Ketamine Infusion Therapy
If you suffer from neuropathy, fibromyalgia, headaches, facial pain, pelvic pain, pudendal neuralgia or even CRPS, this amazing treatment may be an option for you. Intravenous ketamine infusion therapy is effective and supported by decades of evidence. And now we are even using infusions to treat depression!
What is Intravenous (IV) Infusion Therapy for Pain?
Intravenous infusion therapy is an exciting option for treating a variety of different pain syndromes ranging from fibromyalgia and small fiber neuropathy, to complex regional pain syndrome (CRPS) and reflex sympathetic dystrophy (RSD). The first reported uses of IV infusion therapy were in the 1960’s when physicians used it to treat post-operative pain.[1] By infusing special medications intravenously through the body, our doctors can effectively decrease pain at its source.
Intravenous ketamine infusion therapy is performed right in the comfort of our office. After the IV line is placed, you simply doze off and let the medications do the work.
Many different medications have been studied for use in intravenous infusion therapy therapy; some (i.e. ketamine and magnesium) are better at treating certain types of pain than others. IV therapy has shown to be an effective treatment for a wide variety of pain syndromes, including:
How Does it Work?
The procedure itself could not be simpler. An IV line is placed in the patient’s arm and the medication is flows in.
A variety of different medications can be used:
The most effective medications for neuropathic pain are KETAMINE AND MAGNESIUM. Depending on what your specific needs are, the medications are typically mixed with saline in an IV bag and infused slowly over minutes to hours, depending on the medication and/or protocol being used.
Consensus Guidelines on Ketamine
The American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists published consensus guidelines on the use of IV ketamine for chronic pain in the journal of Regional Anesthesia & Pain Medicine.
The authors created guidelines for indications; contraindications; whether there was evidence for a dose-response relationship, or a minimum or therapeutic dose range; and what constitutes a positive treatment response.
Ketamine is most effective when given through an IV. Unfortunately, not every patient has the time to get an infusion or get them as often as they need to keep their pain under control. That’s where ketamine nasal spray comes in handy – it comes in a small nose spray container like any other nasal mist medication that one would use for sinus congestion or allergies and works the same way. The medication is made by a specialty pharmacy upon request from your doctor. Low doses of ketamine from a nasal spray has shown to be an effective treatment unto its own for chronic pain and several mood disorders such as chronic depression – when used in conjunction with IV ketamine infusions, one can improve their pain control in the interim between their infusions and improve their overall quality of life!
There are a variety of medications one can use for intravenous infusion therapy, each with a unique mechanism of action.[2]
| IV Infusion Agent | Mechanism of Action |
|---|---|
| Lidocaine | Blocks sodium channels in the neuronal cell membrane that may potentially play a role in the pathogenesis and maintenance of both neuropathic and inflammatory pain |
| Ketamine | N-methyl-D-aspartate (NMDA) Receptor antagonist – therefore decreases sustained neuronal depolarization and excitatory transmission along afferent pain pathways in the dorsal horn of the spinal cord |
| Intravenous Immunoglobulin (IVIG) | Counteracts neuroinflammation by inhibiting complement deposition, neutralizing cytokines and growth factors, speeds up clearance of potentially pain-inducing auto-antibodies, and activation of macrophages and T cells through FcγRIIb receptor |
| Clonidine | α2-adrenergic receptor agonist believed to reduce of norepinephrine release from the α2-adrenergic in the periphery |
| Dexmedetomidine | Selective α2-adrenergic agonist which may have a role in treating painful conditions that are manipulated and/or attenuated by the sympathetic nervous system |
| Bisphosphonates | Decreases neuropathic bone pain by suppressing bone resorption via osteoclast inhibition, shortens osteoclast life span and decreasing the acidity of the local microenvironment |
| Magnesium | Competitive NMDA receptor antagonist that decreases acute and chronic pain by stabilizing abnormal nerve excitation |
Our practitioners prefer a combination of Ketamine and several other medications in small doses to provide a more comprehensive treatment. All of our infusions are performed in office using sub-anesthetic doses as opposed to inpatient infusions that last for 2 to 3 days at a time. Our infusion protocol typically consists of 2 infusions per week for 3 weeks – a total of 6 infusions. Each infusion lasts approximately 4 hours and the amount of medication used is based on your individual weight.
