P0753 - Prevention of sepsis by inhalation nitrogen oxide

Relevance. It is known, that the molecule NO - is fundamental factor of anti-infectious resistance of an organism.
Purpose. Evaluate the efficacy and safety of inhalation nitrogen oxide (iNO) to prevent sepsis.
Materials and methods. With the permission of local ethical committee and the written consent of parents of patients controlled, randomized, blind clinical trial included 97 full-term newborns with respiratory pathology admitted to the Intensive Therapy department for artificial pulmonary ventilation during the first 48-hour period of their lives; no clinical signs of bacterial infection were diagnosed. Randomization: envelope method. In addition to standard intensive care, group I patients (n=44) received iNO (10 ppm, 48 hours, Pulmonox mini, Austria). Group II patients (n=53) did not receive iNO. Final points: frequency of development of sepsis, lethal outcomes, duration of mechanical ventilation, hospitalization. On the 1th, 3th and 20th days after admission, the plasmа concentration of IL-1ß, IL-6, IL-8, TNF-α, G-CSF, s-Fas, FGF, NO was determined by capture ELISA (Multilabel Coulter Victor-21420, Finland); population, subpopulation structure of lymphocytes, CD14+, CD3-CD56+, lymphocytes with expression AnnexinV-FITC+PI-, AnnexinV-FITC+PI+ were determined by means of immunophenotyping analysis (Beckman Coulter XL-II, USA).
Statistical programs: Excel-2007, Statistica-6, "R". The comparative analysis of the duration of mechanical ventilation; hospitalization - Kaplan-Meyer method. Reliability of results - Fisher-Irwin method; bilateral alternative at 5% significance level.
Results. Research power 86.7% (α≤0.05). Therapy of iNO was not interrupted at one participant; cases of an easy or serious adverse effect of iNO are not registered.
Development of sepsis: I group - 4 patients; II - 13 (p1=0.04; p2=0.005). Fatal outcomes: I - 6 patients, II - 10 (p1=0.37; p2=0.59). Median of the duration of mechanical ventilation: I - 5 days, II - 10 (p=0.00007); hospitalizations: I - 11 days, II - 15 (p=0.026).
The comparative analysis of the plasma concentration of cytokines, NO (Table-1), lymphocyte immunophenotyping (Table-2) in patients of both groups did not reveal differences upon admission (p>0.05), which confirmed the homogeneity of the studied population.
For 3 days in patients of group I relative to II: a decrease (p<0.05) the concentration of TNF-α, IL-8, IL-6; CD3+CD69+; CD3+CD95+, lymphocytes in apoptosis; increase (p<0.05) G-CSF, sFas, FGF, NO; CD14+, CD3+CD19-.
For 20 days in patients of group I relative to II: decrease (p<0.05) TNF-α, CD3+СD19-, CD3+CD69+, CD3+CD95+, CD3+HLA-DR+, lymphocytes in apoptosis; increase (p<0.05) FGF, G-CSF; CD3+CD4+, CD3+CD8+.
Conclusions. iNO as a part of intensive care decrease in frequency of development of sepsis, the duration of mechanical ventilation, hospitalization; provides a tendency to decrease in frequency of lethal outcomes; inhibits apoptosis of lymphocytes, activates the monocyte-macrophage immunity and proliferative processes. It is relevant to continue a research.