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重症急性胰腺炎多器官功能衰竭患者早期发生毛细血管渗漏综合征的临床表征研究

Clinical Manifestations of Early-Onset Capillary Leak Syndrome in Patients With Multiple Organ Failure Due to Severe Acute Pancreatitis

  • 摘要:
    目的 探讨重症急性胰腺炎(severe acute pancreatitis, SAP)患者毛细血管渗漏综合征(capillary leak syndrome, CLS)早期生物标志物的动态变化临床表征及与多器官功能衰竭(multiple organ failure, MOF)相关性。
    方法 选取2019年9月1日–2020年12月31日四川大学华西医院胰腺炎中心收治的171例SAP患者作为研究对象,根据入院5 d内是否发生MOF分为MOF组和Non-MOF组,并进一步根据是否合并中重度腹腔高压(intra-abdominal hypertension, IAH)进行亚组分析。通过动态监测患者血液生物标志物〔血红细胞比容(hematocrit, HCT)、 尿素氮(blood urea nitrogen, BUN)、肌酐(creatinine, Cr)〕、血浆蛋白〔白蛋白(albumin, Alb)、总蛋白(total protein,TP)、非白蛋白血浆蛋白(non-albumin plasma proteins, NAPP)〕及腹腔内压的变化,综合分析这些指标在不同分组中的变化趋势。
    结果 两组基线资料差异无统计学意义,具有可比性;MOF组患者持续48 h的全身炎症反应综合征(systemic inflammatory response syndrome, SIRS),发生率(71.8% vs. 91.3%)、ICU转入率(17.6% vs. 70.4%)、平均住院时间〔(19.0±12.2) d vs. (32±17.7) d〕均高于Non-MOF组(P<0.05);MOF组的呼吸、循环和肾功能衰竭的发生率均高于Non-MOF组,其中循环衰竭(69% vs. 3.5%)和肾功能衰竭(65.5% vs. 3.5%)发生率差异有统计学意义(P<0.05)。与Non-MOF组相比,MOF组患者的入院后5 d内BUN和Cr水平升高,而Alb、TP入院后快速下降后逐渐回升,NAPP水平在入院后持续下降,且入院后第3天NAPP水平低于Non-MOF组,差异有统计学意义(P<0.001);Alb/NAPP入院后第1天显著下降后再迅速上升,入院后第3、4天两组差异有统计学意义(P=0.001)。合并中重度IAH的患者亚组分析,各项指标的动态变化趋势与总体趋势变化类似,且差异更为显著。混合线性模型显示MOF合并IAP组HCT、BUN、Alb/NAPP和Alb/TP平均水平更高并且随着时间的推移而增加(P<0.001)。
    结论 SAP患者CLS模型具有合理性,证实CLS是从SIRS到MOF发生的关键因素,NAPP的丢失是CLS持续并向MOF进展的早期重要指标,中重度IAH也会促使MOF进一步恶化,为阐明MOF潜在机制提供依据,也有待前瞻性大样本的进一步验证。

     

    Abstract:
    Objective To investigate the early dynamic changes of biomarkers associated with capillary leak syndrome (CLS) in patients with severe acute pancreatitis (SAP) and their correlation with multiple organ failure (MOF).
    Methods A total of 171 SAP patients admitted to the West China Centre of Excellence for Pancreatitis, West China Hospital, Sichuan University between September 1, 2019 and December 31, 2020 were enrolled for this study. The patients were divided into MOF and non-MOF groups based on the occurrence of MOF in the first 5 days of hospitalization, and were further divided into subgroups based on the presence of moderate-to-severe intra-abdominal hypertension (IAH). We performed dynamic monitoring of the blood biomarkers (hematocrit HCT, blood urea nitrogen BUN, and creatinine Cr), plasma proteins (albumin Alb, total protein TP, and non-albumin plasma proteins NAPP), and intra-abdominal pressure. Trends in these indicators across groups were analyzed comprehensively.
    Results No significant differences in baseline data between the two groups were observed. The baseline data of the 2 groups were comparable. The MOF group had significantly higher rates of persistent systemic inflammatory response syndrome (SIRS) lasting 48 hours (91.3% vs. 71.8%), ICU admission (70.4% vs. 17.6%), and length-of-stay (32 ± 17.7 days vs. 19.0 ± 12.2 days) compared to those of the non-MOF group (P < 0.05). The incidences of respiratory, circulatory, and renal failures were higher in the MOF group than those in the non-MOF group, showing significant differences in circulatory failure (69% vs. 3.5%) and renal failure (65.5% vs. 3.5%) (P < 0.05). In the first 5 days of hospitalization, the MOF group showed significantly elevated BUN and Cr levels, while Alb and TP levels dropped rapidly upon admission and then gradually recovered. The NAPP level of the MOF group continued to decrease after admission, and on the third day after admission, the NAPP level was lower than that of the Non-MOF group, showing statistically significant difference (P < 0.001). The Alb/NAPP ratio of the MOF group decreased significantly on day 1 and then rapidly increased, showing significant differences between the groups on days 3 and 4 (P = 0.001). Subgroup analysis of MOF patients with moderate-to-severe IAH revealed similar trends in the dynamic changes and the overall changes in the indicators, and the difference was even more pronounced. The mixed linear model showed that the average levels of HCT, BUN, Alb/NAPP, and Alb/TP were higher and increased over time in the MOF combined with IAP subgroup (P < 0.001).
    Conclusion The CLS model of SAP patients is validated, confirming that CLS is a key factor in the progression from SIRS to MOF. The loss of NAPP is an early and important indicator of CLS persistence and progression to MOF. Additionally, moderate-to-severe IAH accelerates the deterioration of MOF. These findings provide valuable insights into the potential mechanisms of MOF and warrant further validation through large-scale prospective studies.

     

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