入院前使用二甲双胍对糖尿病合并脓毒症患者临床结局的影响

doi:10.12114/j.issn.1007-9572.2023.0347

中国全科医学 ›› 2024, Vol. 27 ›› Issue (09): 1034-1041.DOI: 10.12114/j.issn.1007-9572.2023.0347

所属专题：内分泌代谢性疾病最新文章合集

入院前使用二甲双胍对糖尿病合并脓毒症患者临床结局的影响

何宇福¹^,², 佟文英¹^,², 王芳¹^,², 李丽霞¹^,², 何俊冰³, 邵义明¹^,^*()

1．523940　广东省东莞市，广东医科大学附属东莞第一医院重症医学科
2．524000　广东省湛江市，广东医科大学研究生院
3．522000　广东省揭阳市人民医院揭阳市医学科研中心实验室

收稿日期:2023-06-13 修回日期:2023-08-22 出版日期:2024-03-20 发布日期:2023-12-19
通讯作者: 邵义明
作者贡献：何宇福负责研究的实施与可行性分析、文章的修订和审校；佟文英、王芳负责资料收集与整理分类；李丽霞负责监督管理和结果的分析与解释；何俊冰负责数据分析和统计学处理；邵义明负责文章的构思与设计、论文撰写，对文章整体负责，监督管理。
基金资助:
国家自然科学基金资助项目(82072151)

Effects of Pre-hospital Metformin Use on Clinical Outcomes in Patients with Diabetes and Sepsis

HE Yufu¹^,², TONG Wenying¹^,², WANG Fang¹^,², LI Lixia¹^,², HE Junbing³, SHAO Yiming¹^,^*()

1. The Intensive Care Unit, the First Affiliated Dongguan Hospital of Guangdong Medical University, Dongguan 523940, China
2. Graduate School of Guangdong Medical University, Zhanjiang 524000, China
3. Jieyang Medical Research Center, Jieyang People's Hospital, Jieyang 522000, China

Received:2023-06-13 Revised:2023-08-22 Published:2024-03-20 Online:2023-12-19
Contact: SHAO Yiming

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摘要/Abstract

摘要： 背景越来越多的证据表明，入院前使用二甲双胍可降低糖尿病合并脓毒症患者的死亡率，然而，二甲双胍对糖尿病合并脓毒症患者临床结局的影响仍存在争议，因此，有必要对现有研究进行系统回顾和荟萃分析，进一步评估二甲双胍是否有利于改善糖尿病合并脓毒症患者死亡率等临床结局。目的系统评价入院前使用二甲双胍对糖尿病合并脓毒症患者死亡率、初始血浆乳酸水平和器官功能障碍等的影响。方法计算机检索PubMed、Embase、Cochrane Library、Web of Science、Scopus、中国生物医学文献服务系统、万方数据知识服务平台、中国知网以及其他数据库中二甲双胍对糖尿病合并脓毒症患者临床结局影响的相关中、英文文献，试验组（MET组）为入院前使用二甲双胍的糖尿病合并脓毒症的成年患者，对照组（NM组）为入院前未使用二甲双胍的糖尿病合并脓毒症的成年患者，检索时限为数据库建立至2023-03-15。由2名研究人员筛选、提取数据及评价文献质量后，采用RevMan 5.3软件进行Meta分析。结果本研究共纳入12篇文献，共12 320例糖尿病合并脓毒症患者，纳入文献的纽卡斯尔-渥太华量表（NOS）评分为7~8分。Meta分析结果显示：MET组患者死亡率（OR=0.61，95%CI=0.46~0.80，P<0.001）、血管升压药的使用率（OR=0.83，95%CI=0.69~0.98，P=0.03）低于NM组；MET组与NM组患者初始血浆乳酸水平（MD=0.31，95%CI=-0.12~0.75，P=0.16）、血清肌酐水平（MD=-0.81，95%CI=-0.48~0.13，P=0.25）、初始血糖水平（MD=32.94，95%CI=-10.12~76.01，P=0.13）、机械通气（OR=0.90，95%CI=0.77~1.06，P=0.23）比较，差异无统计学意义。结论入院前使用二甲双胍可以降低糖尿病合并脓毒症患者的死亡率，并可减少相应患者血管升压药的使用率，为二甲双胍可降低糖尿病合并脓毒症患者死亡率提供了全新的证据。但对于糖尿病合并脓毒症患者能否降低脓毒症严重程度评分以及减少去甲肾上腺素最大剂量仍有待进一步的研究。

关键词: 糖尿病, 脓毒症, 二甲双胍, 临床结局, 死亡率, 器官功能障碍, Meta分析

Abstract:

Background

There is growing evidence that pre-hospital use of metformin reduces mortality in patients with diabetes and sepsis; however, the effect of metformin on clinical outcomes in patients with diabetes and sepsis remains controversial. Therefore, there is a need for a systematic review and Meta-analysis of existing studies to further evaluate whether metformin can improve mortality and other clinical outcomes in patients with diabetes and sepsis.

Objective

To systematically evaluate the effects of pre-hospital metformin use on mortality, initial plasma lactate level and organ dysfunction in patients with diabetes and sepsis.

Methods

PubMed, Embase, Cochrane Library, Web of Science, Scopus, China Biomedical Literature Service System, Wanfang Data, CNKI and other databases were searched by computer for Chinese and English literature on the effects of pre-hospital metformin use on clinical outcomes in patients with sepsis and diabetes from inception to March 15, 2023. The test group (MET group) involved adult patients with diabetes and sepsis received pre-hospital metformin use, and the control group (NM group) involved adult patients with diabetes and sepsis who did not receive pre-hospital metformin use. After screening, data extraction and literature quality evaluation were conducted by two researchers, Meta-analysis was performed using RevMan 5.3 software.

