Understanding, assessing and treating immune, endothelial and haemostasis dysfunctions in bacterial sepsis.
Coagulation
Endothelium
Immune system
Sepsis
Journal
Intensive care medicine
ISSN: 1432-1238
Titre abrégé: Intensive Care Med
Pays: United States
ID NLM: 7704851
Informations de publication
Date de publication:
02 Sep 2024
02 Sep 2024
Historique:
received:
01
03
2024
accepted:
31
07
2024
medline:
2
9
2024
pubmed:
2
9
2024
entrez:
2
9
2024
Statut:
aheadofprint
Résumé
The interplay between the immune system, coagulation, and endothelium is critical in regulating the host response to infection. However, in sepsis and other critical illnesses, a dysregulated immune response can lead to excessive alterations in these mechanisms, resulting in coagulopathy, endothelial dysfunction, and multi-organ dysfunction. This review aims to provide a comprehensive analysis of the pathophysiological mechanisms that govern the complex interplay between immune dysfunction, endothelial dysfunction, and coagulation in sepsis. It emphasises clinical significance, evaluation methods, and potential therapeutic interventions. Understanding these mechanisms is essential for developing effective treatments that can modulate the immune response, mitigate thrombosis, restore endothelial function, and ultimately improve patient survival.
Identifiants
pubmed: 39222142
doi: 10.1007/s00134-024-07586-2
pii: 10.1007/s00134-024-07586-2
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS et al (2016) Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315:775–787. https://doi.org/10.1001/jama.2016.0289
doi: 10.1001/jama.2016.0289
pubmed: 26903336
pmcid: 4910392
Shankar-Hari M, Calandra T, Soares MP, Bauer M, Wiersinga WJ, Prescott HC, et al. Reframing sepsis immunobiology for translation: towards informative subtyping and targeted immunomodulatory therapies. The Lancet Respiratory Medicine 2024;0. https://doi.org/10.1016/S2213-2600(23)00468-X .
Engelmann B, Massberg S (2013) Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 13:34–45. https://doi.org/10.1038/nri3345
doi: 10.1038/nri3345
pubmed: 23222502
Iba T, Helms J, Levi M, Levy JH (2024) Thromboinflammation in acute injury: infections, heatstroke, and trauma. J Thromb Haemost 22:7–22. https://doi.org/10.1016/j.jtha.2023.07.020
doi: 10.1016/j.jtha.2023.07.020
pubmed: 37541590
Helms J, Iba T, Connors JM, Gando S, Levi M, Meziani F et al (2023) How to manage coagulopathies in critically ill patients. Intensive Care Med 49:273–290. https://doi.org/10.1007/s00134-023-06980-6
doi: 10.1007/s00134-023-06980-6
pubmed: 36808215
Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS et al (2004) Neutrophil extracellular traps kill bacteria. Science 303:1532–1535. https://doi.org/10.1126/science.1092385
doi: 10.1126/science.1092385
pubmed: 15001782
Meziani F, Delabranche X, Asfar P, Toti F (2010) Bench-to-bedside review: circulating microparticles—a new player in sepsis? Crit Care 14:236. https://doi.org/10.1186/cc9231
doi: 10.1186/cc9231
pubmed: 21067540
pmcid: 3219244
Zhang Y, Meng H, Ma R, He Z, Wu X, Cao M et al (2016) Circulating microparticles, blood cells, and endothelium induce procoagulant activity in sepsis through phosphatidylserine exposure. Shock 45:299–307. https://doi.org/10.1097/SHK.0000000000000509
doi: 10.1097/SHK.0000000000000509
pubmed: 26513704
Stiel L, Meziani F, Helms J (2018) Neutrophil Activation During Septic Shock. Shock 49:371–384. https://doi.org/10.1097/SHK.0000000000000980
doi: 10.1097/SHK.0000000000000980
pubmed: 28858142
Robinson N, Ganesan R, Hegedűs C, Kovács K, Kufer TA, Virág L (2019) Programmed necrotic cell death of macrophages: Focus on pyroptosis, necroptosis, and parthanatos. Redox Biol 26:101239. https://doi.org/10.1016/j.redox.2019.101239
doi: 10.1016/j.redox.2019.101239
pubmed: 31212216
pmcid: 6582207
Duprez L, Takahashi N, Van Hauwermeiren F, Vandendriessche B, Goossens V, Vanden Berghe T et al (2011) RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome. Immunity 35:908–918. https://doi.org/10.1016/j.immuni.2011.09.020
doi: 10.1016/j.immuni.2011.09.020
pubmed: 22195746
