Category: Critical Care
Keywords: delirium, ICU, acetylcholinesterase inhibitor (PubMed Search)
Posted: 10/14/2025 by Quincy Tran, MD, PhD
(Updated: 12/5/2025)
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Delirium is common among critically ill patients. Some of the common Acetylcholinesterase inhibitors (AChEI), rivastigmine, donepezil, have been used to prevent delirium in ICU patients. However, their efficacy was just recently re-examined in a meta-analysis of only Randomized Control Trials.
Ten studies and 731 patients were included- 365 in the treatment (AChEI) group and 366 in the control group.
AChEI was associated with lower occurrence of delirium (RR 0.68, 95% CI 0.47-0.98, p=0.039. However, there was no significant difference in the delirium duration (mean difference -0.16 day, 95% CI -0.95 to 0.62 day, p=0.23). There was no difference in delirium severity nor length of hospital stay.
Among the medication, interestingly, rivastigmine 4.5 mg/day significantly reduced delirium occurrence (RR = 0.61 [0.39– 0.97]) and severity (SMD = –0.33 [–0.58 to –0.08]), as well as length of hospital stay (MD = –1.29 [–1.87 to –0.72]).
Discussion:
This meta-analysis was well-conducted.
The cholinergic dysregulation—especially elevated acetylcholinesterase activity—can lead to the imbalance between attention and cognition, contributing to delirium in ICU patients. Thus, the use of AChEI and reduction of occurrence of delirium proves that acetylcholine deficiency may be associated with delirium among ICU patients.
Subgroup analysis showed that prophylactic use of AChEI was associated with significant reduction of delirium duration. Thus, further studies are needed to define which populations will benefit from AChEI.
Conclusion:
AChEIs are effective in reducing occurrence of delirium, but they did not affect delirium duration, severity or hospital LOS.
Pipek LZ, Pascual GS, Nascimento RFV, Silva GD, Castro LH. Acetylcholinesterase Inhibitors for Delirium Prevention: A Systematic Review and Meta-Analysis. Crit Care Med. 2025 Oct 1;53(10):e2054-e2061. doi: 10.1097/CCM.0000000000006786. Epub 2025 Aug 5. PMID: 40758382.
