Recommended intravenous infusion rate of sufentanil during induction of general anesthesia to prevent coughing: a randomized, single-blind, prospective clinical trials

BACKGROUND: Sufentanil-induced cough (SIC) is a prevalent and potentially hazardous reflex during anesthesia induction. While slow injection is known to reduce SIC, the precise dose-response relationship between infusion rate and cough suppression remains poorly defined. This study aimed to identify the optimal intravenous infusion rate of sufentanil to reduce SCI and to estimate the 50% and 95% cough inhibition thresholds (IS₅₀ and IS₉₅) using probit regression analysis. METHODS: A total of 70 adult patients (ASA I-II) scheduled for general anesthesia with tracheal intubation were prospectively enrolled and randomized into seven groups according to different sufentanil infusion rates: Group A, 0.20 mL/s; Group B, 0.225 mL/s; Group C, 0.25 mL/s; Group D, 0.275 mL/s; Group E, 0.30 mL/s; Group F, 0.325 mL/s; and Group G, 0.35 mL/s. All patients received sufentanil at a dose of 0.4 µg/kg (concentration: 5 µg/mL). The incidence and severity of coughing, apnea, hypoxemia, and pruritus within 5 min after injection were recorded. Vital signs-including respiratory rate, heart rate, blood pressure, and oxygen saturation-were measured at baseline and 5 min after drug administration. Cough severity was classified as: none (0 coughs), mild (1-2 coughs), moderate (3-4 coughs), and severe (≥ 5 coughs) during the 5-minute observatiototal period. RESULTS: The incidence of SIC significantly decreased as the infusion rate slowed (P < 0.001). The SIC incidence for rates 0.35, 0.325, 0.30, 0.275, 0.25, 0.225, and 0.20 mL/s were 73.3%, 46.7%, 46.7%, 33.3%, 40.0%, 0.0%, and 13.3%, respectively. Using Probit analysis, the estimated IS₅₀ for cough suppression was 0.310 mL/s(95% CI: 0.288-0.347) and the IS₉₅ was 0.172 mL/s (95% CI: 0.069-0.212). No episodes of severe glottic closure or opioid-induced chest wall rigidity were observed in any group. CONCLUSIONS: To minimize sufentanil-induced coughing in adult patients with normal airway anatomy (ASA I-II, body mass index 16-26 kg/m²), an infusion rate of ≤ 0.172 mL/s (approximately 46 s for 0.4 µg/kg at 5 µg/mL) is recommended, which achieves about 95% cough prevention according to probit regression analysis. However, respiratory depression and apnea remained frequent in this cohort, underscoring the need for adequate preoxygenation, continuous pulse oximetry and capnography monitoring, and immediate availability of airway management equipment during induction with sufentanil 0.4 µg/kg. TRIAL REGISTRATION: ChiCTR2300067455 (Registered on 9 January 2023 ): https://www.chictr.org.cn/.