脓毒症与高血糖及其治疗的研究进展
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摘要
脓毒症及脓毒性休克是急危重症医学面临的重大难题,随着人口老龄化及医疗相关侵入性操作增加等,脓毒症的发病率逐渐增高。目前脓毒症的定义不仅局限于感染与全身炎症反应,更准确地强调机体对感染反应的失控及由此导致的器官功能障碍,其涉及的病理过程还包括神经内分泌、代谢障碍、凝血异常等非免疫方面。脓毒症及脓毒性休克的高血糖状态常见,高血糖得不到有效控制对患者预后不利。
Sepsis and septic shock are the major problems in acute and severe medical care. The incidence of sepsis is increasing as the population ages and the medical-related invasive procedures increase. At present,the definition of sepsis is not only confined to infections and systemic inflammatory response,but accurately stressed the body's response to infections resulting in loss of organ dysfunction,whose pathological process involves the aspects of neuroendocrine,metabolic disorders,coagulation abnormalities and nonimmunological diseases. Hyperglycemia is common in the patients with sepsis and septic shock,whose prognoses are usually bad if high blood sugar is not effectively controlled.
Sepsis and septic shock are the major problems in acute and severe medical care. The incidence of sepsis is increasing as the population ages and the medical-related invasive procedures increase. At present,the definition of sepsis is not only confined to infections and systemic inflammatory response,but accurately stressed the body's response to infections resulting in loss of organ dysfunction,whose pathological process involves the aspects of neuroendocrine,metabolic disorders,coagulation abnormalities and nonimmunological diseases. Hyperglycemia is common in the patients with sepsis and septic shock,whose prognoses are usually bad if high blood sugar is not effectively controlled.
引文
1 Singer M,Deutschman CS,Seymour CW,et al.The Third International Consensus Definitions for Sepsis and Septic Shock(Sepsis-3)[J].Jama,2016,315(8):801-810.
2 Zhou J,Qian C,Zhao M,et al.Epidemiology and outcome of severe sepsis and septic shock in intensive care units in mainland China[J].PLo S One,2014,9(9):e107181.
3 Zhou J,Tian H,Du X,et al.Population-Based Epidemiology of Sepsis in a Subdistrict of Beijing[J].Crit Care Med,2017,45(7):1168-1176.
4 Ofoma UR,Dahdah J,Kethireddy S,et al.Case Volume-Outcomes Associations Among Patients With Severe Sepsis Who Underwent Interhospital Transfer[J].Crit Care Med,2017,45(4):615-622.
5 Whiles BB,Deis AS,Simpson SQ.Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients[J].Crit Care Med,2017,45(4):623-629.
6 Sundén-Cullberg J,Rylance R,Svefors J,et al.Fever in the Emergency Department Predicts Survival of Patients With Severe Sepsis and Septic Shock Admitted to the ICU[J].Crit Care Med,2017,45(4):591-599.
7 Horn P,Metzing UB,Steidl R,et al.Chemerin in peritoneal sepsis and its associations with glucose metabolism and prognosis:a translational cross-sectional study[J].Critical Care,2016,20(1):39.
8 Lee SH,Park MS,Park BH,et al.Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis[J].Biomed Res Int,2015,2015:789298.
9 Malkova OG,Leǐderman IN,Levit AL,et al.Changes in lipid and carbohydrate metabolism in patients with severe sepsis of different etiology[J].Anesteziol Reanimatol,2009,(2):23-26.
10 Singamsetty S,Shah FA,Guo L,et al.Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice[J].Appl Physiol Nutr Metab,2016,41(1):12-19.
11 Tiruvoipati R,Chiezey B,Lewis D,et al.Stress hyperglycemia may not be harmful in critically ill patients with sepsis[J].J Crit Care,2012,27(2):153-158.
12 Agus MS,Wypij D,Hirshberg EL,et al.Tight Glycemic Control in Critically Ill Children[J].N Engl J Med,2017,376(8):729-741.
13 de Miguel-Yanes JM,Méndez-Bailón M,Jiménez-García R,et al.Trends in sepsis incidence and outcomes among people with or without type 2 diabetes mellitus in Spain(2008-2012)[J].Diabetes Res Clin Pract,2015,110(3):266-275.
14 van Vught LA,Wiewel MA,Klein Klouwenberg PM,et al.Admission Hyperglycemia in Critically Ill Sepsis Patients:Association With Outcome and Host Response[J].Crit Care Med,2016,44(7):1338-1346.
