Analgesic Strategies in Adult Intensive Care Units: A Systematic Review of Opioid and Non-opioid Approaches

Effective analgesia and sedation are critical components of care in adult intensive care units, with strategies ranging from opioid and non-opioid regimens to multimodal and protocol-guided approaches. This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Evidence was synthesized from randomized controlled trials and observational studies across PubMed, Cochrane Library, Scopus, and Web of Science through October 2025, evaluating sedative and analgesic interventions - including opioid, non-opioid, alpha-2 agonist, and protocolized approaches - in adult intensive care unit (ICU) populations. The methodological quality of the chosen studies was assessed using the Modified Downs and Black checklist. A total of 11 eligible studies demonstrated that dexmedetomidine provided comparable or superior sedation quality relative to benzodiazepines and propofol, reduced delirium incidence, and shortened time to extubation; remimazolam yielded equivalent sedation to propofol with fewer hypotensive events; and protocolized or nurse-driven sedation strategies improved ventilator-free days and reduced ICU length of stay compared with daily interruption alone. Multimodal and non-opioid adjuvant therapies reduced opioid requirements and nausea while maintaining hemodynamic stability, and across studies, light, cooperative sedation paired with validated pain and sedation assessment tools was associated with better recovery profiles and fewer cognitive complications. Overall, the evidence supports adopting multimodal, analgesia-first, and non-gamma-aminobutyric-acid (non-GABA) sedation approaches in critical care, with dexmedetomidine and remimazolam offering superior safety and delirium prevention compared with benzodiazepines.