Article(id=1200023159505257065, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1200023152219746543, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2107.2023.0317, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1665417600000, receivedDateStr=2022-10-11, revisedDate=null, revisedDateStr=null, acceptedDate=1672156800000, acceptedDateStr=2022-12-28, onlineDate=1764037416573, onlineDateStr=2025-11-25, pubDate=1698422400000, pubDateStr=2023-10-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1764037416573, onlineIssueDateStr=2025-11-25, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1764037416573, creator=13701087609, updateTime=1764037416573, updator=13701087609, issue=Issue{id=1200023152219746543, tenantId=1146029695717560320, journalId=1189873630562394117, year='2023', volume='48', issue='10', pageStart='1115', pageEnd='1236', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1764037414841, creator=13701087609, updateTime=1764038706792, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1200028571126301693, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1200023152219746543, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1200028571126301694, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1200023152219746543, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1167, endPage=1173, ext={EN=ArticleExt(id=1200023160755159684, articleId=1200023159505257065, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Symmetrical peripheral gangrene in septic shock: a case report and literature review, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To report a case of symmetric peripheral gangrene (SPG) in septic shock. The clinical data and related literature were reviewed to discuss its characteristics, pathogenesis and treatment measures, so as to improve clinicians' understanding and treatment of the disease. Methods A 60-year-old male patient was admitted to the Changhai Hospital Affiliated to Naval Medical University on July 31, 2022 due to "left side low back pain". Before operation, he was diagnosed with malignant tumor of the left adrenal gland involving multiple organs and blood vessels. Therefore, he underwent resection of huge retroperitoneal tumor, left colon, left kidney, left suprarenal gland, part of stomach and pancreatic body tail under general anesthesia. Due to the large surgical trauma, more bleeding and low blood pressure, he was admitted to the ICU for blood transfusion, fluid infusion and pressure boosting. The literature about SPG in the past 10 years in the database of the National Library of Medicine (PubMed) was searched, and the characteristics of the disease, the related factors of the disease and the treatment measures were emphatically discussed. Results The patient developed septic shock due to intraperitoneal infection on the 3rd day after operation, and gradually developed symmetrical ischemic necrosis of both hands and feet on the 4th day. According to the characteristics of the disease and clinical features, the patient was diagnosed with SPG. A total of 18 foreign English literatures were retrieved, involving 24 SPG patients. In combination with this case, 25 patients were included, including 10 males (40%) and 15 females (60%). The male to female ratio was 1:1.5. The average age was (48.8±15.1) years for males and (49.8±16.2) years for females. There was no history of vascular related diseases in the past. The main clinical features were symmetrical ischemic necrosis of both hands and (or) lower limbs and feet (100%), which was related to septic shock (100%), microbial infection (52%), disseminated intravascular coagulation (DIC) (52%), liver function damage (20%), and the use of vasoactive drugs (80%). The treatment effect was poor, the death mortality was 24% (6/25), and the amputation rate of the surviving patients was as high as 78.9% (15/19). Only one case of blood adsorption treatment was effective. Conclusions The occurrence of SPG in septic shock patients may be related to the pathophysiological changes such as septic shock, DIC, lack of natural anticoagulants, and the role of vasoactive drugs. Clinicians need to pay great attention to improving the diagnosis and treatment of SPG.

