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

Perioperative respiratory adverse events (PRAEs) remain 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. To clarify the effectiveness of inhaling penehyclidine in reducing PRAEs in pediatric patients at risk scheduled for elective surgery following sevoflurane anesthesia with LMA. This is a prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. Two hundred and four children, aged 3 to 7 years, undergoing elective minor ophthalmic surgery, who are at high risk of PRAEs, 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 within 30 minutes prior to surgery. The primary outcome is the incidence of PRAEs. 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. 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. ClinicalTrials.gov (NCT06624696). Registered on 30 September 2024. https://clinicaltrials.gov/study/NCT06624696.