Ketamine is undergoing a resurgence. For decades, anesthesiologists used ketamine for induction of general anesthesia at 2 mg/kg. However, some patients hallucinated and the use of the drug waned. We are beginning to see a resurgence using small, low-dose ketamine. Low doses inhibit the NMDA receptors, which is responsible for central sensitization, and can work synergistically with many other analgesics. A recent lead article in Anesthesiology noted that low dose IV ketamine in combination with an epidural had a significant reduction (p<0.05) in not just acute pain, but it eliminated chronic postsurgical pain one year later. (Figure 4) Hallucinations are extremely rare with low doses of subanesthestic ketamine of about 20 to 30 mg in the average adult. Furthermore, the risk of hallucinations declines with repeated use of ketamine.
Figure 4. Drawing depicting the sites of action of ketamine. The study by Lavand'homme et al. showed that low dose IV ketamine in combination with an epidural had a significant reduction in acute pain and reduced chronic postsurgical pain one year later. (Lavand’homme P, DeKock M, Waterloos H. Intraoperative epidural analgesia combined with ketamine provides effective preventative analgesia in patients undergoing major digestive surgery. Anesthesiology 2005;103:813-20)
Chronic, intractable CRPS is often associated with major depression. A recent randomized trial using a single low dose infusion of ketamine for 40 minutes showed a rapid and prolonged response in treating major depression. [96] The authors commented:
“To our knowledge, there has never been a report of any other drug or somatic treatment (ie, sleep deprivation, thyrotropin-releasing hormone, antidepressant, dexamethasone, or electroconvulsive therapy) that results in such a dramatic rapid and prolonged response with a single administration.”
Another recent study from Germany suggests that there may be a role for high dose ketamine in treating severe CRPS refractory to treatment. [97, 98] To date, 30 patients have been treated. Treatment is initiated by bolus injections of ketamine (0.5 mg/kg) and midazolam (2.5-5 mg) until deep sedation is reached. Patients are intubated and the therapy is maintained with infusions of ketamine (3-7 mg/kg/h) and midazolam (0.15-0.3 mg/kg/h) over five days. On the fifth day infusions are slowly tapered.
So far, nine of the 30 patients have experienced complete and permanent remission from their previously intransigent symptoms. Of the remaining 21 patients, all of whom had at least a partial remission, seven were entirely pain-free for six to seven months, after which the pain slowly returned. Ten of the patients are now being treated with subanesthetic doses of ketamine in an attempt to boost the initial effect. Side effects have been minimal.
The FDA-approved drug insert supports the safety ketamine:
"Ketamine has a wide margin of safety; several instances of unintentional administration of overdoses of ketamine (up to ten times that usually required) have been followed by prolonged but complete recovery.”
Click Here For CNN Report On Ketamine Coma
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