, correspAuthors=Wei Chang, Ke-Ming Zhu, authorNote=null, correspAuthorsNote=
Chang Wei, E-mail:
Zhu Ke-Ming, E-mail:
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目的 报告1例脓毒性休克并发对称性外周坏死(SPG)患者的临床资料并复习相关文献,探讨其病情特点、发病机制及治疗措施,以提高临床医师对该病的认识及救治水平。方法 患者,男,60岁,因“左侧腰痛”于2022年7月31日入住海军军医大学附属长海医院,术前诊断为左侧肾上腺恶性肿瘤并侵犯多个脏器及血管,遂在全麻下行腹膜后巨大肿瘤、左半结肠、左肾及左肾上腺、部分胃及胰体尾切除术。由于手术创伤大、出血多且血压低,术后入住重症监护室行输血、补液及升压等治疗。检索美国国立医学图书馆(PubMed)数据库近10年有关SPG的文献,着重探讨其病情特点、发病相关因素及治疗措施。结果 该患者术后第3天因腹腔感染发生脓毒性休克,第4天开始逐渐出现双手及双足对称性缺血性坏死,根据病情特点及临床特征诊断为SPG。共检索到国外英文文献18篇,涉及24例SPG患者,结合本次报告病例共纳入25例患者,其中男10例(40%),女15例(60%),男女比例1∶1.5,男性年龄(48.8±15.1)岁,女性年龄(49.8±16.2)岁,既往均无血管性疾病史。临床特征为对称性双手和(或)双下肢、双足缺血坏死(100%),与脓毒性休克(100%)、微生物感染(52%)、弥散性血管内凝血(DIC)(52%)、肝功能损害(20%)及血管活性药物的应用(80%)等因素存在一定关系。治疗效果不佳,病死率为24%(6/25),存活患者中截肢率高达78.9%(15/19),只有1例行血液吸附治疗有效。结论 脓毒性休克患者发生SPG可能与脓毒性休克、DIC、肝功能损害及天然抗凝剂缺乏等病理生理学改变,以及血管活性药物的作用等因素有关。临床医师需高度重视,以提高SPG的诊治水平。

, correspAuthors=昌薇, 朱科明, authorNote=null, correspAuthorsNote=
昌薇,E-mail:
朱科明,E-mail:
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李俊民,医学硕士,主要从事危重症医学等方面的研究

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李俊民,医学硕士,主要从事危重症医学等方面的研究

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李俊民,医学硕士,主要从事危重症医学等方面的研究

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A. 血乳酸水平变化及血管活性药物应用情况;B. 部分凝血功指标变化和血制品输注情况;C. 总胆红素和白蛋白水平变化;D. 血红蛋白、血小板水平变化以及抗凝和抗生素应用情况

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脓毒性休克并发对称性外周坏疽1例并文献复习
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李俊民 1 , 吴鹏 1 , 孟岩 1 , 常永青 1 , 万小健 1 , 昌薇 2, * , 朱科明 1, *
解放军医学杂志 | 临床研究 2023,48(10): 1167-1173
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解放军医学杂志 | 临床研究 2023, 48(10): 1167-1173
脓毒性休克并发对称性外周坏疽1例并文献复习
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李俊民1, 吴鹏1, 孟岩1, 常永青1, 万小健1, 昌薇2, * , 朱科明1, *
作者信息
  • 1海军军医大学附属长海医院重症医学科,上海 200433
  • 2复旦大学附属徐汇医院急诊科,上海 200030
  • 李俊民,医学硕士,主要从事危重症医学等方面的研究

通讯作者:

昌薇,E-mail:
朱科明,E-mail:
Symmetrical peripheral gangrene in septic shock: a case report and literature review
Jun-Min Li1, Peng Wu1, Yan Meng1, Yong-Qing Chang1, Xiao-Jian Wan1, Wei Chang2, * , Ke-Ming Zhu1, *
Affiliations
  • 1Department of Critical Care Medicine, Changhai Hospital Affiliated to Naval Medical University, Shanghai 200433, China
  • 2Department of Emergency, Xuhui Hospital Affiliated to Fudan University, Shanghai 200030, China
出版时间: 2023-10-28 doi: 10.11855/j.issn.0577-7402.2107.2023.0317
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目的 报告1例脓毒性休克并发对称性外周坏死(SPG)患者的临床资料并复习相关文献,探讨其病情特点、发病机制及治疗措施,以提高临床医师对该病的认识及救治水平。方法 患者,男,60岁,因“左侧腰痛”于2022年7月31日入住海军军医大学附属长海医院,术前诊断为左侧肾上腺恶性肿瘤并侵犯多个脏器及血管,遂在全麻下行腹膜后巨大肿瘤、左半结肠、左肾及左肾上腺、部分胃及胰体尾切除术。由于手术创伤大、出血多且血压低,术后入住重症监护室行输血、补液及升压等治疗。检索美国国立医学图书馆(PubMed)数据库近10年有关SPG的文献,着重探讨其病情特点、发病相关因素及治疗措施。结果 该患者术后第3天因腹腔感染发生脓毒性休克,第4天开始逐渐出现双手及双足对称性缺血性坏死,根据病情特点及临床特征诊断为SPG。共检索到国外英文文献18篇,涉及24例SPG患者,结合本次报告病例共纳入25例患者,其中男10例(40%),女15例(60%),男女比例1∶1.5,男性年龄(48.8±15.1)岁,女性年龄(49.8±16.2)岁,既往均无血管性疾病史。临床特征为对称性双手和(或)双下肢、双足缺血坏死(100%),与脓毒性休克(100%)、微生物感染(52%)、弥散性血管内凝血(DIC)(52%)、肝功能损害(20%)及血管活性药物的应用(80%)等因素存在一定关系。治疗效果不佳,病死率为24%(6/25),存活患者中截肢率高达78.9%(15/19),只有1例行血液吸附治疗有效。结论 脓毒性休克患者发生SPG可能与脓毒性休克、DIC、肝功能损害及天然抗凝剂缺乏等病理生理学改变,以及血管活性药物的作用等因素有关。临床医师需高度重视,以提高SPG的诊治水平。

