Sepsis-Trauma-Shock

Sepsis, commonly known as blood poisoning, is a complex disease during which the body abnormally reacts to an infection (bacterial, fungal, viral). During the years, the death rate in sepsis syndromes has increased and has even become higher than in acute myocardial infarctions. There are diverse phenotypes of sepsis regarding both the infectious origin as well as short-/long-term presentations and outcomes. For example, the infected host may mount an excessive immune-inflammatory response or remain immunosuppressed (or most typically feature both types of responses). Simultaneously, organs and tissues may be under-supplied with the blood, cells fail to take up sufficient oxygen from the blood and are undergo damage from self and non-self biologically active mediators circulating in the blood and lymph (so-called Pathogen Activated Molecular Patterns, PAMPs). In the clinical context, such diverse causes and phenotypes mean that the disease is difficult to diagnose and even harder to treat.

Shock, although of different pathogenesis (hypovolemic, cardiogenic, obstructive, distributive), is associated with minor perfusion and consequently oxygen deficiency of vital organs and tissue hypoxia. Hemorrhages resulting in hypovolemic shock are the common cause of microcirculatory disturbances and oxygenation deficiency in trauma patients. Trauma also triggers a production/release of multiple biologically active mediators (so-called Damage Associated Molecular Patterns; DAMPs) with a capacity to both heal and damage. This fine response balance requires an in-depth understanding so that precise diagnostic, prediction and treatment characteristics could be established for patients with various types of traumas.

Our team investigates pathological processes that underlie sepsis, shock states and acute traumas. Thereby, various molecular mechanisms are examined that cause inflammatory responses and organ failure as well as functional changes and damage in cells and subcellular organelles occurring in those critical care conditions. Further research emphasis is put on:

  • Characterizing various biomarkers and their application for prognostication of developing sepsis syndromes and predicting outcomes in septic in trauma patients
  • Modeling of the influence of comorbidities (e.g. diabetes), age and/or gender in acute states
  • Refinement and standardization of pre-clinical models for sepsis and trauma research

One ultimate aim is to enhance the pathophysiological understanding of the Sepsis-Shock-Trauma states. This consequently allows development and testing of targeted therapeutic strategies beneficially modulating the genomic, humoral and cellular signaling in in those states. This is a challenging task not only to our lab but the entire scientific community focused on the intensive care research. For example, no EMEA/FDA-approved sepsis drug specifically modulating the deranged immune-inflammatory responses in sepsis has been developed yet.

In the context of pre-clinical modeling improvements, our Wiggers-Bernard Initiative platform (coordinated by LBI for Traumatology) has recently published new guidelines for animal-based sepsis studies. Until now a large quality gap and confusion with conflicting data, reflecting the variations found in different labs, substantially hampered an efficient translation of research into the clinic. By implementing the MQTiPSS (Minimum Quality Threshold in Pre-Clinical Sepsis Studies) as Expert Consensus Guidelines, an enhanced standardization can be now implemented to pre-clinical models of sepsis worldwide. Such an improvement has a high potential to improve translation of pre-clinical findings into clinics.

The videos were produced by, and are provided with the written permission of ESICM (European Society of Intensive Care Medicine). The MQTiPSS guidelines are openly accessible in the journals Intensive Care Medicine Experimental (link to the article), Infection and Shock.

Selected Publications

Osuchowski MF, Winkler MS, Skirecki T, Cajander S, Shankar-Hari M, Lachmann G, Monneret G, Venet F, Bauer M, Brunkhorst FM, Weis S, Garcia-Salido A, Kox M, Cavaillon JM, Uhle F, Weigand MA, Flohé SB, Joost Wiersinga W, Almansa R, De la Fluente A, Martin-Loeches I, Meisel C, Spinetti T, Schefold JC, Cilloniz C, Torres A, Giamarellos-Bourboulis EJ, Ferrer R, Girardis M, Cossarizza A, Netea MG, Van der Poll T, Bermejo-Marín JF, Rubio I (2021). The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Lancet Respir Med. 2021 Jun;9(6):622-642. 
(free PDF)

