CON: anesthesia versus analgesia: assessing the analgesic effects of anesthetic drugs.

Assessing the analgesic effects of anesthetic drugs can be extremely challenging. The IV anesthetic propofol is commonly used for induction and/or maintenance of anesthesia and sedation in the operating room in combination with opioid and non-opioid analgesic drugs. Analogous to other IV anesthetics with -aminobutyric acid agonist receptor activity, propofol produces dose-dependent central nervous system depression resulting in sedation and hypnosis (i.e., unconsciousness). In the current issue of Anesthesia & Analgesia, Tan et al. report that use of propofol seems to be associated with greater residual postoperative analgesia than the volatile anesthetic sevoflurane. Early studies with propofol in both animals and humans have failed to demonstrate any evidence of analgesic-like activity. In an animal study by Merrill et al., propofol produced anesthesia but failed to produce the experimental findings typically associated with nociception, suggesting that propofol lacks analgesic properties. Another rodent study by Ng and Antognini found that isoflurane and propofol both had similar effects on neuronal “windup” in the spinal cord, a factor associated with persistent pain. Of interest, Boccara et al. compared postoperative pain and analgesic requirements in patients receiving propofol or isoflurane for maintenance of anesthesia and reported that patients receiving propofol actually had increased pain and opioid requirements for the first 6 hours after surgery compared with patients receiving isoflurane. Conducting a more recent clinical study, Fassoulaki et al. were unable to demonstrate any difference in postoperative pain scores or in the requirement for opioid analgesic medication among patients maintained with propofol, sevoflurane, or desflurane. What then is the basis for suggesting that this popular IV sedative-hypnotic drug might possess analgesic properties? As mentioned in the introduction to the article by Tan et al. in the current issue of Anesthesia & Analgesia, a clinical study by Cheng et al. of the potential postoperative analgesic effects of nicotine found that patients anesthetized with propofol experienced less postoperative pain than patients anesthetized with isoflurane. A study in rodents by Guindon et al. demonstrated that in a test of inflammatory pain, locally injected propofol decreased pain behavior in a dose-dependent manner. The authors hypothesized that this antinociceptive activity was mediated, in part, by cannabinoid receptors 1 and 2 (CB1 and CB2). Although Tan et al. reported lower “cumulative” pain scores in the early postoperative period ( 4 hours) when outpatients undergoing brief laparoscopic surgical procedures were induced and maintained with propofol rather than with sevoflurane, several aspects of this study require more careful analysis. First, in examining the differences in the mean visual analog scale (VAS) pain scores in their Figure 1, there is no evidence that any of the individual mean pain scores were significantly different between the 2 anesthetic groups. Given the high degree of variability at each of the individual data points, one could question the clinical relevance, if any, of the alleged difference ( 1 point on an 11-point VAS) between the 2 anesthetic treatment groups with respect to postoperative pain. It would appear that a statistical difference was only achieved by combining the VAS pain scores as part of an area under the curve analysis. Although it was not specified, one would assume that IV lidocaine was administered before injecting the induction dose of propofol (but not before induction with sevoflurane). Depending on the dose of lidocaine, this factor might also contribute to the minor differences reported in the VAS pain scores after these short surgical procedures because IV lidocaine reduces postoperative pain and possesses opioidsparing activity. Curiously, despite a nonsignificant reduction in the morphine analgesic requirement before discharge (and a similar requirement for oral opioidcontaining analgesics in the postdischarge period), the propofol-treated patients had the exact incidence of postoperative nausea and vomiting as those receiving sevoflurane. Given that propofol possesses well-documented antiemetic activity (compared with both IV and volatile From the Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas; Director of Research at Policlinico Abano-Leonardo Foundation, Abano-Terme, Italy.