Peters Anna L, van Hezel Maike E, Cortjens Bart, Tuip-de Boer Anita M, van Bruggen Robin, de Korte Dirk, Jonkers René E, Bonta Peter I, Zeerleder Sacha S, Lutter Rene, Juffermans Nicole P, Vlaar Alexander P J
1Laboratory of Experimental Intensive Care and Anesthesia, Academic Medical Centre, Amsterdam, The Netherlands. 2Department of Intensive Care, Academic Medical Centre, Amsterdam, The Netherlands. 3Department of Blood Cell Research, Sanquin Blood Supply, Amsterdam, The Netherlands. 4Department of Pediatric Intensive Care, Academic Medical Centre, Amsterdam, The Netherlands. 5Department Product and Process Development, Sanquin Blood Supply, Amsterdam, The Netherlands. 6Department of Respiratory Medicine, Academic Medical Centre, Amsterdam, The Netherlands. 7Department of Haematology, Academic Medical Centre, Amsterdam. The Netherlands. 8Department of Immunopathology, Sanquin Research, Plesmanlaan, Amsterdam, The Netherlands. 9Department of Experimental Immunology, Academic Medical Centre, Amsterdam, The Netherlands.
Crit Care Med. 2016 Jun;44(6):e412-9. doi: 10.1097/CCM.0000000000001614.
Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. Preclinical studies have shown that aged RBCs can induce transfusion-related acute lung injury in the presence of a "first hit" (e.g., sepsis). Clinical studies, however, show conflicting results on this matter. We tested whether maximally stored RBCs are able to induce lung injury in the presence of a "first hit" in humans (Dutch Trial Register: NTR4455).
Open-label, randomized controlled trial.
Healthy male volunteers.
Eighteen healthy male volunteers donated one unit of autologous RBCs 2 or 35 days before the experiment. The experiment was started by infusion of 2 ng/kg lipopolysaccharide ("first hit"). After 2 hours, volunteers received normal saline (n = 6), 2-day stored transfusion (n = 6), or 35-day stored transfusion (n = 6) ("second hit"). Blood was sampled hourly. Six hours after transfusion, the diffusion capacity of the lungs for carbon monoxide was tested and volunteers underwent spirometry, chest x-ray study, and a bronchoalveolar lavage.
All volunteers fulfilled sepsis criteria after lipopolysaccharide injection. The stored blood transfusion did not result in significant changes in either hemodynamic or respiratory variables compared with the control groups. Furthermore, chest x-rays, lung function, and PaO2/FIO2 ratios did not differ between groups. Transfusion of stored autologous RBCs did not result in an increased level of protein in the lungs or neutrophil influx.
Transfusion of 35-day stored autologous RBCs in the presence of endotoxemia does not result in lung injury in humans.
输血相关急性肺损伤是输血相关死亡的主要原因。临床前研究表明，衰老的红细胞在存在“首次打击”（如脓毒症）的情况下可诱发输血相关急性肺损伤。然而，临床研究在这一问题上结果相互矛盾。我们测试了在人类中（荷兰试验注册编号：NTR4455），最大限度储存的红细胞在存在“首次打击”的情况下是否能够诱发肺损伤。
开放标签、随机对照试验。
健康男性志愿者。
18名健康男性志愿者在实验前2天或35天捐献1单位自体红细胞。实验通过输注2 ng/kg脂多糖（“首次打击”）开始。2小时后，志愿者接受生理盐水（n = 6）、储存2天的输血（n = 6）或储存35天的输血（n = 6）（“第二次打击”）。每小时采集血液样本。输血后6小时，测试肺一氧化碳弥散能力，志愿者接受肺活量测定、胸部X线检查和支气管肺泡灌洗。
所有志愿者在注射脂多糖后均符合脓毒症标准。与对照组相比，储存血液输血在血流动力学或呼吸变量方面未导致显著变化。此外，各组之间胸部X线、肺功能和PaO2/FIO2比值无差异。输注储存的自体红细胞未导致肺内蛋白质水平升高或中性粒细胞流入增加。
在内毒素血症情况下输注储存35天的自体红细胞不会导致人类肺损伤。
