The aim of the present study was to evaluate outcomes in THR patients in terms of pain management within 96 h after surgery, following the administration of tapentadol or naloxone/oxycodone in combination with ketoprofen. From the results it is clear that patients in the tapentadol group experienced a decrease in pain intensity and collateral effects compared to the control group, with statistically significant differences both in terms of NRS (at rest and during movement) and collateral effects. Consequently, these benefits helped patients adhere to the fast track protocol of rehabilitation better, which nowadays is one of the main goals in joint replacement surgery.
In particular, in the field of hip disease, the ‘experience of pain’ with its neuropathic and inflammatory components often represents a physical and mental burden to patients, to the point that it might condition their approach to surgical intervention first, and subsequently to the rehabilitation process. Tapentadol’s nociceptive and neuropathic components, that reduce the ascendant component of pain while strengthening descending inhibitory stimulation, could represent an effective option in the management of post-op pain, with a good tolerability profile (Tzschentke et al., 2014; Langford, 2016; Pergolizzi et al., 2016). Post-op management has always represented a challenge in major orthopaedic procedures such as joint replacement, and many analgesic protocols have been tested over time: in many cases opioids have been among the drugs of choice to control pain in the very first phases following surgery, but (despite providing satisfactory pain reduction) the unfavorable rate of adverse events typically associated to many opioids has been regarded as their greatest disadvantage. The search for the “ideal opioid”, i.e. a drug with sufficient analgesic power and a low rate of side effects, led to the development of new molecules: tapentadol has been recently proposed as an effective and well tolerated pain killer, suitable for use in many orthopaedic situations, including surgical-related settings (Lee et al., 2014; Lockwood & Dickenson, 2019; Chen et al., 2015).
In particular, tapentadol has reduced pharmacological interactions (low binding to plasma proteins and no impact on CPY450, no active metabolites), which makes the drug more appealing for elderly patients, who represent the majority of the THR patient population admitted to our facility, and often displaying comorbidities and/or concomitant treatments (Tzschentke et al., 2014; Biondi et al., 2015). Another relevant advantage of tapentadol is the low rate of complications associated to its use (Vadivelu et al., 2017), which is inferior to that of other similar molecules. In the present study we used oxycodone/naloxone as a comparator. Oxycodone is a traditional and “popular” opiod, whose use in the field of muscolo-skeletal diseases is well established and reported in many trials so far (Kim et al., 2018; Oppermann et al., 2016), and its combination with naloxone has been developed and marketed more recently, in the attempt of diminishing the well-known gastro-intestinal side effects reported when administering oxycodone alone (Scardino et al., 2015).
In our experience, a dosage of 100 mg twice daily (following surgery), resulted in a satisfactory management of pain for the majority of patients (250 mg being the maximum daily recommended dose).
Post-op pain, both at rest and during movement, throughout T1-T4 was always reported as being bearable, with a NRS < 2. This has certainly contributed to the quick recovery of the patients after surgery as confirmed by the fact that 50% of patients were able to stand on T0 (that is within 4 h from surgery) a value which increased to 90% on T1. Patients treated with tapentadol also displayed a better post-operative recovery, which is not only represented by lower pain scores compared to patients who received oxycodone/naloxone, but also by the absence of recurring acute pain episodes. Specifically, the lower NRS both at rest and in motion was the main factor responsible for the well being of the tapentadol patients, a factor which allowed them to perform physical rehabilitation activities early, bringing with it all the inherent advantages in terms of functional recovery.
Indeed our results are comparable to those reported by Panella et al. (Panella, 2016) who assessed pain treatment following THA in 144 patients with either tapentadol PR (50 mg twice daily) versus paracetamol (1000 mg three times daily). Patients were treated throughout rehabilitation and followed-up for three weeks, showing (in addition to a satisfactory functional recovery) a 4.3 point decrease (83%) in patients treated with tapentadol vs 2.4 points (48%) in those treated with paracetamol. Conversely another study described the administration of tapentadol starting the day before surgery, but in this case, this did not result in statistically significant advantages compared to the standard treatment with oxycodone (Haesler et al., 2017).
In our study, patients treated with tapentadol and ketoprofen on T1 reported no pain, but they did report a higher incidence of symptoms such as nausea and vomiting than on the following days thus suggesting that, at least partially, these symptoms are related to the anesthesia and post-operative analgesia. Furthermore, a higher occurrence of nausea and vomit was described in the control group at T1 and T2, which again, emphasizes the better tolerability of tapentadol compared to oxycodone/naloxone.
This observation was confirmed by the presence of a few fainting episodes, all of which occurred on T1, linked to hypotension following local anesthesia. Additionally, hemodynamic parameters of patients treated with tapentadol, such as oxygen saturation and heart rate remained stable throughout the four days of observation. Overall, the typical collateral effects of opioids such as nausea, vomiting and constipation resulted to be greatly reduced in number in the tapentadol group compared to the oxycodone/naloxone group, an observation which is supported by data present in medical literature (Coluzzi & Ruggeri, 2014; Pergolizzi et al., 2016; Sanchez de Aguila et al., 2015). The higher incidence of PONV in the oxycodone/naloxone group may also be related to the higher request for morphine as rescue-analgesia in the control group.
In brief, results from our study support the use of tapentadol in combination with ketoprofen for the management of moderate-severe pain following major orthopedic surgeries, given its effectiveness in reducing intensity of pain and its satisfactory tolerance, allowing patients to perform post-operative rehabilitation activities early, and resume ambulation quickly after surgery. Indeed, forced immobilization due to pain, post-operative fasting, nausea and vomiting all contribute to comorbidities flares and increase the onset of complications which can compromise post-operative recovery and lengthen hospital stay.
The main limitation of the present study is its retrospective design, which warrants future randomized controlled trials to confirm the findings emerged from the present analysis. Despite data being retrospectively collected, we are confident about their reliability since our Department’s dedicated personnel (i.e. anesthesiology nurses) are in charge of evaluating patient pain NRS, daily, at the same hour. Among other study limitations, the lack of a long-term follow-up is of particular note, since it does not provide any information on the treatment’s long-term outcome. It is currently thought, as suggested by data in the literature, that tapentadol offers a longer-term efficacy compared to other opioids, featuring complete tolerance at 51 days compared to 21 days with morphine (Pergolizzi et al., 2016), with no risk of addiction in the medium-long term (Buynak et al., 2015). However, there is still a substantial paucity in long-term data within the literature, with the longest studies being limited to a maximum of 2 years. Another limitation is the lack of data concerning different post-op dosages of tapentadol, since it might be argued that variations in the dose could have yielded a significantly different therapeutic response and perhaps different incidence of adverse events. Additional randomized studies are therefore needed to understand the best administration protocols to maximize the benefit/risk ratio.