Is There Any Advantage to Colloids versus Crystalloids for Volume Repletion?

Rapid volume repletion is indicated in patients with severe hypovolemic or septic shock, as a delay in therapy can result in ischemic injury and possibly irreversible shock and multiorgan system failure. Various monitoring methods have been used to guide fluid resuscitation. Classically, pressure measurements such as central venous pressure or pulmonary capillary wedge pressure were employed. More recently, volume measurements such as inferior vena cava diameter using echocardiography or bedside ultrasound have been more frequently used. Some data suggest that respiratory variation in the arterial pressure tracing can be used to estimate the adequacy of fluid resuscitation, with large stroke volume or pulse pressure variations suggesting persistent hypovolemia and right ventricular underfilling (Gunn and Pinsky, 2001; Magder, 2004). The use of stroke volume or pulse pressure variation to assess volume responsiveness requires that the patient be mechanically ventilated (Soubrier et al., 2007). Other noninvasive tests, such as hemodynamic response to positional changes and leg raising, have also been employed (Monnet et al., 2006).

There are three major classes of replacement fluids:

Crystalloid solutions—isotonic or “normal” saline, buffered solutions (e.g., Ringer lactate, bicarbonate-buffered 0.45% saline, i.e., 75 mmol/L sodium bicarbonate added to 0.45% saline), and chloride-restrictive fluids (e.g., Hartmann solution)
Colloid-containing solutions—albumin solutions, hyperoncotic starch, dextran, and gelatin
Blood products or substitutes—packed red cells and blood substitutes

What is “normal saline”? It is actually “normal physiologic saline” or more meaningfully “isotonic saline.” It is 0.9% saline, which means that there are 0.9 g of sodium chloride (NaCl) per deciliter (100 mL) of water, or 9 g/L. The molecular weight of sodium chloride is approximately 58.5 g/mol (remember that a mole is the molecular weight in grams, and a millimole is the molecular weight in milligrams). To convert 9 g/L to mmol/L, divide by the molecular weight (58.5 g/mol), which gives 0.154 mol/L (154 mmol/L). Since NaCl dissociates into two ions, sodium and chloride, 154 mmol/L NaCl = 154 mmol/L of Na⁺ and 154 mmol/L of Cl^–. Since both sodium and chloride are univalent, 154 mmol/L = 154 mEq/L for both ions. Note that one cannot technically say NaCl 154 mEq/L, as mEq/L is used only for charged substances (ions) and sodium chloride is uncharged.

One might expect the osmolality of normal saline to be 154 × 2 = 308 mmol/L, but this is not the case. One must take into account the osmotic coefficient, a correction for nonideal solutions. The osmotic coefficient of NaCl is 0.93; therefore, the osmolality of a 0.9% saline solution is 154 × 2 × 0.93 = 286 mmol/L, which is isotonic (or iso-osmolar).

How about albumin solutions? Whether or not one gives iso-oncotic (5%) albumin or hyperoncotic (25%) albumin, the osmolality is dependent on the sodium and chloride concentrations (which vary from 130 to 160 mmol/L depending on the manufacturer). Remember that osmolality is a measure of the number of particles per unit volume and thus smaller molecular weight substances will count just as much as large ones. Albumin is very large compared to electrolytes—the molecular weight of albumin is about 70,000 Da—so in a 5% albumin solution, the albumin contributes only a small portion of the total osmolality:

5% = 5 g/100 mL or 50 g/L × 1 mol/70,000 g= 0.0007 mol/L = 0.7 mmol/L

Even 25% albumin contains only about 0.7 × 5 = 3.5 mmol/L. This is why the electrolytes need to be added—otherwise the solution would be dangerously hypotonic and could cause hemolysis. So when you are administering albumin, you are not giving albumin alone but rather albumin in (approximately) isotonic saline.

The choice of replacement fluid depends in part upon the type of fluid that needs to be replaced. Blood transfusion for hemorrhage/blood loss and plasma products for coagulopathy are self-evident and will not be further discussed. The focus will be on the ongoing colloid (usually albumin) versus crystalloid debate.

IS THERE A ROLE FOR ALBUMIN INFUSIONS RATHER THAN CRYSTALLOID INFUSIONS?

In general, crystalloids are preferred over colloid-containing solutions in patients with volume depletion not due to bleeding. This is because studies have shown that saline solutions are as effective as other crystalloid solutions and colloid-containing solutions, and are much less expensive (Finfer et al., 2004; Annane et al., 2013). Hyperoncotic starch solutions should not be used because of an increased risk of acute kidney injury, need for renal replacement therapy, and mortality (Zarychanski et al., 2013).

Since crystalloids will distribute into the extracellular fluid whereas colloids will primarily stay in the intravascular space, up to three times as much saline as colloid must be administered to cause a similar increase in plasma volume (McIlroy and Kharasch, 2003). This may be an advantage of crystalloids if interstitial fluid deficits are also present, but crystalloids may lead to more peripheral edema in other circumstances (Zarins et al., 1978).

Because of the relatively high permeability of the alveolar capillaries to albumin, colloid administration leads to a higher interstitial oncotic pressure in the lungs than in subcutaneous tissue (Taylor, 1981). If hypoalbuminemia is present, there is a parallel reduction in alveolar interstitial albumin concentration, since less albumin moves across the capillary wall, and thus little tendency to the development of pulmonary edema (Zarins et al., 1978). This differs from the effect of hypoalbuminemia on the development of peripheral edema. However, rapid colloid infusion can indeed precipitate pulmonary edema in some hypoalbuminemic patients, such as those with severe nephrotic syndrome (Reid et al., 1996). This is due to a rapid increase in plasma volume with a resulting increase in pulmonary capillary hydrostatic pressure.

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