<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04454866</url>
  </required_header>
  <id_info>
    <org_study_id>202055076</org_study_id>
    <nct_id>NCT04454866</nct_id>
  </id_info>
  <brief_title>Penehyclidine for Prevention of Nausea and Vomiting After Bimaxillary Surgery</brief_title>
  <official_title>Effects of Penehyclidine in Preventing Postoperative Nausea and Vomiting in Patients Underging Bimaxillary Surgery: A Randomised Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University First Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Peking University Hospital of Stomatology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Peking University First Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Postoperative nausea and vomiting (PONV) is a common complication after surgery. Patients&#xD;
      undergoing orthognathic surgery are reported to have a high rate of PONV, especially those&#xD;
      undergoing bimaxillary surgery. Activation of cholinergic system plays an important role in&#xD;
      the development of PONV. Penehyclidine is an muscarinic antagonists which selectively block&#xD;
      M1 and M3 receptors and is commonly used to decrease oral secretion. The investigators&#xD;
      hypothesize that continuously administrated penehyclidine during perioperative period can&#xD;
      reduce the incidence of PONV in patients undergoing bimaxillary surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Postoperative nausea and vomiting (PONV) is one of the most frequently occurred complications&#xD;
      after surgery, and are associated with patients' dissatisfaction after anesthesia and&#xD;
      surgery. Orthognathic surgery is widely performed for the correction of dentofacial&#xD;
      deformities. Despite of improved anti-emetic prophylaxis, patients undergoing orthognathic&#xD;
      surgery are reported to have a high incidence of PONV, especially those after bimaxillary&#xD;
      surgery.&#xD;
&#xD;
      It is known that activation of central cholinergic system plays an important role in the&#xD;
      development of PONV. Muscarinic antagonists such as scopolamine can block muscarinic&#xD;
      receptors in the cerebral cortex and produce anti-emetic effects. Penehyclidine is a new&#xD;
      muscarinic antagonists which selectively block M1 and M3 receptors. Our previous study&#xD;
      indicated that single-dose of penehyclidine injected before anesthesia induction was&#xD;
      associated with a reduced risk of PONV during the first 6 h postoperatively.The mean&#xD;
      elimination half-life of penehyclidine following single administration is about 10.35 h.&#xD;
      Hence, a single-dose penehyclidine may only produce a short duration of antiemetic effect.&#xD;
&#xD;
      The investigators hypothesize that continuously administrated penehyclidine during&#xD;
      perioperative period reduces PONV more effectively than single-dose injection in patients&#xD;
      undergoing bimaxillary surgery. The purpose of this study is to investigate the effect of&#xD;
      continuous administered penehyclidine in preventing PONV in patients undergoing bimaxillary&#xD;
      surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 7, 2020</start_date>
  <completion_date type="Actual">April 15, 2021</completion_date>
  <primary_completion_date type="Actual">March 15, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of nausea and vomiting within 72 hours after bimaxillary surgery.</measure>
    <time_frame>Up to 72 hours after surgery.</time_frame>
    <description>Nausea was assessed by direct questioning. Vomiting was diagnosed when patients retched or expulsed intra-gastric contents.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of nausea and vomiting at different stages after bimaxillary surgery.</measure>
    <time_frame>Up to 72 hours after surgery.</time_frame>
    <description>Postoperative 0-6 h, 6-12 h, 12-24 h, 24-48 h, and 48-72 h. Nausea was assessed by direct questioning. Vomiting was diagnosed when patients retched or expulsed intra-gastric contents.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of moderate to severe nausea at different stages after bimaxillary surgery.</measure>
    <time_frame>Up to 72 hours after surgery.</time_frame>
