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壹生身份认证协议书
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作者：武警特色医学中心综合重症医学科 蔡湘龙 李国强
病原体侵入机体后，通过病原体、PAMPs、DAMPs的识别而激活、启动广泛的免疫反应，免疫反应失调导致组织损伤、线粒体损伤和凝血病等，从而形成一个失控炎症反应的恶性循环，最终可能因多脏器功能衰竭而死亡[11]，故宿主对感染的反应失调是脓毒症和脓毒性休克的核心病理生理机制，是脓毒症诱发多器官功能障碍综合征(MODS)的理论基础。HP治疗的目标是清除病原体、内毒素等，降低过高的炎症介质水平，从而阻断 “恶性循环”，尽快恢复“免疫稳态”，目前研究显示，HP有以下几个方面的作用：① 降低血液中部分PAMPs、DAMPs水平、减少病原体载量；② 稳定血流动力学等；③ 降低短、长期的病死率。
PMX-HP、CytoSorb、HA330/380、AN69ST Oxiris能广谱、非特异性吸附血液中的炎性介质，但各有其特点。
PMX-HP表面负载的多黏菌素B与内毒素具有高亲和性，主要吸附内毒素[12]，适合于高内毒素血症者，CytoSorb通过疏水作用力吸附分子量范围在5-60KD的多种炎性介质，适合于高细胞因子血症者（TNF、IL-6、IL-8、IL-10等）[13]，HA330/380也通过疏水作用力吸附0.5-60 KDa的细胞因子和内毒素为主的炎性介质[14]，专为改善危重症患者的“细胞因子风暴”而设计，而AN69ST Oxiris为附着在CRRT管路上的高吸附膜，主要通过静电作用、疏水作用力等机制吸附炎性介质，因其特有的结构，是目前唯一具备集内毒素清除、细胞因子清除、肾脏支持及局部抗凝于一体的血液吸附装置[15]。以上吸附装置还能吸附部分活化的单核细胞[16]及高迁移率族蛋白B-1（HMGB1）、可溶性CD14、前降钙素等其他炎性介质[17-19]。
Seraph-100可与病原体不可逆结合，具有广谱的病原体清除能力[20]，对于病毒、革兰阴性菌、革兰阳性菌3种病原体，清除能力逐渐上升，特别是它还能清除耐药革兰氏阳性菌[如耐甲氧西林金黄色葡萄球菌（MRSA）、抗万古霉素肠道球菌（VRE）][21]、耐药革兰氏阴性菌[如耐碳青霉烯类肠球菌(CRE）][22]，可能将是耐药菌的另一有效治疗方式，目前是唯一获准用于减少血液中病原体的血液灌流器械，2019年上市，目前临床研究相对较少，Kielstein J T等[23]报道了7例应用Seraph-100治疗的COVID-19患者，发现其可去除血液中的SARS-CoV-2核壳蛋白，提示Seraph-100灌流可以清除血液中的新冠病毒。
Friesecke S等[24]纳入20名难以再进行扩容且乳酸清除率＜25%的脓毒性休克病人，在应用CytoSorbs灌流后，乳酸清除率在治疗后6h明显增加，血流动力学也随之稳定。Jansen A等[25]通过给健康男性静脉注射内毒素的方式建立内毒素血症模型，随后对建立的模型随机分组，试验组予以CytoSorbs灌流，而对照组进行空白对照，发现CytoSorbs使2组细胞因子浓度-时间曲线下面积（AUC）差异明显[TNF（中位AUC，-58%）、IL-6（中位AUC，-71%）、IL-8（中位AUC，-48%）、IL-10（中位AUC，-26%）]，以及MCP-1、MIP-1α、集落刺激因子（G-CSF）也下降明显，而且，本研究还显示CytoSorbs对上述细胞因子的清除速率在治疗初期达到峰值，随后逐渐下降，此外，CytoSorbs组的心率增快、血压下降（内毒素血症所致）的出现时间更早、持续时间更短，提示其对血流动力学的有益作用。
Cotoia A等[26]对于腹部手术术后脓毒症，且内毒素活性分析(EAA)＞0.6EU的病人进行了研究，分别接受常规治疗、PMX-HP+常规治疗，PMX-HP组在术后第7d可溶性CD14亚型（presepsin）、降钙素原、内毒素分别降低了40%、41%和26%，与术前相比差异具有统计学意义，两组死亡率差异明显（常规治疗组生存率37%，PMX-HP组73%）。
