Procedural sedation and analgesia outside the operating room: Drug selection, safety, and emerging trends

ABSTRACT

Procedures performed outside the operating room now account for a substantial proportion of all anesthetic activity, with nonoperating room anesthesia projected to represent up to 50% of anesthetic interventions within the next decade. Workforce constraints in anesthesiology have accelerated the need for structured frameworks enabling nonanesthesiologists to provide procedural sedation and analgesia (PSA) safely. This narrative review evaluates drug selection, safety principles, and emerging pharmacological trends in PSA outside the operating room, with particular attention to the nonanesthesiologist provider model. Midazolam combined with fentanyl or ketamine remains the evidence-based foundation for nonanesthesiologist PSA. Ketamine’s dissociative profile preserves airway reflexes, spontaneous ventilation, and hemodynamic stability while providing reliable analgesia. Propofol and dexmedetomidine are unsuitable for nonanesthesiologist use: propofol carries the risk of irreversible transition to general anesthesia without a reversal agent, and dexmedetomidine is associated with significant bradycardia (odds ratio [OR]: 3.60; 95% confidence interval [CI]: 2.29–5.67) and hypotension (OR: 1.95; 95% CI: 1.25–3.05) without pharmacological reversal. Remimazolam, an ultra-short-acting reversible benzodiazepine with organ-independent metabolism, is the most promising emerging agent. Structured credentialing, capnography monitoring, and defined rescue competencies are essential institutional requirements for safe nonanesthesiologist practice.