CRPS & RSD: Management of Complex Regional Pain Syndrome (CRPS) or Reflex Sympathetic Dystrophy (RSD) with low dose intravenous ketamine infusion

Ketamine, a potent anesthetic, is being used as an experimental and controversial treatment for Complex Regional Pain Syndrome. The theory of ketamine use in CRPS/RSD is primarily advanced by neurologist Dr Robert J. Schwartzman of Drexel University College of Medicine in Philadelphia, and researchers at the University of Tübingen in Germany, but was first introduced in the United States by Doctor Ronald Harbut of Little Rock Arkansas. The hypothesis is that ketamine manipulates NMDA receptors which might reboot aberrant brain activity.

A 2004 article discussing ketamine infusion therapy states, "Although ketamine may have more than one mechanism of action, the basis for using it to treat CRPS may reside in its strong ability to block NMDA receptors. Experimental evidence suggests that a sufficiently intense or prolonged painful stimulus causes an extraordinary release of glutamate from peripheral nociceptive afferents onto dorsal horn neurons within the spinal cord. The glutamate released, in turn, stimulates NMDA receptors on second-order neurons that produce the phenomena of windup and central sensitization. It is reasonable to consider that, by blocking NMDA receptors, one might also be able to block cellular mechanisms supporting windup and central sensitization. Ketamine is the only potent NMDA-blocking drug currently available for clinical use. Our interpretation is that an appropriately prolonged infusion of ketamine appears to maintain a level of ketamine in the central nervous system long enough to reverse the effects of the sensitization process and associated pain."¹

There are two treatment modalities; the first consist of a low dose subanesthetic Ketamine infusion of between 10–90 mg per hour over several treatment days, this can be delivered in an office or hospital. This is called the awake or subanesthetic technique.

One study[2] demonstrated that 83% of the patients that participated had complete relief and many others had some relief of the symptoms. Another evaluation of a 10-day infusion of intravenous ketamine (awake technique) in the CRPS patient concluded that "A four-hour ketamine infusion escalated from 40–80 mg over a 10-day period can result in a significant reduction of pain with increased mobility and a tendency to decreased autonomic dysregulation". Unfortunately, these study designs are very prone to bias, which means we still need high quality randomized controlled trials of ketamine infusion for CRPS to know about its effects and side effects.

The second treatment modality consists of putting the patient into a medically-induced coma, then administering an extremely high dosage of ketamine; typically between 600 and 900 mg This version, currently not allowed in the United States, is most commonly done in Germany.

No replicated case series, or controlled trials have been done for the coma induced method to date, so care should be taken when interpreting these reports. Proper clinical trials are required before we know the effects and the risks of this procedure.

For more information on Ketamine infusion, see other resources from Reflex Sympathetic Dystrophy Syndrome Association:

• Video explaining Central sensitization in patients with RSD or CRPS. Ketamine helps lower this central sensitization.
  
  
  
   
• http://www.rsdsa.org/3/treatment/ketamine.html
   
• http://www.rsdsa.org/2/library/article_archive/index.html

1. Correll, GE; Maleki, J; Gracely, EJ; Muir, JJ; Harbut, RE (2004). "Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome.". Pain medicine (Malden, Mass.) 5 (3): 263–75. doi:10.1111/j.1526-4637.2004.04043.x. PMID 15367304

2. Correll, Graeme E.; Maleki, Jahangir; Gracely, Edward J.; Muir, Jesse J.; Harbut, Ronald E. (2004). "Subanesthetic Ketamine Infusion Therapy: A Retrospective Analysis of a Novel Therapeutic Approach to Complex Regional Pain Syndrome". Pain Medicine 5 (3): 263. doi:10.1111/j.1526-4637.2004.04043.x. PMID 15367304.