“Opioid-sparing” sounds like an automatic win until you look closely at what replaces the opioids. We take on one of the toughest questions in modern anesthesiology: how do we reduce opioid-related harm without trading it for medication interactions, kidney injury, bleeding risk, rebound pain, or poorly controlled postoperative pain?We break down what individualized multimodal analgesia really means in day-to-day anesthesia practice. That starts before the first dose is ordered, with a preoperative assessment that weighs comorbidities, baseline renal function, hydration status, and potential drug-drug interactions. We also dig into the medication safety side of multimodal protocols, including why CYP2D6 matters for common oral opioids like hydrocodone, oxycodone, and tramadol, and how CYP2D6 inhibitors such as certain antidepressants can change opioid effectiveness and even extend opioid use after discharge.Regional anesthesia remains a cornerstone, but we stay honest about the pitfalls: incomplete coverage, visceral pain that sneaks through, and the timing mismatch that can trigger rebound pain 12 to 24 hours after a single-shot block, sometimes when the patient is already home. We also discuss when continuous peripheral nerve blocks may better match the duration of perioperative stress and inflammation, plus the practical barriers that determine whether advanced regional techniques are feasible.If you care about opioid-sparing anesthesia, patient safety, and better postoperative recovery, listen and share this with a colleague. Subscribe to the podcast, leave a review, and tell us: what’s one change you’ll make to your multimodal analgesia plan after hearing this?For show notes & transcript, visit our episode page at apsf.org: https://www.apsf.org/podcast/313-individualized-multimodal-analgesia/© 2026, The Anesthesia Patient Safety Foundation

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