对称性外周坏疽  /  脓毒性休克  /  弥散性血管内凝血  /  抗凝血因子  /  肝功能损害  /  血管活性药物

Objective To report a case of symmetric peripheral gangrene (SPG) in septic shock. The clinical data and related literature were reviewed to discuss its characteristics, pathogenesis and treatment measures, so as to improve clinicians' understanding and treatment of the disease. Methods A 60-year-old male patient was admitted to the Changhai Hospital Affiliated to Naval Medical University on July 31, 2022 due to "left side low back pain". Before operation, he was diagnosed with malignant tumor of the left adrenal gland involving multiple organs and blood vessels. Therefore, he underwent resection of huge retroperitoneal tumor, left colon, left kidney, left suprarenal gland, part of stomach and pancreatic body tail under general anesthesia. Due to the large surgical trauma, more bleeding and low blood pressure, he was admitted to the ICU for blood transfusion, fluid infusion and pressure boosting. The literature about SPG in the past 10 years in the database of the National Library of Medicine (PubMed) was searched, and the characteristics of the disease, the related factors of the disease and the treatment measures were emphatically discussed. Results The patient developed septic shock due to intraperitoneal infection on the 3rd day after operation, and gradually developed symmetrical ischemic necrosis of both hands and feet on the 4th day. According to the characteristics of the disease and clinical features, the patient was diagnosed with SPG. A total of 18 foreign English literatures were retrieved, involving 24 SPG patients. In combination with this case, 25 patients were included, including 10 males (40%) and 15 females (60%). The male to female ratio was 1:1.5. The average age was (48.8±15.1) years for males and (49.8±16.2) years for females. There was no history of vascular related diseases in the past. The main clinical features were symmetrical ischemic necrosis of both hands and (or) lower limbs and feet (100%), which was related to septic shock (100%), microbial infection (52%), disseminated intravascular coagulation (DIC) (52%), liver function damage (20%), and the use of vasoactive drugs (80%). The treatment effect was poor, the death mortality was 24% (6/25), and the amputation rate of the surviving patients was as high as 78.9% (15/19). Only one case of blood adsorption treatment was effective. Conclusions The occurrence of SPG in septic shock patients may be related to the pathophysiological changes such as septic shock, DIC, lack of natural anticoagulants, and the role of vasoactive drugs. Clinicians need to pay great attention to improving the diagnosis and treatment of SPG.

