成人主动脉手术围术期红细胞输血量与短期不良临床结局的量效关系

中文摘要

背景：主动脉手术患者围术期具有较高的红细胞输血量。既往研究表明，输血是心血管外科手术围术期不良事件发生率和死亡率增加的独立危险因素。现有研究主要集中于冠状动脉搭桥手术或者瓣膜手术，对于主动脉手术中输血的研究较少。本研究旨在探究不同围术期红细胞输血量与短期临床结局之间的关系。

方法：本研究为单中心、回顾性研究，纳入2019年1月1日至2022年6月30日期间在xx医院接受体外循环下全主动脉弓人工血管置换术的成人患者建立研究队列。根据术中及术后48h红细胞输血量，将患者分为0U组（未输血）、1 ~ 2U组、3 ~ 4U组和5 ~ 6U组。本研究主要结局为围术期不良事件发生率，包括急性肾损伤（acute kidney injury，AKI）、机械通气时间延长以及复合并发症。采用Logistic回归分析评估不同围术期红细胞输血分组与短期临床结局之间的关系。敏感性分析在经1：1倾向评分匹配后的患者队列中进行，用于评估研究结果的稳健性。

结果：本研究共纳入符合876名接受全主动脉弓人工血管置换的成人患者建立研究队列。根据红细胞输血量，将患者分为4组：0U组（n = 612，69.8%），1 ~ 2U组（n = 72，6.8%），3 ~ 4U组（n = 148，16.8%），5 ~ 6U组（n = 44，5.0%）。与低输血量分组患者相比，高输血量组患者表现为年龄更大、男性占比更少、合并疾病更多、血糖更高、血红蛋白及血白蛋白更低（p < 0.05）。多因素逻辑回归结果显示，红细胞输血是围术期不良事件发生率的独立危险因素（AKI，1 ~ 2U：OR 2.800，95% CI 1.142 ~ 5.265，p = 0.001；3 ~ 4U：OR 6.239，95% CI 1.909 ~ 13.391，p < 0.001；5 ~ 6U：OR 9.795，95% CI 3.959 ~ 20.232，p < 0.001；机械通气时间延长，5 ~ 6U：OR 1.161，95% CI 1.043 ~ 3.600，p = 0.048；复合并发症，3 ~ 4U：OR 3.543，95% CI 1.424 ~ 8.812，p = 0.007；5 ~ 6U：OR 4.245，95% CI 1.315 ~ 13.704，p = 0.016）。敏感性分析结果与原结果一致（AKI，1 ~ 2U：OR 1.254，95% CI 1.054 ~ 1.493，p = 0.011；3 ~ 4U：OR 4.961，95% CI 1.104 ~ 12.186，p = 0.038；5 ~ 6U：OR 5.245，95% CI 1.315 ~ 13.704，p = 0.016；机械通气时间延长，5 ~ 6U：OR 1.104，95% CI 1.038 ~ 1.298，p = 0.034；复合并发症，5 ~ 6U：OR 1.628，95% CI 1.274 ~ 5.676，p = 0.030）。

结论：成人主动脉手术患者围术期红细胞输血量的增加与围术期急性肾损伤、机械通气时间延长以及复合并发症的发生风险显著相关，风险随红细胞输血量增加而增大。减少患者围术期红细胞输血可能对于改善围术期临床结果有重要意义。

第二部分 减少成人主动脉手术围术期红细胞输血措施：自体血小板单采的创新应用与流程优化

中文摘要

背景：接受主动脉手术的患者在围术期常发生凝血功能障碍，导致过量出血和异体输血风险增加。自体血小板成分（autologous platelet concentrate, APC）的使用为围术期患者血液保护提供了新的方法，但由于各中心采集自体血小板所使用的方法不同、缺乏统一的采集流程规范，因此其应用效果存在差异。本研究旨在评估新使用场景下、流程优化后的自体血小板单采技术是否能有效降低成人主动脉手术患者的红细胞输注率，进而改善其临床结局。

方法：本研究为前瞻性、单中心随机对照试验，纳入自2022年11月1日至2023年10月1日期间在我院行体外循环（cardiopulmonary bypass，CPB）下主动脉手术的成人患者，按1：1的随机化比率随机分为APC组或对照组。APC组患者在肝素化前进行自体血小板采集，对照组患者不进行干预。主要终点是围手术期红细胞（red blood cell，RBC）输血率。次要终点包括围术期RBC输血量；围术期血浆、血小板输血率/量；术后6小时、12小时、24小时、36小时、72小时内手术纵隔胸腔引流量；术后血常规、凝血功能和血小板功能；不良事件发生率。

