Comment on 'Impact of analgesic techniques on early quality of recovery after prostatectomy: A 3-arm, randomized trial' by Beilstein and colleagues.

Abstract

In an investigator-initiated, prospective, randomized, three-arm, parallel-group, active-controlled, interventional superiority trial that included 133 patients undergoing open or robotic-assisted radical prostatectomy, Beilstein et al. (2022) compared the effects of adding spinal anaesthesia, transversus abdominis plane block and intravenous lidocaine to general anaesthesia on quality of early post-operative recovery assessed by the quality of recovery-15 (QoR-15) score. They showed that the addition of three different analgesic techniques to general anaesthesia did not improve the quality of early post-operative recovery. Other than the limitations described by the authors in the discussion, however, we had several questions about the methods and results of this study and wished to get the authors' responses. First, the main purpose of this study was to compare the effects of adding three different analgesic techniques to general anaesthesia on the quality of early post-operative recovery, It was unclear why the change in QoR-15 score from pre-operative admission day to post-operative day (POD) 1 in each group was designed as the primary endpoint. To determine the different effects of various interventions on the quality of early post-operative recovery, we believe that the between-group differences in QoR-15 score on POD 1 should be designed as the primary endpoint. Furthermore, recent literature recommends that a between-group difference of 6 in the mean QoR-15 score is the minimal clinically important difference in a randomized clinical trial assessing the quality of early post-operative recovery (Myles & Myles, 2021). We argue that this issue in study design would have resulted in an improper sample calculation and biased their findings due to a type 2 statistical error. Second, in the method, the authors described that rescue analgesic medications were additional boluses of fentanyl i.v. (during surgery and intermediate care unit stay) or oxycodone 5–10 mg/oral every 3–4 h on the normal ward. However, the readers were not provided the indication of rescue analgesic medications. We noted that 50% or more of patients needed rescue analgesics at 6 h post-operatively and on POD 1 and the use of rescue fentanyl was significantly different among three groups. It was unclear whether the use of oral oxycodone for rescue analgesia was significantly different among three groups. When post-operative analgesic consumption is compared, moreover, it is generally recommended that dosages of all rescue analgesics used for post-operative pain control should be converted into morphine equivalents. In the available literature, the recommended minimal clinically important difference of analgesic consumption for postoperative pain control is an absolute reduction of 10 mg i.v. morphine in 24 h (Doleman et al., 2021). Because of this design limitation, an issue that cannot be answered by this study is whether three analgesic techniques have resulted in different post-operative opioid-sparing effects, an important outcome endpoint of the Enhanced Recovery After Surgery protocols (Rajput et al., 2022). Third, median QoR-15 scores on POD 1 in three groups were 108–114, with interquartile ranges of 98.8–120. We would like to remind the authors and readers that the quality of early post-operative recovery was classified as excellent (QoR-15 > 135), good (122 ≤ QoR-15 ≤ 135), moderate (90 ≤ QoR-15 ≤ 121) or poor (QoR-15 < 90) (Campfort et al., 2022). That is, three analgesic techniques used in this study cannot provide excellent or good quality of early post-operative recovery for patients undergoing open or robotic-assisted radical prostatectomy. We believe that clarification of the above issues will improve the interpretation of findings from this clinical study. All authors carefully read the manuscript by Beilstein et al. and reviewed the methods and data. TYJ suggested comments and drafted the manuscript. FSX critically revised the comments and the manuscript and is the author responsible for this manuscript. XTL and TT revised the comments and the manuscript. All the authors have read and approved the final manuscript. All the authors have no financial support and potential conflict of interest for this work. None declared.