Botulinum Toxin Pyloroplasty to Reduce Postoperative Nausea and Vomiting After Sleeve Gastrectomy

A common problem following sleeve gastrectomy surgery is called postoperative nausea and vomiting (PONV). This problem is uncomfortable for patients, and can also lead to other complications, including pneumonia. It is unclear what exactly causes this problem, but it may be partly caused by slow emptying of the stomach. The current treatments for PONV include medications, but these may only treat the symptoms. Botulinum toxin (BTX, brand name Botox®), produced naturally by the bacterium Clostridium botulinum and adapted for medical use, is an neurotransmitter inhibitor of the neuromuscular junction, and produces temporary muscular paralysis. BTX is widely used in cosmetic and other medical applications. Injecting BTX into the pylorus, which is the circular sphincter muscle at the end of the stomach, temporarily paralyzes the muscle, leaving it wide open, and allowing stomach contents to flow through. This effect lasts for several weeks, and then goes away. This may help prevent PONV.

Study Overview

• Status: Completed
• Conditions: Postoperative Nausea and Vomiting; Bariatric Surgery
• Intervention / Treatment: Drug: Botulinum toxin pyloroplasty; Drug: Normal saline pyloric injection

Detailed Description

Postoperative nausea and vomiting (PONV) remains a common complaint after bariatric surgery such as the sleeve gastrectomy, where the prevalence is estimated to be as high as 60-80%. PONV is frequently of greater concern to patients than postoperative pain, decreasing patient satisfaction and the perioperative experience. In addition, PONV increases the risk for aspiration, dehydration, electrolyte abnormalities, incisional dehiscence, esophageal injury, and other adverse events. Finally, PONV delays postoperative diet resumption and increases hospital length of stay. Numerous medication regimens have been tried to reduce PONV after sleeve gastrectomy, with varying success. A procedure called Botulinum toxin pyloroplasty (BP), which involves injection of botulinum toxin into the muscular sphincter at the end of the stomach, called the pylorus, has been demonstrated to improve gastric emptying. The investigators hypothesize that intraoperative BP during sleeve gastrectomy will decrease rates of PONV.

Botulinum toxin type A (Botox®), produced naturally by the bacterium Clostridium botulinum and adapted for medical use, is an inhibitor of the neurotransmitter acetylcholine at the neuromuscular junction, producing flaccid muscular paralysis. The effects of Botox® injection are temporary and reversible, and its duration of action ranges from weeks to months. Botox® injection has been widely used in many contexts, most familiarly during office-based cosmetic procedures and also in disorders such as torticollis, spasticity, hyperhidrosis, bladder overreactivity, and dystonias. It has been used endoscopically to relieve achalasia and dysphagia by injection into the lower esophageal sphincter. Gastroenterologists have reported successful treatment of gastroparesis using BP, by relieving the tonic contraction of the pylorus and increasing gastric transit time. Postoperative endoscopic BP has been utilized to improve gastroparesis following gastrectomy. The use of BP during bariatric surgery has not been reported. This proposal represents the first study to evaluate the use of intraoperative BP to decrease PONV after sleeve gastrectomy.

This technique involves pyloroplasty following completion of the robot-assisted laparoscopic sleeve gastrectomy. The investigators mix 100 units of Botox® powder in 10ml of saline. Using the robot, the investigators inject the pylorus laparoscopically using an 18-gauge, 0.5-inch laparoscopic needle. Meanwhile, an assistant surgeon intubates the stomach with an endoscope, which the investigators use to assess the gastric staple line and perform a leak test. Prior to injection of Botox® into the pylorus, the investigators confirm endoscopically that the tip of the needle is not intraluminal. After first aspirating to ensure the needle is intramuscular and free from any vascular structures, the investigators then inject the pylorus with approximately 5ml of Botox®. Proper placement of the injection is confirmed by visualizing a rising weal. The anterior, superior, and inferior aspects of the pylorus are injected with approximately 5-6 injections of 1ml each. The posterior aspect of the pylorus is not injected, since this is not readily accessible from a laparoscopic approach, and also contains the major vascular structure of the pylorus, the gastroduodenal artery.

This technique has been performed at Albany Medical Center institution more than 200 times over the past four years. The Albany Medical Center Bariatric Center as participated in the Metabolic and Bariatric Surgery Accreditation for 10 years, and so has collected comprehensive and granular data on complication rates and surgical outcomes. Analysis of this data demonstrates that enteric use of Botox® is safe.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Patients undergoing elective sleeve gastrectomy

Exclusion criteria:

• Prior gastric surgery resulting in altered anatomy
• Documented history of postoperative nausea or vomiting
• Allergy to any of the medications used in the study
• Any use of Botulinum toxin products within six months prior to study enrollment, or plans to use Botulinum toxin products during study enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botulinum toxin pyloroplasty; Intraoperative laparoscopic intramuscular injection of 100units (10cc) of Botulinum toxin into the pylorus	Drug: Botulinum toxin pyloroplasty; Intraoperative laparoscopic injection of Botulinum toxin into the pylorus immediately following sleeve gastrectomy; Other Names: Botox pyloropasty; Botulinum toxin A pyloroplasty
Placebo Comparator: Normal saline pyloric injection; Intraoperative laparoscopic intramuscular injection of 10cc normal saline into the pylorus	Drug: Normal saline pyloric injection; Intraoperative laparoscopic injection of normal saline into the pylorus immediately following sleeve gastrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use of rescue antiemetics	We will sum the number of "as needed" doses of intravenous antiemetics required by patients in both the treatment arm and the control arm of the study	During inpatient hospitalization only, an average of 2-3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient satisfaction survey	Likert scales describing overall satisfaction with postoperative course	2 weeks postoperative
Subjective experience of nausea	Likert score rating subjective experience of nausea	2 weeks postoperative
Number of episodes of vomiting	Number of episodes of emesis	2 weeks postoperative
30 day readmission rate	30 day readmission rate	30 days postoperative
Hospital length of stay	Hospital length of stay	During inpatient hospitalization only, an average of 2-3 days

Collaborators and Investigators

• Sponsor: Albany Medical College
• Collaborators: Allergan
• Investigators: Principal Investigator: Jessica Zaman, MD, Albany Medical College

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2019
• Primary Completion (Actual): November 11, 2022
• Study Completion (Actual): November 11, 2022

Study Registration Dates

• First Submitted: October 1, 2018
• First Submitted That Met QC Criteria: October 8, 2018
• First Posted (Actual): October 10, 2018

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: April 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Signs and Symptoms, Digestive; Nausea; Vomiting; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A
• Other Study ID Numbers: 5090

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No