

IV propofol is a reasonable option for intractable cluster headaches.

Propofol is the most effective IV agent that I had ever employed, with a 95% success rate in reducing ongoing migraine headaches. The total average dose (subanesthetic) was only 120 mg, given slowly in small, successive increments by IV push, and in small, divided doses. Some patients had features of intractable cluster headaches (CH) and other very painful face-pain syndromes, including trigeminal neuralgia.      

The following 6 case reports present my experience using low-dose IV propofol for the management of intractable CH in my outpatient clinic.

IV Propofol

Propofol is an IV anesthetic with a very good safety profile, and it has been used since the 1960s. Millions of doses are used each year in the United States and worldwide, either as sole anesthesia for surgery and procedures, or as part of anesthesia induction and maintenance.

The specific pharmacologic agonist effect of propofol, with sole effects on subtypes of the gamma-aminobutyric acid (GABA)-A receptor, is a unique mechanism of action, shared partly by other anesthetic agents. Propofol augments inhibitory tone in the central nervous system (CNS) and decreases the rate of dissociation of the GABA from its receptor complex, thereby increasing the duration of the GABA-activated opening of the chloride channel with resulting hyperpolarization of cell membranes. Subanesthetically, it has relative specificity for subsets of GABA-A receptors.

Originally, I showed propofol to be highly effective as subanesthetic IV dosing in eradicating intractable migraines and other headaches, and in many painful disorders.1-6 I am currently exploring its efficacy in eliminating nausea accompanying migraines, headaches, and pain in ultra-low IV doses (20-40 mg per dose).

Cluster Headaches

Cluster headaches are considered among the most disabling of the trigeminal autonomic cephalalgias (TACs), which include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headaches. CH have been described under various eponyms since 1867 (eg, red migraine of Moellendorf), and they are classified as episodic or chronic, largely based on the duration of remissions from the painful unilateral episodes.

In a recent compendium of headache medicine, 13 chapters were devoted to CH and other primarily unilateral TACs.8 CH represents a very small fraction of the total number of migraineurs, typically less than 1% in prevalence. To keep this in perspective, there are more than 100 million people in the United States with headaches, and about 40% of them exhibit migraines or migrainous headaches. This is a small but severely disabled clinical population, and they are extremely difficult to treat in the clinical realm. Although the gold standard for treating migraine—the triptans—have been successfully used, they typically are not effective at treating CH, especially if it has become chronic.

While CH was originally thought to be a short-lived unilateral head pain that was more common in men than women (4:1) (as opposed to migraines, which typically present more in women [3:1]), there has been a decrease in sex ratio over the years. The current observed ratio shows that men are twice as likely to have CH as women (2:1).

Study Design

Because I have a private outpatient clinic that functions, in part, as an emergent care setting for IV treatment of intractable headache and pain disorders, I have extended and amplified the use of several IV anesthetic agents (eg, propofol, ketamine, and lidocaine), and used many so-called “standard” medications over the past 20 years. Some medications are quite proprietary, as they do not exist commercially in this country (eg, IV baclofen and tramadol) and are compounded, based on my research of their physiochemical properties.

Part of the mission of my practice is to provide active intervention to relieve disabling symptoms in a way that may not be possible in the community at large or in a local emergency department (ED) setting. This review attempts to show safety and efficacy of subanesthetic IV propofol in a monitored setting in treating refractory ongoing CH and other TACs.

Whether the patient is in acute distress with a disabling migraine or other pain disorder (often both), or has had an escalating or intractable course of pain or headaches of any nature, we are equipped with the materials necessary for the safe use of IV treatments (dimmable lights in treatment rooms, IV treatment chairs, pulse oximetry monitoring, crash cart, and ACLS/CPR trained personnel [RN and MD] on-site).

