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

 

by Wenhua He, Peng Chen, Yupeng Lei, Liang Xia, Pi Liu, Yong Zhu, Hao Zeng, Yao Wu, Huajing Ke, Xin Huang, Wenhao Cai, Xin Sun, Wei Huang, Robert Sutton, Yin Zhu and Nonghua Lu 

 

Critical Care volume 26, Article number: 52 (2022) Published: 03 March 2022

 

 

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).