    <description>Postoperative 0-6 h, 6-12 h, 12-24 h, 24-48 h, and 48-72 h. Severity of nausea is assessed with the numerical rating scale (NRS; an 11-point scale where 0=no nausea and 10=the worst nausea). A score of 4 or higher is defined as moderate to severe nausea.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of moderate to severe nausea within 72 hours after bimaxillary surgery.</measure>
    <time_frame>Up to 72 hours after surgery.</time_frame>
    <description>Severity of nausea is assessed with the numerical rating scale (NRS; an 11-point scale where 0=no nausea and 10=the worst nausea). A score of 4 or higher is defined as moderate to severe nausea.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of nausea and vomiting within 72 hours after bimaxillary surgery.</measure>
    <time_frame>Up to 72 hours after surgery.</time_frame>
    <description>Level I: Absence of any emetic symptoms and nausea during the entire study period.&#xD;
Level II: Occurrence of mild nausea or one episode of vomiting if caused by an exogenous stimulus (e.g., drinking or movement).&#xD;
Level III: Moderate to severe nausea, or vomiting for 2 times or more, or experiences nausea that required a rescue antiemetic therapy only once.&#xD;
Level IV: Patient is suffered more than two emetic episodes or necessitating more than one dose of a rescue antiemetic.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of rescue antiemetics within 72 hours after bimaxillary surgery.</measure>
    <time_frame>Up to 72 hours after surgery.</time_frame>
    <description>Frequency and dose of antiemetics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of delirium within the first 5 days after surgery</measure>
    <time_frame>Up to 5 days after surgery.</time_frame>
    <description>Incidence of delirium within the first 5 days after surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay in hospital after surgery.</measure>
    <time_frame>Up to 30 days after surgery.</time_frame>
    <description>Length of stay in hospital after surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of complications within 30 days after surgery.</measure>
    <time_frame>Up to 30 days after surgery.</time_frame>
    <description>Incidence of complications within 30 days after surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause 30-day mortality.</measure>
    <time_frame>Within 30 days after surgery.</time_frame>
    <description>All-cause 30-day mortality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function on the 30th day after surgery.</measure>
    <time_frame>At 30 days after surgery</time_frame>
    <description>Cognitive function is assessed with the modified Telephone Interview for Cognitive Status (TICS-m; a 12-item questionnaire that provides an assessment of global cognitive function by verbal communication via telephone. The score ranges from 0 to 50, with higher score indicating better function).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence of moderate to severe pain at different stages after bimaxillary surgery.</measure>
    <time_frame>Up to 72 hours after surgery.</time_frame>
    <description>Postoperative 0-6 h, 6-12 h, 12-24 h, 24-48 h, and 48-72 h. Pain intensity is assessed with the numerical rating scale (NRS; an 11-point scale where 0=no pain and 10=the worst pain). A score of 4 or higher is defined as moderate to severe pain.</description>
  </other_outcome>
  <other_outcome>
    <measure>Use of rescue analgesics within 72 hours after bimaxillary surgery.</measure>
    <time_frame>Up to 72 hours after surgery.</time_frame>
    <description>Frequency and dose of analgesics.</description>
  </other_outcome>
  <other_outcome>
    <measure>Subjective sleep quality within 3 days after bimaxillary surgery.</measure>
    <time_frame>In the morning of the 1st, 2nd, and 3rd days after surgery.</time_frame>
    <description>Subjective sleep quality is assessed with the numeric rating scale (NRS; an 11-point scale where 0=the worst sleep and 10=the best sleep).</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">354</enrollment>
  <condition>Penehyclidine</condition>
  <condition>Postoperative Nausea and Vomiting</condition>
