Effects of different doses of ulinastatin on inflammatory response and pulmonary function after cardiopulmonary bypass

Objective: To evaluate the effect of ulinastatin (UTI) on the changes in inflammatory cytokines and inflammatory response as a result of cardiopulmonary bypass (CPB) in cardiac valvular replacement surgery and to investigate the protective effect of UTI on lungs.

Methods: A prospective randomized control clinical trial was designed, and 42 patients scheduled for elective cardiac valvular replacement were randomly divided into three groups: control group, UTI 8 kU/kg group (group U1) and UTI 12 kU/kg group (group U2), with 14 patient in each group. Blood samples were obtained from central vein for determination of plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 concentrations before operation (T1), 1 hour (T2), 4 hours (T3), and 24 hours (T4) after CPB respectively. At the same time points, arterial blood gas analysis were recorded for calculation of oxygen index (PaO2/FiO2) and respiratory index (RI).

Results: (1)There was no significant difference in the plasma concentrations of TNF-alpha, IL-6 and IL-10 at T1 among the three groups (all P>0.05), but increased at T2-4 as compared with the T1 in three group (P<0.05 or P<0.01). Compared with the control group, the plasma level of TNF-alpha and IL-6 of both UTI groups at T2-4 were significantly lower, IL-10 of both UTI groups was significantly higher, and changes were more marked in group U2 than those in group U1 (P<0.05 or P<0.01). (2) There was no significant difference in PaO2/FiO2 and RI at T1 among the three groups (all P>0.05), but PaO2/FiO2 was decreased, RI was increased at T2-4 as compared with the T1 in three group (P<0.05 or P<0.01). Compared with the control group, the PaO2/FiO2 of the two UTI groups was significantly higher, the RI of the two UTI groups was lower at T2-4, and changes were more marked in group U2 than those in group U1 (P<0.05 or P<0.01).

Conclusions: During the CPB, UTI can significantly inhibit the inflammatory cytokine release and reduce the inflammatory response, lessen the lung inflammatory response to CPB and protect lung function, the effect of UTI shows a dose-effect relationship.