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Article(id=1190310108811858719, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1190243275249390089, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.0620.2025.0114, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1715270400000, receivedDateStr=2024-05-10, revisedDate=null, revisedDateStr=null, acceptedDate=1731945600000, acceptedDateStr=2024-11-19, onlineDate=1761721644833, onlineDateStr=2025-10-29, pubDate=1748361600000, pubDateStr=2025-05-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1761721644833, onlineIssueDateStr=2025-10-29, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1761721644833, creator=13701087609, updateTime=1761721644833, updator=13701087609, issue=Issue{id=1190243275249390089, tenantId=1146029695717560320, journalId=1189873630562394117, year='2025', volume='50', issue='5', pageStart='505', pageEnd='640', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1761705710470, creator=13701087609, updateTime=1765784077922, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1207349188233372409, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1190243275249390089, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1207349188233372410, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1190243275249390089, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=536, endPage=544, ext={EN=ArticleExt(id=1190310109080294178, articleId=1190310108811858719, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Predictive value of toe-to-room temperature gradient for 28 d mortality in sepsis patients: a single center prospective observational clinical study, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the predictive value of temperature gradients on the mortality of sepsis patients and their correlation with fluid input. Methods By means of a prospective observational method, 154 patients with sepsis or septic shock admitted to the Department of Critical Care Medicine at Nanfang Hospital, Southern Medical University from November 2019 to November 2021 were included as research subjects. They were divided into a survivor group (n=118) and a non-survivor group (n=36) according to whether they survived within 28 days. The core-to-toe temperature gradient (CTTG) and toe-to-room temperature gradient (TRTG) were monitored and calculated immediately upon admission to the intensive care unit (ICU) and 6 hours after admission. Receiver operating characteristic (ROC) curve was used to explore the predictive value of temperature gradients on mortality, and multivariate Cox regression analysis was performed to explore the risk factors of 28-day mortality in sepsis patients. The results were verified through survival analysis. Correlation analysis and multivariate analysis of variance were used to explore the correlation between temperature gradients and fluid input, as well as noradrenaline doses. Results Among the 154 patients, 118 survived within 28 days (survivor group), and 36 died (non-survivor group). ROC curve and multivariate Cox regression analysis showed that a toe-to-room temperature gradient of ≤5.35 ℃ within 6 hours after admission was a risk factor for 28-day mortality. Compared with patients with a high toe-to-room temperature gradient (>5.35 ℃), patients with a low toe-to-room temperature gradient (≤5.35 ℃) had a 2.74-fold increase in the risk of 28-day mortality (P=0.004, 95%CI 1.54, 9.12). The CTTG and TRTG upon admission to the ICU and 6 hours after admission were not significantly associated with fluid input or noradrenaline doses (P>0.05). Conclusions A toe-to-room temperature gradient of less than or equal to 5.35 ℃ within 6 hours after ICU admission is a risk factor for 28-day mortality in sepsis patients. The improvement of temperature gradients at different time points is not associated with fluid input.

, correspAuthors=Zhen-Hua Zeng, authorNote=null, correspAuthorsNote=
E-mail:
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目的 探讨体温梯度对脓毒症患者病死率的预测价值及其与液体入量的相关性。方法 采用前瞻性观察方法，纳入南方医科大学南方医院重症医学科2019年11月-2021年11月收治的154例脓毒症或脓毒性休克患者作为研究对象，根据28 d内是否存活分为存活组(n=118)与非存活组(n=36)。在入重症监护室(简称入科)即刻及入科6 h监测和计算中心-外周体温梯度(CTTG)、外周-室温体温梯度(TRTG)，采用受试者操作特征(ROC)曲线探讨体温梯度对死亡的预测价值，采用多因素Cox回归分析探讨脓毒症患者28 d内死亡的危险因素，进一步通过生存分析进行验证，并采用Spearman相关分析探讨体温梯度与液体入量、去甲肾上腺素剂量的相关性。结果 154例患者中，存活组118例，非存活组36例。ROC曲线和多因素Cox回归显示，入科6 h的TRTG≤5.35 ℃是28 d内死亡的危险因素。入科6 h后，与TRTG(>5.35 ℃)相比，低TRTG(≤5.35 ℃)患者的28 d内死亡风险增加了2.74倍(P=0.004，95%CI 1.54~9.12)。入科即刻及入科6 h的CTTG、TRTG均与液体入量、去甲肾上腺素剂量相关不明显(P>0.05)。结论 脓毒症患者入科6 h的TRTG≤5.35 ℃是28 d内死亡的危险因素，但不同时间点体温梯度的改善均与患者液体入量不相关。

, correspAuthors=曾振华, authorNote=null, correspAuthorsNote=
曾振华，E-mail：
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李露兰，医学博士，主治医师，主要从事脓毒症方面的研究

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李露兰，医学博士，主治医师，主要从事脓毒症方面的研究

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tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310108811858719, companyId=1190330559785177291, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=4Department of Critical Care Medicine, Yunfu People's Hospital, Yunfu, Guangdong 527399, China), AuthorCompanyExt(id=1190330559806148812, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310108811858719, companyId=1190330559785177291, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=4云浮市人民医院重症医学科，广东云浮　527399;[临床试验注册号] NCT04068298)])], figs=[ArticleFig(id=1190330564923199760, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310108811858719, language=EN, label=Fig.1, caption=Flow chart of the research subjects included, figureFileSmall=GpTRhw/iIOcBmOezckrbvQ==, figureFileBig=xe1J6KqalU33Rt+PKI/JpQ==, tableContent=null), ArticleFig(id=1190330564998697234, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310108811858719, language=CN, label=图1, caption=研究对象纳入流程, figureFileSmall=GpTRhw/iIOcBmOezckrbvQ==, figureFileBig=xe1J6KqalU33Rt+PKI/JpQ==, tableContent=null), ArticleFig(id=1190330565090971924, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310108811858719, language=EN, label=Fig.2, caption=Differences of body temperature gradient and 28-day mortality in patients with sepsis or septic shock, figureFileSmall=mzAHCRXM7Xdoo+qEO0+WVw==, figureFileBig=ik+BrrPxWMbbIjnOBIKH/g==, tableContent=null), ArticleFig(id=1190330565153886486, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310108811858719, language=CN, label=图2, caption=脓毒症或脓毒性休克患者体温梯度与28 d病死情况的相关性

