A sequential dose-finding study of fentanyl during remimazolam induction for tracheal intubation in adults

Remimazolam is associated with relatively stable hemodynamics during anesthetic induction but does not provide analgesia to attenuate the sympathetic response to endotracheal intubation. Although several adjunctive agents may attenuate this response, opioids are commonly used during induction. This prospective sequential study aimed to estimate the ED 50 of fentanyl associated with hemodynamic stability during remimazolam bolus induction. This prospective sequential dose-finding study used Dixon’s up-and-down method in adults undergoing elective surgery with bolus remimazolam 0.2 mg/kg. Success was defined as maintaining mean blood pressure and heart rate within 20% of baseline for 2 min post-intubation. The primary analysis used centered isotonic regression to estimate the ED 50 from the full sequential allocation. To evaluate the quality of induction, integrated hemodynamic indices including average real variability (ARV) and time in target range (TTR) were derived from hemodynamic data. Overall, thirty-one patients were included in the final analysis. The full-sequence centered isotonic regression estimate of ED 50 was 2.85 µg/kg (90% confidence interval [CI] 2.241–3.313). The ARV and TTR showed no marked variation across the observed fentanyl dose range. In this prospective sequential study, the full-sequence centered isotonic regression estimate of the ED 50 of fentanyl associated with hemodynamic stability during tracheal intubation under remimazolam bolus induction was 2.85 µg/kg. This preliminary, protocol-specific estimate requires confirmation in larger prospective studies and should not be interpreted as a recommended fentanyl dose for routine clinical practice.