Neostigmine Treatment of Acute Pancreatitis Combined With Intra-abdominal Hypertension

Acute Pancreatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02543658
• Other study ID #: FAHONCU
• Status: Completed
• Phase: Phase 2
• Start date: September 1, 2015
• Est. completion date: May 30, 2018

Study information

• Verified date: October 2021
• Source: The First Affiliated Hospital of Nanchang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: May 30, 2018
• Est. primary completion date: August 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Age 18-70 year ;

2. The diagnosis of acute pancreatitis according to the revised Atlanta classification.

3. IAH is defined as IAP = 12 mmHg by the World Society of Abdominal;Compartment Syndrome (WSACS);

4. 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;

5. The onset time of acute pancreatitis was within 2 weeks;

6. Signed the informed consent.

Exclusion Criteria:

1. Previous history of laparotomy;

2. Mechanical ileus or abdominal hemorrhage were considered clinically;

3. 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;

4. Allergic to neostigmine;

5. Pregnant or lactating patients.

Related Conditions & MeSH terms

• Acute Pancreatitis
• Hypertension
• Intra-abdominal Hypertension
• Pancreatitis

Intervention

Drug:
• Neostigmine Methylsulfate 1 MG/ML
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.

Combination Product:
• Conservative treatment
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.

Locations

Country	Name	City	State
China	Affiliated Hospital of Nanchang University	Nanchang	Jiangxi

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Nanchang University

Country where clinical trial is conducted

China, 

References & Publications (11)

Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25. — View Citation

Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000 May 25;405(6785):458-62. — View Citation

Kasi PM. The use of intravenous neostigmine in palliation of severe ileus. Case Rep Gastrointest Med. 2013;2013:796739. doi: 10.1155/2013/796739. Epub 2013 Feb 14. — View Citation

Kirkpatrick AW, Roberts DJ, De Waele J, Jaeschke R, Malbrain ML, De Keulenaer B, Duchesne J, Bjorck M, Leppaniemi A, Ejike JC, Sugrue M, Cheatham M, Ivatury R, Ball CG, Reintam Blaser A, Regli A, Balogh ZJ, D'Amours S, Debergh D, Kaplan M, Kimball E, Olvera C; Pediatric Guidelines Sub-Committee for the World Society of the Abdominal Compartment Syndrome. Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med. 2013 Jul;39(7):1190-206. doi: 10.1007/s00134-013-2906-z. Epub 2013 May 15. — View Citation

Ponec RJ, Saunders MD, Kimmey MB. Neostigmine for the treatment of acute colonic pseudo-obstruction. N Engl J Med. 1999 Jul 15;341(3):137-41. — View Citation

Schneider L, Jabrailova B, Soliman H, Hofer S, Strobel O, Hackert T, Büchler MW, Werner J. Pharmacological cholinergic stimulation as a therapeutic tool in experimental necrotizing pancreatitis. Pancreas. 2014 Jan;43(1):41-6. doi: 10.1097/MPA.0b013e3182a85c21. — View Citation

Shaikh N, Kettern MA, Hanssens Y, Elshafie SS, Louon A. A rare and unsuspected complication of Clostridium difficile infection. Intensive Care Med. 2008 May;34(5):963-6. Epub 2007 Nov 20. — View Citation

Tracey KJ. The inflammatory reflex. Nature. 2002 Dec 19-26;420(6917):853-9. Review. — View Citation

Trikudanathan G, Vege SS. Current concepts of the role of abdominal compartment syndrome in acute pancreatitis - an opportunity or merely an epiphenomenon. Pancreatology. 2014 Jul-Aug;14(4):238-43. doi: 10.1016/j.pan.2014.06.002. Epub 2014 Jun 17. Review. — View Citation

van Brunschot S, Schut AJ, Bouwense SA, Besselink MG, Bakker OJ, van Goor H, Hofker S, Gooszen HG, Boermeester MA, van Santvoort HC; Dutch Pancreatitis Study Group. Abdominal compartment syndrome in acute pancreatitis: a systematic review. Pancreas. 2014 Jul;43(5):665-74. doi: 10.1097/MPA.0000000000000108. Review. — View Citation

Vidal MG, Ruiz Weisser J, Gonzalez F, Toro MA, Loudet C, Balasini C, Canales H, Reina R, Estenssoro E. Incidence and clinical effects of intra-abdominal hypertension in critically ill patients. Crit Care Med. 2008 Jun;36(6):1823-31. doi: 10.1097/CCM.0b013e31817c7a4d. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Days in Hospital	Days in hospital within 6 months after randomisation	From randomisation to 6 months
Other	Days in ICU	Days in ICU within 6 months after randomisation	From randomisation to 6 months
Other	Medical Expenses	Medical expenses within 6 months after randomisation	From randomisation to 6 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	Death of 90 Days	Death during from randomization to 90 days after onset.	From randomization to 90 days after onset.
Secondary	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
Secondary	Number of Participants With Deterioration of IAH	IAP rebound = 5mmHg or increase = 20mmHg within 1-7 days after grouping	From randomization to 7 days
Secondary	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