  <condition>Bimaxillar Surgery</condition>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>For patients in the control group, a dose of placebo (normal saline 5 ml) is injected intravenously before anesthesia induction. A patient-controlled intravenous analgesia pump is provided after surgery, which is established with a mixture of placebo (normal saline 5 ml), sufentanil (1.25-1.5 ug/kg) and tropisetron 10 mg, diluted with normal saline to 100 ml, and programmed to administer a continuous infusion at a rate of 2 ml/h for 48 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single injection group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For patients in this group, a dose of penehyclidine (0.5 mg/5 ml) is injected intravenously before anesthesia induction. A patient-controlled intravenous analgesia pump is provided after surgery, which is established with a mixture of placebo (normal saline 5 ml), sufentanil (1.25-1.5 ug/kg) and tropisetron (10 mg), diluted with normal saline to 100 ml, and programmed to administer a continuous infusion at a rate of 2 ml/h for 48 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continuous infusion group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For patients in this group, a dose of penehyclidine (0.25 mg/5 ml) is injected intravenously before anesthesia induction. A patient-controlled intravenous analgesia pump is provided after surgery, which is established with a mixture of penehyclidine (0.25 mg/5 ml), sufentanil (1.25-1.5 ug/kg) and tropisetron (10 mg), diluted with normal saline to 100 ml, and programmed to administer a continuous infusion at a rate of 2 ml/h for 48 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Single injection of penehyclidine</intervention_name>
    <description>A dose of penehyclidine hydrochloride (0.5 mg/5 ml) is injected intravenously before anesthesia induction. A patient-controlled intravenous analgesia pump is provided after surgery, which is established with a mixture of placebo (normal saline 5 ml), sufentanil (1.25-1.5 ug/kg) and tropisetron (10 mg), diluted with normal saline to 100 ml, and programmed to administer a continuous infusion at a rate of 2 ml/h for 48 hours.</description>
    <arm_group_label>Single injection group</arm_group_label>
    <other_name>Penehyclidine hydrochloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Continuous infusion of penehyclidine</intervention_name>
    <description>A dose of penehyclidine hydrochloride (0.25 mg/5 ml) is injected intravenously before anesthesia induction. A patient-controlled intravenous analgesia pump is provided after surgery, which is established with a mixture of penehyclidine hydrochloride (0.25 mg/5 ml), sufentanil (1.25-1.5 ug/kg) and tropisetron (10 mg), diluted with normal saline to 100 ml, and programmed to administer a continuous infusion at a rate of 2 ml/h for 48 hours.</description>
    <arm_group_label>Continuous infusion group</arm_group_label>
    <other_name>Penehyclidine hydrochloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>A dose of placebo (normal saline 5 ml) is injected intravenously before anesthesia induction. A patient-controlled intravenous analgesia pump is provided after surgery, which is established with a mixture of placebo (normal saline 5 ml), sufentanil (1.25-1.5 ug/kg) and tropisetron (10 mg), diluted with normal saline to 100 ml, and programmed to administer a continuous infusion at a rate of 2 ml/h for 48 hours.</description>
    <arm_group_label>Control group</arm_group_label>
    <other_name>Normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥18 years but &lt;60 years; body mass index ≥18 but &lt;30 kg/m2;&#xD;
&#xD;
          2. Scheduled to undergo elective bimaxillary surgery under general anesthesia;&#xD;
&#xD;
          3. Planned to use patient-controlled intravenous analgesia (PCIA) after surgery;&#xD;
&#xD;
          4. Provide written informed consents.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of glaucoma;&#xD;
&#xD;
          2. Allergic to penehyclidine, atropine, scopolamine or other anticholinergic drugs;&#xD;
&#xD;
          3. Acute or chronic nausea and/or vomiting, or gastrointestinal motility disorders before&#xD;
             surgery;&#xD;
&#xD;
          4. Preoperative antiemetic therapy within 12 hours;&#xD;
&#xD;
          5. History of schizophrenia, Parkinson's disease or profound dementia, or language&#xD;
             barrier;&#xD;
&#xD;
          6. Severe hepatic dysfunction (Child-Pugh class C), severe renal dysfunction (requirement&#xD;
             of renal replacement therapy before surgery) or American Society of Anesthesiologists&#xD;