结果：共有134名患者纳入本研究，APC组和对照组各67名患者。两组患者术前基线特征和主动脉病变程度均没有显著差异（p > 0.05）。与对照组相比，APC组的手术总时间更短（289.93±87.22min vs. 340.49±105.98min; p = 0.003），术中出血量更少（688.52±166.50ml vs. 762.58±183.22ml; p = 0.016），凝血因子VIIa用量更少（0.33±0.81mg vs. 0.66±1.07mg; p = 0.047）。自体血小板单采可显著减少围术期各血液成分的输血需求，包括术中、术后及总输血率和输血量（p < 0.05），此效果在多个统计模型中均得到了一致性验证。与对照组相比，APC组患者术后大出血发生率显著降低（1.5% vs. 14.9%; p = 0.005）；术后6小时（230 ml vs. 280 ml; p = 0.012）48小时（700 ml vs. 790 ml; p = 0.044）和72小时（800 ml vs. 930 ml; p = 0.033）纵隔胸腔引流量减少；术后24小时RBC和血红蛋白（RBC：3.43±0.46 vs. 3.22±0.47; p = 0.012; 血红蛋白：104.43±14.55 g/L vs. 98.19±14.96 g/L; p = 0.016）计数增加；术后72小时的RBC和血小板（RBC：3.45±0.50 10¹²/L vs. 3.32±0.46 10¹²/L; p = 0.046; 血小板：151.57±61.91 10⁹/L vs. 131.09±46.54 10⁹/L; p = 0.032）计数增加；重症监护病房住院时间缩短（50.52 h vs. 71.97 h; p = 0.043），改善了临床结果，加快了患者的术后恢复。然而，自体血小板单采可能会导致术中钙剂使用量增加（3.24±1.67g vs. 2.66±0.84g; p = 0.014）以及术后24h白细胞计数增加（13.00±3.79 10⁹/L vs. 11.40±3.77 10⁹/L; p = 0.015）。此外，在仅行主动脉根部手术的患者中，观察到自体血小板采集过程延长了中心静脉置管至全身肝素化之间的时间（52.14±7.75min vs. 42.15±6.13; p < 0.001）。

结论：改良后的自体血小板单采和回输可显著减少围手术期输血，缩短手术时间，改善临床效果，加快术后恢复。必须严密监测钙离子水平，同时也需要根据不同的手术类型协调体外循环前准备时间，以免影响手术进程。

Section 1: Dose-response relationship between perioperative red blood cell transfusion and short-term adverse clinical outcomes in adult aortic surgery

Abstract

Background: The perioperative usage of red blood cell (RBC) transfusions in aortic surgery patients is notably high. Previous studies have identified blood transfusion as an independent risk factor for increased adverse events and mortality in cardiovascular surgery. However, research on transfusion in aortic surgery remains limited compared to coronary artery bypass or valve surgery. This study aims to investigate the relationship between perioperative red blood cell transfusion volume and short-term clinical outcomes.

Methods: This single-center, retrospective study included adult patients who underwent total aortic arch artificial vascular replacement under cardiopulmonary bypass (CPB) at Fuwai Hospital, Chinese Academy of Medical Sciences between January 1, 2019 and June 30, 2022 to establish a study cohort. Patients were categorized into 0U group (without transfusion), 1 ~ 2U group, 3 ~ 4U group and 5 ~ 6U group based on the volume of RBC transfusion at 48h during and after operation. The primary outcome assessed was perioperative adverse events, including acute kidney injury (AKI), prolonged mechanical ventilation, and complex complications. Logistic regression analysis was used to evaluate the relationship between various perioperative RBC transfusion groups and short-term clinical outcomes. Sensitivity analyses were performed in pairs of patients matched by a 1:1 propensity score to assess the robustness of the results.

Results: A total of 876 eligible adult patients undergoing total aortic arch artificial vascular replacement were enrolled in the study cohort. Based on the volume of RBC transfusion, patients were categorized into four groups: the 0U group (n = 612, 69.8%), the 1 ~ 2U group (n = 72, 6.8%), the 3 ~ 4U group (n = 148, 16.8%), and the 5 ~ 6U group (n = 44, 5.0%). Patients in the high blood transfusion group were observed to be older, predominantly female, with more comorbidities, elevated blood glucose levels, and lower hemoglobin and blood albumin levels compared to those in the low blood transfusion group (p < 0.05). Multivariate logistic regression showed that RBC transfusion was an independent risk factor for perioperative adverse events (AKI, 1 ~ 2U: OR 2.800, 95% CI 1.142 ~ 5.265, p = 0.001; 3 ~ 4U: OR 6.239, 95% CI 1.909 ~ 13.391, p < 0.001; 5 ~ 6U: OR 9.795, 95% CI 3.959 ~ 20.232, p < 0.001; prolonged mechanical ventilation, 5 ~ 6U: OR 1.161, 95% CI 1.043 ~ 3.600, p = 0.048; complex complications, 3 ~ 4U: OR 3.543, 95% CI 1.424 ~ 8.812, p = 0.007; 5 ~ 6U: OR 4.245, 95% CI 1.315 ~ 13.704, p = 0.016). The results of sensitivity analysis were congruent with the original results (AKI, 1 ~ 2U: OR 1.254, 95% CI 1.054 ~ 1.493, p = 0.011; 3 ~ 4U: OR 4.961, 95% CI 1.104 ~ 12.186, p = 0.038; 5 ~ 6U: OR 5.245, 95% CI 1.315 ~ 13.704, p = 0.016; prolonged mechanical ventilation, 5 ~ 6U: OR 1.104, 95% CI 1.038 ~ 1.298, p = 0.034; complex complications, 5 ~ 6U: OR 1.628，95% CI 1.274 ~ 5.676，p = 0.030).

