Clinical application of extracorporeal membrane oxygenation in the treatment of burn patients with acute respiratory distress syndrome: a retrospective analysis and systematic review
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摘要:
目的 分析体外膜肺氧合(ECMO)治疗烧伤合并急性呼吸窘迫综合征(ARDS)患者的临床效果。 方法 采用回顾性观察性研究和系统评价研究的方法。2014年3月—2020年7月,陆军军医大学(第三军医大学)第一附属医院全军烧伤研究所收治5例接受ECMO治疗的烧伤合并ARDS患者,均为男性,年龄40~62岁,平均烧伤总面积为58.8%体表总面积(TBSA),其中4例存在重度吸入性损伤。记录患者ECMO开始使用时间、使用模式、持续时长,是否成功脱机及死亡原因等;统计并分析患者ECMO使用前、中、后的氧合和感染指标变化。以“Extracorporeal Membrane Oxygenation”“ECMO”“burn”“inhalation”为检索词,以“Title/Abstract”为检索范围,以建库至2021年8月为检索时间范围,在《PubMed》和《Web of Science》数据库中检索并筛选符合入选标准的回顾性论著。提取文章的基本信息及患者样本量、性别、年龄、烧伤总面积、有无吸入性损伤、ECMO上机指征、ECMO开始时间、ECMO持续时间、ECMO使用模式、ECMO成功脱机率、死亡率、ECMO并发症、CRRT联用情况等资料进行分析。 结果 5例患者于伤后平均10.2 d开始ECMO治疗,均采用静脉到静脉(VV)-ECMO模式,平均持续时间180.4 h。5例患者中3例成功脱机,其中1例患者存活。4例患者均死于多器官功能障碍综合征(MODS)和脓毒症休克。与ECMO使用前相比,使用中、使用后3例成功脱机患者的动脉血氧分压(PaO2)和动脉血氧饱和度(SaO2)均升高;吸入气氧浓度均下降至50%以下;氧合指数(PaO2/吸入气氧浓度)均升高至200 mmHg(1 mmHg=0.133 kPa)以上;乳酸、呼吸频率均基本下降。较ECMO使用前,使用中2例未成功脱机患者的PaO2和SaO2均下降,乳酸均升高;2例未成功脱机病例在ECMO使用前、使用中的氧合指数均<200 mmHg,PaCO2均>40 mmHg。与ECMO使用前相比,使用中、使用后患者的体温均无明显变化,均<38 ℃。与ECMO使用前相比,使用中4例患者的白细胞计数(略去未成功脱机病例无此项的指标,下同)基本呈显著下降趋势,使用后有所回升。与ECMO使用前相比,使用中3例患者的中性粒细胞水平略升高,且在使用后无明显变化。与ECMO使用前相比,使用中3例患者的血小板计数明显降低。ECMO使用中,所有患者的血小板计数低于血小板计数正常水平下限。与ECMO使用前相比,使用中4例死亡患者的降钙素原水平均明显升高。3例成功脱机患者的导管微生物培养结果均为阴性。共纳入13篇文献,研究时间最早为1990年,最晚截止到2019年;6项研究样本量小于10,4项研究介于10~20,仅2篇文献样本量大于50;共295例烧伤患者接受ECMO治疗,包括157例成年和138例儿童烧伤患者;总体死亡率为48.8%(144/295);烧伤人群使用ECMO最常见的指征是重度ARDS。157例成年烧伤患者中,男95例、女62例;36例存在吸入性损伤;5项研究平均烧伤总面积在27%~37%TBSA,2项研究平均烧伤总面积大于50%TBSA;最常用模式为VV-ECMO,平均于伤后26.5 h~7.4 d开始ECMO治疗,持续90 h~18 d,成功脱机率为50%~100%;最常见的并发症是出血和感染;病死率为52.9%(83/157),最常见的死亡原因为MODS和脓毒症。138例儿童烧伤患者中,77例为男童、61例为女童;29例合并吸入性损伤;3项研究平均烧伤总面积在17%~50.2%TBSA;ECMO持续165.2~324.4 h;最常见的并发症是出血;病死率为44.2%(61/138)。 结论 ECMO是挽救性治疗烧伤合并ARDS的有效手段,使用过程中应着重防治出血、感染和脏器功能障碍,亟须基于临床证据的操作指南以进一步提高ECMO的救治效果。 Abstract:Objective To analyze the clinical effect of extracorporeal membrane oxygenation (ECMO) in the treatment of burn patients with acute respiratory distress syndrome (ARDS). Methods The retrospective observational study and the systematic review were applied. From March 2014 to July 2020, five burn patients with ARDS received ECMO treatment in the First Affiliated Hospital of Army Medical University (the Third Military Medical University). All the five patients were male, aged from 40 to 62 years. The average total burn surface area was 58.8% total body surface area (TBSA) and four cases had severe inhalation injury. Patient's ECMO starting time, duration and mode, and whether successfully weaned or the cause of death, and others. were recorded. Furthermore, the changes of oxygenation and infection before, during, and after