Intravenous infusion therapy is NOT a one-size-fits-all treatment – a true infusion center will tailor the medications and their ratios to the individual to optimize the benefits. For example, the amount of medication used in a ketamine infusion should vary not only based on weight but on how many infusions have been done and how the patient has responded to previous infusions.
The response to intravenous ketamine infusion therapy varies. Most patients require several treatments; the amount required depends on the medication and protocol being used. Some people respond immediately, but most will not feel the true benefit until several treatments have been administered.
The positive effects of infusions begin right away.
Is Infusion Therapy Right for Me?
If you suffer from chronic pain that has not responded to medication or other traditional treatment modalities, intravenous ketamine infusion therapy may be an option for you. The procedure is easy to administer and completely painless. There will be an initial evaluation with your doctor to see if you are eligible for IV infusion therapy.
Contact the Ainsworth Institute to set up an initial evaluation to find out if you are a candidate for Intravenous Infusion Therapy
Procedure - Patient Details
Your physician will first select the appropriate medication to be used in the infusion depending on your diagnosis and the type of pain you are experiencing. Then the office staff will weigh you to determine the proper amount of medication needed and mix it with saline in an IV bag. Next your physician will place an IV catheter in your arm or hand; this is no different than any other way an IV would be placed. And lastly, the medication is infused, taking 30 minutes to several hours. It’s that simple. During the infusion process, you will be placed on a monitor and your vitals will closely observed for the duration of the procedure. The key to intravenous infusion therapy is not how much medication goes in, rather how much over how long.
Benefits
IV Infusions were first introduced as a treatment for pain in 1963 when Bartell and Hutaserani used it to treat post-operative pain.[1] Most of the initial publications on the topic were centered on the use of Lidocaine. Studies have shown Lidocaine is effective in the treatment of:
- Neuropathic Pain[2]
- Centralized Pain[3]
- Diabetic Neuropathy[4][5]
- Peripheral Neuropathy[2]
- Headaches[6]
- Peripheral Nerve Injury[2]
- CRPS/RSD[7]
- Post-Herpetic Neuralgia (PHN)[8]
- Fibromyalgia[9]
- Persistent Post-Surgical Pain[10]
In the years following the discovery of the therapeutic effects of IV Lidocaine, physicians have tried a variety of other medications in search of even more effective agents.
- Clonidine – A medication used for controlling blood pressure. It was found to be effective in the treatment of postoperative pain[11] and CRPS.[12]
- Dexmedetomidine – A sedative used in Intensive Care Units and by anesthesiologists. It was discovered to be effective in treating CRPS.[13]
- Bisphosphonates – Typically used to prevent bone loss in osteoporosis, infusions with bisphosphonates can be used to treat neuropathic bone pain and CRPS.[14]
- Magnesium – An important molecule in the formation of DNA and ATP which can be used to treat post-operative pain and post-thoracotomy pain.[15]
One of the most popular medications used presently with infusion therapy is Ketamine. Originally used by the military during the Vietnam War as a “field anesthesia,” Ketamine is a potent NMDA receptor antagonist – a receptor responsible for controlling synaptic plasticity and memory function. Medically, it has been used as an anesthetic for children, asthmatics, those with Chronic Obstructive Pulmonary Disease (COPD), and patients at risk for hypotension. Non-medically, Ketamine was used popular “club drug” in the 1990’s. As it pertains to the treatment of pain, Ketamine is an extremely effective medication for a variety of pain syndromes, such as:
- Central Neuropathic Pain[16]
- Peripheral Neuropathy[17]
- CRPS/RSD[18]
- Peripheral Nerve Injury and PHN[17]
- Cancer Pain[19]
- Fibromyalgia[20]
At present, the attention of the medical community has turned to the use of IVIG for intravenous infusions. Recent data has emerged suggesting peripheral and central neuroimmune activation is necessary to sustain chronic pain.[21] Research has also suggested that the immune system plays a role in the release of pro-inflammatory cytokines and neuropeptides like Substance P (a pain causing compound) that can lead to pain states such as CRPS. IVIG is now being used to treat:
- Small Fiber Neuropathy[22]
- CRPS/RSD[21]
- Chronic Inflammatory Demyelating Polyneuropathy (CIDP)
- Sciatica[23]
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- (Full Presentation) Top 5 Things Pain Patients Need To Know During The Coronavirus Pandemic - March 30, 2020
Risk Factors
As with any medical procedure, there is always a risk of potential complication. The most common complaints one might experience with infusion therapy are associated with the medication being used. In most cases, the symptoms or side effects will abate once the infusion is completed or stopped.
