Mechanisms and treatment of organ failure in sepsis

Lelubre, Christophe; Vincent, Jean‐Louis

doi:10.1038/s41581-018-0005-7

Cited by 530 publications

(488 citation statements)

References 136 publications

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“…Thus, high-dose antibiotics should be taken into consideration to achieve better clinical outcomes [6]. Nevertheless, cellular failure due to the individual dysregulated host responses to pro-inflammatory cytokine and alteration of cellular immune function may also progress and might not have been helped by the higher dose of antibacterial [13,17]. Second, 44.7% of patients included in our study had a negative culture, which might have been from noninfectious causes, viruses, or fungal infection [18,19].…”

Section: Discussionmentioning

confidence: 96%

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Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial

et al. 2020

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Background: Appropriate antimicrobial dosing is challenging because of changes in pharmacokinetics (PK) parameters and an increase in multidrug-resistant (MDR) organisms in critically ill patients. This study aimed to evaluate the effects of an empirical therapy of high-dose versus standard-dose meropenem in sepsis and septic shock patients. Methods: We performed a prospective randomized open-label study to compare the changes of modified sequential organ failure assessment (mSOFA) score and other clinical outcomes of the high-dose meropenem (2-g infusion over 3 h every 8 h) versus the standard-dose meropenem (1-g infusion over 3 h every 8 h) in sepsis and septic shock patients. Patients' characteristics, clinical and microbiological outcomes, 14 and 28-day mortality, vasopressor-and ventilator-free days, intensive care unit (ICU) and hospital-free days, percent of the time of antibiotic concentrations above the minimum inhibitory concentration (%T>MIC), and safety were assessed. Results: Seventy-eight patients were enrolled. Median delta mSOFA was comparable between two groups (-1 in the high-dose group vs. -1 in the standard-dose group; P value = 0.75). There was no difference between the two groups regarding clinical and microbiological cure, 14-and 28-day mortality, vasopressor-and ventilator-free days, and ICU-and hospital-free days. In patients admitted from the emergency department (ED) with a mSOFA score ≥ 7, the high-dose group demonstrated significantly better microbiological cure compared with the standard-dose group (75% (9/12 patients) vs. 20% (2/10 patients); P value = 0.03). Likewise, the high-dose group presented higher microbiological cure rate in patients admitted from ED who had either APACHE II score > 20 (83.3% (10/12) vs. 28.6% (2/7); P value = 0.045) or on mechanical ventilator (87.5% (7/8) vs. 23.1% (3/13); P value = 0.008) than the standard-dose group. Adverse events were comparable between the two groups.(Continued on next page)

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Section: Discussionmentioning

confidence: 96%

“…First, the pathophysiology of sepsis and septic shock starts from dysregulated host responses to infection. A combination of hemodynamic and cellular failures were then followed constantly [13]. Appropriate antibiotic therapy at an early point of sepsis diagnosis will help in reducing microbial load.…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial

et al. 2020

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“…Third, another explanation could be that the two entities, microcirculation and eGC, are controlled by different regulatory and compensatory mechanisms, including hormonal, neural, biochemical, and vascular control systems [53][54][55][56]. We have recently shown, for example, that the activational state of the endothelialspecific Tie2 receptor controls glycocalyx damage in a non-redundant fashion [39].…”

Section: Discussionmentioning

confidence: 99%

Association of sublingual microcirculation parameters and endothelial glycocalyx dimensions in resuscitated sepsis

et al. 2019

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Background The endothelial glycocalyx (eGC) covers the luminal surface of the vascular endothelium and plays an important protective role in systemic inflammatory states and particularly in sepsis. Its breakdown leads to capillary leak and organ dysfunction. Moreover, sepsis-induced alterations of sublingual microcirculation are associated with a worse clinical outcome. The present study was performed to investigate the associations between eGC dimensions and established parameters of microcirculation dysfunction in sepsis. Methods This observational, prospective, cross-sectional study included 40 participants, of which 30 critically ill septic patients were recruited from intensive care units of a university hospital and 10 healthy volunteers served as controls. The established microcirculation parameters were obtained sublingually and analyzed according to the current recommendations. In addition, the perfused boundary region (PBR), an inverse parameter of the eGC dimensions, was measured sublingually, using novel data acquisition and analysis software (GlycoCheck™). Moreover, we exposed living endothelial cells to 5% serum from a subgroup of study participants, and the delta eGC breakdown, measured with atomic force microscopy (AFM), was correlated with the paired PBR values. Results In septic patients, sublingual microcirculation was impaired, as indicated by a reduced microvascular flow index (MFI) and a reduced proportion of perfused vessels (PPV) compared to those in healthy controls (MFI, 2.93 vs 2.74, p = 0.002; PPV, 98.53 vs 92.58, p = 0.0004). PBR values were significantly higher in septic patients compared to those in healthy controls, indicating damage of the eGC (2.04 vs 2.34, p < 0.0001). The in vitro AFM data correlated exceptionally well with paired PBR values obtained at the bedside (rs = − 0.94, p = 0.02). Both PBR values and microcirculation parameters correlated well with the markers of critical illness. Interestingly, no association was observed between the PBR values and established microcirculation parameters. Conclusion Our findings suggest that eGC damage can occur independently of microcirculatory impairment as measured by classical consensus parameters. Further studies in critically ill patients are needed to unravel the relationship of glycocalyx damage and microvascular impairment, as well as their prognostic and therapeutic importance in sepsis. Trial registration Retrospectively registered: Clinicaltrials.gov, NCT03960307 Electronic supplementary material The online version of this article (10.1186/s13054-019-2542-2) contains supplementary material, which is available to authorized users.

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“…34 Sepsis is a dysregulated immune response to an infection that leads to psychological stress and multiple organ dysfunction. 35 The pathophysiology of sepsis-related liver injury includes hypoxic liver injury due to ischemia and shock, cholestasis due to altered bile metabolism, hepatocellular injury due to drug toxicity or overwhelming inflammation. 36 Hence, sepsis in COVID-19 patients might be one of the etiologies of liver injury and substantially impairs the prognosis of COVID-19.…”

Section: Stress and Systemic Inflammation-related Liver Injury In Covmentioning

confidence: 99%

Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease

Li¹,

Fan²

2020

Journal of Clinical and Translational Hepatology

273

286

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An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (2019 coronavirus disease, COVID-19) since December 2019, from Wuhan, China, has been posing a significant threat to global human health. The clinical features and outcomes of Chinese patients with COVID-19 have been widely reported. Increasing evidence has witnessed the frequent incident liver injury in COVID-19 patients, and it is often manifested as transient elevation of serum aminotransferases; however, the patients seldom have liver failure and obvious intrahepatic cholestasis, unless preexisting advanced liver disease was present. The underlying mechanisms of liver injury in cases of COVID-19 might include psychological stress, systemic inflammation response, drug toxicity, and progression of pre-existing liver diseases. However, there is insufficient evidence for SARS-CoV-2 infected hepatocytes or virus-related liver injury in COVID-19 at present. The clinical, pathological and laboratory characteristics as well as underlying pathophysiology and etiology of liver injury in COVID-19 remain largely unclear. In this review, we highlight these important issues based on the recent developments in the field, for optimizing the management and treatment of liver injury in Chinese patients with COVID-19. Citation of this article: Li J, Fan JG. Characteristics and mechanism of liver injury in 2019 coronavirus disease.

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Mechanisms and treatment of organ failure in sepsis

Cited by 530 publications

References 136 publications

Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial

Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial

Association of sublingual microcirculation parameters and endothelial glycocalyx dimensions in resuscitated sepsis

Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease

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