AINS Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie, Thieme Verlag Heft 2-2024, Jahrgang 59) ISSN 1439-1074 Seite(n) 96 bis 112 DOI: 10.1055/a-2070-3516 CareLit-Dokument-Nr: 318600 |
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Bei einer Immundysfunktion kritisch Kranker gibt es nur begrenzte therapeutische Möglichkeiten und bei Persistenz ist sie mit einer hohen Sterblichkeit assoziiert. Das Immunsystem ist das potenteste Antiinfektivum des Menschen – so ist die Kenntnis inflammatorischer Reaktionsmuster, der Besonderheiten in Prophylaxe und Therapie von Sekundärinfektionen und möglicher Therapieoptionen zur Restitution des Immunsystems hochrelevant. Abstract Critically ill patients often experience a dysregulated immune response, leading to immune dysfunction. Sepsis, trauma, severe infections, and certain medical conditions can trigger a state of systemic inflammation, known as the cytokine storm. This hyperactive immune response can cause collateral damage to healthy tissues and organs, exacerbating the patient’s condition. On the other hand, some critically ill patients may suffer from immune paralysis which can increase the risk of nosocomial infections. Fever is an evolutionary adaptation that evolved as an effective defense mechanism to fight invading pathogens. By raising body temperature, fever enhances the immune response, inhibits pathogen growth, promotes recovery, and aids in the formation of immune memory. Understanding the role of fever in the context of immune defense is crucial for optimizing medical interventions and supporting the body’s natural ability to combat infections. Future Directions: Advancements in immunology research and technology hold promise for better understanding the immune system’s complexities in critically ill patients. Personalized medicine approaches may be developed to tailor therapies to individual patients based on their immune profile, optimizing treatment outcomes. Based on recent studies prognostic parameters such as lymphocyte count, IL-10 concentration and mHLA-DR expression can be used to stratify the immunological response pattern in septic patients. Conclusion: The immune system’s response in critically ill patients is a multifaceted process, involving intricate interactions between various immune cells, cytokines, and organs. Striking the delicate balance between immune activation and suppression remains a significant challenge in clinical practice. Continued research and therapeutic innovations are vital to improve patient outcomes and reduce the burden of critical illness on healthcare systems. Kernaussagen Prognostische Parameter wie die Lymphozytenzahl, die IL-10-Konzentration und die mHLA-DR-Expression können zur Stratifizierung der immunologischen Reaktionsmuster bei septischen Patienten genutzt werden. Eine möglicherweise gegensätzliche immunologische Reaktion bezüglich verschiedener Kompartimente sollte beachtet werden. Diagnostische und therapeutische Maßnahmen beeinflussen das Immunsystem unserer Patienten relevant. Eine Kühlung fiebernder Patienten sollte nur in begründeten Ausnahmen erfolgen. Zeigt ein Patient auch im postakuten Verlauf Hinweise auf eine persistierende immunsuppressive Dysregulation (z. B. Lymphopenie, erniedrigte mHLA-DR-Werte) in Zusammenhang mit wiederkehrenden opportunistischen Infektionen, ist es wichtig, dass die entsprechende Prognose früh thematisiert wird und supportive Behandlungsoptionen gemeinsam mit dem Patienten und dessen Angehörigen besprochen werden. Schlüsselwörter kritische Erkrankung - Sepsis - Immunoseneszenz - Fieber - Sekundärinfektionen Keywords critical illness - sepsis - immune senescence - fever - immunosuppression 14 February 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Literatur 1 Weber GF, Chousterman BG, He S. et al. Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis. Science 2015; 347: 1260-1265 DOI: 10.1126/science.aaa4268. (PMID: 25766237) Google Scholar 2 Weis S, Carlos AR, Moita MR. et al. Metabolic Adaptation Establishes Disease Tolerance to Sepsis. Cell 2017; 169: 1263-1275.e14 DOI: 10.1016/j.cell.2017.05.031. (PMID: 28622511) Google Scholar 3 Baghela A, Pena OM, Lee AH. et al. Predicting sepsis severity at first clinical presentation: The role of endotypes and mechanistic signatures. EBioMedicine 2022; 75: 103776 DOI: 10.1016/j.ebiom.2021.103776. (PMID: 35027333) Google Scholar 4 Scicluna BP, van Vught LA, Zwinderman AH. et al. Classification of patients with sepsis according to blood genomic endotype: a prospective cohort study. Lancet Respir Med 2017; 5: 816-826 DOI: 10.1016/s2213-2600(17)30294-1. (PMID: 28864056) Google Scholar 5 Davenport EE, Burnham KL, Radhakrishnan J. et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med 2016; 4: 259-271 DOI: 10.1016/s2213-2600(16)00046-1. (PMID: 26917434) Google Scholar 6 Pfortmueller CA, Meisel C, Fux M. et al. Assessment of immune organ dysfunction in critical illness: utility of innate immune response markers. Intensive Care Med Exp 2017; 5: 49 DOI: 10.1186/s40635-017-0163-0. (PMID: 29063386) Google Scholar 7 Mira JC, Gentile LF, Mathias BJ. et al. Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome. Crit Care Med 2017; 45: 253-262 DOI: 10.1097/ccm.0000000000002074. (PMID: 27632674) Google Scholar 8 Conway-Morris A, Wilson J, Shankar-Hari M. Immune Activation in Sepsis. Crit Care Clin 2018; 34: 29-42 DOI: 10.1016/j.ccc.2017.08.002. (PMID: 29149940) Google Scholar 9 Schenz J, Tamulyte S, Nusshag C. et al. Population-Specific Metabolic Alterations in Professional Antigen-Presenting Cells Contribute to Sepsis-Associated Immunosuppression. Shock 2020; 53: 5-15 DOI: 10.1097/shk.0000000000001337. (PMID: 31738315) Google Scholar 10 Dimitrov E, Enchev E, Minkov G. et al. Poor Outcome Could Be Predicted by Lower Monocyte Human Leukocyte Antigen-DR Expression in Patients with Complicated Intra-Abdominal Infections: A Review. Surg Infect (Larchmt) 2020; 21: 77-80 DOI: 10.1089/sur.2019.050. (PMID: 31483200) Google Scholar 11 Tamulyte S, Kopplin J, Brenner T. et al. Monocyte HLA-DR Assessment by a Novel Point-of-Care Device Is Feasible for Early Identification of ICU Patients With Complicated Courses-AProof-of-PrincipleStudy. Front Immunol 2019; 10: 432 DOI: 10.3389/fimmu.2019.00432. (PMID: 30915080) Google Scholar 12 Jung B, Le Bihan C, Portales P. et al. Monocyte human leukocyte antigen-DR but not β-D-glucan may help early diagnosing invasive Candida infection in critically ill patients. Ann Intensive Care 2021; 11: 129 DOI: 10.1186/s13613-021-00918-1. (PMID: 34417900) Google Scholar 13 Andreu-Ballester JC, Pons-Castillo A, González-Sánchez A. et al. Lymphopenia in hospitalized patients and its relationship with severity of illness and mortality. PLoS One 2021; 16: e0256205 DOI: 10.1371/journal.pone.0256205. (PMID: 34388210) Google Scholar 14 Baïsse A, Daix T, Hernandez Padilla AC. et al. High prevalence of infections in non-COVID-19 patients admitted to the Emergency Department with severe lymphopenia. BMC Infect Dis 2022; 22: 