Inhaling Penehyclidine to Prevent Perioperative Respiratory Adverse Events in Children at Risk Undergoing Sevoflurane Anesthesia

NCT06624696 | Recruiting Phase 4

• 1 other identifier: IIT2024111
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 2

Brief Summary

This randomized controlled study is to evaluate the effectiveness of inhaling penehyclidine hydrochloride in reducing perioperative respiratory adverse events in children at risk undergoing minor elective surgery.

Conditions

Respiratory Hypersensitivity; Perioperative Respiratory Adverse Events; Anticholinergics; Inhalation Therapy; Complications; High Risk

Keywords

perioperative respiratory adverse events; pediatric anesthesia; penehyclidine; sevoflurane

Outcome Measures

Primary Outcomes (1)

• The incidence of PRAEs

  PRAEs are subdivided into two types: major (bronchospasm and laryngospasm) and minor (severe coughing, breath holding, desaturation, upper airway obstruction, and stridor) events. The primary outcome is the incidence of PRAEs. Patients will be considered positive for respiratory adverse events if at least 1 of the above adverse events occurs.

  From beginning of anesthesia induction until the completion of postoperative recovery in PACU (including the phases of anesthesia induction, anesthesia maintenance, postoperative emergency and postoperative recovery), assessed up to 24 hours.

Secondary Outcomes (12)

• The severity of major respiratory adverse events if occurs

  From beginning of anesthesia induction until the completion of postoperative recovery in PACU (including the phases of anesthesia induction, anesthesia maintenance, postoperative emergency and postoperative recovery), assessed up to 24 hours.

• Ease of LMA insertion

  From the beginning of LMA insertion until the completion of successful LMA insertion, assessed up to 24 hours

• The episode and degree of salivation during removal of LMA

  At the time of LMA removal, assessed up to 24 hours

• The airway hyperreactivity score

  From the time of LMA removal until regaining consciousness from anesthesia, assessed up to 24 hours

• The anesthesia-related time

  During the phases of anesthesia emergence and recovery, assessed up to 24 hours

Study Arms (2)

The penehyclidine hydrochloride group

EXPERIMENTAL

Inhaling penehyclidine hydrochloride (a dose of 0.05 mg/kg, diluted and mixed with normal saline to a total volume of 5 ml) for nebulization therapy within 30 min prior to surgery.

Drug: Penehyclidine hydrochloride

The normal saline group

PLACEBO COMPARATOR

Inhaling normal saline in a total volume of 5 ml for nebulization therapy within 30 min prior to surgery.

Drug: Normal Saline

Interventions

Penehyclidine hydrochloride DRUG

The penehyclidine hydrochloride will be diluted to a total volume of 5 mL with normal saline, added to the nebulizer cup for inhalation. Patients will be asked to inhale the entire volume of nebulized drugs within 30 min prior to surgery. The trial drugs will be administered using a jet nebulizer with compressed air flow. Each child will be intructed to begin the nebulization by using a face mask that covers the nose and mouth while the child is seated upright. Children will be encouraged to take deep and slow breaths, inhaling through the mouth and exhaling through the nose, to ensure the drugs effectively reaches the airway.

The penehyclidine hydrochloride group

Normal Saline DRUG

The normal saline with a total volume of 5 mL will be added to the nebulizer cup for inhalation. Patients will be asked to inhale the entire volume of nebulized drugs within 30 min prior to surgery. The trial drugs will be administered using a jet nebulizer with compressed air flow. Each child will be intructed to begin the nebulization by using a face mask that covers the nose and mouth while the child is seated upright. Children will be encouraged to take deep and slow breaths, inhaling through the mouth and exhaling through the nose, to ensure the drugs effectively reaches the airway.

The normal saline group

Eligibility Criteria

• Age: 3 Years - 7 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Pediatric patients aged 3 to 7 years.
• Scheduled to undergo ophthalmic surgery.
• Judged to be at risk of PRAEs (with at least one parentally reported risk factor for the PRAEs, including history of a recent cold, wheezing during exercise, wheezing more than three times in the past 12 months, nocturnal dry cough, eczema, or a family history of asthma, rhinitis, eczema, or exposure to passive smoke).