symmetric peripheral gangrene  /  septic shock  /  disseminated intravascular coagulation  /  anticoagulant factors  /  liver function damage  /  vasoactive drugs
李俊民, 吴鹏, 孟岩, 常永青, 万小健, 昌薇, 朱科明. 脓毒性休克并发对称性外周坏疽1例并文献复习. 解放军医学杂志, 2023 , 48 (10) : 1167 -1173 . DOI: 10.11855/j.issn.0577-7402.2107.2023.0317
Jun-Min Li, Peng Wu, Yan Meng, Yong-Qing Chang, Xiao-Jian Wan, Wei Chang, Ke-Ming Zhu. Symmetrical peripheral gangrene in septic shock: a case report and literature review[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (10) : 1167 -1173 . DOI: 10.11855/j.issn.0577-7402.2107.2023.0317
对称性外周坏疽(symmetric peripheral gangrene,SPG)是一种少见的严重并发症,典型表现为四肢远端双侧对称性缺血性坏死,多见于脓毒性休克、心力衰竭及弥散性血管内凝血(disseminated intravascular coagulation,DIC)等重症患者[1-3]。脓毒症休克患者发生SPG后的病死率高达40%,约50%的存活患者需要截肢[2]。而《拯救脓毒症运动:2021年脓毒症及脓毒性休克管理国际指南》(简称指南)[4]未提及SPG的诊治。目前SPG较少见,发病机制尚不清楚,病因复杂,临床缺乏足够重视,一旦发生,预后极差。本文报道1例脓毒性休克并发SPG患者并复习文献,探讨SPG的临床特征、发病原因及治疗措施,以提高对SPG的认识及临床诊治水平。
患者,男,60岁,因“左侧腰痛”1个月余于2022年7月31日入住海军军医大学附属长海医院。术前影像学检查提示:左侧肾上腺区团块,考虑为恶性肿瘤,侵犯左肾、胰尾部、贲门-胃底、左侧腰大肌、左肾动静脉及脾动静脉。于2022年8月4日在全麻下行腹膜后巨大肿瘤切除+左半结肠切除+左肾及左肾上腺切除+部分胃切除+胰体尾切除术,术中出血6000 ml,予以输注红细胞悬液2000 ml,血浆400 ml,冷沉淀20单位,血小板10单位。由于手术创伤大、术中出血多且血压低,患者术后入住重症监护室(ICU)。患者既往有高血压病史,规律服用厄贝沙坦氢氯噻嗪、富马酸比索洛尔,否认糖尿病、免疫性疾病及血管性疾病等,余无特殊。
根据有创动脉压监测、实验室检查及液体出入量评估等指标,予以去甲肾上腺素维持灌注压、间断成分输血、输液补充血容量及输注白蛋白等针对性治疗,同时根据手术情况予以头孢呋辛抗感染、雷贝拉唑制酸、奥曲肽抑制胰酶、适当利尿,以及维持水电解质平衡等预防性治疗及支持治疗。术后第1天开始,肝功能检查结果提示谷丙转氨酶及总胆红素水平逐渐升高,凝血功能检查结果提示D-二聚体及凝血酶原时间国际标准化比值(INR)逐渐升高。术后第3天(2022年8月7日)自腹腔引流管引流出黄色脓性液体,细菌培养为耐药肺炎克雷伯菌,患者出现高热伴休克加重。实验室检查结果:白细胞1.6×109/L,C反应蛋白344.88 mg/L,降钙素原2.97 ng/ml,血乳酸7.5 mmol/L,动脉血氧合指数<150 mmHg,纤维蛋白原及血小板下降。考虑为腹腔感染导致严重脓毒症及脓毒性休克。遂予以美罗培南联合替加环素加强抗感染、容量复苏及气管插管机械通气等治疗,并先后予以大量血管活性药物(去甲肾上腺素+垂体后叶素+多巴胺)行升压治疗。主要病情发展、相关实验室检查结果及治疗情况详见图1
术后第4天(2022年8月8日),患者双上肢第一指关节出现瘀斑伴腕关节以下皮温减低,后逐渐加重致全部第一指关节干性坏死;双足出现不同程度对称性缺血及坏死,但双侧桡动脉及足背动脉仍可触及。患者双耳廓亦出现轻度皮肤缺血坏死(图2)。根据临床特征诊断为SPG。
