En randomisert kontrollert studie av inhalering av penehyclidin for å forhindre perioperative respiratoriske bivirkninger hos barn i risiko (PEPSI)
Inhalering av penehyclidin for å forhindre perioperative respiratoriske bivirkninger hos barn i risiko som gjennomgår mindre elektiv kirurgi
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.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Fase
- Fase 4
Kontakter og plasseringer
Studiesteder
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Guangdong
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Guangzhou, Guangdong, Kina, 510060
- Zhongshan Ophthalmic Center, Sun Yat-sen University
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Shenzhen, Guangdong, Kina, 518040
- Shenzhen Eye Hospital
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Forebygging
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: The penehyclidine hydrochloride group
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 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. |
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Placebo komparator: The normal saline group
Inhaling normal saline in a total volume of 5 ml for nebulization therapy within 30 min prior to surgery. |
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. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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The incidence of PRAEs
Tidsramme: 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.
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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.
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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The severity of major respiratory adverse events if occurs
Tidsramme: 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.
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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. |
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.
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Ease of LMA insertion
Tidsramme: From the beginning of LMA insertion until the completion of successful LMA insertion, assessed up to 24 hours
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This outcome includes time to successful insertion, the number of insertion attempts, and difficulty at insertion. |
From the beginning of LMA insertion until the completion of successful LMA insertion, assessed up to 24 hours
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The episode and degree of salivation during removal of LMA
Tidsramme: At the time of LMA removal, assessed up to 24 hours
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Degree of salivation is evaluated as follows: 1=none; 2=minimal, no suction; 3=moderate, suction 1×; 4=copious, suction>1×. |
At the time of LMA removal, assessed up to 24 hours
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The airway hyperreactivity score
Tidsramme: From the time of LMA removal until regaining consciousness from anesthesia, assessed up to 24 hours
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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. |
From the time of LMA removal until regaining consciousness from anesthesia, assessed up to 24 hours
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The anesthesia-related time
Tidsramme: During the phases of anesthesia emergence and recovery, assessed up to 24 hours
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The anesthesia-related time includes time to LMA removal, and PACU stay time. |
During the phases of anesthesia emergence and recovery, assessed up to 24 hours
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Emergence agitation
Tidsramme: From the time of LMA removal until regaining consciousness from anesthesia, assessed up to 24 hours
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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. |
From the time of LMA removal until regaining consciousness from anesthesia, assessed up to 24 hours
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Postoperative pain score
Tidsramme: From the time of arrival in PACU until the time of discharge from PACU, assessed up to 24 hours
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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. |
From the time of arrival in PACU until the time of discharge from PACU, assessed up to 24 hours
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The change of systolic blood pressure (SBP)
Tidsramme: 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
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The changes of SBP will be recorded. |
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
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The change of heart rate (HR)
Tidsramme: 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
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The changes of HR will be recorded. |
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
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The change of SpO2
Tidsramme: 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
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The change of SpO2 will be recorded. |
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
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Other adverse events
Tidsramme: From beginning of inhalation until the 24 postoperative hours.
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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. |
From beginning of inhalation until the 24 postoperative hours.
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The incidence of respiratory infections within 7 days after surgery
Tidsramme: Within 7 days after surgery.
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Children who develop respiratory infections within 7 days after surgery will be recorded during postoperative follow-up. |
Within 7 days after surgery.
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Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 Jun;77(6):649-658. doi: 10.1111/anae.15716. Epub 2022 Mar 23.
- 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;27(1):366. doi: 10.1186/s13063-026-09671-x.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
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- IIT2024111
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