Balancing benefit and risk: clinical considerations in the use of acetaminophen, non-steroidal anti-inflammatory drugs, and dexamethasone for perioperative multimodal analgesia.

Multimodal analgesia, incorporating agents with diverse mechanisms of action, is a cornerstone of perioperative pain management, aiming to optimize analgesia while minimizing opioid-related adverse effects. Despite well-established guidelines, its adoption remains inconsistent due to entrenched practices and concerns about potential risks. This review focuses on the rationale and clinical considerations for foundational multimodal agents-acetaminophen, non-steroidal anti-inflammatory drugs, and dexamethasone-highlighting their benefits, contraindications, and controversies. Evidence regarding key concerns, including hepatotoxicity, nephrotoxicity, anastomotic leakage, bleeding, infection, and hyperglycemia, is comprehensively reviewed. While these concerns are not entirely unfounded, clear supporting data is often limited, highlighting the importance of a critical and thorough evaluation of the available evidence. Indiscriminate advocacy for or reluctance to adopt multimodal analgesia is equally undesirable; instead, a balanced, evidence-based approach is necessary. By refining the understanding of these agents, practitioners can support the broader implementation of multimodal analgesia in perioperative care, ultimately improving patient recovery and optimizing postoperative outcomes.