Gastrointestinal Dysfunction
Conditions
Keywords
Gastrointestinal Dysfunction, Zusanli(ST 36), neostigmine, Mechanical Ventilation
Brief summary
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
DRUGNeostigmine 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. The intervention period is 1 day, with interventions administered twice daily (bid), 12 hours apart.
DRUGNeostigmine 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.
DRUGAcupoint 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 period is 1 day, with interventions administered twice daily (bid), 12 hours apart.
Sponsors
Southeast University, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remission rate of gastrointestinal symptoms within 24 hours | within 24 hours after treatment | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 28-day mortality | From randomization to Day 28 | Mortality was calculated on day 28 of treatment |
| ICU mortality | up to 24 months | the survival rate(survival/total) during ICU stay |
| Length of ICU stay | up to 28 days | Time of staying in ICU within 28 days |
| Infection condition | From randomization to Day 28 | Infection condition within 28 days |
| 28-day vasopressor-free days | From randomization to Day 28 | 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. |
| 28-day ventilator-free days | From randomization to Day 28 | Ventilator-free days are defined as the number of days alive and free from invasive mechanical ventilation during the first 28 days after randomization. |
| Length of hospital stay | prior to hospital discharge | Length of hospital stay |
| Enteral Nutrition Prescription | before treatment,on day 1 of treatment,on day 3 of treatment,on day 7 of treatment | Enteral Nutrition Prescription was recorded before treatment,on day 1 of treatment,on day 3 of treatment,and on day 7 of treatment. |
| Intra-abdominal pressure(mmHg) | before treatment,on day 1 of treatment,on day 3 of treatment | 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. |
| Bowel sounds | before treatment,on day 1 of treatment,on day 3 of treatment | Bowel sounds (times/min) were auscultated daily at a fixed time point before and after treatment over the right lower abdomen with a stethoscope. Each continuous auscultation lasted 3 minutes; the frequency of bowel sounds per minute was recorded, and the mean value of three repeated measurements was calculated. |
| motilin | before treatment,on day 1 of treatment,on day 3 of treatment | Venous blood samples of 2 mL were collected in the early morning before treatment, on day 1 and day 3 after treatment. The levels of motilin (MTL) were determined and recorded. |
| gastrin | before treatment,on day 1 of treatment,on day 3 of treatment | Venous blood samples of 2 mL were collected in the early morning before treatment, on day 1 and day 3 after treatment. The levels of gastrin (GAS) were determined and recorded. |
| vasoactive intestinal peptide | before treatment,on day 1 of treatment,on day 3 of treatment | Venous blood samples of 2 mL were collected in the early morning before treatment, on day 1 and day 3 after treatment. The levels of vasoactive intestinal peptide (VIP) were determined and recorded. |
| electrogastroenterography changes:FP(cpm) | before treatment,on day 1 of treatment,on day 3 of treatment | An electrogastroenterograph (Model EGEG-8D) was adopted. During examination, all subjects were placed in the supine position. Electrogastroenterography was performed before treatment, at 1 day and 3 days after treatment, and the main frequency (FP) (cpm) were recorded. |
| hemoglobin | before treatment,on day 1 of treatment,on day 3 of treatment | Hemoglobin(g/L) are measured at baseline ,Day1, and Day3 as a marker of nutritional condition. |
| albumin | before treatment,on day 1 of treatment,on day 3 of treatment | Serum albumin levels(g/L) are measured at baseline ,Day1, and Day3 as a marker of nutritional condition. |
| prealbumin | before treatment,on day 1 of treatment,on day 3 of treatment | Serum prealbumin levels(mg/L) are measured at baseline ,Day1, and Day3 as a marker of nutritional condition. |
| White blood cell count | before treatment, on day 1 of treatment, on day 3 of treatment | Serum White blood cell count (10\^9/L) is measured at baseline ,Day1, and Day3 as a marker of a systemic inflammatory response. |
| Lymphocyte count | before treatment, on day 1 of treatment, on day 3 of treatment | Serum lymphocyte count (10\^9/L) is measured at baseline ,Day1, and Day3 as a marker of a systemic inflammatory response. |
| C-reactive protein | before treatment, on day 1 of treatment, on day 3 of treatment | Serum C-reactive protein levels(mg/L) are measured at baseline ,Day1, and Day3 as a marker of a systemic inflammatory response. |
| Procalcitonin | before treatment, on day 1 of treatment, on day 3 of treatment | Serum procalcitonin protein levels(ng/mL) are measured at baseline ,Day1, and Day3 as a marker of a systemic inflammatory response. |
| electrogastroenterography changes:FC(cpm) | before treatment, on day 1 of treatment, on day 3 of treatment | An electrogastroenterograph (Model EGEG-8D) was adopted. During examination, all subjects were placed in the supine position. Electrogastroenterography was performed before treatment, at 1 day and 3 days after treatment, and the mean frequency (FC) were recorded. |
| electrogastroenterography changes:AP(uV) | before treatment, on day 1 of treatment, on day 3 of treatment | An electrogastroenterograph (Model EGEG-8D) was adopted. During examination, all subjects were placed in the supine position. Electrogastroenterography was performed before treatment, at 1 day and 3 days after treatment, and amplitude was recorded. |
| Actual feeding amount | before treatment, on day 1 of treatment, on day 3 of treatment, on day 7 of treatment. | Actual feeding amount (kcal)was recorded before treatment, on day 1 of treatment, on day 3 of treatment, on day 7 of treatment. |
| Intestinal diameter | before treatment, on day 1 of treatment, on day 3 of treatment | Using a Philips ultrasound machine, the intestinal diameter（cm） was assessed by scanning with a convex probe while the patient was in the supine position before treatment, 1 day after treatment, and 3 days after treatment. |
Contacts
CONTACTAiran Liu professor
Outcome results
None listed