在加强抗感染、抗休克、机械通气及积极输血补液等治疗的基础上,给予那曲肝素(低分子肝素)皮下注射(0.4 ml/d),无明显效果,SPG逐渐加重。术后第11天(2022年8月15日)患者病情恶化,发生重度急性呼吸窘迫综合征(ARDS)(氧合指数<80 mmHg)、严重脓毒性休克(大剂量血管活性药物支持下,平均动脉压<40 mmHg)、急性肾衰竭(尿量<100 ml/24 h,肌酐>500 μmol/L,K+ >6 mmol/L)及严重酸中毒[pH值<7.2,乳酸8 mmol/L,血气分析示碱剩余(BE)<-15 mmol/L],经积极治疗无效,最终因多器官衰竭而死亡。
以[(Symmetric Peripheral Gangrene) AND (sepsis) Filters:in the last 10 years]为检索式,检索美国国立医学图书馆(PubMed)数据库近10年有关SPG的文献,共检索出国外文献29篇,排除非英文文献及无原文文献8篇,共检索到国外文献18篇,包括24例患者[5-22],结合本文报告的病例,共纳入25例患者进行分析。以“对称性外周坏死”及“脓毒症”为检索词,检索维普、中国知网、万方等数据库近10年有关SPG的文献,未检索到国内核心期刊刊登过相关文献。
25例患者中,男10例(40%),女15例(60%),男女比例1∶1.5,男性年龄(48.8±15.1)岁,女性年龄(49.8±16.2)岁。既往均无血管性疾病史。
25例患者肢体动脉搏动均可触及,均出现对称性双手和(或)双下肢、双足缺血坏死,其中合并其他部位缺血坏死者3例(1例并发鼻子、1例并发臀部、1例并发面部及阴茎缺血坏死)。
25例患者均存在休克(休克时都使用血管活性药物),其中17例(68%)记录休克与缺血症状发生的时间间隔,小于1 d者2例(11.8%),1~3 d者6例(35.3%),3 d以上者9例(52.9%)。
25例患者中有13例(52%)提供了病原学资料,其余均未检测或未提供病原学数据。13例患者中,共检测出(单独或合并)大肠埃希菌3例,鲍曼不动杆菌3例,肺炎克雷伯菌3例,奇异变形杆菌1例,耐甲氧西林金黄色葡萄球菌2例,流感嗜血杆菌1例,脑膜炎链球菌1例,热带念珠菌1例,铜绿假单胞菌1例,肺炎链球菌1例,流感病毒1例。
25例患者中,13例(52%)发生DIC,11例没有记录具体情况,1例排除DIC。25例患者中仅有2例(8%)监测抗凝因子且发现机体天然抗凝因子水平低下。
25例患者中,仅有5例(20%)记录了肝功能损害指标(转氨酶、胆红素升高,白蛋白下降等),其余未提及肝功能相关数据。5例患者中有3例的缺血症状发生在肝功能损伤后0.5~2 d。
25例患者中,20例(80%)使用血管活性药物,以去甲肾上腺素使用频次最多且用量最大,4例未记录使用血管活性药物,1例否认使用血管活性药物。
25例患者中有1例失访。所用针对肢体缺血的治疗方法包括低分子肝素3例、阿加曲班抗凝1例、血液滤过1例、血液吸附1例及高压氧治疗1例,除1例血液吸附可逆转局部缺血症状外,其余治疗效果均不理想。25例患者中6例死亡(24%),19例存活者中15例实施截肢,存活患者中截肢率高达78.9%。
脓毒性休克患者常见皮肤花斑样改变及四肢末梢循环充盈障碍,经过液体复苏及血管活性药物支持治疗,一旦休克纠正,末梢循环功能一般可以得到改善,而发生不可逆的SPG并不多见。本文回顾分析了25例脓毒症休克并发SPG患者的临床资料,结果显示对称性外周坏死大多表现为对称性四肢远端缺血坏死,女性患者似乎更多见。SPG具有3个临床特征[20]:(1)两处及以上的肢体远端不可逆坏死;(2)双侧对称性;(3)动脉性缺血损害但无大动脉闭塞性疾病。本例脓毒性休克患者发生典型的对称性四肢远端缺血坏死,符合上述临床特征。
分析总结25例SPG患者的临床资料并复习相关文献,提示SPG的发病机制可能与各种微生物导致的严重感染、脓毒性休克、DIC、机体天然抗凝剂水平低下及血管活性药物的应用有关。
