Effect of Ulinastatin in the Treatment of Postperative Cognitive Dysfunction: Review of Current Literature

Lv, Zheng‐tao; Huang, Jian; Zhang, Jinming; Zhang, Jiaming; Guo, Jipeng; Chen, Anmin

doi:10.1155/2016/2571080

Cited by 17 publications

(14 citation statements)

References 28 publications

(26 reference statements)

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“…The inflammatory response is currently considered to be the most important mechanism for the occurrence of POCD. Clinically, anti-inflammatory drugs, such as ulinastatin and parecoxib, can reduce the level of inflammatory factors and reduce the incidence of POCD to some degree (8,12). Animal studies have found that inhibition of key enzymes in inflammatory response, use of inflammatory factor antagonists, regulation of the peripheral immune system, and regulation of neurohumoral mechanisms can alleviate neuroinflammatory reactions and improve cognitive impairment (13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

“…Ulinastatin is a serine protease inhibitor extracted from human urine, inhibiting the activity of various enzymes to reduce inflammation (7), stabilizing lysosomal membranes and scavenging free radicals. Clinically, the application of ulinastatin can reduce the level of inflammatory factors, thereby reducing the incidence of POCD to some degree (8).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Ulinastatin Combined With Dexmedetomidine on Postoperative Cognitive Dysfunction in Patients Who Underwent Cardiac Surgery

et al. 2019

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Background: Recent studies have shown that early diagnosis and intervention promote the patient's good prognosis. For patients who underwent cardiac surgery and require extracorporeal circulation support, the incidence of postoperative cognitive dysfunction (POCD) is higher than in other types of surgery due to greater changes in brain perfusion compared with normal physiological conditions. Recent studies have confirmed that the use of ulinastatin or dexmedetomidine in the perioperative period effectively reduces the incidence of POCD. In this study, ulinastatin was combined with dexmedetomidine to assess whether the combination of the two drugs could reduce the incidence of POCD. Methods: One hundred and eighty patients with heart valve replacement surgery undergoing cardiopulmonary bypass from August 2017 to December 2018 were enrolled, with age 60-80 years, American Society of Anesthesiologists (ASA) grades I-III, education level above elementary school, and either gender. According to the random number table method, patients were grouped into ulinastatin + dexmedetomidine (U+D) group, ulinastatin (U) group, dexmedetomidine (D) group, and normal saline (N) control group. Group U was pumped 20,000 UI/kg immediately after induction and the first day after surgery, group D continued to pump 0.4 µg/kg/h from induction to 2 h before extubation, group U+D dexmedetomidine 0.4 µg/kg/h + ulinastatin 20,000 UI/kg, and group N equal volume of physiological saline. The patients were enrolled with Mini-Mental State Examination (MMSE) before surgery. The cognitive function was assessed by Montreal Cognitive Assessment (MoCA) on the first day before surgery and on the seventh day after surgery. Inflammatory factors, such as S100β protein, interleukin (IL)-6, matrix metalloproteinase (MMP)-9, and tumor necrosis factor (TNF)-α, were detected in peripheral blood before anesthesia (T0), immediately after surgery (T1), and immediately after extubation (T2). Results: One hundred and fifty-four patients enrolled in this study. Compared with group N, the incidence of POCD in group U+D was the lowest (P < 0.05), followed by group U and group D. Group U+D had the lowest concentration of inflammatory factors at the T1 and T2 time points, followed by group U and group D. Zhou et al. Ulinastatin and Dexmedetomidine for Postoperative Cognitive Dysfunction Conclusions: Both ulinastatin and dexmedetomidine can reduce the perioperative inflammatory response and the incidence of POCD in patients with heart valve surgery, and their combination can better reduce the incidence of POCD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Ulinastatin Combined With Dexmedetomidine on Postoperative Cognitive Dysfunction in Patients Who Underwent Cardiac Surgery

et al. 2019

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“…It can reduce the body’s inflammatory response through various ways such as antioxidant reaction, anti-proteolysis, and inhibition of inflammatory mediator release. Lv et al (2016) reported that Ulinastatin administration was effective in treating early POCD (post-operative days 3 and 7) and reducing IL-6 and S100β concentrations within 2 days after operations. Lili et al (2013) reported that the ulinastatin group had a lower incidence of POCD than the control group (2.5 versus 27.5%, p < 0.05) and the ulinastatin group had lower serum S100β protein and IL-6 concentrations than those in the control group.…”

Section: Discussionmentioning

confidence: 99%

Ulinastatin May Significantly Improve Postoperative Cognitive Function of Elderly Patients Undergoing Spinal Surgery by Reducing the Translocation of Lipopolysaccharide and Systemic Inflammation

Zhang

et al. 2018

Front. Pharmacol.

