Dexmedetomidine versus propofol or midazolam in patients with abdominal sepsis regarding inflammatory response and capillary leak

ABSTRACTSepsis is a serious syndrome characterised by a dysregulated systemic inflammatory response. Here we have analysed the role and the therapeutic potential of Granzyme A (GzmA) in the pathogenesis of peritoneal sepsis using the Cecal Ligation and Puncture (CLP) polymicrobial sepsis model and samples from humans undergoing abdominal sepsis.Elevated GzmA was observed in serum from patients with abdominal sepsis suggesting that GzmA plays an important role in this pathology. In the CLP model GzmA deficient mice, or WT mice treated with an extracellular GzmA inhibitor, showed increased survival, which correlated with a reduction in proinflammatory markers in both serum and peritoneal lavage fluid. GzmA deficiency did not influence bacterial load in blood and spleen indicating that GzmA has no role in bacterial control. Mechanistically, we found that extracellular active GzmA acts as a proinflammatory mediator in macrophages by inducing the TLR4-dependent expression of IL-6 and TNFα.Our findings implicate GzmA as a key regulator of the inflammatory response during abdominal sepsis, and suggest that it could be targeted for treatment of this severe pathology.

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Soluble P-selectin as a Biomarker for Infection and Survival in Patients With a Systemic Inflammatory Response Syndrome on the Intensive Care Unit

Biomarker Insights ◽

10.1177/1177271916684823 ◽

2017 ◽

Vol 12 ◽

pp. 117727191668482 ◽

Cited By ~ 3

Author(s):

Irene T Schrijver ◽

Hans Kemperman ◽

Mark Roest ◽

Jozef Kesecioglu ◽

Dylan W de Lange

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Subsequent Development ◽

Abdominal Sepsis ◽

Systemic Inflammatory Response ◽

Skin Infections ◽

Prognostic Role ◽

Platelet Selectin

Aims: This study investigated the ability of soluble platelet selectin (sP-selectin) to identify infection and predict 30-day mortality in patients with a systemic inflammatory response syndrome (SIRS) on the intensive care unit. Methods: Soluble platelet selectin levels were measured daily in the first 48 hours in patients presenting with SIRS. The outcome, proven infection, was established using predefined definitions. The 30-day mortality was retrospectively assessed. Results: In a total of 313 patients with SIRS, sP-selectin levels were measured. Of these, 114 patients had proven infection on admission or developing during their intensive care unit (ICU) stay. Patients with proven infection had moderately higher levels of sP-selectin (147 ng/mL; interquartile range [IQR], 93.4-203 ng/mL) compared with noninfected patients (143.8 ng/mL; IQR, 89.6-194.7 ng/mL). This difference was not statistically significant ( P = .072). However, in patients who were not admitted for infection (n = 235), sP-selectin levels were significantly related to the subsequent development of infection ( P = .013). Soluble platelet selectin levels were particularly high in patients with abdominal sepsis and skin infections. Higher sP-selectin levels were associated with higher mortality (although not statistically significant, P = .08). Conclusions: This study shows that in patients with SIRS not admitted for infection, sP-selectin levels are significantly related to the subsequent development of infection. Furthermore, patients with higher sP-selectin levels in the first 2 days of admission had higher 30-day mortality, although this association is not statistically significant. Therefore, we conclude that sP-selectin is a potential future biomarker for both mortality and infection in patients with SIRS, but more research is needed to confirm its prognostic role.

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Proinflammatory mediator activity, endogenous antagonists and the systemic inflammatory response in intra-abdominal sepsis

British Journal of Surgery ◽

10.1046/j.1365-2168.1998.00710.x ◽

1998 ◽

Vol 85 (6) ◽

pp. 818-825 ◽

Cited By ~ 34

Author(s):

C. H. Wakefield ◽

and the Scottish Sepsis Intervention Group ◽

G. R. Barclay ◽

K. C. H. Fearon ◽

A. S. Goldie ◽

...

Keyword(s):

Inflammatory Response ◽

Abdominal Sepsis ◽

Systemic Inflammatory Response ◽

Proinflammatory Mediator

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Expression and Function of Granzymes A and B inEscherichia coliPeritonitis and Sepsis

Mediators of Inflammation ◽

10.1155/2017/4137563 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

M. Isabel García-Laorden ◽

Ingrid Stroo ◽

Sanne Terpstra ◽

Sandrine Florquin ◽

Jan Paul Medema ◽

...