脓毒症是严重感染引发的宿主异常免疫反应并导致危及生命的器官功能障碍,脓毒性休克是严重脓毒症的典型表现[23]。研究表明,SPG是各种感染性疾病的并发症,大肠埃希菌、假单胞菌、肺炎克雷伯菌、脑膜炎球菌及肺炎球菌已被确定为致病因素[24]。本研究总结的25例SPG患者中,明确有细菌感染者占52%,其余未检测或未提供病原学数据。Davis等[25]发现,脓毒症患者出现的对称性四肢远端坏死与休克综合征(低血压、少尿等)相关。脓毒性休克导致外周低灌注并缺血,而纠正脓毒性休克的血管活性药物具有收缩外周血管的作用,可能加重外周缺血。外周缺血往往发生于脓毒性休克后48~96 h,表现为肢体远端发冷、苍白或发绀,缺血性变化最终导致坏疽的发生[26]。本例患者手术创伤大,术后血压低,入ICU后即使用了去甲肾上腺素维持血压,术后第3天,由于腹腔肺炎克雷伯菌感染导致患者发生严重脓毒症及脓毒性休克(发热、白细胞明显降低、C反应蛋白及降钙素原明显升高、动脉血乳酸升至7.5 mmol/L、动脉血氧合指数<150 mmHg),先后予以大剂量血管活性药物(去甲肾上腺素+垂体后叶素+多巴胺)升压治疗,术后第4天,患者出现四肢远端缺血症状,逐渐恶化并最终发生SPG。
25例SPG患者中,13例(52%)发生DIC、11例没有记录、1例排除DIC。DIC导致皮肤、四肢远端血管内微血栓形成及栓塞,而休克的低血流状态加重了四肢微循环的血栓性闭塞。尽管动脉搏动可触及,仍会发生四肢远端缺血性坏死,因为发病机制涉及微血栓形成[25]。本例术后早期即出现凝血酶原时间延长(INR升高)及D-二聚体水平明显升高,随着脓毒性休克的发生,血小板明显减少且纤维蛋白原水平下降,可以诊断DIC。因此,脓毒性休克患者发生DIC可能是导致SPG的重要原因。
缺血性肝损害(休克肝)导致机体天然抗凝剂生成减少,以及输注大量液体导致天然抗凝剂水平稀释性下降,造成天然抗凝剂严重不足,可能是SPG发生的另一个重要机制。天然抗凝剂绝大部分由肝脏及血管内皮细胞产生,而脓毒性休克患者由于低灌注及微循环障碍常发生休克肝及血管内皮细胞损伤,从而导致机体天然抗凝剂的合成减少及缺乏。Safdar等[27]研究发现,肝脏抗凝血酶及蛋白C基因均被沉默后,实验动物发生了急性凝血病,表现为纤维蛋白沉积及后腿坏死,认为这种“双重抗凝剂损耗”作用与脓毒性休克肝的影响类似,有助于解释SPG的发生。休克肝在脓毒性休克患者中很常见。Warkentin等[1]研究发现,休克肝可导致SPG患者抗凝血酶和蛋白C活性分别低于正常值的40%及20%,并呈现一种特征性时间关系,即SPG出现在休克肝发生后2~5 d(中位时间为3 d),认为这种特征性表现反映了肝脏合成的天然抗凝剂、蛋白C及抗凝血酶达到临界耗尽水平所需的时间。此外,机体天然抗凝剂严重不足可能与脓毒性休克患者大量液体容量复苏的稀释作用有关。Warkentin等[5]报道了2例脓毒性休克患者发生SPG,虽然肝转氨酶轻度升高(休克肝不是主要病因),但在发生SPG前都接受了大量液体(晶体、胶体、白蛋白及免疫球蛋白等)输注,2例患者的3种天然抗凝剂(蛋白C、蛋白S、抗凝血酶)水平均明显降低,认为大量液体输注可能导致天然抗凝剂稀释性减少,是SPG发病的重要因素之一。本例患者发生严重脓毒性休克,提示存在缺血性肝损害(休克肝)及血管内皮细胞损伤,有可能导致机体天然抗凝剂生成减少,虽然没有检测天然抗凝剂的水平,且谷丙转氨酶升高并不明显。此外,由于手术创伤大、术中出血多及血压低,术中及术后输注了大量红细胞悬液、血小板、冷沉淀、凝血酶原复合物、纤维蛋白原及白蛋白等液体,大量液体输注可能导致天然抗凝剂稀释性减少,而输注凝血成分有可能加重DIC。
对于脓毒性休克患者,去甲肾上腺素是首选的升压药,血管加压药及多巴胺也被推荐应用[4]。25例SPG患者中,20例(80%)使用血管活性药物,以去甲肾上腺素使用频次最多且用量最大。本例由于术后低血压及脓毒性休克,先后应用大剂量的去甲肾上腺素[最大剂量3 μg/(kg·min)]、垂体后叶素(最大剂量3 U/h)及多巴胺[最大剂量30 μg/(kg·min)]。这些血管活性药物对外周血管的收缩作用与SPG发生的相关性值得关注。Raj等[28]报道应用去甲肾上腺素及多巴胺后发生SPG,认为外周血管长时间的收缩可导致外周坏疽。有Meta分析认为,大剂量应用垂体后叶素或去氨加压素能收缩小动脉及毛细血管,可减少外科患者术后输血量,但增加了血栓的发生风险,有可能导致外周缺血,从而引起SPG[29]。但更多研究文献否定了这一观点,否定的关键依据是:临床许多使用血管活性药物纠正休克的患者并未发生SPG,如果血管加压药物引起SPG,肢体缺血应该在几小时内发生,而不是至少2 d后[5,13,26]。SPG发生呈现的特征性时间间隔(休克肝发生后2~5 d)提示一种时间依赖性病理生理变化,反映了脓毒性休克的进展及DIC加重,尤其是天然抗凝剂的耗竭,而不是血管活性药物的缩血管作用[30]