15 Stegenga ME,Vincent JL,Vail GM,et al.Diabetes does not alter mortality or hemostatic and inflammatory responses in patients with severe sepsis[J].Crit Care Med,2010,38(2):539-545.
16 Moreli JB,Correa-Silva S,Damasceno DC,et al.Changes in the TNF-alpha/IL-10 ratio in hyperglycemia-associated pregnancies[J].Diabetes Res Clin Pract,2015,107(3):362-369.
17 Moreli JB,Morceli G,De Luca AK,et al.Influence of maternal hyperglycemia on IL-10 and TNF-alpha production:the relationship with perinatal outcomes[J].J Clin Immunol,2012,32(3):604-610.
18 Daniele G,Guardado Mendoza R,Winnier D,et al.The inflammatory status score including IL-6,TNF-alpha,osteopontin,fractalkine,MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus[J].Acta Diabetol,2014,51(1):123-131.
19 Colak A,Akinci B,Diniz G,et al.Postload hyperglycemia is associated with increased subclinical inflammation in patients with prediabetes[J].Scand J Clin Lab Invest,2013,73(5):422-427.
20 Lin CC,Pan CS,Wang CY,et al.Tumor necrosis factor-alpha induces VCAM-1-mediated inflammation via c-Src-dependent transactivation of EGF receptors in human cardiac fibroblasts[J].J Biomed Sci,2015,22(1):53.
21 Chu DK,Al-Garawi A,Llop-Guevara A,et al.Therapeutic potential of anti-IL-6 therapies for granulocytic airway inflammation in asthma[J].Allergy Asthma Clin Immunol,2015,11(1):14.
22 Spindler MP,Ho AM,Tridgell D,et al.Acute hyperglycemia impairs IL-6 expression in humans[J].Immun Inflamm Dis,2016,4(1):91-97.
23 Liu R,Bai J,Xu G,et al.Multi-allergen challenge stimulates steriod-resistant airway inflammation via NF-kappa B-mediated IL-8 expression[J].Inflammation,2013,36(4):845-854.
24 Marchelletta RR,Gareau MG,Okamoto S,et al.Salmonella-induced Diarrhea Occurs in the Absence of IL-8 Receptor(CXCR2)-Dependent Neutrophilic Inflammation[J].J Infect Dis,2015,212(1):128-136.
25 Wu N,Shen H,Liu H,et al.Acute blood glucose fluctuation enhances rat aorta endothelial cell apoptosis,oxidative stress and proinflammatory cytokine expression in vivo[J].Cardiovasc Diabetol,2016,15(1):109.
26 Priya SP,Sakinah S,Ling MP,et al.Micro-anatomical changes in major blood vessel caused by dengue virus(serotype 2)infection[J].Acta Trop,2017,171:213-219.
27 Li Y,Hadden C,Cooper A,et al.Sepsis-induced elevation in plasma serotonin facilitates endothelial hyperpermeability[J].Sci Rep,2016,6:22747.
28 Ma N,Xing C,Xiao H,et al.C5a regulates IL-12+DC migration to induce pathogenic Th1 and Th17 cells in sepsis[J].PLo S One,2013,8(7):e69779.
29 Xu R,Lin F,Bao C,et al.Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis[J].Cell Mol Immunol,2016,13(1):103-109.
30 Rittirsch D,Flierl MA,Ward PA.Harmful molecular mechanisms in sepsis[J].Nat Rev Immunol,2008,8(10):776-787.
31 LszlóI,Trsy D,Molnr Z,et al.Sepsis:From Pathophysiology to Individualized Patient Care[J].J Immunol Res,2015,2015:510436.
32 Quoilin C,Mouithys-Mickalad A,Lecart S,et al.Evidence of oxidative stress and mitochondrial respiratory chain dysfunction in an in vitro model of sepsis-induced kidney injury[J].Biochim Biophys Acta,2014,1837(10):1790-1800.
33 Szumiel I.Ionizing radiation-induced oxidative stress,epigenetic changes and genomic instability:the pivotal role of mitochondria[J].Int J Radiat Biol,2015,91(1):1-12.
34 Lowes DA,Webster NR,Murphy MP,et al.Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress,improve mitochondrial function,and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis[J].Br J Anaesth,2013,110(3):472-480.
