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Reflex Sympathetic Dystrophy (RSD) (CRPS) Message Board

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Low doses of common anesthetic may relieve debilitating pain syndrome
Thursday, September 23, 2004

Hershey, Pa. -- Limited, low-dose infusions of a widely used anesthetic drug may relieve the often intolerable and debilitating pain of Complex Regional Pain Syndrome (CRPS), a Penn State Milton S. Hershey Medical Center researcher found.

"This pain disorder is very difficult to treat. Currently-available therapies, at best, oftentimes only make the pain bearable for many CRPS sufferers," said Ronald E. Harbut, assistant professor of anesthesiology, Penn State Hershey Medical Center. "In our retrospective study, some patients who underwent a low-dose infusion of ketamine experienced complete relief from their pain, suggesting that this therapy may be an option for some patients with intolerable CRPS."

The study, titled "Subanesthetic Ketamine Infusion Therapy: A Retrospective Analysis of a Novel Therapeutic Approach to Complex Regional Pain Syndrome," was published in the September 2004 issue of Pain Medicine, the official journal of the American Academy of Pain Medicine.

CRPS (type I), also known as Reflex Sympathetic Dystrophy Syndrome (RSD), affects between 1.5 million and 7 million people in the United States and often is marked by a severe, burning pain that can be very resistant to conventional therapies. The pain frequently begins after a fall or sprain, a fracture, infections, surgery or trauma. The pain often is present in the limbs with possible later spreading to other parts of the body. Patients also may experience skin-color changes, sweating abnormalities, tissue swelling, and an extreme sensitivity to light touch or vibrations. The McGill Pain Index rates CRPS as 42 on the scale of 50, with 50 being most severe.

Although much is unknown about CRPS, the pain experienced by patients appears to be caused by over-stimulation of a nerve receptor complex involved in the process of feeling pain. Therefore, efforts have been made to treat CRPS by blocking these receptors. Whereas most pain medications do not effectively block these receptor complexes (often referred to as NMDA-receptors), ketamine does.

The study was initiated by Graeme E. Correll, and involved reviewing the medical records of 33 patients with CRPS treated by Correll. The patients, some of whom had failed to obtain pain relief from conventional therapies, were treated with low-dose inpatient intravenous infusions of ketamine between 1996 and 2002 in Mackay, Queensland, Australia. Ketamine infusions were started at very low rates and were slowly increased in small increments as tolerated by selected patients. The therapy was then continued as long as the patient tolerated the drug and continued to benefit from it. Treatment cycles generally continued until the patient experienced complete pain relief; until initially-obtained relief would not improve any further; or for no more than 48 hours if there was no improvement in pain severity.

Pain was completely relieved for 25 (76 percent) patients, partially relieved for six (18 percent) patients and not relieved for two (6 percent) patients. Although the relief obtained did not last indefinitely, 54 percent remained completely pain-free for three months or more and 31 percent for six months or more. For 12 patients who received a second treatment, 58 percent experienced relief for one year or more with 33 percent remaining pain-free for more than three years.

The most frequent side-effect reported was a feeling of inebriation. Hallucinations occurred in six patients with less frequent side effects including complaints of light-headedness, dizziness and nausea. Liver enzymes were altered in four patients but resolved after therapy.

The exact mechanism of sustained pain relief is unknown, but is currently under study at Penn State Hershey Medical Center. Harbut likened the ketamine treatment to the healing of a broken bone. "If someone breaks a bone and you simply put the two pieces back together, they won't immediately heal. However, if you add a splint and hold the bones steady for a period of time, and then later take away the splint the bone is healed. I believe that the ketamine treatment does something similar that lends support and allows the nerve cells to heal themselves, so that when you take away the ketamine, the pain is reduced or gone."

Harbut began studying CRPS with Correll during a work assignment Harbut volunteered to take in far northern Queensland, Australia, in the late 1990s. Correll was developing a therapy for CRPS but wanted a collaborator to formally research the effectiveness of the therapy. Harbut brought Correll's method back to the United States, where he developed an FDA-approved study protocol (used at the Mayo Clinic Scottsdale) using this method to attempt to treat post herpetic neuralgia, another pain disorder with symptoms somewhat similar to CRPS. At the same time, Harbut met a patient who had suffered with intolerable CRPS for nine years who wanted to try this new therapy. That patient became the first successful treatment of intractable CRPS in the United States. (A Case Report of this treatment appeared in the June 2002 issue of Pain Medicine.)

"Ultimately, we want to find a way to improve the quality of life for those who suffer with intolerable CRPS, some of whom at times contemplate suicide because of their endless pain," Harbut said. "Although optimistic about these early findings, certainly more study is needed to further establish the safety and efficacy of this novel approach." A large clinical study currently is planned and under development at Penn State Hershey Medical Center.

In addition to Harbut and Correll, the team involved in this study included: Jahangir Maleki and Edward J. Gracely, Drexel University College of Medicine; and Jesse J. Muir, Mayo Clinic Scottsdale.
Diana, you should be able to get some information directly from your doctor, since he is involved in it. At the RSD conference, one of the lectures was on new treatments. As I understand it from looking at the Powerpoint notes we have, Dr. Schwartzman has something to do with two different ketamine techniques. The notes say that allodynia and hyperalgesia can be related to central sensitization and increased N-methly-D-aspartate (NMDA) receptor activity. Ketamine is an NMDA receptor antagonist. The Ketamine coma technique was performed in Germany with 18 patients thusfar, all with severe CRPS. The coma technique was 5 days with .7 to .8 mg/kg per hour IV with Versed. 6/18 got relief without needing any more treatment. 12/18 got relief for a short time and needed retreatment. The other technique is called Outpatient Low dose ketamine infusion. It is an FDA approved study. Ketamine is given 40-80 mg daily over 4 hours for 10 days. Its 29 people reported decreased shooting, sharp, burning pain, and decreased color/temperature and posture change. Again, this is what we heard about at the conference, I don't have any personal knowledge of it.
Hope this helps.
Hi there,
I am new to this site.
I might have some information on Ketamine that may be useful. Ketamine has been used in Australia for RSD for several years.
I have had approximately 3 Treatments of Ketamine per year for the last 5 years and I am surprised that it isn't as well known there.
I have a working knowledge of the drug also.
Ketamine is not Ecstacy. It is known on the street as special K and some ecstacy tablets may contains parts of KETAMINE but it is a different drug altogether.
Ketamine has been used for many years as an anaesthetic drug, it was used a lot in the emergency room as a quick acting anaesthetic for children to use while they had broken limbs plastered. It wears off quickly and there are few side effects.
When it is used for pain management it is usually given Intravenously although can be given sub-cutaneous [under the skin] I usually have it for 2 weeks at a time but some have it for shorter periods depending on how well it is working.
There can be some minor side effects when you first use it but this is mainly hallucinating. This can be controlled by turning down the infusion until the effects wear off.The major benefit of course is significant pain relief. For some it lasts foe a long time. I know of someone who had 7 months of relief, but for me , it only lasts while the infusion is running but to me , any pain relief is worth it.
Good luck to all.

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