Randomized controlled trial: neostigmine for intra-abdominal hypertension in acute pancreatitis

Abstract

Background Intra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine for IAH in patients with AP. Methods In this single-center, randomized trial, consenting patients with IAH within 2 weeks of AP onset received conventional treatment for 24 h. Patients with sustained intra-abdominal pressure (IAP) ≥ 12 mmHg were randomized to receive intramuscular neostigmine (1 mg every 12 h increased to every 8 h or every 6 h, depending on response) or continue conventional treatment for 7 days. The primary outcome was the percent change of IAP at 24 h after randomization. Results A total of 80 patients were recruited to neostigmine (n = 40) or conventional treatment (n = 40). There was no significant difference in baseline parameters. The rate of decrease in IAP was significantly faster in the neostigmine group compared to the conventional group by 24 h (median with 25th–75th percentile: −18.7% [− 28.4 to − 4.7%] vs. − 5.4% [− 18.0% to 0], P = 0.017). This effect was more pronounced in patients with baseline IAP ≥ 15 mmHg (P = 0.018). Per-protocol analysis confirmed these results (P = 0.03). Stool volume was consistently higher in the neostigmine group during the 7-day observational period (all P < 0.05). Other secondary outcomes were not significantly different between neostigmine and conventional treatment groups. Conclusion Neostigmine reduced IAP and promoted defecation in patients with AP and IAH. These results warrant a larger, placebo-controlled, double-blind phase III trial. Trial registration Clinical Trial No: NCT02543658 (registered August /27, 2015).

Intra-Abdominal Hypertension: A Systemic Complication of Severe Acute Pancreatitis

“…IAP was reduced by approximately in 24 h. The stool volume was higher in the neostigmine group during the 7-day observational period. No adverse events related to neostigmine were observed [33].…”

Neostigmine for non-mild acute pancreatitis: A systematic review and meta-analysis of randomized controlled trials

“…Trial sequential analyses (TSA) were used to control the risk of random errors and assess the conclusions. Based on previous clinical experiences and RCTs in this field, we used the mean difference (MD) and a variance of power of 80% to calculate the required sample size and assess the clinical significance of the primary outcome in our review (He et al, 2022). Decisions were made based on the position of cumulative Z curves with the conventional boundary, trial sequential monitoring boundary, and futility boundary (Wetterslev et al, 2017).…”

“…It is widely used as a prokinetic drug in the treatment of AP, especially with gut dysfunction and IAH. Several previous studies showed that it had positive effects on AP with the latest randomized controlled trials (RCTs) published in March 2022, suggesting that neostigmine could reduce IAH and promote defecation (Schneider et al, 2014;He et al, 2022;Mancilla Asencio and Berger Fleiszig, 2022). However, its clinical value for AP has remained debatable so far, and the current international clinical guidelines did not attribute enough importance to this drug.…”

Efficacy and safety of neostigmine on treating gastrointestinal dysmotility in severe acute pancreatitis patients: study protocol for a randomized controlled trial

“…It has been used for postoperative recovery of gastrointestinal function [ 28 , 29 ]. One study have shown that neostigmine could reduce intra-abdominal pressure (IAP) in SAP patients [ 30 ]. however, this is a single-center study with small sample size and no blinding was used.…”