Keyword(s):

Inflammatory Response ◽

Serine Proteases ◽

Abdominal Cavity ◽

Lavage Fluid ◽

Abdominal Sepsis ◽

Hepatic Necrosis ◽

Primary Site ◽

E Coli ◽

And Function

Escherichia(E.)coliis the most common causative pathogen in peritonitis, the second most common cause of sepsis. Granzymes (gzms) are serine proteases traditionally implicated in cytotoxicity and, more recently, in the inflammatory response. We here sought to investigate the role of gzms in the host response toE. coli-induced peritonitis and sepsis in vivo. For this purpose, we used a murine model ofE. coliintraperitoneal infection, resembling the clinical condition commonly associated with septic peritonitis by this bacterium, in wild-type and gzmA-deficient (gzmA−/−),gzmB−/−, andgzmAxB−/−mice. GzmA and gzmB were predominantly expressed by natural killer cells, and during abdominal sepsis, the percentage of these cells expressing gzms in peritoneal lavage fluid decreased, while the amount of expression in the gzm+cells increased. Deficiency of gzmA and/or gzmB was associated with increased bacterial loads, especially in the case of gzmB at the primary site of infection at late stage sepsis. While gzm deficiency did not impact neutrophil recruitment into the abdominal cavity, it was accompanied by enhanced nucleosome release at the primary site of infection, earlier hepatic necrosis, and more renal dysfunction. These results suggest that gzms influence bacterial growth and the host inflammatory response during abdominal sepsis caused byE. coli.

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Bilirubin, Interleukin 6 (IL 6) and Lipopolysaccharide �Binding Protein (LBP) � Biomarkers of Sepsis in Appendicular Peritonitis

Revista de Chimie ◽

10.37358/rc.20.7.8262 ◽

2020 ◽

Vol 71 (7) ◽

pp. 444-454

Author(s):

Dragos Serban ◽

Cristian Mihai Branescu ◽

Daniel Alin Cristian ◽

Ana Maria Dascalu

Keyword(s):

Inflammatory Response ◽

Biochemical Parameters ◽

Abdominal Sepsis ◽

Infectious Complications ◽

Septic Complications ◽

Clinical Evolution ◽

Normal Limits ◽

Acute Peritonitis ◽

Intraperitoneal Infection ◽

Inflammatory Syndrome

Peritonitis remains, despite the diagnostic and therapeutic developments, a serious condition, the main cause of septic shock with lethal potential in abdominal surgery Identifying and characterizing the dynamics of early biomarkers of the inflammatory response in abdominal sepsis is important to better follow-up evolution and postoperative infectious complications. The paper aims to study the dynamics of serum concentration of biomarkers LBP, IL6 and bilirubin in patients with acute peritonitis of appendicular cause, in the pre and postoperative stage and the correlation with the clinical evolution of inflammatory syndrome. A prospective 6-month study was performed, including patients for appendicular peritonitis. LBP, IL6, bilirubin, leukocytes were sampled preoperatively, then postoperatively at 72 h, and repeated at 72 h until values returned to normal. Clinical evolution and leukocytes were correlated with biochemical parameters. The mean preoperative values for the studied biochemical parameters were for Il6 of 14.81 +/- 4,047 pg / mL, for LBP of 33,826 +/- 5.5.02 microgram / mL and for bilirubin of 1.77 +/- 0.55mg / mL. The postoperative values decreased in all cases, but remained above normal limits in cases with septic complications. LBP, Il 6 and bilirubin are biomarkers useful in the pre- and postoperative evaluation of sepsis in appendicular peritonitis, correlating more accurately with the evolution of the inflammatory response than leukocytosis. Bilirubin is useful in monitoring intraperitoneal infection, but is not influenced by the existence of extraperitoneal infection. The dynamics of LBP is the most accurate description of bacterial infectious factor exposure.

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Systemic capillary leak syndrome due to systemic inflammatory response syndrome in infants: a report on 31 patients

Open Medicine ◽

10.2478/s11536-013-0292-0 ◽

2014 ◽

Vol 9 (3) ◽

pp. 477-480

Author(s):

Chun-Yan Yang ◽

Ping Xu ◽

Yu-Jun Yang ◽

Bao-Yun Li ◽

Shi-Zhi Sun ◽

...