CTTG. 中心-外周体温梯度；TRTG. 外周-室温体温梯度

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CTTG. 中心-外周体温梯度；TRTG. 外周-室温体温梯度；ROC. 受试者操作特征；AUC. ROC曲线下面积；A. H0 CTTG；B. H0 TRTG；C. H6 CTTG；D.H6 TRTG

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TRTG. 外周-室温体温梯度

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CTTG. 中心-外周体温梯度

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Clinical characteristics of the patients with sepsis or septic shock in survivors or non-survivors

, figureFileSmall=null, figureFileBig=null, tableContent=
指标存活组(n=118)非存活组(n=36)合计(n=154)P
性别[例(%)]0.230
男83(70.3)29(80.6)112(72.7)
女35(29.7)7(19.4)42(27.3)
年龄(岁, x±s)59.0(17.4)61.4(12.2)59.6(16.3)0.742
BMI[kg/m2, M(Q1, Q3)]23.0(20.7, 24.6)23.4(22.0, 25.0)23.0(20.9, 24.6)0.458
原发感染部位[例(%)]0.749
腹部56(47.5)16(44.4)72(46.8)
肺部43(36.4)13(36.1)56(36.4)
泌尿道3(2.5)3(8.3)6(3.9)
皮肤软组织6(5.1)2(5.6)8(5.2)
其他10(8.5)2(5.6)12(7.8)
慢性基础疾病[例(%)]
高血压39(33.1)11(30.6)50(32.5)0.780
糖尿病20(16.9)6(16.7)26(16.9)0.969
心血管疾病11(9.3)1(2.8)12(7.8)0.201
肺部疾病7(5.9)2(5.6)9(5.8)0.933
脑血管疾病9(7.6)3(8.3)12(7.8)0.890
慢性肾衰竭终末期4(3.4)1(2.8)5(3.2)0.857
恶性肿瘤15(12.7)4(11.1)19(12.3)0.799
HR(次/min, x±s)105.7±23.9105.8±19.1105.7±22.80.971
MAP(mmHg, x±s)82.6±14.584.3±15.983.0±14.80.547
NE[μg/(kg.min), M(Q1, Q3)]0.1(0, 0.2)0.2(0.2, 0.5)0.1(0, 0.2)0.004
RR(次/min, x±s)19.1±7.319.3±6.719.1±7.10.884
CVP[mmHg, M(Q1, Q3)]8.0(6.0, 11.0)8.9(6.0, 11.0)8.0(6.0, 11.0)0.932
WBC[×109/L, M(Q1, Q3)]11.0(5.0, 16.0)11.5(5.7, 18.5)11.0(5.0, 16.0)0.718
PLT[×109/L, M(Q1, Q3)]154.0(105.5, 226.0)96.5(37.8, 195.8)146.0(71.8, 218.8)0.016
CRP(mg/L, x±s)158.2±103.8163.4±100.6159.4±102.80.792
PCT[ng/ml, M(Q1, Q3)]9.0(1.8, 44.9)12.5(3.0, 83.9)9.6(2.0, 48.5)0.287
IL-6 [pg/ml, M(Q1, Q3)]429.0(92.9, 1686.6)332.5(69.5, 1150.0)404.0(91.1, 1403.3)0.510
SOFA(分, x±s)8.1±4.17.8±4.28.0±4.10.749
APACHE Ⅱ评分(分, x±s)21.4±8.319.7±7.321.0±8.10.284
入ICU时接受机械通气[例(%)]87(73.7)26(72.2)113(73.4)0.858
入科6 h内启动抗凝治疗[例(%)]53(44.9)18(50.0)71(46.1)0.622
入科6 h内行CRRT[例(%)]27(22.9)8(22.2)35(22.7)0.934
H0 CTTG( ℃, x±s)9.68±3.0011.23±2.4410.40±2.950.005
H0 TRTG(℃, x±s)3.20±3.301.80±2.363.32±3.100.007
H6 CTTG(℃, x±s)9.30±3.3310.45±2.849.45±3.270.021
H6 TRTG(℃, x±s)4.80±3.563.45±2.694.10±3.460.005
CTTG差值[℃, M(Q1, Q3)]a-0.70(-1.95, 0.40)-0.85(-1.80, 0.40)-0.70(-1.90, 0.40)0.784
TRTG差值[℃, M(Q1, Q3)]b0.80(0.20, 2.00)0.85(-0.18, 1.98)0.80(0, 2.0)0.642
), ArticleFig(id=1190330565824975140, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310108811858719, language=CN, label=表1, caption=

