Ulinastatin is effective in reducing mortality for critically ill patients with sepsis: a causal mediation analysis

Xu, Qiancheng; Yan, Qian; Chen, Shanghua

doi:10.1038/s41598-018-32533-9

Cited by 16 publications

(12 citation statements)

References 36 publications

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“…Ulinastatin is a glycoprotein which can be obtained from human urine or produced synthetically. Proteolytic enzymes, including trypsin, elastase, and plasmin can be effectively inhibited by ulinastatin, lipase, and amylase, thus relieving the systemic inflammatory response and diminishing the severity of pancreatitis (9)(10)(11)(12). However, the dose-response effect of ulinastatin in SAP has not been established.…”

Section: Original Articlementioning

confidence: 99%

The efficacy of different doses of ulinastatin in the treatment of severe acute pancreatitis

He¹,

Zhang²

2020

Ann Palliat Med

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Background: Severe acute pancreatitis (SAP) is a severe form of inflammatory disease with a high mortality rate. Ulinastatin, a urinary trypsin inhibitor, has anti-inflammatory properties and may be beneficial to critically ill patients with SAP. Nevertheless, there is currently insufficient evidence to conclude whether there is a dose-effect relationship between ulinastatin and SAP treatment outcomes. The present study examined the efficacy of ulinastatin at different doses in the treatment of SAP.Methods: A retrospective study was conducted examining the clinical outcomes of 130 SAP patients.Patients were categorized into a control group and three groups receiving different daily doses of ulinastatin (200,000; 400,000; and 600,000 IU). The study compared the 1-week mortality rate; the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score; abdominal pain relief time; time to recover a normal heart and respiratory rate; blood amylase, glucose, C-reactive protein, and procalcitonin levels; and white blood cell (WBC) count among the different groups.Results: The 400,000 and 600,000 IU groups had significantly lower mortality rates and WBC count compared to the 200,000 IU group (P<0.05). Furthermore, the 400,000 IU group had a significantly shorter abdominal pain relief time compared to the 200,000 IU group (P<0.05). Compared to the 200,000 IU group, the 600,000 IU group had significantly shorter time to recover a normal respiratory rate and a lower APACHE-II score (P<0.05).Conclusions: Ulinastatin can improve the clinical outcomes of patients with SAP but efficacy varies with the dosage.

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Section: Original Articlementioning

confidence: 99%

The efficacy of different doses of ulinastatin in the treatment of severe acute pancreatitis

He¹,

Zhang²

2020

Ann Palliat Med

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“…UTI can also suppress MAPK-signaling pathway, which mediates the release of inflammatory cytokines such as TNF-α, IL-1, and IL-6 (Inoue and Takano, 2010; Fang et al, 2018). Recently, a retrospective study of 263 critically ill patients with sepsis found that 28-day mortality decreased significantly with UTI (Xu et al, 2018). The authors concluded that 35% of the total effect of UTI was associated with the reduction in C-reactive protein (CRP), a major marker of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Improvement of Sepsis Prognosis by Ulinastatin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

et al. 2019

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Background: Ulinastatin has been prescribed to treat sepsis. However, there is doubt regarding the extent of any improvement in outcomes to guide future decision making.Objectives: To evaluate the effects of ulinastatin on mortality and related outcomes in sepsis patients.Methods: Thirteen randomized controlled trials and two prospective studies published before September 1, 2018, that included 1358 patients with sepsis, severe sepsis, or septic shock were evaluated. The electronic databases searched in this study were PubMed, Medline, Embase, and China National Knowledge Infrastructure (CNKI) for Chinese Technical Periodicals.Results: Ulinastatin significantly decreased the all-cause mortality {odds ratio (OR) = 0.48, 95% confidence interval (CI) [0.35–0.66], p < 0.00001, I2 = 13%}, Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score {mean difference (MD) = −2.40, 95% CI [−4.37, −0.44], p = 0.02, I2 = 66%}, and reduced the incidence of multiple organ dysfunction syndrome (MODS) (OR = 0.3, 95% CI [0.18, 0.49], p < 0.00001, I2 = 0%). Ulinastatin also decreased the serum levels of IL-6 (MD = −88.5, 95% CI [−123.97, −53.04], p < 0.00001), TNF-α (MD = −56.22, 95% CI [−72.11, −40.33], p < 0.00001), and increased the serum levels of IL-10 (MD = 37.73, 95% CI [16.92, 58.54], p = 0.0004). Ulinastatin administration did not lead to any difference in the occurrence of adverse events.Conclusions: Ulinastatin improved all-cause mortality and other related outcomes in patients with sepsis or septic shock. The results of this meta-analysis suggest that ulinastatin may be an effective treatment for sepsis and septic shock.

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“…Ulinastatin can reduce the pro-inflammatory levels (including TNF-α, IL-6, and IFN-γ), increase the anti-inflammatory factor IL-10 level (Tao et al, 2017), and promote the balance between proinflammatory and anti-inflammatory responses, thus blocking the cytokine storm induced by the vicious circle of inflammatory responses. Animal studies suggest that high-dose ulinastatin achieves a comparable anti-inflammatory effect to glucocorticoids (Xu et al, 2018). In 2017, a meta-analysis of eight RCTs suggested that ulinastatin combined with thymosin α1 (Tα1) in sepsis patients suppressed pro-inflammatory factor production, reduced the Acute Physiology and Chronic Health Evaluation (APACHE) II score, shortened the durations of mechanical ventilation, and improved the 28-days survival rate (Liu et al, 2017).…”

Section: Ulinastatinmentioning

confidence: 99%

Immune Intervention in Sepsis

Chen

Wei

2021

Front. Pharmacol.

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Sepsis is a host immune disorder induced by infection. It can lead to multiple organ dysfunction syndrome (MODS), which has high morbidity and mortality. There has been great progress in the clinical diagnosis and treatment of sepsis, such as improvements in pathogen detection technology, innovations regarding anti-infection drugs, and the development of organ function support. Abnormal immune responses triggered by pathogens, ranging from excessive inflammation to immunosuppression, are recognized to be an important cause of the high mortality rate. However, no drugs have been approved specifically for treating sepsis. Here, we review the recent research progress on immune responses in sepsis to provide a theoretical basis for the treatment of sepsis. Constructing and optimizing a dynamic immune system treatment regimen based on anti-infection treatment, fluid replacement, organ function support, and timely use of immunomodulatory interventions may improve the prognosis of sepsis patients.

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Ulinastatin is effective in reducing mortality for critically ill patients with sepsis: a causal mediation analysis

Cited by 16 publications

References 36 publications

The efficacy of different doses of ulinastatin in the treatment of severe acute pancreatitis

The efficacy of different doses of ulinastatin in the treatment of severe acute pancreatitis

Improvement of Sepsis Prognosis by Ulinastatin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Immune Intervention in Sepsis

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