35 Watanabe Y,Singamsetty S,Zou B,et al.Exogenous glucose administration impairs glucose tolerance and pancreatic insulin secretion during acute sepsis in non-diabetic mice[J].PLo S One,2013,8(6):e67716.
36 Nakamura M,Oda S,Sadahiro T,et al.Correlation between high blood IL-6 level,hyperglycemia,and glucose control in septic patients[J].Crit Care,2012,16(2):R58.
37 Nackiewicz D,Dan M,He W,et al.TLR2/6 and TLR4-activated macrophages contribute to islet inflammation and impair beta cell insulin gene expression via IL-1 and IL-6[J].Diabetologia,2014,57(8):1645-1654.
38 Singamsetty S,Shah FA,Guo L,et al.Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice[J].Appl Physiol Nutr Metab,2016,41(1):12-19.
39 Sonneville R,Derese I,Marques MB,et al.Neuropathological Correlates of Hyperglycemia During Prolonged Polymicrobial Sepsis in Mice[J].Shock,2015,44(3):245-251.
40 Moriyama N,Ishihara M,Noguchi T,et al.Admission hyperglycemia is an independent predictor of acute kidney injury in patients with acute myocardial infarction[J].Circ J,2014,78(6):1475-1480.
41 Chen Y,Yang X,Meng K,et al.Stress-induced hyperglycemia after hip fracture and the increased risk of acute myocardial infarction in nondiabetic patients[J].Diabetes Care,2013,36(10):3328-3332.
42 Rossi E,Longo F,Barbagallo M,et al.Glucose availability enhances lipopolysaccharide production and immunogenicity in the opportunistic pathogen Acinetobacter baumannii[J].Future Microbiol,2016,11(3):335-349.
43 Mayer K,Weigand MA,Seeger W.How much insulin does the critical ill need?[J].Anasthesiol Intensivmed Notfallmed Schmerzther,2011,46(4):276-282.
44 Ssekitoleko R,Jacob ST,Banura P,et al.Hypoglycemia at admission is associated with inhospital mortality in Ugandan patients with severe sepsis[J].Crit Care Med,2011,39(10):2271-2276.
45 Sanches LC,Pontes Azevedo LC,Salomao R,et al.Association between early glycemic control and improvements in markers of coagulation and fibrinolysis in patients with septic shock-induced stress hyperglycemia[J].J Crit Care,2014,29(5):884,e1-e6.
46 Jiang X,Lin X,Cheng Q,et al.Effects of target blood glucose control with insulin therapy on systolic and diastolic cardiac function in septic patients[J].Zhonghua Yi Xue Za Zhi,2015,95(9):663-667.
47 Chan MC,Tseng JS,Hsu KH,et al.A minimum blood glucose value less than or equal to 120 mg/d L under glycemic control is associated with increased 14-day mortality in nondiabetic intensive care unit patients with sepsis and stress hyperglycemia[J].J Crit Care,2016,34:69-73.
48 Miranda MP,Crespo JC,Secoli SR.Insulin infusion in intensive care:randomized controlled trial[J].Rev Esc Enferm USP,2013,47(3):615-620.
2 Zhou J,Qian C,Zhao M,et al.Epidemiology and outcome of severe sepsis and septic shock in intensive care units in mainland China[J].PLo S One,2014,9(9):e107181.
3 Zhou J,Tian H,Du X,et al.Population-Based Epidemiology of Sepsis in a Subdistrict of Beijing[J].Crit Care Med,2017,45(7):1168-1176.
4 Ofoma UR,Dahdah J,Kethireddy S,et al.Case Volume-Outcomes Associations Among Patients With Severe Sepsis Who Underwent Interhospital Transfer[J].Crit Care Med,2017,45(4):615-622.
5 Whiles BB,Deis AS,Simpson SQ.Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients[J].Crit Care Med,2017,45(4):623-629.
6 Sundén-Cullberg J,Rylance R,Svefors J,et al.Fever in the Emergency Department Predicts Survival of Patients With Severe Sepsis and Septic Shock Admitted to the ICU[J].Crit Care Med,2017,45(4):591-599.
7 Horn P,Metzing UB,Steidl R,et al.Chemerin in peritoneal sepsis and its associations with glucose metabolism and prognosis:a translational cross-sectional study[J].Critical Care,2016,20(1):39.
