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脓毒症(sepsis)是由于宿主对细菌、真菌、病毒等感染的反应失调而引起的多器官功能障碍,具有很高的致死率,是感染致死的首要原因[1]。近年来,虽然人类在重症监护领域已经取得了长足的进步,但是严重脓毒症的总死亡率仍高达26.7%[2]。针对脓毒症的治疗,目前绝大多数仍是采用支持性疗法,临床可用的干预措施只有非常有限的几种,如液体复苏、应用抗生素和类固醇药物等。然而,这些措施往往收效甚微。因此,研发抗脓毒症新药, 改善患者预后,降低脓毒症死亡率,是目前亟待解决的问题。本文对近年来脓毒症治疗相关的研究进行综述,以期为今后抗脓毒症的研究提供思路。
Progress on the treatment of sepsis
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摘要: 脓毒症是危及人类生命的急危重症,目前脓毒症的临床治疗仍以提供支持治疗为主,但是针对脓毒症的新药研发在不断推进,针对脓毒症的免疫功能、炎症通路、凝血功能及血管内皮稳态相关治疗的研究已经取得了一定进展。该文就近年来脓毒症治疗领域的研究进展进行综述。Abstract: Sepsis is a severe and life-threatening symptom that poses a significant risk to human health. Treatment mainly involves supportive care, but research on new drugs is ongoing. Advancements have been achieved in the management of immune function, inflammatory pathway, blood coagulation, and vascular endothelial homeostasis in sepsis. The advances in the treatment of sepsis in recent years were these reviewed in this article.
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Key words:
- sepsis /
- pharmacotherapy /
- immunotherapy /
- inflammation /
- coagulation management
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[1] SINGER M, DEUTSCHMAN C S, SEYMOUR C W, et al. The third international consensus definitions for sepsis and septic shock(sepsis-3)[J]. JAMA, 2016, 315(8):801-810. doi: 10.1001/jama.2016.0287 [2] FLEISCHMANN-STRUZEK C, MELLHAMMAR L, ROSE N, et al. Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis[J]. Intensive Care Med, 2020, 46(8):1552-1562. doi: 10.1007/s00134-020-06151-x [3] EVANS L, RHODES A, ALHAZZANI W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021[J]. Intensive Care Med, 2021, 47(11):1181-1247. doi: 10.1007/s00134-021-06506-y [4] GOTTS J E, MATTHAY M A. Sepsis: pathophysiology and clinical management[J]. BMJ, 2016, 353(8059):i1585. [5] OTTO G P, SOSSDORF M, CLAUS R A, et al. The late phase of sepsis is characterized by an increased microbiological burden and death rate[J]. Crit Care, 2011, 15(4):R183. doi: 10.1186/cc10332 [6] BOOMER J S, TO K, CHANG K C, et al. Immunosuppression in patients who die of sepsis and multiple organ failure[J]. JAMA, 2011, 306(23):2594-2605. doi: 10.1001/jama.2011.1829 [7] UNSINGER J, MCGLYNN M, KASTEN K R, et al. IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis[J]. J Immunol, 2010, 184(7):3768-3779. doi: 10.4049/jimmunol.0903151 [8] KASTEN K R, PRAKASH P S, UNSINGER J, et al. Interleukin-7(IL-7) treatment accelerates neutrophil recruitment through gamma delta T-cell IL-17 production in a murine model of sepsis[J]. Infect Immun, 2010, 78(11):4714-4722. doi: 10.1128/IAI.00456-10 [9] VENET F, FORAY A P, VILLARS-MÉCHIN A, et al. IL-7 restores lymphocyte functions in septic patients[J]. J Immunol, 2012, 189(10):5073-5081. doi: 10.4049/jimmunol.1202062 [10] FRANCOIS B, JEANNET R, DAIX T, et al. Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial[J]. JCI Insight, 2018, 3(5):e98960. doi: 10.1172/jci.insight.98960 [11] DAIX T, MATHONNET A, BRAKENRIDGE S, et al. Intravenously administered interleukin-7 to reverse lymphopenia in patients with septic shock: a double-blind, randomized, placebo-controlled trial[J]. Ann Intensive Care, 2023, 13(1):17. doi: 10.1186/s13613-023-01109-w [12] ZHANG Y, LI J B, LOU J S, et al. Upregulation of programmed death-1 on T cells and programmed death ligand-1 on monocytes in septic shock patients[J]. Crit Care, 2011, 15(1):R70. doi: 10.1186/cc10059 [13] PATERA A C, DREWRY A M, CHANG K, et al. Frontline Science: Defects in immune function in patients with sepsis are associated with PD-1 or PD-L1 expression and can be