Effect of Ulinastatin on Early Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Surgery: A Systemic Review and Meta-Analysis

Abstract

Background: Postoperative cognitive dysfunction (POCD) is associated with neuroinflammation by triggering the systemic inflammatory responses. Related studies have demonstrated that ulinastatin, which is a urinary trypsin inhibitor, inhibited the release of inflammatory mediators and improved postoperative cognitive function in elderly patients undergoing major surgery. However, there are controversial results put forwarded by some studies. This systemic review aimed to evaluate the effect of ulinastatin on POCD in elderly patients undergoing surgery.Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, and Ovid to find relevant randomized controlled trials (RCTs) of ulinastatin on POCD in elderly patients undergoing surgery. The primary outcomes included the incidence of POCD and the Mini-Mental State Examination (MMSE) scores. The secondary outcome was the levels of inflammatory cytokines such as tumor necrosis factor (TNF)-α, S100β, C-reactive protein (CRP), interleukin (IL)-6, and IL-10. RevMan 5.3 was used to conduct the meta-analysis.Results: Ten RCTs were included finally. Compared with controls, ulinastatin significantly reduced the incidence of POCD [risk ratio (RR) = 0.29, 95% CI 0.21–0.41, test of RR = 1: Z = 7.05, p < 0.00001]. In addition, patients in the ulinastatin group have lower levels of TNF-α, S100β, CRP, and IL-6 and higher level of IL-10 in serum following surgery.Conclusion: These findings suggested that ulinastatin can be used as an anti-inflammatory drug for POCD prevention in elderly patients undergoing surgery.Systematic Review Registration Number: CRD42019137449.

Progress in Research on the Effect of Melatonin on Postoperative Cognitive Dysfunction in Older Patients

“…POCD is the result of various mechanisms, such as neuroinflammation, oxidative stress, dysfunction of neurotransmitters or their receptors, circadian rhythm disorders, iron overload ( Gögenur et al, 2007 ; Li et al, 2016 ; Netto et al, 2018 ; Luo et al, 2019 ; Wang C. M. et al, 2021 ). At present, the drugs for the prevention and treatment of POCD include non-steroidal anti-inflammatory drugs (parecoxib, acetaminophen, ibuprofen), anesthesia-related drugs (dexmedetomidine, etomidate, oxycodone), ulinastatin, desferrioxamine, antipsychotics, and so on ( Zhou et al, 2019 ; Gan et al, 2020 ; Huang et al, 2020 ; Yu and Xie, 2020 ; Zhao et al, 2020 ; Duan et al, 2021 ). However, there is still a lack of safe and effective ideal drugs.…”

Effects of LncRNA GAS5/miR-137 general anesthesia on cognitive function by TCF4 inflammatory bodies in patients undergoing lumbar spinal canal decompression

“…[ 24 ] Its diagnosis requires neuropsychological testing. [ 25 ] Herein, this experiment showed that LncRNA GAS5 raised cognitive impairment and increased neuroinflammation in mice model. Zhao et al suggests silencing GAS5 protects against brain injury in hypoxia/ischemia model.…”

Effects of anesthetic adjunctive agents on postoperative cognitive dysfunction in elderly patients undergoing noncardiac surgery: A Bayesian network meta‐analysis

“…Clinical studies and meta-analysis suggest that ulinastatin may attenuate POCD by reducing the release of TNF-α and IL-6 (Duan et al, 2021;Hirsch et al, 2016;Li et al, 2018;Lili et al, 2013). Ulinastatin reduces proinflammatory cytokine levels, such as TNF-α, CRP, and IL-6, by activating the PI3K/Akt/Nrf2 pathway (Li et al, 2018).…”

“…In view of the different incidence rates of POCD at different time points after operation, we performed summary statistics and metaanalyses on the occurrence of POCD on postoperative days 1, 3, and 7 (Duan et al, 2021;Huang et al, 2020a;Li et al, 2021a;Mansouri et al, 2019).…”