Choice of opioid analgesics in postoperative care – Authors' Reply

Abstract

Simon Maxwell and Nicholas Bateman are correct that the pharmacogenetics of tramadol are variable. That is one of the reasons why we recommend its use as a second-line or third-line analgesic drug in the postoperative setting. Tramadol does, however, offer several advantages over opioid-based regimens in that there is less sedation, respiratory depression, and constipation,1Australian and New Zealand College of Anaesthetists and Faculty of Pain MedicineAcute pain management: scientific evidence. 2nd edn. Australian and New Zealand College of Anaesthetists, Melbourne2005http://www.anzca.edu.au/publications/acutepain.htmGoogle Scholar each of which can be problematic postoperatively. Codeine, a prodrug, has its own pharmacogenetic variability because of its dependence on CYP2D6 to produce the pharmacologically active metabolite, morphine.2Poulsen L Riishede L Brosen K Clemensen S Sindrup SH Codeine in post-operative pain. Study of the influence of sparteine phenotype and serum concentrations of morphine and morphine-6-glucuronide.Eur J Clin Pharmacol. 1998; 54: 451-454Crossref PubMed Scopus (38) Google Scholar, 3Enggaard TP Poulsen L Arendt-Nielsen L et al.The opioid effect of (+)-M1 appears to contribute to the analgesic effect of tramadol, but the monoaminergic effect of tramadol itself seems to create an analgesic effect.Anesth Analg. 2006; 102: 146-150Crossref PubMed Scopus (117) Google Scholar Codeine has been shown to be an unreliable analgesic postoperatively.2Poulsen L Riishede L Brosen K Clemensen S Sindrup SH Codeine in post-operative pain. Study of the influence of sparteine phenotype and serum concentrations of morphine and morphine-6-glucuronide.Eur J Clin Pharmacol. 1998; 54: 451-454Crossref PubMed Scopus (38) Google Scholar Tramadol, unlike codeine, can still provide analgesia in patients lacking CYP2D6 activity because its direct monoaminergic analgesic effect is independent of CYP2D6.3Enggaard TP Poulsen L Arendt-Nielsen L et al.The opioid effect of (+)-M1 appears to contribute to the analgesic effect of tramadol, but the monoaminergic effect of tramadol itself seems to create an analgesic effect.Anesth Analg. 2006; 102: 146-150Crossref PubMed Scopus (117) Google Scholar Codeine 60 mg has weak analgesic efficacy, with a number needed to treat (NNT) of 17 and a poor side-effect profile.4Oxford league table of analgesics in acute pain.http://www.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/Leagtab.htmlGoogle Scholar, 5Sachs CJ Oral analgesics for acute nonspecific pain.Am Fam Physician. 2005; 71: 913-918PubMed Google Scholar Similarly, dihydrocodeine, a synthetic form of codeine, was found to have weak analgesic properties in a meta-analysis of trials in a moderate-to-severe postoperative pain setting, with an NNT of 8 (95% CI 4–540) when compared with placebo.4Oxford league table of analgesics in acute pain.http://www.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/Leagtab.htmlGoogle Scholar A meta-analysis of 18 surgical or dental pain trials found that tramadol was an effective analgesic when compared with placebo, and had a clear dose response: higher doses of tramadol were associated with higher benefit and lower NNTs. Tramadol 100 mg had an NNT of 4·6 (3·6–6·4).4Oxford league table of analgesics in acute pain.http://www.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/Leagtab.htmlGoogle Scholar Unlike codeine, and to a lesser extent tramadol, oxycodone is not a prodrug and is not dependent on cytochrome P450 enzymes for its analgesic efficacy. For a single dose of oxycodone 15 mg compared with placebo, the NNT was 2·4 (1·5–4·9) for moderate to severe postoperative pain, indicating comparable analgesic efficacy to that of morphine 10 mg and oral non-steroidal anti-inflammatory drugs.4Oxford league table of analgesics in acute pain.http://www.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/Leagtab.htmlGoogle Scholar Widespread experience in Australia with oxycodone has found it to have practical advantages postoperatively:1Australian and New Zealand College of Anaesthetists and Faculty of Pain MedicineAcute pain management: scientific evidence. 2nd edn. Australian and New Zealand College of Anaesthetists, Melbourne2005http://www.anzca.edu.au/publications/acutepain.htmGoogle Scholar reliable oral bioavailability, ease of dose adjustment, and a sustained release preparation. This factor improves the simple and effective administration of oral opioid therapy in the postoperative setting where pain intensity is fluctuating and reducing over time. We believe that there is sufficient evidence to recommend the preferential use of oxycodone,5Sachs CJ Oral analgesics for acute nonspecific pain.Am Fam Physician. 2005; 71: 913-918PubMed Google Scholar tramadol, or both over codeine. There is, however, a need for head-to-head clinical trials of these drugs in the postoperative setting to determine the optimum first-line and second-line therapy in specific patient groups and types of surgery. We declare that we have no conflict of interest. Choice of opioid analgesics in postoperative careAlthough many aspects of the Clinical Update on post-operative analgesia by Paul Myles and Ian Power (March 10, p 810)1 were extremely helpful, we were surprised that it laid such emphasis on the use of tramadol and oxycodone as opioid analgesics of choice for moderate and severe pain. Full-Text PDF