utilizing ECMO were analyzed. PubMed and Web of Science from the establishment of each database to August 2021 were searched using "Extracorporeal Membrane Oxygenation", "ECMO", "burn", "inhalation" as the search terms and "Title/Abstract" as the field to retrieve the clinical articles that meet the selection criteria . Basic information were extracted from the articles, including sample size, gender, age, total burn area, inhalation injury, the indication of ECMO, the start and lasting time of ECMO, ECMO mode, rate of successful weaning, complications of ECMO, mortality, the combined application of continuous renal replacement therapy (CRRT). Results Five patients started venovenous ECMO on an average of 10.2 days after injury and lasted an average of 180.4 hours. Three out of 5 patients were weaned successfully with one patient survived. Four patients died of multiple organ dysfunction syndrome (MODS) and septic shock. Compared with those before ECMO treatment, the arterial oxygen partial pressure (PaO2) and oxygen saturation in arterial blood (SaO2) of three successfully weaned patients obviously increased during and after ECMO treatment. The fraction of inspired oxygen (FiO2) decreased below 50% and PaO2/FiO2 ratio increased above 200 mmHg (1 mmHg=0.133 kPa) during and after ECMO. Furthermore, lactic acid and respiratory rate decreased, basically. Compared with those before ECMO, PaO2 and SaO2 in the other two patients during ECMO, who failed to be weaned, continuously decreased while lactic acid increased. Before and during ECMO, the PaO2/FiO2 ratios of unsuccessfullg weaned cases were less than 200 mmHg, and partial pressure of carbon dioxide in arterial blood (PaCO2) were more than 40 mmHg. Compared with those before ECMO, there were no significant changes in body temperature during and after ECMO, which were less than 38 ℃. Compared with those before ECMO, the leucocyte number (the index without this in unsuccessfully weaned cases was omitted, the same as below) in four patients showed a significant decrease during ECMO, but rose after removal of ECMO. The proportion of neutrophils in three patients were slightly higher during ECMO than before ECMO, and did not change significantly after removal of ECMO. Compared with those before ECMO, platelet counts in three patients were significantly reduced during ECMO, and all five patients during ECMO were below normal levels. Compared with those before ECMO, the procalcitonin levels in four deaths were significantly increased during ECMO. Catheter culture of microorganism was performed in three successfully weaned patients, all of which were negative. A total of 13 literature were included, ranging from 1990 to 2019. The sample size in 6 studies was