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

N/ANot Yet RecruitingNCT07692282

Southeast University, China90 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Gastrointestinal Dysfunction

Interventions

Neostigmine Acupoint InjectionDRUG

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. The intervention period is 1 day, with interventions administered twice daily (bid), 12 hours apart.

Neostigmine subcutaneous injectionDRUG

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.

Acupoint normal saline injectionDRUG

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 period is 1 day, with interventions administered twice daily (bid), 12 hours apart.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Remission rate of gastrointestinal symptoms within 24 hours

Gastrointestinal symptom relief is defined as meeting both recovery of spontaneous defecation (i.e., the first defecation after initial intervention with a defecation volume \> 100 mL) and improvement in 24-hour gastric retention (24-hour gastric retention volume ≤ 500 mL).

Time frame: within 24 hours after treatment

Secondary Outcomes

28-day mortality

Mortality was calculated on day 28 of treatment

Time frame: From randomization to Day 28

ICU mortality

the survival rate(survival/total) during ICU stay

Time frame: up to 24 months

Length of ICU stay

Time of staying in ICU within 28 days

Time frame: up to 28 days

Infection condition

Infection condition within 28 days

Time frame: From randomization to Day 28

28-day vasopressor-free days

28-day vasopressor-free days is defined as a continuous period of 28 days, beginning from the time a patient is weaned from shock, circulatory failure, or mechanical circulatory support, during which no vasoactive drugs are used at any time, and the patient maintains stable circulation without the need for vasopressors agents to sustain blood pressure and tissue perfusion.

Time frame: From randomization to Day 28

28-day ventilator-free days

Ventilator-free days are defined as the number of days alive and free from invasive mechanical ventilation during the first 28 days after randomization.

Time frame: From randomization to Day 28

Length of hospital stay

Time frame: prior to hospital discharge

Enteral Nutrition Prescription

Enteral Nutrition Prescription was recorded before treatment,on day 1 of treatment,on day 3 of treatment,and on day 7 of treatment.

Time frame: before treatment,on day 1 of treatment,on day 3 of treatment,on day 7 of treatment

Intra-abdominal pressure(mmHg)

The patient was placed in the supine position. A urinary catheter was inserted transurethrally and connected to a three-way stopcock. Then 25 mL of 0.9% normal saline was injected. Taking the level of the pubic symphysis as the zero point, the water column height at the end of expiration was measured and recorded.IAP readings must be converted to mmHg.