Outcome of Ulinastatin vs Metabolic Resuscitation using Ascorbic Acid, Thiamine and Glucocorticoid in Early Treatment of Sepsis- A Randomised Controlled Trial

Abstract

Introduction: Sepsis is one the most common cause of morbidity and mortality worldwide. Sepsis and septic shock are life-threatening disease which increases mortality with circulatory, cellular and metabolic abnormalities. Urinary trypsin inhibitor is an important protease inhibitor found in human blood and urine, it is known as Ulinastatin (ULI) or bikunin. It is an acidic glycoprotein (molecular weight 30 kDa) and Kunitz-type serine protease inhibitor. It is derived from the larger inter-αtrypsin inhibitor molecule by action of neutrophil elastase in the presence of inflammation, and is believed to play an important anti-inflammatory role. Aim: To compare the outcome of intravenous ULI (protease inhibitor known as urinary trypsin inhibitor) versus the combination of hydrocortisone, ascorbic acid (vitamin C) and thiamine regarding outcome in sepsis and septic shock. Materials and Methods: In this randomised controlled trial conducted between July 2018 to June 2019 on total 60 sepsis patients were included and divided into two equal groups. Group A patients received combination of intravenous Hydrocortisone, Ascorbic acid and Thiamine (HAT) and group B Ulinastatin received intravenous Intensive Care Unit(ICU). Baseline demographic, clinical and laboratory data were recorded along with Acute Physiology and Chronic Health Evaluation (APACHE) 2 and Sequential Organ Failure Assessment (SOFA) scoring system at the time of admission in ICU. All statistical test were performed using SPSS 21.0 windows software. Comparisons between groups were assessed by using student t-test and chisquare test. Results: Mean age was comparable in both the groups (36.7±12.5 years in group A vs 37.5±12.9 years in group B). SOFA Score were significantly lower in group B as compared to group A on day 3 (7.76±3.67 vs 12.03±4.77) and day 5 (4.79±4.02 vs 12.10±7.36). Rate of reduction in serum procalcitonin level was also found to be significant in group B (p=0.008) as compared to group A (p=0.103). Lactate clearance rate was also fast in group B as compared to group A on day 3 and day 5. There was significant mortality benefit in group B (20%) as compared to group A (50%). Patients were followed up for 28 days till the start of treatment. Conclusion: This study showed that the ULI may play a beneficial role in early management of sepsis and septic shock.

Keywords

• hydrocortisone
• lactate
• procalcitonin
• septic shock protease inhibitor