All treatments are preceded by an evaluation, including vital signs and physical/neurological examination, to assess the course of treatment. In many cases, the patient is in unremitting pain and headache, and I treat him or her with newer medication approaches that most likely have not been tried or employed. In most cases, it is likely that IV therapies were not used at all in prior treatments (except for opioids, steroids, and antinauseants in the ED). Knowing which medications are compatible with each other in the IV solution (usually normal saline) at the same time can save time in the treatment process strategy. Ideally, 1 agent is tried at a time, starting with low doses based on body weight, and progressing over several administered timed IV propofol dosages. The patient’s rating of the severity of his or her painful symptoms is a vital component of the overall treatment plan in the clinic. Dosages of IV propofol were likely to be higher than those used for refractory migraine headaches in the clinic, as originally studied.1

After a treatment is decided upon, IV access is established (antecubital or other site) by myself or a nurse. Pulse oximetry monitoring is used for every IV or intramuscular (IM) treatment, even if the treatment is IV magnesium, valproate, dihydroergotamine mesylate (DHE), or other non-anesthetic agent. Patients are asked to rate their symptoms on a 0-10 Visual Analog Scale (VAS) or a 0-11 Likert scale before starting any treatment. Ratings for individual symptoms are also taken approximately every 15 to 30 minutes during and after the infusion of IV medication(s), and this includes any accompanying spasm, allodynia, or neck/face pain symptoms. If the patient also has anxiety and/or depression, the Hamilton Anxiety Rating Scale (Ham-A) and Hamilton Depression Rating Scale (Ham-D) are completed before any initial IV treatment and again 3 to 5 days after the treatment cycle.

Once the IV is running and IV propofol dosages are calculated, subanesthetic dosing begins. Typical individual doses with IV propofol are 30-40 mg. Because propofol typically burns at the administration site, 1 mL of 2% lidocaine is admixed with the propofol in the same syringe. It has been my experience that this dose of lidocaine is ineffective by itself in reducing migraines, and certainly does not affect the course or severity of refractory CH. Patients are asked to rate their pain, migraine, and/or headache symptoms, including associated nausea, pain, spasm, photo/phonophobia, and allodynia, every 15 minutes. If there is significant nausea at the outset, low-dose propofol IV or 2 mg to 4 mg of ondansetron is given via IM or IV immediately after IV placement.

IV propofol can be given in intermittent dosing over several hours and repeated on succeeding days if the patient lives a long distance away or we have a limited number of days of treatment.

CASE 1: History of Migraine and CH

A 39-year-old man with a history of migraine and CH since age 17 had a sudden onset of CH beginning at 1 to 2 AM, after no such episodes for at least 3 years. They were right-sided and accompanied by nausea, severe light sensitivity, facial allodynia, and neck pain. They occurred 3 to 5 times per day, and he came into my clinic about 4 to 5 weeks after the episodes had begun. He had been treated in a local ED with oxygen via face mask, opiates, steroids, and antinauseants. Nothing helped the pattern. He had also failed many oral prophylaxis agents for prior intractable CH episodes, including verapamil (high-dose), lithium, opioids, divalproex sodium, lamotrigine, topiramate, and 4 other agents.

Initially, he rated his headache pain as 10 out of 10 with vomiting. An IV line was placed with pulse oximetry monitoring, and IV ondansetron (4 mg) helped the nausea and vomiting, but they had no effect on the CH episode. IV propofol (100 mg with 40 mg 2% lidocaine) was pushed slowly over 3 to 5 minutes. After he woke up, the patient stated that the CH pain had reduced by 25%. A second dose of the same mixture was given. The second dose of IV propofol further reduced the headache severity to about 50% of the original severity, with the nausea all but gone. A third and fourth set of propofol doses were administered, and his CH pain was rated as 1 out of 10 in severity, with residual facial and eye soreness.

I discontinued treatment at that point and gave him tizanidine (8-12 mg) to take before bedtime that night. He had no further CH episodes that evening or overnight. The following afternoon, he had only 1 episode, rated as 3 out of 10 in severity. He returned to the clinic the day after for further treatment with IV propofol. He was given IV propofol (300 mg in 4 divided doses) as described. He then began a short oral course of dexamethasone (5 days) with resolution of the CH  flare-up.

Thus, I terminated an ongoing intractable CH flare-up with the IV propofol, which had worked more efficaciously than prior treatments (both IV and oral).

CASE 2: 40-Year History of CH

A 72-year-old retired police officer with more than 40 years of chronic CH (left-sided), with a family history of CH and migraine, presented with an unremitting flare-up of left-sided head pain. It was accompanied by vomiting, facial and neck pain, lacrimation, and eye droop with reddened conjunctival tissue of his left eye. The CH was rated as 10 out of 10 in severity. He also had a history of neck, back, shoulder, and knee injuries throughout his working life as a police officer.

