Tegileridine 0.5 mg reduces fentanyl-induced cough incidence from 28.7% to 11.1%Tegileridine reduces coughing during surgery after fentanyl injection

BackgroundFentanyl-induced cough (FIC) is a common adverse reaction during anesthetic induction. Although usually transient, FIC may increase intracranial, intraocular, and intra-abdominal pressures and cause serious complications. Tegileridine (SHR8554), a G-protein-biased μ-opioid receptor agonist, may modulate opioid-induced cough, although the underlying mechanism remains unproven. This study evaluated whether tegileridine pretreatment reduces FIC.MethodsIn this prospective, randomized, double-blind, placebo-controlled trial, 232 adults scheduled for elective surgery under general anesthesia were screened, and 216 were randomized to receive tegileridine 0.5 mg diluted to 5 mL (Group T) or 5 mL normal saline (Group C). The study drug was injected intravenously over 10 s immediately before rapid fentanyl injection (4 μg·kg−1 over 2 s). The primary endpoint was FIC incidence within 2 min after fentanyl injection. Secondary endpoints included cough severity, hemodynamic changes, and adverse events.ResultsFIC occurred in 31 of 108 patients in Group C and 12 of 108 patients in Group T (28.7% vs. 11.1%; χ2 = 10.48, P = 0.001). Tegileridine reduced the relative risk of FIC by 61.3% (RR, 0.39; 95% CI, 0.21–0.71), with an absolute risk reduction of 17.6% and a number needed to treat of 5.7. Cough severity was lower in Group T (P < 0.001). MAP and HR changes did not differ significantly, and immediate adverse events were uncommon.ConclusionTegileridine 0.5 mg pretreatment reduced the incidence and severity of FIC without evidence of immediate hemodynamic instability. Further active-comparator, dose-finding, and broader safety studies are required before routine clinical adoption.Clinical trial registrationhttps://www.chictr.org.cn/searchproj.html, identifier: ChiCTR2500115512.