restored by antibodies targeting PD-1 or PD-L1[J]. J Leukoc Biol, 2016, 100(6):1239-1254. doi: 10.1189/jlb.4HI0616-255R [14] HOTCHKISS R S, COLSTON E, YENDE S, et al. Immune checkpoint inhibition in sepsis: a phase 1b randomized, placebo-controlled, single ascending dose study of antiprogrammed cell death-ligand 1 antibody(BMS-936559)[J]. Crit Care Med, 2019, 47(5):632-642. doi: 10.1097/CCM.0000000000003685 [15] HOTCHKISS R S, COLSTON E, YENDE S, et al. Immune checkpoint inhibition in sepsis: a phase 1b randomized study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of nivolumab[J]. Intensive Care Med, 2019, 45(10):1360-1371. doi: 10.1007/s00134-019-05704-z [16] INGERSOLL M A, PLATT A M, POTTEAUX S, et al. Monocyte trafficking in acute and chronic inflammation[J]. Trends Immunol, 2011, 32(10):470-477. doi: 10.1016/j.it.2011.05.001 [17] KIM S, CHO W, KIM I, et al. Oxidized LDL induces vimentin secretion by macrophages and contributes to atherosclerotic inflammation[J]. J Mol Med, 2020, 98(7):973-983. doi: 10.1007/s00109-020-01923-w [18] DUAN Y L, LEAROYD J, MELITON A Y, et al. Inhibition of Pyk2 blocks airway inflammation and hyperresponsiveness in a mouse model of asthma[J]. Am J Respir Cell Mol Biol, 2010, 42(4):491-497. doi: 10.1165/rcmb.2008-0469OC [19] ZHU X D, BAO Y H, GUO Y C, et al. Proline-rich protein tyrosine kinase 2 in inflammation and cancer[J]. Cancers, 2018, 10(5):139. doi: 10.3390/cancers10050139 [20] ALVES G F, AIMARETTI E, EINAUDI G, et al. Pharmacological inhibition of FAK-Pyk2 pathway protects against organ damage and prolongs the survival of septic mice[J]. Front Immunol, 2022, 13:837180. doi: 10.3389/fimmu.2022.837180 [21] DING R Y, ZHAO D M, LI X X, et al. Rho-kinase inhibitor treatment prevents pulmonary inflammation and coagulation in lipopolysaccharide-induced lung injury[J]. Thromb Res, 2017, 150:59-64. doi: 10.1016/j.thromres.2016.12.020 [22] SEYMOUR C W, KENNEDY J N, WANG S, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis[J]. JAMA, 2019, 321(20):2003-2017. doi: 10.1001/jama.2019.5791 [23] LEVI M, VAN DER POLL T. Coagulation and sepsis[J]. Thromb Res, 2017, 149:38-44. doi: 10.1016/j.thromres.2016.11.007 [24] LYONS P G, MICEK S T, HAMPTON N, et al. Sepsis-associated coagulopathy severity predicts hospital mortality[J]. Crit Care Med, 2018, 46(5):736-742. doi: 10.1097/CCM.0000000000002997 [25] LEVI M, VINCENT J L, TANAKA K, et al. Effect of a recombinant human soluble thrombomodulin on baseline coagulation biomarker levels and mortality outcome in patients with sepsis-associated coagulopathy[J]. Crit Care Med, 2020, 48(8):1140-1147. doi: 10.1097/CCM.0000000000004426 [26] VINCENT J L, FRANCOIS B, ZABOLOTSKIKH I, et al. Effect of a recombinant human soluble thrombomodulin on mortality in patients with sepsis-associated coagulopathy: the SCARLET randomized clinical trial[J]. JAMA, 2019, 321(20):1993-2002. doi: 10.1001/jama.2019.5358 [27] VALERIANI E, SQUIZZATO A, GALLO A, et al. Efficacy and safety of recombinant human soluble thrombomodulin in patients with sepsis-associated coagulopathy: a systematic review and meta-analysis[J]. J Thromb Haemost, 2020, 18(7):1618-1625. doi: 10.1111/jth.14812 [28] DENIAU B, TAKAGI K, ASAKAGE A, et al. Adrecizumab: an investigational agent for the biomarker-guided treatment of sepsis[J]. Expert Opin Investig Drugs, 2021, 30(2):95-102. doi: 10.1080/13543784.2021.1857365 [29] LATERRE P F, PICKKERS P, MARX G, et al. Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial[J]. Intensive Care Med, 2021, 47(11):1284-1294. doi: 10.1007/s00134-021-06537-5
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