Review article: Preventive analgesia: quo vadimus?

Abstract

The classic definition of preemptive analgesia requires 2 groups of patients to receive identical treatment before or after incision or surgery. The only difference between the 2 groups is the timing of administration of the drug relative to incision. The constraint to include a postincision or postsurgical treatment group is methodologically appealing, because in the presence of a positive result, it provides a window of time within which the observed effect occurred, and thus points to possible mechanisms underlying the effect: the classic view assumes that the intraoperative nociceptive barrage contributes to a greater extent to postoperative pain than does the postoperative nociceptive barrage. However, this view is too restrictive and narrow, in part because we know that sensitization is induced by factors other than the peripheral nociceptive barrage associated with incision and subsequent noxious intraoperative events. A broader approach to the prevention of postoperative pain has evolved that aims to minimize the deleterious immediate and long-term effects of noxious perioperative afferent input. The focus of preventive analgesia is not on the relative timing of analgesic or anesthetic interventions, but on attenuating the impact of the peripheral nociceptive barrage associated with noxious preoperative, intraoperative, and/or postoperative stimuli. These stimuli induce peripheral and central sensitization, which increase postoperative pain intensity and analgesic requirements. Preventing sensitization will reduce pain and analgesic requirements. Preventive analgesia is demonstrated when postoperative pain and/or analgesic use are reduced beyond the duration of action of the target drug, which we have defined as 5.5 half-lives of the target drug. This requirement ensures that the observed effects are not direct analgesic effects. In this article, we briefly review the history of preemptive analgesia and relate it to the broader concept of preventive analgesia. We highlight clinical trial designs and examples from the literature that distinguish preventive analgesia from preemptive analgesia and conclude with suggestions for future research.