The most important thing to address before considering IV infusion therapy is that many painful conditions can adequately be treated through other established treatment methods and medications. While having been available for over 50 years as a medical treatment and effective in many cases, IV infusions are still considered somewhat experimental. The Ainsworth Institute recommends this particular treatment modality be pursued only after conservative treatments and conventional medications have been exhausted. As with anything considered experimental, results may vary and not every patient will have success.
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Evidence of Performance
There is an abundance of scientific evidence supporting the use of IV infusions for the treatment of a variety of different types of pain.
Complex Regional Pain Syndrome (CRPS) & Reflex Sympathetic Dystrophy (RSD): CRPS/RSD have been studied extensively as they pertain to IV infusion therapy. There are a plethora of well-designed studies on the use of infusions for the treatment of CRPS/RSD and most reported success. In 2000, Wallace and colleagues performed a randomized, double-blind, placebo controlled crossover study on the use of IV Lidocaine for CRPS.[24] The authors reported significant changes in response to temperature-induced pain. In another study by Tremont-Lukats et al on 32 patients with CRPS, the author found that treating patients with 5mg/kg of IV Lidocaine had a significant effect on pain intensity.
There were also a number of studies on IV infusions of Bisphosphonates[14][25] for the treatment of CRPS, as well as IVIG,[21] Dexmedetomidine[13] and Clonidine[11][12] – all reporting success.
Ketamine infusions seem to show the most promise in the realm of CRPS as there are a multitude of studies on the topic with most reporting varying degrees of success. In 2009, Schwartzman et al reported on a double-blind, randomized-controlled study on the use of outpatient ketamine infusions to treat CRPS.[18] In addition to reporting a statistically significant decrease in overall pain, those treated with ketamine also had decreased burning and improved sleep.
Centralized Pain: Centralized pain, or Central Pain Syndrome, can present a particular challenge to physicians when endeavoring to treat it. The difficulty in understanding this especially enigmatic syndrome is matched only by the struggle one will encounter when attempting to find an adequate treatment regimen. Centralized pain can present after any number or events – Parkinson’s disease, strokes, trauma (motor vehicle accident) or multiple sclerosis. Medications are rarely effective. Infusions, on the other hand, have demonstrated good results in a number or published studies on the topic. One such study was published by Eide et al on the use of IV Ketamine in the onset of pain after a spinal cord injury. In this study, 9 patients who were given infusions of Ketamine reported decreases in continuous and evoked pain.[16]
Neuropathy & Diabetic Peripheral Polyneuropathy (DPPN): The use of IV infusions to treat neuropathy and neuropathic pain is WELL DOCUMENTED. The majority of the studies at present are focused on the use of Lidocaine, Ketamine, and more presently IVIG.
Viola and colleagues published a study on the use of IV Lidocaine in 15 patients with painful diabetic neuropathy. The authors reported a significant reduction in pain.[4] Kastrup et al also published on the effects of IV Lidocaine on peripheral neuropathy. In this study, the authors reported a significant decrease in pain with patients treated at a higher dose (5mg/kg).[5]
Most reported successes on the use of infusion therapy for the treatment of neuropathy and neuropathic pain appear to be with IV Ketamine. In 2003, Jorum et al reported on a double-blind, placebo-controlled, crossover study where IV Ketamine was evaluated in the treatment of peripheral neuropathy. The authors demonstrated that Ketamine caused a decrease in hyperalgesia and allodynia.[26]
In recent years, those interested in neuropathy and neuropathic pain have turned their attention to the use of IVIG. There are limited studies available on the use of IVIG, but the initial data appears promising. Currently, IVIG is being used to treat CIPD, small fiber neuropathy, and multifocal motor neuropathy (off-label).
