Sufentanil in Intensive Care: A Narrative Review

Background: Modern intensive care paradigms prioritize optimal analgesia over heavy sedation. While morphine, fentanyl, and remifentanil are widely used, sufentanil is relatively unknown in several countries. Aimed primarily at intensive care physicians, this narrative review evaluates the utilization of sufentanil in critically ill adult patients across four fundamental dimensions: (1) translational pharmacology (chemical structure, pharmacokinetics, pharmacodynamics, and pharmacogenomics); (2) indications and safety precautions; (3) clinical evidence in ICU patients; and (4) therapeutic positioning in contemporary ICU analgosedation and future research directions. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE focusing on the translational pharmacology, safety parameters, and clinical studies of sufentanil critically ill adults. The synthesis was structured according to SANRA principles for high-quality narrative reviews and includes articles published up to February 2026. Results: Sufentanil exhibits an exceptionally high affinity for the µ-opioid receptor, providing a potency 10-fold greater than fentanyl and 1000-fold greater than morphine. It has an experimental therapeutic index (LD50/ED50) nearly two orders of magnitude wider than that of fentanyl, enabling safe, highly granular bedside titration. Unlike morphine, hepatic CYP3A4 biotransformation yields completely inactive metabolites, preventing toxic accumulation during acute kidney injury. Furthermore, receptor-binding dynamics suggest a lower propensity for recruiting β-arrestins and activating NMDA pathways, potentially reducing opioid-induced hyperalgesia (OIH). Clinically, pilot trials in neurocritical cohorts demonstrate that sufentanil maintains reliable cerebral hemodynamic stability. In postoperative cardiac surgery and large ICU registries, sufentanil may reduce the mechanical ventilation duration, accelerate extubation, and shorten ICU length of stay. Conclusions: For critically ill adults, sufentanil is an excellent alternative to traditional opioids because it offers high-precision titratability, potent analgesia, and a safer metabolic profile.