             physical status ≥IV.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>59 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dong-Xin Wang, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University First Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peking Univeristy Hospital Stomatology</name>
      <address>
        <city>Beijing</city>
        <zip>100081</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Myles PS, Williams DL, Hendrata M, Anderson H, Weeks AM. Patient satisfaction after anaesthesia and surgery: results of a prospective survey of 10,811 patients. Br J Anaesth. 2000 Jan;84(1):6-10. doi: 10.1093/oxfordjournals.bja.a013383.</citation>
    <PMID>10740539</PMID>
  </reference>
  <reference>
    <citation>Naran S, Steinbacher DM, Taylor JA. Current Concepts in Orthognathic Surgery. Plast Reconstr Surg. 2018 Jun;141(6):925e-936e. doi: 10.1097/PRS.0000000000004438.</citation>
    <PMID>29794714</PMID>
  </reference>
  <reference>
    <citation>Laskin DM, Carrico CK, Wood J. Predicting postoperative nausea and vomiting in patients undergoing oral and maxillofacial surgery. Int J Oral Maxillofac Surg. 2020 Jan;49(1):22-27. doi: 10.1016/j.ijom.2019.06.016. Epub 2019 Jun 21.</citation>
    <PMID>31230771</PMID>
  </reference>
  <reference>
    <citation>Phillips C, Brookes CD, Rich J, Arbon J, Turvey TA. Postoperative nausea and vomiting following orthognathic surgery. Int J Oral Maxillofac Surg. 2015 Jun;44(6):745-51. doi: 10.1016/j.ijom.2015.01.006. Epub 2015 Feb 2.</citation>
    <PMID>25655765</PMID>
  </reference>
  <reference>
    <citation>Dobbeleir M, De Coster J, Coucke W, Politis C. Postoperative nausea and vomiting after oral and maxillofacial surgery: a prospective study. Int J Oral Maxillofac Surg. 2018 Jun;47(6):721-725. doi: 10.1016/j.ijom.2017.11.018. Epub 2018 Jan 1.</citation>
    <PMID>29301675</PMID>
  </reference>
  <reference>
    <citation>Shaikh SI, Nagarekha D, Hegade G, Marutheesh M. Postoperative nausea and vomiting: A simple yet complex problem. Anesth Essays Res. 2016 Sep-Dec;10(3):388-396. doi: 10.4103/0259-1162.179310.</citation>
    <PMID>27746521</PMID>
  </reference>
  <reference>
    <citation>Han XY, Liu H, Liu CH, Wu B, Chen LF, Zhong BH, Liu KL. Synthesis of the optical isomers of a new anticholinergic drug, penehyclidine hydrochloride (8018). Bioorg Med Chem Lett. 2005 Apr 15;15(8):1979-82. doi: 10.1016/j.bmcl.2005.02.071.</citation>
    <PMID>15808451</PMID>
  </reference>
  <reference>
    <citation>Zhang Z, Zhuang Y, Ouyang F, Zhang A, Zeng B, Gu M. Penehyclidine enhances the efficacy of tropisetron in prevention of PONV following gynecological laparoscopic surgery. J Anesth. 2012 Dec;26(6):864-9. doi: 10.1007/s00540-012-1443-1. Epub 2012 Aug 10.</citation>
    <PMID>22878869</PMID>
  </reference>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>September 14, 2021</last_update_submitted>
  <last_update_submitted_qc>September 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking University First Hospital</investigator_affiliation>
    <investigator_full_name>Dong-Xin Wang</investigator_full_name>
    <investigator_title>Professor and Chairman, Department of Anaesthesiology and Critical Care Medicine</investigator_title>
  </responsible_party>
  <keyword>Penehyclidine</keyword>
  <keyword>Postoperative Nausea and Vomiting</keyword>
  <keyword>Bimaxillar Surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nausea</mesh_term>
    <mesh_term>Vomiting</mesh_term>
    <mesh_term>Postoperative Nausea and Vomiting</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04454866
org study id: 202055076
nct id: NCT04454866
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Postoperative nausea and vomiting (PONV) is a common complication after surgery. Patients
      undergoing orthognathic surgery are reported to have a high rate of PONV, especially those
      undergoing bimaxillary surgery. Activation of cholinergic system plays an important role in
      the development of PONV. Penehyclidine is an muscarinic antagonists which selectively block
      M1 and M3 receptors and is commonly used to decrease oral secretion. The investigators
      hypothesize that continuously administrated penehyclidine during perioperative period can
      reduce the incidence of PONV in patients undergoing bimaxillary surgery.