Headaches: In a study by Williams and Stark, 71 patients presenting with chronic daily headaches were treated with IV Lidocaine. The patients were treated for a mean of 8.7 days at a dose of 2mg/kg. Of those treated, 90% reported an improvement in symptoms or a complete absence of headaches upon completion of the treatment. At 1-month and 6-month follow-up visits, the patients reported a 76% and 70% overall improvement in their symptoms, respectively.[6]
Post Herpetic Neuralgia (PHN): PHN has become a particularly relevant topic as of late. There are a number of treatments now available, such as pregabalin and topic lidocaine patches. As with any type of neuropathic pain, there is almost never a “one size fits all” treatment. There are several studies on PHN that was refractory to conventional treatment but subsequently responsive to IV infusions of Lidocaine[9] or Ketamine.[27]
Fibromyalgia: As anyone with Fibromyalgia will tell you, oral medications like pregabalin or duloxetine are rarely effective if at all. As such, physicians have been in search of additional treatment modalities for this particularly troubling pain syndrome. Several published studies on IV infusion for the treatment of Fibromyalgia have reported good results. In a study by Graven-Neilsen et al, patients with Fibromylagia were given IV Ketamine infusions on an outpatient basis. The study was designed as a randomized, double-blind crossover study involving 29 patients. The authors reported a decrease in pain at rest, local and referred pain areas, the span between the pain threshold to single and repeated intramuscular stimuli, and increased the pain pressure pain intolerance.[20]
In a study by Sorensen et al in 1995, the authors conducted a double-blind placebo-controlled crossover study on the use of IV Lidocaine on 12 patients with Fibromyalgia. The authors used a higher dose (5mg/kg) than conventionally reported in most medical journals when utilizing Lidocaine intravenously, and reported statistically significant changes in tender points, muscle strength and muscle endurance.[9]
Cancer Pain: The pain associated with cancer is typically treated with a combination of opioid pain medications and/or nerve blocks. Unfortunately for some, this regimen does not provide optimal relief. IV infusions of Ketamine have been shown to provide significant relief and offer a degree of comfort for those suffering from this terrible disease. In 2000, Mercadante et al published a paper on the use of IV Ketamine on patients with cancer reporting uncontrolled pain despite the usage of morphine. In those given IV Ketamine, there was a significant decrease in reported pain.[19]
Persistent Post-Surgical Pain: In most cases, pain after surgery is easily controlled with oral and/or IV pain medications. As time passes and wounds heal, the need for such treatments will decrease. In some cases, the pain will persist well beyond the expected need for these medications. Anecdotally, many institutions have reported overwhelming successes in these cases with the addition of IV Ketamine – particularly after orthopedic procedures such as joint replacements or reconstructions. Lidocaine, on the other hand, has a well-documented history of decreasing the need for opiate in the post-surgical setting and has been shown to improve the course of recovery.[2]
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- (Full Presentation) Top 5 Things Pain Patients Need To Know During The Coronavirus Pandemic - March 30, 2020
Schedule an Appointment Today
If you are suffering from chronic pain and would like to see if you could be a candidate for this exciting treatment option, contact the Ainsworth Institute of Pain Management today. Schedule an appointment with one of our Board Certified Physicians to learn more about IV Ketamine Infusion Therapy.
References
[1] Bartlett EE, Hutaserani Q. Lidocaine (xylocaine) for the relief of postoperative pain. J Am Med Womens Assoc. 1962;17:809-15. Boas RA, Covino BG, Shahnarian. Analgesic responses to i.v. lignocaine. Br J Anaesth 1982;86:235-239.
[2] Kosharskyy B, Almonte W, Shaparin N, et al. Intravenous Infusions in Chronic Pain Management. Pain Physician 2013; 16:231-49.
[3] Wechsler RJ, Frank ED, Halpern EH, et al. Percutaneous lumbar sympathetic plexus catheter placement for short- and long-term pain relief: CT technique and results. J Comp Assisted Tomography 1998; 22:518-23.
[4] Viola V, Newnham H, Simpson R. Treatment of intractable painful diabetic neuropathy with intravenous lignocaine. J Diabetes Complications. 2006; 20:34-9.
[5] Kastrup J, Petersen P, Dejgard A, et al. Intravenous lidocaine—a new treatment of chronic painful diabetic neuropathy? Pain 1987; 28:69-75.
[6] Williams DR, Stark RJ. Intravenous lignocaine (lidocaine) infusion for the treatment of chronic daily headache with substantial medication overuse 2003; 23:963-71.
[7] Tretmont-Lukats IW, Challapalli V, McNicol ED, et al. Systemic administration of local anesthetics to relieve neuropathic pain: A systemic review and meta-analysis. Anesth Analg 2005; 101:1738-49.