脓毒症或脓毒性休克患者存活组和非存活组的临床特征

, figureFileSmall=null, figureFileBig=null, tableContent=
指标存活组(n=118)非存活组(n=36)合计(n=154)P
性别[例(%)]0.230
男83(70.3)29(80.6)112(72.7)
女35(29.7)7(19.4)42(27.3)
年龄(岁, x±s)59.0(17.4)61.4(12.2)59.6(16.3)0.742
BMI[kg/m2, M(Q1, Q3)]23.0(20.7, 24.6)23.4(22.0, 25.0)23.0(20.9, 24.6)0.458
原发感染部位[例(%)]0.749
腹部56(47.5)16(44.4)72(46.8)
肺部43(36.4)13(36.1)56(36.4)
泌尿道3(2.5)3(8.3)6(3.9)
皮肤软组织6(5.1)2(5.6)8(5.2)
其他10(8.5)2(5.6)12(7.8)
慢性基础疾病[例(%)]
高血压39(33.1)11(30.6)50(32.5)0.780
糖尿病20(16.9)6(16.7)26(16.9)0.969
心血管疾病11(9.3)1(2.8)12(7.8)0.201
肺部疾病7(5.9)2(5.6)9(5.8)0.933
脑血管疾病9(7.6)3(8.3)12(7.8)0.890
慢性肾衰竭终末期4(3.4)1(2.8)5(3.2)0.857
恶性肿瘤15(12.7)4(11.1)19(12.3)0.799
HR(次/min, x±s)105.7±23.9105.8±19.1105.7±22.80.971
MAP(mmHg, x±s)82.6±14.584.3±15.983.0±14.80.547
NE[μg/(kg.min), M(Q1, Q3)]0.1(0, 0.2)0.2(0.2, 0.5)0.1(0, 0.2)0.004
RR(次/min, x±s)19.1±7.319.3±6.719.1±7.10.884
CVP[mmHg, M(Q1, Q3)]8.0(6.0, 11.0)8.9(6.0, 11.0)8.0(6.0, 11.0)0.932
WBC[×109/L, M(Q1, Q3)]11.0(5.0, 16.0)11.5(5.7, 18.5)11.0(5.0, 16.0)0.718
PLT[×109/L, M(Q1, Q3)]154.0(105.5, 226.0)96.5(37.8, 195.8)146.0(71.8, 218.8)0.016
CRP(mg/L, x±s)158.2±103.8163.4±100.6159.4±102.80.792
PCT[ng/ml, M(Q1, Q3)]9.0(1.8, 44.9)12.5(3.0, 83.9)9.6(2.0, 48.5)0.287
IL-6 [pg/ml, M(Q1, Q3)]429.0(92.9, 1686.6)332.5(69.5, 1150.0)404.0(91.1, 1403.3)0.510
SOFA(分, x±s)8.1±4.17.8±4.28.0±4.10.749
APACHE Ⅱ评分(分, x±s)21.4±8.319.7±7.321.0±8.10.284
入ICU时接受机械通气[例(%)]87(73.7)26(72.2)113(73.4)0.858
入科6 h内启动抗凝治疗[例(%)]53(44.9)18(50.0)71(46.1)0.622
入科6 h内行CRRT[例(%)]27(22.9)8(22.2)35(22.7)0.934
H0 CTTG( ℃, x±s)9.68±3.0011.23±2.4410.40±2.950.005
H0 TRTG(℃, x±s)3.20±3.301.80±2.363.32±3.100.007
H6 CTTG(℃, x±s)9.30±3.3310.45±2.849.45±3.270.021
H6 TRTG(℃, x±s)4.80±3.563.45±2.694.10±3.460.005
CTTG差值[℃, M(Q1, Q3)]a-0.70(-1.95, 0.40)-0.85(-1.80, 0.40)-0.70(-1.90, 0.40)0.784
TRTG差值[℃, M(Q1, Q3)]b0.80(0.20, 2.00)0.85(-0.18, 1.98)0.80(0, 2.0)0.642
), ArticleFig(id=1190330565938221350, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310108811858719, language=EN, label=Tab.2, caption=

Cox regression analysis of 28 d mortality of patients with sepsis or septic shock

, figureFileSmall=null, figureFileBig=null, tableContent=
变量HR(95% CI)PaHR(95% CI)aP
SOFA评分1.15(1.06~1.25)0.001
APACHE Ⅱ评分≥15分1.09(1.05~1.13)0.0001.09(1.04~1.15)0.000
MAP0.98(0.95~1.00)0.047
NE剂量1.11(0.93~1.43)0.044
PLT0.99(0.99~1.00)0.022
血乳酸1.14(1.02~1.26)0.014
男性0.45(0.23~0.88)0.0190.40(0.21~0.80)0.009
肺部基础疾病4.08(1.57~10.59)0.0045.15(1.71~15.55)0.004
入科6 h内启动抗凝治疗0.43(0.21~0.90)0.0240.42(0.19~0.91)0.028
腹部感染0.41(0.19~0.87)0.019
肺部感染2.03(1.05~3.92)0.035
低H0 CTTG0.37(0.18~0.76)0.007
低H0 TRTG2.60(1.3~5.21)0.007
低H6 CTTG0.31(0.11~0.88)0.028
低H6 TRTG3.43(1.43~8.25)0.0063.74(1.54~9.12)0.004
), ArticleFig(id=1190330566013718824, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310108811858719, language=CN, label=表2, caption=

脓毒症及脓毒性休克患者28 d内死亡情况的Cox分析

, figureFileSmall=null, figureFileBig=null, tableContent=
变量HR(95% CI)PaHR(95% CI)aP
SOFA评分1.15(1.06~1.25)0.001
APACHE Ⅱ评分≥15分1.09(1.05~1.13)0.0001.09(1.04~1.15)0.000
MAP0.98(0.95~1.00)0.047
NE剂量1.11(0.93~1.43)0.044
PLT0.99(0.99~1.00)0.022
血乳酸1.14(1.02~1.26)0.014
男性0.45(0.23~0.88)0.0190.40(0.21~0.80)0.009
肺部基础疾病4.08(1.57~10.59)0.0045.15(1.71~15.55)0.004
入科6 h内启动抗凝治疗0.43(0.21~0.90)0.0240.42(0.19~0.91)0.028
腹部感染0.41(0.19~0.87)0.019
肺部感染2.03(1.05~3.92)0.035
低H0 CTTG0.37(0.18~0.76)0.007
低H0 TRTG2.60(1.3~5.21)0.007
低H6 CTTG0.31(0.11~0.88)0.028
低H6 TRTG3.43(1.43~8.25)0.0063.74(1.54~9.12)0.004
), ArticleFig(id=1190330566093410602, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310108811858719, language=EN, label=Tab.3, caption=

