In this issue of Anesthesia & Analgesia Tan et al.1 compare pain scores and morphine requirements following anesthesia with either propofol or sevoflurane. They report that pain scores measured at regular intervals over 6 hours were higher in the patients receiving a sevoflurane-based anesthetic than it was in those receiving a propofol-based anesthetic as measured by area under the visual analog scale (VAS) curve over time. Their findings are similar to those previously published by Cheng et al.2 The study by Cheng et al. generated an editorial questioning whether this observed reduction in pain perception was a statistical anomaly or a new paradigm.3 When I (PG) received the manuscript I asked 3 experts in the field of analgesia to review the article. One reviewer was Pamela Flood, senior author of the Cheng et al. study. A second reviewer was Paul White, one of the foremost experts on propofol pharmacology. I knew these experts held very different opinions on the value and clinical utility of this line of research. Although they agreed that the study by Tan et al. was well conducted, they disagreed on the clinical relevance of the work. It is not surprising that they differed strongly in their opinions. The question of whether propofol reduces or sevoflurane worsens postoperative pain perception is not apparent in our everyday use of volatile anesthetics. Additionally, an underlying mechanism of how propofol and volatile anesthetics might affect nociception is not well established. Thus I (PG) asked Drs. Flood4 and White5 to write editorials to accompany this study representing their divergent views. As was pointed out by Tan et al.1 and the accompanying editorials,4,5 there are previous articles that support or refute either an analgesic effect of propofol or a hyperalgesic effect of volatile anesthetics. We now have another article supporting this claim. Is it true? If it is, what do these findings mean in clinical practice? We know that the effect, if it exists at all, is modest. In both clinical studies by Tan et al. and Cheng et al., the differences in pain perception at any given moment were generally <1 cm on a VAS scale. Given the patient-to-patient variability in pain scores, an average difference of 1 point in VAS score could be completely invisible to the busy anesthesiologist. This may explain why our clinical impression is that there is no difference between a propofol-based anesthetic and a sevoflurane-based anesthetic. If the differences were larger (e.g., 3 to 4 points on a VAS scale), it is more likely that it would have been noticed. Clinical impressions may often be a poor determinant of the underlying truth, particularly when there are small differences in an effect, such as VAS, that varies enormously in the population. We face the same conundrum with volatile anesthetics and postoperative cognitive dysfunction (POCD).6 POCD is a subtle and perhaps transient phenomenon that can be detected only with meticulous neuropsychological testing. However, POCD is a predictor of 1-year mortality and social decline in afflicted elderly patients.6 Similarly, we are now investigating the possibility of small but significant effects of volatile anesthetics on long-term cognitive development in the newborn.7 We have used volatile anesthetics for over 150 years, but only recently have we begun to suspect that they might cause small, but measurable, and potentially important effects on cognition in patients at risk. Thus, it should come as no surprise that investigators looking at postoperative analgesia are finding unexpected effects when comparing propofol to sevoflurane. Differences of opinion are healthy, and indeed necessary to advance science. Differences of opinion motivate investigators to rigorously seek the truth. We once believed that the Earth was flat, which was affirmed in our daily experience. More recently we believed that stem cells did not exist in the adult brain,8 and that peptic ulcer disease was a psychosomatic disorder.9 Ingrained beliefs change slowly, and many scientists spend their careers developing the evidentiary base to change these notions. Fortunately, nature behaves predictably, and eventually the truth becomes apparent. In this spirit of discovery we need to rigorously determine whether volatile-based anesthesia increases postoperative pain when compared with a propofol-based anesthesia. If so, we need to determine whether this is due to a mild analgesic effect of propofol or a hyperalgesic effect of volatile anesthetics. This is not because this finding will change our anesthetic management. Instead, understanding the subtle toxicities of volatile anesthetics, or the subtle benefits of propofol, will guide our search for better alternatives. Nitrous oxide was also a standard anesthetic for more than 100 years, yet it is rarely used today (at least at the State University of New York, Stonybrook) because our present knowledge has led to better alternatives. Stimulated by debate, science will provide answers, insight, and better care for our patients.
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Open Access
Jan 3, 2024
Isaac D Juárez + 5