8 Lee SH,Park MS,Park BH,et al.Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis[J].Biomed Res Int,2015,2015:789298.
9 Malkova OG,Leǐderman IN,Levit AL,et al.Changes in lipid and carbohydrate metabolism in patients with severe sepsis of different etiology[J].Anesteziol Reanimatol,2009,(2):23-26.
10 Singamsetty S,Shah FA,Guo L,et al.Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice[J].Appl Physiol Nutr Metab,2016,41(1):12-19.
11 Tiruvoipati R,Chiezey B,Lewis D,et al.Stress hyperglycemia may not be harmful in critically ill patients with sepsis[J].J Crit Care,2012,27(2):153-158.
12 Agus MS,Wypij D,Hirshberg EL,et al.Tight Glycemic Control in Critically Ill Children[J].N Engl J Med,2017,376(8):729-741.
13 de Miguel-Yanes JM,Méndez-Bailón M,Jiménez-García R,et al.Trends in sepsis incidence and outcomes among people with or without type 2 diabetes mellitus in Spain(2008-2012)[J].Diabetes Res Clin Pract,2015,110(3):266-275.
14 van Vught LA,Wiewel MA,Klein Klouwenberg PM,et al.Admission Hyperglycemia in Critically Ill Sepsis Patients:Association With Outcome and Host Response[J].Crit Care Med,2016,44(7):1338-1346.
15 Stegenga ME,Vincent JL,Vail GM,et al.Diabetes does not alter mortality or hemostatic and inflammatory responses in patients with severe sepsis[J].Crit Care Med,2010,38(2):539-545.
16 Moreli JB,Correa-Silva S,Damasceno DC,et al.Changes in the TNF-alpha/IL-10 ratio in hyperglycemia-associated pregnancies[J].Diabetes Res Clin Pract,2015,107(3):362-369.
17 Moreli JB,Morceli G,De Luca AK,et al.Influence of maternal hyperglycemia on IL-10 and TNF-alpha production:the relationship with perinatal outcomes[J].J Clin Immunol,2012,32(3):604-610.
18 Daniele G,Guardado Mendoza R,Winnier D,et al.The inflammatory status score including IL-6,TNF-alpha,osteopontin,fractalkine,MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus[J].Acta Diabetol,2014,51(1):123-131.
19 Colak A,Akinci B,Diniz G,et al.Postload hyperglycemia is associated with increased subclinical inflammation in patients with prediabetes[J].Scand J Clin Lab Invest,2013,73(5):422-427.
20 Lin CC,Pan CS,Wang CY,et al.Tumor necrosis factor-alpha induces VCAM-1-mediated inflammation via c-Src-dependent transactivation of EGF receptors in human cardiac fibroblasts[J].J Biomed Sci,2015,22(1):53.
21 Chu DK,Al-Garawi A,Llop-Guevara A,et al.Therapeutic potential of anti-IL-6 therapies for granulocytic airway inflammation in asthma[J].Allergy Asthma Clin Immunol,2015,11(1):14.
22 Spindler MP,Ho AM,Tridgell D,et al.Acute hyperglycemia impairs IL-6 expression in humans[J].Immun Inflamm Dis,2016,4(1):91-97.
23 Liu R,Bai J,Xu G,et al.Multi-allergen challenge stimulates steriod-resistant airway inflammation via NF-kappa B-mediated IL-8 expression[J].Inflammation,2013,36(4):845-854.
24 Marchelletta RR,Gareau MG,Okamoto S,et al.Salmonella-induced Diarrhea Occurs in the Absence of IL-8 Receptor(CXCR2)-Dependent Neutrophilic Inflammation[J].J Infect Dis,2015,212(1):128-136.
25 Wu N,Shen H,Liu H,et al.Acute blood glucose fluctuation enhances rat aorta endothelial cell apoptosis,oxidative stress and proinflammatory cytokine expression in vivo[J].Cardiovasc Diabetol,2016,15(1):109.
26 Priya SP,Sakinah S,Ling MP,et al.Micro-anatomical changes in major blood vessel caused by dengue virus(serotype 2)infection[J].Acta Trop,2017,171:213-219.
27 Li Y,Hadden C,Cooper A,et al.Sepsis-induced elevation in plasma serotonin facilitates endothelial hyperpermeability[J].Sci Rep,2016,6:22747.
