Scavengers of hemoproteins as potential biomarkers for severe sepsis and septic shock

Abstract Background Despite improvements in diagnosis, interventions and supportive care, mortality among sepsis patients is still high. Research of the past decade has attempted to identify biomarkers that can accurately discriminate sepsis from other diseases with comparable symptoms to improve diagnosis, but results have been lackluster. Recent studies have shown that hemoproteins and damage-associated molecular patterns (DAMPs) such as mitochondrial DNA (mtDNA) released as the result of hemolysis play an important role in the pathogenesis of sepsis. The aim of this study was to measure plasma levels of the indirect markers for hemoproteins hemopexin, haptoglobin and heme oxygenase-1 (HO-1) as well as the mitochondrial damage marker mtDNA in the plasma of a cohort of sepsis patients to determine the feasibility of their use as biomarkers in the diagnosis of sepsis. Methods Hemopexin, haptoglobin and HO-1 were measured in plasma by ELISA and mtDNA was measured by digital droplet PCR. Plasma levels of hemopexin, haptoglobin, HO-1 and mtDNA were measured in 32 patients with severe sepsis and 8 patients with septic shock at baseline and 4 days after admission to the ICU and in 20 healthy donors. Results Plasma levels of hemopexin were significantly lower and plasma levels of HO-1, haptoglobin and mtDNA were significantly higher in patients with severe sepsis and septic shock at baseline compared to healthy controls. Additionally, HO-1 levels were significantly higher in patients with septic shock compared to patients with severe sepsis. Finally, levels of HO-1 and mtDNA, but not of hemopexin, seemed to slowly revert back towards levels measured in healthy donors within 5 days after admission. Conclusions Our results indicate that plasma levels of the hemoprotein scavengers hemopexin, haptoglobin and HO-1 and the mitochondrial damage marker mtDNA might be useful as additional biomarkers for the early diagnosis of sepsis and disease severity.

Download Full-text

Elevated plasma levels of heparin-binding protein in intensive care unit patients with severe sepsis and septic shock

Critical Care ◽

10.1186/cc11353 ◽

2012 ◽

Vol 16 (3) ◽

pp. R90 ◽

Cited By ~ 53

Author(s):

Adam Linder ◽

Per Åkesson ◽

Malin Inghammar ◽

Carl-Johan Treutiger ◽

Anna Linnér ◽

...

Keyword(s):

Intensive Care Unit ◽

Septic Shock ◽

Severe Sepsis ◽

Intensive Care ◽

Plasma Levels ◽

Binding Protein ◽

Heparin Binding ◽

Elevated Plasma ◽

Heparin Binding Protein ◽

Sepsis And Septic Shock

Download Full-text

Relationship between Plasma Levels of Lipopolysaccharide (LPS) and LPS‐Binding Protein in Patients with Severe Sepsis and Septic Shock

The Journal of Infectious Diseases ◽

10.1086/315093 ◽

1999 ◽

Vol 180 (5) ◽

pp. 1584-1589 ◽

Cited By ~ 346

Author(s):

Steven M. Opal ◽

Patrick J. Scannon ◽

Jean‐Louis Vincent ◽

Mark White ◽

Stephen F. Carroll ◽

...

Keyword(s):

Septic Shock ◽

Severe Sepsis ◽

Plasma Levels ◽

Binding Protein ◽

Sepsis And Septic Shock ◽

Lps Binding

Download Full-text

Effect of fluid bolus triggers and their combination on fluid responsiveness in optimization phase of severe sepsis and septic shock resuscitation

MedPharmRes ◽

10.32895/ump.mpr.2.3.27 ◽

2018 ◽

Vol 2 (3) ◽

pp. 27-32

Author(s):

Bien Le ◽

Dai Huynh ◽

Mai Tuan ◽

Minh Phan ◽

Thao Pham ◽

...

Keyword(s):

Blood Pressure ◽

Septic Shock ◽

Severe Sepsis ◽

Fluid Responsiveness ◽

Statistical Significance ◽

Venous Pressure ◽

Fluid Bolus ◽

Low Blood Pressure ◽

Low Central Venous Pressure ◽

Sepsis And Septic Shock

Objectives: to evaluate the fluid responsiveness according to fluid bolus triggers and their combination in severe sepsis and septic shock. Design: observational study. Patients and Methods: patients with severe sepsis and septic shock who already received fluid after rescue phase of resuscitation. Fluid bolus (FB) was prescribed upon perceived hypovolemic manifestations: low central venous pressure (CVP), low blood pressure, tachycardia, low urine output (UOP), hyperlactatemia. FB was performed by Ringer lactate 500 ml/30 min and responsiveness was defined by increasing in stroke volume (SV) ≥15%. Results: 84 patients were enrolled, among them 30 responded to FB (35.7%). Demographic and hemodynamic profile before fluid bolus were similar between responders and non-responders, except CVP was lower in responders (7.3 ± 3.4 mmHg vs 9.2 ± 3.6 mmHg) (p 0.018). Fluid response in low CVP, low blood pressure, tachycardia, low UOP, hyperlactatemia were 48.6%, 47.4%, 38.5%, 37.0%, 36.8% making the odd ratio (OR) of these triggers were 2.81 (1.09-7.27), 1.60 (0.54-4.78), 1.89 (0.58-6.18), 1.15 (0.41-3.27) and 1.27 (0.46-3.53) respectively. Although CVP < 8 mmHg had a higher response rate, the association was not consistent at lower cut-offs. The combination of these triggers appeared to raise fluid response but did not reach statistical significance: 26.7% (1 trigger), 31.0% (2 triggers), 35.7% (3 triggers), 55.6% (4 triggers), 100% (5 triggers). Conclusions: fluid responsiveness was low in optimization phase of resuscitation. No fluid bolus trigger was superior to the others in term of providing a higher responsiveness, their combination did not improve fluid responsiveness as well.

Download Full-text