Biomarkers can be useful for identifying or ruling out sepsis, identifying patients who may benefit from specific therapies or assessing the response to therapy. We used an electronic search of the PubMed database using the key words "sepsis" and "biomarker" to identify clinical and experimental studies which evaluated a biomarker in sepsis. The search retrieved 3370 references covering 178 different biomarkers. Many biomarkers have been evaluated for use in sepsis. Most of the biomarkers had been tested clinically, primarily as prognostic markers in sepsis; relatively few have been used for diagnosis. None has sufficient specificity or sensitivity to be routinely employed in clinical practice. PCT and CRP have been most widely used, but even these have limited ability to distinguish sepsis from other inflammatory conditions or to predict outcome.

/pdf/sepsis-biomarkers-a-review-4665vgzfzb.pdf

Sepsis biomarkers: a review

Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers. Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms “Biomarker” AND “Sepsis.” There were no restrictions by age or language, and all studies, clinical and experimental, were included. We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis. The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.

/pdf/biomarkers-of-sepsis-time-for-a-reappraisal-1os8yb6o8k.pdf

Biomarkers of sepsis: time for a reappraisal

Hyaluronan is a connective tissue polysaccharide which has also been found in blood serum in concentrations < 100 micrograms/L (average 30-40 micrograms/L in middle-aged persons). The serum level is regulated by the influx of the polysaccharide from the tissues via lymph and its receptor-mediated clearance by liver endothelial cells. Markedly high serum levels are noted in certain liver diseases, especially in patients with cirrhosis, when the clearance is impaired. In these cases serum hyaluronan can be used to follow the development of the disease. Serum hyaluronan is also a sensitive marker for impending rejection of liver transplants. Patients with rheumatoid arthritis constitute another major group with increased serum hyaluronan, but in this case the level varies markedly during the day corresponding to physical activity. There are good indications that in these subjects the excess hyaluronan comes from the joints. Under stringent sampling conditions of serum it should be possible to extract interesting information on the inflammatory joint process. Increased hyaluronan levels are also seen in other inflammatory diseases and it is of special interest that high hyaluronan levels in patients with septic conditions is a sign of poor prognosis. Certain tumours, notably Wilms' tumour and mesothelioma, produce factors which activate synthesis of hyaluronan and increase its serum level. Rare hereditary diseases with disturbances of hyaluronan metabolism and elevated blood levels have also been discovered, e.g. Werner's syndrome and cutaneous hyaluronanosis. Information accumulated during the last decade regarding the metabolism of hyaluronan has made this polysaccharide an interesting clinical marker for a number of pathological conditions.

Serum Hyaluronan as a Disease Marker

Introduction Mechanical ventilation with even moderate-sized tidal volumes synergistically increases lung injury in sepsis and has been associated with proinflammatory low-molecular-weight hyaluronan production. High-molecular-weight hyaluronan (HMW HA), in contrast, has been found to be anti-inflammatory. We hypothesized that HMW HA would inhibit lung injury associated with sepsis and mechanical ventilation.

/pdf/high-molecular-weight-hyaluronan-a-possible-new-treatment-2b58noia1e.pdf

High-molecular-weight hyaluronan – a possible new treatment for sepsis-induced lung injury: a preclinical study in mechanically ventilated rats

Large volume fluid resuscitation is currently viewed as the cornerstone of the treatment of septic shock. The surviving sepsis campaign (SSC) guidelines provide a strong recommendation to rapidly administer a minimum of 30 mL/kg crystalloid solution intravenously in all patients with septic shock and those with elevated blood lactate levels. However, there is no credible evidence to support this recommendation. In fact, recent findings from experimental, observational and randomized clinical trials demonstrate improved outcomes with a more restrictive approach to fluid resuscitation. Accumulating evidence suggests that aggressive fluid resuscitation is harmful. Paradoxically, excess fluid administration may worsen shock. In this review, we critically evaluate the scientific evidence for a weight-based fluid resuscitation approach. Furthermore, the potential mechanisms and consequences of harm associated with fluid resuscitation are discussed. Finally, we recommend an individualized, conservative and physiologic guided approach to fluid resuscitation.

/pdf/fluid-resuscitation-in-sepsis-the-great-30-ml-per-kg-hoax-54risgai34.pdf

Fluid resuscitation in sepsis: the great 30 mL per kg hoax

Objective:To investigate the changes in plasma hyaluronan concentrations after intravenous infusion of crystalloid solution in healthy subjects.Design:Crossover, controlled study.Setting:General intensive care unit in a university hospital.Subjects:Twelve healthy medical students.Interventions:Infus

Crystalloid infusion increases plasma hyaluronan

Background and methods Hyaluronan is a polysaccharide normally present in low concentrations in the blood, and is rapidly cleared from the blood by the liver. Increased plasma hyaluronan concentrations have been found in patients with sepsis. We studied changes in serum hyaluronan concentrations and their relationship to hemodynamics and survival in a 48-hr porcine model of injury and sepsis. Results Circulating hyaluronan concentrations increased to high values after induction of experimental sepsis (from mean baseline values of 242 +/- 26 [SEM] to mean maximum concentrations of 964 +/- 255 micrograms/L [p less than .01]) compared with controls (199 +/- 38 to 303 +/- 32 micrograms/L). A weak negative correlation between mean arterial pressure (MAP) and serum hyaluronan values was found (r2 = .47; p less than .01). Nonsurvivors had higher mean serum hyaluronan concentrations than survivors (603 +/- 147 vs. 285 +/- 43 micrograms/L [p less than .05]). Conclusions Experimental sepsis is associated with an increase in serum hyaluronan values. The relationship between decreased MAP and increased serum hyaluronan concentrations could point to reduced liver perfusion as a cause. An association between high hyaluronan values and nonsurvival in sepsis is possible.

Hyaluronan: relationship to hemodynamics and survival in porcine injury and sepsis.

OBJECTIVE To investigate the changes in serum hyaluronan concentrations in response to surgery DESIGN A prospective case series evaluating serum hyaluronan concentrations before, during, and after surgery SETTING Operating room and recovery room of a university hospital PATIENTS Twelve consecutive patients undergoing vascular surgery because of arterial insufficiency of the lower extremities MEASUREMENTS AND MAIN RESULTS Serum hyaluronan concentrations were measured before and after induction of anesthesia and before, during, and after surgery Routine chemical analyses of blood samples were made before and after surgery Blood loss and fluid volumes infused were registered Mean serum hyaluronan concentrations increased from baseline 25 +/- 10 (SD) to 36 +/- 15 micrograms/L (p < 05) during surgery, and increased further at 1 hr after the end of surgery to 52 +/- 38 micrograms/L (p < 001 compared with baseline), but had decreased nearly to baseline levels at 2 hrs postoperatively A positive correlation was seen between peak hyaluronan concentrations and baseline serum hyaluronan levels (r2 = 73; p < 001), but no strong relationship was seen between serum hyaluronan concentrations and other parameters studied CONCLUSIONS Surgery is accompanied by a small increase in serum hyaluronan concentrations in humans The major increase is seen in the postoperative period, and is probably due to increased influx of interstitial hyaluronan when the returning muscular tone activates lymph flow

Influence of surgery on serum concentrations of hyaluronan

High serum hyaluronan in porcine sepsis - relation to hypotension

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Papers

Crystalloid infusion increases plasma hyaluronan

Hyaluronan: relationship to hemodynamics and survival in porcine injury and sepsis.

Influence of surgery on serum concentrations of hyaluronan

High serum hyaluronan in porcine sepsis - relation to hypotension