The patient’s medication history included many prophylaxis medications, including oxygen by face mask, but he never received any IV medication strategies. He saw me during a major winter flare-up of CH. They had worsened from their usual baseline pattern. I started an IV with pulse oximetry monitoring in the clinic, and gave him low-dose propofol IV to reduce nausea and ensure he had no negative effects. I used IV propofol to eliminate his intractable CH at weekly intervals for more than a year at doses of 80 mg every 15 minutes. However, the inconvenience for the patient to come to the clinic, along with the presence of severe headaches overnight and on weekends, prompted me to refer him to a specialist who implanted an occipital nerve stimulator. The device reduced his chronic CH occurrence by more than 90% after implantation.

The remaining breakthrough CH are still successfully treated with IV propofol or IM ketamine via suboccipital nerve blocks in the clinic. Unfortunately, the patient’s headaches can occur on weekends or when the clinic is closed, and a different and effective delivery system for the propofol would be a large step forward in this severe case example.

CASE 3: CH After Car Accident

A 55-year-old woman who sustained a traumatic brain injury in a car accident developed severe, right-sided CH that would wake her from sleep. They were stabbing and pounding, with facial numbness, allodynia, confusion, and severe nausea and vomiting.

She had a history of migraines with aura and perimenstrual migraines since age 14. She had a family history of migraines but not familial CH—the CH began only after her accident. While her severe nausea was eliminated with IV propofol at 50 mg doses, her right-sided migraine and CH were only reduced by 20% to 30%.

I took a more aggressive approach, giving her 80 mg IV doses of propofol every 10 to 15 minutes for up to 8 doses, before the CH would break and resolve. Several days of daily IV propofol treatment was beneficial, and allowed her to have up to 2 weeks of reduced pain intensity and relative freedom from the debilitating post-traumatic CH.                

The need to treat repeated episodes of CH, the distance from the clinic, and the lack of ability to use IV propofol in a facility closer to home put severe limitations on the patient’s treatment. If a more user-friendly dosing system had been available closer to her home, such as an inhalable form of propofol, the patient may have received further reduction in CH pattern and improvement in her quality of life.

CASE 4: Chronic Pain, Migraine, and CH  

A 42-year-old cattle rancher had a history of migraines and left-sided CH since his early 20s, along with neck and back pain since age 15.  He had experienced a flare-up of unremitting left-sided CH after several months of respite, having had them for more than 20 years at intervals of 1 to 2 years and lasting up to 6 months. He had failed numerous prophylaxis treatments with many medications, including opioids, although these helped his chronic neck and back pain.

When he presented at the clinic, he was unable to work due to daily CH episodes. Vomiting; facial numbness; lacrimation; allodynia of his face, head, and neck; and stabbing ice pick-like jolts with confusion and dizziness were daily features. Most of the CH were left-sided, but they could occasionally be right-sided. They occurred 4 to 6 times a day.

Initially he was treated with IV propofol for 5 days, which successfully reduced the frequency and severity of the CH by 80%. IV propofol (60-80 mg per dose every 20 to 30 minutes for a total of 1,200 mg per treatment day) was used with a high degree of safety and efficacy. IV magnesium treatment (2-3 g) also helped in his overall treatment plan. His migraines and spine pain were also greatly reduced, as was his chronic depression, especially with the addition of IV ketamine (100-299 mg given after the IV propofol). At the time of this report, the patient had just successfully finished his fourth treatment cycle with IV propofol.  

The patient is being considered for an occipital nerve stimulator to help manage flare-ups at home. He likely would have benefited from a propofol delivery system that could be used at home under local physician supervision, as he lives 150 miles from my clinic.  

CASE 5: Bilateral CH

A 56-year-old woman with a history of chronic migraines presented to my clinic after experiencing 3- to 4-month-long episodes of unremitting bilateral CH. Though the CH were mostly left-sided, she experienced stabbing head pain with facial allodynia, facial droop, confusion, extreme dizziness, and vertigo. She was awakened from a sound sleep by the head jolts around 3 am each morning. Throwing up would temporarily abate the symptoms. Early use of oxygen had some beneficial effect for 10 minutes, but it lost its ability to reduce the headache. She also suffered from extreme anxiety and depression for many years, always exacerbated by her cluster-like headaches. She was trying to work full time when the CH episode came on. She had partial success 2 years prior with IV lidocaine, magnesium, baclofen, and ketamine in my clinic. She lives 1.5 hours from my clinic.