Postoperative nausea and vomiting (PONV) is one of the most frequently occurred complications
      after surgery, and are associated with patients' dissatisfaction after anesthesia and
      surgery. Orthognathic surgery is widely performed for the correction of dentofacial
      deformities. Despite of improved anti-emetic prophylaxis, patients undergoing orthognathic
      surgery are reported to have a high incidence of PONV, especially those after bimaxillary
      surgery.

      It is known that activation of central cholinergic system plays an important role in the
      development of PONV. Muscarinic antagonists such as scopolamine can block muscarinic
      receptors in the cerebral cortex and produce anti-emetic effects. Penehyclidine is a new
      muscarinic antagonists which selectively block M1 and M3 receptors. Our previous study
      indicated that single-dose of penehyclidine injected before anesthesia induction was
      associated with a reduced risk of PONV during the first 6 h postoperatively.The mean
      elimination half-life of penehyclidine following single administration is about 10.35 h.
      Hence, a single-dose penehyclidine may only produce a short duration of antiemetic effect.

      The investigators hypothesize that continuously administrated penehyclidine during
      perioperative period reduces PONV more effectively than single-dose injection in patients
      undergoing bimaxillary surgery. The purpose of this study is to investigate the effect of
      continuous administered penehyclidine in preventing PONV in patients undergoing bimaxillary
      surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Incidence of nausea and vomiting within 72 hours after bimaxillary surgery.
time frame: Up to 72 hours after surgery.
description: Nausea was assessed by direct questioning. Vomiting was diagnosed when patients retched or expulsed intra-gastric contents.
measure: Incidence of nausea and vomiting at different stages after bimaxillary surgery.
time frame: Up to 72 hours after surgery.
description: Postoperative 0-6 h, 6-12 h, 12-24 h, 24-48 h, and 48-72 h. Nausea was assessed by direct questioning. Vomiting was diagnosed when patients retched or expulsed intra-gastric contents.
measure: Incidence of moderate to severe nausea at different stages after bimaxillary surgery.
time frame: Up to 72 hours after surgery.
description: Postoperative 0-6 h, 6-12 h, 12-24 h, 24-48 h, and 48-72 h. Severity of nausea is assessed with the numerical rating scale (NRS; an 11-point scale where 0=no nausea and 10=the worst nausea). A score of 4 or higher is defined as moderate to severe nausea.
measure: Incidence of moderate to severe nausea within 72 hours after bimaxillary surgery.
time frame: Up to 72 hours after surgery.
description: Severity of nausea is assessed with the numerical rating scale (NRS; an 11-point scale where 0=no nausea and 10=the worst nausea). A score of 4 or higher is defined as moderate to severe nausea.
measure: Severity of nausea and vomiting within 72 hours after bimaxillary surgery.
time frame: Up to 72 hours after surgery.
description: Level I: Absence of any emetic symptoms and nausea during the entire study period.
Level II: Occurrence of mild nausea or one episode of vomiting if caused by an exogenous stimulus (e.g., drinking or movement).
Level III: Moderate to severe nausea, or vomiting for 2 times or more, or experiences nausea that required a rescue antiemetic therapy only once.