Aird WC (2003) The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 101:3765–3777. https://doi.org/10.1182/blood-2002-06-1887
doi: 10.1182/blood-2002-06-1887
pubmed: 12543869
Pape T, Hunkemöller AM, Kümpers P, Haller H, David S, Stahl K (2021) Targeting the “sweet spot” in septic shock - A perspective on the endothelial glycocalyx regulating proteins Heparanase-1 and -2. Matrix Biol Plus 12:100095. https://doi.org/10.1016/j.mbplus.2021.100095
doi: 10.1016/j.mbplus.2021.100095
pubmed: 34917926
pmcid: 8669377
Iba T, Levy JH (2019) Derangement of the endothelial glycocalyx in sepsis. J Thromb Haemost 17:283–294. https://doi.org/10.1111/jth.14371
doi: 10.1111/jth.14371
pubmed: 30582882
Delabranche X, Helms J, Meziani F (2017) Immunohaemostasis: a new view on haemostasis during sepsis. Ann Intensive Care 7:117. https://doi.org/10.1186/s13613-017-0339-5
doi: 10.1186/s13613-017-0339-5
pubmed: 29197958
pmcid: 5712298
Stahl K, Schmidt JJ, Seeliger B, Schmidt BMW, Welte T, Haller H et al (2020) Effect of therapeutic plasma exchange on endothelial activation and coagulation-related parameters in septic shock. Crit Care 24:71. https://doi.org/10.1186/s13054-020-2799-5
doi: 10.1186/s13054-020-2799-5
pubmed: 32122366
pmcid: 7053051
Yipp BG, Kubes P (2013) NETosis: how vital is it? Blood 122:2784–2794. https://doi.org/10.1182/blood-2013-04-457671
doi: 10.1182/blood-2013-04-457671
pubmed: 24009232
Hahn RG, Patel V, Dull RO (2021) Human glycocalyx shedding: Systematic review and critical appraisal. Acta Anaesthesiol Scand 65:590–606. https://doi.org/10.1111/aas.13797
doi: 10.1111/aas.13797
pubmed: 33595101
Minasyan H, Flachsbart F (2019) Blood coagulation: a powerful bactericidal mechanism of human innate immunity. Int Rev Immunol 38:3–17. https://doi.org/10.1080/08830185.2018.1533009
doi: 10.1080/08830185.2018.1533009
pubmed: 30633597
Sun H, Ringdahl U, Homeister JW, Fay WP, Engleberg NC, Yang AY et al (2004) Plasminogen is a critical host pathogenicity factor for group A streptococcal infection. Science 305:1283–1286. https://doi.org/10.1126/science.1101245
doi: 10.1126/science.1101245
pubmed: 15333838
van der Poll T, Herwald H (2014) The coagulation system and its function in early immune defense. Thromb Haemost 112:640–648. https://doi.org/10.1160/TH14-01-0053
doi: 10.1160/TH14-01-0053
pubmed: 24696161
Anglés-Cano E (1994) Overview on fibrinolysis: plasminogen activation pathways on fibrin and cell surfaces. Chem Phys Lipids 67–68:353–362. https://doi.org/10.1016/0009-3084(94)90157-0
doi: 10.1016/0009-3084(94)90157-0
pubmed: 8187235
Morser J, Gabazza EC, Myles T, Leung LLK (2010) What has been learnt from the thrombin-activatable fibrinolysis inhibitor-deficient mouse? J Thromb Haemost 8:868–876. https://doi.org/10.1111/j.1538-7836.2010.03787.x
doi: 10.1111/j.1538-7836.2010.03787.x
pubmed: 20128866
Zeerleder S, Schroeder V, Hack CE, Kohler HP, Wuillemin WA (2006) TAFI and PAI-1 levels in human sepsis. Thromb Res 118:205–212. https://doi.org/10.1016/j.thromres.2005.06.007
doi: 10.1016/j.thromres.2005.06.007
pubmed: 16009400
da Cruz DB, Helms J, Aquino LR, Stiel L, Cougourdan L, Broussard C et al (2019) DNA-bound elastase of neutrophil extracellular traps degrades plasminogen, reduces plasmin formation, and decreases fibrinolysis: proof of concept in septic shock plasma. FASEB J 33:14270–14280. https://doi.org/10.1096/fj.201901363RRR
doi: 10.1096/fj.201901363RRR
pubmed: 31682515
Mast AE, Ruf W (2022) Regulation of coagulation by tissue factor pathway inhibitor: Implications for hemophilia therapy. J Thromb Haemost 20:1290–1300. https://doi.org/10.1111/jth.15697
doi: 10.1111/jth.15697
pubmed: 35279938
pmcid: 9314982
Chalmers E, Cooper P, Forman K, Grimley C, Khair K, Minford A et al (2011) Purpura fulminans: recognition, diagnosis and management. Arch Dis Child 96:1066–1071. https://doi.org/10.1136/adc.2010.199919
doi: 10.1136/adc.2010.199919
pubmed: 21233082
Ed Rainger G, Chimen M, Harrison MJ, Yates CM, Harrison P, Watson SP, et al. The role of platelets in the recruitment of leukocytes during vascular disease. Platelets 2015;26:507–20. https://doi.org/10.3109/09537104.2015.1064881 .
