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

Official title

Inhaling Penehyclidine to Prevent Perioperative Respiratory Adverse Events in Children at Risk Undergoing Sevoflurane Anesthesia: a Double-blind, Randomized, Placebo-controlled Trial

Overview

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.

Interventions

• Drug Penehyclidine hydrochloride
  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 tak
• Drug Normal Saline
  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 throug

Primary outcome measures

• The incidence of PRAEs [Time frame: 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 outcome measures (12)

• The severity of major respiratory adverse events if occurs [Time frame: 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 [Time frame: 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 [Time frame: At the time of LMA removal, assessed up to 24 hours]
• The airway hyperreactivity score [Time frame: From the time of LMA removal until regaining consciousness from anesthesia, assessed up to 24 hours]
• The anesthesia-related time [Time frame: During the phases of anesthesia emergence and recovery, assessed up to 24 hours]
• Emergence agitation [Time frame: From the time of LMA removal until regaining consciousness from anesthesia, assessed up to 24 hours]
• Postoperative pain score [Time frame: From the time of arrival in PACU until the time of discharge from PACU, assessed up to 24 hours]
• The change of systolic blood pressure (SBP) [Time frame: 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 heart rate (HR) [Time frame: 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 [Time frame: 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]
• Other adverse events [Time frame: From beginning of inhalation until the 24 postoperative hours.]
• The incidence of respiratory infections within 7 days after surgery [Time frame: Within 7 days after surgery.]

Eligibility criteria

Inclusion criteria

• 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).

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

China · 2 centers

• Zhongshan Ophthalmic Center, Sun Yat-sen University — Guangzhou
• Shenzhen Eye Hospital — Shenzhen

Publications

• 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
• 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
• 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
• 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
• 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. PMID 35226725
• 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
• 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
• 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

Identifiers

NCT: NCT06624696 · IIT2024111

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