Anaesthesia maintenance with propofol versus sevoflurane to reduce postoperative pain: Still too early for recommendations?

Abstract

In this issue you will find a paper by Sau Ching Wong et al. entitled "The effect of total intravenous anaesthesia with propofol on postoperative pain after third molar surgery: a double blind randomized controlled trial (Wong, Leung, & Cheung, 2018 in press, will be assigned to an 2019-issue). This paper reports results of a trial conducted in a standard surgical model of pain: the bilateral third molar extraction surgery. The results demonstrated that the anaesthesia maintenance, based on intravenous propofol instead of sevoflurane, reduced postoperative pain for 72 hr but not analgesics requirements or postoperative side effects (aside from headache reduction). Surprisingly, the intraoperative remifentanil requirements were higher in the propofol group in the present study. However, the group receiving propofol maintenance of anaesthesia showed less pain after surgery, suggesting that propofol might also decrease some of the classically described remifentanil induced hyperalgesia. These findings agree with a previous clinical study (Shin et al., 2010). This present study is of interest as it brings more elements into the discussion surrounding the impact of the anaesthetic agents used during surgery and anaesthesia maintenance on postoperative pain outcomes. Interestingly, the same group (Sau Ching Wong et al.) already reported on the mechanisms of propofol to reduce pain in an inflammatory model and in a model of postoperative pain in rodents via a regulation of spinal GluN2B-p38MAPK/EPAC1 pathway. Other authors have demonstrated that propofol decreased the hyperalgesia induced by remifentanil infusion in a well-known model in human volunteers (Singler, Troster, Manering, Schuttler, & Koppert, 2007) and after surgery (Shin et al., 2010). Whether or not this molecular mechanism can translate into a significant clinical impact for postoperative pain outcomes and management, to the point where it leads to new recommendations for our anaesthesia community, remains questionable. Moreover, a pertinent question to answer is whether it is applicable to all types of surgery. Indeed, Sau Ching Wong et al. wrote a systematic review and meta-analysis on propofol's impact on postoperative pain outcomes and reported that propofol was associated with less postoperative pain at 24 hr after surgery. However, the difference was very marginal, meaning it had very small clinical relevance (delta of pain scores: −0.134 [−0.248 to −0.021] on a scale of 10). Other authors in their meta-analysis did not arrive at the same conclusion. They explained this might be due to the small number of studies and patients included in their systematic review and the substantially high level of heterogeneity of the reported studies performed in a wide range of surgeries (Peng et al., 2016). Their conclusion was that none of the postoperative pain outcomes was significantly changed or improved by using propofol instead of sevoflurane for maintenance of anaesthesia. Besides meta-analyses, randomized controlled studies performed in major surgeries, such as laparoscopic hysterectomies, did not report significant difference in postoperative pain management and outcomes between intraoperatively administered propofol and sevoflurane (Pokkinen, Yli-Hankala, & Kalliomaki, 2014). This was confirmed by studies published in 2018 by Sau Ching Wong et al. in colorectal surgery that demonstrated lower morphine consumption at POD1, 2, 3 but no impact on postoperative pain scores, patient satisfaction or side effects. Certainly, the current literature lacks enough capacity to answer the question whether there is a real and clinically significant impact on postoperative outcomes for the patient that will change their general satisfaction and the quality of their postoperative recovery. Nowadays, most of our research agencies recommend performing clinical trials that will change the postoperative outcomes of our patients generally and significantly. Slightly changing, even if significantly, some postoperative pain outcomes might not be sufficient enough to lead to large recommendations regarding the practice of anaesthesia. As each surgery goes with a specific type of analgesic regimen, protocol, and levels of inflammation and pain sensitization (at the peripheral and central level) that can interfere with postoperative pain outcomes, more precise and larger studies are needed. The present study included patients without any chronic pain or chronic opioid exposure. Moreover, no other analgesics were given preventively prior to surgery in order to avoid any impact on the main outcome of this study. This suggests that if non-steroidal anti-inflammatory drugs and acetaminophen would have been given prior to surgery (as is often recommended in this type of surgery), this trial might have reported different and, perhaps, negative results on their primary outcome. Finally, in this competition between propofol and halogenous gases for anaesthesia maintenance and the impact on postoperative pain outcomes, one also needs to consider the environmental impact of our anaesthetic agents. Indeed, inhaled anaesthesia gases are known to be deleterious for the environment as they have a strong global warming potential. Additionally, and even if propofol does not contribute directly to the greenhouse gas effect, its use has other detrimental environmental impacts, such as its contribution to plastic waste and also some direct pollution. In conclusion, as mentioned in the two meta-analyses published so far, there is a real need to generate procedure specific evidences with randomized controlled trials in different type of surgeries before evidence-based recommendations regarding the use of anaesthetic agents for clinical practice can be made. Dr. Philippe Richebé is a member of the advisory board of the company Medasense Biometrics Ltd. and a consultant for this company; as such, he perceived honorarium from 2015 until present. Nevertheless, all the studies he performed as a PI were done after a contract signed between both the parties (Research Center of HMR, CR-HMR, and Medasense Biometrics Ltd.) and always under the manner of an Independent Investigator Initiated Trial.