Lorant DE, Topham MK, Whatley RE, McEver RP, McIntyre TM, Prescott SM et al (1993) Inflammatory roles of P-selectin. J Clin Invest 92:559–570. https://doi.org/10.1172/JCI116623
doi: 10.1172/JCI116623
pubmed: 7688760
pmcid: 294887
Peerschke EIB, Yin W, Ghebrehiwet B (2008) Platelet mediated complement activation. Adv Exp Med Biol 632:81–91. https://doi.org/10.1007/978-0-387-78952-1_7
doi: 10.1007/978-0-387-78952-1_7
pubmed: 19025116
pmcid: 2637649
Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT (2015) Complement System Part I - Molecular Mechanisms of Activation and Regulation. Front Immunol 6:262. https://doi.org/10.3389/fimmu.2015.00262
doi: 10.3389/fimmu.2015.00262
pubmed: 26082779
pmcid: 4451739
Esmon CT (2004) The impact of the inflammatory response on coagulation. Thromb Res 114:321–327. https://doi.org/10.1016/j.thromres.2004.06.028
doi: 10.1016/j.thromres.2004.06.028
pubmed: 15507261
Taylor FB, Toh CH, Hoots WK, Wada H, Levi M, Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001;86:1327–30.
Gando S, Iba T, Eguchi Y, Ohtomo Y, Okamoto K, Koseki K et al (2006) A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria. Crit Care Med 34:625–631. https://doi.org/10.1097/01.ccm.0000202209.42491.38
doi: 10.1097/01.ccm.0000202209.42491.38
pubmed: 16521260
Iba T, Levy JH, Yamakawa K, Thachil J, Warkentin TE, Levi M et al (2019) Proposal of a two-step process for the diagnosis of sepsis-induced disseminated intravascular coagulation. J Thromb Haemost 17:1265–1268. https://doi.org/10.1111/jth.14482
doi: 10.1111/jth.14482
pubmed: 31099127
Schmoch T, Möhnle P, Weigand MA, Briegel J, Bauer M, Bloos F et al (2023) The prevalence of sepsis-induced coagulopathy in patients with sepsis - a secondary analysis of two German multicenter randomized controlled trials. Ann Intensive Care 13:3. https://doi.org/10.1186/s13613-022-01093-7
doi: 10.1186/s13613-022-01093-7
pubmed: 36635426
pmcid: 9837358
Chen Y, Chen W, Ba F, Zheng Y, Zhou Y, Shi W et al (2023) Prognostic Accuracy of the Different Scoring Systems for Assessing Coagulopathy in Sepsis: A Retrospective Study. Clin Appl Thromb Hemost 29:10760296231207630. https://doi.org/10.1177/10760296231207630
doi: 10.1177/10760296231207630
pubmed: 37920943
pmcid: 10623916
Li J, Liu H, Wang N, Wang F, Shang N, Guo S et al (2024) Persistent high sepsis-induced coagulopathy and sequential organ failure assessment scores can predict the 28-day mortality of patients with sepsis: A prospective study. BMC Infect Dis 24:282. https://doi.org/10.1186/s12879-024-09154-x
doi: 10.1186/s12879-024-09154-x
pubmed: 38438863
pmcid: 10913246
Lerolle N, Nochy D, Guérot E, Bruneval P, Fagon J-Y, Diehl J-L et al (2010) Histopathology of septic shock induced acute kidney injury: apoptosis and leukocytic infiltration. Intensive Care Med 36:471–478. https://doi.org/10.1007/s00134-009-1723-x
doi: 10.1007/s00134-009-1723-x
pubmed: 19924395
Tani VM, Assis-Mendonça GR, da Silva TB, Rogerio F, De Paula EV (2017) Microvascular thrombosis in sepsis: An autopsy study. Thromb Res 156:23–25. https://doi.org/10.1016/j.thromres.2017.05.031
doi: 10.1016/j.thromres.2017.05.031
pubmed: 28578247
White KC, Serpa-Neto A, Hurford R, Clement P, Laupland KB, See E, et al. Sepsis-associated acute kidney injury in the intensive care unit: incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes. A multicenter, observational study. Intensive Care Med 2023;49:1079–89. https://doi.org/10.1007/s00134-023-07138-0 .