Level IV: Patient is suffered more than two emetic episodes or necessitating more than one dose of a rescue antiemetic.
measure: Use of rescue antiemetics within 72 hours after bimaxillary surgery.
time frame: Up to 72 hours after surgery.
description: Frequency and dose of antiemetics.
measure: Incidence of delirium within the first 5 days after surgery
time frame: Up to 5 days after surgery.
description: Incidence of delirium within the first 5 days after surgery.
measure: Length of stay in hospital after surgery.
time frame: Up to 30 days after surgery.
description: Length of stay in hospital after surgery.
measure: Incidence of complications within 30 days after surgery.
time frame: Up to 30 days after surgery.
description: Incidence of complications within 30 days after surgery.
measure: All-cause 30-day mortality.
time frame: Within 30 days after surgery.
description: All-cause 30-day mortality.
measure: Cognitive function on the 30th day after surgery.
time frame: At 30 days after surgery
description: Cognitive function is assessed with the modified Telephone Interview for Cognitive Status (TICS-m; a 12-item questionnaire that provides an assessment of global cognitive function by verbal communication via telephone. The score ranges from 0 to 50, with higher score indicating better function).
measure: Incidence of moderate to severe pain at different stages after bimaxillary surgery.
time frame: Up to 72 hours after surgery.
description: Postoperative 0-6 h, 6-12 h, 12-24 h, 24-48 h, and 48-72 h. Pain intensity is assessed with the numerical rating scale (NRS; an 11-point scale where 0=no pain and 10=the worst pain). A score of 4 or higher is defined as moderate to severe pain.
measure: Use of rescue analgesics within 72 hours after bimaxillary surgery.
time frame: Up to 72 hours after surgery.
description: Frequency and dose of analgesics.
measure: Subjective sleep quality within 3 days after bimaxillary surgery.
time frame: In the morning of the 1st, 2nd, and 3rd days after surgery.
description: Subjective sleep quality is assessed with the numeric rating scale (NRS; an 11-point scale where 0=the worst sleep and 10=the best sleep).
arm group label: Control group
arm group type: Placebo Comparator
description: For patients in the control group, a dose of placebo (normal saline 5 ml) is injected intravenously before anesthesia induction. A patient-controlled intravenous analgesia pump is provided after surgery, which is established with a mixture of placebo (normal saline 5 ml), sufentanil (1.25-1.5 ug/kg) and tropisetron 10 mg, diluted with normal saline to 100 ml, and programmed to administer a continuous infusion at a rate of 2 ml/h for 48 hours.
arm group label: Single injection group
arm group type: Experimental
description: For patients in this group, a dose of penehyclidine (0.5 mg/5 ml) is injected intravenously before anesthesia induction. A patient-controlled intravenous analgesia pump is provided after surgery, which is established with a mixture of placebo (normal saline 5 ml), sufentanil (1.25-1.5 ug/kg) and tropisetron (10 mg), diluted with normal saline to 100 ml, and programmed to administer a continuous infusion at a rate of 2 ml/h for 48 hours.
arm group label: Continuous infusion group
arm group type: Experimental
description: For patients in this group, a dose of penehyclidine (0.25 mg/5 ml) is injected intravenously before anesthesia induction. A patient-controlled intravenous analgesia pump is provided after surgery, which is established with a mixture of penehyclidine (0.25 mg/5 ml), sufentanil (1.25-1.5 ug/kg) and tropisetron (10 mg), diluted with normal saline to 100 ml, and programmed to administer a continuous infusion at a rate of 2 ml/h for 48 hours.
intervention type: Drug
intervention name: Single injection of penehyclidine
description: A dose of penehyclidine hydrochloride (0.5 mg/5 ml) is injected intravenously before anesthesia induction. A patient-controlled intravenous analgesia pump is provided after surgery, which is established with a mixture of placebo (normal saline 5 ml), sufentanil (1.25-1.5 ug/kg) and tropisetron (10 mg), diluted with normal saline to 100 ml, and programmed to administer a continuous infusion at a rate of 2 ml/h for 48 hours.
arm group label: Single injection group
other name: Penehyclidine hydrochloride
intervention type: Drug
intervention name: Continuous infusion of penehyclidine
description: A dose of penehyclidine hydrochloride (0.25 mg/5 ml) is injected intravenously before anesthesia induction. A patient-controlled intravenous analgesia pump is provided after surgery, which is established with a mixture of penehyclidine hydrochloride (0.25 mg/5 ml), sufentanil (1.25-1.5 ug/kg) and tropisetron (10 mg), diluted with normal saline to 100 ml, and programmed to administer a continuous infusion at a rate of 2 ml/h for 48 hours.