Correlation of CTTG, TRTG difference and fluid input

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液体入量CTTG差值(℃)aTRTG差值(℃)b
rPrP
液体入量-0.0500.5370.0710.379
液体入量≥30 ml/kg或<30 ml/kg-0.0540.5080.0840.298
液体入量≥26 ml/kg或<26 ml/kg-0.0310.6980.0140.866
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液体入量与CTTG差值、TRTG差值的相关性

, figureFileSmall=null, figureFileBig=null, tableContent=
液体入量CTTG差值(℃)aTRTG差值(℃)b
rPrP
液体入量-0.0500.5370.0710.379
液体入量≥30 ml/kg或<30 ml/kg-0.0540.5080.0840.298
液体入量≥26 ml/kg或<26 ml/kg-0.0310.6980.0140.866
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外周-室温体温梯度对脓毒症患者28 d内死亡的预测价值：一项单中心前瞻性观察性临床研究
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李露兰 1 , 刘易林 2 , 刘勇 3 , 陈少武 4 , 胡鸿彬 1 , 曾振华 1, *
解放军医学杂志 | 临床研究 2025,50(5): 536-544
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解放军医学杂志 | 临床研究 2025, 50(5): 536-544
外周-室温体温梯度对脓毒症患者28 d内死亡的预测价值：一项单中心前瞻性观察性临床研究
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李露兰1, 刘易林2, 刘勇3, 陈少武4, 胡鸿彬1, 曾振华1, *
作者信息
  • 1南方医科大学南方医院重症医学科，广东广州 510515
  • 2粤北人民医院重症医学科，广东韶关 512000
  • 3南方医科大学深圳医院重症医学科，广东深圳 518101
  • 4云浮市人民医院重症医学科，广东云浮　527399;[临床试验注册号] NCT04068298

    • 李露兰，医学博士，主治医师，主要从事脓毒症方面的研究

通讯作者:

曾振华，E-mail：
Predictive value of toe-to-room temperature gradient for 28 d mortality in sepsis patients: a single center prospective observational clinical study
Lu-Lan Li1, Yi-Lin Liu2, Yong Liu3, Shao-Wu Chen4, Hong-Bin Hu1, Zhen-Hua Zeng1, *
Affiliations
  • 1Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
  • 2Department of Critical Care Medicine, Yuebei People's Hospital, Shaoguan, Guangdong 512000, China
  • 3Department of Critical Care Medicine, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong 518101, China
  • 4Department of Critical Care Medicine, Yunfu People's Hospital, Yunfu, Guangdong 527399, China
出版时间: 2025-05-28 doi: 10.11855/j.issn.0577-7402.0620.2025.0114
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摘要
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目的 探讨体温梯度对脓毒症患者病死率的预测价值及其与液体入量的相关性。方法 采用前瞻性观察方法，纳入南方医科大学南方医院重症医学科2019年11月-2021年11月收治的154例脓毒症或脓毒性休克患者作为研究对象，根据28 d内是否存活分为存活组(n=118)与非存活组(n=36)。在入重症监护室(简称入科)即刻及入科6 h监测和计算中心-外周体温梯度(CTTG)、外周-室温体温梯度(TRTG)，采用受试者操作特征(ROC)曲线探讨体温梯度对死亡的预测价值，采用多因素Cox回归分析探讨脓毒症患者28 d内死亡的危险因素，进一步通过生存分析进行验证，并采用Spearman相关分析探讨体温梯度与液体入量、去甲肾上腺素剂量的相关性。结果 154例患者中，存活组118例，非存活组36例。ROC曲线和多因素Cox回归显示，入科6 h的TRTG≤5.35 ℃是28 d内死亡的危险因素。入科6 h后，与TRTG(>5.35 ℃)相比，低TRTG(≤5.35 ℃)患者的28 d内死亡风险增加了2.74倍(P=0.004，95%CI 1.54~9.12)。入科即刻及入科6 h的CTTG、TRTG均与液体入量、去甲肾上腺素剂量相关不明显(P>0.05)。结论 脓毒症患者入科6 h的TRTG≤5.35 ℃是28 d内死亡的危险因素，但不同时间点体温梯度的改善均与患者液体入量不相关。

脓毒症  /  体温梯度  /  液体复苏  /  皮肤温度

Objective To investigate the predictive value of temperature gradients on the mortality of sepsis patients and their correlation with fluid input. Methods By means of a prospective observational method, 154 patients with sepsis or septic shock admitted to the Department of Critical Care Medicine at Nanfang Hospital, Southern Medical University from November 2019 to November 2021 were included as research subjects. They were divided into a survivor group (n=118) and a non-survivor group (n=36) according to whether they survived within 28 days. The core-to-toe temperature gradient (CTTG) and toe-to-room temperature gradient (TRTG) were monitored and calculated immediately upon admission to the intensive care unit (ICU) and 6 hours after admission. Receiver operating characteristic (ROC) curve was used to explore the predictive value of temperature gradients on mortality, and multivariate Cox regression analysis was performed to explore the risk factors of 28-day mortality in sepsis patients. The results were verified through survival analysis. Correlation analysis and multivariate analysis of variance were used to explore the correlation between temperature gradients and fluid input, as well as noradrenaline doses. Results Among the 154 patients, 118 survived within 28 days (survivor group), and 36 died (non-survivor group). ROC curve and multivariate Cox regression analysis showed that a toe-to-room temperature gradient of ≤5.35 ℃ within 6 hours after admission was a risk factor for 28-day mortality. Compared with patients with a high toe-to-room temperature gradient (>5.35 ℃), patients with a low toe-to-room temperature gradient (≤5.35 ℃) had a 2.74-fold increase in the risk of 28-day mortality (P=0.004, 95%CI 1.54, 9.12). The CTTG and TRTG upon admission to the ICU and 6 hours after admission were not significantly associated with fluid input or noradrenaline doses (P>0.05). Conclusions A toe-to-room temperature gradient of less than or equal to 5.35 ℃ within 6 hours after ICU admission is a risk factor for 28-day mortality in sepsis patients. The improvement of temperature gradients at different time points is not associated with fluid input.