less than 10, and the sample size in 4 studies was between 10 and 20, and only 2 literatures had a sample size larger than 50. ECMO was applied in 295 burn patients with overall mortality of 48.8% (144/295), including 157 adults and 138 children. The most common indication of ECMO was severe ARDS. Among 157 adult burn patients (95 males and 65 females), 36 cases had inhalation injury. The average burn area was 27%-37%TBSA in 5 reported studies and was more than 50%TBSA in 2 reported studies. The most common mode was venovenous ECMO. ECMO treatment began 26.5 hours to 7.4 days after injury and lasted from 90 hours to 18 days, and the rate of successful weaning ranged from 50% to 100%. The most common complications were bleeding and infection. The mortality was 52.9% (83/157). MODS and sepsis were the leading causes of death. Among 138 pediatric burn patients (77 boys and 61 girls), 29 patients had inhalation injury. The average burn area was 17%-50.2%TBSA in 3 studies. ECMO treatment lasted from 165.2 hours to 324.4 hours. Bleeding was the most common complication. The mortality was 44.2% (61/138). Conclusions ECMO is an effective strategy for the salvage treatment of burns complicated with ARDS. Furthermore, the prevention and treatment of bleeding, infection and organ dysfunction should be emphasized during the use of ECMO. More importantly, evidence-based guidelines for burns are urgently needed to further improve the clinical effect of ECMO. -
参考文献
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表1 5例接受体外膜肺氧合治疗的烧伤合并急性呼吸窘迫综合征患者的临床资料
患者编号 年龄(岁) 致伤原因 烧伤总面积(%TBSA) Ⅲ度烧伤面积(%TBSA) 吸入性损伤 合并症 APACHEⅡ评分(分) 病例1 43 汽油火焰烧伤 85.0 28.0 无 无 24 病例2 49 高温蒸汽烫伤 87.0 46.0 重度 无 19 病例3 40 瓦斯爆炸伤 80.0 35.0 重度 右侧气胸 10 病例4 47 氨水烧伤 27.0 10.0 重度 呼吸衰竭、急性氨中毒 16 病例5 62 氨水烧伤 15.0 0 重度 右侧气胸、呼吸衰竭、急性氨中毒 9 注:TBSA为体表总面积,APACHEⅡ评分为急性生理学和慢性健康状况评价Ⅱ评分 表2 5例烧伤合并急性呼吸窘迫综合征患者行体外膜肺氧合(ECMO)治疗的总体情况
患者编号 治疗年份 是否成功脱机 是否存活 伤后死亡时间(d) 死亡原因 上机前24 h氧合指数<100 mmHg时长(h) ECMO使用模式 伤后ECMO开始时间(d) ECMO持续时长(h) 是否使用血管活性药物 是否使用镇静镇痛药物 是否使用CRRT 病例1 2014 否 否 23 MODS、脓毒症休克 12 VV 20 80 是 是 是 病例2 2018 否 否 17 MODS、脓毒症休克 7 VV 9 178 是 是 是 病例3 2014 是 否 34 MODS、脓毒症休克 8 VV 12 279 是 是 是 病例4 2020 是 否 19 MODS、脓毒症休克 11 VV 7 118 是 是 是 病例5 2020 是 是 — — 14 VV 3 247 否 是 否 注:MODS为多器官功能障碍综合征,VV为静脉到静脉,CRRT为连续性肾脏替代治疗;“—”表示无此项;1 mmHg=0.133 kPa 表3 5例行体外膜肺氧合治疗的烧伤合并急性呼吸窘迫综合征患者各时间点氧合作用的变化[M(min,max)]
