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PAIN MEDICINE

Ketamine in Chronic Pain Management: An Evidence-Based Review

Graham Hocking, MB ChB, DMCC, FRCA, FFPMANZCA^*,, and Michael J. Cousins, MB BS, MD, FANZCA, FRCA, FFPMANZCA, FAChP (RACP)^*

*Pain Management and Research Centre, University of Sydney, Royal North Shore Hospital, St. Leonards, Sydney, NSW 2065, Australia; and Consultant in Anesthesia and Pain Management, Oxford Radcliffe Hospitals NHS Trust, Oxford, United Kingdom

Address correspondence and reprint requests to Professor M. J. Cousins, Pain Management and Research Centre, University of Sydney, Royal North Shore Hospital, St. Leonards, Sydney, NSW 2065, Australia. Address email to MCousins{at}doh.health.nsw.gov.au

Ketamine has diverse effects that may be of relevance to chronic pain including: N-methyl-D-aspartic acid, -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, -aminobutyric acid_A receptors; inhibition of voltage gated Na⁺ and K⁺ channels and serotonin, dopamine re-uptake. Ketamine has been in clinical practice for over 30 yr; however, there has been little formal research on the effectiveness of ketamine for chronic pain management. In this review we evaluate the available clinical data as a basis for defining the potential use of ketamine for chronic pain. Literature referenced in this review was obtained from a computer search of EMBASE and MEDLINE from 1966 through August, 2002. Search terms included ketamine, ketalar, pain, painful, analgesic, and analgesia. Abstracts were screened for relevance and publications relating to chronic pain use were obtained. Levels of evidence were stratified according to accepted guidelines (level I-IV). For central pain, there is level II and level IV evidence of efficacy for parenteral and oral ketamine. For complex regional pain syndromes, there is only level IV evidence of efficacy of epidural ketamine. For fibromyalgia, there is level II evidence of pain relief, reduced tenderness at trigger points, and increased endurance. For ischemic pain, a level II study reported a potent dose-dependent analgesic effect, but with a narrow therapeutic window. For nonspecific neuropathic pain, level II and level IV studies reported divergent results with questionable long-term effects on pain. For phantom limb pain and postherpetic neuralgia, level II and level II studies provided objective evidence of reduced hyperpathia and pain relief was usually substantial either after parenteral or oral ketamine. Acute on chronic episodes of severe neuropathic pain represented the most frequent use of ketamine as a "third line analgesic," often by IV or subcutaneous infusion (level IV). In conclusion, the evidence for efficacy of ketamine for treatment of chronic pain is moderate to weak. However, in situations where standard analgesic options have failed ketamine is a reasonable "third line" option. Further controlled studies are needed.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999