The difference in postoperative quality of recovery between the two groups varied depending on the time after surgery. Although propofol-based TIVA significantly improved the quality of recovery at 24 and 48 h after minimally invasive nephrectomy compared with desflurane anesthesia, their effect size was smaller than the predefined MCID. Furthermore, this difference did not remain at 72 h postoperatively. There was no significant difference between the two groups in any other postoperative clinical outcomes, including quality of life, at three weeks after discharge.
Several studies have investigated the effect of general anesthetic techniques on postoperative recovery using the QoR-40 (De Oliveira, Bialek, Rodes, Kendall, & McCarthy 2017; Joe et al., 2021; W. K. Lee, Kim, Kang, Kim, & Lee 2015; Liu, Gu, Chen, & Shen 2019; Na, Jeong, Eum, Park, & Kim 2018; Niu et al., 2021; Park et al., 2020). An RCT including female patients undergoing thyroid surgery reported the superiority of propofol-based TIVA for early postoperative recovery, mainly due to the reduction in PONV (W. K. Lee et al. 2015). However, differences in patient characteristics and insufficient PONV prophylaxis made this result difficult to apply to other surgeries, and subsequent RCTs have yielded conflicting results (De Oliveira et al. 2017; Joe et al. 2021; Liu et al. 2019; Na et al. 2018; Niu et al. 2021; Park et al. 2020). Moreover, in most previous studies, outcomes were assessed only within POD 1, except in two recently published RCTs (Joe et al. 2021; Niu et al. 2021). One involving patients undergoing pancreatectomy reported that postoperative recovery was significantly better on POD 3 in the propofol-based TIVA group than in the DES group (Joe et al. 2021). However, the clinical implications of a significant difference only on POD 3 may be debatable considering the relatively long length of hospital stay following pancreatectomy. Rather, this difference seen only on POD 3 might have resulted from the transient effect of type of general anesthetic techniques, similar to our result. Another recent RCT for laparoscopic hysterectomy reported no significant difference between the two techniques in terms of postoperative recovery (Niu et al. 2021). However, the study only included relatively young female patients, making the results difficult to generalize. Additionally, unlike this study, transient but significant improvement of early postoperative recovery in the TIVA group could accept the improvement of early postoperative recovery in the TIVA reported in several studies (W. K. Lee et al. 2015; Liu et al. 2019; Na et al. 2018; Park et al. 2020).
Our study differs from previous investigations in that we aimed to mitigate the impact of the antiemetic effect of propofol-based TIVA by implementing multimodal PONV prophylaxis in both groups, in accordance with recent guidelines (Gan et al. 2020). Furthermore, we included the patients undergoing minimally invasive cancer surgeries. Given the growing interest in the effects of anesthetic type on oncologic outcomes (Hasselager et al. 2021; Makito, Matsui, Fushimi, & Yasunaga 2020; Wall, Sherwin, Ma, & Buggy 2019), our study may provide additional meaningful information regarding anesthetic selection in the patients undergoing cancer surgeries. We also reduced the impact of confounding factors on postoperative recovery using a homogeneous sample of patients and a standardized perioperative protocol. Lastly, we used the QoR-15, which has higher clinical feasibility than the QoR-40 (Stark, Myles, & Burke 2013) and was the first validated measurement for postoperative recovery under the standardized criteria (Kleif et al. 2018). Therefore, our results may provide more reliable information regarding the effect of general anesthetic techniques on postoperative recovery.
