Plasma fibronectin and associated variables in surgical intensive care patients.

An acute depletion of plasma fibronectin or FN has been observed in critically ill, surgical, or trauma patients, but there is little information on the relationships between FN levels and the final outcome in such cases, and on the simultaneous behaviour of other serum proteins. The daily values of FN, antithrombin III, IgG, C3, prealbumin, and transferrin were monitored in 98 intensive care patients after major elective surgery or trauma. According to their clinical course, they were divided retrospectively into three groups. Group A (33 patients) had sepsis. Group B (31 patients) had nonseptic complications, and group C (34 patients) had no complications in the ICU. The individual, nadir levels of FN, AT III, prealbumin, and transferrin were lower (p less than 0.01) in the septic group A than in B and C. Within the septic group, the nadir levels of AT III, but not those of FN, were lower (p less than 0.01) in the 14 nonsurvivors than in the 19 survivors. The FN and AT III levels had returned at least temporarily to the normal range in the six ultimate fatalities from sepsis who survived for more than two weeks. In the septic group, transferrin showed the highest percentages of actually subnormal levels and differed from FN in this respect with p less than 0.05. Furthermore, all six proteins showed a significant overall pattern (p less than 0.01) of parallel variations. The results confirm other reports on the behavior of fibronectin in septic patients as a group, but it was not informative as to the individual outcome, and its reduction might be viewed as part of a general plasma protein depletion associated with acute septic disease. This pattern is probably attributable to a combination of intravascular consumption and an overall excess of protein catabolism over synthesis.

Colloids versus crystalloids as volume substitutes: clinical relevance of the serum oncotic pressure.

With some amplifications, Starling's concept of the serum colloid osmotic or oncotic pressure as the determinant of fluid partition between the intravascular and the interstitial compartment has been confirmed by modern physiological research. The relationship between serum oncotic pressure and interstitial edema is non-linear, i.e. edema becomes progressively greater per mm decrease of the oncotic pressure. The intravascular volume effect of crystalloids is inseparable from interstitial edema, because it depends on an expansion of the interstitium which increases the hydrostatic pressure in that compartment sufficiently to compensate for a lowered capillary oncotic pressure. With large crystalloid fluid loads, about 90% of the total edema accumulates in skeletal muscle, subcutaneous fat, and the skin. The skin is particularly susceptible to the development of edema associated with a hypoproteinemic fluid overload, presumably because its extracellular space is three times larger than the average whole-body value. The intestine also shows a marked reaction to a hypoproteinemic fluid overload. There is evidence for a pathogenetic significance of hypoproteinemic edema in the myocardium, the intestine, and the skin. To rid a patient of this type of edema, concentrated albumin is indispensable, and its effects are demonstrable in the above-mentioned tissues, whereas a diuretic alone is ineffective. The therapeutic implications of these mechanisms and findings are discussed. In the lung, fluid exchange and distribution between the intravascular and the interstitial compartment is influenced by additional factors, and opinions on the use of colloids versus crystalloids continue to differ, particularly with respect to those circumstances where capillary permeability is presumably or demonstrably abnormal. However, the weight of the evidence still favours the concept that in patients with a much greater than respiratory distress syndromes much greater than, the serum oncotic pressure should at any rate not be permitted to drop below a certain critical level. A condensed review of these complex and as yet incompletely clarified problems is presented.

Clinical indications for human serum albumin.

Three indications have been considered for the clinical use of human serum albumin: nutrition, binding and transport, and the volume effect due to the oncotic properties of the protein. The use of albumin as an intravenous nutrient is clearly inappropriate. The literature on its binding and transport properties is as yet clinically inconclusive, and it seems premature to enforce product specifications based on these characteristics. The effects on blood volume and hypoproteinemia are firmly established in patients with an intact capillary system. The therapeutic implications of a capillary "permeability lesion" are a subject of current debate. Such lesions occur following extensive injuries and in patients with septic pulmonary failure. Although the data are contradictory, it is largely agreed that the serum albumin level should be kept above 30 g/litre or the total serum protein above 50 g/litre.

Perfusate oncotic pressure during cardiopulmonary bypass. Optimum level as determined by metabolic acidosis, tissue edema, and renal function.

Current practice with respect to the use of a dilutional prime for cardiopulmonary bypass (CPB) varies widely, and the safe lower limit of perfusate protein content has not been defined. We studied this question in 75 rabbits subjected to a 1-hour CPB with a perfusate colloid osmotic pressure (COP) ranging from 26 to 4 mm Hg. Metabolic acidosis was inversely related to COP; acid-base equilibrium is thus best maintained with a high perfusate protein content. Tissue edema rapidly increased at COP levels below 16 mm Hg, i.e. with a protein level less than 4.2 g%. Urinary excretion during CPB was antagonized by the COP, the reason being that glomerular filtration rate was proportional to the difference between perfusion pressure and COP. The safety margin for renal function during CPB thus widens with a decreasing perfusate protein content. We conclude that the optimum levels of perfuste oncotic pressure and protein content during experimental cardiopulmonary bypass are 16 mm Hg and 4.2 g%.

Acute hypoproteinemic fluid overload: its determinants, distribution, and treatment with concentrated albumin and diuretics.

We simulated the use of massive volumes of crystalloid fluids as a treatment of acute plasma loss in a standardized experimental model and studied the factors determining the retention or excretion of the resulting acute hypoproteinemic fluid overload, its distribution within the body, and its treatment with concentrated albumin and diuretics. In accordance with the classic Starling concept, the serum protein level, i.e. the serum colloid osmotic pressure, determined the excretion/retention ratio of a given water and sodium load. Of the total fluid retention, fat and muscle each accommodated 25%, whereas the skin, which contributes only 7% to the total body weight, accounted for 37% and increased its volume by roughly one third. Concentrated albumin promoted fluid excretion in direct proportion to the achieved increment of the serum protein level and abolished the edema of fat, muscle and skin. Furosemide was virtually ineffective. The implications of these results for the 'adult respiratory distress syndrome' and disturbed wound healing are discussed and related to the concept of a critical threshold of the serum protein level.