Helms J, Merdji H, Loewert S, Severac F, Monnier A, Kaurin J et al (2023) Disseminated intravascular coagulation is strongly associated with severe acute kidney injury in patients with septic shock. Ann Intensive Care 13:119. https://doi.org/10.1186/s13613-023-01216-8
doi: 10.1186/s13613-023-01216-8
pubmed: 38038826
pmcid: 10692023
Seymour CW, Kennedy JN, Wang S, Chang C-CH, Elliott CF, Xu Z, et al. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis. JAMA 2019;321:2003–17. https://doi.org/10.1001/jama.2019.5791 .
Langenberg C, Bagshaw SM, May CN, Bellomo R (2008) The histopathology of septic acute kidney injury: a systematic review. Crit Care 12:R38. https://doi.org/10.1186/cc6823
doi: 10.1186/cc6823
pubmed: 18325092
pmcid: 2447560
Torres LK, Pickkers P, van der Poll T (2022) Sepsis-Induced Immunosuppression. Annu Rev Physiol 84:157–181. https://doi.org/10.1146/annurev-physiol-061121-040214
doi: 10.1146/annurev-physiol-061121-040214
pubmed: 34705481
Cajander S, Kox M, Scicluna BP, Weigand MA, Mora RA, Flohé SB et al (2024) Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine. Lancet Respir Med 12:305–322. https://doi.org/10.1016/S2213-2600(23)00330-2
doi: 10.1016/S2213-2600(23)00330-2
pubmed: 38142698
Bozza FA, Salluh JI, Japiassu AM, Soares M, Assis EF, Gomes RN et al (2007) Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care 11:R49. https://doi.org/10.1186/cc5783
doi: 10.1186/cc5783
pubmed: 17448250
pmcid: 2206478
Russell JA, Fjell C, Hsu JL, Lee T, Boyd J, Thair S et al (2013) Vasopressin compared with norepinephrine augments the decline of plasma cytokine levels in septic shock. Am J Respir Crit Care Med 188:356–364. https://doi.org/10.1164/rccm.201302-0355OC
doi: 10.1164/rccm.201302-0355OC
pubmed: 23796235
Venet F, Monneret G (2018) Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol 14:121–137. https://doi.org/10.1038/nrneph.2017.165
doi: 10.1038/nrneph.2017.165
pubmed: 29225343
Grimaldi D, Pradier O, Hotchkiss RS, Vincent J-L (2017) Nivolumab plus interferon-γ in the treatment of intractable mucormycosis. Lancet Infect Dis 17:18. https://doi.org/10.1016/S1473-3099(16)30541-2
doi: 10.1016/S1473-3099(16)30541-2
pubmed: 27998559
Cusack R, Leone M, Rodriguez AH, Martin-Loeches I (2022) Endothelial Damage and the Microcirculation in Critical Illness. Biomedicines 10:3150. https://doi.org/10.3390/biomedicines10123150
doi: 10.3390/biomedicines10123150
pubmed: 36551905
pmcid: 9776078
Hinson JP, Kapas S, Smith DM (2000) Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev 21:138–167. https://doi.org/10.1210/edrv.21.2.0396
doi: 10.1210/edrv.21.2.0396
pubmed: 10782362
Valenzuela-Sánchez F, Valenzuela-Méndez B, Rodríguez-Gutiérrez JF, Estella-García Á, González-García MÁ. New role of biomarkers: mid-regional pro-adrenomedullin, the biomarker of organ failure. Ann Transl Med 2016;4:329. https://doi.org/10.21037/atm.2016.08.65 .