[8] Rowbothman MC, Reisner-Keller LA, Fields HL. Both intravenous lidocaine and morphine reduce the pain of post-herpetic neuralgia. Neurology 1991; 41:1024-8.
[9] Sorensen J, Bengtssn A, Backman E, et al. Pain analysis in patients with fibromyalgia, effects of intravenous morphine, lidocaine and ketamine. Scan J Rheumatol 1995; 24
[10] Grigoras A, Lee P, Sattar, et al. Perioperative intravenous lidocaine decreases the incidence of persistent pain after breast surgery. Clin J Pain 2012; 28:567-72.
[11] Reuben SS, Sklar J. Intravenous Regional Anesthesia with Clonidine in Management of Complex Regional Pain Syndrome of the Knee. J Clin Anesth. 2002;14:97-91.
[12] Nama S, Meenan DR, Fritz WT. Ketamine and Adjuvant Demedetomidine when Treating Acutre Pain from CRPS. Pain Physician. 2010;13:365-68.
[13] Fischer SG, Collins S, Boogaard S, et al. Intravenous Magnesium for Chronic Complex Regional Pain Syndyome Type 1 (CRPS-1). Pain Medicine 2013; 14:1388-99.
[14] Kubalek I, Fain O, Paries J, et al. Treatment of reflex sympathetic dystrophy with pamidronate: 29 cases. Rheumatology (Oxford) 2001; 40:1394-7.
[15] Quibell, Rachel; Prommer, Eric E., Mihalyo, Mary, Twycross, Robert, Wilcock, Andrew (1 March 2011). “Ketamine*”. Journal of Pain and Symptom Management 41 (3): 640–649.
[16] Eide PK, Stubhaug A, Stenehjem AE. Central dysesthesia pain after traumatic spinal cord injury is dependent on N-methyl-D-aspartate receptor activation. Neurosurgery 1995; 37:1080-7.
[17] Eichenberger U, Neff F, Sveticic G, et al. Chronic phantom limb pain: The effects of calcitonin, ketamine, and their combination on pain and sensory thresholds, Anesth Analg 2008; 106:1265-73.
[18] Schwartzman RJ, Alexander GM, Grothusen JR, et al. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: A double-blind placebo controlled study. Pain. 2009;147:107-15.
[19] Mercadante S, Arcuri E, Tirelli W, et al. Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: A randomized, controlled, double-blind, crossover, double-dose study. J Pain Symptom Manage 2000; 20:246-52.
[20] Graven-Nielsen T, Aspegren Kendall S, Henriksson KG, et al. Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients. Pain 2000; 85;483-91.
[21] Goebel A, Baranowski AP, Maurer K, et al. Intravenous immunoglobulin treatment of complex regional pain syndrome: a randomized, controlled trial. Ann Intern Med. 2010; 152:152-8.
[22] Goebel A, Netal S, Schedal R, et al. Human pooled immunoglobulin in the treatment of chronic pain syndromes. Pain Med. 2002; 3:119-27.
[23] Medlin F, Zekeridou A, Renaud S, et al. Favorable outcome of an acute complex regional pain syndrome with immunoglobulin infusions. Clin J Pain 2013; 29:e33-4.
[24] Wallace MS, Ridgeway BM, Leung AY, et al. Concentration effect relationship of intravenous lidocaine on allodynia of complex regional pain syndromes I and II. Anesthesiology 2000; 92:75-83.
[25] Varenna M, Adami S, Rossini M, et al. Treatment of complex regional pain syndrome type I with neridronate: A randomized, double-blind, placebo-controlled study. Rheumatology (Oxford) 2013; 53:534-42.
[26] Jorum E, Warncke T, Stubhaug A. Cold allodynia and hyperalgesia in neuropathic pain: The effect of N-methyl-D-aspartate (NMDA) receptor antagonist ketamine-a double blind, cross-over comparison with alfentanil and placebo. Pain 2003; 101:229-35.
[27] Gottrup H, Bach FW, Juhl G, et al. Differential effect of ketamine and lidocaine on spontaneous and mechanical evoked pain in patients with nerve injury pain. Anesthesiology 2006; 104:527-36.
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- (Full Presentation) Top 5 Things Pain Patients Need To Know During The Coronavirus Pandemic - March 30, 2020