Neuromuscular Blocking Agents on Gastrointestinal Function Following Colorectal Surgery

Effect of Neuromuscular Reversal With Neostigmine/Atropine Versus Sugammadex on Postoperative Gastrointestinal Function Recovery Following Colorectal Surgery

This study is a clinical research project conducted at Xijing Hospital to compare the effects of two different neuromuscular blockade reversal strategies on the recovery of gastrointestinal (GI) function after colorectal surgery.

Many patients experience slow recovery of bowel function after colorectal surgery, which can lead to discomfort, nausea, vomiting, and a longer hospital stay. This study investigates whether using one medication (sugammadex) to reverse muscle relaxants used during anesthesia leads to better and faster recovery of gastrointestinal function compared to a traditional combination of medications (neostigmine with atropine).

The study will include 560 adults scheduled for elective colorectal surgery. Participants will be randomly assigned to one of two groups to receive either:

Sugammadex (2 mg/kg), OR Neostigmine (30 μg/kg) + Atropine (15 μg/kg) The assigned study drug will be given by intravenous injection at the end of surgery, once measurements show the muscle relaxant is starting to wear off. The patients, surgeons, outcome assessors, and statisticians will be blinded.

The main goal is to see if more patients in one group recover their gastrointestinal function within 72 hours after surgery. Gastrointestinal recovery is strictly defined as both being able to tolerate food/drinks without significant nausea/vomiting AND having passed gas or had a bowel movement.

The study will also compare many other important outcomes between the groups, including:

1. Time to first passage of gas, first bowel movement, and first toleration of food.
2. Pain scores and opioid pain medication use.
3. Rates of nausea and vomiting.
4. Overall quality of recovery and patient satisfaction.
5. Length of hospital stay and total hospitalization costs.
6. Occurrence of complications within 30 days after surgery.
7. The safety of both reversal strategies will be closely monitored throughout the study by recording any adverse events.

This research aims to provide high-quality evidence to help anesthesiologists and surgeons choose the best method to reverse muscle relaxation, potentially leading to faster recovery, fewer complications, and a better overall experience for patients undergoing colorectal surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Surgery; Postoperative Ileus; Postoperative Gastrointestinal Dysfunction (POGD)
• Intervention / Treatment: Drug: Sugammadex; Drug: Neostigmine + Atropine

• Study Type: Interventional
• Enrollment (Estimated): 560
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• American Society of Anesthesiologists (ASA) physical status classification I-III
• Preoperative Mini-Mental State Examination (MMSE) score > 23
• Patients scheduled for elective colorectal surgery under general anesthesia. Disease diagnoses include colorectal cancer, benign polyps, benign strictures, or diverticular disease.
• Provide informed consent

Exclusion Criteria:

• Presence of psychiatric disorders, cognitive impairment, or language communication barriers that may affect assessment compliance.
• Body Mass Index (BMI) ≥ 35 kg/m².
• Severe hepatic dysfunction (Child-Pugh Class C) or renal dysfunction (estimated glomerular filtration rate < 30 ml/min/1.73m² and/or receiving renal replacement therapy).
• Pre-existing severe gastrointestinal dysfunction (e.g., intestinal obstruction, active inflammatory bowel disease, severe constipation/diarrhea); receipt of neoadjuvant therapy preoperatively; planned stoma creation surgery; or scheduled for low rectal surgery (e.g., low anterior resection, abdominoperineal resection).
• History of neuromuscular disorders (e.g., myasthenia gravis) or malignant hyperthermia.
• History of opioid abuse, or chronic non-surgical pain requiring long-term analgesic therapy.
• Anticipated difficult airway, or patients planned for postoperative transfer to the intensive care unit (ICU) while intubated.
• Contraindications to the use of neostigmine, atropine, sugammadex, or rocuronium (e.g., known drug allergy, epilepsy, unstable angina, asthma, glaucoma, uncontrolled malignant arrhythmias especially atrioventricular block, severe cardiac valve stenosis); or current use of medications that may significantly influence the effects of neuromuscular blocking agents (e.g., antibiotics such as tetracyclines, aminoglycosides, polymyxins, and clindamycin; antiepileptic drugs; lithium; certain antidepressants such as sertraline and amitriptyline).
• Pregnant or lactating women.
• Current participation in other clinical trials that may interfere with the results of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sugammadex group; Sugammadex 2 mg/kg administered after surgery	Drug: Sugammadex; Participants received sugammadex 2 mg/kg after surgery once a train-of-four ratio of 0.9 and sufficient spontaneous breathing were confirmed.
Active Comparator: Neostigmine group; Neostigmine 30 μg/kg + Atropine 15 μg/kg administered after surgery	Drug: Neostigmine + Atropine; Participants received Neostigmine 30 μg/kg + Atropine 15 μg/kg after surgery once a train-of-four ratio of 0.9 and sufficient spontaneous breathing were confirmed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients recovering gastrointestinal function within 72 hours after surgery (assessed using the GI-3 criterion).	GI-3 is defined as the ability to tolerate oral intake (no significant nausea or vomiting during three consecutive meals of solid food and beverages) and the passage of flatus or stool (whichever occurs first).	up to 72 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to achieve GI-3 (hours)	Defined as the time from the end of anesthesia until the patient meets the GI-3 criteria.	up to 10 days after surgery
Time to achieve GI-2 (hours)	GI-2 is defined as the ability to tolerate oral intake (no significant nausea or vomiting during three consecutive instances of eating and drinking) and having a bowel movement	up to 10 days after surgery
Incidence of Prolonged Postoperative Ileus (PPOI)	Defined as the proportion of patients who fail to meet the GI-3 criteria by 120 hours (5 days) after surgery. Diagnosis requires radiographic imaging (e.g., abdominal X-ray or CT scan) to rule out mechanical obstruction, intra-abdominal infection, or other related complications (e.g., anastomotic leakage).	120 hours (5 days) after surgery
Time to first oral intake	record the time from surgery to first time of oral intake	Assessed up to 10 days after surgery
Time to first passage of flatus	record the time from surgery to first time passage of flatus	Assessed up to 10 days after surgery
Time to first defecation	record the time from surgery to first time defecation	Assessed up to 10 days after surgery
Time to first ambulation	record the time from surgery to first time ambulation	Assessed up to 10 days after surgery
Incidence of adverse events during the recovery period	any adverse events such as hypoxia will be recorded within this 2hrs time frame	Within 2 hours after extubation
Intake, Feeling nausea, Emesis, physical Exam, and Duration of symptoms (I-FEED) score at 24, 48, and 72 hours after surgery	The I-FEED scoring system incorporates five elements: intake (score: 0, 1, 3), feeling nauseated (score: 0, 1, 3), emesis (score: 0, 1, 3), results of physical exam (score: 0, 1, 3), and duration of symptoms (score: 0, 1, 2), with a total score ranging from 0 to 14. A higher score indicates poorer postoperative gastrointestinal recovery.	At 24, 48, and 72 hours after surgery
Visual Analog Scale (VAS) score at rest and during activity	The VAS score ranges from 0 to 10, with a higher score indicating greater pain intensity	At 24, 48, and 72 hours after surgery
Total opioid consumption	the postoperative opioid comsumption will recorded in morphine equivalent dose.	Within 24, 48, and 72 hours after surgery
Postoperative Nausea and Vomiting (PONV)	PONV scores (range from 0-3, a higher score indicates that the patient is experiencing more severe and frequent symptoms of postoperative nausea and vomiting), number of vomiting episodes, and the use of rescue antiemetic medications (name and dose)	At 24, 48, and 72 hours after surgery
Postoperative Quality of Recovery	Assessed using the QoR-15 questionnaire preoperatively and daily	From postoperative day 1 to day 7 (or until discharge, whichever comes first)
Incidence of postoperative delirium	Assessed using the Confusion Assessment Method (CAM)	Within 7 days after surgery (or until discharge, whichever comes first)
Time to meet medically defined discharge criteria (days)	Defined as the time when the patient meets all of the following criteria: ability to independently consume fluids/nutrition, adequate pain control with oral analgesics, ability to ambulate independently, recovery of gastrointestinal function according to GI-3 criteria, and absence of medical contraindications.	Assessed up to 30 days after surgery
Patient-assessed time to readiness for discharge (days)	Defined as the time when the patient meets the medically defined discharge criteria and subjectively agrees to be discharged.	Assessed up to 30 days after surgery
Quality of life assessment using the European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) questionnaire	The EQ-5D-5L consists of 25 items (rated from 1 = best condition to 5 = worst condition) across five domains: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression, with a cumulative score ranging from 5 to 25. Higher EQ-5D-5L scores indicate poorer health status, reflecting greater difficulty in daily activities, higher levels of pain, or emotional distress. Conversely, lower scores indicate better health with fewer or no problems.	Preoperatively, postoperative day 7, and postoperative day 30
Postoperative length of hospital stay	the time from surgery to hospital discharge	From postoperative Day 1 to hospital discharge, assessed up to postoperative 30 days
Total hospitalization costs	in Chinese Yuan, RMB	From hospital admission to hospital discharge, assessed up to postoperative 30 days
Incidence of complications	All complications occurring within 30 days after surgery will be recorded and graded according to the Clavien-Dindo classification system	Within 30 days after surgery
Days Alive and Out of Hospital within 30 days after surgery (DAOH30)	DAOH30 is defined as the number of days the patient is alive and not hospitalized in any medical facility (including rehabilitation institutions) within 30 days after surgery	Within 30 days after surgery
Adverse events (AEs)	Recorded any adverse event during the study peroid, no matter the AEs related to the intervention or not.	From the time the patient signs the informed consent form until the end of the study follow-up (30 days after surgery)

Collaborators and Investigators

• Sponsor: Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: September 22, 2025
• First Submitted That Met QC Criteria: November 26, 2025
• First Posted (Estimated): December 9, 2025

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds; Carbohydrates; Alkaloids; Polycyclic Compounds; Amines; Aza Compounds; Polysaccharides; Macrocyclic Compounds; Phenylammonium Compounds; Quaternary Ammonium Compounds; Onium Compounds; gamma-Cyclodextrins; Cyclodextrins; Dextrins; Starch; Glucans; Heterocyclic Compounds, Bridged-Ring; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Atropine; Neostigmine; Sugammadex
• Other Study ID Numbers: KY20252236

Drug and device information, study documents

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