Fang Y, Li C, Shao R, Yu H, Zhang Q (2018) The role of biomarkers of endothelial activation in predicting morbidity and mortality in patients with severe sepsis and septic shock in intensive care: A prospective observational study. Thromb Res 171:149–154. https://doi.org/10.1016/j.thromres.2018.09.059
doi: 10.1016/j.thromres.2018.09.059
pubmed: 30312800
Chi Y, Yu S, Yin J, Liu D, Zhuo M, Li X (2024) Role of Angiopoietin/Tie2 System in Sepsis: A Potential Therapeutic Target. Clin Appl Thromb Hemost 30:10760296241238010. https://doi.org/10.1177/10760296241238010
doi: 10.1177/10760296241238010
pubmed: 38449088
pmcid: 10921858
Iba T, Nisio MD, Levy JH, Kitamura N, Thachil J (2017) New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open 7:e017046. https://doi.org/10.1136/bmjopen-2017-017046
doi: 10.1136/bmjopen-2017-017046
pubmed: 28963294
pmcid: 5623518
Iba T, Levy JH, Thachil J, Susen S, Levi M, Scarlatescu E (2023) Communication from the Scientific Standardization Committees of the International Society on Thrombosis and Haemostasis on vascular endothelium-related biomarkers in disseminated intravascular coagulation. J Thromb Haemost 21:691–699. https://doi.org/10.1016/j.jtha.2022.11.032
doi: 10.1016/j.jtha.2022.11.032
pubmed: 36696178
Vincent JL, Francois B, Zabolotskikh I, Daga MK, Lascarrou JB, Kirov MY et al (2019) Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients with Sepsis-Associated Coagulopathy: The SCARLET Randomized Clinical Trial. JAMA - Journal of the American Medical Association 321:1993–2002. https://doi.org/10.1001/jama.2019.5358
doi: 10.1001/jama.2019.5358
pubmed: 31104069
Levi M, Vincent J-L, Tanaka K, Radford AH, Kayanoki T, Fineberg DA et al (2020) Effect of a Recombinant Human Soluble Thrombomodulin on Baseline Coagulation Biomarker Levels and Mortality Outcome in Patients With Sepsis-Associated Coagulopathy. Crit Care Med 48:1140–1147. https://doi.org/10.1097/CCM.0000000000004426
doi: 10.1097/CCM.0000000000004426
pubmed: 32697484
pmcid: 7365672
Greinacher A, Selleng S (2016) How I evaluate and treat thrombocytopenia in the intensive care unit patient. Blood 128:3032–3042. https://doi.org/10.1182/blood-2016-09-693655
doi: 10.1182/blood-2016-09-693655
pubmed: 28034871
Russell L, Madsen MB, Dahl M, Kampmann P, Perner A (2018) Prediction of bleeding and thrombosis by standard biochemical coagulation variables in haematological intensive care patients. Acta Anaesthesiol Scand 62:196–206. https://doi.org/10.1111/aas.13036
doi: 10.1111/aas.13036
pubmed: 29124749
Davies GR, Lawrence M, Pillai S, Mills GM, Aubrey R, Thomas D et al (2018) The effect of sepsis and septic shock on the viscoelastic properties of clot quality and mass using rotational thromboelastometry: A prospective observational study. J Crit Care 44:7–11. https://doi.org/10.1016/j.jcrc.2017.09.183
doi: 10.1016/j.jcrc.2017.09.183
pubmed: 28988002
Müller MC, Meijers JC, Vroom MB, Juffermans NP (2014) Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review. Crit Care 18:R30. https://doi.org/10.1186/cc13721
doi: 10.1186/cc13721
pubmed: 24512650
pmcid: 4056353
Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C et al (2021) Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med 47:1181–1247. https://doi.org/10.1007/s00134-021-06506-y
doi: 10.1007/s00134-021-06506-y
pubmed: 34599691
pmcid: 8486643
Hippensteel JA, Uchimido R, Tyler PD, Burke RC, Han X, Zhang F et al (2019) Intravenous fluid resuscitation is associated with septic endothelial glycocalyx degradation. Crit Care 23:259. https://doi.org/10.1186/s13054-019-2534-2
doi: 10.1186/s13054-019-2534-2
pubmed: 31337421
pmcid: 6652002
Fisher J, Douglas JJ, Linder A, Boyd JH, Walley KR, Russell JA (2016) Elevated Plasma Angiopoietin-2 Levels Are Associated With Fluid Overload, Organ Dysfunction, and Mortality in Human Septic Shock. Crit Care Med 44:2018–2027. https://doi.org/10.1097/CCM.0000000000001853
doi: 10.1097/CCM.0000000000001853
pubmed: 27441903
Sivapalan P, Ellekjaer KL, Jessen MK, Meyhoff TS, Cronhjort M, Hjortrup PB et al (2023) Lower vs Higher Fluid Volumes in Adult Patients With Sepsis: An Updated Systematic Review With Meta-Analysis and Trial Sequential Analysis. Chest 164:892–912. https://doi.org/10.1016/j.chest.2023.04.036
doi: 10.1016/j.chest.2023.04.036
pubmed: 37142091
pmcid: 10567931
Lewis SR, Pritchard MW, Evans DJ, Butler AR, Alderson P, Smith AF, et al. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev 2018;8:CD000567. https://doi.org/10.1002/14651858.CD000567.pub7 .