Conclusion: The increase in perioperative RBC transfusions among adult aortic surgery patients exhibited a notable correlation with heightened risks of perioperative AKI, prolonged mechanical ventilation, and complex complications, with risks amplifying alongside increased RBC transfusion volumes. Therefore, minimizing perioperative RBC transfusions holds significant importance for enhancing perioperative clinical outcomes.

Section 2: Reducing perioperative red blood cell transfusion in adult aortic surgery: innovative application and process optimization of autologous plateletpheresis

Abstract

Background: Patients undergoing aortic surgery often face perioperative coagulopathy, resulting in excessive bleeding and increased risk of allogeneic transfusions. Autologous platelet concentrate (APC) presents a novel avenue for blood preservation during perioperative care. However, due to the different methods used in the collection of autologous platelets and the lack of uniform collection procedures, the application effect is different. The purpose of this study was to evaluate whether autologous plateletpheresis can effectively reduce the red blood cell transfusion rate in adult aortic surgery patients under new use scenarios and optimized procedures, and thus improve the clinical outcome.

Methods: This study was a prospective, randomized controlled trial. Adult patients undergoing cardiopulmonary bypass (CPB) aortic surgery in our hospital from November 1, 2022 to October 1, 2023 were included. The patients were randomly divided into APC group or control group at a 1:1 randomization rate. Patients in the APC group received autologous plateletpheresis before heparinization, while patients in the control group received no intervention. The primary endpoint was perioperative red blood cell (RBC) transfusion rate. Secondary endpoints included perioperative RBC blood transfusion volume; perioperative plasma and platelet transfusion rate/volume; drainage volume within 6 hours, 12 hours, 24 hours, 36 hours, 72 hours after surgery; postoperative coagulation function and platelet function; incidence of adverse events.

Results: A total of 134 patients participated in the study, with 67 patients each in the APC and control groups. There were no significant differences between the two groups in preoperative baseline characteristics and the degree of aortic lesion (p＞0.05). This effect has been consistently verified in several statistical models. Compared with the control group, the APC group exhibited shorter operation times (289.93±87.22min vs. 340.49±105.98min; p = 0.003), reduced intraoperative blood loss (688.52±166.50ml vs. 762.58±183.22ml; p = 0.016), decreased factor VIIa usage (0.33±0.81mg vs. 0.66±1.07mg; p = 0.047). Autologous platelet collection can significantly reduce the perioperative blood transfusion requirements for all blood components, including intraoperative, postoperative and total transfusion rate and transfusion volume (p < 0.05). It also demonstrated enhancements in clinical outcomes and expedited postoperative recovery among patients by a reduced occurrence of major bleeding (1.5% vs. 14.9%; p = 0.005), diminished post ~ surgical drainage at the 6-hour (230 ml vs. 280 ml; p = 0.012), 48-hour (700 ml vs. 790 ml; p = 0.044), and 72-hour (800 ml vs. 930 ml; p = 0.033), elevated RBC and Hb count at 24 hours after surgery (RBC: 3.43±0.46 vs. 3.22±0.47; p = 0.012; Hb: 104.43±14.55 g/L vs. 98.19±14.96 g/L; p = 0.016), elevated RBC and platelet count at 72 hours after surgery (RBC: 3.45±0.50 10¹²/L vs. 3.32±0.46 10¹²/L; p = 0.046; Platelets: 151.57±61.91 10⁹/L vs. 131.09±46.54 10⁹/L; p = 0.032), decreased length of stay in intensive care unit (50.52 h vs. 71.97 h; p = 0.043), improved clinical outcomes and accelerated postoperative recovery of patients. However, autologous plateletpheresis may lead to increased intraoperative calcium usage (3.24±1.67g vs. 2.66±0.84g; p = 0.014) and increased leukocyte counts at 24h after surgery (13.00±3.79 10⁹/L vs. 11.40±3.77 10⁹/L; p = 0.015). In addition, in patients undergoing root ~ only procedures, the duration of autologous plateletpheresis was notably longer in the APC group (52.14±7.75 min vs. 42.15±6.13 min; p < 0.001).

Conclusion: The modified autologous plateletpheresis can significantly reduce perioperative transfusions, shorten surgical durations, and improve clinical outcomes and faster postoperative recovery. Careful monitoring of calcium levels and other indicators is essential, adapting the procedure to different surgeries is needed.