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

Phase 4

Recruiting

• Conditions: Respiratory Hypersensitivity; Perioperative Respiratory Adverse Events; Anticholinergics; Inhalation Therapy; Complications; High Risk
• Interventions: Drug: Penehyclidine hydrochloride; Drug: Normal Saline

• Registration Number: NCT06624696
• Lead Sponsor: Sun Yat-sen University

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.

Detailed Description

Children with high risk factors of perioperative respiratory adverse events (PRAEs) remains a challenge for general anesthesia, inhalation of penehyclidine hydrochloride (PHC) has been showed to reduce postoperative pulmonary complications and enhance the recovery in high-risk surgical patients. Thus, prophylactic PHC inhalation might show promising benefits against PRAEs in pediatric anesthesia. This clinical study is designed to test the hypothesis that pediatric patients who exist at least 1 risk factor of PRAEs prophylactically to inhale PHC have a lower prevalence of PRAEs.

Study Timeline

• Study First Submitted: 2024-09-30
• Study First Submitted QC: 2024-10-02
• Study First Posted: 2024-10-03
• Study Start: 2024-11-12
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-01
• Last Update Posted: 2025-01-03
• Primary Completion: 2025-09-30
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 204

Inclusion Criteria

1. Pediatric patients aged 3 to 7 years.
2. Scheduled to undergo ophthalmic surgery.
3. 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).

Read More

Exclusion Criteria

1. American Society of Anesthesiologists (ASA) physical classification ≥ IV.
2. Known cardiopulmonary diseases (eg. uncorrected congenital heart disease, primary or secondary pulmonary hypertension, tumors, or structural lung diseases).
3. Severe renal dysfunction (requirement of renal replacement therapy) or severe hepatic dysfunction (Child-Pugh grade C);
4. Neurological disorders.
5. Neuromuscular diseases.
6. Contraindication for PHC.
7. Inhalation of β2-receptor activator, M-receptor blockers and/or glucocorticoids within 1 month before surgery.
8. Allergy to anticholinergic drugs.
9. Use of endotracheal tube (ETT) for ventilation.
10. Known difficult airway.
11. Severe upper respiratory tract infections (URTIs) and the anesthesiologist recommended delaying surgery.
12. 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.
13. Parents refusing to allow their children to participate.
14. Obesity, with a body mass index (BMI) over 95th percentile according to the WHO guideline.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
The penehyclidine hydrochloride group	Penehyclidine hydrochloride	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.
The normal saline group	Normal Saline	Inhaling normal saline in a total volume of 5 ml for nebulization therapy within 30 min prior to surgery.

Primary Outcome Measures

Name	Time	Method
The incidence of PRAEs	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.	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.

Secondary Outcome Measures

Name	Time	Method
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.	Major respiratory adverse events include laryngospasm and bronchospasm. Laryngospasm will be scored according to its severity as follows: 1=none, 2=partial-reposition airway, 3=partial-continuous positive airway pressure (CPAP), 4=complete-muscle relaxant. Bronchospasm will be scored according to its severity as follows: 1=none, 2= expiration only, 3= expiration and inspiration, 4=difficult to ventilate, require treatment.
Ease of LMA insertion	From the beginning of LMA insertion until the completion of successful LMA insertion, assessed up to 24 hours	This outcome includes time to successful insertion, the number of insertion attempts, and difficulty at insertion.
The episode and degree of salivation during removal of LMA	At the time of LMA removal, assessed up to 24 hours	Degree of salivation is evaluated as follows: 1=none; 2=minimal, no suction; 3=moderate, suction 1×; 4=copious, suction\>1×.
The airway hyperreactivity score	From the time of LMA removal until regaining consciousness from anesthesia, assessed up to 24 hours	This score is used to assessed severity of PRAEs, accounting for the intensity of coughing, breath holding, and oxygen desaturation on a scale ranging from 0 (none) to 4 (severe). The maximum score is 12, and a score of ≤3 is categorized as mild, 4 to 8 as moderate, and ≥9 as severe.
The anesthesia-related time	During the phases of anesthesia emergence and recovery, assessed up to 24 hours	The anesthesia-related time includes time to LMA removal, and PACU stay time.
Emergence agitation	From the time of LMA removal until regaining consciousness from anesthesia, assessed up to 24 hours	Emergence agitation will be evaluated within stay in PACU using the Aono's four point scale (1: calm; 2: not calm but easily consolable; 3: not easily calmed restless or moderately agitated; 4: combative, disoriented, or excited). The scale scoring of 1 and 2 are considered as the absence of EA, and scale of 3 and 4 are considered as the presence of EA.
Postoperative pain score	From the time of arrival in PACU until the time of discharge from PACU, assessed up to 24 hours	Postoperative pain score will be assessed within stay in the PACU using the Wong-Baker Pain Scale. A score higher than 4 is defined as moderate-to-severe pain which need to be timely managed.
The change of systolic blood pressure (SBP)	At baseline; 5 minutes after inhaling PHC; the completion of inhaling PHC; LMA insertion; upon arrival in PACU; pre-LMA mask removal; post-LMA mask removal; ready to discharge from PACU, assessed up to 24 hours	The changes of SBP will be recorded.
The change of heart rate (HR)	At baseline; 5 minutes after inhaling PHC; the completion of inhaling PHC; LMA insertion; upon arrival in PACU; pre-LMA mask removal; post-LMA mask removal; ready to discharge from PACU, assessed up to 24 hours	The changes of HR will be recorded.
The change of SpO2	At baseline; 5 minutes after inhaling PHC; the completion of inhaling PHC; LMA insertion; upon arrival in PACU; pre-LMA mask removal; post-LMA mask removal; ready to discharge from PACU, assessed up to 24 hours	The change of SpO2 will be recorded.
Other adverse events	From beginning of inhalation until the 24 postoperative hours.	Other adverse events potentially related to inhale the study drug from beginning of inhalation until the 24 postoperative hours, including postoperative nausea and vomitting (PONV), dry month, palpation, dizziness, fever, cough, urine retention, and flushing.
The incidence of respiratory infections within 7 days after surgery	Within 7 days after surgery.	Children who develop respiratory infections within 7 days after surgery will be recorded during postoperative follow-up.

Trial Locations

Locations (2)

Shenzhen Eye Hospital; 🇨🇳 Shenzhen, Guangdong, China

Zhongshan Ophthalmic Center, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China