SPG一旦发生,干预治疗可能为时已晚,约50%的存活患者需要截肢[2]。本研究总结文献报道的25例SPG患者中,6例死亡(24%),19例存活者中15例实施截肢,截肢率高达78.9%。目前缺乏针对SPG的有效治疗方法。根据SPG的发病机制,某些治疗在理论上可能有效,包括抗凝血酶、蛋白C浓缩物、肝素抗凝、血浆输注,但抗凝物质浓缩物临床难以获取,肝素抗凝由于严重的血小板减少及出血风险而应用受限[25]。Warkentin等[1]认为血浆置换可能是针对脓毒性休克患者SPG有效的潜在治疗方法,建议对严重脓毒性休克患者在休克发生后48 h内进行血浆置换,以去除内毒素及有害的促炎细胞因子并替换补充缺乏的抗凝及凝血因子。Uncu Ulu等[14]报道1例脓毒性休克期间发生SPG的患者,通过血液吸附方法去除细胞因子,同时加强感染性休克治疗,患者完全康复。
复习SPG相关文献并结合本例患者,笔者认为以下几点值得反思:(1)优化液体输注量并控制凝血物质输注。为了纠正休克,本例患者术中及术后输注了大量的红细胞悬液、白蛋白及晶体液,有可能导致天然抗凝剂稀释性减少。由于对SPG发病机制认识不深,本例患者还输注了血小板、冷沉淀、凝血酶原复合物及纤维蛋白原等凝血物质,有可能加重DIC而导致SPG的发生。应优化液体输注量,维持平均动脉压>65 mmHg即可,同时应监测凝血功能、出血情况及抗凝因子水平,以调整凝血物质输注。(2)优化血管活性药物的应用。尽管目前认为血管活性药物与SPG的发生无关[5],但其对外周血管的收缩作用仍不能忽视。只要MAP维持在65 mmHg以上,就应随时下调去甲肾上腺素、垂体后叶素及多巴胺的用量,以降低对SPG发生可能的潜在作用。(3)加强对SPG的认识,尽早发现SPG的早期临床表现。外周缺血往往在脓毒性休克发作后48~96 h发生[29],一旦肢体远端发冷、苍白或发绀,就要高度警惕SPG的可能,应调整输液及优化血管活性药物,并及时开展血浆置换。
总之,SPG的发生涉及休克、DIC、休克肝及天然抗凝剂缺乏等病理生理学改变,以及血管活性药物的作用等,严重脓毒症患者往往存在这些因素,而在脓毒症救治过程中还可能存在不恰当的治疗,故更容易发生SPG。SPG一旦发生,目前尚缺乏有效的治疗方法,预后极差,需要临床医生高度重视并开展相关研究,总结治疗经验,以提高SPG的救治水平。
  • 上海市科委医学创新项目(20Y11900800)
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2023年第48卷第10期
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doi: 10.11855/j.issn.0577-7402.2107.2023.0317
  • 接收时间:2022-10-11
  • 首发时间:2025-11-25
  • 出版时间:2023-10-28
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  • 收稿日期:2022-10-11
  • 录用日期:2022-12-28
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Medical Innovation Project of Shanghai Municipal Science and Technology Commission(20Y11900800)
上海市科委医学创新项目(20Y11900800)
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    1海军军医大学附属长海医院重症医学科,上海 200433
    2复旦大学附属徐汇医院急诊科,上海 200030

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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