The Role of Leu-Enkephalin Synthetic Analogue in Regulation of Systemic Inflammatory Response and Prevention of ARDS in Severe Combined Injury

Abstract

The aim of the study. To study the effect of ley-enkephalin synthetic analogue on the dynamics of inflammatory response markers and organ dysfunction in patients with severe combined trauma.Materials and methods. A prospective clinical study with historical control from two clinical centers — N. I. Pirogov State Clinical Hospital No. 1 and N.V. Sklifosovsky Clinical and Research Institute for Emergency Medicine — included men and women with severe combined trauma and the ISS scores values of 18–44, aged 18 to 70 years. Diagnostic and therapeutic approaches in all patients followed current international, national& local protocols and 2022 clinical recommendations of the Russian Society of Surgeons «Combined and multiple trauma in combination with shock (Polytrauma)». In the study group, treatment was supplemented with extended (72 hours from the admission) infusion of the test drug through a syringe dispenser following the study protocol. Effects of the test drug prolonged infusion were evaluated for the following laboratory parameters: levels of cortisol, procalcitonin, interleukin 6, NTproBNP and leukocyte count. Laboratory tests were performed at 4 time points: prior to test drug infusion, 24 hours and 72 hours after initiation of infusion, and on Day 7. The study evaluated patient’s dynamics using APACHE II, SOFA and SAPS II scales and percentage of patients developing organ dysfunction (renal, respiratory, cardiovascular), rates of sepsis complications and mortality.Results. Patients who received the test drug had significantly lower concentrations of systemic inflammatory response markers, i. e. PCT (P=0.001) and IL-6 (P=0.010) after 24 hours of follow-up vs the control group patients. The incidence of ARDS has also decreased in the study group (P=0.011 vs control). Acute kidney injury (AKI) rate was insignificantly higher in the control group (P=0.349). The duration of hospital stay in the control group was 35 (17; 51) days vs 18 (14; 30) days in the study group (P=0.140)Conclusion. The use of ley-enkephalin synthetic analogue inhibits production of such key systemic inflammatory response markers as PCT and IL-6, and reduces PCT concentrations within 24 hours in patients with severe combined trauma. ARDS developed less frequently in the study group, but there was no significant difference in the incidence of AKI, AHF and infectious complications between the groups.

Keywords

• synthetic analogue of leu-enkephalin
• dalargin
• systemic inflammatory response
• combined trauma
• ards
• intensive care