Rasmussen KC, Secher NH, Pedersen T (2016) Effect of perioperative crystalloid or colloid fluid therapy on hemorrhage, coagulation competence, and outcome: A systematic review and stratified meta-analysis. Medicine (Baltimore) 95:e4498. https://doi.org/10.1097/MD.0000000000004498
doi: 10.1097/MD.0000000000004498
pubmed: 27495098
Kozek-Langenecker SA (2009) Influence of fluid therapy on the haemostatic system of intensive care patients. Best Pract Res Clin Anaesthesiol 23:225–236. https://doi.org/10.1016/j.bpa.2008.11.002
doi: 10.1016/j.bpa.2008.11.002
pubmed: 19653441
Kellum JA, Song M, Almasri E (2006) Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis. Chest 130:962–967. https://doi.org/10.1378/chest.130.4.962
doi: 10.1378/chest.130.4.962
pubmed: 17035425
Fernández-Sarmiento J, Salazar-Peláez LM, Acevedo L, Niño-Serna LF, Flórez S, Alarcón-Forero L et al (2023) Endothelial and Glycocalyx Biomarkers in Children With Sepsis After One Bolus of Unbalanced or Balanced Crystalloids. Pediatr Crit Care Med 24:213–221. https://doi.org/10.1097/PCC.0000000000003123
doi: 10.1097/PCC.0000000000003123
pubmed: 36598246
Saravi B, Goebel U, Hassenzahl LO, Jung C, David S, Feldheiser A et al (2023) Capillary leak and endothelial permeability in critically ill patients: a current overview. Intensive Care Med Exp 11:96. https://doi.org/10.1186/s40635-023-00582-8
doi: 10.1186/s40635-023-00582-8
pubmed: 38117435
pmcid: 10733291
Sandoo A, van Zanten JJCSV, Metsios GS, Carroll D, Kitas GD. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J 2010;4:302–12. https://doi.org/10.2174/1874192401004010302 .
Lambden S (2019) Bench to bedside review: therapeutic modulation of nitric oxide in sepsis-an update. Intensive Care Med Exp 7:64. https://doi.org/10.1186/s40635-019-0274-x
doi: 10.1186/s40635-019-0274-x
pubmed: 31792745
pmcid: 6888802
Coloretti I, Genovese A, Teixeira JP, Cherian A, Ferrer R, Landoni G et al (2024) Angiotensin ii therapy in refractory septic shock: which patient can benefit most? A narrative review. J Anesth Analg Crit Care 4:13. https://doi.org/10.1186/s44158-024-00150-w
doi: 10.1186/s44158-024-00150-w
pubmed: 38383521
pmcid: 10882873
Leisman DE, Privratsky JR, Lehman JR, Abraham MN, Yaipan OY, Brewer MR et al (2022) Angiotensin II enhances bacterial clearance via myeloid signaling in a murine sepsis model. Proc Natl Acad Sci U S A 119:e2211370119. https://doi.org/10.1073/pnas.2211370119
doi: 10.1073/pnas.2211370119
pubmed: 35969740
pmcid: 9407661
Stolk RF, van der Poll T, Angus DC, van der Hoeven JG, Pickkers P, Kox M (2016) Potentially Inadvertent Immunomodulation: Norepinephrine Use in Sepsis. Am J Respir Crit Care Med 194:550–558. https://doi.org/10.1164/rccm.201604-0862CP
doi: 10.1164/rccm.201604-0862CP
pubmed: 27398737