Brouwer W P等[27]纳入了116例（CytoSorbs灌流+CRRT 67例，CRRT 49例）脓毒性休克病例，平均在1.66 d、2.1 d开始治疗，联合治疗组基线血流动力学更差[入院时、治疗开始时乳酸水平更高，去甲肾上腺素使用剂量更高，平均动脉压（MAP）更低]，经治疗后，两组28 d病死率较SOFA评分所预测的更低，联合治疗组下降更为显著，sIPTW多变量分析示CytoSorb灌流与28d预后的改善显著相关，该研究团队对上述2组存活病人进行了长达一年的院外观察，发现1年后2组病例的存活率相似，提示CytoSorb灌流对生存率的提高是长期的[28]。
Schmidt J J等[29]对应用Seraph-100治疗的来自两大洲6个国家12家医院的78例COVID-19病人进行了观察性研究，发现应用Seraph-100的ICU病人30 d病死率（50.7%）较SOFA评分预测的（56.7%）下降，经Seraph-100治疗的普通病房病人30d病死率（11.1%）也较冠状病毒临床特征联盟(4C)评分所预测的（38%）明显下降。对于短时间内难以去除的导管相关血流感染，也可能是Seraph-100灌流的适应证，Pavlov M等[30]报道了1例因慢性心力衰竭急性加重行V-A ECMO治疗过程中出现了阴沟肠杆菌血流感染的患者，予以积极Seraph-100灌流及抗生素治疗，1次Seraph-100治疗后菌血症消失、脓毒性休克好转，最终存活出院。此外文献还报道[31]，该装置可能不会影响部分常用抗生素的药代动力学/药效学。
但并非所有的研究都显示了临床获益，Wendel Garcia P D等[32]纳入208例严重难治性脓毒性休克患者[IL-6≥1000 ng/L，血管升压素依赖指数≥3（充分液体复苏后）]，48例进行CytoSorbs灌流，160例为“遗传”匹配的对照组，结果显示2组血液中IL-6、升压药物剂量无明显差异，CytoSorbs未增加生存率，甚至还可能增加了病死率。Stockmann H等[33]进行了一项前瞻性开放标签的随机对照研究，共8家ICU参加，纳入50例已出现休克的COVID-19患者，对照组进行了常规治疗，试验组额外进行了3-7d的CytoSorbs灌流（24h/次）治疗，结果发现2组在休克持续时间、ICU病死率以及存活患者ICU/住院时间、ECMO时间，此外还有IL-6、SOFA评分等方面，均无明显差异。Schadler D等[34]也在随机对照多中心研究中发现，对于合并急性肺损伤或急性呼吸窘迫综合征而需机械通气的脓毒症/脓毒性休克患者，CytoSorbs灌流虽能去除灌流管路血液中5%~18%的IL-6，但对全身IL-6的对数值的变化趋势无明显影响，也未发现明显的生存获益。
未完待续
武警特色医学中心综合重症医学科科主任，医学博士，主任医师，硕士研究生导师,从事临床工作30余年,在呼吸支持技术为主的各种抢救治疗中有独特的见解，在复杂的有创机械通气技术及床旁呼吸力学监测、无创机械通气、ECMO、MODS 的救治(包括连续血滤及人工肝技术)有较深入的研究;并在各种中毒抢救，体外清除技术(全血灌流、血浆吸附流、持续床旁血液滤过、血浆置换)在中毒领域有深厚的造诣;担任中国毒理学会中毒与救治专业委员会副主任委员、全军重症医学专业委员会委员、全军热射病防治专家组专家、全军热射病天津市医师协会急诊医师分会常务委员、天津市医学会重症医学专业委员会委员、天津市中西医结合学会呼吸病专业委员会委员、中华医学会呼吸病学分会呼吸危重症委员、天津市医师协会重症医学医师分会第三届委员会常委等职务。
承担各级科研课题5项，在发表论文40 余篇，国家实用新型专利9项。多次执行重大行动卫勤保障任务，省部级科技进步奖一等奖1项，三等奖2项，医疗成果三等奖2项，6次荣立个人三等功;所带领的综合重症医学科团队被表彰为“基层建设先进单位”、“优秀党支部”、武警部队、56后勤部及特色医学中心“四铁”先进单位，2022年提名全军“四铁”先进单位，3次荣立集体三等功。
武警特色医学中心综合重症医学科主治医师，医学硕士，从事临床工作10年，对于中毒、脓毒症、多脏器功能障碍综合征等疾病的重症救治有一定的临床和科研经验，发表核心期刊论文数篇。
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[29] !!! INVALID CITATION !!! [26].
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本文由中国医学论坛报社呼吸与危重症编委会编委宋立强教授组稿
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