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The fentanyl doses were comparable among the groups. Is this difference in postoperative pain also seen in smokers? The protocol was designed to keep patients at the same anesthetic depth by providing strict guidelines for anesthetic titration. Is this a fluke, or does it represent the pharmacology of propofol and isoflurane? Can the pharmacodynamic difference between the propofol and isoflurane patient groups be explained by a hyperalgesic effect of isoflurane, 7 a hitherto undocumented analgesic effect of propofol, or both? The present study was limited to nonsmokers. Postoperative pain scores were identical at 2 hours, but diverged again at 24 hours. performed only two Visual Analog Scale assessments after the first hour: one at 2 hours, and one at 24 hours. Unexpected results merit scrutiny, which helps guide future studies. 1 Clinical investigators need to repeat this study to see whether the difference in postoperative pain is a reproducible finding. 6 A single study is inadequate to reach the conclusion that propofol is associated with less postoperative pain than isoflurane, despite a P value less than 0.01. Bayesian inference and common sense demand that extraordinary findings be supported by extraordinary evidence. We would like these findings to be true, but what we would like counts for nothing. We practice this way, in part, because our N = 2 consensus is that patients awakening from propofol have less pain than patients awakening from inhaled anesthetics. We are both avid practitioners of propofol-based anesthesia, nearly to the exclusion of inhaled anesthetics. Here we must disclose our conflict of interest. found that propofol significantly reduced pain in the second hour compared with patients receiving isoflurane, 5 corroborating the results of the present study. In patients with sleep apnea undergoing uvulopalatopharyngoplasty, Hendolin et al. 4 Patients receiving propofol had increased pain and opioid requirements for the first 6 hours compared with patients receiving isoflurane, exactly the opposite of the findings of Cheng et al., but equally surprising. compared postoperative pain and analgesic requirements in patients receiving propofol for maintenance with patients receiving isoflurane. The few previous studies that found differences do not agree. Unless studies are powered to examine pain as an outcome, and incorporate repeated assessments of postoperative pain over time to separate intersubject from intrasubject variability, differences in postoperative pain may easily be missed. Nearly all of these reported no difference. The short answer is “yes, and no.” As of today (October 18, 2007), PubMed lists 644 clinical trials with the search terms “isoflurane propofol.” Our quick review identified about a dozen that measured postoperative pain and opioid consumption. Haven’t the many clinical trials comparing isoflurane and propofol recovery already measured postoperative pain and addressed this question? 2,3 However, postoperative pain is fundamentally different from lidocaine spinal toxicity. After nearly 40 years of apparently safe spinal administration, anesthesiologists discovered that lidocaine was potentially neurotoxic in the intrathecal space. The short answer is “yes.” There are many examples in medicine of important clinical findings being missed for decades. 1 Is this possible? After nearly three decades of research specifically comparing the recovery characteristics of propofol and isoflurane, could such an obvious finding be missed? suggest we have missed something similarly familiar: maintenance of anesthesia with propofol is associated with less postoperative pain than maintenance of anesthesia with isoflurane. In this month’s issue of Anesthesia & Analgesia, Cheng et al. Having played with even and prime numbers since elementary school, how could anyone miss something so obvious? It is unproven, but there are no counterexamples below 10 18. The Goldbach conjecture states that every even number is the sum of two primes. Last month one of us (SLS) learned about the “Goldbach conjecture,” which your children probably already know. Every so often we are startled to discover something new about a topic we thought we understood completely.