Balancing Analgesia vs ORAEs in Postoperative Acute Pain: Consequences, Strategies, and New Approaches

Author: Charles E. Argoff

This presentation will review the consequences of not adequately addressing postoperative acute pain, strategies for balancing analgesia against opioid related adverse events in this setting, and new approaches on the horizon. Postoperative acute pain continues to be undertreated in a large number of cases. This may be due to a wide variety of factors, notably drug related adverse events. Conventional opioids, for example, are widely employed for the management of moderate to severe acute pain. They function by binding to μ receptors and nonselectively activating 2 downstream pathways: the G protein pathway, associated with analgesia, and the β-arrestin pathway, associated with opioid related adverse events (ORAEs) and inhibition of G proteinmediated analgesia. ORAEs, including respiratory depression, are serious, pose a risk to patient safety, and limit dosing required for optimal analgesia. Consequences of suboptimal acute pain management are numerous and include prolonged opioid use, potential development of chronic pain, and increased morbidity, length of stay, time to discharge, and time before ambulation. Greater spotlight is needed on this unmet need, particularly in patient groups--the opioid tolerant, obese, respiratory compromised, elderly, and those with sleep apnea--at greater risk for undertreatment of acute postoperative pain, where prevalence and impact of adverse events is heightened. New therapeutic approaches have been developed in the past decade to address some of these issues, including use of multimodal therapy, reformulations in analgesics, innovations in drug delivery, and μ-GPS modulators, which are novel μ receptor modulators that differentially activate G protein while causing low β-arrestin recruitment to the μ receptor. (Recorded at PAINWeek 2016)

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