28 Ma N,Xing C,Xiao H,et al.C5a regulates IL-12+DC migration to induce pathogenic Th1 and Th17 cells in sepsis[J].PLo S One,2013,8(7):e69779.
29 Xu R,Lin F,Bao C,et al.Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis[J].Cell Mol Immunol,2016,13(1):103-109.
30 Rittirsch D,Flierl MA,Ward PA.Harmful molecular mechanisms in sepsis[J].Nat Rev Immunol,2008,8(10):776-787.
31 LszlóI,Trsy D,Molnr Z,et al.Sepsis:From Pathophysiology to Individualized Patient Care[J].J Immunol Res,2015,2015:510436.
32 Quoilin C,Mouithys-Mickalad A,Lecart S,et al.Evidence of oxidative stress and mitochondrial respiratory chain dysfunction in an in vitro model of sepsis-induced kidney injury[J].Biochim Biophys Acta,2014,1837(10):1790-1800.
33 Szumiel I.Ionizing radiation-induced oxidative stress,epigenetic changes and genomic instability:the pivotal role of mitochondria[J].Int J Radiat Biol,2015,91(1):1-12.
34 Lowes DA,Webster NR,Murphy MP,et al.Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress,improve mitochondrial function,and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis[J].Br J Anaesth,2013,110(3):472-480.
35 Watanabe Y,Singamsetty S,Zou B,et al.Exogenous glucose administration impairs glucose tolerance and pancreatic insulin secretion during acute sepsis in non-diabetic mice[J].PLo S One,2013,8(6):e67716.
36 Nakamura M,Oda S,Sadahiro T,et al.Correlation between high blood IL-6 level,hyperglycemia,and glucose control in septic patients[J].Crit Care,2012,16(2):R58.
37 Nackiewicz D,Dan M,He W,et al.TLR2/6 and TLR4-activated macrophages contribute to islet inflammation and impair beta cell insulin gene expression via IL-1 and IL-6[J].Diabetologia,2014,57(8):1645-1654.
38 Singamsetty S,Shah FA,Guo L,et al.Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice[J].Appl Physiol Nutr Metab,2016,41(1):12-19.
39 Sonneville R,Derese I,Marques MB,et al.Neuropathological Correlates of Hyperglycemia During Prolonged Polymicrobial Sepsis in Mice[J].Shock,2015,44(3):245-251.
40 Moriyama N,Ishihara M,Noguchi T,et al.Admission hyperglycemia is an independent predictor of acute kidney injury in patients with acute myocardial infarction[J].Circ J,2014,78(6):1475-1480.
41 Chen Y,Yang X,Meng K,et al.Stress-induced hyperglycemia after hip fracture and the increased risk of acute myocardial infarction in nondiabetic patients[J].Diabetes Care,2013,36(10):3328-3332.
42 Rossi E,Longo F,Barbagallo M,et al.Glucose availability enhances lipopolysaccharide production and immunogenicity in the opportunistic pathogen Acinetobacter baumannii[J].Future Microbiol,2016,11(3):335-349.
43 Mayer K,Weigand MA,Seeger W.How much insulin does the critical ill need?[J].Anasthesiol Intensivmed Notfallmed Schmerzther,2011,46(4):276-282.
44 Ssekitoleko R,Jacob ST,Banura P,et al.Hypoglycemia at admission is associated with inhospital mortality in Ugandan patients with severe sepsis[J].Crit Care Med,2011,39(10):2271-2276.
45 Sanches LC,Pontes Azevedo LC,Salomao R,et al.Association between early glycemic control and improvements in markers of coagulation and fibrinolysis in patients with septic shock-induced stress hyperglycemia[J].J Crit Care,2014,29(5):884,e1-e6.
46 Jiang X,Lin X,Cheng Q,et al.Effects of target blood glucose control with insulin therapy on systolic and diastolic cardiac function in septic patients[J].Zhonghua Yi Xue Za Zhi,2015,95(9):663-667.
47 Chan MC,Tseng JS,Hsu KH,et al.A minimum blood glucose value less than or equal to 120 mg/d L under glycemic control is associated with increased 14-day mortality in nondiabetic intensive care unit patients with sepsis and stress hyperglycemia[J].J Crit Care,2016,34:69-73.
48 Miranda MP,Crespo JC,Secoli SR.Insulin infusion in intensive care:randomized controlled trial[J].Rev Esc Enferm USP,2013,47(3):615-620.