Effects of ulinastatin combined with mechanical ventilation on oxygen metabolism, inflammation and stress response and antioxidant capacity of ARDS

Ji, Mingxia; Chen, Tiejiang; Wang, Baiming; Chen, Mengyan; Ding, Qianqian; Chen, Lingchao; Fang, Yuejuan; Yu, Xiaofang; Chen, Yanzhen; Wang, Xiaohua; He, Yiyue; Jiang, Yong

doi:10.3892/etm.2018.6012

Cited by 15 publications

(18 citation statements)

References 18 publications

(17 reference statements)

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“…Firstly, ulinastatin has an inhibitory effect on the production of in ammatory cytokines and adhesion molecules [25]. Meanwhile, ulinastatin improves the stability of lysosomal membrane and reduces the synthesis and delivery of lysosomal enzymes, thus scavenging oxygen or hydroxyl radicals [11]. In the present study, we observed the bene cial effect of ulinastatin for patients with Covid-19.…”

Section: Discussionsupporting

confidence: 58%

“…It inhibits the activity of various proteolytic enzymes and has been widely used for the treatment of acute pancreatitis [9]. Meanwhile, ulinastatin has been demonstrated as an important antiin ammatory and anti-oxidation agent and has been clinically used as a potential treatment for circulatory shock, severe sepsis and acute respiratory distress syndrome (ARDS) [10][11][12]. As a protease inhibitor, whether ulinastatin has bene cial effects on Covid-19 or not is unknown to date.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of Covid-19 Patients With High Dose of Ulinastatin

Huang

Sun

et al. 2020

Preprint

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Background No specific therapeutic agents or vaccines are available for the treatment of Coronavirus disease 2019 (Covid-19) yet. In this study, we aimed to assess the efficacy of high dose ulinastatin for patients with Covid-19.Methods Twelve patients hospitalized with confirmed SARS-CoV-2 infection were treated with high dose of ulinastatin beyond standard care. The changes of clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. Results A total of 10 patients with severe Covid-19 and 2 patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0 ± 11.9 years, ranging from 48 to 87 years. Nine of 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), cough (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12), and 58.3% of patients (7/12) had elevated hypersensitive C-reactive protein (CRP) levels (mean, 49.70 ± 77.70 mg/L). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP decreased significantly and returned to normal in 83.3% of patients (10/12; mean, 6.87 ± 6.63 mg/L) on the seventh day after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not need further oxygen therapy seven days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. No obvious adverse events were observed.Conclusions Our preliminary data revealed that high dose of ulinastatin treatment was safe and showed a potential beneficial effect for patients with Covid-19.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Treatment of Covid-19 Patients With High Dose of Ulinastatin

Huang

Sun

et al. 2020

Preprint

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“…The conventional therapy included mechanical ventilation, anti-infective therapy, nutritional support, treatment of primary diseases, etc. Although all the trials announced the randomization, 7 RCTs adequately described randomization procedures [31, 33, 38, 42, 43, 45, 49, 61], and 1 study [60] explicitly mentioned the method of allocation concealment using opaque envelope. Table 2 displays the quality and characteristics of these studies.…”

Section: Resultsmentioning

confidence: 99%

Ulinastatin treatment for acute respiratory distress syndrome in China: a meta-analysis of randomized controlled trials

Zhang

Zhu

Jiao³

et al. 2019

BMC Pulm Med

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BackgroundEpidemiologic studies have shown inconsistent conclusions about the effect of ulinastain treatment for acute respiratory distress syndrome (ARDS). It is necessary to perform a meta-analysis of ulinastatin’s randomized controlled trials (RCTS) to evaluate its efficacy for treating ARDS.MethodsWe searched the published RCTs of ulinastatin treatment for ARDS from nine databases (the latest search on April 30th, 2017). Two authors independently screened citations and extracted data. The meta-analysis was performed using Rev. Man 5.3 software.ResultsA total of 33 RCTs involving 2344 patients satisfied the selection criteria and were included in meta-analysis. The meta-analysis showed that, compared to conventional therapy, ulinastatin has a significant benefit for ARDS patients by reducing mortality (RR = 0.51, 95% CI:0.43~0.61) and ventilator associated pneumonia rate (RR = 0.50, 95% CI: 0.36~0.69), and shortening duration of mechanical ventilation (SMD = -1.29, 95% CI: -1.76~-0.83), length of intensive care unit stay (SMD = -1.38, 95% CI: -1.95~-0.80), and hospital stay (SMD = -1.70, 95% CI:-2.63~−0.77). Meanwhile, ulinastatin significantly increased the patients’ oxygenation index (SMD = 2.04, 95% CI: 1.62~2.46) and decreased respiratory rate (SMD = -1.08, 95% CI: -1.29~-0.88) and serum inflammatory factors (tumor necrosis factor-α: SMD = -3.06, 95% CI:-4.34~-1.78; interleukin-1β: SMD = -3.49, 95% CI: -4.64~-2.34; interleukin-6: SMD = -2.39, 95% CI: -3.34~-1.45; interleukin-8: SMD = -2.43, 95% CI: -3.86~-1.00).ConclusionsUlinastatin seemly showed a beneficial effect for ARDS patients treatment and larger sample sized RCTs are needed to confirm our findings.

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“…Ulinastatin is a urinary glycoprotein and protease inhibitor with potent antioxidant and anti-inflammatory effects [ 5 ]. In a small phase 2 trial, patients ( n = 40 per group) with ARDS treated with ulinastatin injection (12 hourly for 14 days) demonstrated improved lung oxygenation and function and reduced duration of mechanical ventilation and reduced hospital stays compared to standard care [ 5 ]. Ulinastatin therapy also significantly lowered inflammatory cytokines and increased antioxidant activities [ 5 ].…”

Section: Therapies In Clinical Trials For Ardsmentioning

confidence: 99%

“…In a small phase 2 trial, patients ( n = 40 per group) with ARDS treated with ulinastatin injection (12 hourly for 14 days) demonstrated improved lung oxygenation and function and reduced duration of mechanical ventilation and reduced hospital stays compared to standard care [ 5 ]. Ulinastatin therapy also significantly lowered inflammatory cytokines and increased antioxidant activities [ 5 ]. Another phase 2 trial of ulinastatin is currently enrolling, and a number of other protease inhibitors are in the preclinical stages of testing.…”

Section: Therapies In Clinical Trials For Ardsmentioning

confidence: 99%

Emerging pharmacological therapies for ARDS: COVID-19 and beyond

et al. 2020

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ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure. Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome. Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition. The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS. We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution. We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS. Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing. The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation. Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies ‘precision medicines.’ It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS.

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Effects of ulinastatin combined with mechanical ventilation on oxygen metabolism, inflammation and stress response and antioxidant capacity of ARDS

Cited by 15 publications

References 18 publications

Treatment of Covid-19 Patients With High Dose of Ulinastatin

Treatment of Covid-19 Patients With High Dose of Ulinastatin

Ulinastatin treatment for acute respiratory distress syndrome in China: a meta-analysis of randomized controlled trials

Emerging pharmacological therapies for ARDS: COVID-19 and beyond

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