sepsis  /  temperature gradient  /  fluid resuscitation  /  skin temperature
李露兰, 刘易林, 刘勇, 陈少武, 胡鸿彬, 曾振华. 外周-室温体温梯度对脓毒症患者28 d内死亡的预测价值：一项单中心前瞻性观察性临床研究. 解放军医学杂志, 2025 , 50 (5) : 536 -544 . DOI: 10.11855/j.issn.0577-7402.0620.2025.0114
Lu-Lan Li, Yi-Lin Liu, Yong Liu, Shao-Wu Chen, Hong-Bin Hu, Zhen-Hua Zeng. Predictive value of toe-to-room temperature gradient for 28 d mortality in sepsis patients: a single center prospective observational clinical study[J]. Medical Journal of Chinese People’s Liberation Army, 2025 , 50 (5) : 536 -544 . DOI: 10.11855/j.issn.0577-7402.0620.2025.0114
正文
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脓毒症是机体对感染反应失调引起的危及生命的器官功能障碍[1-2]，脓毒性休克是其严重形式[3]，病死率可高达38%[4]。早期识别、诊断和及时的液体复苏是治疗的关键。其中，液体复苏通过快速补充液体纠正血容量不足，保证心输出量和器官灌注[4]。微循环功能障碍和组织低灌注在脓毒症的病理生理中起重要作用，是导致器官衰竭和患者死亡的重要因素[6-7]。研究表明，中心-外周体温梯度(core-to-toe temperature gradient，CTTG)与微循环参数[如血乳酸、毛细血管再充盈时间(CRT)、皮肤花斑评分]呈明显正相关，而外周-室温体温梯度(toe-to-room temperature gradient，TRTG)则与这些指标呈负相关，提示体温梯度可作为反映组织灌注状况的一个潜在指标[8]，然而，目前关于体温梯度与脓毒症病死率预测和液体复苏效果关系的研究较少，体温梯度对脓毒症患者液体复苏效果及预后的影响尚不明确。鉴于此，本研究探讨CTTG及TRTG预测ICU脓毒症患者28 d内死亡的价值，并探讨体温梯度与脓毒症患者液体入量、去甲肾上腺素(NE)剂量的相关性，为体温梯度在ICU脓毒症患者中的应用提供试验依据。
1 资料与方法
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1.1 研究设计
本研究为前瞻性观察性临床研究。所有受试者或受试者家属(当受试者本人无法提供知情同意时)均签署知情同意书，并被告知受试者将匿名参与此研究，相关个人信息及图片仅用于学术研究。本研究已获南方医科大学南方医院伦理委员会审批(NFEC-2019-062)。
1.2 研究对象
将2019年11月-2021年11月入住南方医科大学南方医院综合ICU的脓毒症或脓毒性休克患者作为研究对象。纳入标准：(1)年龄≥18岁；(2)2 h内获得知情同意，符合脓毒症或脓毒性休克诊断标准。排除标准：(1)已证实的怀孕或尿妊娠试验阳性；(2)低体温(中心体温<35 ℃)或存在中枢性发热；(3)患有影响外周灌注评估的疾病，如下肢血管闭塞性脉管炎、多发性大动脉炎、雷诺病；(4)任何限制使用液体复苏的疾病，如心衰竭[美国纽约心脏病学会(New York Heart Association，NYHA)分级Ⅲ-Ⅳ级]、心脏大手术后、心肺复苏术后、严重心脏疾病等[9]。
脓毒症诊断标准：(1)存在感染或可疑感染；(2)脓毒症相关性器官衰竭评价(sepsis-related organ failure assessment，SOFA)评分≥2分。脓毒性休克诊断标准：脓毒症患者经充分容量复苏后仍存在持续性低血压，需缩血管药物维持平均动脉压(mean arterial pressure，MAP)≥65 mmHg且血乳酸>2 mmol/L。
所有受试者均随访28 d，若受试者在第28天前自ICU出院，其生存状况通过电话联系的方式获得。
1.3 研究方案
根据SSC2021年拯救脓毒症指南[2]，由南方医科大学南方医院重症医学科医师按照指南的推荐对脓毒症/脓毒性休克患者进行治疗，以液体复苏的起始时间为H0，液体复苏的第1小时为H1，以此类推。
对脓毒症/脓毒性休克导致的低灌注进行液体复苏，以晶体液作为复苏的首选液体，由主管医师决定是否输注人血白蛋白注射液，并使用床旁超声心动图和(或)脉搏指示连续心排血量监测(pulse index continuous cardiac output，PICCO)等动态指标来进行血流动力学监测。使用NE作为血管活性药物使患者状态达到预期初始值(MAP≥65 mmHg)。在不延迟使用抗生素的情况下，在使用前常规进行微生物培养(包括血培养)，在确诊后1 h内进行静脉抗生素治疗，推荐使用一种或多种广谱抗生素。在无法达到血流动力学稳定时可使用氢化可的松(200 mg/d)。控制血糖≤180 mg/dl(10 mmol/L)，待血糖水平达到稳定后每隔4 h对血糖进行监测并记录。对于无禁忌证的患者可使用低分子肝素预防静脉血栓。必要时进行机械通气、连续性肾脏替代治疗(continuous renal replacement therapy，CRRT)等多脏器支持治疗[2]。
1.4 数据收集
