Study on Neostigmine Acupoint Injection at Zusanli(ST36) for Treating Mechanical Ventilation-Associated Gastrointestinal Dysfunction

Official title

A Single-Center,Randomized Controlled Study on Neostigmine Acupoint Injection at Zusanli(ST36) for Treating Mechanical Ventilation-Associated Gastrointestinal Dysfunction

Overview

Mechanical ventilation is a common method of respiratory support for critically ill patients, and gastrointestinal dysfunction (GIDF) is a frequent complication. In the ICU, more than 60% of mechanically ventilated patients experience gastrointestinal dysfunction. Currently, the exact causes of mechanical ventilation-induced gastrointestinal dysfunction remain unclear, but they primarily include increased intra-abdominal pressure resulting from positive-pressure ventilation, which inhibits gastrointestinal motility; inflammatory responses, prolonged bed rest, electrolyte imbalances, and the use of sedatives, analgesics, and even muscle relaxants . Manifestations such as gastroparesis and constipation further lead to delayed gastric emptying, increased intra-abdominal pressure, and heightened risks of bacterial translocation, multiple organ failure, and ventilator-associated pneumonia. Primary Objective is to investigate, through a prospective randomized controlled trial, the efficacy of neostigmine injection at the Zusanli acupoint compared to Zusanli acupoint stimulation alone or subcutaneous neostigmine injection in improving gastrointestinal function in patients with mechanical ventilation and gastrointestinal dysfunction. Secondary objectives: （1）To evaluate the effects of acupoint injection of neostigmine on the duration of mechanical ventilation, enteral nutrition intake, and ICU length of stay in critically ill patients; （2）To assess the safety of acupoint injection of neostigmine.

Interventions

• Drug Neostigmine Acupoint Injection
  On the basis of standard treatment, neostigmine was injected into the bilateral Zusanli (ST36) acupoints. The patient was placed in the supine position with knees flexed. Following routine local disinfection, a 5 mL disposable syringe was used to extract 0.5 mg of neostigmine for vertical subcutaneous needling and injection. Upon needle withdrawal, the puncture site was compressed with sterile cotton swabs for hemostasis. The identical procedure was applied to the contralateral Zusanli acupoint.
• Drug Neostigmine subcutaneous injection
  On the basis of standard treatment, subcutaneous injection was performed at non-acupoint sites. A 5 mL disposable syringe was used to aspirate 1 mg of neostigmine injection for single-site injection. The injection site received routine disinfection beforehand. Following the injection, the needle was withdrawn, and the puncture site was compressed with sterile cotton swabs for hemostasis.The intervention period is 1 day, with interventions administered twice daily (bid), 12 hours apart.
• Drug Acupoint normal saline injection
  On the basis of standard treatment, normal saline was injected into bilateral Zusanli (ST36) acupoints. The patient was placed in the supine position with knees flexed. After routine local disinfection, a 5 mL disposable syringe was used for vertical needle insertion, and an equal volume of normal saline was injected subcutaneously into each acupoint. Following injection, the needle was withdrawn, and the puncture site was compressed with sterile cotton swabs for hemostasis.The intervention peri

Primary outcome measures

• Remission rate of gastrointestinal symptoms within 24 hours [Time frame: within 24 hours after treatment]

Secondary outcome measures (12)

• 28-day mortality [Time frame: From randomization to Day 28]
• ICU mortality [Time frame: up to 24 months]
• Length of ICU stay [Time frame: up to 28 days]
• Infection condition [Time frame: From randomization to Day 28]
• 28-day vasopressor-free days [Time frame: From randomization to Day 28]
• 28-day ventilator-free days [Time frame: From randomization to Day 28]
• Length of hospital stay [Time frame: prior to hospital discharge]
• Enteral Nutrition Prescription [Time frame: before treatment,on day 1 of treatment,on day 3 of treatment,on day 7 of treatment]
• Intra-abdominal pressure(mmHg) [Time frame: before treatment,on day 1 of treatment,on day 3 of treatment]
• Bowel sounds [Time frame: before treatment,on day 1 of treatment,on day 3 of treatment]
• motilin [Time frame: before treatment,on day 1 of treatment,on day 3 of treatment]
• gastrin [Time frame: before treatment,on day 1 of treatment,on day 3 of treatment]

Eligibility criteria

Inclusion criteria

• Respiratory failure due to any cause requiring mechanical ventilation, with an anticipated duration of mechanical ventilation of ≥48 hours;
• No spontaneous bowel movements for ≥48 hours or increased gastric residual volume (gastric residual volume >500 mL within 24 hours);
• Anticipated ICU stay of ≥3 days;
• Age ≥18 years and ≤85 years.

Exclusion criteria

• Use of prokinetic agents, subcutaneous or acupoint injections of neostigmine, or acupuncture at the Zusanli acupoint within 12 hours prior to enrollment;
• History of gastrointestinal surgery within the past 8 weeks; diarrhea within the past week; or history of severe gastrointestinal diseases such as mechanical intestinal obstruction, intestinal ischemia and necrosis, inflammatory bowel disease, or active gastrointestinal bleeding;
• Patients with an allergy to neostigmine or contraindications to its use, such as mechanical intestinal obstruction, urinary tract obstruction, bronchial asthma, bradycardia, hypotension, epilepsy, or Parkinson's disease;
• Patients unable to undergo acupoint injection due to skin lesions, infection, limb loss, or inability to cooperate at the Zusanli acupoint;
• Patients currently requiring routine treatment with neostigmine or similar cholinesterase inhibitors for other indications (e.g., myasthenia gravis, multiple sclerosis, Parkinson's disease);
• Patients with a platelet count <50 × 10⁹/L on complete blood count or severe coagulation disorders (International Normalized Ratio \[INR\] >3);
• Severe hepatic impairment (Child-Pugh Class C) or hepatic encephalopathy;
• End-stage renal failure requiring dialysis prior to admission;
• Patients with hemodynamic instability (norepinephrine equivalent > 1.0 μg/kg·min);
• Patients who have participated in other interventional clinical trials within the past month;
• Pregnant, perinatal, or lactating women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07692282 · ST36 Acupoint injection · 2026ZDSYLL103-P01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