The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans.
BACKGROUND
Ketamine in sub-dissociative doses has been shown to have analgesic effects in various pain conditions, including neuropathic and phantom-limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.


METHODS
Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).


RESULTS
Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all the patients at the highest dose (0.45 mg/kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. These 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/kg ketamine doses than for morphine 10 mg.


CONCLUSIONS
We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.
Pain section, Division of Anaesthesiology and Intensive Care, Huddinge University Hospital, Sweden.
J
J
Persson
J
J
Hasselström
B
B
Wiklund
A
A
Heller
J O
JO
Svensson
L L
LL
Gustafsson
D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D001162:Arteriosclerosis Obliterans / Q000150:complications* / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007511:Ischemia / Q000209:etiology / Q000503:physiopathology*; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D010465:Perception / Q000187:drug effects; D016491:Peripheral Vascular Diseases / Q000150:complications / Q000503:physiopathology
D000700:Analgesics; D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D009020:Morphine