所有研究对象均严格按照要求记录基本资料及临床检查结果等相关资料，储存每一位研究对象的原始资料，由研究人员做好专门记录，进行核查工作，包括数据完整性和逻辑性核查，录入人员要及时录入临床研究报告表，对于关键数据则由第二人独立进行核对确认。(1)收集受试者的一般临床资料，包括性别、年龄、身高、体重、基础疾病等。(2)确诊为脓毒症/脓毒性休克后液体复苏开始时(入科时，H0)及液体复苏开始后6 h(入科6 h时，H6)测量中心体温(血温或直肠温度)、外周(大脚趾)及室温(恒定在20~24 ℃)并进行记录，计算出CTTG、TRTG。其中，中心温度通过有创血流动力学测量血温或直肠体温探头测量直肠温度得到，外周温度通过皮肤温度传感器测量受试者大脚趾腹面得到，室温维持在20~24 ℃的相对恒温条件下，在测量和记录中心温度及外周温度的同时记录当下的室温。体温梯度计算公式为：CTTG=中心温度-外周温度，TRTG=外周温度-室温[9]。(3)评估收治6 h内SOFA和首个24 h急性生理学和慢性健康状况评价Ⅱ(acute physiology and chronic health evaluation Ⅱ，APACHE Ⅱ)评分，受试者的主要感染部位、是否机械通气、是否抗凝治疗、是否接受CRRT等。(4)收集和记录6 h时的液体入量和出量，液体种类，所使用的血管活性药物种类和剂量。(5)同时记录同一时间点血压(收缩压/舒张压)、MAP、心率(HR)、呼吸频率(RR)、血氧饱和度(SpO2)、中心静脉压(CVP)、尿量、血乳酸、血气分析等指标。(6)收集和记录H0 的检查指标，包括血常规[白细胞计数(WBC)、中性粒细胞百分比(NEU%)、血小板计数(PLT)]、炎性指标[C反应蛋白(CRP)、降钙素原(PCT)、白细胞介素-6(IL-6)]等。(7)所有受试者均跟踪随访至入组后28 d，记录ICU入住时间、住院时间、机械通气时间、肾脏替代治疗时间，随访和记录住院及28 d病死情况。
1.5 研究终点及指标分析
主要研究终点为体温梯度能否预测脓毒症患者28 d内死亡情况：分析比较H0、H6时CTTG、TRTG的差异，筛选出与预后相关的危险因素，并进行生存分析，以评价其预测效能。次要研究终点为体温梯度与液体复苏的相关性：分别将H0、H6时的CTTG、TRTG及体温梯度差值与入科6 h内的液体入量进行相关性分析。
1.6 统计学处理
采用SPSS 22.0进行统计分析。连续变量符合正态分布者以x±s表示，不符合正态分布者以M(Q1，Q3)表示，脓毒症/脓毒性休克两组间定量变量的比较采用独立样本t检验或Mann-Whitney U检验；分类变量以例(%)表示，组间比较采用χ2检验。采用ROC曲线分析体温梯度对脓毒症患者28 d内死亡的预测价值，并根据约登指数获得体温梯度界值，采用Cox回归分析死亡相关的危险因素，在单因素Cox回归分析时以P=0.05为界值，将有统计学差异的影响因素纳入多因素Cox回归中进一步分析，得出风险比值(hazard ratio，HR)及95%可信区间(CI)。采用Spearman相关进行相关性分析。双侧检验，P<0.05为差异有统计学意义。
2 结果
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2.1 研究人群一般情况
共纳入260例患者，根据纳入、排除标准，最终纳入154例，其中28 d内存活118例(存活组)，死亡36例(非存活组)，具体流程见图1。两组最主要的感染部位为腹部和肺部；两组患者在年龄、性别、BMI、原发感染部位、慢性基础疾病、HR、RR、CVP、WBC、CRP，以及入科6 h内接受抗凝治疗、接受CRRT等差异均无统计学意义(P>0.05)。与存活组比较，非存活组患者的NE升高、PLT明显降低(P=0.016)，H0及H6时的CTTG增高、TRTG降低(P<0.05)，而两组间在H6与H0的体温梯度差值差异无统计学意义(P>0.05)(表1)。
2.2 入科6 h内体温梯度与28 d内死亡的相关性
2.2.1 H0及H6体温梯度的差异分析
28 d内非存活组H0、H6时的CTTG较存活组明显升高(H0 CTTG：P=0.005，H6 CTTG：P=0.021)，而28 d内非存活组H0、H6时的TRTG较存活组明显降低(H0 TRTG：P=0.007，H6 TRTG：P=0.005)，但两组间CTTG差值及TRTG差值差异无统计学意义(CTTG差值：P=0.784，TRTG差值：P=0.642)(图2)。
2.2.2 H0及H6体温梯度界值的探讨
进一步利用ROC曲线对H0 CTTG和H0 TRTG进行分析，结果显示，H0 CTTG的AUC为0.645(95%CI 0.645~0.747，P=0.008)，H0 TRTG的AUC为0.636(95%CI 0.538~0.734，P=0.013)(图3A、B)。根据约登指数最大得出H0 CTTG的最佳临界点为10.25 ℃，此时的约登指数为0.233，敏感度为0.694，特异度为0.538。以10.25 ℃为截点对H0 CTTG进行分组，分为低H0 CTTG组(≤10.25 ℃)与高H0 CTTG组(>10.25 ℃)。同理，得出H0 TRTG的最佳临界点为2.95 ℃，此时的约登指数为0.239，敏感度为0.573，特异度为0.667。以2.95 ℃为截点对H0 TRTG进行分组，分为低TRTG组(≤2.95℃)与高TRTG组(>2.95 ℃)。
