ABSTRACT
Coronavirus disease 2019 (COVID-19) is still spreading worldwide. At present, no specific drug has been developed for the virus. Ulinastatin plays an important role in anti-inflammatory. Clinically, it is mainly used in acute pancreatitis, shock and disseminated intravascular coagulation. It also has the effects of antioxidant stress, anticoagulation and immune regulation, which may be of great significance to reduce the severity and mortality of COVID-19. Combined with the pharmacological effect of ulinastatin and its clinical application in the treatment of COVID-19 complications such as acute respiratory distress syndrome and sepsis lung injury, this paper discusses the feasibility of its application in COVID-19, so as to provide help for the clinical treatment and new drug research and development of this disease.Copyright © 2022 Tianjin Press of Chinese Herbal Medicines. All Rights Reserved.
ABSTRACT
Introduction: In critically ill patients with AKI, unacceptably high mortality rates reaching up to 50-80% in all dialyzed ICU patients are seen despite the availability of intensive renal support. At present there is no specific or targeted therapy for AKI. Pathophysiology of AKI is multifactorial. Systemic inflammation, mediated in part by cytokines, might be contributing majorly to the development of AKI. This mandates a multipronged approach to the treatment of AKI. There are hardly any studies on the use of ulinastatin in AKI. Our premise regarding the use of molecule in AKI was based on the fact that this molecule acts at multiple levels in the sepsis and can act to stop the cascade and thereby stop the "storm." Methods: We studied a total of 200 patients with AKI who needed ICU care in our hospital in the period between June 2017 - Jan 2020. Out of these, 100 patients received Injection ulinastatin 3 doses a day for 5 days, against a similar number of control patients. We included those patients with AKI who had SOFA scores more than 8. None of the patients had COVID 19 infection. We compared the same number of patients who had received ulinastatin with controls. Injection ulinastatin 1,50,000IU was given three times a day for 5 days. All the patients included had received dialytic therapy. We recorded the age of the patients, it varied from 11-94 years (mean age 52 years), > 60 % (120) of the patients being in the age group of 26-40 years. The ratio of males to females 1.8:1 (M: F 129:71). The etiologies were as follows: Malaria - complicated - P vivax, P falciparum (n= 76) 38% Enteric fever (n= 40) 20% UTI (n=30) 15% Post-partum (n=20) 10% Dengue (n = 14) 7% Acute gastroenteritis/diarrheal diseases (n= 12) 6% Pancreatitis (n= 6) 3% Obstructive uropathy (n= 3) 1.5% 33 % (n= 66) patients had diabetes as a co morbid condition. The renal function tests of all the patients along with liver function tests, sepsis parameters like d-dimer, serum procalcitonin levels, CRP-hs levels, coagulation tests, complete blood counts, and arterial blood gas analysis were done We recorded the length of stay, need and duration of renal replacement therapy, time to stoppage of renal replacement therapy, need for mechanical ventilation, mortality and post AKI recovery and progression to CKD. Result(s): The patients who received ulinastatin had a shorter stay in the ICU (p <0.01 vs control group);also, the time to stoppage of renal replacement therapy was shorter (p < 0.05). The recovery of renal function was seen in 84% (n=168). The progression to CKD was seen in 11% (n=22) of patients. The average number of sittings of dialysis needed were 11 (range3-20), lesser number of dialysis were needed in the ulinastatin group. The overall mortality was 36 %(n=72).The average follow up period post discharge has been 141 days (21 - 240 days) Conclusion(s): There definitely seem to be advantages in using ulinastatin and results look promising. But there are limitations to this study - this was a retrospective analysis hence not all the patients received ulinastatin. Moreover, the drug is expensive. This study was done in a semi urban set up where causes for AKI are predominantly infective. A larger prospective double-blind study will be needed to consider ulinastatin as a routine option for treating AKI. Till then preventing AKI should be the aim for us. No conflict of interestCopyright © 2023
ABSTRACT
Aim and objective: Ulinastatin is a glycoprotein extracted from fresh human urine. It inhibits the activity of various proteolytic enzymes. Patient with severe COVID-19 exhibit elevated serum levels of proinflammatory cytokines IL-6, tumour necrosis factor, IL-I beta, characterised as cytokine storm, which is believed to progress, leading to deterioration and death. Ulinastatin dampens inflammatory response. However, data on efficacy and the doses are limited. We evaluated the efficacy and doses of ulinastatin in the hospital all-cause mortality in patients with moderate to severe COVID-19. Materials and methods: This retrospective study was conducted between April 1 and June 30, 2021, at tertiary care centre. COVID-19 was confirmed with RT PCR by nasopharyngeal swab. Patients with moderate to severe COVID-19 (moderate SPO2<94%, severe SPO2<90%) on room air were included. This is the first study comparing the doses of ulinastatin in COVID-19. Results: In total 145 patients, 75 patients with moderate to severe COVID-19 were treated with ulinastatin + other standard treatment. 70 patients were treated only with standard treatment regime. Allcourse mortality was significantly lower in patients treated with ulinastatin (15.3% vs 20.5%). In a total of 75 patients treated with ulinastatin, 40 patients were given 200,000 units BD and 35 patients were given 200,000 units QID. There was not much difference in the all-cause mortality (15% vs 13%) between the two doses. No adverse effects were noted. Conclusion: Our observational data showed a beneficial effect in moderate-severe COVID-19 patients and there was not much difference in beneficial effects with regular doses 200,000 q12th hourly as compared to higher doses of 200,000 q 6th hourly. This is the first observational study comparing the doses and having highest number of patients treated with ulinastatin.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is still spreading worldwide. At present, no specific drug has been developed for the virus. Ulinastatin plays an important role in anti-inflammatory. Clinically, it is mainly used in acute pancreatitis, shock and disseminated intravascular coagulation. It also has the effects of antioxidant stress, anticoagulation and immune regulation, which may be of great significance to reduce the severity and mortality of COVID-19. Combined with the pharmacological effect of ulinastatin and its clinical application in the treatment of COVID-19 complications such as acute respiratory distress syndrome and sepsis lung injury, this paper discusses the feasibility of its application in COVID-19, so as to provide help for the clinical treatment and new drug research and development of this disease. © 2022 Tianjin Press of Chinese Herbal Medicines. All Rights Reserved.