Results

A total of 12 papers were included in this study, involving 12 320 patients with diabetes and sepsis, with Newcastle-Ottawa Scale (NOS) scores of 7-8. The results of Meta-analysis showed that the mortality rate (OR=0.61, 95%CI=0.46 to 0.80, P<0.001) and the use rate of vasopressors (OR=0.83, 95%CI=0.69 to 0.98, P=0.03) in MET group were lower than those in NM group; there was no significant difference in initial plasma lactate level (MD=0.31, 95%CI=-0.12 to 0.75, P=0.16) , serum creatinine level (MD=-0.81, 95%CI=-0.48 to 0.13, P=0.25) , initial blood glucose level (MD=32.94, 95%CI=-10.12 to 76.01, P=0.13) and mechanical ventilation (OR=0.90, 95%CI=0.77 to 1.06, P=0.23) between the MET group and NM group.

Conclusion

The pre-hospital use of metformin can reduce the mortality of patients with diabetes and sepsis, and reduce the use rate of vasoppressors in corresponding patients, providing updated evidence that metformin can reduce the mortality of patients with diabetes and sepsis. However, whether it can reduce the sepsis severity score and reduce the maximum dose of norepinephrine in patients with diabetes and sepsis remains to be further studied.

Key words: Diabetes mellitus, Sepsis, Metformin, Clinical outcomes, Mortality rate, Organ dysfunction, Meta-analysis

何宇福,佟文英,王芳,等. 入院前使用二甲双胍对糖尿病合并脓毒症患者临床结局的影响[J]. 中国全科医学, 2024, 27(09): 1034-1041. DOI: 10.12114/j.issn.1007-9572.2023.0347.
HE Yufu,TONG Wenying,WANG Fang, et al. Effects of Pre-hospital Metformin Use on Clinical Outcomes in Patients with Diabetes and Sepsis[J]. Chinese General Practice, 2024, 27(09): 1034-1041. DOI: 10.12114/j.issn.1007-9572.2023.0347.

图/表 11

图1 文献筛选流程图

Figure 1 Literature screening flow chart

表1 纳入文献基本特征

Table 1 Basic characteristics of included literature

第一作者	发表时间（年）	研究类型	国家	多中心/单中心	诊断	样本量（例）		研究周期（月）	主要观察指标	次要观察指标	NOS评分（分）
第一作者	发表时间（年）	研究类型	国家	多中心/单中心	诊断	MET组	NM组	研究周期（月）	主要观察指标	次要观察指标	NOS评分（分）
SCALE^[24]	2011	RC	英国	单中心	脓毒症	12	53	43	LA发生率、死亡率	②	7
GREEN^[20]	2012	RC	美国	单中心	脓毒症	192	1 755	20	28 d死亡率	①②③⑧	8
HLOCH^[25]	2012	RC	捷克共和国	单中心	感染性休克	4	21	31	死亡率	②	7
CHRISTIANSEN^[26]	2013	RC	丹麦	多中心	糖尿病；脓毒症	73	182	84	30 d死亡率	⑧	8
VAN VUGHT^[21]	2016	PO	荷兰	多中心	脓毒症	114	127	31	住院死亡率	①②⑤⑥⑦⑧	7
DOENYAS-BARAK^[27]	2016	RC	以色列	单中心	感染性休克	44	118	30	住院死亡率	①②③④⑤	8
PARK^[28]	2017	RC	韩国	单中心	严重脓毒症；感染性休克	71	1 247	73	28 d死亡率	①②③⑥⑦⑧	8
JOCHMANS^[29]	2017	RC	法国	单中心	感染性休克	52	79	38	住院死亡率	①②③④⑤⑥⑦	8
CHEN^[22]	2019	RC	中国	单中心	脓毒症；菌血症	198	392	84	28 d死亡率	②③	8
OH^[30]	2020	RC	韩国	单中心	脓毒症	1 045	1 467	48	30 d死亡率		8
YANG^[19]	2021	RC	中国	多中心	脓毒症	476	1 907	132	30 d死亡率	①②④⑥⑦⑧	7
GÓMEZ^[31]	2022	RC	美国	多中心	脓毒症	599	2 092	74	90 d死亡率	⑤	8

图2 纳入研究偏倚风险图

Figure 2 Risk of bias graph for included studies

图3 纳入研究偏倚风险汇总图注：+表示达标，-表示未达标，？表示不清楚。

Figure 3 Risk of bias summary for included studies

图4 MET组与NM组患者死亡率比较森林图

Figure 4 Forest plot comparing mortality between MET and NM patients

图5 MET组与NM组患者初始血浆乳酸水平比较森林图

Figure 5 Forest plot comparing initial plasma lactate levels between MET group and NM group

图6 MET组与NM组患者血清肌酐水平比较森林图

Figure 6 Forest plot comparing serum creatinine levels in MET group and NM group

图7 MET组与NM组患者初始血糖水平比较森林图

Figure 7 Forest plot comparing initial blood glucose levels between MET group and NM group

图8 MET组与NM组患者机械通气比较森林图

Figure 8 Forest plot comparing mechanical ventilation between MET group and NM group

图9 MET组与NM组患者血管升压药的使用率比较森林图

Figure 9 Forest plot comparing use of vasopressors between MET group and NM group

图10 二甲双胍对糖尿病合并脓毒症患者死亡率影响的漏斗图

Figure 10 Funnel plot of the effect of metformin on mortality in patients with diabetes and sepsis

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入院前使用二甲双胍对糖尿病合并脓毒症患者临床结局的影响

Effects of Pre-hospital Metformin Use on Clinical Outcomes in Patients with Diabetes and Sepsis

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