Heming N, Sivanandamoorthy S, Meng P, Bounab R, Annane D (2018) Immune Effects of Corticosteroids in Sepsis. Front Immunol 9:1736. https://doi.org/10.3389/fimmu.2018.01736
doi: 10.3389/fimmu.2018.01736
pubmed: 30105022
pmcid: 6077259
Barabutis N, Khangoora V, Marik PE, Catravas JD (2017) Hydrocortisone and Ascorbic Acid Synergistically Prevent and Repair Lipopolysaccharide-Induced Pulmonary Endothelial Barrier Dysfunction. Chest 152:954–962. https://doi.org/10.1016/j.chest.2017.07.014
doi: 10.1016/j.chest.2017.07.014
pubmed: 28739448
pmcid: 5812759
Mansart A, Bollaert PE, Seguin C, Levy B, Longrois D, Mallié JP (2003) Hemodynamic effects of early versus late glucocorticosteroid administration in experimental septic shock. Shock 19:38–44. https://doi.org/10.1097/00024382-200301000-00008
doi: 10.1097/00024382-200301000-00008
pubmed: 12558142
Lim H-Y, Müller N, Herold MJ, van den Brandt J, Reichardt HM (2007) Glucocorticoids exert opposing effects on macrophage function dependent on their concentration. Immunology 122:47–53. https://doi.org/10.1111/j.1365-2567.2007.02611.x
doi: 10.1111/j.1365-2567.2007.02611.x
pubmed: 17451463
pmcid: 2265978
Venkatesh B, Finfer S, Cohen J, Rajbhandari D, Arabi Y, Bellomo R et al (2018) Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med 378:797–808. https://doi.org/10.1056/NEJMoa1705835
doi: 10.1056/NEJMoa1705835
pubmed: 29347874
Annane D, Renault A, Brun-Buisson C, Megarbane B, Quenot J-P, Siami S et al (2018) Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med 378:809–818. https://doi.org/10.1056/NEJMoa1705716
doi: 10.1056/NEJMoa1705716
pubmed: 29490185
Pirracchio R, Annane D, Waschka AK, Lamontagne F, Arabi YM, Bollaert P-E, et al. Patient-Level Meta-Analysis of Low-Dose Hydrocortisone in Adults with Septic Shock. NEJM Evid 2023;2:EVIDoa2300034. https://doi.org/10.1056/EVIDoa2300034 .
Torres A, Sibila O, Ferrer M, Polverino E, Menendez R, Mensa J et al (2015) Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA 313:677–686. https://doi.org/10.1001/jama.2015.88
doi: 10.1001/jama.2015.88
pubmed: 25688779
Dequin P-F, Meziani F, Quenot J-P, Kamel T, Ricard J-D, Badie J et al (2023) Hydrocortisone in Severe Community-Acquired Pneumonia. N Engl J Med 388:1931–1941. https://doi.org/10.1056/NEJMoa2215145
doi: 10.1056/NEJMoa2215145
pubmed: 36942789
Saleem N, Kulkarni A, Snow TAC, Ambler G, Singer M, Arulkumaran N (2023) Effect of Corticosteroids on Mortality and Clinical Cure in Community-Acquired Pneumonia: A Systematic Review, Meta-analysis, and Meta-regression of Randomized Control Trials. Chest 163:484–497. https://doi.org/10.1016/j.chest.2022.08.2229
doi: 10.1016/j.chest.2022.08.2229
pubmed: 36087797
Lansbury L, Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Lim WS. Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database Syst Rev 2019;2:CD010406. https://doi.org/10.1002/14651858.CD010406.pub3 .
