The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Acta Anaesthesiol Scand. 1998 Aug;42(7):750-8. doi: 10.1111/j.1399-6576.1998.tb05317.x.


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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analgesics / administration & dosage
  • Analgesics / adverse effects
  • Analgesics / blood
  • Analgesics / therapeutic use*
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / therapeutic use
  • Arteriosclerosis Obliterans / complications*
  • Arteriosclerosis Obliterans / physiopathology
  • Chromatography, High Pressure Liquid
  • Cognition / drug effects
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / adverse effects
  • Excitatory Amino Acid Antagonists / blood
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Female
  • Humans
  • Infusions, Intravenous
  • Ischemia / etiology
  • Ischemia / physiopathology*
  • Ketamine / administration & dosage
  • Ketamine / adverse effects
  • Ketamine / blood
  • Ketamine / therapeutic use*
  • Leg / blood supply*
  • Male
  • Middle Aged
  • Morphine / administration & dosage
  • Morphine / therapeutic use
  • Pain / drug therapy*
  • Pain Measurement
  • Perception / drug effects
  • Peripheral Vascular Diseases / complications
  • Peripheral Vascular Diseases / physiopathology


  • Analgesics
  • Analgesics, Opioid
  • Excitatory Amino Acid Antagonists
  • Ketamine
  • Morphine