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, M.D., Ph.D., 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 is oftentimes 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. Often 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, B.E., M.B.B.S., 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.