Ulinastatin administration of 5000–20 000 U/kg intraoperatively improved inflammation, cardiac, and renal function indicators in patients following cardiopulmonary bypass.
Meta-Analysis (n=3,325)
Does Ulinastatin improve inflammatory, cardiac, and renal function indicators in patients after cardiopulmonary bypass?
Elevated inflammatory and renal indicators post-CPB are associated with worse prognosis, which may be mitigated by intraoperative Ulinastatin administration.
Background: The primary aim of this study is to investigate the association between changes in laboratory indicators and clinical outcomes in patients who have undergone cardiopulmonary bypass (CPB). The secondary aim is to determine whether Ulinastatin can reliably modify these laboratory indicators and to identify the most appropriate clinical strategy for its use. Methods: First, a retrospective study was performed by identifying patients who had undergone CPB grafting with Sequential Organ Failure Assessment (SOFA) scores using the MIMIC-IV database. Associations between changes in laboratory indicator values after CPB within 24 hours, compared with baseline values before CPB, and SOFA scores were evaluated through univariate and multivariate logistic regression (Model 1 was unadjusted; Model 2 was adjusted for age, gender, height, and weight; Model 3 included variables from Model 2 and was further adjusted for race, insurance, and marital status; and Model 4 incorporated Model 3 variables plus adjustments for diagnosis, comorbidities, and baseline platelet, creatinine (CRE), oxygen saturation, pH value, and Ca 2+ levels, as well as locally weighted scatterplot smoothing (LOWESS) analyses. Second, a systematic literature search was conducted for studies to preliminarily evaluate the therapeutic effects of Ulinastatin. Additionally, meta-regression, permutation importance analyses, dose-dependent response effect analysis, and network meta-analysis were performed to determine the most appropriate administration strategy for Ulinastatin. Results: In total, 3325 patients were included from the MIMIC-IV database. It was observed that patients with higher SOFA scores following CPB grafting exhibited elevated mortality rates and longer intensive care unit stays, indicating a worse prognosis. After adjusting for confounders, patients in the high SOFA group demonstrated significant increases in the inflammatory indicator white blood cells (WBC) and the renal function indicator CRE. Furthermore, the LOWESS curve indicated that both WBC and CRE increase in parallel with rising SOFA scores. In the subsequent meta-analysis, 63 studies met the inclusion criteria. The use of Ulinastatin was associated with improvements in inflammatory indicators and reduced elevations in cardiac and renal function indicators in the pairwise meta-analysis. Meta-regression and permutation importance analysis demonstrated that Ulinastatin dosage and timing of administration were the primary determinants of its efficacy. Dose-dependent response analysis and network meta-analysis showed the most appropriate Ulinastatin dosage is 5000–20 000 U/kg, with the optimal timing being during the CPB process. Conclusion: Changes in values of inflammatory and renal dysfunction indicators are significantly associated with poor prognosis in patients following CPB. Meta-analysis further confirms that Ulinastatin can improve inflammation, cardiac, and renal function indicators; administration of 5000–20 000 U/kg intraoperatively may be beneficial to patients after CPB.
Zhang et al. (Fri,) conducted a meta-analysis in Cardiac surgery with cardiopulmonary bypass (n=3,325). Ulinastatin was evaluated on Association between changes in laboratory indicators and clinical outcomes (SOFA scores), and therapeutic effects of Ulinastatin. Ulinastatin administration of 5000–20 000 U/kg intraoperatively improved inflammation, cardiac, and renal function indicators in patients following cardiopulmonary bypass.