Keyword(s):

Mechanical Ventilation ◽

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Early Stage ◽

Systemic Inflammatory Response ◽

Capillary Leak Syndrome ◽

Lower Limbs ◽

High Rate ◽

Capillary Leak ◽

Systemic Capillary Leak Syndrome

AbstractThe aim of this study was to describe the clinical features, management strategies and outcomes of 31 infants with systemic capillary leak syndrome (SCLS) secondary to sepsis or systemic inflammatory response syndrome. There were 23 boys and 8 girls, with an average age 9.6 ± 2.1 days (range, 3.1 to 20 days). The primary disease was pneumonia in 11 patients and sepsis in other 20. Within 72 hrs of admission, all had progressive skin and mucosal edema, septic shock, respiratory distress, oliguria and severe hypoalbuminemia (10–20g/L). Other complications were pulmonary edema or hemorrhage, disseminated intravascular coagulopathy, heart failure, renal or liver dysfunction. All patients were treated with mechanical ventilation with a mean mechanical ventilation time of 19.7± 3.5 days. Intravenous hydroxyethyl starch was also applied at an early stage for 4–12 days, together with broad spectrum antibiotics, plasma and albumin infusion. Twenty one patients (67.0%) were discharged from the neonatal intensive care unit after a median stay of 29 days, and 7 died (37.0%) in the hospital. During a 6.3-month follow-up, 4 patients had hydrocephalus and another 4 had muscle spasm or rigidity in the lower-limbs. We conclude that SCLS is a serious complication of neonatal sepsis with a high rate of in-hospital mortality and post-discharge disability.

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Essential Role of Gamma Interferon in Survival of Colon Ascendens Stent Peritonitis, a Novel Murine Model of Abdominal Sepsis

Infection and Immunity ◽

10.1128/iai.66.5.2300-2309.1998 ◽

1998 ◽

Vol 66 (5) ◽

pp. 2300-2309 ◽

Cited By ~ 134

Author(s):

Niko Zantl ◽

Annette Uebe ◽

Brigitte Neumann ◽

Hermann Wagner ◽

Jörg-Rüdiger Siewert ◽

...

Keyword(s):

Inflammatory Response ◽

Murine Model ◽

Essential Role ◽

Abdominal Sepsis ◽

Gamma Interferon ◽

Interleukin 12 ◽

Septic Focus ◽

Ifn Γ ◽

Colon Ascendens

ABSTRACT Despite considerable progress, peritonitis and sepsis remain life-threatening conditions. To improve the understanding of the pathophysiology encountered in sepsis, a new standardized and highly reproducible murine model of abdominal sepsis termed colon ascendens stent peritonitis (CASP) was developed. In CASP, a stent is inserted into the ascending colon, which generates a septic focus. CASP employing a stent of 14-gauge diameter (14G stent) results in a mortality of 100% within 18 to 48 h after surgery. By inserting stents of small diameters, mortality can be exactly controlled. Thus, CASP surgery with insertion of a 22G or 18G stent (22G or 18G CASP surgery) results in 38 or 68% mortality, respectively. 14G CASP surgery leads to a rapid invasion of bacteria into the peritoneum and the blood. As a consequence, endotoxemia occurs, inflammatory cells are recruited, and a systemic inflammatory response syndrome develops. Interestingly, the most pronounced upregulation of inflammatory cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α] and interleukin-12) is observed in spleen and lungs. CASP surgery followed by stent removal at specific time intervals revealed that all animals survived if intervention was performed after 3 h, whereas removal of the septic focus after 9 h did not prevent death, suggesting induction of autonomous mechanisms of a lethal inflammatory response syndrome. 18G CASP surgery in IFN-γ receptor-deficient (IFNγR−/−) mice revealed an essential role of IFN-γ in survival of sepsis, whereas TNF receptor p55-deficient (TNFRp55−/−) mice did not show altered survival rates. In summary, this study describes a novel animal model that closely mimics human sepsis and appears to be highly suitable for the study of the pathophysiology of abdominal sepsis. Importantly, this model demonstrates a protective role of IFN-γ in survival of bacterial sepsis.

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