Penehyclidine for Prevention of Nausea and Vomiting After Bimaxillary Surgery

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Effects of Penehyclidine in Preventing Postoperative Nausea and Vomiting in Patients Underging Bimaxillary Surgery: A Randomised Controlled Trial

Conditions
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Penehyclidine, Postoperative Nausea and Vomiting, Bimaxillar Surgery

Intervention / Treatment
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* Drug: Single injection of penehyclidine
* Drug: Continuous infusion of penehyclidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years but <60 years; body mass index ≥18 but <30 kg/m2; Scheduled to undergo elective bimaxillary surgery under general anesthesia; Planned to use patient-controlled intravenous analgesia (PCIA) after surgery; Provide written informed consents. Exclusion Criteria: Presence of glaucoma; Allergic to penehyclidine, atropine, scopolamine or other anticholinergic drugs; Acute or chronic nausea and/or vomiting, or gastrointestinal motility disorders before surgery; Preoperative antiemetic therapy within 12 hours; History of schizophrenia, Parkinson's disease or profound dementia, or language barrier; Severe hepatic dysfunction (Child-Pugh class C), severe renal dysfunction (requirement of renal replacement therapy before surgery) or American Society of Anesthesiologists physical status ≥IV.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>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. | Drug: Placebo<br>* 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.<br>* Other names: Normal saline;|
| Experimental: Single injection group<br>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. | Drug: Single injection of penehyclidine<br>* 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.<br>* Other names: Penehyclidine hydrochloride;|
| Experimental: Continuous infusion group<br>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. | Drug: Continuous infusion of penehyclidine<br>* 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.<br>* Other names: Penehyclidine hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of nausea and vomiting within 72 hours after bimaxillary surgery. | Nausea was assessed by direct questioning. Vomiting was diagnosed when patients retched or expulsed intra-gastric contents. | Up to 72 hours after surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of nausea and vomiting at different stages after bimaxillary surgery. | 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. | Up to 72 hours after surgery. | 
| Incidence of moderate to severe nausea at different stages after bimaxillary surgery. | 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. | Up to 72 hours after surgery. | 
| Incidence of moderate to severe nausea within 72 hours after bimaxillary surgery. | 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. | Up to 72 hours after surgery. | 
| Severity of nausea and vomiting within 72 hours after bimaxillary surgery. | 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. | Up to 72 hours after surgery. | 
| Use of rescue antiemetics within 72 hours after bimaxillary surgery. | Frequency and dose of antiemetics. | Up to 72 hours after surgery. | 
| Incidence of delirium within the first 5 days after surgery | Incidence of delirium within the first 5 days after surgery. | Up to 5 days after surgery. | 
| Length of stay in hospital after surgery. | Length of stay in hospital after surgery. | Up to 30 days after surgery. | 
| Incidence of complications within 30 days after surgery. | Incidence of complications within 30 days after surgery. | Up to 30 days after surgery. | 
| All-cause 30-day mortality. | All-cause 30-day mortality. | Within 30 days after surgery. | 
| Cognitive function on the 30th day after surgery. | 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). | At 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Penehyclidine, Postoperative Nausea and Vomiting, Bimaxillar Surgery