Chaudhuri D, Nei AM, Rochwerg B, Balk RA, Asehnoune K, Cadena R et al (2024) 2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia. Crit Care Med 52:e219–e233. https://doi.org/10.1097/CCM.0000000000006172
doi: 10.1097/CCM.0000000000006172
pubmed: 38240492
Rice TW, Wheeler AP, Bernard GR, Vincent J-L, Angus DC, Aikawa N et al (2010) A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis. Crit Care Med 38:1685–1694. https://doi.org/10.1097/CCM.0b013e3181e7c5c9
doi: 10.1097/CCM.0b013e3181e7c5c9
pubmed: 20562702
Shakoory B, Carcillo JA, Chatham WW, Amdur RL, Zhao H, Dinarello CA et al (2016) Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial. Crit Care Med 44:275–281. https://doi.org/10.1097/CCM.0000000000001402
doi: 10.1097/CCM.0000000000001402
pubmed: 26584195
pmcid: 5378312
François B, Lambden S, Fivez T, Gibot S, Derive M, Grouin J-M et al (2023) Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial. Lancet Respir Med 11:894–904. https://doi.org/10.1016/S2213-2600(23)00158-3
doi: 10.1016/S2213-2600(23)00158-3
pubmed: 37269870
Cui J, Wei X, Lv H, Li Y, Li P, Chen Z et al (2019) The clinical efficacy of intravenous IgM-enriched immunoglobulin (pentaglobin) in sepsis or septic shock: a meta-analysis with trial sequential analysis. Ann Intensive Care 9:27. https://doi.org/10.1186/s13613-019-0501-3
doi: 10.1186/s13613-019-0501-3
pubmed: 30725235
pmcid: 6365591
Laterre P-F, Pickkers P, Marx G, Wittebole X, Meziani F, Dugernier T et al (2021) Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial. Intensive Care Med 47:1284–1294. https://doi.org/10.1007/s00134-021-06537-5
doi: 10.1007/s00134-021-06537-5
pubmed: 34605947
pmcid: 8487806
Aman J, Peters MJL, Weenink C, van Nieuw Amerongen GP, Vonk NA (2013) Reversal of vascular leak with imatinib. Am J Respir Crit Care Med 188:1171–1173. https://doi.org/10.1164/rccm.201301-0136LE
doi: 10.1164/rccm.201301-0136LE
pubmed: 24180451
Jaimes F, De La Rosa G, Morales C, Fortich F, Arango C, Aguirre D et al (2009) Unfractioned heparin for treatment of sepsis: A randomized clinical trial (The HETRASE Study). Crit Care Med 37:1185–1196. https://doi.org/10.1097/CCM.0b013e31819c06bc
doi: 10.1097/CCM.0b013e31819c06bc
pubmed: 19242322
Tagami T, Matsui H, Horiguchi H, Fushimi K, Yasunaga H (2014) Antithrombin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study. J Thromb Haemost 12:1470–1479. https://doi.org/10.1111/jth.12643
doi: 10.1111/jth.12643
pubmed: 24943516
Ranieri VM, Thompson BT, Barie PS, Dhainaut J-F, Douglas IS, Finfer S et al (2012) Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 366:2055–2064. https://doi.org/10.1056/NEJMoa1202290
doi: 10.1056/NEJMoa1202290
pubmed: 22616830
Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001;286:1869–78. https://doi.org/10.1001/jama.286.15.1869 .
Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL et al (2003) Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 290:238–247. https://doi.org/10.1001/jama.290.2.238
doi: 10.1001/jama.290.2.238
pubmed: 12851279
Vincent J-L, Francois B, Zabolotskikh I, Daga MK, Lascarrou J-B, Kirov MY et al (2019) Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy: The SCARLET Randomized Clinical Trial. JAMA 321:1993–2002. https://doi.org/10.1001/jama.2019.5358
doi: 10.1001/jama.2019.5358
pubmed: 31104069
pmcid: 6547077
François B, Fiancette M, Helms J, Mercier E, Lascarrou J-B, Kayanoki T et al (2021) Efficacy and safety of human soluble thrombomodulin (ART-123) for treatment of patients in France with sepsis-associated coagulopathy: post hoc analysis of SCARLET. Ann Intensive Care 11:53. https://doi.org/10.1186/s13613-021-00842-4
doi: 10.1186/s13613-021-00842-4
pubmed: 33788052
pmcid: 8012451
Saito H, Maruyama I, Shimazaki S, Yamamoto Y, Aikawa N, Ohno R et al (2007) Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost 5:31–41. https://doi.org/10.1111/j.1538-7836.2006.02267.x
doi: 10.1111/j.1538-7836.2006.02267.x
pubmed: 17059423
Silasi-Mansat R, Zhu H, Popescu NI, Peer G, Sfyroera G, Magotti P et al (2010) Complement inhibition decreases the procoagulant response and confers organ protection in a baboon model of Escherichia coli sepsis. Blood 116:1002–1010. https://doi.org/10.1182/blood-2010-02-269746
doi: 10.1182/blood-2010-02-269746
pubmed: 20466856
pmcid: 2924221
Keshari RS, Silasi R, Popescu NI, Patel MM, Chaaban H, Lupu C et al (2017) Inhibition of complement C5 protects against organ failure and reduces mortality in a baboon model of Escherichia coli sepsis. Proc Natl Acad Sci U S A 114:E6390–E6399. https://doi.org/10.1073/pnas.1706818114
doi: 10.1073/pnas.1706818114
pubmed: 28720697
pmcid: 5547645