Neostigmine Treatment of Acute Pancreatitis Combined With Intra-abdominal Hypertension

Study Overview
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Brief Summary
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Acute pancreatitis(A) often complicated with Intra-abdominal Hypertension. After the onset of acute pancreatitis, capillary leakage causing ascites,upper gastrointestinal tract obstruction and paralytic ileus leading to an elevated IAP, severe IAH leads to ACS with high mortality. Neostigmine is an anti-cholinesterase drugs, can enhance intestinal peristalsis, promote flatus defecation. The aim of this study was to determine the effect of neostigmine on reducing abdominal pressure and clinical prognosis in patients with AP by promoting intestinal peristalsis and defecation.

Detailed Description
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Acute pancreatitis(AP) runs a severe course in around 20% of patients and is associated with a mortality up to 30%. Intra-abdominal hypertension(IAH）is a common complication of severe acute pancreatitis(SAP). The inflammation of the pancreas starts a cascade of pancreatic and visceral edema, acute peripancreatic fluid collections, capillary leakage causing ascites, paralytic ileus, and gastric dilatation by upper gastrointestinal tract obstruction leading to an elevated intra-abdominal pressure (IAP). A sustained or repeated pathological elevation in IAP ≥12 mmHg is defined as IAH, it generally occurs often within the first week after onset of SAP. Persistent and serious IAH (IAP >20 mmHg ) often leads to new onset organ failure or acute worsening of existing organ failure, which is defined as ACS and associated with a mortality rate of 49%. In the past practice, many patients with ACS undergo decompressive laparotomy, which obviously has a risk of complications. Therefore, numerous medical, nonmedical, and minimally invasive therapies have been introduced. Neostigmine is an anti-cholinesterase drugs, can enhance intestinal peristalsis, promote flatus defecation. World Society for Abdominal Compartment Syndrome (WSACS)guidelines,suggest that neostigmine be used for the treatment of established colonic ileus not responding to other simple measures and associated with IAH.However, no data exist on the effects of pharmacologic promotility therapy on IAP or outcomes among those with IAH/ACS. The aim of this study was to evaluate the efficacy of neostigmine on reducing IAP in AP patients with IAH.

Official Title
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The Curative Effect and Security of Neostigmine Treatment of Acute Pancreatitis Combined With Intra-abdominal Hypertension

Conditions
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Acute Pancreatitis, Intra-abdominal Hypertension

Intervention / Treatment
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* Drug: Neostigmine Methylsulfate 1 MG/ML
* Combination Product: Conservative treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 year ; The diagnosis of acute pancreatitis according to the revised Atlanta classification. IAH is defined as IAP ≥ 12 mmHg by the World Society of Abdominal;Compartment Syndrome (WSACS); After 24 hours of conventional treatment(such as gastrointestinal decompression or percutaneous drainage of ascites), the IAP of AP patients with IAH was still ≥ 12 mmHg; The onset time of acute pancreatitis was within 2 weeks; Signed the informed consent. Exclusion Criteria: Previous history of laparotomy; Mechanical ileus or abdominal hemorrhage were considered clinically; Those who have contraindications to neostigmine: 1) Patients with angina; 2) myocardial infarction; 3) ventricular tachycardia; 4) bradycardia; 5) acute circulatory failure; 6) epilepsy; 7) bronchial asthma; 8) mechanical intestinal obstruction; 9) urinary tract infarction; 10) hyperthyroidism; 11) serious arrhythmia; 12) bladder operation; 13) intestinal fistula; Allergic to neostigmine; Pregnant or lactating patients.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neostigmine<br>Intramuscular injection of neostigmine on the basis of conventional conservative treatment | Drug: Neostigmine Methylsulfate 1 MG/ML<br>* The initial dose was 1mg, intramuscular injection(IM) once every 12 hours. If there is no defecation after 12 hours, the dose is increased to 1mg IM once every 8 hours; if there is no defecation after 24 hours, the dose is increased to 1mg IM once every 6 hours. If the abdominal pressure drops below 12mmhg, neostigmine will be stopped, otherwise it will be used continuously for 7 days.<br>* Other names: Prostigmin;Combination Product: Conservative treatment<br>* Intragastric administration of paraffin oil, 50ml,once every 8 hours；gastrointestinal decompression with nasogastric tube and rectal tub; lycerin enema promotes defecation; patients with ascites undergo percutaneous puncture drainage. Other conservative medical treatment recommended by the guidelines.<br>* Other names: Non-surgical treatment;|
| Other: Conservative treatment<br>Intragastric administration of paraffin oil, 50ml,once every 8 hours；gastrointestinal decompression with nasogastric tube and rectal tub; lycerin enema promotes defecation; patients with ascites undergo percutaneous puncture drainage. Other conservative medical treatment recommended by the guidelines. | Combination Product: Conservative treatment<br>* Intragastric administration of paraffin oil, 50ml,once every 8 hours；gastrointestinal decompression with nasogastric tube and rectal tub; lycerin enema promotes defecation; patients with ascites undergo percutaneous puncture drainage. Other conservative medical treatment recommended by the guidelines.<br>* Other names: Non-surgical treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change of IAP After Treatment | Monitor the intra-abdominal pressure within 1 to 7 days after randomization, and calculate the percent change compared with that before randomization | From randomization to 7 days after treatment,Measured IAP every 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change of Stool Volume at 1-7 Days After Randomization | After randomization, the change of stool volume (ML) was calculated every 24 hours.For example, the amount of stool volume decreased or increased in 24 hours after grouping compared to before grouping. | From randomization to 7 days | 
| New-onset Abdominal Compartment Syndrom | Abdominal compartment syndrome is defined as a sustained IAP>20 mmHg (with or without an APP<60 mmHg) that is associated with new organ dysfunction/failure | From randomization to discharge or death, assessed up to 4 weeks | 
| New-onset Organ Failure | Incidence of organ failure from randomization to discharge or death, assessed up to 3 months | From randomization to discharge or death, assessed up to 3 months | 
| Death of 90 Days | Death during from randomization to 90 days after onset. | From randomization to 90 days after onset. | 
| Timing of Enteral Nutrition | From date of randomization to enteral nutrition, assessed up to 30 days | Start time of enteral nutrition after randomization, assessed up to 30 days | 
| Number of Participants With Deterioration of IAH | IAP rebound ≥ 5mmHg or increase ≥ 20mmHg within 1-7 days after grouping | From randomization to 7 days | 
| Number of Participants With Adverse Effects on the Cardiovascular System | Due to that neostigmine has an inhibitory effect on the cardiovascular system, new-onset cardiovascular failure after grouping is considered as a possible adverse event related to neostigmine.Cardiovascular failure was defined as circulatory systolic blood pressure <90 mm Hg, despite adequate fluid resuscitation, or need for inotropic catecholamine support | From randomization to 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Pancreatitis, Intra-abdominal hypertension, Abdominal compartment syndrome, Curative Effect, Security, Neostigmine