ABSTRACT
Purpose: End-organ damage in coronavirus disease-2019 (COVID-19) is linked to "cytokine storm" and excessive release of inflammatory mediators. Various novel therapies have been used in COVID-19 including urinary trypsin inhibitor therapy. This study explores the efficacy of ulinastatin in COVID-19. Materials and methods: We retrieved the medical records of patients admitted during one month and did a propensity score analysis to create matched treatment and control groups. We analyzed these groups and the outcomes were presented with appropriate statistics. Survival curve was prepared to compare the survival effect of ulinastatin therapy at the end of hospitalization, among both the groups. Results: A total of 736 patients were admitted, and after adjusting the data with propensity score matching, 55 cases were selected by the system. On the final outcome analysis, we found that intensive care unit (ICU) length of stay [median (interquartile range) days 3 (3.5-7.8) vs 2 (0-4); p-value 0.28] in control vs intervention groups, and in hospital mortality (odds ratio: 0.491, CI 95%: 0.099-2.44, p-value 0.435) were not statistically different among the groups. In survival plot analysis also, there was no statistical difference (p-value 0.414) among both the groups.Conclusion: In this retrospective study, we conclude that the final outcome of the ICU length of stay, and overall, in hospital mortality were not different among both the groups. Hence, adequately powered randomized control trials are urgently required to confirm any benefit of ulinastatin therapy in COVID-19 treatment. How to cite this article: Jain A, Kasliwal R, Jain SS, Jain R, Gupta D, Gupta P, et al. Effect of Urinary Trypsin Inhibitor (Ulinastatin) Therapy in COVID-19. Indian J Crit Care Med 2022;26(6):696-703.
ABSTRACT
Currently, there are no specific therapeutic agents available for the treatment of coronavirus disease 2019 (Covid-19). The present study aimed to assess the efficacy of high-dose ulinastatin for the treatment of patients with Covid-19. A total of 12 patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 infection were treated with a high dose of ulinastatin alongside standard care. Changes in clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. A total of 10 patients with severe Covid-19 and two patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0±11.9 years (age range, 48-87 years). In total, nine of the 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 was significantly decreased and returned to normal in 83.3% of patients (10/12;mean, 6.87±6.63 mg/l) on day 7 after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not require further oxygen therapy 7 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. Compared with the standard care group, ulinastatin treatment significantly prevented illness deterioration. In conclusion, these preliminary data revealed that high-dose ulinastatin treatment was safe and exhibited a potential beneficial effect for patients with Covid-19. [ FROM AUTHOR] Copyright of Experimental & Therapeutic Medicine is the property of Spandidos Publications UK Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
Currently, there are no specific therapeutic agents available for the treatment of coronavirus disease 2019 (Covid-19). The present study aimed to assess the efficacy of high-dose ulinastatin for the treatment of patients with Covid-19. A total of 12 patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 infection were treated with a high dose of ulinastatin alongside standard care. Changes in clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. A total of 10 patients with severe Covid-19 and two patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0±11.9 years (age range, 48-87 years). In total, nine of the 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 was significantly decreased and returned to normal in 83.3% of patients (10/12; mean, 6.87±6.63 mg/l) on day 7 after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not require further oxygen therapy 7 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. Compared with the standard care group, ulinastatin treatment significantly prevented illness deterioration. In conclusion, these preliminary data revealed that high-dose ulinastatin treatment was safe and exhibited a potential beneficial effect for patients with Covid-19.
ABSTRACT
Immunomodulation has long been an adjunct approach in treating critically ill patients with sepsis, acute respiratory distress syndrome (ARDS), and acute pancreatitis (AP). Hyperactive immune response with immunopathogenesis leads to organ dysfunction and alters the clinical outcomes in critically ill. Though the immune response in the critically ill might have been overlooked, it has gathered greater attention during this novel coronavirus disease 2019 (COVID-19) pandemic. Modulating hyperactive immune response, the cytokine storm, especially with steroids, has shown to improve the outcomes in COVID-19 patients. In this review, we find that immune response pathogenesis in critically ill patients with sepsis, ARDS, and AP is nearly similar. The use of immunomodulators such as steroids, broad-spectrum serine protease inhibitors such as ulinastatin, thymosin alpha, intravenous immunoglobulins, and therapies such as CytoSorb and therapeutic plasma exchange may help in improving the clinical outcomes in these conditions. As the experience of the majority of physicians in using such therapeutics may be limited, we provide our expert comments regarding immunomodulation to optimize outcomes in patients with sepsis/septic shock, ARDS, and AP.
ABSTRACT
COVID-19 is known for its magical infectivity, fast transmission and high death toll based on the large number of infected people. From the perspective of the clinical manifestation, autopsy examination and pathophysiology, the essence of COVID-19 should be viewed as a sepsis induced by viral infection, and has the essential characteristics as sepsis induced by other pathogens. Therefore, in addition to etiological and supportive treatment, immunomodulatory therapy is also appropriate to severe COVID-19. Although there is still a lack of consensus on immunotherapy for sepsis so far, relatively rich experiences have been accumulated in the past decades, which will help us in the treatment of severe COVID-19. This article will elaborate immunotherapy of sepsis, though it may not be consistent.