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

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

Fluid management has been a vital part of routine clinical care for more than 180 years. The increasing number of available fluids has generated controversy about the optimal choice of resuscitation fluid. In this review, we provide a critical overview of the different fluids available, their composition, the relevant physiology as well as the published evidence on clinical outcomes to guide their use. Commonly used infusion fluids include semisynthetic colloids and crystalloids; the latter comprises both normal saline (NaCl 0.9%) and the more chloride-restricted 'balanced' crystalloids. Despite their significantly greater intravascular persistence, semisynthetic colloids have an importantly adverse safety profile and are associated with greater incidence of renal failure and increased mortality; their use should be restricted. To date, evidence for clinical benefits associated with albumin solutions is generally lacking; its merits in specific clinical situations are the subject of further investigation. Infusion of normal saline, with its supraphysiological chloride content, is associated with higher serum chloride concentrations and metabolic acidosis, as well as renal vasoconstriction in animal and human models. Infusion of 'balanced' crystalloids is not linked to such changes. Although data on clinical outcomes associated with crystalloid infusion are heterogeneous, advantages of balanced salt solutions might include a lower need of blood products, and lower incidence of renal replacement therapy, hyperkalaemia and postoperative infections. Taken together, a critical appraisal of the data suggests that balanced salt solutions deserve consideration as infusates of first choice.

/pdf/a-critical-appraisal-of-intravenous-fluids-from-the-3lnd6x8okj.pdf

A critical appraisal of intravenous fluids: from the physiological basis to clinical evidence

Purpose of reviewThe review focuses on fluid resuscitation of critically ill patients with either colloid or crystalloid solutions.Recent findingsIn healthy patients, the volume expanding effect of colloids is greater than that of crystalloids. However, in critically ill patients, a similar amount o

Role of albumin, starches and gelatins versus crystalloids in volume resuscitation of critically ill patients.

Anaesthetists are cautioned to avoid hypervolaemia in their patients. The most cited reason is that hypervolaemia elicits the release of atrial natriuretic peptides that damage the endothelial glycocalyx layer. Although shedding of the glycocalyx causes extravasation of protein in inflammatory disorders, it is more uncertain whether hypervolaemia alone is enough to cause clinically important shedding. This review scrutinises the methodology used in two key papers that propose such a link. The most cited one reports that hydroxyethyl starch and 5% albumin, when creating a hypervolaemic state, only expands the plasma by 40% of the infused volume. This result was obtained by comparing measurements of the plasma volume performed with the indocyanine green (ICG) dye method before and after the infusion. However, the transit time of the dye, as well as inequality in the concentration between vascular beds, both act to underestimate the plasma volume, particularly as times were extrapolated backwards to time zero instead of to (the more correct) 1 minute. A re-calculation based on theoretical ICG data, taking account of the transit time, shows the plasma volume expansion was closer to 100% than to 40% of the infused volume. This figure is supported by the dilution of the reported blood haemoglobin and plasma protein concentrations, as well as by other sources. In conclusion, only weak evidence supports a fluid-induced release of atrial peptides of sufficient size to alter the kinetics of colloid fluid by shedding of the endothelial glycocalyx layer.

Must hypervolaemia be avoided? A critique of the evidence

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

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

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Crystalloid infusion increases plasma hyaluronan

Influence of surgery on serum concentrations of hyaluronan