You may not qualify if:

• American Society of Anesthesiologists (ASA) physical classification ≥ IV.
• Known cardiopulmonary diseases (eg. uncorrected congenital heart disease, primary or secondary pulmonary hypertension, tumors, or structural lung diseases).
• Severe renal dysfunction (requirement of renal replacement therapy) or severe hepatic dysfunction (Child-Pugh grade C);
• Neurological disorders.
• Neuromuscular diseases.
• Contraindication for PHC.
• Inhalation of β2-receptor activator, M-receptor blockers and/or glucocorticoids within 1 month before surgery.
• Allergy to anticholinergic drugs.
• Use of endotracheal tube (ETT) for ventilation.
• Known difficult airway.
• Severe upper respiratory tract infections (URTIs) and the anesthesiologist recommended delaying surgery.
• Participation in other clinical trial during the last month or within the six half-life periods of the study drug used in the last trial.
• Parents refusing to allow their children to participate.
• Obesity, with a body mass index (BMI) over 95th percentile according to the WHO guideline.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Shenzhen Eye Hospital: collaborator

Study Sites (2)

Zhongshan Ophthalmic Center, Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

RECRUITING

Shenzhen Eye Hospital

Shenzhen, Guangdong, 518040, China

RECRUITING

Related Publications (17)

• Tait AR, Malviya S, Voepel-Lewis T, Munro HM, Seiwert M, Pandit UA. Risk factors for perioperative adverse respiratory events in children with upper respiratory tract infections. Anesthesiology. 2001 Aug;95(2):299-306. doi: 10.1097/00000542-200108000-00008.

  PMID: 11506098 BACKGROUND

• Ramgolam A, Hall GL, Sommerfield D, Slevin L, Drake-Brockman TFE, Zhang G, von Ungern-Sternberg BS. Premedication with salbutamol prior to surgery does not decrease the risk of perioperative respiratory adverse events in school-aged children. Br J Anaesth. 2017 Jul 1;119(1):150-157. doi: 10.1093/bja/aex139.

  PMID: 28974069 BACKGROUND

• Tait AR, Voepel-Lewis T, Burke C, Kostrzewa A, Lewis I. Incidence and risk factors for perioperative adverse respiratory events in children who are obese. Anesthesiology. 2008 Mar;108(3):375-80. doi: 10.1097/ALN.0b013e318164ca9b.

  PMID: 18292674 BACKGROUND

• An MZ, Xu CY, Hou YR, Li ZP, Gao TS, Zhou QH. Effect of intravenous vs. inhaled penehyclidine on respiratory mechanics in patients during one-lung ventilation for thoracoscopic surgery: a prospective, double-blind, randomised controlled trial. BMC Pulm Med. 2023 Sep 19;23(1):353. doi: 10.1186/s12890-023-02653-8.

  PMID: 37726724 BACKGROUND

• Yan T, Liang XQ, Wang GJ, Wang T, Li WO, Liu Y, Wu LY, Yu KY, Zhu SN, Wang DX, Sessler DI. Prophylactic Penehyclidine Inhalation for Prevention of Postoperative Pulmonary Complications in High-risk Patients: A Double-blind Randomized Trial. Anesthesiology. 2022 Apr 1;136(4):551-566. doi: 10.1097/ALN.0000000000004159. Erratum In: Anesthesiology. 2023 Feb 1;138(2):232. doi: 10.1097/ALN.0000000000004203.

  PMID: 35226725 BACKGROUND

• Wang NA, Su Y, Che XM, Zheng H, Shi ZG. Penehyclidine ameliorates acute lung injury by inhibiting Toll-like receptor 2/4 expression and nuclear factor-kappaB activation. Exp Ther Med. 2016 May;11(5):1827-1832. doi: 10.3892/etm.2016.3154. Epub 2016 Mar 11.

  PMID: 27168812 BACKGROUND

• Wang Y, Gao Y, Ma J. Pleiotropic effects and pharmacological properties of penehyclidine hydrochloride. Drug Des Devel Ther. 2018 Oct 5;12:3289-3299. doi: 10.2147/DDDT.S177435. eCollection 2018.

  PMID: 30323561 BACKGROUND

• Tait AR, Burke C, Voepel-Lewis T, Chiravuri D, Wagner D, Malviya S. Glycopyrrolate does not reduce the incidence of perioperative adverse events in children with upper respiratory tract infections. Anesth Analg. 2007 Feb;104(2):265-70. doi: 10.1213/01.ane.0000243333.96141.40.