arm group label: Continuous infusion group
other name: Penehyclidine hydrochloride
intervention type: Drug
intervention name: Placebo
description: A dose of placebo (normal saline 5 ml) is injected intravenously before anesthesia induction. A patient-controlled intravenous analgesia pump is provided after surgery, which is established with a mixture of placebo (normal saline 5 ml), sufentanil (1.25-1.5 ug/kg) and tropisetron (10 mg), diluted with normal saline to 100 ml, and programmed to administer a continuous infusion at a rate of 2 ml/h for 48 hours.
arm group label: Control group
other name: Normal saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 59 Years
healthy volunteers: No
last name: Dong-Xin Wang, MD, PhD
role: Principal Investigator
affiliation: Peking University First Hospital
facility: 
country: China
citation: Myles PS, Williams DL, Hendrata M, Anderson H, Weeks AM. Patient satisfaction after anaesthesia and surgery: results of a prospective survey of 10,811 patients. Br J Anaesth. 2000 Jan;84(1):6-10. doi: 10.1093/oxfordjournals.bja.a013383.
PMID: 10740539
citation: Naran S, Steinbacher DM, Taylor JA. Current Concepts in Orthognathic Surgery. Plast Reconstr Surg. 2018 Jun;141(6):925e-936e. doi: 10.1097/PRS.0000000000004438.
PMID: 29794714
citation: Laskin DM, Carrico CK, Wood J. Predicting postoperative nausea and vomiting in patients undergoing oral and maxillofacial surgery. Int J Oral Maxillofac Surg. 2020 Jan;49(1):22-27. doi: 10.1016/j.ijom.2019.06.016. Epub 2019 Jun 21.
PMID: 31230771
citation: Phillips C, Brookes CD, Rich J, Arbon J, Turvey TA. Postoperative nausea and vomiting following orthognathic surgery. Int J Oral Maxillofac Surg. 2015 Jun;44(6):745-51. doi: 10.1016/j.ijom.2015.01.006. Epub 2015 Feb 2.
PMID: 25655765
citation: Dobbeleir M, De Coster J, Coucke W, Politis C. Postoperative nausea and vomiting after oral and maxillofacial surgery: a prospective study. Int J Oral Maxillofac Surg. 2018 Jun;47(6):721-725. doi: 10.1016/j.ijom.2017.11.018. Epub 2018 Jan 1.
PMID: 29301675
citation: Shaikh SI, Nagarekha D, Hegade G, Marutheesh M. Postoperative nausea and vomiting: A simple yet complex problem. Anesth Essays Res. 2016 Sep-Dec;10(3):388-396. doi: 10.4103/0259-1162.179310.
PMID: 27746521
citation: Han XY, Liu H, Liu CH, Wu B, Chen LF, Zhong BH, Liu KL. Synthesis of the optical isomers of a new anticholinergic drug, penehyclidine hydrochloride (8018). Bioorg Med Chem Lett. 2005 Apr 15;15(8):1979-82. doi: 10.1016/j.bmcl.2005.02.071.
PMID: 15808451
citation: Zhang Z, Zhuang Y, Ouyang F, Zhang A, Zeng B, Gu M. Penehyclidine enhances the efficacy of tropisetron in prevention of PONV following gynecological laparoscopic surgery. J Anesth. 2012 Dec;26(6):864-9. doi: 10.1007/s00540-012-1443-1. Epub 2012 Aug 10.
PMID: 22878869
responsible party type: Principal Investigator
investigator affiliation: Peking University First Hospital
investigator full name: Dong-Xin Wang
investigator title: Professor and Chairman, Department of Anaesthesiology and Critical Care Medicine
mesh term: Nausea
mesh term: Vomiting
mesh term: Postoperative Nausea and Vomiting
sharing ipd: No