At this visit, the patient was given 70-80 mg propofol IV at 20-minute intervals in the clinic. With repeated dosing, up to an average of 800-1,200 mg propofol per treatment, she reduced the daily paroxysms by approximately 80% (from 7 to 8 episodes to 1 to 2 episodes per day). Her CH pain severity reduced from 10 out of 10 to 2 out of 10, and it lasted about 3 to 4 weeks.

She manages pain with prophylaxis medications—topiramate, tizanidine, and oxcarbazepine—but has no local resources to help treat any future flare-ups of cluster headache.


A 26-year-old woman with a history of migraines since age 12 developed complex regional pain syndrome (CRPS) and new onset of unilateral face pain and head paroxysms after a unicycle accident. Both the CRPS and CH were resistant to multiple attempts at prophylaxis therapy. She saw headache specialists when she lived on the West Coast before moving back home to Texas.

The headaches had progressed to a daily intractable cluster-like headache disorder over the course of 7 months. I opted to use IV propofol in the clinic at 50 mg in 1 to 2 doses, which markedly reduced her nausea. After increasing the propofol dose to 80 mg per dose, 6 to 8 doses nearly eradicated the headache.

Three to 4 days of such treatment allowed the CH episode to abate, leaving her with her usual migraine and CRPS pain pattern, though both were markedly reduced as well. Her anxiety and depression scores were lowered by more than half, and her mood improved greatly. Neck, back, and hip pain were also much easier to manage with less pain medication. I also prescribed ketamine in a timed-release base, 75 mg per dose, 3 times a day, because she lives more than 3 hours from the clinic. She has not had any more CH flare-ups thus far.


The dedicated use of IV pharmacological agents with differing but often complementary and even synergistic effects may result in reductions in chronic pain and headache patterns. Not everything works for everyone, and multiple infusion trials with dosage adjustments are often needed to gain the benefits of IV therapy.

The cases presented are anecdotal, but they represent the extreme end of the spectrum of a rare and very disabling TAC, such as CH. In my experience, one-time IV treatment and rapid infusions do not offer long-term benefits to the patient. Patients who were treated more aggressively, repeatedly, or for longer periods of time may benefit from this approach.

Therefore, alternative delivery systems that are more self-directed may represent a novel change in effective treatment. Aggressive oral inhalational treatment is an alternative method that may maintain the response to IV propofol treatment, at least in theory. Therefore, it is most desirable to find a route of administration for propofol that not only has the potential to reduce or eliminate the CH episode, but also has the convenience of a self-administered dosing system.

Reduction and/or removal of opioids is always a goal, particularly in chronic daily headache and neuropathic pain syndromes. Ketamine, low-dose naltrexone, human chorionic gonadotropin (hCG), and other approaches like low-dose buprenorphine or use of neuronal stabilizing agents may also be useful in reducing opiate usage. Ketamine, if successful via IV, can be considered in other delivery systems. Likewise, lidocaine offers the possibility of trying many neuronal stabilizing oral agents that block sodium channels. IV lidocaine, by itself, indiscriminately blocks many, if not most, sodium channels, while different oral agents are more limited in their pharmacological blockade.

Thus, insoluble medications, such as propofol, which currently must be given via IV, may be considered for novel delivery systems or devices for administration. This would represent a large step forward in the rapid, at-home treatment of severe, debilitating CH and other rare pain syndromes that arise at night or very quickly. The increased costs and inconvenience of IV propofol in an outpatient setting, both to the patient and the clinician and staff, are limiting factors in this treatment scenario.

Self-administration by the patient, with appropriate safeguards, may represent a new and efficacious degree of treatment for this and other rare disabling disorders, such as hemicrania continua, paroxysmal hemicrania, trigeminal neuralgia, CRPS, vulvodynia, pudendal nerve entrapment, atypical face pain syndromes, and other rare and highly disabling syndromes.

Last updated on: June 15, 2017
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