利用ROC曲线对H6 CTTG和H6 TRTG进行分析，结果显示，H6 CTTG的AUC为0.613(95%CI 0.514~0.712，P=0.004)，H6 TRTG的AUC为0.645(95%CI 0.549~0.741，P=0.009)(图3C、D)。根据约登指数最大得出H6 CTTG的最佳临界点为7.20 ℃，此时的约登指数为0.211，敏感度为0.889，特异度为0.322。以7.20 ℃为截点对H6 CTTG进行分组，分为低H6 CTTG组(≤7.20 ℃)与高H6 CTTG组(>7.20 ℃)。同理，得出H6 TRTG的最佳临界点为5.35℃，此时的约登指数为0.274，敏感度为0.441，特异度为0.833。以5.35 ℃为截点对H6 TRTG进行分组，分为低H6 TRTG组(≤5.35 ℃)与高H6 TRTG组(>5.35 ℃)。
2.2.3 脓毒症患者28 d内死亡的危险因素分析
单因素Cox回归分析显示，低H0 CTTG组患者的死亡风险是高H0 CTTG组的0.37倍(P=0.007，95%CI 0.18~0.76)；低H0 TRTG组患者的死亡风险是高H0 TRTG的2.60倍(P=0.007，95%CI 1.30~5.21)；低H6 CTTG组患者的死亡风险是高H6 CTTG的0.31倍(P=0.028，95%CI 0.11~0.88)；低H6 TRTG组患者的死亡风险是高H6 TRTG的3.43倍(P=0.006，95%CI 1.43~8.25)。
对基线资料进行单因素分析发现，SOFA评分、APACHE Ⅱ评分≥15分、MAP、血乳酸NE剂量、PLT、性别、肺部基础疾病、原发感染来源-腹部感染、原发感染来源-肺部感染、入科6 h内启动抗凝治疗、低H0 CTTG、低H0 TRTG、低H6 CTTG和低H6 TRTG等差异有统计学意义(P<0.05)，将以上因素纳入多因素Cox回归分析，结果显示，APACHE Ⅱ评分≥15分、男性、肺部基础疾病、入科6 h内启动抗凝治疗及低H6 TRTG是28 d内死亡的危险因素(P<0.05，表2)。进一步分析，对于H6 TRTG分组，与高H6 TRTG(>5.35 ℃)组相比，低H6 TRTG(≤5.35 ℃)组患者的28 d内死亡风险增加了2.742倍(Log-rank P=0.003)(图4)。
2.3 液体复苏和体温梯度改善的相关性分析
Spearman相关性分析显示，脓毒症患者的CTTG差值、TRTG差值与入科6 h内液体入量无关(CTTG差值：P=0.537，TRTG差值：P=0.379)。进一步对液体入量进行亚组分析，第一种情况是根据指南推荐液体复苏量至少30 ml/kg，第二种情况是根据本研究液体入量的平均值26 ml/kg进行分析。Spearman相关分析结果显示，当液体复苏量分别以30 ml/kg及均值26 ml/kg为截点时，仍显示脓毒症/脓毒性休克患者的CTTG差值、TRTG差值与液体复苏量无关(P>0.05)(表3)。
2.4 CTTG和NE剂量的相关性分析
Spearman相关性分析显示，脓毒症/脓毒性休克患者H0与H6 CTTG与相应时间点的NE剂量呈现正相关趋势，但相关性均无统计学意义(H0：P=0.199；H6：P=0.139)(图5)。
3 讨论
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目前，临床上可用于帮助评估ICU患者疾病严重程度和死亡风险的监测手段包括临床检查如皮肤花斑评分、CRT，血流动力学参数(如血压、心排血量)，血乳酸水平，以及重症相关评分系统如APACHE Ⅱ评分、SOFA评分等[10]。近年来，有研究报道CTTG与脓毒性休克患者早期的MAP水平呈负相关，与NE剂量[11]、皮肤花斑评分、CRT、血乳酸水平呈正相关[12-13]。本研究结果显示，CTTG与NE剂量间虽然差异无统计学意义，但呈现出一定的正相关趋势，提示体温梯度可能可用于脓毒症患者的死亡风险预测。其中，TRTG是更精确的指标，可用于先前没有低温的患者，包括深色皮肤的患者，可提供具有良好再现性的定量信息[14]，因此，本研究以测定脚趾的皮肤温度作为外周温度，为统一测量标准，规定每位受试者均选择大脚趾腹面进行测温以减小误差。
有研究探讨了体温梯度与疾病严重程度的关系，发现与脓毒症患者相比，感染性休克患者CTTG更高，TRTG更低[9]。一项探索性试验发现膝盖-脚趾体温梯度与SOFA评分明显相关[10]。在新生儿脓毒症的诊断中，有两项前瞻性观察性临床研究报道，CTTG监测对于迟发性脓毒症的诊断具有较高的敏感度和特异度[15-16]；一篇Meta分析显示外周组织灌注指标体温梯度可用于识别脓毒症和感染性休克患者中病死率较高的患者[17]，提示体温梯度与脓毒症患者病情严重程度密切相关。进而有研究指出，体温梯度与脓毒症患者的病死率相关[9-12]，但目前的研究尚未明确具体的体温梯度界值，临床使用上尚有限。
本研究发现，APACHE Ⅱ评分>15分、男性、存在肺部基础疾病、入科6 h内启动抗凝治疗及低H6 TRTG是28 d内死亡的危险因素。在一篇回顾性多中心队列研究中，Qu等[18]收集了1194例脓毒症患者的资料进行分析，同样发现高APACHE Ⅱ评分可使28 d病死率明显增高，其他危险因素还有年龄、高乳酸血症、低血压、恶性肿瘤等。由于Qu等[18]纳入了所有脓毒症患者，且为根据血压和乳酸水平进行分组进而得出相关危险因素进行的回顾性队列研究，而本研究则是基于体温梯度与疾病严重程度和液体复苏关系为目的的前瞻性观察性临床试验，着重探讨了体温梯度对脓毒症患者死亡的预测价值。与H6 TRTG>5.35 ℃的患者比较，H6的TRTG≤5.35 ℃可使脓毒症患者28 d内的死亡风险增加2.74倍。类似地，Joly等[19]的研究也证实，TRTG与病死率相关，且非存活者TRTG较存活者低。但这两项研究仅报道了体温梯度与病死率相关，未明确具体的体温梯度值，而本研究通过ROC曲线的AUC获得体温梯度界值后，进一步通过Cox回归分析和生存分析确定了TRTG是影响28 d内死亡的危险因素，由于体温是ICU常规监测项目之一，简单易测且无创[20]，可以结合其他参数或评分对患者死亡风险作出预测，这将有助于临床诊断及评估，因此，TRTG不失为一项临床可监测的实用工具，尤其是在院前或在急诊情况下，基于临床变量(如血压、心率、体温梯度等)和实验室测量变量[乳酸、中心静脉血氧饱和度(ScvO2)等]可初步实现从大血管到微循环的病情判断，进而预测死亡风险[21]。