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Background: Studies have shown that perioperative inflammatory response is one of the important factors that caused postoperative cognitive dysfunction (POCD). Ulinastatin is a broad-spectrum protease inhibitor that inhibits inflammatory. We investigated the effects of ulinastatin on inflammatory response and early postoperative cognitive function in elderly patients undergoing spinal surgery.Methods: This clinical trial was approved by the Xuanwu Hospital Ethical Committee (Registration number: ChiCTR-IPR-16008931). Sixty elderly patients undergoing elective spinal surgery with American Society of Anesthesiologists (ASA) status of I–II were randomized into ulinastatin and control groups; total intravenous anesthesia was performed. The elderly patients in ulinastatin group underwent intravenous infusion of ulinastatin 10,000 units/kg following anesthesia induction and before surgical incision, and 5000 units/kg on post-operative days 1 and 2. Cognitive function was determined with Montreal Cognitive Assessment (MOCA) test preoperatively and on post-operative day 7 by a neurologist. Serum lipopolysaccharide (LPS), interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloprotease-9 (MMP-9) concentration levels were measured at baseline, the end of surgery, and on post-operative days 1 and 3.Results: All elderly patients completed the study. Ulinastatin infusion significantly reduced the incidence of POCD in elderly patients undergoing spine surgery (ulinastatin group 16% vs. control group 43%, χ2 = 5.079, P = 0.024, P < 0.05). The elderly patients in ulinastatin group exhibited lower serum LPS, IL-6, CRP, and MMP-9 concentrations, as well as a shortened peak value duration, compared with those in the control group following surgery (P < 0.05).Conclusion: Systemic inflammation and translocation of LPS were inhibited by the infusion of ulinastatin in elderly patients undergoing spinal surgery. The anti-inflammation intervention with ulinastatin can significantly improve the elderly patients’ postoperative cognitive function.

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“…Ulinastatin is associated with reduced circulating inflammatory mediators and reduced blood brain barrier permeability in animal models of SIRS [ 106 ]. A recent meta-analysis of 5 studies and over 450 patients has reported a 60% reduction in the rate of POCD [ 107 ].…”

Section: Therapeutic Options For Post-operative Neurological Complicamentioning

confidence: 99%

Surgery, neuroinflammation and cognitive impairment

et al. 2018

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Trauma experienced during surgery can contribute to the development of a systemic inflammatory response that can cause multi-organ dysfunction or even failure. Post-surgical neuroinflammation is a documented phenomenon that results in synaptic impairment, neuronal dysfunction and death, and impaired neurogenesis. Various pro-inflammatory cytokines, such as TNFα, maintain a state of chronic neuroinflammation, manifesting as post-operative cognitive dysfunction and post-operative delirium. Furthermore, elderly patients with post-operative cognitive dysfunction or delirium are three times more likely to experience permanent cognitive impairment or dementia. We conducted a narrative review, considering evidence extracted from various databases including Pubmed, MEDLINE and EMBASE, as well as journals and book reference lists. We found that further pre-clinical and well-powered clinical studies are required to delineate the precise pathogenesis of post-operative delirium and cognitive dysfunction. Despite the burden of post-operative neurological sequelae, clinical studies investigating therapeutic agents, such as dexmedetomidine, ibuprofen and statins, have yielded conflicting results. In addition, evidence supporting novel therapeutic avenues, such as nicotinic and HMGB-1 targeting and remote ischaemic pre-conditioning, is limited and necessitates further investigation.

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Effect of Ulinastatin in the Treatment of Postperative Cognitive Dysfunction: Review of Current Literature

Cited by 17 publications

References 28 publications

Effect of Ulinastatin Combined With Dexmedetomidine on Postoperative Cognitive Dysfunction in Patients Who Underwent Cardiac Surgery

Effect of Ulinastatin Combined With Dexmedetomidine on Postoperative Cognitive Dysfunction in Patients Who Underwent Cardiac Surgery

Ulinastatin May Significantly Improve Postoperative Cognitive Function of Elderly Patients Undergoing Spinal Surgery by Reducing the Translocation of Lipopolysaccharide and Systemic Inflammation

Surgery, neuroinflammation and cognitive impairment

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