Pharmacology of Crystalloids and Colloids
Pharmacology of Crystalloids and Colloids
Pharmacology of Crystalloids and Colloids
INTRODUCTION
Blood volume is a critical factor in maintaining hemodynamic equilibrium and
tissue oxygenation. Intravascular volume is regulated very closely by means of
several complex mechanisms, for which the onset of action varies widely. In
some situations, such as acute bleeding, sepsis or with the use of certain drugs,
the body must withstand absolute or relative changes in blood volume that
cannot be immediately compensated for by the regulatory mechanisms. In these
situations, the main goal of volume therapy is to temporarily increase plasma
volume until the bodys own mechanisms can correct the hypovolemia.Treatment
of hypovolemia has changed significantly in recent years. In the past, fresh
frozen plasma (FFP) or its equivalent was long the volume expander most
commonly used. Now, indications for FFP are limited to the correction of some
hemostatic disorders. A by-product of this legitimate change in practice was
increased use of human albumin. Because of the financial consequences of this
strategy, several consensus conferences have issued recommendations on the
best indications for the use of various plasma volume expanders.Despite these
recommendations, the choice of the appropriate agent in the treatment of
hypovolemia has not yet been settled. The debate on crystalloids versus colloids
continues, besides a debate on the choice of colloid.
HYPOVOLEMIC SHOCK
ISOTONIC CRYSTALLOIDS
HYPERTONIC CRYSTALLOIDS
HUMAN ALBUMIN
DEXTRANS
Of all the colloids used in clinical practice, dextrans are those with which
we have the most experience. The physical, chemical and pharmacological
properties of dextrans are particularly well known and among the most studied of
all plasma substitutes. The use of dextrans has been declining noticeably in
Europe because of their side effects. Dextran is a single-chain polysaccharide of
bacterial origin. The average molecular weight of these of variably dispersed
solutions is an important product characteristic. The average molecular weight in
weight (Mw), which is the arithmetic mean of molecular weights of the
constituent particles, is different from the molecular weight in number (Mn),
which is the average molecular weight of the particles with colloid oncotic power.
The main types of dextran solutions are designated according to their Mw:
70,000 D (dextran 70), 60,000 D (dextran 60) and 40,000 D (dextran 40).Dextran
70 and 60 are generally prepared as 6% solutions, while dextran 40 is available
in a 10% concentration. The colloid oncotic power of the various dextran
solutions is very high: 1 g of dextran 40 retains 30 mL of water and 1 g of
dextran 70, 20 to 25 mL of water. Following intravenous administration, dextran
is eliminated by three routes. Most is eliminated by the kidneys. A smaller
fraction enters the interstitial space and returns to the bloodstream via lymphatic
drainage or is metabolized by certain organs. A third, even smaller fraction is
eliminated via the gastrointestinal tract. The variety of routes of elimination and
the influence of Mw on most of these routes mean that the pharmcokinetics of
dextrans are very complex. Briefly, following intravenous administration of
dextran 40, half of the dose given is eliminated within 2 h and 80% within 6 h.
Following intravenous administration of dextran 70, 50% of the dose infused is
eliminated within 24 h. The rheologic effect of dextran 40 solutions is especially
pronounced since these solutions reduce viscosity of whole blood more for the
same degree of hemodilution compared to other plasma substitutes <|[48]|>.
Following dilution with various colloid plasma substitutes, low shear-rate viscosity
is reduced with dextran 40, whereas it is increased with dextran 70 and dextran
60. Dextran 40 solutions also have a beneficial effect on red cell rouleau
formation since they increase the time of red cell aggregation, unlike dextran 60
et 70. A new finding regarding beneficial rheologic effects of dextrans involves
leukocyte adherence, an effect that may be useful in the setting of ischemia-
reperfusion injury <|[49]|>. Longer bleeding time is generally seen after
administration of more than 1.5 g/kg of dextran <|[50]|>. This effect is greater
with high molecular weight dextrans. Reduction of platelet adhesiveness is
related to a reduction of factor VIII which acts as a cofactor for ristocetine
aggregation activity, likened to the von Willebrand factor. Hemostatic
abnormalities induced by dextrans are similar to those seen in type I von
Willebrand syndrome. This explains why this side effect can be reversed by the
administration of desmopressin. Dextran also impairs the polymerization of
fibrin. Onset of oliguric or anuric kidney failure is exceptional and has been
reported exclusively with the use of 10% dextran 40 solutions. Analysis of most
published case reports has revealed contributing factors such as age, repeated
infusion of large quantities and arteritis <|[51]|>. Experimental models have
enabled us to understand the pathophysiology of this type of kidney failure,
which is an acute hyperoncotic syndrome. Anaphylactoid reactions appear to be
frequent with dextrans <|[47]|>. The mechanisms of allergic reactions have been
thoroughly studied, particularly by Hedin and Richter <|[52]|> who showed the
role of dextran antibodies. These pathophysiological findings are the basis for
preventing allergic reactions to dextrans by means of hapten inhibition <|[53]|>.
Several studies have shown that prior injection of 20 mL of dextran 1,000 D
(Promit) a few minutes before a dextran infusion will considerably reduce the
incidence of reactions, especially severe reactions. This step should always be
taken before infusion of any type of dextran. Furthermore, signs of acute fetal
distress due to uterine hypertonia have been described when dextrans have
been used during delivery <|[54]|>. Dextrans are therefore absolutely
contraindicated in this setting. Use of dextrans is declining in most European
countries because of dextrans side effects.
GELATINS
HYDROXYETHYL STARCHES
CONCLUSION
Crystalloids remain the intravenous solutions of first choice, and their use
provides essential benefit in the replacement of blood losses by correcting water
and sodium deficits in the interstitial compartment. In major hypovolemia, the
use of crystalloids is inappropriate since the amounts needed do not sufficiently
treat the shock, especially the microcirculatory disturbances, a key factor in
limiting the consequences of shock on tissues. Evidence is building that albumin
should be restricted to a few well-defined situations and be considered as a
infusion solution of second choice, for use when other products are not indicated,
are contraindicated or have been used up to their maximum dose. In particular,
it seems that the use of albumin to correct hypoalbuminemia should be
abandoned. Hydroxyethyl starches are the synthetic colloids with the
pharmcological properties that are the closest to natural colloids. In addition,
there is evidence to support the use of hydroxyethyl starches in intensive care
patients. Their beneficial effects appear to be related more to their action on
inflammatory processes than to their colloid osmotic power. In a risk/benefit
analysis of hydroxyethyl starches, their side effects should also be weighed. Side
effects are limited when hydroxyethyl starches with a low in vivo Mw are used.