Letters to the Editor: Letters & Announcements
To the Editor:
We disagree with Marcou et al. (1) that the combination of tramadol and morphine cannot be recommended for postoperative analgesia. Although their study did not find a synergistic analgesic effect in a study population with mild-to-moderate pain, this finding should not be extrapolated to other groups, such as those having major surgery. Our study compared the morphine/tramadol combination with morphine alone after major abdominal surgery and found the combination improved analgesic efficacy without increasing side effects (2).
The different conclusions of these two studies may be explained in a number of ways. Marcou et al. (3) assessed the outcome of treatment only 20 min after the administration of the analgesia. The onset of analgesia from tramadol is generally acknowledged to be slower than that of morphine. Marcou et al. (3) state in their discussion that maximal analgesia with tramadol is not reached for 15–30 min. In a study comparing tramadol with morphine in patients with severe postoperative pain (visual analog scale score>7), the median time to patient comfort was 135 min. Thus, pain assessments done at 20 min may yield misleading data on the efficacy of a treatment, particularly where pain is more severe.
We also question some of the statistical assumptions used in the study by Marcou et al. The staircase bioassay method described by Dixon relates to all-or-none events such as death or emesis (4). Reductions in pain intensity are not all-or-none events, but the authors used a pain score of <3 to define a successful analgesic outcome. However, this concept is flawed, as a reduction in pain intensity from 3 to 2 would be considered a successful outcome, whereas a reduction from 8 to 3 would not. The surgical procedures were also quite diverse in the study and a power analysis was not presented.
Finally, the frequency of opioid side effects observed in the study was not surprising, given the rate at which the analgesia must have been given between T = 0 min (first pain assessment) and T = 20 min (second pain assessment). This included patients receiving in excess of 100 mg of tramadol, which in our institution would be given over at least 15 min. A slow initial titration rate of tramadol has been shown to reduce side effects (5) and may be an important reason for the low incidence of nausea and vomiting in our study on the morphine/tramadol combination.
Marcou et al. should be congratulated for providing further data on this relatively unexplored area, but their conclusion that the combination of tramadol and morphine cannot be recommended should not be generalized to all surgical groups.
Ashley Webb, FANZCA
Sam Leong, FANZCA
Department of Anaesthesia
Frankston, Victoria, Australia
1. Marcou TA, Marque S, Mazoit JX, et al. The median effective dose of tramadol and morphine for postoperative patients: a study of interactions. Anesth Analg 2005;100:469–74.
2. Webb AR, Leong S, Myles PS, et al. The addition of a tramadol infusion to morphine patient-controlled analgesia after abdominal surgery: a double-blinded, placebo-controlled randomized trial. Anesth Analg 2002;95:1713–8.
3. Wiebalck A, Tryba M, Hoell T, et al. Efficacy and safety of tramadol and morphine in patients with extremely severe postoperative pain. Acute Pain 2000;3:113–9.
4. Dixon WJ. Staircase bioassay: the up-and-down method. Neurosci Biobehav Rev 1991;15:47–50.
5. Ruoff GE. Slowing the initial titration rate of tramadol improves tolerability. Pharmacotherapy 1999;19:88–93.