患者编号 PaO2(mmHg) FiO2(%) 氧合指数(mmHg) PaCO2(mmHg) 使用前 使用中 使用后 使用前 使用中 使用后 使用前 使用中 使用后 使用前 使用中 使用后 病例1 80(57,140) 57(43,100) — 90(80,100) 33(33,100) — 86(61,175) 173(100,195) — 44(30,59) 47(25,57) — 病例2 101(64,137) 67(44,135) — 70(70,100) 90(37,100) — 132(67,166) 74(44,365) — 48(39,72) 44(35,52) — 病例3 86(64,161) 89(67,121) 165(120,201) 70(70,80) 38(15,48) 45(41,48) 123(91,201) 238(149,318) 380(267,447) 37(31,43) 34(27,40) 38(29,49) 病例4 79(64,132) 94(33,158) 102(63,167) 65(45,100) 40(40,100) 45(40,100) 121(94,173) 224(74,351) 227(80,410) 54(38,97) 41(36,57) 55(50,102) 病例5 62(56,68)* 94(57,162) 116(59,207) 70(55,70)* 35(35,50) 35(35,41) 97(89,102)* 271(114,437) 327(169,591) 37(35,38)* 35(29,39) 30(23,36) 注:PaO2为动脉血氧分压,FiO2为吸入气氧浓度,PaCO2为动脉血二氧化碳分压,SaO2为动脉血氧饱和度;“*”表示该数据样本量为3,“φ”表示该指标样本量为8~72,其余数据样本量为7~65;“—”表示无此项;1 mmHg=0.133 kPa 表4 5例行体外膜肺氧合治疗的烧伤合并急性呼吸窘迫综合征患者各时间点感染指标的变化[M(min,max)]
患者编号 体温(℃)φ 白细胞计数(×109/L) 中性粒细胞比例 使用前 使用中 使用后 使用前 使用中 使用后 使用前 使用中 使用后 病例1 37.9(36.6,39.1) 36.4(35.3,36.9) — 11.3(2.3,28.7) 5.3(2.0,13.9) — 0.94(0.76,0.96) 0.94(0.81,0.97) — 病例2 37.6(36.8,38.3) 36.9(36.2,37.9) — 10.9(9.1,15.0) 7.8(6.8,13.0) — 0.89(0.85,0.92) 0.90(0.80,0.93) — 病例3 36.8(35.6,37.8) 37.2(35.4,37.9) 37.1(35.6,39.6) 11.5(8.6,12.3) 8.1(6.8,13.7) 16.6(11.2,29.8) 0.88(0.85,0.89) 0.91(0.88,0.94) 0.93(0.90,0.96) 病例4 37.2(36.7,40) 36.6(36.5,37.0) 36.7(36.0,38.1) 8.5(4.4,13.7) 20.1(18.3,36.6) 37.1(35.7,38.5)# 0.89(0.85,0.91) 0.95(0.91,0.96) 0.95(0.94,0.95)# 病例5 37.5(37.0,38.5) 37.8(37.0,39.3) 37.4(36.6,40.0) 12.7* 9.4(7.5,16.2) 9.5(4.5,31.0) 0.89* 0.85(0.80,0.96) 0.81(0.70,0.97) 注:“*”表示该数据样本量为1,“#”表示该数据样本量为2,“φ”表示该指标样本量为8~70,其余数据样本量为3~12;“—”表示无此项 表5 13篇回顾性论著的烧伤人群体外膜肺氧合(ECMO)使用情况
人群类别与第一作者(发表年份) 例数 烧伤总面积(%TBSA) 吸入性损伤(例) ECMO指征 伤后ECMO开始时间 ECMO持续时间 ECMO模式 CRRT(例) 死亡(例) 死亡原因 成年烧伤人群 Marcus[16](2019) 20 30 2 ARDS — 249 h 静脉到静脉 — 8 ARDS、颅内出血 Dadras[17](2019) 8 37 1 ARDS — 388 h — 4 3 脓毒症 Szentgyorgyi[18](2018) 5 27.8 5 重度ARDS 7.4 d 18 d 静脉到静脉 4 1 MODS Chiu(2018)[19] 5 82.9 5 重度ARDS — 119 h 静脉到静脉 4 3 — Ainsworth[20](2018) 14 27 4 重度ARDS — 276 h — 9 6 — Nosanov[21](2017) 30 17.0 8 呼吸衰竭、肺部感染、ARDS — — — — 16 MODS Hsu[22](2017) 6 89.0 5 ARDS、心源性休克 26.5 h 169.6 h 2例静脉到静脉、4例静脉到动脉 — 5 MODS、脓毒症休克、 心源性休克 Burke[23](2017) 58 — — 重度ARDS 130 h 185 h 44例静脉到静脉、14例静脉到动脉 32 33 — Soussi[24](2016) 11 31 6 重度ARDS 4 d 90 h 8例静脉到静脉、2例静脉到动脉、1例静脉到静脉与静脉到动脉混合使用 — 8 MODS 儿童烧伤人群 Thompson[12](2020) 113 — 19 重度ARDS — 177.0 h 37例静脉到静脉、73例静脉到动脉、3例未报道 51 54 — Eldredge[13](2019) 8 17 3 重度ARDS 7.5 d 11 d 静脉到静脉 — 1 — Kane[14](1999) 12 50.2 4 重度ARDS 7.8 d 165.2 h — — 4 ARDS Pierre[15](1998) 5 41.8 3 — — 324.4 h — 3 2 — 注:ARDS为急性呼吸窘迫综合征,MODS为多器官功能障碍综合征,TBSA为体表总面积,CRRT为连续性肾脏替代治疗;“—”表示无此项 脱细胞真皮基质(ADM) 重症监护病房(ICU) 动脉血氧分压(PaO2) 丙氨酸转氨酶(ALT) 白细胞介素(IL) 磷酸盐缓冲液(PBS) 急性呼吸窘迫综合征(ARDS) 角质形成细胞(KC) 反转录-聚合酶链反应(RT-PCR) 天冬氨酸转氨酶(AST) 半数致死烧伤面积(LA50) 全身炎症反应综合征(SIRS) 集落形成单位(CFU) 内毒素/脂多糖(LPS) 超氧化物歧化酶(SOD) 细胞外基质(ECM) 丝裂原活化蛋白激酶(MAPK) 动脉血氧饱和度(SaO2) 表皮生长因子(EGF) 最低抑菌浓度(MIC) 体表总面积(TBSA) 酶联免疫吸附测定(ELISA) 多器官功能障碍综合征(MODS) 转化生长因子(TGF) 成纤维细胞(Fb) 多器官功能衰竭(MOF) 辅助性T淋巴细胞(Th) 成纤维细胞生长因子(FGF) 一氧化氮合酶(NOS) 肿瘤坏死因子(TNF) 3-磷酸甘油醛脱氢酶(GAPDH) 负压伤口疗法(NPWT) 血管内皮生长因子(VEGF) 苏木精-伊红(HE) 动脉血二氧化碳分压(PaCO2) 负压封闭引流(VSD)