295 DOI: 10.1186/s12879-022-07295-5. (PMID: 35346082) Google Scholar 15 Adrie C, Lugosi M, Sonneville R. et al. Persistent lymphopenia is a risk factor for ICU-acquired infections and for death in ICU patients with sustained hypotension at admission. Ann Intensive Care 2017; 7: 30 DOI: 10.1186/s13613-017-0242-0. (PMID: 28303547) Google Scholar 16 Pei F, Song W, Wang L. et al. Lymphocyte trajectories are associated with prognosis in critically ill patients: A convenient way to monitor immune status. Front Med (Lausanne) 2022; 9: 953103 DOI: 10.3389/fmed.2022.953103. (PMID: 35991659) Google Scholar 17 Tang Y, Wu J, Tian Y. et al. Predictive value of peripheral lymphocyte subsets for the disease progression in patients with sepsis. Int Immunopharmacol 2023; 117: 109922 DOI: 10.1016/j.intimp.2023.109922. (PMID: 37012888) Google Scholar 18 Nakamori Y, Park EJ, Shimaoka M. Immune Deregulation in Sepsis and Septic Shock: Reversing Immune Paralysis by Targeting PD-1/PD-L1 Pathway. Front Immunol 2020; 11: 624279 DOI: 10.3389/fimmu.2020.624279. (PMID: 33679715) Google Scholar 19 Lisowska KA, Pindel M, Pietruczuk K. et al. The influence of a single hemodialysis procedure on human T lymphocytes. Sci Rep 2019; 9: 5041 DOI: 10.1038/s41598-019-41619-x. (PMID: 30911040) Google Scholar 20 Wu H, Dong J, Yu H. et al. Single-Cell RNA and ATAC Sequencing Reveal Hemodialysis-Related Immune Dysregulation of Circulating Immune Cell Subpopulations. Front Immunol 2022; 13: 878226 DOI: 10.3389/fimmu.2022.878226. (PMID: 35720370) Google Scholar 21 Remy KE, Hall MW, Cholette J. et al. Mechanisms of red blood cell transfusion-related immunomodulation. Transfusion 2018; 58: 804-815 DOI: 10.1111/trf.14488. (PMID: 29383722) Google Scholar 22 Miller M, Singer M. Do antibiotics cause mitochondrial and immune cell dysfunction? A literature review. J Antimicrob Chemother 2022; 77: 1218-1227 DOI: 10.1093/jac/dkac025. (PMID: 35211738) Google Scholar 23 Stolk RF, van der Pasch E, Naumann F. et al. Norepinephrine Dysregulates the Immune Response and Compromises Host Defense during Sepsis. Am J Respir Crit Care Med 2020; 202: 830-842 DOI: 10.1164/rccm.202002-0339OC. (PMID: 32520577) Google Scholar 24 Gentile LF, Cuenca AG, Efron PA. et al. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care. J Trauma Acute Care Surg 2012; 72: 1491-1501 DOI: 10.1097/TA.0b013e318256e000. (PMID: 22695412) Google Scholar 25 Lian J, Yue Y, Yu W. et al. Immunosenescence: a key player in cancer development. J Hematol Oncol 2020; 13: 151 DOI: 10.1186/s13045-020-00986-z. (PMID: 33168037) Google Scholar 26 Aiello A, Farzaneh F, Candore G. et al. Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention. Front Immunol 2019; 10: 2247 DOI: 10.3389/fimmu.2019.02247. (PMID: 31608061) Google Scholar 27 Clifford KM, Dy-Boarman EA, Haase KK. et al. Challenges with Diagnosing and Managing Sepsis in Older Adults. Expert Rev Anti Infect Ther 2016; 14: 231-241 DOI: 10.1586/14787210.2016.1135052. (PMID: 26687340) Google Scholar 28 Foster MA, Bentley C, Hazeldine J. et al. Investigating the potential of a prematurely aged immune phenotype in severely injured patients as predictor of risk of sepsis. Immun Ageing 2022; 19: 60 DOI: 10.1186/s12979-022-00317-5. (PMID: 36471343) Google Scholar 29 Alpert A, Pickman Y, Leipold M. et al. A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring. Nat Med 2019; 25: 487-495 DOI: 10.1038/s41591-019-0381-y. (PMID: 30842675) Google Scholar 30 Poissy J, Damonti L, Bignon A. et al. Risk factors for