一项大型随机对照临床研究纳入1563例脓毒症合并低血压患者，发现相比于自由液体复苏策略，限制性液体复苏策略并不能降低90 d的死亡发生率[22]。然而，无论是哪种液体复苏策略，均以大循环改善为目标，有学者提出，尽管采用了液体复苏，仍有部分患者存在微循环障碍进而可能增加预后不良的风险[23]。为了探讨液体复苏能否改善体温梯度，本研究进一步探讨了初始及入科6 h体温梯度差值与液体复苏的关系，发现两者间无明显相关性，而拯救脓毒症指南建议脓毒症合并低血压或脓毒性休克患者在入科3 h内接受至少30 ml/kg的晶体液进行液体复苏[2]，因此，本研究将液体入量以30 ml/kg为截点分为≥30 ml/kg与<30 ml/kg进行体温梯度差值与液体复苏的相关性分析。结果发现两者间仍无相关性，且以均值26 ml/kg为截点分析时仍均无相关性。此外，有一项纳入41例脓毒性休克患者的研究发现，在6 h时CRT及CTTG恢复至正常值范围与成功复苏明显相关[24]，但该研究是以24 h乳酸正常化作为成功复苏的标志，探讨外周灌注指标CRT、CTTG与成功复苏的关系，而不是具体的液体量。本研究探讨了液体复苏量与体温梯度的相关性，结果发现液体复苏量与体温梯度并不相关，即使液体复苏量≥30 ml/kg，液体复苏依然未能改善体温梯度。由于本研究为前瞻性观察性临床试验，可能存在一些潜在的混杂因素，如液体复苏的速度、白蛋白注射液及血浆等胶体的补充，均可能影响液体复苏量与体温梯度的相关程度[25-26]，两者的具体关联及对患者结局的影响尚需进一步的随机对照试验进行验证。
此外，本研究存在一定的局限性：(1)为单中心前瞻性观察性临床试验，与随机对照试验比较，可能存在潜在的偏倚；(2)目前建议CRT可作为其他灌注指标的补充来指导液体复苏[27]，但本研究未进行CRT的评估，尽管文献[28]指出体温梯度与CRT相关性良好，结合本研究结果发现体温梯度与液体复苏量不相关，因此，本研究结论尚无法推广为液体复苏不能改善外周灌注，仍需要进一步的随机对照临床试验验证；(3)观察时间为入科6 h内，所得结果均反映的是短期内的体温梯度与相关指标的关联程度，尚需进一步研究以探讨较长时间内的体温梯度对脓毒症患者预后的影响。
综上所述，H6 TRTG≤5.35 ℃是ICU脓毒症患者28 d内死亡的危险因素。与高体温梯度(>5.35 ℃)相比，低体温梯度(≤5.35 ℃)患者的28 d内死亡风险增加了2.742倍；不同时间点的体温梯度的改善均与患者液体入量不相关。未来可在本研究的基础上进一步探讨液体复苏策略对体温梯度的长期影响，以及如何优化液体复苏以改善微循环灌注和患者预后，同时考虑其他潜在的混杂因素和不同的患者亚组，以期为临床实践提供更精确的指导。
基金
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  • 南方医科大学南方医院临床研究专项基金(2018CR047)
  • 吴阶平医学基金会临床科研专项资助基金(320.6750.18431)
文献
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参考文献 引证文献
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doi: 10.11855/j.issn.0577-7402.0620.2025.0114
  • 接收时间：2024-05-10
  • 首发时间：2025-10-29
  • 出版时间：2025-05-28
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  • 收稿日期：2024-05-10
  • 录用日期：2024-11-19
基金
Clinical Research Special Foundation of Nanfang Hospital, Southern Medical University(2018CR047)
南方医科大学南方医院临床研究专项基金(2018CR047)
Clinical Research Special Grant Fund of Wu Jie-Ping Medical Foundation(320.6750.18431)
吴阶平医学基金会临床科研专项资助基金(320.6750.18431)
作者信息
    1南方医科大学南方医院重症医学科，广东广州 510515
    2粤北人民医院重症医学科，广东韶关 512000
    3南方医科大学深圳医院重症医学科，广东深圳 518101
    4云浮市人民医院重症医学科，广东云浮　527399;[临床试验注册号] NCT04068298

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曾振华，E-mail：
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
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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