Effect of tegileridine pretreatment on fentanyl-induced cough during general anesthesia induction: a randomized controlled trial.

BACKGROUND

Fentanyl-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.

METHODS

In 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.

RESULTS

FIC 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.

CONCLUSION

Tegileridine 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 REGISTRATION: https://www.chictr.org.cn/searchproj.html, identifier: ChiCTR2500115512.