Table_1_The Sublingual Microcirculation Throughout Neonatal and Pediatric Extracorporeal Membrane Oxygenation Treatment: Is It Altered by Systemic Extracorporeal Support?.docx

Background: Extracorporeal membrane oxygenation (ECMO) treatment alleviates systemic cardiorespiratory failure. However, it is unclear whether ECMO also improves microcirculatory function, as the microcirculation can be disturbed despite normal systemic hemodynamics. We therefore aimed to study the sublingual microcirculation (SMC) throughout neonatal and pediatric ECMO treatment. We hypothesized that the SMC improves after starting ECMO, that the SMC differs between venovenous (VV) and venoarterial (VA) ECMO, and that insufficient recovery of microcirculatory disturbances during ECMO predicts mortality.
Methods: This single-center prospective longitudinal observational study included 34 consecutive children (April 2016—September 2018). The SMC was assessed daily with a handheld vital microscope (integrated with incident dark field illumination) before, during, and after ECMO. Validated parameters of vessel density, perfusion, and flow quality were assessed for all vessels (diameter <100 μm) and small vessels (<20 μm). Linear mixed models and logistic regression models were built to assess changes over time and identify significant covariates. Using ROC curves, the predictive values of microcirculatory parameters were assessed for mortality on ECMO and overall mortality.
Results: The study population comprised 34 patients (median age 0.27 years, 16 neonates, 16 females). Twelve patients were treated with VV and 22 with VA ECMO. Twelve patients died during ECMO (stopped due to futility) and 3 died after ECMO but before discharge. Microcirculatory parameters did not change significantly before, during or after ECMO. Except between microcirculatory flow index (MFI) and mean arterial pressure (MAP), no significant associations were found between microcirculatory parameters and global systemic hemodynamics. The probability of an undisturbed MFI (>2.6) increased with higher MAP (OR: 1.050, 95%CI: 1.008–1.094). Microcirculatory parameters did not significantly differ between VV and VA ECMO or between survivors and non-survivors. None of the microcirculatory parameters could predict mortality on ECMO or overall mortality.
Conclusion: In this heterogeneous study population, we were not able to demonstrate an effect of ECMO on the sublingual microcirculation. Microcirculatory parameters did not change throughout ECMO treatment and did not differ between VV and VA ECMO or between survivors and non-survivors. Future research should focus on determining which neonatal and pediatric ECMO patients would benefit from microcirculatory monitoring and how.

研究背景：体外膜肺氧合（Extracorporeal membrane oxygenation, ECMO）治疗可缓解全身心肺功能衰竭。然而，目前尚不清楚体外膜肺氧合是否同样可改善微循环功能，因为即便全身血流动力学处于正常水平，微循环仍可能发生紊乱。因此本研究旨在探讨新生儿与儿童接受体外膜肺氧合治疗全程中的舌下微循环（sublingual microcirculation, SMC）变化。本研究提出如下假说：启动体外膜肺氧合后，舌下微循环可得到改善；静脉-静脉（venovenous, VV）与静脉-动脉（venoarterial, VA）体外膜肺氧合患者的舌下微循环存在差异；体外膜肺氧合治疗期间微循环紊乱恢复不充分可预测患者死亡率。
研究方法：本研究为单中心前瞻性纵向观察性研究，纳入了2016年4月至2018年9月期间的34例连续性儿科患者。分别在体外膜肺氧合治疗前、治疗期间及治疗后，每日使用搭载落射暗场照明系统的手持活体显微镜对舌下微循环进行评估。针对所有直径＜100μm的血管以及直径＜20μm的微小血管，对经过验证的血管密度、灌注状态及血流质量相关参数进行评估。构建线性混合模型与逻辑回归模型，以评估随时间变化的趋势并识别具有统计学意义的协变量。采用受试者工作特征（Receiver Operating Characteristic, ROC）曲线，评估微循环参数对体外膜肺氧合期间死亡率及总体死亡率的预测价值。
研究结果：本研究共纳入34例患者，中位年龄为0.27岁，其中16例为新生儿，16例为女性患者。12例患者接受静脉-静脉体外膜肺氧合治疗，22例接受静脉-动脉体外膜肺氧合治疗。12例患者在体外膜肺氧合治疗期间死亡（因治疗无效终止治疗），另有3例患者在体外膜肺氧合治疗结束后、出院前死亡。舌下微循环参数在体外膜肺氧合治疗前、治疗期间及治疗后均未发生显著变化。除微循环血流指数（microcirculatory flow index, MFI）与平均动脉压（mean arterial pressure, MAP）之间存在关联外，未发现其他微循环参数与全身整体血流动力学指标存在显著相关性。微循环血流指数未发生紊乱（＞2.6）的概率随平均动脉压升高而升高（优势比：1.050，95%置信区间：1.008~1.094）。静脉-静脉与静脉-动脉体外膜肺氧合患者之间，以及存活者与非存活者之间的微循环参数均未呈现显著差异。所有微循环参数均无法有效预测体外膜肺氧合期间死亡率及总体死亡率。
研究结论：在本研究的异质性研究人群中，我们未发现体外膜肺氧合对舌下微循环存在影响。微循环参数在体外膜肺氧合治疗全程中未发生显著变化，且静脉-静脉与静脉-动脉体外膜肺氧合患者之间、存活者与非存活者之间的微循环参数均无显著差异。未来的研究应聚焦于明确哪些新生儿与儿科体外膜肺氧合患者可从微循环监测中获益，以及应如何开展此类监测。