The main perceived advantages of propofol-based TIVA compared to desflurane anesthesia in this study were its opioid-sparing effect and improvement of pain dimension in the QoR-15K. Propofol may improve postoperative pain through its anti-inflammatory and antioxidant effects and antagonistic effects at NMDA receptors, which can play an important role in pain signaling (Qiu et al. 2016; Shin et al., 2010). Several meta-analyses have supported the superiority of propofol-based TIVA for improving postoperative pain compared with inhalation anesthesia (Peng et al., 2016; Qiu et al. 2016; Schraag et al., 2018). However, since the analgesic effect of propofol-based TIVA can vary depending on the degree of surgical trauma and postoperative pain management, our results should be interpreted cautiously. In an aforementioned RCT that addressed laparoscopic hysterectomy outcomes, no differences in postoperative recovery were observed between propofol-based TIVA and sevoflurane anesthesia (Niu et al. 2021). In this study, the intensity of postoperative pain was low, indicating that propofol-based TIVA may not have induced a significant difference in postoperative pain outcomes. Additionally, regional analgesia—which was not included in our study—can negate the analgesic and opioid-sparing effects of propofol-based TIVA (Dam et al., 2021), which may further contribute to insignificant differences in QoR-15 scores between the two groups.
Our findings suggested that propofol-based TIVA improved postoperative recovery during the early postoperative period, which is also in line with the opinion of anesthesiologists who participated in a relevant survey (79% somewhat to strongly agreed that TIVA leads to superior quality of recovery) (Lim, Braat, Hiller, & Riedel 2018). However, considering its transient and marginal effect during hospitalization and the time course of postoperative recovery in our patients, it may be difficult to show that propofol-based TIVA leads to significant improvements in other postoperative outcomes.
Our study has several limitations. First, as this study was a single-blinded RCT, some biases may have influenced our results. However, although attending anesthesiologists could not be blinded, the investigator who evaluated postoperative outcomes was completely blinded to the group allocation. Second, the sample size was calculated based on the QoR-15K score at 24 h postoperatively, according to our previous study (Yoon et al. 2020), although this was not sufficiently powered to detect significant differences in other outcomes. Additionally, we considered a QoR-15K score of 10 as the MCID, greater than the previously reported MCID of 8 for the QoR-15 (Paul S. Myles et al., 2016). In the planning stage of this study, we initially considered a QoR-15K score of 8 to be MCID based on the previous study (Paul S. Myles et al. 2016). However, considering the difference in QoR-15K scores between the two groups may decrease over time after surgery (W. K. Lee et al. 2015), we had set the MCID of 10 at 24 h postoperatively as the primary outcome, which was a greater value than 8. Thus, we recalculated the sample size before patient enrollment after the approval of IRB. Third, our study was conducted at a single tertiary university hospital and thus may not reflect perioperative management at other institutions. Fourth, there was a significant difference in the total amount of intraoperative remifentanil used between the two groups. The type of general anesthesia technique and amount of intraoperative remifentanil could have affected postoperative pain severity and opioid consumption (Shin et al. 2010). Although we assumed that this difference would have been due to the vasodilatory or analgesic effect of desflurane (Ryu et al., 2020; Ryu et al., 2018), we found it difficult to explain the mechanism behind this difference from our results. However, since there was no significant difference in postoperative pain severity, but rather, less postoperative opioid consumption in the TIVA group, the difference in intraoperative remifentanil amount would not have had a significant effect on our primary and secondary outcomes. Lastly, since we followed the conventional discharge criteria determined by attending surgeons, this may explain why a significant difference in postoperative recovery during the early postoperative period did not lead to significant differences in the length of hospital stay. Further research is required to investigate the clinical impact of these two anesthetic techniques under a discharge protocol adjusted according to the degree of postoperative recovery. Despite these limitations, to our best knowledge, this is the first study to evaluate the impact of general anesthetic techniques on the quality of postoperative recovery, as measured using the QoR-15K in patients undergoing minimally invasive cancer surgeries.
In conclusion, our findings indicate that propofol-based TIVA provides better early postoperative recovery at 24 and 48 h postoperatively than inhalation anesthesia. However, this transient and marginal improvement did not last until 72 h postoperatively. Additionally, this transient and slight improvement led to no significant differences in other postoperative outcomes, including quality of life, at the early discharge phase of our study. However, considering our modest sample size, further studies with sufficient power are needed to establish a standardized anesthetic technique to improve postoperative recovery.