Winkler MS, Skirecki T, Brunkhorst FM, Cajander S, Cavaillon JM, Ferrer R, Flohé SB, García-Salido A, Giamarellos-Bourboulis EV, Girardis M, Kox M, Lachmann G, Martin-Loeches I, Netea MG, Spinetti T, Schefold JC, Torres A, Uhle F, Venet F, Weis S, Scherag A, Rubio I, Osuchowski MF (2021). Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge. EBioMedicine2021 Apr;66:103291.
(free PDF)

Skirecki T, Drechsler S, Jeznach A, Hoser G, Jafarmadar M, Kawiak J, Osuchowski MF (2021) An Early Myelosuppression in the Acute Mouse Sepsis Is Partly Outcome-Dependent. Front. Immunol. 2021 Jul 22;12:708670.
(free PDF)

Rubio I, Osuchowski MF, Shankar-Hari M, Skirecki T, Winkler MS, Lachmann G, La Rosée P, Monneret G, Venet F, Bauer M, Brunkhorst FM, Kox M, Cavaillon JM, Uhle F, Weigand MA, Flohé SB, Wiersinga WJ, Martin-Fernandez M, Almansa R, Martin-Loeches I, Torres A, Giamarellos-Bourboulis EJ, Girardis M, Cossarizza A, Netea MG, Van der Poll T, Scherag A, Meisel C, Schefold JC, Bermejo-Martín (2019). Current gaps in sepsis immunology: new opportunities for translational research. Lancet Infect Dis2019 Dec;19(12):e422-e436.

Osuchowski MF, Ayala A, Bahrami S, Bauer M, Boros M, Cavaillon JM, Chaudry IH, Coopersmith CM, Deutschman CS, Drechsler S, Efron P, Frostell C, Fritsch G, Gozdzik W, Hellman J, Huber-Lang M, Inoue S, Knapp S, Kozlov AV, Libert C, Marshall JC, Moldawer LL, Radermacher P, Redl H, Remick DG, Singer M, Thiemermann C, Wang P, Wiersinga WJ, Xiao X, Zingarelli B. (2018). Minimum Quality Threshold in Pre-Clinical Sepsis Studies (Mqtipss): An International Expert Consensus Initiative for Improvement of Animal Modeling in Sepsis. Shock 50(4):377-380.
(free PDF)

Osuchowski MF, Thiemermann C, & Remick DG. (2017). SEPSIS-3 On the Block: What Does It Mean for Pre-Clinical Sepsis Modeling? Shock 47(5):658-660.

Drechsler S, Weixelbaumer KM, Weidinger A, Raeven P, Khadem A, Redl H, van Griensven M, Bahrami S, Remick D, Kozlov A, & Osuchowski MF. (2015). Why do they die? Comparison of selected aspects of organ injury and dysfunction in mice surviving and dying in acute abdominal sepsis. Intensive Care Med Exp, 3(1):48.
(free PDF)

Raeven P, Drechsler S, Weixelbaumer KM, Bastelica D, Peiretti F, Klotz A, Jafarmadar M, Redl H, Bahrami S, Alessi MC, Declerck PJ, & Osuchowski MF. (2014). Systemic inhibition and liver-specific over-expression of PAI-1 failed to improve survival in all-inclusive populations or homogenous cohorts of CLP mice. J Thromb Haemost, 12(6):958-969.

Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ, Kurosawa S, Stepien D, Valentine C, & Remick DG. (2013). Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding. Physiol Rev, 93(3):1247-1288.
(free full text)

Osuchowski MF, Craciun F, Weixelbaumer KM, Duffy ER, & Remick DG. (2012). Sepsis chronically in MARS: systemic cytokine responses are always mixed regardless of the outcome, magnitude, or phase of sepsis. J Immunol, 189(9):4648-4656.
(free PDF)

Drechsler S, Weixelbaumer K, Raeven P, Jafarmadar M, Khadem A, van Griensven M, Bahrami S, & Osuchowski MF. (2012). Relationship between age/gender-induced survival changes and the magnitude of inflammatory activation and organ dysfunction in post-traumatic sepsis. PLoS One, 7(12):e51457.
(free PDF)

Osuchowski MF, Connett J, Welch K, Granger J, Remick DG (2009). Stratification is the key: inflammatory biomarkers accurately direct immunomodulatory therapy in experimental sepsis. Crit Care Med2009 May;37(5):1567-73.
(free PDF)

Osuchowski MF, Welch K, Siddiqui J, Remick DG (2006). Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality. J Immunol2006 Aug 1;177(3):1967-74.