Discussion
postoperative pain, bleeding, hyperalgesia, low pain, allodynia, pain, renal dysfunction
THROMBOPHLEBITIS, EVENTS, BLEEDING, PCP
In the present study, there was no significant difference for the postoperative opioid PCA requirements between the diclofenac-orphenadrin, the diclofenac and the placebo group for the treatment of postoperative pain in patients receiving cruciate ligament surgery. However, a distinct trend towards a reduction of hydromorphone requirement in the first 24 h postsurgery was found when administering diclofenac-orphenadrine, albeit being non-significant. Furthermore, our findings are in line with existing literature regarding high interindividual differences of opioid effectiveness as well as responsiveness to pain and a wide variety in postoperative opioid demand after arthroscopic cruciate ligament surgery [Overall, subjective pain intensity was similar in all groups. Due to adequate dosing of rescue medication a difference in pain intensity between the groups was not to be expected. Following the development of PCA systems with the ability to record delivered dose in the early 1970s reduction of opioid consumption became a cornerstone for the assessment of pain medication [To the best of our knowledge there previously were three studies examining the intravenous use of a diclofenac-orphenadrine combination in a postoperative setting. However, two of these studies were published in Hungarian and in Czech, respectively [Orphenadrine binds to the phencyclidine (PCP) binding site of the NMDA receptor which has been shown to delay the emergence and maintenance of mechanical and thermal hyperalgesia and allodynia [The most extensively discussed AEs in the literature on diclofenac are renal dysfunction, cardiovascular events, bleeding and thrombophlebitis, all of which occur infrequently and at similar rates as in other NSAIDs [An additional limitation of this study is the lack of pain assessment during joint movement. A study by Cho et al. on perioperative use of pregabalin failed to detect a reduction in postoperative opioid demand in patients undergoing cruciate ligament surgery but resulted in a reduction in pain during joint movement [It seems possible that there is an opioid-sparing effect of orphenadrine-diclofenac which we failed to detect because of insufficient power. The effect size for the sample size analysis may have been overestimated, and more patients per group likely might have been needed. Finally, a significant difference for PCA analgesic consumption between placebo and diclofenac/orphenadrine-diclofenac was detected after removal of two datapoint outliers resulting from two patients excessively pressing their respective PCA pumps, while both reporting low pain levels post hoc. However, as we cannot exclude that this particular PCA activation was due to pain and not “PCA misuse” this result needs to be interpreted with caution and is exploratory.An additional limitation of our study is the lack of evaluation of further variables that might influence pain perception such as social and cultural background as well as ethnicity [