Danger in the Intensive Care Unit

Timmermans, Kim; Kox, Matthijs; Scheffer, Gert Jan; Pickkers, Peter

doi:10.1097/shk.0000000000000506

Cited by 58 publications

(33 citation statements)

References 70 publications

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“…There has been considerable speculation about what drives this persistent inflammation in the absence of microbial pathogens and their PAMPs. The persistent inflammation of hospitalized patients with CCI could be attributed to the increased release of DAMPs or endogenous alarmins from damaged tissue and organ injury[83, 84]. Increased concentrations of many of these endogenous compounds are commonly reported in sepsis survivors and the chronic critically ill[85, 86].…”

Section: Clinical Implications Of Pics Mdscs and Chronic Critical Ilmentioning

confidence: 99%

Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome

Mira

Gentile²,

Mathias³

et al. 2017

Critical Care Medicine

384

355

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Objective To provide an appraisal of the evolving paradigms in the pathophysiology of sepsis, propose the evolution of a new phenotype of critically ill patients, its potential underlying mechanism, and its implications for the future of sepsis management and research. Design Literature search using PubMed, MEDLINE, EMBASE, and Google Scholar. Results Sepsis remains one of the most debilitating and expensive illnesses, and its incidence is not declining. What is changing is our definition(s), its clinical course, and how we manage the septic patient. Once thought to be predominantly a syndrome of over exuberant inflammation, sepsis is now recognized as a syndrome of aberrant host protective immunity. Earlier recognition and compliance with treatment bundles has fortunately led to a decline in multiple organ failure and in-hospital mortality. Unfortunately, more and more sepsis patients, especially the aged, are suffering chronic critical illness (CCI), rarely fully recover and often experience an indolent death. Patients with CCI often exhibit ‘a persistent inflammatory-immunosuppressive and catabolic syndrome’ or PICS, and it is proposed here that PICS contributes to many of these adverse clinical outcomes. The underlying cause of PICS is currently unknown, but there is increasing evidence that altered myelopoiesis, reduced effector T-cell function and expansion of immature myeloid-derived suppressor cells are all contributory. Conclusion Although newer therapeutic interventions are targeting the inflammatory, the immunosuppressive, and the protein catabolic responses individually, successful treatment of the septic patient with CCI and PICS may require a more complementary approach.

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Section: Clinical Implications Of Pics Mdscs and Chronic Critical Ilmentioning

confidence: 99%

Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome

Mira

Gentile²,

Mathias³

et al. 2017

Critical Care Medicine

384

355

View full text Add to dashboard Cite

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“…DAMPs are potential biomarkers and attractive therapeutic targets for critically ill patients [46]. Cellular disruption by trauma releases DAMPs that are one of the key linkers between tissue damage, inflammation and systemic inflammatory response syndrome (SIRS) [32].…”

Section: Discussionmentioning

confidence: 99%

Nucleic acid scavenging microfiber mesh inhibits trauma-induced inflammation and thrombosis

et al. 2017

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Trauma patients produce a host of danger signals and high levels of damage-associated molecular patterns (DAMPs) after cellular injury and tissue damage. These DAMPs are directly and indirectly involved in the pathogenesis of various inflammatory and thrombotic complications in patients with severe injuries. No effective therapeutic agents for the removal of DAMPs from blood or tissue fluid have been developed. Herein, we demonstrated that nucleic acid binding polymers, e.g., polyethylenimine (PEI) and polyamidoamine dendrimers, immobilized onto electrospun microfiber mesh can effectively capture various DAMPs, such as extracellular DNAs and high mobility group box 1 (HMGB1). Furthermore, treatment with PEI-immobilized microfiber mesh abrogated the ability of DAMPs, released from dead and dying cells in culture or found in patients following traumatic injury, to activate innate immune responses and coagulation in vitro and in vivo. Nucleic acid scavenging microfiber meshes represent an effective strategy to combat inflammation and thrombosis in trauma.

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“…The innate immune system can be activated via a myriad of pattern recognition receptors (PRRs), depending on which modality causes SIRS (6). Ligands for these PRRs include pathogen associated molecular patterns (PAMPs) derived from invading microbes and danger associated molecular patterns (DAMPs), which are released either passively or actively from host cells (7). The relative contributions of PAMPs and DAMPs to the nature and scope of inflammatory responses and pathophysiological outcomes undoubtedly depends on the specific insult or experimental model.…”

Section: Introductionmentioning

confidence: 99%

Zymosan-Induced Peritonitis

Monroe

Armstrong

Zhang

et al. 2016

Shock

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Zymosan-induced peritonitis is a model commonly used to study systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). However, effects of zymosan on cardiac function have not been reported. We evaluated cardiac responses to zymosan in mice and the role of β-glucan and dectin-1 in mediating these responses. Temperature and cardiac function were evaluated before and after intraperitoneal (i.p.) injection of zymosan (100 or 500 mg/kg) or saline. Chronotropic and dromotropic functions were measured using electrocardiograms collected from conscious mice. Cardiac inotropic function was determined by echocardiography. High-dose zymosan caused rapid and maintained hypothermia along with visual signs of illness. Baseline heart rate (HR) was unaffected but HR variability increased, and there was a modest slowing of ventricular conduction. High-dose zymosan also caused prominent decreases in cardiac contractility at 4 and 24 h. Since zymosan is known to cause gastrointestinal tract pathology, peritoneal wash and blood samples were evaluated for bacteria at 24 h after zymosan or saline injection. Translocation of bacterial occurred in all zymosan-treated mice (n=3), and two had bacteremia. Purified β-glucan (50 and 125 mg/kg, i.p.) had no effect on temperature or ECG parameters. However, deletion of dectin-1 modified the ECG responses to high-dose zymosan; slowing of ventricular conduction and the increase in HR variability were eliminated but a marked bradycardia appeared at 24 h post-zymosan treatment. Zymosan-treated dectin-1 knockout mice also showed hypothermia and visual signs of illness. Fecal samples from dectin-1 knockout mice contained more bacteria than wild types, but zymosan caused less translocation of bacteria. Collectively, these findings demonstrate that zymosan induced systemic inflammation causes cardiac dysfunction in mice. The data suggest that dectin-1 dependent and independent mechanisms are involved. While zymosan treatment causes translocation of bacteria this effect does not have a major role in the overall systemic response to zymosan.

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Danger in the Intensive Care Unit

Cited by 58 publications

References 70 publications

Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome

Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome

Nucleic acid scavenging microfiber mesh inhibits trauma-induced inflammation and thrombosis

Zymosan-Induced Peritonitis

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