candidemia: a prospective matched case-control study. Crit Care 2020; 24: 109 DOI: 10.1186/s13054-020-2766-1. (PMID: 32188500) Google Scholar 31 Mallet F, Diouf L, Meunier B. et al. Herpes DNAemia and TTV Viraemia in Intensive Care Unit Critically Ill Patients: A Single-Centre Prospective Longitudinal Study. Front Immunol 2021; 12: 698808 DOI: 10.3389/fimmu.2021.698808. (PMID: 34795661) Google Scholar 32 Raman G, Avendano EE, Chan J. et al. Risk factors for hospitalized patients with resistant or multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis. Antimicrob Resist Infect Control 2018; 7: 79 DOI: 10.1186/s13756-018-0370-9. (PMID: 29997889) Google Scholar 33 Conway Morris A, Rynne J, Shankar-Hari M. Compartmentalisation of immune responses in critical illness: does it matter?. Intensive Care Med 2022; 48: 1617-1620 DOI: 10.1007/s00134-022-06871-2. (PMID: 36050558) Google Scholar 34 Henning DJ, Carey JR, Oedorf K. et al. The Absence of Fever Is Associated With Higher Mortality and Decreased Antibiotic and IV Fluid Administration in Emergency Department Patients With Suspected Septic Shock. Crit Care Med 2017; 45: e575-e582 DOI: 10.1097/ccm.0000000000002311. (PMID: 28333759) Google Scholar 35 Drewry AM, Mohr NM, Ablordeppey EA. et al. Therapeutic Hyperthermia Is Associated With Improved Survival in Afebrile Critically Ill Patients With Sepsis: A Pilot Randomized Trial. Crit Care Med 2022; 50: 924-934 DOI: 10.1097/ccm.0000000000005470. (PMID: 35120040) Google Scholar 36 Circiumaru B, Baldock G, Cohen J. A prospective study of fever in the intensive care unit. Intensive Care Med 1999; 25: 668-673 DOI: 10.1007/s001340050928. (PMID: 10470569) Google Scholar 37 Marik PE. Fever in the ICU. Chest 2000; 117: 855-869 DOI: 10.1378/chest.117.3.855. (PMID: 10713016) Google Scholar 38 Jampel HD, Duff GW, Gershon RK. et al. Fever and immunoregulation. III. Hyperthermia augments the primary in vitro humoral immune response. J Exp Med 1983; 157: 1229-1238 DOI: 10.1084/jem.157.4.1229. (PMID: 6220108) Google Scholar 39 Schortgen F, Clabault K, Katsahian S. et al. Fever control using external cooling in septic shock: a randomized controlled trial. Am J Respir Crit Care Med 2012; 185: 1088-1095 DOI: 10.1164/rccm.201110-1820OC. (PMID: 22366046) Google Scholar 40 Holgersson J, Ceric A, Sethi N. et al. Fever therapy in febrile adults: systematic review with meta-analyses and trial sequential analyses. Bmj 2022; 378: e069620 DOI: 10.1136/bmj-2021-069620. (PMID: 35820685) Google Scholar 41 Dias A, Gomez VC, Viola LR. et al. Fever is associated with earlier antibiotic onset and reduced mortality in patients with sepsis admitted to the ICU. Sci Rep 2021; 11: 23949 DOI: 10.1038/s41598-021-03296-7. (PMID: 34907254) Google Scholar 42 Marques A, Torre C, Pinto R. et al. Treatment Advances in Sepsis and Septic Shock: Modulating Pro- and Anti-Inflammatory Mechanisms. J Clin Med 2023; 12: 2892 DOI: 10.3390/jcm12082892. (PMID: 37109229) Google Scholar 43 Becker S, Lang H, Vollmer Barbosa C. et al. Efficacy of CytoSorb®: a systematic review and meta-analysis. Crit Care 2023; 27: 215 DOI: 10.1186/s13054-023-04492-9. (PMID: 37259160) Google Scholar 44 Schädler D, Pausch C, Heise D. et al. The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial. PLoS One 2017; 12: e0187015 DOI: 10.1371/journal.pone.0187015. (PMID: 29084247) Google Scholar 45 Stahl K, Wand P, Seeliger B. et al. Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial. Crit Care 2022; 26: 134 DOI: 10.1186/s13054-022-04003-2. (PMID: 35551628) Google Scholar 46 Knaup H, Stahl K, Schmidt BMW. et al. Early therapeutic plasma exchange in septic shock: a prospective open-label nonrandomized pilot study focusing on safety, hemodynamics, vascular barrier function, and biologic markers. Crit Care 2018; 22: 285 DOI: 10.1186/s13054-018-2220-9. (PMID: 30373638) Google Scholar 47 Stahl K, Bode C, David S. Extracorporeal Strategies in Sepsis Treatment: Role of Therapeutic Plasma Exchange. Anasthesiol Intensivmed Notfallmed Schmerzther 2021; 56: 101-110 DOI: 10.1055/a-1105-0572. (PMID: 33607671) Google Scholar 48 Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324: 1029-1033 DOI: 10.1126/science.1160809. (PMID: 19460998) Google Scholar 49 O’Neill LA, Hardie DG. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 2013; 493: 346-355 DOI: 10.1038/nature11862. (PMID: 23325217) Google Scholar 50 Shapiro NI, Howell MD, Talmor D. et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med 2005; 45: 524-528 DOI: 10.1016/j.annemergmed.2004.12.006. (PMID: 15855951) Google Scholar 51 Luo P, Zhang Q, Zhong TY. et al. Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect. Mil Med Res 2022; 9: 22 DOI: 10.1186/s40779-022-00381-4. (PMID: 35596191) Google Scholar 52 Zhang Q, Luo P, Xia F. et al. Capsaicin ameliorates inflammation in a TRPV1-independent mechanism by inhibiting PKM2-LDHA-mediated Warburg effect in sepsis. Cell Chem Biol 2022; 29: 1248-1259.e6 DOI: 10.1016/j.chembiol.2022.06.011. (PMID: 35858615) Google Scholar 53 Bar-Or D, Carrick M, Tanner 2nd A. et al. Overcoming the Warburg Effect: Is it the key to survival in sepsis?. J Crit Care 2018; 43: 197-201 DOI: 10.1016/j.jcrc.2017.09.012. (PMID: 28915394) Google Scholar 54 Leventogiannis K, Kyriazopoulou E, Antonakos N. et al. Toward personalized immunotherapy in sepsis: The PROVIDE randomized clinical trial. Cell Rep Med 2022; 3: 100817 DOI: 10.1016/j.xcrm.2022.100817. (PMID: 36384100) Google Scholar 55 Kotsaki A, Pickkers P, Bauer M. et al. ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocol. BMJ Open 2022; 12: e067251 DOI: 10.1136/bmjopen-2022-067251. (PMID: 36600424) Google Scholar 56 Joshi I, Carney WP, Rock EP. Utility of monocyte HLA-DR and rationale for therapeutic GM-CSF in sepsis immunoparalysis. Front Immunol 2023; 14: 1130214 DOI: 10.3389/fimmu.2023.1130214. (PMID: 36825018) Google Scholar 57 Mathias B, Szpila BE, Moore FA. et al. A Review of GM-CSF Therapy in Sepsis. Medicine (Baltimore) 2015; 94: e2044 DOI: 10.1097/md.0000000000002044. (PMID: 26683913) Google Scholar 58 Meisel C, Schefold JC, Pschowski R. et al. Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med 2009; 180: 640-648 DOI: 10.1164/rccm.200903-0363OC. (PMID: 19590022) Google Scholar 59 Klingensmith NJ, Coopersmith CM. Gut Microbiome in Sepsis. Surg Infect (Larchmt) 2023; 24: 250-257 DOI: 10.1089/sur.2022.420. (PMID: 31306584) Google Scholar 60 Schuijt TJ, Lankelma JM, Scicluna BP. et al. The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia. Gut 2016; 65: 575-583 DOI: 10.1136/gutjnl-2015-309728. (PMID: 26511795) Google Scholar 61 Schuurman AR, Sloot PMA, Wiersinga WJ. et al. Embracing complexity in sepsis. Crit Care 2023; 27: 102 DOI: 10.1186/s13054-023-04374-0. (PMID: 36906606) Google Scholar 62 Renner C, Jeitziner MM, Albert M. et al. Guideline on multimodal rehabilitation for patients with post-intensive care syndrome. Crit Care 2023; 27: 301 DOI: 10.1186/s13054-023-04569-5. (PMID: 37525219) Google Scholar
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