Inhaling penehyclidine to prevent perioperative respiratory adverse events in children at risk undergoing sevoflurane anesthesia (PEPSI trial): study protocol for a double-blind, randomized, placebo-controlled trial

Background Perioperative respiratory adverse events (PRAEs) remains a challenge for pediatric anesthesia, inhalation of penehyclidine has been showed to reduce postoperative pulmonary complications and enhance the recovery in high-risk surgical adults. Thus, prophylactic penehyclidine inhalation might show promising benefits against PRAEs in children with high risk factors. Aims To clarify the effectiveness of inhaling penehyclidine in reducing PRAEs in pediatric patients at risk scheduled for elective surgery following sevoflurane anesthesia with LMA. Methods This is a prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. Two hundred and four children, aged 3 to 7 years, undergoing ophthalmic surgery (minor surgery), will be randomized in a ratio of 1:1 to receive either inhaling penehyclidine hydrochloride (PHC, a dose of 0.05 mg/kg, diluted and mixed with normal saline to a total volume of 5 ml) or identical volumes and colour of normal saline before anesthesia. The primary outcome is the incidence of PRAEs between the 2 groups. Secondary outcomes include the airway hyperreactivity (AHR) score, and the severity of laryngospasm and bronchospasm if occurs. Moreover, ease of laryngeal mask airway (LMA) insertion, episode and degree of salivation during removal of LMA, anesthesia-related recovery time, postoperative pain score, incidence of emergence agitation (EA), hemodynamic parameters, other postoperative adverse events related to the study drug within the first 24 postoperative hours, and the development of respiratory infections within 7 days after surgery will be also collected. Discussion The results of this study will provide valuable insights into the potential role of inhaling PHC in reducing PRAEs in a high-risk pediatric cohort during sevofurane anesthesia with LMA, thereby promoting clinical practice. Trial registration ClinicalTrials.gov (NCT06624696). Registered on 30 September 2024. https://clinicaltrials.gov/study/NCT06624696