Opioid-induced hyperalgesia: low-dose ketamine does work for some orthopaedic problems already

Abstract

Editor—I read with interest the original article and accompanying editorial on opioid-induced hyperalgesia (OIH).1Minville V Fourcade O Girolami J-P Tack I Opiod-induced hyperalgesia in a mice model of orthopaedic pain: preventive effect of ketamine.Br J Anaesth. 2010; 104: 231-238doi:10.1093/bja/aep363Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar 2Colvin LA Fallon MT Opioid-induced hyperalgesia: a clinical challenge.Br J Anaesth. 2010; 104: 125-127doi:10.1093/bja/aep392Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar There are already clinical studies, which support some of the findings, although the type of pain may be slightly different. I have used low-dose ketamine, usually 0.15 mg kg−1, for the prevention of tourniquet-induced hypertension and pain3Segerdahl M Ekblom A Sollevi A The influence of adenosine, ketamine and morphine on experimentally induced ischemic pain in healthy volunteers.Anesth Analg. 1994; 79: 787-791doi:10.1213/00000539-199410000-00029Crossref PubMed Scopus (98) Google Scholar for a number of years. Low-dose ketamine is also successful at reducing morphine requirements after anterior cruciate reconstruction surgery.4Menigaux C Fletcher D Dupont X Guignard B Guirimand F Chauvin Ml The benefits of intraoperative small-dose ketamine on postoperative pain after anterior cruciate ligament repair.Anesth Analg. 2000; 90: 129-135doi:10.1097/00000539-200001000-00029Crossref PubMed Scopus (191) Google Scholar For orthopaedic lower limb arthroplasty surgery, I add ketamine 0.15 mg kg−1 to my analgesic mixture. I think that these clinical studies are good supporting evidence for the work done by Minville and colleagues.1Minville V Fourcade O Girolami J-P Tack I Opiod-induced hyperalgesia in a mice model of orthopaedic pain: preventive effect of ketamine.Br J Anaesth. 2010; 104: 231-238doi:10.1093/bja/aep363Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar I agree that more good-quality clinical studies are needed, and there is an urgent requirement for S-ketamine to be made available to anaesthetists in the UK. Editor—We thank Dr Griffiths for his interesting observations on the clinical use of ketamine. There is indeed an increasing number of clinical studies on the use of ketamine, with opioid-sparing effects in the postoperative period.5Berti M Baciarello M Troglio R Fanelli G Clinical uses of low-dose ketamine in patients undergoing surgery.Curr Drug Targets. 2009; 10: 707-715doi:10.2174/138945009788982496Crossref PubMed Scopus (33) Google Scholar A Cochrane review of perioperative ketamine deemed 37 randomized controlled trials, with a total of 2240 patients, to be of sufficient quality to include in their analysis—of these 27 trials found that subanaesthetic doses of ketamine were effective in pain control, reducing opioid requirements, and with minimal adverse effects.6Bell RF Dahl JB Moore RA Kalso E Perioperative ketamine for acute postoperative pain. 2006doi:10.1002/14651858.CD004603.pub2Crossref Google Scholar It seems clear from this that ketamine, or perhaps other N-methyl d-aspartate (NMDA) receptor antagonists, has a role in perioperative management. S-ketamine may have a better side-effect profile, or other agents, selective for different subtypes of the NMDA receptor, might have improved clinical utility. The specific role of ketamine in preventing OIH is also of interest: whether its site of action is in the spinal cord, where we know central sensitization involving the NMDA receptor occurs, or in higher centres does require further study. Clinical imaging studies have certainly demonstrated effects on pain processing areas in the brain, but the clinical significance of this is not yet understood.7Sprenger T Valet M Woltmann R et al.Imaging pain modulation by subanesthetic s-(+)-ketamine.Anesth Analg. 2006; 103: 729-737doi:10.1213/01.ane.0000231635.14872.40Crossref PubMed Scopus (57) Google Scholar 8Rogers R Wise RG Painter DJ Longe SE Tracey I An investigation to dissociate the analgesic and anesthetic properties of ketamine using functional magnetic resonance imaging.Anesthesiology. 2004; 100: 292-301doi:10.1097/00000542-200402000-00018Crossref PubMed Scopus (102) Google Scholar By using a combination of approaches to the problem, with evidence from basic science studies, volunteer and clinical imaging studies, and good-quality clinical trials, it may be possible to develop clinical strategies to address OIH and minimize its impact on delivering effective analgesia in a variety of settings. None declared. L. A. Colvin* M. T. Fallon Edinburgh, UK E-mail: [email protected]