  PMID: 17242078 BACKGROUND

• Wudineh DM, Berhe YW, Chekol WB, Adane H, Workie MM. Perioperative Respiratory Adverse Events Among Pediatric Surgical Patients in University Hospitals in Northwest Ethiopia; A Prospective Observational Study. Front Pediatr. 2022 Feb 11;10:827663. doi: 10.3389/fped.2022.827663. eCollection 2022.

  PMID: 35223702 BACKGROUND

• Ramgolam A, Hall GL, Zhang G, Hegarty M, von Ungern-Sternberg BS. Deep or awake removal of laryngeal mask airway in children at risk of respiratory adverse events undergoing tonsillectomy-a randomised controlled trial. Br J Anaesth. 2018 Mar;120(3):571-580. doi: 10.1016/j.bja.2017.11.094. Epub 2018 Jan 27.

  PMID: 29452814 BACKGROUND

• von Ungern-Sternberg BS, Sommerfield D, Slevin L, Drake-Brockman TFE, Zhang G, Hall GL. Effect of Albuterol Premedication vs Placebo on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomies: The REACT Randomized Clinical Trial. JAMA Pediatr. 2019 Jun 1;173(6):527-533. doi: 10.1001/jamapediatrics.2019.0788.

  PMID: 31009034 BACKGROUND

• Peterson MB, Gurnaney HG, Disma N, Matava C, Jagannathan N, Stein ML, Liu H, Kovatsis PG, von Ungern-Sternberg BS, Fiadjoe JE; PAWS-COVID-19 Group. Complications associated with paediatric airway management during the COVID-19 pandemic: an international, multicentre, observational study. Anaesthesia. 2022 Mar 23;77(6):649-58. doi: 10.1111/anae.15716. Online ahead of print.

  PMID: 35319088 BACKGROUND

• Oofuvong M, Geater AF, Chongsuvivatwong V, Chanchayanon T, Sriyanaluk B, Saefung B, Nuanjun K. Excess costs and length of hospital stay attributable to perioperative respiratory events in children. Anesth Analg. 2015 Feb;120(2):411-9. doi: 10.1213/ANE.0000000000000557.

  PMID: 25517194 BACKGROUND

• Hii J, Templeton TW, Sommerfield D, Sommerfield A, Matava CT, von Ungern-Sternberg BS. Risk assessment and optimization strategies to reduce perioperative respiratory adverse events in pediatric anesthesia-Part 1 patient and surgical factors. Paediatr Anaesth. 2022 Feb;32(2):209-216. doi: 10.1111/pan.14377. Epub 2021 Dec 20.

  PMID: 34897906 BACKGROUND

• Shen F, Zhang Q, Xu Y, Wang X, Xia J, Chen C, Liu H, Zhang Y. Effect of Intranasal Dexmedetomidine or Midazolam for Premedication on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial. JAMA Netw Open. 2022 Aug 1;5(8):e2225473. doi: 10.1001/jamanetworkopen.2022.25473.

  PMID: 35943745 BACKGROUND

• Lin Y, Chen Y, Huang J, Chen H, Shen W, Guo W, Chen Q, Ling H, Gan X. Efficacy of premedication with intranasal dexmedetomidine on inhalational induction and postoperative emergence agitation in pediatric undergoing cataract surgery with sevoflurane. J Clin Anesth. 2016 Sep;33:289-95. doi: 10.1016/j.jclinane.2016.04.027. Epub 2016 May 18.

  PMID: 27555179 BACKGROUND

• Zhu Y, Mai Y, Wang Y, Huang T, Huang J, Lin Y, Zhao D, Gan X. 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. Trials. 2026 Apr 2. doi: 10.1186/s13063-026-09671-x. Online ahead of print.

  PMID: 41928281 DERIVED

MeSH Terms

Conditions

Respiratory Hypersensitivity

Interventions

penehyclidine; Saline Solution

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Xiaoliang Gan, PhD

CONTACT

86+13688893908; ganxl@mail.sysu.edu.cn

Yanling Zhu, MD

CONTACT

86+18898600243; zhuyling8@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The head of Anesthesiology, Zhongshan Ophthalmic Center, Sun Yat-sen University

Study Record Dates

• First Submitted: September 30, 2024
• First Posted: October 3, 2024
• Study Start: November 12, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)